Syntheses of bottromycin derivatives Ugi-reactions and Matteson homologations.

New bottromycin derivatives have been prepared using flexible Ugi and Matteson reactions. The Ugi reaction allows the fast and direct assembly of sterically hindered peptide fragments, while the Matteson homologation is excellently suited for the stereoselective synthesis of unusual amino acids like β-methylphenylalanine. Some of the new compounds show excellent activity against .

Evaluation of Early Insulin Glargine Administration in the Treatment of Pediatric Diabetic Ketoacidosis.

Objective: In the management of diabetic ketoacidosis (DKA), the standard of care is to administer insulin glargine after ketoacidosis has resolved and the patient is transitioning from intravenous (IV) insulin to subcutaneous insulin; however, there is evidence to suggest that earlier administration of insulin glargine may accelerate resolution of ketoacidosis. The objective of this research is to determine the efficacy of early subcutaneous insulin glargine on time to resolution of ketoacidosis in children with moderate to severe DKA.

Methods: This retrospective chart review evaluated children age 2 to 21 years old admitted for moderate to severe DKA who received insulin glargine within 6 hours of hospital admission (early insulin glargine) compared with those who received insulin glargine greater than 6 hours from admission (late insulin glargine).

Hydrocarbon Products Occluded within Zeolite Micropores Impose Transport Barriers that Regulate Brønsted Acid-Catalyzed Propene Oligomerization.

Brønsted acid zeolites catalyze alkene oligomerization to heavier hydrocarbon products of varied size and branching. Propene dimerization rates decrease monotonically with increasing crystallite size for MFI zeolites synthesized with fixed H-site density, revealing the strong influence of intrazeolite transport limitations on measured rates, which has gone unrecognized in previous studies. Transient changes in dimerization rates upon step-changes in reactant pressure (150-470 kPa CH) or temperature (483-523 K) reveal that intrazeolite diffusion limitations become more severe under reaction conditions that favor the formation of heavier products.

Looking at individual symptoms: the dynamic network structure of depressive symptoms in cancer survivors and their preferences for psychological care.

Purpose: The majority of depressed cancer survivors do not receive psychological care, possibly because offered care does not align with their experiences and preferences. We examined (1) which depressive symptoms cancer survivors would like to receive psychological care for; (2) how distinct depressive symptoms are related to each other in the contemporaneous and temporal network of depressive symptoms; and (3) whether survivors' care needs correspond to the interconnectedness of these specific symptoms.

Method: Fifty-two cancer survivors suffering from at least mild depressive symptoms and were not receiving psychological care filled out a baseline questionnaire about their care needs for distinct depressive symptoms, followed by ecological momentary assessments (EMA) assessing depressive symptoms (14 days, five times a day).

Are cancer patients with high depressive symptom levels able to manage these symptoms without professional care? The role of coping and social support.

Objective: Around 25% of cancer patients experiences depressive symptoms. However, the majority does not receive formal psychological care because patients often prefer managing symptoms alone or with informal social support. Previous research has shown that adaptive coping and social support can indeed be effective in managing relatively mild depressive symptoms.

Understanding care needs of cancer patients with depressive symptoms: The importance of patients' recognition of depressive symptoms.

Objective: The majority of cancer patients with depressive symptoms does not perceive a need for psychological care. Reasons for this are still unclear. We examined the mediating role of cancer patients' perceptions of depressive symptoms in the relationship between depressive symptoms and perceived need for psychological care.

A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome.

Background: Gamma-aminobutyric acid (GABA) system deficits are integral to the pathophysiologic development of fragile X syndrome (FXS). Ganaxolone, a GABA receptor positive allosteric modulator, is hypothesized to improve symptoms such as anxiety, hyperactivity, and attention deficits in children with FXS.

Methods: This study was a randomized, double-blind, placebo-controlled, crossover trial of ganaxolone in children with FXS, aged 6-17 years.

Controlling Reaction Selectivity through the Surface Termination of Perovskite Catalysts.

Although perovskites have been widely used in catalysis, tuning of their surface termination to control reaction selectivity has not been well established. In this study, we employed multiple surface-sensitive techniques to characterize the surface termination (one aspect of surface reconstruction) of SrTiO (STO) after thermal pretreatment (Sr enrichment) and chemical etching (Ti enrichment). We show, by using the conversion of 2-propanol as a probe reaction, that the surface termination of STO can be controlled to greatly tune catalytic acid/base properties and consequently the reaction selectivity over a wide range, which is not possible with single-metal oxides, either SrO or TiO .

Improving IQ measurement in intellectual disabilities using true deviation from population norms.

Background: Intellectual disability (ID) is characterized by global cognitive deficits, yet the very IQ tests used to assess ID have limited range and precision in this population, especially for more impaired individuals.

Methods: We describe the development and validation of a method of raw z-score transformation (based on general population norms) that ameliorates floor effects and improves the precision of IQ measurement in ID using the Stanford Binet 5 (SB5) in fragile X syndrome (FXS; n = 106), the leading inherited cause of ID, and in individuals with idiopathic autism spectrum disorder (ASD; n = 205). We compared the distributional characteristics and Q-Q plots from the standardized scores with the deviation z-scores.

Pro-apoptotic Bid is required for the resolution of the effector phase of inflammatory arthritis.

Rheumatoid arthritis is an autoimmune disease characterized by hyperplasia of the synovial lining and destruction of cartilage and bone. Recent studies have suggested that a lack of apoptosis contributes to the hyperplasia of the synovial lining and to the failure in eliminating autoreactive cells. Mice lacking Fas or Bim, two pro-apoptotic proteins that mediate the extrinsic and intrinsic death cascades, respectively, develop enhanced K/BxN serum transfer-induced arthritis.

Bim deficiency leads to exacerbation and prolongation of joint inflammation in experimental arthritis.

Objective: : Rheumatoid arthritis (RA) is characterized by hyperplasia of the synovial lining, inflammation, and destruction of cartilage and bone. Since there are only a few detectable cells undergoing apoptosis in the joint, it is possible that a defect in apoptosis may contribute to synovial hyperplasia. This study sought to identify and characterize the direct role of apoptotic regulators in a mouse model of inflammatory arthritis.

p21Cip1 is required for the development of monocytes and their response to serum transfer-induced arthritis.

One of the central functions of cyclin-dependent kinase inhibitors, such as p21, p27, or p16, is to prevent entry into the cell cycle. However, the question remains as to whether they have other functions in the cell. We previously demonstrated that overexpression of p21 in fibroblasts isolated from patients with rheumatoid arthritis decreases the production of pro-inflammatory molecules.

Combined loss of proapoptotic genes Bak or Bax with Bim synergizes to cause defects in hematopoiesis and in thymocyte apoptosis.

The proapoptotic members of the Bcl-2 family can be subdivided into members that contain several Bcl-2 homology (BH) domains and those that contain only the BH3 domain. Although it is known that BH3-only proteins and the multi-BH domain proteins, Bak and Bax, are essential for programmed cell death, the overlapping role of these two subgroups has not been examined in vivo. To investigate this, we generated Bak/Bim and Bax/Bim double deficient mice.

Fas death receptor signaling represses monocyte numbers and macrophage activation in vivo.

Over 1 billion monocytes are produced daily, with a small percentage differentiating into macrophages, suggesting that excess monocytes are deleted through a tightly regulated process. Although the in vivo mechanism governing monocyte/macrophage homeostasis is unknown, deletion of monocytes in culture is mediated by the Fas death pathway and is blocked by M-CSF. To determine the in vivo significance of Fas in monocyte development, mice lacking Fas (lpr/lpr) and mice deficient in Fas and M-CSF were examined.

IL-4 and IL-10 inhibition of spontaneous monocyte apoptosis is associated with Flip upregulation.

Human peripheral blood monocytes undergo spontaneous apoptosis in culture. Spontaneous monocyte apoptosis is regulated by the death ligand, Fas Ligand (FasL) binding to its receptor Fas. The pro-inflammatory molecules, LPS and IL-1beta, prevent spontaneous monocyte apoptosis.

Assessment of ambulatory behavior in nursing home residents who pace or wander: a comparison of four commercially available devices.

This study evaluated four devices--a Pedometer, Step Sensor, Actigraph, and Personal Activity Meter (PAM)--as measures of pacing behavior. Ten nursing home residents who frequently paced in a long-term care facility underwent 1 day of data collection with each of the devices. Data derived from devices were compared to behavioral observations regarding the number of steps taken.

[Synthesis of C14-flupirtine maleate].

Starting from 14C-p-fluorobenzoic acid the synthesis of 14C-labelled 2-amino-3-ethoxycarbonylamino-6-(p-fluorobenzylamino)-pyridi ne maleate (flupiritine maleate, D 9998) is described.

[Syntheses of 14C-1-erythro-norephedrine and its N-substitution products 14C-oxyfedrine and 14C-D 13,625].

Starting from 14C-benzene (--)-erythro-norephedrine (14C-1-norephedrine) was obtained in a 6-step synthesis. 14C-1-Norephedrine functioned as an intermediate for the synthesis of the carbon labelled partial beta-agonist oxyfedrine hydrochloride (ildamen) and the new positive inotropic agent D 13 625 (alifedrine hydrochloride).

[Studies on the surgical approach in vital pulp excision in relation to the root canal cross section].

The authors examined in 38 teeth the condition of the pulp stump after vital extirpation of the pulp in relation to the cross-section of the root canal. They found that the wound conditions could not be evaluated in 17 teeth as there was no pulp stump in the apical region. Relatively favourable conditions were seen in 11 teeth, which was achieved only in case of circular or oval cross-section of the root canal.

[Synthesis of radioactively labelled reproterol hydrochloride (author's transl)].

Synthesis of radioactively labelled 7-(3-[2-(3,5-dihydroxy-phenyl)-2-hydroxy-ethylamino]-propyl)-theophylline (reproterol) as needed for pharmacokinetic examinations, is described. The 14C-malonic diethyl ester was proven to be the suitable starting compound. The synthesis of the tritium-labelled reproterol is briefly described.