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Objective: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post‐RI and compare effectiveness of common management strategies. Design: Retrospective, multicentre and observational study. Patients: Adult patients with Graves' disease treated with RI with 12 months' follow‐up. Measurements: Euthyroidism was defined as both serum thyrotropin (thyroid‐stimulating hormone [TSH]) and free thyroxine (FT4) within their reference ranges or, when only one was available, it was within its reference range; hypothyroidism as TSH ≥ 10 mU/L, or subnormal FT4 regardless of TSH; hyperthyroidism as TSH below and FT4 above their reference ranges; dysthyroidism as the sum of hypo‐ and hyperthyroidism; subclinical hypothyroidism as normal FT4 and TSH between the upper limit of normal and <10 mU/L; and subclinical hyperthyroidism as low TSH and normal FT4. Results: Of 812 patients studied post‐RI, hypothyroidism occurred in 80.7% and hyperthyroidism in 48.6% of patients. Three principal post‐RI management strategies were employed: (a) antithyroid drugs alone, (b) levothyroxine alone, and (c) combination of the two. Differences among these were small. Adherence to national guidelines regarding monitoring thyroid function in the first 6 months was low (21.4%–28.7%). No negative outcomes (new‐onset/exacerbation of Graves' orbitopathy, weight gain, and cardiovascular events) were associated with dysthyroidism. There were significant differences in demographics, clinical practice, and thyroid status postradioiodine between centres. Conclusions: Dysthyroidism in the 12 months post‐RI was common. Differences between post‐RI strategies were small, suggesting these interventions alone are unlikely to address the high frequency of dysthyroidism. [ABSTRACT FROM AUTHOR]

Ras homologous guanosine triphosphatases (RhoGTPases) control several cellular functions, including cytoskeletal actin remodeling and cell migration. Their activities are downregulated by GTPase‐activating proteins (GAPs). Although RhoGTPases are implicated in bone remodeling and osteoclast and osteoblast function, their significance in human bone health and disease remains elusive. Here, we report defective RhoGTPase regulation as a cause of severe, early‐onset, autosomal‐dominant skeletal fragility in a three‐generation Finnish family. Affected individuals (n = 13) presented with multiple low‐energy peripheral and vertebral fractures despite normal bone mineral density (BMD). Bone histomorphometry suggested reduced bone volume, low surface area covered by osteoblasts and osteoclasts, and low bone turnover. Exome sequencing identified a novel heterozygous missense variant c.652G>A (p.G218R) in ARHGAP25, encoding a GAP for Rho‐family GTPase Rac1. Variants in the ARHGAP25 5′ untranslated region (UTR) also associated with BMD and fracture risk in the general population, across multiple genomewide association study (GWAS) meta‐analyses (lead variant rs10048745). ARHGAP25 messenger RNA (mRNA) was expressed in macrophage colony‐stimulating factor (M‐CSF)–stimulated human monocytes and mouse osteoblasts, indicating a possible role for ARHGAP25 in osteoclast and osteoblast differentiation and activity. Studies on subject‐derived osteoclasts from peripheral blood mononuclear cells did not reveal robust defects in mature osteoclast formation or resorptive activity. However, analysis of osteosarcoma cells overexpressing the ARHGAP25 G218R‐mutant, combined with structural modeling, confirmed that the mutant protein had decreased GAP‐activity against Rac1, resulting in elevated Rac1 activity, increased cell spreading, and membrane ruffling. Our findings indicate that mutated ARHGAP25 causes aberrant Rac1 function and consequently abnormal bone metabolism, highlighting the importance of RhoGAP signaling in bone metabolism in familial forms of skeletal fragility and in the general population, and expanding our understanding of the molecular pathways underlying skeletal fragility. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Background: Nonhuman primates (NHPs) exhibit age‐related cognitive impairments, synaptic loss, and accumulation of tau and amyloid in dorsolateral prefrontal cortex (dlPFC) and entorhinal cortex (ERC). In a cohort of NHPs with longitudinal cognitive data, we perform SV2A ([11C]UCB‐J), amyloid ([11C]PIB), and tau ([18F]MK‐6240) PET. We aim to 1) investigate in vivo relationships and age‐related change in amyloid, tau, and synaptic density (SV2A) and 2) to relate these to cognition in NHPs. Method: Middle‐aged (n = 5, 10.4 ± 0.5 y.o.) and old (n = 17, 19.9 ± 2.7 y.o.) NHPs were dynamically PET scanned (FOCUS 220) following i.v. injection of each of [18F]MK‐6240 (173 ± 12 MBq), [ 11C]PIB (131 ± 52 MBq), and [11C]UCB‐J (105 ± 34 MBq). Structural MR scans were acquired for registering PET to template space. Outcome measures were SUVR40‐60 for [11C]PIB, SRTM2‐derived DVR for [11C]UCB‐J, and SUVR90‐110 for [18F]MK‐6240. Cerebellum was used as reference ([11C]PIB, [11C]UCB‐J), and cerebellar gray matter for [18F]MK‐6240. A subset of the old NHPs (n = 15) were tested with the spatial‐delayed response task to assess working memory performance. Outcome measures: number‐of‐wells, time‐delay, and combined score (number‐of‐wells × time‐delay); higher score indicates better memory performance. Result: No regional mean differences were observed in amyloid or SV2A between middle‐aged and old NHPs, though old NHPs exhibited higher variance for all tracers; mean tau was elevated in dlPFC (p = 0.0031) and hippocampus (HC, p = 0.011) in old NHP compared with middle‐aged (Figure 1). In ERC, a positive relationship was found between tau and amyloid), and in HC, a negative correlation was found between tau and SV2A (Figure 2A). Synaptic density displayed a positive relationship with combined score both in dlPFC (p = 0.0055, R2 = 0.46) and HC (p = 0.029, R2 = 0.32) (Figure 2B). Tau had a negative relationship with number‐of‐wells in dlPFC (p = 0.05, R2 = 0.40), and combined score in HC (p = 0.015, R2 = 0.40). Conclusion: NHPs exhibit age‐related changes in canonical AD biomarkers as seen by PET. PET markers of SV2A, tau, and amyloid in known early‐pathology regions (dlPFC, HC) correlate appropriately with working memory performance. These studies demonstrate the potential of NHPs as a highly useful model for human AD. [ABSTRACT FROM AUTHOR]

ABSTRACT: With population aging, prevalence of low bone mineral density (BMD) and associated fracture risk are increased. To determine whether low circulating thyroid stimulating hormone (TSH) levels within the normal range are causally related to BMD, we conducted a two‐sample Mendelian randomization (MR) study. Furthermore, we tested whether common genetic variants in the TSH receptor (TSHR) gene and genetic variants influencing expression of TSHR (expression quantitative trait loci [eQTLs]) are associated with BMD. For both analyses, we used summary‐level data of genomewide association studies (GWASs) investigating BMD of the femoral neck (n = 32,735) and the lumbar spine (n = 28,498) in cohorts of European ancestry from the Genetic Factors of Osteoporosis (GEFOS) Consortium. For the MR study, we selected 20 genetic variants that were previously identified for circulating TSH levels in a GWAS meta‐analysis (n = 26,420). All independent genetic instruments for TSH were combined in analyses for both femoral neck and lumbar spine BMD. In these studies, we found no evidence that a genetically determined 1–standard deviation (SD) decrease in circulating TSH concentration was associated with femoral neck BMD (0.003 SD decrease in BMD per SD decrease of TSH; 95% CI, –0.053 to 0.048; p = 0.92) or lumbar spine BMD (0.010 SD decrease in BMD per SD decrease of TSH; 95% CI, −0.069 to 0.049; p = 0.73). A total of 706 common genetic variants have been mapped to the TSHR locus and expression loci for TSHR. However, none of these genetic variants were associated with BMD at the femoral neck or lumbar spine. In conclusion, we found no evidence for a causal effect of circulating TSH on BMD, nor did we find any association between genetic variation at the TSHR locus or expression thereof and BMD. © 2018 The Authors. Journal of Bone and Mineral Research Published by WileyPeriodicals, Inc. [ABSTRACT FROM AUTHOR]

The stratigraphic, subsidence and structural history of Orphan Basin, offshore the island of Newfoundland, Canada, is described from well data and tied to a regional seismic grid. This large (400 by 400 km) rifted basin is part of the non-volcanic rifted margin in the northwest Atlantic Ocean, which had a long and complex rift history spanning Middle Jurassic to Aptian time. The basin is underlain by variably thinned continental crust, locally <10-km thick. Our work highlights the complex structure, with major upper crustal faults terminating in the mid-crust, while lower crustal reflectivity suggests ductile flow, perhaps accommodating depth-dependent extension. We describe three major stratigraphic horizons connected to breakup and the early post-rift. An Aptian-Albian unconformity appears to mark the end of crustal rifting in the basin, and a second, more subdued Santonian unconformity was also noted atop basement highs and along the proximal margins of the basin. Only minor thermal subsidence occurred between development of these two horizons. The main phase of post-rift subsidence was delayed until post-Santonian time, with rapid subsidence culminating in the development of a major flooding surface in base Tertiary time. Conventional models of rifting events predict significant basin thermal subsidence immediately following continental lithospheric breakup. In the Orphan Basin, however, this subsidence was delayed for about 25-30 Myr and requires more thinning of the mantle lithosphere than the crust. Models of the subsidence history suggest that extreme thinning of the lithospheric mantle continued well into the post-rift period. This is consistent with edge-driven, small-scale convective flow in the mantle, which may thin the lithosphere from below. A hot spot may also have been present below the region in Aptian-Albian time. [ABSTRACT FROM AUTHOR]

The management of primary hypothyroidism with levothyroxine (L-T4) is simple, effective and safe, and most patients report improved well-being on initiation of treatment. However, a proportion of individuals continue to suffer with symptoms despite achieving adequate biochemical correction. The management of such individuals has been the subject of controversy and of considerable public interest. The American Thyroid Association ( ATA) and the European Thyroid Association ( ETA) have recently published guidelines on the diagnosis and management of hypothyroidism. These guidelines have been based on extensive reviews of the medical literature and include sections on the role of combination therapy with L-T4 and liothyronine (L-T3) in individuals who are persistently dissatisfied with L-T4 therapy. This position statement by the British Thyroid Association ( BTA) summarises the key points in these guidelines and makes recommendations on the management of primary hypothyroidism based on the current literature, review of the published positions of the ETA and ATA, and in line with best principles of good medical practice. The statement is endorsed by the Association of Clinical Biochemistry, ( ACB), British Thyroid Foundation, ( BTF), Royal College of Physicians ( RCP) and Society for Endocrinology ( SFE). [ABSTRACT FROM AUTHOR]

The article discusses the guidelines from the British Thyroid Association for the management of thyroid cancer. Topics include the overview and key recommendations for thyroid cancer management, the prognostic factors, risk stratification and staging of uncertainty in cancer, and differentiated thyroid cancer surgery, and persistent and recurrent differentiated thyroid cancer.

Micro-RNAs (miRNAs) can be specifically expressed in forensically relevant body fluids such as blood or saliva. The aim of the study was to develop a simultaneous extraction and analysis protocol that allows for the acquisition of a DNA profile and the identity of the body fluid using a single process. DNA and micro-RNA were extracted from blood and saliva before undergoing a cDNA synthesis step by using stem-loop reverse transcription PCR. The resulting extracts containing DNA and cDNA synthesized from body fluid-specific miRNA markers then underwent standard STR analysis using a modified ABI AmpFℓSTR® NGM SElect™ kit. In all samples, a full DNA profile was obtained along with additional peaks corresponding to the miRNA marker targeted. In all cases, blood samples profiled exhibited a peak indicating the presence of the blood-specific miRNA marker and the saliva sample profiled exhibited a peak indicating the presence of the saliva-specific miRNA marker. [ABSTRACT FROM AUTHOR]

Understanding how bone growth is regulated by hormonal and mechanical factors during early growth periods is important for optimizing the attainment of peak bone mass to prevent or postpone the occurrence of fragility fractures later in life. Using genetic mouse models that are deficient in thyroid hormone (TH) ( Tshr−/− and Duox2−/−), growth hormone (GH) ( Ghrhrlit/lit), or both ( Tshr−/−; Ghrhrlit/lit), we demonstrate that there is an important period prior to puberty when the effects of GH are surprisingly small and TH plays a critical role in the regulation of skeletal growth. Daily administration of T3/T4 during days 5 to 14, the time when serum levels of T3 increase rapidly in mice, rescued the skeletal deficit in TH-deficient mice but not in mice lacking both TH and GH. However, treatment of double-mutant mice with both GH and T3/T4 rescued the bone density deficit. Increased body fat in the TH-deficient as well as TH/GH double-mutant mice was rescued by T3/T4 treatment during days 5 to 14. In vitro studies in osteoblasts revealed that T3 in the presence of TH receptor (TR) α1 bound to a TH response element in intron 1 of the IGF-I gene to stimulate transcription. In vivo studies using TRα and TRβ knockout mice revealed evidence for differential regulation of insulin-like growth factor (IGF)-I expression by the two receptors. Furthermore, blockade of IGF-I action partially inhibited the biological effects of TH, thus suggesting that both IGF-I-dependent and IGF-I-independent mechanisms contribute to TH effects on prepubertal bone acquisition. © 2012 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Progeny of mice treated with the mutagen N-ethyl- N-nitrosourea (ENU) revealed a mouse, designated Longpockets (Lpk), with short humeri, abnormal vertebrae, and disorganized growth plates, features consistent with spondyloepiphyseal dysplasia congenita (SEDC). The Lpk phenotype was inherited as an autosomal dominant trait. Lpk/+ mice were viable and fertile and Lpk/ Lpk mice died perinatally. Lpk was mapped to chromosome 15 and mutational analysis of likely candidates from the interval revealed a Col2a1 missense Ser1386Pro mutation. Transient transfection of wild-type and Ser1386Pro mutant Col2a1 c-Myc constructs in COS-7 cells and CH8 chondrocytes demonstrated abnormal processing and endoplasmic reticulum retention of the mutant protein. Histology revealed growth plate disorganization in 14-day-old Lpk/+ mice and embryonic cartilage from Lpk/+ and Lpk/ Lpk mice had reduced safranin-O and type-II collagen staining in the extracellular matrix. The wild-type and Lpk/+ embryos had vertical columns of proliferating chondrocytes, whereas those in Lpk/ Lpk mice were perpendicular to the direction of bone growth. Electron microscopy of cartilage from 18.5 dpc wild-type, Lpk/+, and Lpk/ Lpk embryos revealed fewer and less elaborate collagen fibrils in the mutants, with enlarged vacuoles in the endoplasmic reticulum that contained amorphous inclusions. Micro-computed tomography (CT) scans of 12-week-old Lpk/+ mice revealed them to have decreased bone mineral density, and total bone volume, with erosions and osteophytes at the joints. Thus, an ENU mouse model with a Ser1386Pro mutation of the Col2a1 C-propeptide domain that results in abnormal collagen processing and phenotypic features consistent with SEDC and secondary osteoarthritis has been established. © 2012 American Society for Bone and Mineral Research [ABSTRACT FROM AUTHOR]

Background A survey of physicians’ practice relating to radioiodine administration for hyperthyroidism was carried out in the UK over 15 years ago and showed wide variations in patient management. This led to the development of national guidelines for the use of radioiodine in hyperthyroidism. As there have been significant advances in the field since that survey, we carried out another survey to study the prevalent practices relating to radioiodine therapy for benign thyroid disorders across the UK. Subjects and methods We mailed 698 UK consultant endocrinologists a questionnaire on radioiodine treatment based on three patient scenarios: hyperthyroid Graves’ disease, subclinical hyperthyroidism and nontoxic goitre. Results The response rate was 40%. For the scenario of an initial presentation of Graves’ disease, 80%, 19% and 0·4% of respondents preferred thionamide, radioiodine or thyroidectomy, respectively. There were inconsistencies in respondents’ recommendations on radioiodine dose, the use of pre- and post-radioiodine supplementary treatments, timing of a repeat dose, and the use of radioiodine in thyroid eye disease. For the case of subclinical hyperthyroidism, one-third of respondents would generally initiate treatment. The majority were more likely to treat subclinical hyperthyroidism in the presence of paroxysmal atrial fibrillation or osteoporosis. If a decision were made to treat subclinical hyperthyroidism, 63%, 35%, 1% and 0·4% would recommend radioiodine, thionamide, beta-blocker and thyroidectomy, respectively. For the scenario of nontoxic goitre, 62%, 21%, 13% and 5% favoured observation, thyroidectomy, radioiodine and thyroxine, respectively. Conclusions There remain significant differences in several aspects of clinical practice relating to the use of radioiodine treatment for benign thyroid disorders in the UK. [ABSTRACT FROM AUTHOR]

Aim The aim of this study is to answer the questions: (1) do small organisms disperse farther than large, or vice versa; and (2) does the observed pattern differ for passive and active dispersers? These questions are central to several themes in biogeography (including microbial biogeography), macroecology, metacommunity ecology and conservation biology. Location The meta-analysis was conducted using published data collected worldwide. Methods We collected and analysed 795 data values in the peer-reviewed literature for direct observations of both maximal dispersal distance and mass of the dispersing organisms (e.g. seeds, not trees). Analysed taxa ranged in size from bacteria to whales. We applied macroecology analyses based on null models (using Monte Carlo randomizations) to test patterns relative to specific hypotheses. Results Collected dispersal distance and mass data spanned 9 and 21 orders of magnitude, respectively. Active dispersers dispersed significantly farther ( P < 0.001) and were significantly greater in mass ( P < 0.001) than passive dispersers. Overall, size matters: larger active dispersers attained greater maximum observed dispersal distances than smaller active dispersers. In contrast, passive-disperser distances were random with respect to propagule mass, but not uniformly random, in part due to sparse data available for tiny propagules. Conclusions Size is important to maximal dispersal distance for active dispersers, but not for passive dispersers. Claims that microbes disperse widely cannot be tested by current data based on direct observations of dispersal: indirect approaches will need to be applied. Distance–mass relationships should contribute to a resolution of neutral and niche-based metacommunity theories by helping scale expectations for dispersal limitation. Also, distance–mass relationships should inform analyses of latitudinal species richness and conservation biology topics such as fragmentation, umbrella species and taxonomic homogenization. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) numerical modelling of fault displacement enables the building of geological models to represent the complex 3D geometry and geological properties of faulted sedimentary basins. Using these models, cross-fault juxtaposition relationships are predicted in 3D space and through time, based on the geometries of strata that are cut by faults. Forward modelling of fault development allows a 3D prediction of fault-zone argillaceous smear using a 3D application of the Shale Gouge Ratio. Numerical models of the Artemis Field, Southern North Sea, UK and the Moab Fault, Utah, USA are used to demonstrate the developed techniques and compare them to traditional one- and two-dimensional solutions. These examples demonstrate that a 3D analysis leads to significant improvements in the prediction of fault seal, the analysis of the interaction of the sealing properties of multiple faults, and the interpretation of fault seal within the context of sedimentary basin geometry. [ABSTRACT FROM AUTHOR]

Explores the bone biology and skeletal consequences of thyroid disease. Side effects associated with thyroxine; Molecular actions of thyroid hormone; Observation on the clinical effects of childhood thyroid dysfunction.

Evolutionary models that have been proposed for the Pyrenean orogenic belt involve gravitational gliding of major thrust sheets to both the north and south of an uplifted central Axial Zone. It has been suggested by previous workers that uplift is a result of Alpine compression, or long lived strike slip movement on the North Pyrenean Fault. We critically assess these models and propose a new model based on the generation of a thin-skinned, linked thrust system, due to Alpine collision of Iberia and Europe. Pyrenean Alpine tectonics is dominated by southward thrusting on a major sole fault dipping north at approximately 6° within Hercynian basement. Northerly directed thrusts of the North Pyrenean Zone and Northern Folded Foreland are backthrusts from this sole fault. A total orogenic shortening of 106 km in the central Pyrenees was achieved between the Palaeocene and Oligocene at a time-averaged rate of 0.62 cm yr−1. A thin- skinned model requires that the North Pyrenean Fault is truncated by both northward and southward moving thrusts and occurs in the footwall of the sole fault some 60km north of its present surface trace. [ABSTRACT FROM AUTHOR]

The article offers the author's insights on various issues related to the Association of Coloproctology of Great Britain and Ireland (ACPGBI), in which he is President. The author discusses the debates on the possible extension of a President's tenure. He mentions the benefits delivered by the adoption of teleconferences, however, he argues that it is unlikely that the technology take the place of Council meetings. He discusses concerns regarding specialties related to colorectal surgery.

An allegation of sexual assault was made in which a bra was torn off by the assailant causing extensive damage; however, it was observed that the hook and eye fastening was still intact. It was felt that it was not possible for a garment to receive such damage without damage to the hook and eye fastening, thus indicating that the complainant caused the damage to the bra herself to support a false allegation. Reconstruction experiments were conducted in which the conditions of the allegation were simulated utilizing a range of similar bras. Following the infliction of damage, the hook and eye fastenings were examined. In eight of nine experiments, the hook and eye fastening were intact, despite the application of enough force to cause separation of the bra cups in five of the experiments. This shows that bras may suffer extensive damage without damage to the hook and eye fastening. [ABSTRACT FROM AUTHOR]

The article presents a proposal to maintain the names Selenopemphix against Margosphaera velata (Dinophyceae) and Selenopemphix nephroides. Several bases are identified including the decision of dinoflagellate scientists not to use Margosphaera and Margosphaera velata, the certainty of placing Selenopemphiz as Cenozoic fossil dinoflagellate cysts, and the similarity between Selenopemphix and Margosphaera in 1993. The morphological distinction between these species are mentioned.

The article presents several case studies. A 26-year-old woman who had a background of diabetes mellitus was diagnosed with Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like episodes or MELAS syndrome confirmed by analyzing mitochondrial DNA. A 23-year-old woman having a history of hypothyrodism at age 12 was clinically diagnosed of MELAS syndrome through mitochondrial DNA sequencing and muscle biopsy. Details on mitochondria and the causes of MELAS are presented.

A letter to the editor is presented regarding a thyroid cancer patient who was diagnosed increasing thyroglobulin tumour marker during her pregnancy.

The article discusses the criteria for colorectal surgery certification that will meet the future changes posted by the Intercollegiate Surgical Curriculum Project (ISCP). It cites that the trainees' assessment is the most important part of the certification process to ensure satisfactory achievement of practice standards. Moreover, the response of colorectal surgeons will determine the success of colorectal surgery.