A house is not a home: a network model perspective on the dynamics between subjective quality of living conditions, social support, and mental health of refugees and asylum seekers.

BACKGROUND: Providing adequate living conditions for forcibly displaced people represents a significant challenge for host countries such as Germany. This study explores refugee mental health's reciprocal, dynamic relationship with post-migration living conditions and social support. METHODS: The study sample included 325 Arabic- or Farsi-speaking asylum seekers and refugees residing in Germany since 2014 and seeking mental health treatment. Associations between reported symptoms of post-traumatic stress and depression and the subjective quality of living conditions and perceived social support were analyzed using a two-level approach including multiple linear regression and network analyses. RESULTS: Post-migration quality of living conditions and perceived social support were significantly associated with negative mental health outcomes on both levels. In the network, both post-migration factors were negatively connected with overlapping symptoms of psychiatric disorders, representing potential target symptoms for psychological treatment. CONCLUSION: Post-migration quality of living conditions and social support are important factors for refugee mental health and should be targeted by various actors fostering mental well-being and integration.

Adaptor bypass mutations of Bacillus subtilis†spx suggest a mechanism for YjbH-enhanced proteolysis of the regulator Spx by ClpXP.

The global regulator, Spx, is under proteolytic control exerted by the adaptor YjbH and ATP-dependent protease ClpXP in Bacillus subtilis. While YjbH is observed to bind the Spx C-terminus, YjbH shows little affinity for ClpXP, indicating adaptor activity that does not operate by tethering. Chimeric proteins derived from B. subtilis AbrB and the Spx C-terminus showed that a 28-residue C-terminal section of Spx (AbrB28), but not the last 12 or 16 residues (AbrB12, AbrB16), was required for YjbH interaction and for ClpXP proteolysis, although the rate of AbrB28 proteolysis was not affected by YjbH addition. The result suggested that the YjbH-targeted 28 residue segment of the Spx C-terminus bears a ClpXP-recognition element(s) that is hidden in the intact Spx protein. Residue substitutions in the conserved helix α6 of the C-terminal region generated Spx substrates that were degraded by ClpXP at accelerated rates compared to wild-type Spx, and showed reduced dependency on the YjbH activity. The residue substitutions also weakened the interaction between Spx and YjbH. The results suggest a model in which YjbH, through interaction with residues of helix α6, exposes the C-terminus of Spx for recognition and proteolysis by ClpXP.

A phase I, single-center, open-label study to investigate the absorption, distribution, metabolism and excretion of encorafenib following a single oral dose of 100 mg [14 C] encorafenib in healthy male subjects.

Encorafenib is a novel kinase inhibitor of BRAF V600E as well as wild-type BRAF and CRAF and has received approval, in combination with binimetinib, to treat BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma or in combination with cetuximab to treat BRAF V600E mutation-positive colorectal cancer. The absorption, distribution, metabolism and excretion (ADME) of encorafenib was studied by administering [14 C] encorafenib (100 mg containing 90 µCi of radiolabeled material) to 4 healthy male subjects (NCT01436656). Following a single oral 100-mg dose of [14 C] encorafenib to healthy male subjects, the overall recovery of radioactivity in the excreta was ≥93.9% in all four subjects, indicating that good mass balance was achieved. An equal mean of 47.2% for the radioactivity dose was eliminated in the feces and urine. The percentage of the dose eliminated in the feces (5.0%) and urine (1.8%) as unchanged encorafenib was minor. Metabolism was found to be the major clearance pathway (~88% of the recovered radioactive dose) for encorafenib in humans and is predominantly mediated through N-dealkylation of the isopropyl carbamic acid methyl ester to form the primary phase 1 direct metabolite M42.5 (LHY746). Oral absorption was estimated from the radioactive dose recovered in the urine (47.2%) and the total radioactive dose recovered in the feces as metabolites (39%). Based on these values and the assumptions that encorafenib and its metabolites are stable in feces, the fraction of oral absorption was estimated to be at least ~86%.

Impact of posaconazole and diltiazem on pharmacokinetics of encorafenib, a BRAF V600 kinase inhibitor for melanoma and colorectal cancer with BRAF mutations.

Encorafenib is a potent and selective ATP competitive inhibitor of BRAF V600-mutant kinase approved for patients with BRAF-mutant melanoma and colorectal cancer. Encorafenib is mainly metabolized by cytochrome P450 (CYP) 3A4 in vitro and may be susceptible to drug-drug interactions when co-administered with CYP3A inhibitors or inducers. The primary objective was to assess the impact of the strong CYP3A inhibitor posaconazole (part 1) and the moderate CYP3A and P-gp inhibitor diltiazem (part 2) on encorafenib pharmacokinetics in healthy volunteers following a single 50-mg dose. A total of 32 participants were enrolled (16 each in parts 1 and 2). The area under the curve extrapolated to infinity (AUCinf ) and maximum plasma concentration (Cmax ) geometric mean for encorafenib increased by 183% and 68.4%, respectively, when co-administered with posaconazole. Apparent encorafenib clearance decreased from 26.0 to 9.2 L/h when coadministered with posaconazole, and plasma terminal half-life (t½ ) of encorafenib increased from 4.3 to 7.3 h. The AUCinf and Cmax geometric mean for encorafenib increased by 83.0% and 44.7%, respectively, when co-administered with diltiazem. Similarly, the apparent encorafenib clearance decreased from 29.0 to 16.0 L/h when co-administered with diltiazem, and plasma t½ of encorafenib increased from 6.6 to 7.9 h. There were no deaths, serious adverse events (AEs), or patient discontinuations due to AEs in parts 1 or 2. The most frequently reported treatment-related AEs were erythema (n = 14; 88%) and headache (n = 11; 69%) in part 1 and headache (n = 7; 44%) in part 2. The results of this study indicate that co-administration of encorafenib with strong or moderate CYP3A4 inhibitors should be avoided.

Preoperative Variables Associated with Surgical Outcome for the Correction of Exodeviation.

The success rate of exodeviation surgery in existing literature has been shown to be variable. This study sought to determine the success rate of surgery for exodeviation in Atlantic Canada and determine variables associated with surgical outcome. A retrospective chart review was performed, considering patients who had been assessed and surgically treated for exodeviation at the IWK Health Centre between 2011-2018. This study included 176 subjects, aged 1-75 years. Preoperative variables were compared between subjects with successful versus unsuccessful surgical outcomes, using the chi square, Fischer's exact test and binary logistic regression. A success rate of 43% was determined. Smaller preoperative deviation size at near and distance fixation, as well as the basic type classification were associated with successful operative outcome. Left eye acuity showed a statistically significant association with surgical success outcome. In conclusion, these findings compliment those of previous groups, suggesting exodeviation surgery outcome is variable. Our results add to a growing list of variables implicated in outcomes for these subjects. A smaller deviation preoperatively was associated with success in existing data and in this study, and these findings may suggest a potential role for basic subtype into future exodeviation literature.

A Comparison of the Maximum Deviation Measured in Intermittent Exotropia Using Various Clinical Conditions.

Background and Purpose: In the Intermittent Exotropia (IXT) population determining the largest deviation for surgical planning has been suggested for desired surgical outcomes Throughout the literature, the clinical tests that elicit largest deviation remains unclear. Patients and Methods: 24 IXT subjects were measured at the customary 1/3 m and 6 m fixation, with +3D lenses at 1/3 m, at far distance (20 m), 1/3 m and 6 m after PMO, with +3D lenses at 1/3 m after PMO, and far distance (20 m) after PMO, in an attempt to determine which of these conditions elicit the largest exodeviation. Results: At near, all subjects had clinically significant increases with at least one condition. In 87.5%, clinical and statistical increases occurred with +3D lenses and/or with +3D after PMO. There was no statistically significant difference between those conditions. At distance, 16.7% demonstrated clinically significant increases. Two increased at 20 m and 6 m after PMO similarly, and all increased at 20 m fixation with or without PMO, without a significant difference between measurements at 20 m and 20 m after PMO. All increases at 20m, with and without PMO were statistically significant. Conclusion: This research indicates that measurements with +3D lenses and at 20 m are the most efficient for the maximum deviation in IXT patients.

Enhanced capture of bacteria and endotoxin by antimicrobial WLBU2 peptide tethered on polyethylene oxide spacers.

Severe sepsis is a life threatening immune response that may be caused by endotoxins (lipopolysaccharides) in circulating bacterial cell wall fragments. Hemoperfusion through a sorbent column coated with the antimicrobial peptide polymyxin B (PMB) is a promising treatment for sepsis. However, PMB is cytotoxic and neurotoxic, and is a membrane disruptor that may fragment endotoxin vesicles. In addition, the blood is not protected from nonspecific interactions with the synthetic surface of the solid support. These effects may be responsible for the variety of undesirable clinical outcomes, including nonspecific adsorption of proteins, blood cell damage, platelet activation, and a lack of clear evidence of efficacy of the current hemoperfusion products. An alternative endotoxin-binding agent is WLBU2, a synthetic cationic amphiphilic peptide that exhibits better selectivity for bacterial cell membranes and reduced host cell cytotoxicity. Tethering the peptide at the periphery of a hydrophilic polyethylene oxide (PEO) brush should also mask the underlying surface, preventing cell and protein adsorption, and is expected to increase the solvent accessibility and molecular mobility of the tethered peptides. WLBU2 tethered on pendant PEO chains exhibited significantly greater capture of intact bacterial cells and endotoxin than surface-immobilized WLBU2. Tethered WLBU2 also captured amounts of endotoxin comparable to PMB. These results suggest that PEO-tethered WLBU2 coatings may be safer and more effective than the state-of-the-art PMB-based technology.

Exploring the 3D molecular architecture of Escherichia coli type 1 pili.

An integrated approach combining information gained by Fourier transformation, linear Markham superposition (real space) and mass-per-length measurement by scanning transmission electron microscopy was used to analyze the helical structure of the rod-like type 1 pili expressed by uropathogenic Escherichia coli strain W3110. The 3D reconstruction calculated from the experimental data showed the pili to be 6.9nm wide, right-handed helical tubes with a 19.31(+/-0.34)nm long helical repeat comprising 27 FimA monomers associated head-to-tail in eight turns of the genetic one-start helix. Adjacent turns of the genetic helix are connected via three binding sites making the pilus rod rather stiff. In situ immuno-electron microscopy experiments showed the minor subunit (FimH) mediating pilus adhesion to bladder epithelial cells to be the distal protein of the pilus tip, which had a spring-like appearance at higher magnification. The subunits FimG and FimF connect FimH to the FimA rod, the sequential orientation being FimA-FimF-FimG-FimH. The electron density map calculated at 18A resolution from an atomic model of the pilus rod (built using the pilin domain FimH together with the G1 strand of FimC as a template for FimA and applying the optimal helical parameters determined to the head-to-tail interaction model for pilus assembly) was practically identical with that of the actual 3D reconstruction.

Family System Interventions for Families of Children with Autism Spectrum Disorder.

The increasing prevalence of autism spectrum disorder (ASD), the severity of impairment, and its impact on systems are a source of ever-growing concern. This article (1) describes briefly the spectrum of ASD and its treatments; (2) discusses the impact that ASD has on the individual, family, and external environment; and (3) discusses the application of family therapy principles in order to meet the needs of children and families affected by ASD. Illustrative case examples are presented.

The method of treatment cessation and recurrence rate of amblyopia.

BACKGROUND AND PURPOSE: To date, much of the research regarding amblyopia has been focused on which therapeutic modality is the most efficacious in amblyopia management. Unfortunately, there is a lack of research into which method of treatment cessation is the most appropriate once therapy has been completed. The purpose of this study is to investigate if the cessation method affects the recurrence rate of amblyopia. METHODS: This study was a prospective randomized clinical trial of 20 subjects who were wearing full-time occlusion and were at the end point of their therapy. The subjects were randomized into one of two groups: abrupt cessation or therapy tapering. All subjects were followed for 3 consecutive 4-week intervals, for a total of 12 weeks, to assess the short-term recurrence rate of amblyopia. Subjects who were in the tapered group had their occlusion reduced from full-time occlusion (all waking hours minus one) to 50% of waking hours at study enrollment (i.e., from 12 hours/day to 6 hours per day); occlusion was reduced by an additional 50% at the first 4-week study visit (i.e., from 6 hours/day to 3 hours), with occlusion being discontinued completely at the week 8 visit. All subjects who were in the abrupt cessation group had their full-time occlusion discontinued completely at the start of the study (i.e., from 12 hours/day to none). Additional assessments were also conducted at week 26 and week 52 post-therapy cessation to determine the longer term amblyopia regression rate. For the purposes of this study, recurrence was defined as a 0.2 (10 letters) or more logarithm of the minimum angle of resolution (logMAR) loss of visual acuity. RESULTS: A recurrence of amblyopia occurred in 4 of 17 (24%; CI 9%-47%) participants completing the study by the week 52 study end point. There were 2 subjects from each treatment group who demonstrated a study protocol-defined recurrence. CONCLUSION: There was a 24% risk of amblyopia recurrence if therapy was discontinued abruptly or tapered in 8 weeks. In this small sample, the assigned cessation method did not affect the rate of amblyopia recurrence. It is recognized that the smaller sample size in our study prevents us from making definitive conclusions on the potential role that abrupt cessation has on the regression rate of amblyopia. The sample size was too small to reach an acceptable level of statistical power; therefore the generalizability of the findings to the broad population of all patients with amblyopia requires continuing research. This study therefore could be considered as a pilot study.

Stability of visual acuity after the cessation of amblyopia treatment: review of the literature.

INTRODUCTION AND PURPOSE: The treatment of amblyopia in children is frequently discussed in the literature. Less attention, however, has been given to the durability of the visual acuity results attained with therapy. The objective of this review is to conduct an in-depth analysis of the existing literature, on the stability of visual acuity following cessation of amblyopia treatment, and to identify any gaps in the literature, which could guide future investigations. RESULTS: There did not appear to be any one consistent risk factor affecting the stability of vision after cessation of amblyopia treatment. Most of the reviewed studies varied with respect to lengths of follow-up visits, patient population, and method of visual acuity assessment. There was also a generalized lack of standardization of visual acuity measurements in these previous investigations. Only one of the studies analyzed was a prospective design. CONCLUSION: The area of study in amblyopia is fraught with contradictions. It is obvious from this review that there exists uncertainty regarding the recurrence of amblyopia following treatment. Previous studies have failed to identify any common, predictive, influencing factors necessary for the maintenance of visual acuity after cessation of therapy. Also lacking is discussion on the potential role that therapy tapering plays in the recurrence of amblyopia following the cessation of treatment.

Controversy in amblyopia management.

BACKGROUND AND PURPOSE: Much has been written about amblyopia treatment. However, there is no consensus on the most efficacious therapeutic modality for amblyopia. The intensity of therapy needed to maximize visual acuity is also widely debated. The diversity of opinions emphasizes that the optimum treatment for amblyopia is unknown. Part of the uncertainty stems from the lack of standardization in the management of amblyopia. The objective of this paper is to conduct an in-depth review of the literature in an attempt to clarify the amblyopia treatment conundrum. CONCLUSIONS: The treatment of amblyopia in children is frequently discussed in the literature. It is obvious from the literature that there is the need for prospective studies with consistent controls, clear definitions of what constitutes successful therapy endpoints, and standardization of testing procedures.