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This prospective, randomized trial in normo-ovulatory women was designed to test whether administration of low-dose exogenous FSH initiated during the early, mid to late follicular phase can induce multiple dominant follicle development. Forty normal weight women (age 19-35 years, cycle length 25-32 days) participated. A fixed dose (75 IU/day) of recombinant FSH was started on either cycle day 3 (n = 13), 5 (n = 13) or 7 (n = 14) until the induction of ovulation with human chorionic gonadotrophin. Frequent transvaginal ultrasound scans and blood sampling were performed. Multifollicular growth occurred in all groups (overall in 60%), although day 7 starters showed less multifollicular growth. Age, cycle length and initial FSH and inhibin B concentrations were similar between subjects with single or multiple follicle development. However, for all women the lower the body mass index (BMI), the more follicles emerged (r = -0.44, P = 0.007). If multifollicular growth occurred, the length of the luteal phase was reduced (P = 0.002) and midluteal serum concentrations of LH (P = 0.03) and FSH (P = 0.004) were decreased and oestradiol (P = 0.002) and inhibin A (P = 0.01) were increased. In conclusion, interference with decremental serum FSH concentrations by administration of low dose FSH starting on cycle day 3, 5 or as late as day 7, is capable of disrupting single dominant follicle selection. The role of BMI in determining ovarian response suggests that differences in pharmacokinetics of exogenous FSH are involved. Multifollicular growth per se has a distinct effect on luteal phase characteristics. These observations may be relevant for the design of mild ovarian stimulation protocols. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of a validated chest computed tomography (Chest-CT) severity score in COVID-19 patients with their respiratory outcome in the Intensive Care Unit., Methods: A single-center, prospective study evaluated patients with positive RT-PCR for COVID-19, who underwent Chest-CT and had a final COVID-19 clinical diagnosis needing invasive mechanical ventilation in the ICU. The admission chest-CT was evaluated according to a validated Chest-CT Severity Score in COVID-19 (Chest-CTSS) divided into low ≤50% (<14 points) and >50% high (≥14 points) lung parenchyma involvement. The association between the initial score and their pulmonary clinical outcomes was evaluated., Results: 121 patients were clustered into the > 50% lung involvement group and 105 patients into the ≤ 50% lung involvement group. Patients ≤ 50% lung involvement (<14 points) group presented lower PEEP levels and FiO2 values, respectively GEE P = 0.09 and P = 0.04. The adjusted COX model found higher hazard to stay longer on invasive mechanical ventilation HR: 1.69, 95% CI, 1.02-2.80, P = 0.042 and the adjusted logistic regression model showed increased risk ventilator-associated pneumonia OR = 1.85 95% CI 1.01-3.39 for COVID-19 patients with > 50% lung involvement (≥14 points) on Chest-CT at ICU admission., Conclusion: COVID-19 patients with >50% lung involvement on Chest-CT admission presented higher chances to stay longer on invasive mechanical ventilation and more chances to developed ventilator-associated pneumonia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Esper Treml et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Acute respiratory distress syndrome (ARDS) represents the most severe course of COVID-19 (caused by the SARS-CoV-2 virus), usually resulting in a prolonged stay in an intensive care unit (ICU) and high mortality rates. Despite the fact that most affected individuals need invasive mechanical ventilation (IMV), evidence on specific ventilation strategies for ARDS caused by COVID-19 is scarce. Spontaneous breathing during IMV is part of a therapeutic concept comprising light levels of sedation and the avoidance of neuromuscular blocking agents (NMBA). This approach is potentially associated with both advantages (e.g. a preserved diaphragmatic motility and an optimised ventilation-perfusion ratio of the ventilated lung), as well as risks (e.g. a higher rate of ventilator-induced lung injury or a worsening of pulmonary oedema due to increases in transpulmonary pressure). As a consequence, spontaneous breathing in people with COVID-19-ARDS who are receiving IMV is subject to an ongoing debate amongst intensivists., Objectives: To assess the benefits and harms of early spontaneous breathing activity in invasively ventilated people with COVID-19 with ARDS compared to ventilation strategies that avoid spontaneous breathing., Search Methods: We searched the Cochrane COVID-19 Study Register (which includes CENTRAL, PubMed, Embase, Clinical Trials.gov WHO ICTRP, and medRxiv) and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies from their inception to 2 March 2022., Selection Criteria: Eligible study designs comprised randomised controlled trials (RCTs) that evaluated spontaneous breathing in participants with COVID-19-related ARDS compared to ventilation strategies that avoided spontaneous breathing (e.g. using NMBA or deep sedation levels). Additionally, we considered controlled before-after studies, interrupted time series with comparison group, prospective cohort studies and retrospective cohort studies. For these non-RCT studies, we considered a minimum total number of 50 participants to be compared as necessary for inclusion. Prioritised outcomes were all-cause mortality, clinical improvement or worsening, quality of life, rate of (serious) adverse events and rate of pneumothorax. Additional outcomes were need for tracheostomy, duration of ICU length of stay and duration of hospitalisation., Data Collection and Analysis: We followed the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors independently screened all studies at the title/abstract and full-text screening stage. We also planned to conduct data extraction and risk of bias assessment in duplicate. We planned to conduct meta-analysis for each prioritised outcome, as well as subgroup analyses of mortality regarding severity of oxygenation impairment and duration of ARDS. In addition, we planned to perform sensitivity analyses for studies at high risk of bias, studies using NMBA in addition to deep sedation level to avoid spontaneous breathing and a comparison of preprints versus peer-reviewed articles. We planned to assess the certainty of evidence using the GRADE approach., Main Results: We identified no eligible studies for this review., Authors' Conclusions: We found no direct evidence on whether early spontaneous breathing in SARS-CoV-2-induced ARDS is beneficial or detrimental to this particular group of patients.  RCTs comparing early spontaneous breathing with ventilatory strategies not allowing for spontaneous breathing in SARS-CoV-2-induced ARDS are necessary to determine its value within the treatment of severely ill people with COVID-19. Additionally, studies should aim to clarify whether treatment effects differ between people with SARS-CoV-2-induced ARDS and people with non-SARS-CoV-2-induced ARDS., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Research software has become a central asset in academic research. It optimizes existing and enables new research methods, implements and embeds research knowledge, and constitutes an essential research product in itself. Research software must be sustainable in order to understand, replicate, reproduce, and build upon existing research or conduct new research effectively. In other words, software must be available, discoverable, usable, and adaptable to new needs, both now and in the future. Research software therefore requires an environment that supports sustainability. Hence, a change is needed in the way research software development and maintenance are currently motivated, incentivized, funded, structurally and infrastructurally supported, and legally treated. Failing to do so will threaten the quality and validity of research. In this paper, we identify challenges for research software sustainability in Germany and beyond, in terms of motivation, selection, research software engineering personnel, funding, infrastructure, and legal aspects. Besides researchers, we specifically address political and academic decision-makers to increase awareness of the importance and needs of sustainable research software practices. In particular, we recommend strategies and measures to create an environment for sustainable research software, with the ultimate goal to ensure that software-driven research is valid, reproducible and sustainable, and that software is recognized as a first class citizen in research. This paper is the outcome of two workshops run in Germany in 2019, at deRSE19 - the first International Conference of Research Software Engineers in Germany - and a dedicated DFG-supported follow-up workshop in Berlin., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Anzt H et al.)

Polycystic ovary syndrome (PCOS) affects 8-13% of women. The Rotterdam diagnostic criteria include polycystic ovarian morphology (PCOM) on ultrasound, but given recognized challenges, serum anti-Müllerian hormone (AMH) is proposed as an alternative. To inform international PCOS guidelines, a systematic review was completed. Key identified gaps include large international studies in well-defined populations across the lifespan, clustering of AMH with PCOS features, relationships to long-term health outcomes, and improved quality, assay standardization, and sample handling, all needed to determine cut offs. Here we identify research priorities to address these gaps and enhance AMH utility in PCOS. Once issues are addressed, AMH levels could replace more costly and less accessible ultrasound in PCOS diagnosis., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Milder ovarian stimulation protocols for in vitro fertilization (IVF) are being developed to minimize adverse effects. Mild stimulation regimens result in a decreased number of oocytes at retrieval. After conventional ovarian stimulation for IVF, a low number of oocytes are believed to represent poor ovarian reserve resulting in reduced success rates. Recent studies suggest that a similar response following mild stimulation is associated with better outcomes., Methods: This review investigates whether the retrieval of a low number of oocytes following mild ovarian stimulation is associated with impaired implantation rates. Three randomized controlled trials comparing the efficacy of the mild ovarian stimulation regimen (involving midfollicular phase initiation of FSH and GnRH co-treatment) for IVF with a conventional long GnRH agonist co-treatment stimulation protocol could be identified by means of a systematic literature search., Results: These studies comprised a total of 592 first treatment cycles. Individual patient data analysis showed that the mild stimulation protocol results in a significant reduction of retrieved oocytes compared with conventional ovarian stimulation (median 6 versus 9, respectively, P < 0.001). Optimal embryo implantation rates were observed with 5 oocytes retrieved following mild stimulation (31%) versus 10 oocytes following conventional stimulation (29%) (P = 0.045)., Conclusions: The optimal number of retrieved oocytes depends on the ovarian stimulation regimen. After mild ovarian stimulation, a modest number of oocytes is associated with optimal implantation rates and does not reflect a poor ovarian response. Therefore, the fear of reducing the number of oocytes retrieved following mild ovarian stimulation appears to be unjustified.

Study Design: In this study, 14 conservatively treated patients were reviewed who had eosinophilic granuloma of the spine, which had been diagnosed on the basis of histologic study of the vertebral lesion or of specimens from other sites in patients with multiple involvement. The remodeling of the vertebral body was studied in an average follow-up of 5.6 years., Objectives: To analyze the remodeling process of the involved growing vertebral body in Langerhans Cell Histiocytosis after conservative treatment and to assess the sagittal and frontal profile of the spine at the end of growth. Fourteen patients, aged between 1.2 and 11.3 years, with spinal involvement of a Langerhans' cell histiocytosis were treated in the department of orthopedics between 1980 and 1990. All patients had immobilization of the affected region by a custom-made brace. Six patients with symptomatic lesions had radiotherapy and four patients with disseminated disease were treated with chemotherapy. Clinical and radiologic examinations were made at regular intervals to evaluate the development of the vertebrae during the remodeling process., Summary of Background Data: In the 14 patients, both sexes were affected equally. The disease was located in the cervical spine in two patients and in thoracic and lumbar vertebrae in seven patients each. Two patients had two vertebral lesions., Methods: The radiologic evolution of the 16 vertebral lesions was evaluated using follow-up standardized lateral radiographs. The reconstitution of the vertebral height in the presence of vertebra plana was calculated by measuring the ventral distance between the superior and inferior margins of the vertebral body in relation to the adjacent uninvolved vertebra., Results: The measurements showed a growth rate of 1.5-6 (average, 3) in vertebrae with vertebra plana and a growth rate of 1.1-2.7 (average, 1.4) in the unaffected vertebra. The reconstitution of the vertebral height was between 18.2% and 63.8% of the adjacent vertebrae before and between 72.2% and 97% after skeletal maturity., Conclusions: The results demonstrate that conservative orthopedic treatment with immobilization in a brace is sufficient to allow for optimal vertebral remodeling. Partial to nearly complete reconstitution of vertebral height was seen in all cases. Thus, operative treatment with curettage of the lesion and bone grafting including multisegmental fusion with instrumentation is not necessary. In instances with neurologic impairment, rarely seen in adults, surgical decompression and short fusion of the spine is necessary. Nevertheless, complete staging and biopsy are mandatory for an accurate diagnosis.

The indication for operative treatment in spondylolisthesis results from pain, progressive sliding and, in up to 60% of the patients with progressive dislocation, from radicular malfunction. The posterolateral fusion in situ is a safe procedure, but the deformation remains and in spondyloptosis plastic deformation of the fusion mass can lead to further dislocation. With the external fixator as an instrument for reduction and the internal fixator for stabilization the reduction of even serious spondyloptosis and the recovery of a normal spine alignement and posture is possible, with an acceptable neurological risk. Therefore a concept of treatment is suggested, which as a rule is aiming at the anatomical reduction of the dislocated vertrebra beside stabilization and nerveroot decompression. Depending on the extent of the slip, reduction and stabilization is to be performed in one, two or three stages. An anterior or posterior fusion is sufficient in grade I dislocation. In grade II-V a combined posterior and anterior surgical proceedure is recommended.

In the period from October 1986 to November 1988 in the Medisch Spectrum Twente of Enschede, 25 patients were treated for a tibial plateau fracture by means of arthroscopic surgery. The mean hospital stay was 18 days. Active movement of the leg was prescribed from the fifth day. The results were very good in 23 and poor in 2 patients. Complications such as wound infections and skin necrosis were not seen. Additional meniscal lesions could be diagnosed and treated better using this surgical technique. In addition, the limited incisions and consequently the avoidance of extensive arthrotomy allowed faster rehabilitation and a higher probability of healing the chondral tissue.

The interaction between Botrytis cinerea Pers. and grapevine (Vitis vinifera L.) was studied in a model system of reduced complexity. Cultured plant cells and fragments of fungal cell wall were used to simulate some of the processes taking place upon infection of grapevine with B. cinerea. A soluble glucan elicitor was prepared from the fungal cell wall by acid hydrolysis. Like the insoluble wall preparation, the soluble fragment derived from the cell wall acted upon plant cells in eliciting stilbene formation. In grapevine cells, the interaction with the fungus led to a dramatic shut-off general protein synthesis and to the selective formation of a small set of proteins involved in induced resistance. The proteins synthesized de novo with highest rates were stilbene synthase (StiSy) and L-phenylalanine ammonia-lyase (PAL). Stilbene synthase was purified to apparent homogeneity and its molecular properties were characterized. The enzyme is a homodimer with subunit Mr 43 000 and pl = 5.4. Although there were indications of the presence of isoenzymes, these were not distinguished by charge differences. In size, the grapevine StiSy shows microheterogeneity and differs from the appreciably larger enzyme prepared from peanut. Prior to induction by fungal attack, virtually no stilbenes are formed in the plant cell. Upon induction of the pathway leading to the stilbene resveratrol, StiSy activity determines the ratelimiting step in the metabolic sequence. The highly induced grapevine cells produce and secrete resveratrol and derivatives which are known to be fungistatic.

The treatment of axillary-subclavian vein thrombosis is still controversial. Development of a post-phlebitic syndrome in patients treated conservatively occurs in many patients. Therefore more aggressive treatment is advocated. We report six patients treated with selective low-dose streptokinase infusion with excellent short-term results. Major complications did not occur. Recanalisation was observed in all patients. Long-term results are not yet available.

Based on the case histories of six patients with carcinoma of the thyroglossal duct, the literature on the origin and treatment of this disease was reviewed. As to the treatment of papillary adenocarcinoma there is some controversy, although in most cases treatment is limited to local excision as described by Sistrunk, provided that tumor growth is restricted to the cyst. The prognosis of this carcinoma seems favorable. Squamous cell carcinoma of the thyroglossal duct is rare; there is no uniform advice as to its treatment, and the prognosis is poor.

Because of its fibrinolytic action, streptokinase is believed to reduce the severity of the postthrombotic syndrome in patients with deep vein thrombosis. A prospective and a retrospective study have been undertaken in an attempt to determine when this therapy is useful for patients with deep vein thrombosis. The prospective study included 15 patients with deep vein thrombosis: 5 were treated in the hospital with streptokinase and heparin and 5 only with heparin, 5 were treated at home with only phenprocoumon. All the patients received oral anticoagulant therapy for at least 6 months. Three to four months after the acute episode, phlebography and venous pressure measurements were carried out. Streptokinase appeared to give the best results but with more side-effects. In the retrospective study, 51 patients who had had deep vein thrombosis in 1969 were reexamined 31-47 months later. It was found that more than 50% of the patients with a thrombosis in the femoral and/or iliac vein developed a severe postthrombotic syndrome, in contrast to only 9% of those with a thrombosis in the popliteal vein or lower. It is recommended, on the basis of both the prospective and the retrospective study, that patients with a thrombosis in the femoral and/or iliac vein should be treated with either heparin or streptokinase during the early stage. It is probable that streptokinase will significantly decrease the frequency and severity of the postthrombotic syndrome in these patients in particular, although this has not yet been proven.

Case histories are described of two young patients, both known to have recurrent infections of one pulmonary lobe. Further investigations (especially aortography) disclosed the cause in both to be an intrapulmonary sequestration. Surgical intervention made both patients symptom-free. The aetiology, clinical and investigational findings as well as therapy are discussed. The need for further investigations in patients with recurring infections of one pulmonary lobe is stressed.