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© 2020 John Wiley & Sons, Ltd.The therapeutic alliance is central to couples' therapy success. The current study examined associations between couples' initial agreement and causal attributions of the presenting problem and changes in the therapeutic alliance. To test study hypotheses, 85 couples were recruited from a university training clinic focused on couple and family therapy. Couples completed an intake questionnaire concerning their attribution of the presenting problem, either as systemic or individual, and therapeutic alliance was assessed at the end of sessions 2-8. A dyadic multilevel model revealed that a disagreement in the couple's attributions of the problem (with one viewing it as systemic, the other as individual) was associated with a larger initial discrepancy in the couple's therapeutic alliance, as well as a decline in the discrepancy over time. Findings were discussed in the context of systemic family theory, with implications for improving assessment, treatment, and psychoeducation aimed toward couples in distress. © 2020 American Association for Marriage and Family Therapy.The examination of the complex cell biology of the human malaria parasite Plasmodium falciparum usually relies on the time-consuming generation of transgenic parasites. Here, metabolic labeling and click chemistry are employed as a fast transfection-independent method for the microscopic examination of protein S-palmitoylation, an important post-translational modification during the asexual intraerythrocytic replication of P. falciparum. Applying various microscopy approaches such as confocal, single-molecule switching, and electron microscopy, differences in the extent of labeling within the different asexual developmental stages of P. falciparum and the host erythrocytes over time are observed. © 2020 The Authors. BioEssays published by WILEY Periodicals, Inc.Diagnostics is the key in screening and treatment of cancer. As an emerging tool in precision medicine, metabolic analysis detects end products of pathways, and thus is more distal than proteomic/genetic analysis. However, metabolic analysis is far from ideal in clinical diagnosis due to the sample complexity and metabolite abundance in patient specimens. A further challenge is real-time and accurate tracking of treatment effect, e.g., radiotherapy. Here, Pd-Au synthetic alloys are reported for mass-spectrometry-based metabolic fingerprinting and analysis, toward medulloblastoma diagnosis and radiotherapy evaluation. A core-shell structure is designed using magnetic core particles to support Pd-Au alloys on the surface. Optimized synthetic alloys enhance the laser desorption/ionization efficacy and achieve direct detection of 100 nL of biofluids in seconds. Medulloblastoma patients are differentiated from healthy controls with average diagnostic sensitivity of 94.0%, specificity of 85.7%, and accuracy of 89.9%, by machine learning of metabolic fingerprinting. Furthermore, the radiotherapy process of patients is monitored and a preliminary panel of serum metabolite biomarkers is identified with gradual changes. This work will lead to the application-driven development of novel materials with tailored structural design and establishment of new protocols for precision medicine in near future. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The mechanisms by which immunoglobulin (Ig)G can modulate immunity have been investigated over the past few decades. In the past three years, some studies have demonstrated that IgG can play a pivotal role in mediating complex interactions that result in functional lymphocyte modulation during maturation in self or offspring primary lymphoid organs. This effect appears to be dependent on the IgG repertoire in the absence of the influence of antigens and the functionality of diverse cell populations, including B, αβT (CD4 T and CD8 T), invariant natural killer T and γδT cells, in mice and humans. Based on the literature, especially on findings resulting from the therapeutic use of purified IgG (intravenous Ig) and recent pieces of evidence obtained by my group, the "hooks without bait" theory is described here to guide the future development of therapies for specific immune regulation. © 2020 Australian and New Zealand Society for Immunology Inc.We report a case of a newly recognized primary immunodeficiency due to biallelic mutations in CARMIL2 manifesting as an actinic prurigo-like photodermatitis, allergic diathesis and recurrent infections in a child. We present this case to highlight a rare phenotype seen in this T-cell immunodeficiency and provide an overview of other dermatologic manifestations among published reports of this condition. © 2020 Wiley Periodicals, LLC.BACKGROUND The Quality Assurance and Laboratory Standards Committee of the American Society for Veterinary Clinical Pathology and the guidelines of the Clinical and Laboratory Standards Institute provide a framework for establishing reference intervals of physiological parameters in reputedly healthy individuals, humans, and terrestrial animals, respectively. This framework was applied for the first time to the Pacific cupped oyster, Crassostrea gigas. Reference intervals (RIs) would, first, be of interest for research purposes, including pathophysiology studies. RI determination is the first step before considering the use of RIs for field applications by farmers and marine shellfish health services. OBJECTIVES The purpose of this study was to propose reference intervals of feeding and respiration parameters, the clearance rate (CR), and oxygen consumption rate (OCR), in a reference population of hatchery-reared diploid Pacific oysters. METHODS A de novo, a priori, and a direct approach were applied. The reference values acquired from 214 healthy diploid C gigas (total wet weight 6.23-83.64 g, DW 0.06-1.87 g) were analyzed using a non-parametric statistical method. RESULTS Reference intervals were proposed for CR, 0.7-4.1 L/h/g dry flesh weight (DW), and OCR, 0.4-1.3 mg O2/h/g DW in C gigas in a seawater at a temperature of 22℃ and a salinity of 32‰. Animals were fed 30-40 cells/µL of Isochrysis affinis galbana. The confidence intervals at 90% of the upper limits of the two parameters were found to be higher than those of the Clinical and Laboratory Standards Institute (CLSI) recommendations. CONCLUSIONS Obtaining reference intervals is an important step and must be completed by proposed decision limits to facilitate the early detection of health disorders in C gigas. © 2020 American Society for Veterinary Clinical Pathology.Resveratrol is a natural phytoestrogen produced by plants to protect themselves from injury, UV irradiation, and fungal attack. The main active structure is E-resveratrol, which has many pharmacological activities. As the structure of resveratrol is similar to the natural estrogen 17β-estradiol and the synthetic estrogen E-diethylstilbestrol, resveratrol is used in reducing the incidence of breast cancer. NCB-0846 in vivo However, the therapeutic application of resveratrol is limited due to its low bioavailability. To improve its bioavailability and pharmacological activity, some resveratrol derivatives have been designed and synthesized by substitutions of methoxy, hydroxyl, and other functional groups or heterocyclic esterification either on the "A" or "B" ring, and double bonds were replaced by imine bonds and isometric heterocycles such as naphthyl and imidazole, or synthetic resveratrol oligomers. The structures, synthetic routes, and evaluation of the biological activities of these compounds are discussed. These are aimed at providing some references for the study of resveratrol derivatives in anti-breast cancer treatment. © 2020 Deutsche Pharmazeutische Gesellschaft.OBJECTIVE To describe low-field MRI findings associated with lumbosacral foraminal stenosis and radiculopathy and correlate these with clinical signs. STUDY DESIGN Retrospective study. ANIMALS Client-owned dogs (n = 240) that underwent a clinical examination and standardized MRI protocol of the lumbosacral junction. METHODS Medical records of dogs with degenerative lumbosacral stenosis with neurological clinical evaluation and MRI of the lumbosacral junction were used to describe imaging pathologies and relate them to clinical status. RESULTS In total, 480 L7 neuroforamina were evaluated. A loss of foraminal fat signal was identified in 364 of 480 neuroforamina of which 87.9% (n=320) showed also concurrent nerve root changes. Magnetic resonance imaging features of L7 radiculopathy included nerve root enlargement and hyperintensity to surrounding connective tissue in dorsal oblique gradient echo short time inversion recovery sequences and specific changes in shape, size, or position of the nerve root in transverse T1-weighted sequences. Radiculopathy was noted as a consequence of either circumferential (entrapment) or focal (impingement) foraminal stenosis. Lateral vertebral spondylotic and intervertebral facet joint changes were the most common underlying spinal and neuroforaminal pathologies. Clinical signs were present in the ipsilateral hind leg in 85% (n = 65) of dogs with unilateral lumbosacral imaging findings. CONCLUSION A loss of foraminal fat signal was likely to be associated with L7 radiculopathy and foraminal stenosis. Unilateral lesions were generally associated with clinical signs on the ipsilateral limb. CLINICAL SIGNIFICANCE Loss of foraminal fat signal revealed by low-field MRI should prompt the assessment of concurrent radiculopathy and underlying stenosis, and in coherence with clinical findings, when is combined with clinical findings, improves the diagnosis of lumbosacral foraminal stenosis. © 2020 The American College of Veterinary Surgeons.Prolonged serum half-life is required for the efficacy of most protein therapeutics. One strategy for half-life extension is to exploit the long circulating half-life of serum albumin by incorporating a binding moiety that recognizes albumin. Here, we describe camelid single-domain antibodies (VH Hs) that bind the serum albumins of multiple species with moderate to high affinity at both neutral and endosomal pH and significantly extend the serum half-lives of multiple proteins in rats from minutes to days. We serendipitously identified an additional VH H (M75) that is naturally pH-sensitive at endosomal pH, binding affinity for human serum albumin (HSA) was dramatically weakened and binding to rat serum albumin (RSA) was undetectable. Domain mapping revealed that M75 bound to HSA domain 1 and 2. Moreover, alanine scanning of HSA His residues suggested a critical role for His247, located in HSA domain 2, in M75 binding and its pH dependence. Isothermal titration calorimetry experiments were suggestive of proton-linked binding of M75 to HSA, with differing binding enthalpies observed for full-length HSA and an HSA domain 1-domain 2 fusion protein in which surface-exposed His residues were substituted with Ala. M75 conferred moderate half-life extension in rats, from minutes to hours, likely due to rapid dissociation from RSA during FcRn-mediated endosomal recycling in tandem with albumin conformational changes induced by M75 binding that prevented interaction with FcRn. Humanized VH Hs maintained in vivo half-life extension capabilities. These VH Hs represent a new set of tools for extending protein therapeutic half-life and one (M75) demonstrates a unique pH-sensitive binding interaction that can be exploited to achieve modest in vivo half-life. © 2020 Her Majesty the Queen in Right of Canada The FASEB Journal © 2020 John Wiley & Sons Ltd.