Measurement and assessment of grief in a large international sample.

BACKGROUND: In 2022, the International Classification of Diseases (ICD-11) and an update of the Diagnostic Statistical Manual of Mental Disorders (DSM 5 TR) were released for implementation worldwide and now include the new Prolonged Grief Disorder (PGD). The newest definition of PGD is based on robust clinical research from the Global North yet until now has not been tested for global applicability. METHODS: The current study assesses the new PGD ICD-11 criteria in a large international sample of 1393 bereaved adults. The majority of the sample was included from the USΑ. Additionally, we conduct a sub-sample analysis to evaluate the psychometric properties, probable caseness of PGD, and differences in network structure across three regions of residency (USA, Greece-Cyprus, Turkey-Iran). RESULTS: The psychometric validity and reliability of the 33-item International Prolonged Grief Disorder Scale (IPGDS) were confirmed across the whole sample and for each regional group. Using the strict diagnostic algorithm, the probable caseness for PGD for the whole sample was 3.6 %. Probable caseness was highest for the Greece-Cyprus group (6.9 %) followed by Turkey-Iran (3.2 %) and the USA (2.8 %). Finally, the network structure of the IPGDS standard items and cultural supplement items (total of 33 items) confirmed the strong connection between central items of PGD, and revealed unique network connections within the regional groups. LIMITATIONS: Future research is encouraged to include larger sample sizes and a more systematic assessment of culture. CONCLUSION: Overall, our findings confirm the global applicability of the new ICD-11 PGD disorder definition as evaluated through the newly developed IPGDS. This scale includes culturally sensitive grief symptoms that may improve clinical precision and decision-making.

Optimising cell-based bioassays via integrated design of experiments (ixDoE) - A practical guide.

For process optimisation Design of Experiments (DoE) has long been established as a more powerful strategy than a One Factor at a Time approach. Nevertheless, DoE is not widely used especially in the field of cell-based bioassay development although it is known that complex interactions often exist. We believe that biopharmaceutical manufacturers are reluctant to move beyond standard practices due to the perceived costs, efforts, and complexity. We therefore introduce the integrated DoE (ixDoE) approach to target a smarter use of DoEs in the bioassay setting, specifically in optimising resources and time. Where in a standard practice 3 to 4 separate DoEs would be performed, our ixDoE approach includes the necessary statistical inference from only a single experimental set. Hence, we advocate for an innovative, ixDoE approach accompanied by a suitable statistical analysis strategy and present this as a practical guide for a typical bioassay development from basic research to biopharmaceutical industry.

Interleukin-4 and interferon-γ orchestrate an epithelial polarization in the airways.

Interferon-γ (IFN-γ) and interleukin-4 (IL-4) are key effector cytokines for the differentiation of T helper type 1 and 2 (Th1 and Th2) cells. Both cytokines induce fate-decisive transcription factors such as GATA3 and TBX21 that antagonize the polarized development of opposite phenotypes by direct regulation of each other's expression along with many other target genes. Although it is well established that mesenchymal cells directly respond to Th1 and Th2 cytokines, the nature of antagonistic differentiation programs in airway epithelial cells is only partially understood. In this study, primary normal human bronchial epithelial cells (NHBEs) were exposed to IL-4, IFN-γ, or both and genome-wide transcriptome analysis was performed. The study uncovers an antagonistic regulation pattern of IL-4 and IFN-γ in NHBEs, translating the Th1/Th2 antagonism directly in epithelial gene regulation. IL-4- and IFN-γ-induced transcription factor hubs form clusters, present in antagonistically and polarized gene regulation networks. Furthermore, the IL-4-dependent induction of IL-24 observed in rhinitis patients was downregulated by IFN-γ, and therefore IL-24 represents a potential biomarker of allergic inflammation and a Th2 polarized condition of the epithelium.

In vitro hydrolytic digestion, glycemic response in dogs, and true metabolizable energy content of soluble corn fibers.

The objective of this research was to measure in vitro hydrolytic digestion, glycemic and insulinemic responses in dogs, and true ME (TMEn) content of select soluble corn fibers (SCF) in roosters. The first generation (G1) SCF included hydrochloric acid-treated corn syrup (G1-CS-HCl), an SCF with an increased total dietary fiber (TDF) content (G1-SCF-HCl), an SCF that was spray-dried (G1-SCF-SD), and a hydrogenated SCF (G1-SCF-hydrog). The second generation (G2) SCF included those prepared using phosphoric acid catalyzation in both a liquid [G2-SCF-phos (Lq)] and powder [G2-SCF-phos (Pw)] form, and SCF that were prepared using hydrochloric acid catalyzation in both a liquid [G2-SCF-HCl (Lq)] and powder [G2-SCF-HCl (Pw)] form. Also, in the G2 set of samples were SCF prepared using the same method, but in 3 separate batches, all of which contained 70% TDF and 15% sugars. Two were in liquid form [G2-SCF-phos+HCl (Lq1)] and [G2-SCF-phos+HCl (Lq2)], and one in powder form ([G2-SCF-phos+HCl (Pw)]. A lower sugar form (80% TDF and 5% sugar) of SCF was also evaluated (G2-SCF-low sugar). Glucose was the major free sugar and bound monosaccharide in all SCF except for G1-SCF-hydrog that had greater concentrations of sorbitol. All SCF had intermediate to low amounts of monosaccharides released as a result of in vitro hydrolytic digestion, with glucose being the primary sugar component released. The G1-SCF were more digestible in vitro (approximately 50%) compared to G2-SCF (approximately 32%). All SCF had attenuated glycemic responses in adult dogs compared to a maltodextrin control (P < 0.05). The G2-SCF, on average, had lower glycemic responses and TMEn values in roosters than G1-SCF. All SCF had low free sugar concentrations with varying degrees of resistance to digestion, reduced caloric content, and attenuated glycemic and insulinemic responses in adult dogs. These ingredients are potential candidates for inclusion in reduced calorie and low glycemic canine diets.

Blending of soluble corn fiber with pullulan, sorbitol, or fructose attenuates glycemic and insulinemic responses in the dog and affects hydrolytic digestion in vitro.

The objective of these experiments was to measure in vitro hydrolytic digestion and glycemic and insulinemic responses of select carbohydrate blends, all containing the novel carbohydrate soluble corn fiber (SCF). Two SCF that varied in their method of production were used to formulate the carbohydrate blends. One set of blends contained a SCF that was spray dried (SCFsd) and then blended with different amounts of either pullulan, sorbitol, or fructose. The other set of blends contained a SCF produced using longer evaporation time (SCF) and then blended with different ratios of pullulan, sorbitol, and fructose. Free sugar concentrations found in the individual SCFsd and SCF substrates were low but varied. Spray-dried soluble corn fiber had a reduced free sugar concentration compared with SCF (2.8 vs. 14.2%). Glucose was the main free sugar found in both SCFsd and SCF but at different concentrations (2.7 vs. 12.7%, respectively). The majority of the SCFsd blends were completely hydrolyzed to their monosaccharide components. Glucose accounted for most of the hydrolyzed monosaccharides for SCFsd and all the SCFsd blends. Hydrolyzed monosaccharide concentrations for the SCF:pullulan:sorbitol:fructose blends followed similar trends to the SCFsd blends where greater percentages of fructose and sorbitol resulted in decreased (P < 0.05) hydrolyzed monosaccharide concentrations. The SCFsd blends had intermediate to high amounts of monosaccharides released as a result of in vitro hydrolytic digestion. The SCFsd:pullulan blends were more digestible in vitro (approximately 91%; P < 0.05) than SCFsd:fructose or SCFsd:sorbitol. Total released monosaccharides were high in SCFsd blends containing either 50% fructose or sorbitol, but the combination resulted in reduced concentrations of glucose released (P < 0.05). The SCF:pullulan:sorbitol:fructose blends also had intermediate to high released monosaccharides as a result of in vitro hydrolytic digestion. All SCF blends resulted in decreased glycemic and insulinemic responses compared with the maltodextrin control (P < 0.05) using a canine model. The addition of pullulan reduced the glycemic response compared with maltodextrin at all concentrations, but only 50:50 SCFsd:pullulan resulted in a reduction of the glycemic response compared with SCFsd alone (P < 0.05). The addition of fructose and sorbitol in the blends had the greatest impact on glycemic and insulinemic responses, even at concentrations as low as 5% of the blends. Overall, SCF and their blends may prove beneficial as components of low glycemic foodstuffs.

MH2c: Characterization of major histocompatibility α-helices - an information criterion approach.

Major histocompatibility proteins share a common overall structure or peptide binding groove. Two binding groove domains, on the same chain for major histocompatibility class I or on two different chains for major histocompatibility class II, contribute to that structure that consists of two α-helices ("wall") and a sheet of eight anti-parallel beta strands ("floor"). Apart from the peptide presented in the groove, the major histocompatibility α-helices play a central role for the interaction with the T cell receptor. This study presents a generalized mathematical approach for the characterization of these helices. We employed polynomials of degree 1 to 7 and splines with 1 to 2 nodes based on polynomials of degree 1 to 7 on the α-helices projected on their principal components. We evaluated all models with a corrected Akaike Information Criterion to determine which model represents the α-helices in the best way without overfitting the data. This method is applicable for both the stationary and the dynamic characterization of α-helices. By deriving differential geometric parameters from these models one obtains a reliable method to characterize and compare α-helices for a broad range of applications. PROGRAM SUMMARY: Program title: MH2c (MH helix curves) Catalogue identifier: AELX_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AELX_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 327 565 No. of bytes in distributed program, including test data, etc.: 17 433 656 Distribution format: tar.gz Programming language: Matlab Computer: Personal computer architectures Operating system: Windows, Linux, Mac (all systems on which Matlab can be installed) RAM: Depends on the trajectory size, min. 1 GB (Matlab) Classification: 2.1, 4.9, 4.14 External routines: Curve Fitting Toolbox and Statistic Toolbox of Matlab Nature of problem: Major histocompatibility (MH) proteins share a similar overall structure. However, identical MH alleles which present different peptides differ by subtle conformational alterations. One hypothesis is that such conformational differences could be another level of T cell regulation. By this software package we present a reliable and systematic way to compare different MH structures to each other. Solution method: We tested several fitting approaches on all available experimental crystal structures of MH to obtain an overall picture of how to describe MH helices. For this purpose we transformed all complexes into the same space and applied splines and polynomials of several degrees to them. To draw a general conclusion which method fits them best we employed the "corrected Akaike Information Criterion". The software is applicable for all kinds of helices of biomolecules. Running time: Depends on the data, for a single stationary structure the runtime should not exceed a few seconds.

Is an intuitive convergence definition of molecular dynamics simulations solely based on the root mean square deviation possible?

Molecular dynamics is a commonly used technique in computational biology. One key issue of each molecular dynamics simulation is: When does this simulation reach equilibrium state? A widely used way to determine this is the visual and intuitive inspection of root mean square deviation (RMSD) plots of the simulation. Although this technique has been criticized several times, it is still often used. Therefore, we present a study proving that this method is not reliable at all. We conducted a survey with participants from the field in which we illustrated different RMSD plots to scientists in the field of molecular dynamics. These plots were randomized and repeated, using a statistical model and different variants of the plots. We show that there is no mutual consent about the point of equilibrium. The decisions are severely biased by different parameters. Therefore, we conclude that scientists should not discuss the equilibration of a molecular dynamics simulation on the basis of a RMSD plot.

Bacterial community composition of the gut microbiota of Cylindroiulus fulviceps (diplopoda) as revealed by molecular fingerprinting and cloning.

Bacterial clone libraries of the gut microbiota of nurtured and starved Cylindroiulus fulviceps specimens displayed the predominance of the phyla Bacteroidetes (55 and 37 %, respectively) and Proteobacteria (40 and 35 %, respectively) and a high similarity to bacteria previously detected in the intestinal tract of termites and beetles, which are known to harbor symbiotic bacteria essential for digestive activity. Bacterial isolates were dominated by Proteobacteria (74 %), followed by members of the phyla Actinobacteria, Firmicutes and Bacteroidetes. PCR-DGGE fingerprints of the gut samples showed that intestinal bacteria were affected by starvation, although the change was not significant.

Graphical user interfaces for molecular dynamics-quo vadis?

In the past years an increasing number of graphical user interfaces for Molecular Dynamics (MD) were presented and concomitantly, more and more Molecular Dynamics studies were published. With the easier application of MD software packages the field runs the risk however, of being pervaded with unreliable results. Therefore, possible benefits and caveats have to be carefully balanced. Here we outline in which respects a broader access of MD via graphical user interfaces may help to increase the usability of Molecular Dynamics simulations while maintaining their quality.

Application of denaturing gradient gel electrophoresis for analysing the gut microflora of Lumbricus rubellus Hoffmeister under different feeding conditions.

The earthworm, Lumbricus rubellus, plays an essential role in soil ecosystems as it affects organic matter decomposition and nutrient cycling. By ingesting a mixture of organic and mineral material, a variety of bacteria and fungi are carried to the intestinal tract of the earthworm. To get a better understanding of the interactions between L. rubellus and the microorganisms ingested, this study tried to reveal if the diet affects the composition of the gut microflora of L. rubellus or if its intestinal tract hosts an indigenous, species-specific microbiota. A feeding experiment with L. rubellus was set up; individuals were collected in the field, transferred to a climate chamber and fed with food sources of different quality (dwarf shrub litter, grass litter or horse dung) for six weeks. DNA was extracted from the guts of the earthworms, as well as from the food sources and the surrounding soil, and further analysed by a molecular fingerprinting method, PCR-DGGE (Polymerase Chain Reaction -- Denaturing Gradient Gel Electrophoresis). We were able to demonstrate that the gut microbiota was strongly influenced by the food source ingested and was considerably different to that of the surrounding soil. Sequencing of dominant bands of the bacterial DGGE fingerprints revealed a strong occurrence of y-Proteobacteria in all gut samples, independent of the food source. A specific microflora in the intestinal tract of L. rubellus, robust against diet changes, could not be found.

Search for exotic baryons in 800 GeV pp-->pXi+/-piX reactions.

We report the results of a high-statistics, sensitive search for narrow baryon resonances decaying to Xi-pi-, Xi-pi+, Xi+pi-, and Xi+pi+. The only resonances observed are the well known Xi0(1530) and Xi0(1530). No evidence is found for the states near 1862 MeV, previously reported by NA49 [Phys. Rev. Lett. 92, 042003 (2003)]. At the 95% confidence level, we find the upper limit for the production of a Gaussian enhancement with sigma=7.6 MeV in the Xi-pi- effective mass spectrum to be 0.3% of the number of observed Xi0(1530)-->Xi-pi+. We find similarly restrictive upper limits for an enhancement at 1862 MeV in the Xi-pi+, Xi+pi-, and Xi+pi+ mass spectra.