Evidence that human thyroid cells express uncleaved, single-chain thyrotropin receptors on their surface

The prevailing concept is that, in human thyroid tissue in vivo, all cell-surface TSH receptors (TSHR) cleave into disulfide linked A and B subunits. Because this viewpoint is based on studies using homogenized thyroid tissue and because of TSHR fragility, we studied TSHR subunit structure in intact thyroid cells, primary human thyrocyte cultures, FRTL-5 rat thyroid cells, and WRO (follicular) and NPA (papillary) thyroid cancer cell lines. To overcome the handicap of very low TSHR expression in thyroid cells, we generated a TSHR-expressing adenovirus (TSHR-Ad-RGD) with an integrin-binding RGD motif enabling efficient entry into cells lacking the coxsackie-adenovirus receptor. Two days after TSHR-Ad-RGD infection, [125I]TSH cross-linking to intact cells revealed uncleaved, single-chain TSHR as well as cleaved TSHR A subunits on the surface of all four thyroid cell types. The extent of TSHR cleavage, which is independent of the level of TSHR expression, was consistently lower in the human thyroid cancer cell lines than in the other cell lines. In flow cytometry studies after TSHR-Ad-RGD infection, strong signals were detected in all four thyroid cell types using a monoclonal antibody that primarily recognizes the uncleaved TSHR. Finally, using the same monoclonal antibody, confocal microscopy confirmed the presence of single-chain TSHR on TSHR-Ad-RGD-infected thyroid cells. In summary, TSH covalent cross-linking, flow cytometry, and confocal microscopy demonstrate the presence of uncleaved TSHR on the human thyrocyte surface. These data provide stronger evidence for this alternative than the contrary view based on the finding of only cleaved TSHR in homogenized thyroid cells.     

Multimodal neuroimaging measures and intelligence influence pedophile child sexual offense behavior

Pedophilia is a heterogeneous disorder for which the neurobiological correlates are not well established. In particular, there are no biological markers identifying individuals with high risk to commit child sexual offense (CSO). Pedophiles with CSO (P+CSO; N = 73), pedophiles without CSO (P-CSO; N = 77), and non-pedophilic controls (NPC; N = 133) were assessed using multimodal structural neuroimaging measures including: cortical thickness (CT), surface area (SA), and white matter fractional anisotropy (FA), as well as full scale IQ (FSIQ) performance. Cortex-wise mediation analyses were used to assess the relationships among brain structure, FSIQ and CSO behavior. Lower FSIQ performance was strongly predict with P+CSO (Wald Chi² = 13.0, p = 3.1 × 10^-5). P+CSO had lower CT in the right motor cortex and pronounced reductions in SA spanning the bilateral frontal, temporal, cingulate, and insular regions (P_{FWE-corrected} < 0.05). P+CSO also had lower FA particularly in the corpus callosum (P_{FWE-corrected} < 0.05). The relationship between SA and P+CSO was significantly mediated by FSIQ, particularly in the prefrontal and anterior insular cortices (P_{FWE-corrected} < 0.05). Within P+CSO, left prefrontal and right anterior cingulate SA negatively correlated with number of CSOs (P_{FWE-corrected} < 0.05). This study demonstrates converging neurobiological findings in which P+CSO had lower FSIQ performance, reduced CT, reduced SA, and reduced FA, compared to P-CSO as well as NPC. Further, FSIQ potentially mediates abuse by pedophiles via aberrant SA, whereas the CT and FA associations were independent of FSIQ differences. These findings suggest aberrant neuroanatomy and lower intelligence as a potential core feature underlying child sexual abuse behavior by pedophiles.     

Possibilities and limitations of electrospun chitosan‐coated polycaprolactone grafts for rotator cuff tear repair

Acute and chronic rotator cuff tears remain challenging for therapy. A wide range of therapeutic approaches were developed but re‐tears and postoperative complications occur regularly. Especially in elderly people, the natural regeneration processes are decelerated, and graft materials are often necessary to stabilize the tendon‐to‐bone attachment and to improve the healing process. We here investigated in a small animal model a newly developed electrospun polycaprolactone fiber implant coated with a chitosan‐polycaprolactone graft copolymer and compared these implants biomechanically and histologically with either a commercially available porous polyurethane implant (Biomerix 3D Scaffold) or suture‐fixed tendons. Fifty‐one rats were divided into three groups of 17 animals each. In the first surgery, the left infraspinatus tendons of all rats were detached, and the animals recovered for 4 weeks. In the second surgery, the tendons were fixed with suture material only (suture‐fixed group; n = 17), whereas in the two experimental groups, the tendons were fixed with suture material and the polyurethane implant (Biomerix scaffold group; n = 17) or the modified electrospun polycaprolactone fiber implant (CS‐g‐PCL scaffold group; n=17), respectively. The unaffected right infraspinatus tendons were used as native controls. After a recovery of 8 weeks, all animals were clinically inconspicuous. In 12 animals of each group, repaired entheses were biomechanically tested for force at failure, stiffness, and modulus of elasticity, and in five animals, repaired entheses were analyzed histologically. Biomechanically, all parameters did not differ statistically significant between both implant groups, and the entheses failed typically at the surgical site. However, with respect to the force at failure, the median values of the two implant groups were smaller than the median value of the suture‐fixed group. Histologically, the modified polycaprolactone fiber implant showed no acute inflammation processes, a good infiltration with cells, ingrowth of blood vessels and tendinous tissue, and a normal fibrous ensheathment. Further improvement of the implant material could be achieved by additional implementation of drug delivery systems. Therewith, the used CS‐g‐PCL fiber mat is a promising basic material to reach the goal of a clinically usable graft for rotator cuff tear repair.     

Operative treatment of geriatric ankle fractures with conventional or locking plates. A retrospective case-control study

BackgroundThe incidence of geriatric ankle fractures continues to rise due to demographic changes. While locking plates have become standard implants for injuries of other body regions, clinical studies on their use for geriatric ankle fractures are rare.MethodsTherefore, a retrospective case-control study, including 333 patients with a mean age of 73.5 years was performed. 263 patients underwent operative fixation with one- third tubular plates and 70 were treated with locking plates. Early outcomes and complication rates of locking plates as compared with conventional one- third tubular plates are described.ResultsIn the present study, patients treated with locking plates were older and suffered from more severe fracture patterns. In addition, these patients had more severe comorbidities. Treatment with conventional or locking plate fixation resulted in a comparable complication and revision rate. A matched pair analysis showed significantly more complications and required revision surgeries and a trend towards more implant failures in the group that underwent conventional plating.ConclusionsTherefore, we conclude that precontoured locking plates represent an appropriate treatment option for severe ankle fractures in patients suffering from relevant co-morbidities. Prospective randomized trials are warranted to prove superiority of locking plates for treatment of geriatric ankle fractures.Level 3: Retrospective case- control study.     

Recurrent NMYC copy number gain and high protein expression in basal cell carcinoma

Formation of basal cell carcinoma (BCC) has been linked to deregulation in the sonic hedgehogh (Shh) signalling pathway. Though mutations of the genes, PTCH1 and SMO, are known to be involved in aberrant Shh signalling, the distinct downstream effectors of these genes are poorly described. Studies have indicated that the NMYC oncogene is a potential Shh downstream effector. To assess the expression of Nmyc protein and gene copy numbers of the NMYC gene locus in a representative BCC tumour collection, immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) were performed on 273 BCC specimens of different growth patterns and anatomic localisations on tissue microarray (TMA) sections. High Nmyc protein expression was detected in 72.7% (160/220) of all BCC specimens. Strong Nmyc immunopositivity was more frequently found in infiltrative BCCs compared to nodular/superficial BCCs (p=0.005), and in BCCs of the head compared to BCCs of other anatomic localisations (p=0.021). The prevalence of NMYC copy number gains was 17.5% (37/211), including three tumours with nodular differentiation that exhibited a distinct high-level amplification of the NMYC locus. These data indicate that high expression of the Shh downstream mediator, Nmyc, is a frequent event in BCC, predominantly in more aggressive subtypes. Although the NMYC copy number gain found in a subset of cases might contribute to this aberrant Nmyc protein expression by a gene dosage effect, our data suggests that Nmyc protein can also be induced by aberrant Shh signalling, acting as an effector molecule of the Shh pathway. Novel systemic anti-sense NMYC inhibition strategies could be a promising option for therapy-refractory BCC.     

Resistance of permethrin to weathering in fabrics treated for protection against mosquitoes (Diptera: Culicidae)

Two different methods of treating cotton and nylon-cotton fabrics with permethrin were evaluated for protection from mosquito bites after laboratory weathering. Cotton fabric treated by the individual dynamic absorption method provided consistently better protection than cotton fabric treated by the aerosol method. The nylon-cotton fabric provided similar protection regardless of the treatment method. After weathering, the toxic effects of both types of permethrin-treated fabrics treated by both methods diminished much more rapidly than did the repellent effect. Low residual amounts of permethrin in the fabrics provided 85% protection from bites against Aedes aegypti (L.) and 93% protection against Anopheles stephensi Liston. Permethrin-treated fabrics were effective in providing protection from mosquito bites for long periods, even after exposure to weathering, and appear to be an effective means of reducing nuisance effects and disease transmission by mosquitoes.