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Past research has constructed a medicalized model of trans women's sexuality, where trans women are believed to be hyposexual and distressed by their bodies pre-transition, and are cured of their sexual dysfunction as a result of gender affirmative medical procedures. The current study engaged a community sample ( N = 169) of trans feminine and nonbinary individuals assigned male at birth (TFNB) to investigate predictors of sexual experiences after addressing methodological biases of prior studies, including body satisfaction (using a modified Body Image Scale) and social contextual factors. Hierarchical regressions were conducted to test the hypothesis that after accounting for demographic variables and social contextual aspects (i.e., body satisfaction, social dysphoria, and fetishization), medical transition (i.e., hormone therapy) would not significantly predict five outcomes of sexual experience (i.e., receptive penetration, insertive penetration, importance of sex, sexual pleasure, and sexual intimacy). Across all models, medical transition was not a significant predictor of sexual experiences; however, sexual orientation, age, body satisfaction, and experiences of fetishization were frequent predictors. Results suggest that the sexual experiences of TFNB individuals do not align with the medicalized model and that demographic and contextual factors play an important role in the sexual outcomes for this population.

Retail store prices are frequently set to either a just-below (e.g., $1.99) or rounded to (e.g., $2.00) integer levels. Previous studies proposed two price-perception effects that may underly such psychological pricing strategies. First, the left-digit effect (LDE) assumes consumers read prices left-to-right. Cognitive limitations let consumers overweight the impact of digits on the left side of the price while underweighting digits on the right side of the price. This effect appears to conflict with the contradictory perceptual fluency effect (PFE), which proposes that a rounded price is more perceptual fluent and, thus, more attractive to consumers. To address these paradoxical effects, we conducted an online experiment with 266 participants making a total of 4788 purchasing decisions where we systematically varied the purchasing prices of otherwise identical lottery tickets across two price levels. Against expectations, we found no support for either of the two price-perception effects. We propose three possible explanations of these null results., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonfl ikt besteht.

Despite discernible improvements in the last decades, speeding is still a pertinent problem for road safety, fuel efficiency, and greenhouse gas mitigation. In order to understand individual speeding decisions, we need a better understanding of who speeds. In our paper, we test whether individuals' general pace of life is associated with speeding decisions. We use a novel speed-choice experiment that confronts participants with a scenario in which they repeatedly decide between driving fast or slow. This decision is associated with different accident risks. Before the experiment, each participant's pace of life was measured. Our results show that individuals with a slower pace of life are more likely to choose slow in the experiment and are also more likely to switch to slow, even when they had success by driving fast in the preliminary round. Therefore, individuals' pace of life may contribute to our understanding of speeding., Competing Interests: The authors have declared that no competing interests exist.

Coastal areas are under increasing pressure from rapid human population growth, yet empirical research on the effect of migration on coastal and marine resources is scarce. We contribute to this understudied literature by conducting an original household survey in a coastal region of Southeastern Ghana. This study employs two proxies for pro-environmental behavior that have not, to our knowledge, been used in the context of coastal migration, to explicitly compare migrant and non-migrant populations. Environmental attitudes toward coastal resources and individual extraction behavior in common-pool resource (CPR) experiments have shown broad relevance in the literature to understand natural resource decision making. We found that migrants in general did not differ significantly from non-migrants in relation to their environmental attitudes or their extraction behavior in the CPR game. However, when focusing on migrant fishers only, results suggested that this subgroup was less concerned about the utilization of coastal resources than non-migrant fishers and behaved less cooperatively in the CPR experiment. These findings, though, held true only for the subgroup of fishers, and could not be found for other occupational groups. Therefore, we conclude that migrants do not per se value coastal resources less or cooperate less in CPR situations, but that socioeconomic characteristics, and particularly their occupational status and their relation to the resource, matter., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

HLA-A2 transgenic mice bearing established HLA-A2(neg) B16 melanomas were effectively treated by intratumoral (i.t.) injection of syngeneic dendritic cells (DCs) transduced to express high levels of interleukin (IL)-12, resulting in CD8(+) T cell-dependent antitumor protection. In this model, HLA-A2-restricted CD8(+) T cells do not directly recognize tumor cells and therapeutic benefit was associated with the crosspriming of HLA-A2-restricted type-1 CD8(+) T cells reactive against antigens expressed by stromal cells [i.e., pericytes and vascular endothelial cells (VEC)]. IL-12 gene therapy-induced CD8(+) T cells directly recognized HLA-A2(+) pericytes and VEC flow-sorted from B16 tumor lesions based on interferon (IFN)-γ secretion and translocation of the lytic granule-associated molecule CD107 to the T cell surface after coculture with these target cells. In contrast, these CD8(+) T effector cells failed to recognize pericytes/VEC isolated from the kidneys of tumor-bearing HHD mice. The tumor-associated stromal antigen (TASA)-derived peptides studied are evolutionarily conserved and could be recognized by CD8(+) T cells harvested from the blood of HLA-A2(+) normal donors or melanoma patients after in vitro stimulation. These TASA and their derivative peptides may prove useful in vaccine formulations against solid cancers, as well as, in the immune monitoring of HLA-A2(+) cancer patients receiving therapeutic interventions, such as IL-12 gene therapy.

In the classical form of alpha1-antitrypsin (AT) deficiency, a point mutation in AT alters the folding of a liver-derived secretory glycoprotein and renders it aggregation-prone. In addition to decreased serum concentrations of AT, the disorder is characterized by accumulation of the mutant alpha1-antitrypsin Z (ATZ) variant inside cells, causing hepatic fibrosis and/or carcinogenesis by a gain-of-toxic function mechanism. The proteasomal and autophagic pathways are known to mediate degradation of ATZ. Here we show that the autophagy-enhancing drug carbamazepine (CBZ) decreased the hepatic load of ATZ and hepatic fibrosis in a mouse model of AT deficiency-associated liver disease. These results provide a basis for testing CBZ, which has an extensive clinical safety profile, in patients with AT deficiency and also provide a proof of principle for therapeutic use of autophagy enhancers.

Transplant vasculopathy has not been systematically investigated in composite tissue allotransplantation (CTA). The impact of multiple acute rejections (ARs) on long-term graft outcomes in reconstructive transplantation remains unknown. This study in a rat hind-limb allotransplantation model systematically analyzes vasculopathy and tissue-specific pathological changes secondary to multiple AR episodes. LEW rats were transplanted with BN rat hind limbs and treated as follows: Group 1 (Iso): isografts. Group 2 (CsA): Cyclosporine (CsA) qd; Group 3 (mult AR): CsA and dexamethasone only when AR was observed. No AR was observed in Groups 1 and 2. Multiple AR were observed in Group 3, and each episode was completely reversed (clinically) with pulsed CsA + dexamethasone treatment. Group 3 animals demonstrated significant vascular lesions along with skin and muscle atrophy, upregulation of profibrotic gene expression and fibrosis when compared to Groups 1 and 2. In addition, allograft bone was sclerotic, weak and prone to malunion and nonunion. Interestingly, vasculopathy was a late finding, whereas muscle atrophy with macrophage infiltration was seen early, after only a few AR episodes. Taken together, multiple AR episodes lead to vasculopathy and tissue-specific pathology in CTA. This is the first evidence of 'composite tissue vasculopathy and degeneration (CTVD)' in CTA.

T-bet (TBX21) is a transcription factor required for the optimal development of type 1 immune responses. Although initially characterized for its intrinsic role in T cell functional polarization, endogenous T-bet may also be critical to the licensing of type 1-biasing APCs. Here, we investigated whether human dendritic cells (DC) genetically engineered to express high levels of T-bet (i.e., DC.Tbet) promote superior type 1 T cell responses in vitro. We observed that DC.Tbet were selective activators of type 1 effector T cells developed from the naive pool of responder cells, whereas DC.Tbet and control DC promoted type 1 responses equitably from the memory pool of responder cells. Naive T cells primed by (staphylococcal enterotoxin B or tumor-associated protein-loaded) DC.Tbet exhibited an enhancement in type 1- and a concomitant reduction in Th2- and regulatory T cell-associated phenotype/function. Surprisingly, DC.Tbets were impaired in their production of IL-12 family member cytokines (IL-12p70, IL-23, and IL-27) when compared with control DC, and the capacity of DC.Tbet to preferentially prime type 1 T cell responses was only minimally inhibited by cytokine (IL-12p70, IL-23, IFN-gamma) neutralization or receptor (IL-12Rbeta2, IL-27R) blockade during T cell priming. The results of transwell assays suggested the DC.Tbet-mediated effects are predominantly the result of direct DC-T cell contact or their close proximity, thereby implicating a novel, IL-12-independent mechanism by which DC.Tbets promote improved type 1 functional polarization from naive T cell responders. Given their superior type 1 polarizing capacity, DC.Tbet may be suitable for use in vaccines designed to prevent/treat cancer or infectious disease.

Background: Despite the widely accepted implication of antidonor antibodies and complement in solid organ transplantation, their role in reconstructive allotransplantation is not clear. The aim of this study was to analyze the humoral immune response using a rat orthotopic limb transplantation model., Methods: We used the Brown Norway to Lewis rat orthotopic hind-limb transplant model: Group 1, isografts; group 2, allografts with daily continuous cyclosporine treatment to prevent acute rejection; and group 3, allografts undergoing multiple episodes of acute rejection. Samples were taken at 30, 60, and 90 days. Serum was analyzed by FACS for antidonor antibodies. Tissue deposition of antibodies and complement was investigated by immunofluorescence., Results: By day 90, animals in group 3 had undergone 19 (+/-3.2) acute rejection episodes. There was no difference in the occurrence of serum antidonor antibodies between the three groups at any time point. However, at 90 days, anti-third-party antibodies were significantly greater among group 3. There was no difference in antibody or complement deposition in muscles between the 3 groups., Conclusion: Despite the increased antibody against a third party after multiple rejection episodes in this animal model, there was no clear evidence of an antibody-mediated alloresponse in limb transplantation.

Introduction: In spite of carpal tunnel release's prevalent good postoperative results, the number of revision surgeries needed should not be underestimated. In this study, subjective and functional results after carpal tunnel revision surgery were determined., Materials and Methods: Thirty-eight patients were examined approximately 2 years after their revision surgery of the carpal tunnel release. The subjective outcome of the patients was assessed using two different questionnaires (Amadio and DASH). A clinical examination was undertaken on selected patients who had persistent complaints. The clinical assessment analyzed grip strength, thumb opposition, pulp-to-pulp-pinch, key-pinch, hook-grip, Moberg-Pickup-test, two-point-discrimination, Phalen-test, and the Hoffmann-Tinel-sign., Results: The subjective assessment showed that after the revision surgery, patients experienced load induced pain that occurred during daytime. However, the revision was able to improve the impaired sensibility. The functional outcome showed a persistent lack of strength when performing daily activities. The clinical assessment of the patients with relevant complaints confirmed the subjective outcome., Conclusion: The revision surgery can improve the impaired sensibility, particularly, paresthesia nocturna. The persistent weakness of the hand can only partly be improved. In spite of remaining complaints, revision surgery can yield satisfactory results for the patients.

Accumulating data suggest that hepatic tolerance, initially demonstrated by spontaneous acceptance of liver allografts in many species, results from an immune regulatory activity occurring in the liver. However, the responsible cellular and molecular components have not been completely understood. We have recently described profound T cell inhibitory activity of hepatic stellate cells (HSCs) in vitro. In this study, we demonstrate in vivo evidence of immune modulatory activity of HSCs in mice using an islet transplantation model. Co-transplanted HSCs effectively protected islet allografts from rejection, forming a multi-layered capsule, which reduced allograft immunocyte infiltrates by enhancement of apoptotic death. The immune modulation by HSCs appeared to be a local effect, and regulated by inducible expression of B7-H1, an inhibitory molecule of B7 family. This may reflect an intrinsic mechanism of immune inhibition mediated by liver-derived tissue cells. In conclusion, these results may lead to better understanding of liver immunobiology and development of new strategies for treatment of liver diseases.

Background: The goal of this study was the reexamination, description, and analysis of postoperative results after carpal tunnel release reoperation., Patients and Methods: Thirty-eight patients were examined retrospectively 2 years after reoperation of carpal tunnel release. All of them had had complaints after the first operation. On the basis of DASH and Amadio questionnaires after the reoperation, the patients were divided into two groups: good results and inadequate results., Results: The reasons for reoperation included incomplete division of the retinaculum, early fibrosis, reoccurrence, late fibrosis, intraoperative complication, and one unclear situation. A quarter of the patients were free of complaints; three quarters had symptoms in which sensation improved but strength and function did not., Conclusion: The clinical findings showed satisfying results for the patients. Reoperation is indicated after early postoperative deterioriation or if there is no improvement.