Ugi multicomponent-reaction: Syntheses of cytotoxic dehydroabietylamine derivatives.

Isocyanide-based multicomponent reactions - especially the standard four component Ugi reaction - provide an easy and powerful access to compounds with an auspicious pharmacological potential. Therefore, a set of 16 novel derivatives of the diterpene dehydroabietylamine was synthesized by the Ugi-4CR. The subsequent screening of the synthesized α-acylamino carboxamides in colorimetric sulforhodamine B assays revealed an in vitro cytotoxicity towards several human tumor cell lines.

Lrp4/Wise regulates palatal rugae development through Turing-type reaction-diffusion mechanisms.

Periodic patterning of iterative structures is diverse across the animal kingdom. Clarifying the molecular mechanisms involved in the formation of these structure helps to elucidate the process of organogenesis. Turing-type reaction-diffusion mechanisms have been shown to play a critical role in regulating periodic patterning in organogenesis.

[Treatment-Refractory Pain].

Pain therapy concepts should be based on a biopsychosocial model. A prerequisite for adequate pain therapy is the detailed medical history. The questions about the intensity of pain and especially about the quality of pain are crucial for the selection of drug therapy.

What are the Demographics and Epidemiology of Legg-Calvé-Perthes Disease in a Large Southern California Integrated Health System?

Background: Although many authors have reported the incidence of Legg-Calvé-Perthes disease (LCPD), there have been few incidence studies in the United States on large, self-contained populations such as those within an integrated health system. Understanding the epidemiology and demographics of LCPD in this setting may help clinicians identify patients at the greatest risk and aid in diagnosis and subsequent treatment.

Questions/purposes: In this study we sought (1) to determine the incidence and demographics of LCPD in a large cohort of children and adolescents in a Southern California integrated healthcare system, and (2) to identify any demographic or clinical factors (such as age, sex, race/ethnicity, or BMI) that are independently associated with LCPD.

Estimated date of delivery based on second trimester fetal head circumference: A population-based validation of 21 451 deliveries.

Introduction: Fetal biometry is used for determining gestational age and estimated date of delivery (EDD). However, the accuracy of the EDD depends on the assumed length of pregnancy included in the calculation. This study aimed at assessing the actual pregnancy length and accuracy of EDD prediction based on fetal head circumference measured at the second trimester.

Predominance of Spinal Metastases Involving the Posterior Vertebral Body.

Background: Spinal metastases pose significant morbidity. For many histologies, the spine is a frequent site for bone metastases. This predilection is not fully understood, and there are conflicting reports regarding the distribution within the vertebral body itself.

[Conversions of cognitive screenings : Mini-Mental State Examination vs. Montreal Cognitive Assessment vs. DemTect].

Background: For a comprehensive specification and quantification of neuropsychological deficits, extensive neuropsychological assessment is needed. Due to its time intensiveness, this cannot be accomplished in every clinical setting and is not always necessary. Therefore, screening instruments provide a first step.

Using value of information methods to determine the optimal sample size for effectiveness trials of alcohol interventions for HIV-infected patients in East Africa.

Background: Unhealthy alcohol consumption exacerbates the HIV epidemic in East Africa. Potential benefits of new trials that test the effectiveness of alcohol interventions could not be evaluated by traditional sampling methods. Given the competition for health care resources in East Africa, this study aims to determine the optimal sample size given the opportunity cost of potentially re-allocating trial funds towards cost-effective alcohol treatments.

Full Factorial Microfluidic Designs and Devices for Parallelizing Human Pluripotent Stem Cell Differentiation.

Human pluripotent stem cells (hPSCs) are promising therapeutic tools for regenerative therapies and disease modeling. Differentiation of cultured hPSCs is influenced by both exogenous factors added to the cultures and endogenously secreted molecules. Optimization of protocols for the differentiation of hPSCs into different cell types is difficult because of the many variables that can influence cell fate.

Structure of supramolecular astaxanthin aggregates revealed by molecular dynamics and electronic circular dichroism spectroscopy.

Biomolecular aggregation is omnipresent in nature and important for metabolic processes or in medical treatment; however, the phenomenon is rather difficult to predict or understand on the basis of computational models. Recently, we found that electronic circular dichroism (ECD) spectroscopy and closely related resonance Raman optical activity (RROA) are extremely sensitive to the aggregation mechanism and structure of the astaxanthin dye. In the present study, molecular dynamics (MD) and quantum chemical (QC) computations (ZIndo/S, TDDFT) are used to link the aggregate structure with ECD spectral shapes.

Genome-wide methylomic and transcriptomic analyses identify subtype-specific epigenetic signatures commonly dysregulated in glioma stem cells and glioblastoma.

Glioma stem cells (GSCs), a subpopulation of tumor cells, contribute to tumor heterogeneity and therapy resistance. Gene expression profiling classified glioblastoma (GBM) and GSCs into four transcriptomically-defined subtypes. Here, we determined the DNA methylation signatures in transcriptomically pre-classified GSC and GBM bulk tumors subtypes.

Concomitant Radioembolization and Immune Checkpoint Inhibition in Metastatic Renal Cell Carcinoma.

This case represents the challenge and creativity necessary when treating patients with metastatic renal cell carcinoma who have been exposed to multiple lines of therapy. At present, treatment with immune checkpoint inhibition has stabilized and improved the metastatic disease of this patient with the exception of hepatic lesions. This isolated progression within the liver led the employment of radioembolization, which successfully treated those metastases.

Maternal exercise, season and sex modify the daily fetal heart rate rhythm.

Aim: The knowledge on biological rhythms is rapidly expanding. We aimed to define the longitudinal development of the daily (24-hour) fetal heart rate rhythm in an unrestricted, out-of-hospital setting and to examine the effects of maternal physical activity, season and fetal sex.

Methods: We recruited 48 women with low-risk singleton pregnancies.

Maternal diabetes alters the development of ductus venosus shunting in the fetus.

Introduction: Despite adequate glycemic control, the risks of fetal macrosomia and perinatal complications are increased in diabetic pregnancies. Adjustments of the umbilical venous distribution, including increased ductus venosus shunting, can be important fetal compensatory mechanisms, but the impact of pregestational diabetes on umbilical venous and ductus venosus flow is not known.

Material And Methods: In this prospective study, 49 women with pregestational diabetes mellitus underwent monthly ultrasound examinations from gestational week 20 to 36.

Fibronectin EDA forms the chronic fibrotic scar after contusive spinal cord injury.

Gliosis and fibrosis after spinal cord injury (SCI) lead to formation of a scar that is an impediment to axonal regeneration. Fibrotic scarring is characterized by the accumulation of fibronectin, collagen, and fibroblasts at the lesion site. The mechanisms regulating fibrotic scarring after SCI and its effects on axonal elongation and functional recovery are not well understood.

[Interprofessional symptom management at the end of life].

At the end of life patients often show distressful symptoms which significantly reduce their quality of life. The goal of all healthcare professionals should be to recognize the beginning of this end of life period in order to provide good symptom management. For this purpose, existing symptoms have to be recorded, suitable therapeutic goals have to be defined for the current situation and potential therapeutic strategies have to be individually formulated.

Childhood Obesity is Associated With Osteochondritis Dissecans of the Knee, Ankle, and Elbow in Children and Adolescents.

Background: Osteochondritis dissecans (OCD) is a joint disorder of the subchondral bone and articular cartilage whose association with obesity in children is not clearly known. The purpose of this study was to assess the magnitude of the association between childhood obesity and the occurrence of OCD of the knee, ankle, and elbow in children.

Methods: A retrospective chart review of an integrated health system was performed on OCD patients aged 2 to 19 from 2007 to 2011, with over 1 million patients in this cohort.

Incidence of Osteochondritis Dissecans in Adults.

Background: Osteochondritis dissecans (OCD) has frequently been described in children and adolescents, but cases of OCD in adults are certainly encountered. Little has been published on the epidemiology of OCD in adult patients.

Purpose: To assess the frequency of OCD lesions in adults and assess the risk by age, sex, and ethnicity.

Monitoring mAb cultivations with in-situ raman spectroscopy: The influence of spectral selectivity on calibration models and industrial use as reliable PAT tool.

Raman spectroscopy is a suitable monitoring technique for CHO cultivations. However, a thorough discussion of peaks, bands, and region assignments to key metabolites and culture attributes, and the interpretability of produced calibrations is scarce. That understanding is vital for the long-term predictive ability of monitoring models, and to facilitate lifecycle management that comply with regulatory guidelines.

Extreme umbilical cord lengths, cord knot and entanglement: Risk factors and risk of adverse outcomes, a population-based study.

Objectives: To determine risk factors for short and long umbilical cord, entanglement and knot. Explore their associated risks of adverse maternal and perinatal outcome, including risk of recurrence in a subsequent pregnancy. To provide population based gestational age and sex and parity specific reference ranges for cord length.

Partners and Alerts in Medication Adherence: A Randomized Clinical Trial.

Background: Poor medication adherence is common and limits the effectiveness of treatment.

Objective: To investigate how social supports, automated alerts, and their combination improve medication adherence.

Design: Four-arm, randomized clinical trial with a 6-month intervention.

'Song of Life': music therapy in terminally ill patients with cancer.

Objectives: Music therapy (MT) holds a promising potential to meet emotional and existential needs in palliative care patients. The aim of the present pilot study was to assess the feasibility, acceptance and potential effectiveness of a novel MT intervention to improve life closure and spiritual well-being of terminally ill patients with cancer receiving palliative care.

Methods: The 'Song of Life' (SOL) intervention was provided on two consecutive sessions containing a biographical interview and a live performance of a song with high biographical relevance to the patient in a lullaby style.

BMP-Responsive Protease HtrA1 Is Differentially Expressed in Astrocytes and Regulates Astrocytic Development and Injury Response.

Astrocytes perform a wide array of physiological functions, including structural support, ion exchange, and neurotransmitter uptake. Despite this diversity, molecular markers that label subpopulations of astrocytes are limited, and mechanisms that generate distinct astrocyte subtypes remain unclear. Here we identified serine protease high temperature requirement A 1 (HtrA1), a bone morphogenetic protein 4 signaling regulated protein, as a novel marker of forebrain astrocytes, but not of neural stem cells, in adult mice of both sexes.

Cryoprecipitate transfusions in the neonatal intensive care unit: a performance improvement study to decrease donor exposure.

Background: The objective of this study was to determine if a change in cryoprecipitate transfusion policy impacts donor exposure and fibrinogen level in a neonatal intensive care unit (NICU) population.

Study Design And Methods: The cryoprecipitate policy was changed from transfusing 10ml/kg to a maximum of 1 unit per transfusion in January 2013. Data were obtained via retrospective chart review of all infants receiving cryoprecipitate transfusions from January 2008 to February 2015 in the NICU at Christiana Hospital.