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Abstract Background Inversion ankle sprains, or lateral ankle sprains, often result in symptomatic lateral ankle instability, and some patients need lateral ankle ligament reconstruction to reduce pain, improve function, and prevent subsequent injuries. Although anatomically reconstructed ligaments should behave in a biomechanically normal manner, previous studies have not measured the strain patterns of the anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) after anatomical reconstruction. This study aimed to measure the strain patterns of normal and reconstructed ATFL and CFLs using the miniaturization ligament performance probe (MLPP) system. Methods The MLPP was sutured into the ligamentous bands of the ATFLs and CTLs of three freshly frozen cadaveric lower-extremity specimens. Each ankle was manually moved from 15° dorsiflexion to 30° plantar flexion, and a 1.2-N m force was applied to the ankle and subtalar joint complex. Results The normal and reconstructed ATFLs exhibited maximal strain (100) during supination in three-dimensional motion. Although the normal ATFLs were not strained during pronation, the reconstructed ATFLs demonstrated relative strain values of 16–36. During the axial motion, the normal ATFLs started to gradually tense at 0° plantar flexion, with the strain increasing as the plantar flexion angle increased, to a maximal value (100) at 30° plantar flexion; the reconstructed ATFLs showed similar strain patterns. Further, the normal CFLs exhibited maximal strain (100) during plantar flexion-abduction and relative strain values of 30–52 during dorsiflexion in three-dimensional motion. The reconstructed CFLs exhibited the most strain during dorsiflexion-adduction and demonstrated relative strain values of 29–62 during plantar flexion-abduction. During the axial motion, the normal CFLs started to gradually tense at 20° plantar flexion and 5° dorsiflexion. Conclusion Our results showed that the strain patterns of reconstructed ATFLs and CFLs are not similar to those of normal ATFLs and CFLs.

Abstract. Pancreatic neuroendocrine tumors (PNETs) are a rare group of neoplasms originating from the endocrine pancreas. PNETs are classified as functional or non-functional tumors. PNETs are more often diagnosed at a higher stage with distant metastases or advanced locoregional disease. The majority of individuals with hepatic metastases will ultimately die of liver failure; therefore, the treatment of liver tumor burden is critical to providing a survival impact. While surgical resection remains the only chance of cure for disease confined to the pancreas or for locoregional disease, the treatment of advanced or metastatic PNETs is more complex and often requires a multimodal approach. This review focuses on treatment options for well and moderately differentiated PNETs with metastatic disease to the liver. These include surgery, liver-directed therapies including ablative and intra-arterial therapies, and systemic therapies such as somatostatin analogues, targeted therapies, chemotherapy, and peptide receptor radionuclide therapy. Developing an individualized treatment strategy requires careful assessment of liver tumor burden and predicted biological behavior. Aggressive surgical resection of hepatic metastases secondary to PNET primary tumors is associated with improved survival in multiple retrospective studies. General goals of treatment for metastatic disease include prolonging overall survival and progression free survival, improving quality of life, and control of symptoms.

Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease. Using a transgenic mouse model of Parkinson's disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage. Interestingly, we found that overexpressed ASYN interacted with dynein and induced a significant increase in the activated levels of small Rab GTPases such as Rab5 and Rab7, both key regulators of endocytic processes. Furthermore, expression of ASYN resulted in neuronal atrophy in DIV7 cortical cultures of either from E18 transgenic mouse model or from rat E18 embryos that were transiently transfected with ASYN-GFP for 72 hrs. Our studies suggest that excessive ASYN likely alters endocytic pathways leading to axonal dysfunction in embryonic cortical neurons in PD mouse models.

Abstract Osteoid osteoma is a painful, benign and common bone tumor that is prevalent in young adults. The typical clinical presentation consists of pain that becomes worse at night and is relieved by nonsteroidal anti-inflammatory drugs. The most common imaging finding is a lytic lesion, known as a nidus, with variable intralesional mineralization, accompanied by bone sclerosis, cortical thickening and surrounding bone marrow edema, as well as marked enhancement with intravenous contrast injection. When the lesion is located in typical locations (intracortical bone and the diaphyses of long bones), both characteristic clinical and radiological features are diagnostic. However, osteoid osteoma is a multifaceted pathology that can have unusual presentations, such as intraarticular osteoid osteoma, epiphyseal location, lesions at the extremities and multicentric nidi, and frequently present atypical clinical and radiological manifestations. In addition, many conditions may mimic osteoid osteoma and vice versa, leading to misdiagnosis. Therefore, it is essential to understand these musculoskeletal diseases and their imaging findings to increase diagnostic accuracy, enable early treatment and prevent poor prognosis.

Boron (specifically 10B) is the element of choice to shield thermal neutrons due to its large (n, α) cross‐section; however, very few polymer composites containing high boron concentrations are available. This study aimed to determine the maximum possible amount of boron that could be introduced into a polymer matrix. Diverse manufacturing techniques, ranging from additive manufacturing to compression molding, were employed to fabricate inks and filaments for 3D printing, foams, and flexible pads. Composites using siloxanes, poly(lactic acid), and acrylonitrile butadiene styrene containing up to 80 wt% boron were sucessufully fabricated. The addition of known plasticizers (polyethylene glycol) and reinforcing agents (carbon nanofibers and fumed silica) helped to overcome fabrication problems such as clogging of the printing nozzle or crumbling of compression molded parts. In addition, the thermal‐mechanical properties of these novel boron composites were determined and shown to vary according to boron concentration, presence of additives, and fabrication techniques utilized. [ABSTRACT FROM AUTHOR]

Adeno-associated virus (AAV) vector serotypes vary in their ability to transduce hepatocytes from different species. Chimeric mouse models harboring human hepatocytes have shown translational promise for liver-directed gene therapies. However, many variables that influence human hepatocyte transduction and transgene expression in such models remain poorly defined. Here, we aimed to test whether three experimental conditions influence AAV transgene expression in immunodeficient, fumaryl-acetoactetate-hydrolase-deficient (Fah−/−) chimeric mice repopulated with primary human hepatocytes. We examined the effects of the murine liver injury cycle, human donor variability, and vector doses on hepatocyte transduction with various AAV serotypes expressing a green fluorescent protein (GFP). We determined that the timing of AAV vector challenge in the liver injury cycle resulted in up to 7-fold differences in the percentage of GFP expressing human hepatocytes. The GFP+ hepatocyte frequency varied 7-fold between human donors without, however, changing the relative transduction efficiency between serotypes for an individual donor. There was also a clear relationship between AAV vector doses and human hepatocyte transduction and transgene expression. We conclude that several experimental variables substantially affect human hepatocyte transduction in the Fah−/− chimera model, attention to which may improve reproducibility between findings from different laboratories.

Abstract. There has been a rising trend in the incidence and prevalence of non-functioning pancreatic neuroendocrine tumors (NFPanNETs). While a significant number of the newly diagnosed NFPanNETs are asymptomatic, a majority of patients will present with liver metastasis (LM) at the time of diagnosis. Surgical resection remains the only curative treatment, especially for localized NFPanNETs. While a majority of small NFPanNETs are indolent, some are not. This heterogeneity in tumor biology presents the surgeon with the unique challenge of determining which patient will benefit from surgery, given the morbidity of pancreatic surgery. There has been a recent push for a more aggressive approach to the care of these patients, given the emergence of data supporting such measures. However, the risk of over or under treatment has generated immense debate amongst experts in the field. The heterogeneity of current practice guidelines and institutional practices around the world is a reflection of the disparate opinion on the management of NFPanNET. In this review, we set out to examine the evidence regarding some of the most controversial and challenging aspects of the surgical treatment of NFPanNET. We evaluate the following questions; should patients with small NFPanNETs ≤ 2 cm in size be resected; should patients with metastatic NFPanNETs undergo surgical debulking, and should there be resection of the primary tumor in the setting of non-resectable metastatic disease? Although there are currently no Level 1 data to answer these questions conclusively, we believe that the current literature supports a more aggressive approach to the management of NFPanNET.

Abstract Background There are few reports on the detailed biomechanics of the deltoid ligament, and no studies have measured the biomechanics of each ligamentous band because of the difficulty in inserting sensors into the narrow ligaments. This study aimed to measure the strain pattern of the deltoid ligament bands directly using a Miniaturization Ligament Performance Probe (MLPP) system. Methods The MLPP was sutured into the ligamentous bands of the deltoid ligament in 6 fresh-frozen lower extremity cadaveric specimens. The strain was measured using a round metal disk (clock) fixed on the plantar aspect of the foot. The ankle was manually moved from 15° dorsiflexion to 30° plantar flexion, and a 1.2-N-m force was applied to the ankle and subtalar joint complex. Then the clock was rotated every 30° to measure the strain of each ligamentous band at each endpoint. Results The tibionavicular ligament (TNL) began to tense at 10° plantar flexion, and the tension becomes stronger as the angle increased; the TNL worked most effectively in plantar flex-abduction. The tibiospring ligament (TSL) began to tense gradually at 15° plantar flexion, and the tension became stronger as the angle increased. The TSL worked most effectively in abduction. The tibiocalcaneal ligament (TCL) began to tense gradually at 0° dorsiflexion, and the tension became stronger as the angle increased. The TCL worked most effectively in pronation (dorsiflexion-abduction). The superficial posterior tibiotalar ligament (SPTTL) began to tense gradually at 0° dorsiflexion, and the tension became stronger as the angle increased, with the SPTTL working most effectively in dorsiflexion. Conclusion Our results show the biomechanical function of the superficial deltoid ligament and may contribute to determining which ligament is damaged during assessment in the clinical setting.

Miguel Xavier,1 Lorena García-Hevia,1 Isabel R Amado,1,2 Lorenzo Pastrana,1 Catarina Gonçalves1 1Department of Life Sciences, International Iberian Nanotechnology Laboratory, Braga 4715-330, Portugal; 2Department of Food and Analytical Chemistry, Faculty of Sciences, University of Vigo, Ourense 32004, SpainCorrespondence: Catarina GonçalvesDepartment of Life Sciences, International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, Braga 4715-330, PortugalEmail catarina.goncalves@inl.intBackground: Oral administration remains the most common mode of drug delivery. However, orally administered bioactive compounds must first survive digestion and then be absorbed at the intestine in order to reach other tissues or organs. The efficiency of both processes can be improved by encapsulation or conjugation with polymeric nanoparticles. Here we report the synthesis of amphiphilic hyaluronic acid (HyA) nanogels as nanocarriers for drug delivery.Methods: HyA nanogels were prepared by self-assembly from amphiphilic HyA conjugates produced by grafting hydrophobic alkyl chains to the HyA backbone. The dye Cy5.5 was covalently bonded and used for tracking. The nanogels were characterised according to their structure, size and zeta potential, as well as biocompatibility towards an intestinal epithelial cell line. The uptake and intestinal permeability of the nanogels were assessed using in vitro models, which physiological relevance was verified regarding the morphology of the epithelium, the production of mucus, the expression of occludin and the transepithelial electrical resistance.Results: The covalent binding of Cy5.5 did not affect significantly the size and surface charge of the nanogels at 125.1 ± 3.2 nm and −57.6 ± 6.2 mV respectively after labelling. Studies of biocompatibility showed that the nanogels were non-toxic to Caco-2 cells up to the concentration of 0.1 mg∙mL−1. The presence of mucus affected the nanogel uptake and highlighted the importance of considering mucus-producing cells in in vitro intestinal models. The uptake or adsorption to a Caco-2/HT29-MTX co-culture (8.1%) was higher than with single Caco-2 cell cultures (4.3%). Interestingly, both models led to minute (

Background: Little is known about the nature and reactions to sexual abuse of children with intellectual disability (ID). The aim was to fill this gap. Method: Official reports of sexual abuse of children with ID in state care were examined (N = 128) and compared with children without ID (N = 48). Results: Clear signs of penetration or genital touching by male (adolescent) peers or (step/foster) fathers were found in most ID reports. Victims often received residential care and disclosed themselves. Type of perpetrator seemed to affect the nature and reaction to the abuse. Cases of children with and without ID seemed to differ in location and reports to police. Conclusions: Screening of (foster) homes seems crucial. Residential facilities should find a balance between independence of children and protection. Care providers should be trained in addressing sexual issues and sexual education, accounting for different types of perpetrators (peers/adults). Uniform reporting guidelines are needed.

Abstract Background We previously identified, in newly diagnosed rheumatoid arthritis (RA) patients, networks of co-expressed genes and proteomic biomarkers associated with achieving sustained drug-free remission (sDFR) after treatment with tocilizumab- or methotrexate-based strategies. The aim of this study was to identify, within the same patients, metabolic pathways important for achieving sDFR and to subsequently study the complex interactions between different components of the biological system and how these interactions might affect the therapeutic response in early RA. Methods Serum samples were analyzed of 60 patients who participated in the U-Act-Early trial (ClinicalTrials.gov number NCT01034137) and initiated treatment with methotrexate, tocilizumab, or the combination and who were thereafter able to achieve sDFR (n = 37); as controls, patients were selected who never achieved a drug-free status (n = 23). Metabolomic measurements were performed using mass spectrometry on oxidative stress, amine, and oxylipin platforms covering various compounds. Partial least square discriminant analyses (PLSDA) were performed to identify, per strategy arm, relevant metabolites of which the biological pathways were studied. In addition, integrative analyses were performed correlating the previously identified transcripts and proteins with the relevant metabolites. Results In the tocilizumab plus methotrexate, tocilizumab, and methotrexate strategy, respectively, 19, 13, and 12 relevant metabolites were found, which were subsequently used for pathway analyses. The most significant pathway in the tocilizumab plus methotrexate strategy was “histidine metabolism” (p

Review of Daniel P. Castillo, _An Ecological Theology of Liberation: Salvation and Political Ecology