The changing landscape of SARS-CoV-2: Implications for the maternal-infant dyad.

The COVID-19 pandemic represents the greatest challenge to date faced by the medical community in the 21st century. The rate of rapid dissemination, magnitude of viral contagiousness, person to person transmission at an asymptomatic phase of illness pose a unique and dangerous challenge for all patients, including neonatal and obstetric patients. Although scientific understanding of the pathophysiology of the disease, nature of transmission, and efficacy of mitigation strategies is growing, neither a cure or vaccine have been developed. While COVID-19 is primarily a disease of older patients, infection is now seen across all age demographics with reports of illness in pregnant patients and infants. Altered hormone status and predominance of Th-2 immune helper cells may result in increased predisposition to SARS-CoV-2. Case reports of pregnant patients demonstrate a clinical presentation comparable to non-pregnant adults, but evidence of vertical transmission to the fetus is controversial. Neonatal reports demonstrate an inconsistent and non-specific phenotype, and it is often difficult to separate COVID-19 from the underlying conditions of prematurity or bacterial infection. The development of international registries to enable risk profiling of COVID-19 positive pregnant mothers and/or their offspring may facilitate the development of enhanced mitigation strategies, medical treatments and effective vaccinations.

[Radium-223 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) : The androgen receptor-independent active agent in the therapeutic sequence]. / Radium-223 zur Therapie des metastasierten kastrationsresistenten Prostatakarzinoms (mCRPC) : Der androgenrezeptorunabhängige Wirkstoff in der therapeutischen Sequenz.

BACKGROUND: Radium-223 improves overall survival and preserves quality of life in patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases and no known visceral metastases. Radium-223 can be used in combination with a luteinizing hormone releasing hormone (LHRH) analogue and as part of a sequential treatment scheme if disease progresses after at least two prior lines of systemic mCRPC therapies or if no other available systemic treatment is eligible. OBJECTIVES: Today physicians are faced with a previously unknown multitude and complexity of options for the treatment of mCRPC. An increasing number of clinical trials contribute to the dynamics of the therapeutic landscape. Radium-223 was approved for mCRPC treatment in 2013. Up to now the recommendations of use have been adjusted several times. Highlighting recent clinical trials and practice, this paper explores the position of radium-223 within the therapeutic sequence and outlines key elements for the interdisciplinary cooperation between uro-oncologists and nuclear medicine specialists. RESULTS: The mode of action of radium-223 does not depend on the androgen receptor (AR) pathway. Thus, it is an option in the therapeutic sequence when the efficacy of other agents is reduced by resistance. Furthermore, the efficacy of prior or subsequent medications are neither reduced nor enhanced by radium-223. The opportunity of an AR-independent and survival-prolonging medication should be taken as soon as the indication criteria are met because the incidence of visceral metastases increases during disease progression. According to current mCRPC guidelines, the osteoprotective use of bisphosphonates or denosumab is recommended, before treatment with radium-223 is started or resumed.

Animal movement drives variation in seed dispersal distance in a plant-animal network.

Frugivores play differing roles in shaping dispersal patterns yet seed dispersal distance is rarely quantified across entire communities. We model seed dispersal distance using gut passage times and bird movement for the majority (39 interactions) of known bird-tree interactions on the island of Saipan to highlight differences in seed dispersal distances provided by the five avian frugivores. One bird species was found to be a seed predator rather than a disperser. The remaining four avian species dispersed seeds but differences in seed dispersal distance were largely driven by interspecific variation in bird movement rather than intraspecific variation in gut passage times. The median dispersal distance was at least 56 m for all species-specific combinations, indicating all species play a role in reducing high seed mortality under the parent tree. However, one species-the Micronesian Starling-performed 94% of dispersal events greater than 500 m, suggesting this species could be a key driver of long-distance dispersal services (e.g. linking populations, colonizing new areas). Assessing variation in dispersal patterns across this network highlights key sources of variation in seed dispersal distances and suggests which empirical approaches are sufficient for modelling how seed dispersal mutualisms affect populations and communities.

A randomised, non-crossover study of the GuardianCPV Laryngeal Mask versus the LMA Supreme in paralysed, anaesthetised female patients.

We investigated the hypothesis that the oropharyngeal leak pressure would differ between the GuardianCPV™ and the LMA Supreme™ in anaesthetised patients. We randomly assigned 120 patients to receive either the GuardianCPV or the LMA Supreme for airway management. Oropharyngeal leak pressure was measured during cuff inflation from 0 to 40 ml in 10-ml steps. In addition, intracuff pressure, fibreoptic position of the airway and drain tube, device insertion success, ventilation success, blood staining and airway morbidity were determined. Mean (SD) oropharyngeal leak pressures for clinically acceptable cuff volumes of 20-40 ml were 31 (7) cmH2O for the GuardianCPV and 27 (7) cmH2O for the LMA Supreme (p < 0.0001); mean (SD) intracuff pressures were 68 (33) cmH2O and 88 (43) cmH2O (p < 0.0001), respectively. We found no differences in device insertion success, ventilation success, fibreoptic position of the airway and drain tube, blood staining or airway morbidity. We conclude that the oropharyngeal leak pressure is better for the GuardianCPV than for the LMA Supreme in anaesthetised patients.

Sentinel Lymph Node Biopsy in Patients with Breast Cancer: Comparison of Peritumoral and Periareolar Injection.

Introduction: Intradermal periareolar injection technique for sentinel lymph node biopsy (SLNB) may offer an advantage by including multifocal breast cancer as an additional indication. In May 2008 we changed our standard procedure from peritumoral (PT) to periareolar (PA) injection. We compared the results for corresponding periods before and after the change in procedure. Material and Method: A total of 117 patients (pts.) were investigated the year after we changed our technique; a total of 152 pts were investigated in the reference period 2007. We investigated the identification rates for sentinel lymph nodes (SLN) identified scintigraphically and surgically as well as the rates of metastatic involvement (LN). Results: After PT injection, scintigraphic detection of SLN failed in 5/152 pts., and in a further 10 pts. SLN was not found at surgery. In 7 of 15 pts. in whom SLN was not detected, histology demonstrated nodal involvement. Metastases were found in the SLN of 28 of 137 pts. with successful detection of SLN; no other lymph nodes were affected in 21 of these pts. (75.0 % of pts. with positive SLN detection). With PA injection at least one SLN could always be detected using scintigraphy; only 2/117 SLN could not be found intraoperatively. Metastasis was found in SLN in 34/115 pts.; in 19/34 pts., metastatic involvement was limited to the SLN with no other lymph nodes involved (55.9 % of pts. with positive detection of SLN). Discussion: The detection rate for SLN was significantly higher using PA injection (98.3 % vs. 90.1 %). As axillary dissection was not done in SLN-negative patients, rates of false-negative detection cannot be determined. PA injection not only results in better detection rates, it also offers the advantage that the technique can be performed correctly regardless of tumour localisation.

Myocardial sympathetic innervation in diabetic patients with symptomatic coronary artery disease.

AIM: In non-diabetic patients, sympathetic innervation can be preserved even if there is major impairment of myocardial blood supply. Matters may be more complex in diabetic patients because denervation can be caused by cardiac autonomic neuropathy (CAN) or by ischemic injury. Our aim was to determine whether restrictions in myocardial blood supply have a pronounced influence on sympathetic innervation in diabetics and if this effect can be differentiated from CAN. PATIENTS, METHODS: We analyzed 20 diabetics with advanced coronary artery disease (CAD) and without known CAN. We determined quantitative myocardial blood flow using (13)N-ammonia-PET, myocardial viability with (18)F-FDG, and cardiac innervation with (11)C-HED. We investigated the relationship between regional HED retention, blood flow, and coronary flow reserve (CFR). Attenuated heart rate response to adenosine was taken as indicator for CAN (HR ratio). RESULTS: There was minor correlation of segmental stress flow and HED retention (r(2)=0.063, p<0.0001). Correlation improved when stress flow as well as HED retention were normalized to the individual maximum (r(2)=0.162, p<0.0001). In nine patients, a HR ratio <1.2 implicated subclinical CAN. Duration of diabetic disease or glycaemic control (HbA1c) did not correlate with mean HED retention in the viable segments, but with its variation coefficient. CONCLUSIONS: As in non-diabetic patients, a slight correlation exists between CFR and sympathetic innervation. The sensitivity of sympathetic nerves to reductions in CFR does not seem to be increased as compared to the results reported for non-diabetics. Besides impaired blood supply, long duration of diabetic disease and bad glycaemic control also seem to impair sympathetic innervation provoking higher heterogeneity.

Cardiac re-synchronization therapy: effects on myocardial perfusion at rest, after vasodilation and oxygen consumption.

AIM: Cardiac resynchronization therapy (CRT) has been shown to improve haemodynamics and clinical symptoms in heart failure patients. The present study evaluated the effects of a 4-month CRT on myocardial blood flow (MBF) at rest, after vasodilation and on myocardial oxygen consumption (MVO(2)). PATIENTS, METHODS: We studied 16 patients with idiopathic dilated cardiomyopathy prior to and during CRT performed as biventricular pacing. Resting MBF and MVO(2) were determined from an (11)C-acetate PET study and vasodilator MBF from a (13)N-ammonia study. RESULTS: MBF at rest (0.55 +/- 0.10 ml/min/g), after vasodilation (1.20 +/- 0.45 ml/min/g), and MVO2 (0.082 +/- 0.014/min) did not change by mid-term CRT at a global level (0.57 +/- 0.11 ml/min/g; 1.32 +/- 0.49 ml/min/g; 0.085 +/- 0.018/min), whereas the rate pressure product (RPP) normalised MVO(2) decreased from 0.104 +/- 0.024 to 0.086 +/- 0.018/min (p = 0.02). At baseline, the regional analysis revealed significantly higher values for all parameters in the lateral wall than for those in the other walls. Under CRT the regional differences between the resting parameters equalized and all parameters showed significant lower coefficients of variation. CONCLUSION: Effects of mid-term CRT on resting MBF, vasodilator MBF and MVO(2) occur at a regional level. The resynchronization is associated with a more homogenous distribution pattern of these parameters among the myocardial walls. Substantial alterations to global MBF at rest, after vasodilation or to MVO(2) are not detectable. Regarding the RPP normalised MVO(2), there is evidence of improved ventricular efficiency through CRT.

TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes.

The TRANSFAC database on transcription factors, their binding sites, nucleotide distribution matrices and regulated genes as well as the complementing database TRANSCompel on composite elements have been further enhanced on various levels. A new web interface with different search options and integrated versions of Match and Patch provides increased functionality for TRANSFAC. The list of databases which are linked to the common GENE table of TRANSFAC and TRANSCompel has been extended by: Ensembl, UniGene, EntrezGene, HumanPSD and TRANSPRO. Standard gene names from HGNC, MGI and RGD, are included for human, mouse and rat genes, respectively. With the help of InterProScan, Pfam, SMART and PROSITE domains are assigned automatically to the protein sequences of the transcription factors. TRANSCompel contains now, in addition to the COMPEL table, a separate table for detailed information on the experimental EVIDENCE on which the composite elements are based. Finally, for TRANSFAC, in respect of data growth, in particular the gain of Drosophila transcription factor binding sites (by courtesy of the Drosophila DNase I footprint database) and of Arabidopsis factors (by courtesy of DATF, Database of Arabidopsis Transcription Factors) has to be stressed. The here described public releases, TRANSFAC 7.0 and TRANSCompel 7.0, are accessible under http://www.gene-regulation.com/pub/databases.html.

[Effect of caffeine on myocardial blood flow during pharmacological vasodilation]. / Effekt von Koffein auf den myokardialen Blutfluss unter pharmakologischer Vasodilatation.

Pharmacologic stress with adenosine is frequently used for noninvasive detection of coronary artery disease. Dietary intake of caffeinated food, beverages or medications might alter adenosine-induced hyperemic blood flow, thereby compromising the diagnostic sensitivity of adenosine stress testing. In this case we report on a male patient with CAD. Myocardial blood flow at rest and during adenosine-induced hyperemia 2 hours after consumption of decaffeinated coffee and again without caffeine intake were quantified by ammonia PET. After caffeine intake there was a clearly diminished increase of myocardial blood flow during adenosine. The average coronary flow reserve in the myocardium was 1.3 after caffeine. In the baseline study without caffeine the coronary flow reserve has been improved to 2.3. Caffeine intake alters the coronary vasodilatory capacity. These findings emphasize the importance of carefully screening patients for intake of caffeinated food prior to adenosine stress testing.

Positron emission tomography with 11C-acetate and 18F-FDG in prostate cancer patients.

Visualisation of primary prostate cancer, its relapse and its metastases is a clinically relevant problem despite the availability of state-of-the-art methods such as CT, MRI, transrectal ultrasound and fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). The aim of this study was to evaluate the efficacy of carbon-11 acetate and (18)F-FDG PET in the detection of prostate cancer and its metastases. Twenty-five patients were investigated during the follow-up of primary prostate cancer, suspected relapse or metastatic disease using (11)C-acetate PET; 15 of these patients were additionally investigated using (18)F-FDG PET. Fourteen patients were receiving anti-androgen treatment at the time of the investigation. Lesions were detected in 20/24 (83%) patients using (11)C-acetate PET and in 10/15 (75%) patients using (18)F-FDG PET. Based on the results of both PET scans, one patient was diagnosed with recurrent lung cancer. Median (18)F-FDG uptake exceeded that of (11)C-acetate in distant metastases (SUV =3.2 vs 2.3). However, in local recurrence and in regional lymph node metastases, (11)C-acetate uptake (median SUVs =2.9 and 3.8, respectively) was higher than that of (18)F-FDG (median SUVs =1.0 and 1.1, respectively). A positive correlation was observed between serum PSA level and both (11)C-acetate uptake and (18)F-FDG uptake. (11)C-acetate seems more useful than (18)F-FDG in the detection of local recurrences and regional lymph node metastases. (18)F-FDG, however, appears to be more accurate in visualising distant metastases. There may be a role for combined (11)C-acetate/(18)F-FDG PET in the follow-up of patients with prostate cancer and persisting or increasing PSA.

TRANSFAC: transcriptional regulation, from patterns to profiles.

The TRANSFAC database on eukaryotic transcriptional regulation, comprising data on transcription factors, their target genes and regulatory binding sites, has been extended and further developed, both in number of entries and in the scope and structure of the collected data. Structured fields for expression patterns have been introduced for transcription factors from human and mouse, using the CYTOMER database on anatomical structures and developmental stages. The functionality of Match, a tool for matrix-based search of transcription factor binding sites, has been enhanced. For instance, the program now comes along with a number of tissue-(or state-)specific profiles and new profiles can be created and modified with Match Profiler. The GENE table was extended and gained in importance, containing amongst others links to LocusLink, RefSeq and OMIM now. Further, (direct) links between factor and target gene on one hand and between gene and encoded factor on the other hand were introduced. The TRANSFAC public release is available at http://www.gene-regulation.com. For yeast an additional release including the latest data was made available separately as TRANSFAC Saccharomyces Module (TSM) at http://transfac.gbf.de. For CYTOMER free download versions are available at http://www.biobase.de:8080/index.html.

The TRANSFAC system on gene expression regulation.

The TRANSFAC database on transcription factors and their DNA-binding sites and profiles (http://www.gene-regulation.de/) has been quantitatively extended and supplemented by a number of modules. These modules give information about pathologically relevant mutations in regulatory regions and transcription factor genes (PathoDB), scaffold/matrix attached regions (S/MARt DB), signal transduction (TRANSPATH) and gene expression sources (CYTOMER). Altogether, these distinct database modules constitute the TRANSFAC system. They are accompanied by a number of program routines for identifying potential transcription factor binding sites or for localizing individual components in the regulatory network of a cell.

The new graduate in the operating room.

New graduate nurses today come to their first positions in nursing with varying knowledge bases and minimal clinical nursing skills. Gone are the days when new graduates begin functioning fully in a budgeted position on day one of employment. Mastery of psychomotor, cognitive, and affective skills necessary for nursing practice must be acquired through experience in the work situation. The more complex the clinical setting, the more stressful is the period of learning. The O.R. can be a highly stressful place. The need for anticipation, planning and organization to provide efficient care with meticulous attention to detail is coupled with the need to perform smoothly numerous technical skills. Safe, humanistic care cannot be implemented unless the nurse is also able to assess each patient's individual biopsychosocial status, and identify his unique nursing care needs. In order to learn to cope with this level of complexity, the neophyte nurse must be provided with a planned, supportive experiential learning situation that also provides the time necessary to achieve a beginning level of mastery. The program in Basic O.R. Nursing described here was one attempt to provide such an experience for new graduates.