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Background: Surgeon visual estimation of shoulder range of motion (ROM) is commonplace in the outpatient office setting and routinely reported in clinical research, but the reliability and accuracy of this practice remain unclear. The purpose of this study is to establish the reliability and accuracy of remote visual estimation of shoulder ROM in healthy volunteers and symptomatic patients among a large group of shoulder surgeons. Our hypothesis is that remote visual estimation would be reliable and accurate compared with the digital goniometer method. Methods: Fifty shoulder surgeon members of the PacWest Shoulder and Elbow Society independently determined the active shoulder forward flexion (FF), internal rotation at 90° abduction (IR90), external rotation at 90° abduction, external rotation at the side , and maximal spinal level reached with internal rotation (IRspine) through visual estimation of video recordings taken from 10 healthy volunteers and 10 symptomatic patients. Variations in measurements were quantified using the interobserver reliability through calculation of the intraclass correlation coefficient. Accuracy was determined through comparison with digital goniometer measurements obtained with an on-screen protractor application using Bland–Altman mean differences and 95% limits of agreement. Results: The interobserver reliability among examiners showed moderate to excellent correlation, with intraclass correlation coefficient ranging from 0.768 to 0.928 for the healthy volunteers and 0.739 to 0.878 for the symptomatic patients. Accuracy was limited, with upper limits of agreement exceeding the established minimal clinically important differences (MCIDs) for FF (20° vs. MCID of 14°) and IR90 (25° vs. 18°) in the healthy volunteers and for FF (33° vs. 16°), external rotation at 90° abduction (21° vs. 18°), and IR90 (31° vs. 20°) in the symptomatic patients. Conclusion: Despite generally high intersurgeon reliability in the visual estimation of shoulder ROM, there was questionable accuracy when compared to digital goniometer measurements,with measurement errors often exceeding established MCID values. Given the potential implications for the clinical response to treatment and the significance of research findings, the adoption of validated instruments to measure ROM and the standardization of examination procedures should be considered.

The frequency and persistence of tidal inundation varies along the coastal terrestrial-aquatic interface, from frequently inundated wetlands to rarely inundated upland forests. This inundation gradient controls soil and sediment biogeochemistry and influence the exchange of soils and sediments from terrestrial to aquatic domains. Although a rich literature exist on studies of the influence of tidal waters on the biogeochemistry of coastal ecosystem soils, few studies have experimentally addressed the reverse question: How do soils (or sediments) from different coastal ecosystems influence the biogeochemistry of the tidal waters that inundate them? To better understand initial responses of coastal waters that flood coastal wetlands and uplands, we conducted short-term laboratory experiments where seawater was amended with sediments and soils collected across regional gradients of inundation exposure (i.e., frequently to rarely inundated) for 14 sites across the Mid-Atlantic, USA. Measured changes in dissolved oxygen and greenhouse gas concentrations were used to calculate gas consumption or production rates occurring during seawater exposure to terrestrial materials. We also measured soil and water physical and chemical properties to explore potential drivers. We observed higher oxygen consumption rates for seawater incubated with soils/sediments from frequently inundated locations and higher carbon dioxide production for seawater incubated with soils from rarely inundated transect locations. Incubations with soil from rarely inundated sites produced the highest global warming potential, primarily driven by carbon dioxide and secondarily by nitrous oxide. We also found environmental drivers of gas rates varied notably between transect locations. Our findings indicate that seawater responses to soil and sediment inputs across coastal terrestrial-aquatic interfaces exhibit some consistent patterns and high intra- and inter-site variability, suggesting potential biogeochemical feedback loops as inundation regimes shift inland.

Abstract Background Little is known about the peopling of the Sahara during the Holocene climatic optimum, when the desert was replaced by a fertile environment. Results In order to investigate the role of the last Green Sahara in the peopling of Africa, we deep-sequence the whole non-repetitive portion of the Y chromosome in 104 males selected as representative of haplogroups which are currently found to the north and to the south of the Sahara. We identify 5,966 mutations, from which we extract 142 informative markers then genotyped in about 8,000 subjects from 145 African, Eurasian and African American populations. We find that the coalescence age of the trans-Saharan haplogroups dates back to the last Green Sahara, while most northern African or sub-Saharan clades expanded locally in the subsequent arid phase. Conclusions Our findings suggest that the Green Sahara promoted human movements and demographic expansions, possibly linked to the adoption of pastoralism. Comparing our results with previously reported genome-wide data, we also find evidence for a sex-biased sub-Saharan contribution to northern Africans, suggesting that historical events such as the trans-Saharan slave trade mainly contributed to the mtDNA and autosomal gene pool, whereas the northern African paternal gene pool was mainly shaped by more ancient events.

Isolated Growth Hormone Deficiency (IGHD) is a rare cause of short stature, treated with the standard regimen of subcutaneous synthetic growth hormone (GH). Patients typically achieve a maximum height velocity in the first year of treatment, which then tapers shortly after treatment is stopped. We report a case of a 9-year-old male who presented with short stature (95th percentile for age and race. In conclusion, this is a case of primary hypopituitarism with differential diagnosis of IGHD vs Idiopathic Short Stature vs Constitutional Growth Delay. This case supports two objectives: Firstly, it highlights the importance of confirmatory genetic testing in patients with suspected, though diagnostically uncertain, IGHD. Secondly, it demonstrates a novel secondary growth pattern with implications for better understanding the tremendous variability of GH treatment response.

Quantifying carbon sequestration by tidal wetlands is important for the management of carbon stocks as part of climate change mitigation. This data publication includes a spatial analysis of carbon accumulation rates in Barnegat and Delaware Bay tidal wetlands. One method calculated long-term organic carbon accumulation rates from radioisotope-dated (Cs-137) sediment cores. The second method measured organic carbon density of sediment accumulated above feldspar marker beds. Carbon accumulation rates generated by these two methods were interpolated across emergent wetland areas, using kriging, with uncertainty estimated by leave-one-out cross validation. This spatial analysis revealed greater carbon sequestration within Delaware, compared to Barnegat Bay. Sequestration rates were found to be more variable within Delaware Bay, and rates were greatest in the tidal freshwater area of the upper bay.

Ildr2, a modifier of diabetes susceptibility in obese mice, is expressed in most organs, including islets and hypothalamus, with reduced levels in livers of diabetes-susceptible B6.DBA mice congenic for a 1.8 Mb interval of Chromosome 1. In hepatoma and neuronal cells, ILDR2 is primarily located in the endoplasmic reticulum membrane. We used adenovirus vectors that express shRNA or are driven by the CMV promoter, respectively, to knockdown or overexpress Ildr2 in livers of wild type and ob/ob mice. Livers in knockdown mice were steatotic, with increased hepatic and circulating triglycerides and total cholesterol. Increased circulating VLDL, without reduction in triglyceride clearance suggests an effect of reduced hepatic ILDR2 on hepatic cholesterol clearance. In animals that overexpress Ildr2, hepatic triglyceride and total cholesterol levels were reduced, and strikingly so in ob/ob mice. There were no significant changes in body weight, energy expenditure or glucose/insulin homeostasis in knockdown or overexpressing mice. Knockdown mice showed reduced expression of genes mediating synthesis and oxidation of hepatic lipids, suggesting secondary suppression in response to increased hepatic lipid content. In Ildr2-overexpressing ob/ob mice, in association with reduced liver fat content, levels of transcripts related to neutral lipid synthesis and cholesterol were increased, suggesting "relief" of the secondary suppression imposed by lipid accumulation. Considering the fixed location of ILDR2 in the endoplasmic reticulum, we investigated the possible participation of ILDR2 in ER stress responses. In general, Ildr2 overexpression was associated with increases, and knockdown with decreases in levels of expression of molecular components of canonical ER stress pathways. We conclude that manipulation of Ildr2 expression in liver affects both lipid homeostasis and ER stress pathways. Given these reciprocal interactions, and the relatively extended time-course over which these studies were conducted, we cannot assign causal primacy to either the effects on hepatic lipid homeostasis or ER stress responses.

In 404 Lep(ob/ob) F2 progeny of a C57BL/6J (B6) x DBA/2J (DBA) intercross, we mapped a DBA-related quantitative trait locus (QTL) to distal Chr1 at 169.6 Mb, centered about D1Mit110, for diabetes-related phenotypes that included blood glucose, HbA1c, and pancreatic islet histology. The interval was refined to 1.8 Mb in a series of B6.DBA congenic/subcongenic lines also segregating for Lep(ob). The phenotypes of B6.DBA congenic mice include reduced beta-cell replication rates accompanied by reduced beta-cell mass, reduced insulin/glucose ratio in blood, reduced glucose tolerance, and persistent mild hypoinsulinemic hyperglycemia. Nucleotide sequence and expression analysis of 14 genes in this interval identified a predicted gene that we have designated "Lisch-like" (Ll) as the most likely candidate. The gene spans 62.7 kb on Chr1qH2.3, encoding a 10-exon, 646-amino acid polypeptide, homologous to Lsr on Chr7qB1 and to Ildr1 on Chr16qB3. The largest isoform of Ll is predicted to be a transmembrane molecule with an immunoglobulin-like extracellular domain and a serine/threonine-rich intracellular domain that contains a 14-3-3 binding domain. Morpholino knockdown of the zebrafish paralog of Ll resulted in a generalized delay in endodermal development in the gut region and dispersion of insulin-positive cells. Mice segregating for an ENU-induced null allele of Ll have phenotypes comparable to the B.D congenic lines. The human ortholog, C1orf32, is in the middle of a 30-Mb region of Chr1q23-25 that has been repeatedly associated with type 2 diabetes.

Background and Purpose: Glucocorticoids are powerful anti‐inflammatory drugs, but are associated with many side‐effects. Topical application in atopic dermatitis leads to skin thinning, metabolic changes, and adrenal suppression. 5α‐Tetrahydrocorticosterone (5αTHB) is a potential selective anti‐inflammatory with reduced metabolic effects. Here, the efficacy and side‐effect profile of 5αTHB were compared with hydrocortisone in preclinical models of irritant dermatitis. Experimental Approach: Acute irritant dermatitis was invoked in ear skin of male C57BL/6 mice with a single topical application of croton oil. Inflammation was assessed as oedema via ear weight following treatment with 5αTHB and hydrocortisone. Side‐effects of 5αTHB and hydrocortisone were assessed following chronic topical steroid treatment (28 days) to non‐irritated skin. Skin thinning was quantified longitudinally by caliper measurements and summarily by qPCR for transcripts for genes involved in extracellular matrix homeostasis; systemic effects of topical steroid administration also were assessed. Clearance of 5αTHB and hydrocortisone were measured following intravenous and oral administration. Key Results: 5αTHB suppressed ear swelling in mice, with ED50 similar to hydrocortisone (23 μg vs. 13 μg). Chronic application of 5αTHB did not cause skin thinning, adrenal atrophy, weight loss, thymic involution, or raised insulin levels, all of which were observed with topical hydrocortisone. Transcripts for genes involved in collagen synthesis and stability were adversely affected by all doses of hydrocortisone, but only by the highest dose of 5αTHB (8× ED50). 5αTHB was rapidly cleared from the systemic circulation. Conclusions and Implications: Topical 5αTHB has potential to treat inflammatory skin conditions, particularly in areas of delicate skin. [ABSTRACT FROM AUTHOR]

Creativity is increasingly understood as a social phenomenon, especially in organizational contexts. This article offers a conceptual framework for social creativity that integrates perspectives from published literature. The foundational questions that structured the literature review are twofold. First, because both individuals and entities, such as teams, can be agents of creativity, who or what creates? Second, through what sites of action or contexts does creative engagement by individuals, groups, and organizations occur? An integrative review of the literature reveals that the engagement occurs in individuals, in individuals interacting, in group work, and in complex multilevel systems. A concept map is used to represent the literature in this domain. This is then discussed with reference to the representative authors in each of the identified sectors. A set of names for the outcomes of the creative process is suggested, including individually generated creative outcomes, socially influenced creative outcomes, socially constructed creative outcomes, and socially generated creative outcomes. [ABSTRACT FROM AUTHOR]

1. The vgf gene encodes a neuropeptide precursor with a restricted pattern of expression that is limited to a subset of neurons in the central and peripheral nervous systems and to specific populations of endocrine cells in the adenohypophysis, adrenal medulla, gastrointestinal tract, and pancreas. In responsive neurons, vgf transcription is upregulated by neurotrophins, the basis for the original identification of VGF as nerve growth factor- (NGF) inducible in PC12 cells (A. Levi, J. D. Eldridge, and B. M. Paterson, Science 229:393–395, 1985).2. In this review, we shall summarize data concerning the transcriptional regulation of vgf in vitro, the structural organization of the vgf promoter as well as the transcription factors which regulate its activity.3. On the basis of in situ hybridization and immunohistochemical studies, the in vivo tissue-specific expression of VGF during differentiation and in the adult will be summarized.4. Parallel biochemical data will be reviewed, addressing the proteolytical processing of the pro-VGF precursor within the secretory compartment of neuroendocrine cells.5. Finally, analysis of the phenotype of VGF knockout mice will be discussed, implying a nonredundant role of VGF products in the regulation of energy storage and expenditure. [ABSTRACT FROM AUTHOR]

The recent Chandos House meeting of the Alport Variant Collaborative extended the indications for screening for pathogenic variants in the COL4A5, COL4A3 and COL4A4 genes beyond the classical Alport phenotype (haematuria, renal failure; family history of haematuria or renal failure) to include persistent proteinuria, steroid-resistant nephrotic syndrome, focal and segmental glomerulosclerosis (FSGS), familial IgA glomerulonephritis and end-stage kidney failure without an obvious cause. The meeting refined the ACMG criteria for variant assessment for the Alport genes (COL4A3-5). It identified 'mutational hotspots' (PM1) in the collagen IV α5, α3 and α4 chains including position 1 Glycine residues in the Gly-X-Y repeats in the intermediate collagenous domains; and Cysteine residues in the carboxy non-collagenous domain (PP3). It considered that 'well-established' functional assays (PS3, BS3) were still mainly research tools but sequencing and minigene assays were commonly used to confirm splicing variants. It was not possible to define the Minor Allele Frequency (MAF) threshold above which variants were considered Benign (BA1, BS1), because of the different modes of inheritances of Alport syndrome, and the occurrence of hypomorphic variants (often Glycine adjacent to a non-collagenous interruption) and local founder effects. Heterozygous COL4A3 and COL4A4 variants were common 'incidental' findings also present in normal reference databases. The recognition and interpretation of hypomorphic variants in the COL4A3-COL4A5 genes remains a challenge., (© 2021. The Author(s).)