The role of environmental factors in insulin-dependent diabetes mellitus: an unresolved issue.

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease characterized by the destruction of the insulin-secreting beta cells found in the islets of Langerhans. Reduced beta-cell mass results in overt diabetes, requiring lifelong exogenous insulin administration and the possibility of numerous sequelae. Incidence and development of IDDM depend upon a variety of genetic and nongenetic factors. Environmental factors such as chemicals, diet, and infection are suspected to influence the development of disease. This review describes the work performed to date to elucidate the role of these environmental factors in IDDM

Cumulative Autoimmunity: T Cell Clones Recognizing Several Self-Epitopes Exhibit Enhanced Pathogenicity

T cell receptor (TCR) recognition is intrinsically polyspecific. In the field of autoimmunity, recognition of both self- and microbial peptides by a single TCR has led to the concept of molecular mimicry. However, findings made by our group and others clearly demonstrate that a given TCR can also recognize multiple distinct self-peptides. Based on experimental data we argue that recognition of several self-peptides increases the pathogenicity of an autoreactive T cell; a property we refer to as “cumulative autoimmunity.” The mechanisms of such increased pathogenicity, and the implications of cumulative autoimmunity regarding the pathophysiology of T cell-mediated autoimmune diseases will be discussed

Injection adipocytolysis for body and jawline contouring: Real-world experience and treatment considerations

BACKGROUND: The role of ATX-101 in submental fat reduction has been well documented; however, its applicability across multiple anatomic areas is to be explored. OBJECTIVES: The authors sought to describe the experience with ATX-101 subcutaneous injections for body and jawline contouring and evaluate its safety. METHODS: This single-arm, single-center observational study included 201 patients who underwent injection adipocytolysis with ATX-101 (area-adjusted dose of 2 mg/cm2) in the jowl, abdomen (upper/lower), thigh (inner/outer/banana roll), arm, anterior periaxillary fat, back (lower/upper/nape/lipoma), knee (anterior/medial), chest, and/or neck. The number of treatment sessions, treatment volumes, doses, injections required for each anatomic area, and associated adverse events were recorded. RESULTS: The mean number of treatment sessions conducted was 1.8. Multiple sessions were common for the jowl (mean: 2.0 and mean volume administered varied significantly between persons receiving 1 or multiple sessions [P = 0.005]). The mean volume and mean number of injections per session were highest in the chest (84.7 mL and 423.5, respectively) and lowest in the jowl (0.8 mL and 4.6, respectively). The chest (0.2 mL) and nape (0.2 mL) received the highest mean ATX-101 dose per injection site per session, whereas the inner thigh (0.11 mL) and upper back (0.11 mL) received the least. Adverse events observed were localized to the injection site. All patients experienced edema after each session, whereas numbness, tenderness, bruising, and paresis were experienced by 99.6%, 94.2%, 33.1%, and 2.6% of patients, respectively. Alopecia was not observed. CONCLUSIONS: ATX-101 was well tolerated for body and jawline contouring

Type 1 Diabetes: A Chronic Anti-Self-Inflammatory Response

Inflammation is typically induced in response to a microbial infection. The release of proinflammatory cytokines enhances the stimulatory capacity of antigen-presenting cells, as well as recruits adaptive and innate immune effectors to the site of infection. Once the microbe is cleared, inflammation is resolved by various mechanisms to avoid unnecessary tissue damage. Autoimmunity arises when aberrant immune responses target self-tissues causing inflammation. In type 1 diabetes (T1D), T cells attack the insulin producing β cells in the pancreatic islets. Genetic and environmental factors increase T1D risk by in part altering central and peripheral tolerance inducing events. This results in the development and expansion of β cell-specific effector T cells (Teff) which mediate islet inflammation. Unlike protective immunity where inflammation is terminated, autoimmunity is sustained by chronic inflammation. In this review, we will highlight the key events which initiate and sustain T cell-driven pancreatic islet inflammation in nonobese diabetic mice and in human T1D. Specifically, we will discuss: (i) dysregulation of thymic selection events, (ii) the role of intrinsic and extrinsic factors that enhance the expansion and pathogenicity of Teff, (iii) defects which impair homeostasis and suppressor activity of FoxP3-expressing regulatory T cells, and (iv) properties of β cells which contribute to islet inflammation

Plasmon signatures in high harmonic generation

High harmonic generation in polarizable multi-electron systems is investigated in the framework of multi-configuration time-dependent Hartree-Fock. The harmonic spectra exhibit two cut offs. The first cut off is in agreement with the well established, single active electron cut off law. The second cut off presents a signature of multi-electron dynamics. The strong laser field excites non-linear plasmon oscillations. Electrons that are ionized from one of the multi-plasmon states and recombine to the ground state gain additional energy, thereby creating the second plateau.Comment: Major revision, 12 pages, 5 figures, submitted to J. Phys. B (2005), accepte

My Wealth, (Y)Our Life Satisfaction? Sole and Joint Wealth Ownership and Life Satisfaction in Marriage

This study examines the money-subjective well-being nexus by studying the link between changes in jointly and solely (i.e. respondents’ own and their partner’s own) held gross wealth and changes in married individuals’ subjective well-being. Joint assets reflect norms of sharing responsibilities and resources. Solely held assets, in contrast, offer individual economic independence. Using wealth data from the German Socio-Economic Panel Study (SOEP; 2002, 2007, 2012, 2017), we estimate individual fixed effects regressions. Although coefficients for all three wealth measures are positive, our results highlight that only increases in jointly held wealth are associated with statistically significant increases in spouses’ life satisfaction in Germany. Despite expectations about a stronger relevance of joint wealth for men compared to women in line with men’s role as a financial provider for the family, we do not find substantial gender differences in the positive association between increases in joint wealth and life satisfaction. In light of the individualisation of marriages, our results highlight that the personal benefits associated with marital sharing of wealth seem to trump those of economic independence and financial autonomy

Single cell analysis shows decreasing FoxP3 and TGFβ1 coexpressing CD4+CD25+ regulatory T cells during autoimmune diabetes

Natural CD4+CD25+ regulatory T (CD4+CD25+ T reg) cells play a key role in the immunoregulation of autoimmunity. However, little is known about the interactions between CD4+CD25+ T reg cells and autoreactive T cells. This is due, in part, to the difficulty of using cell surface markers to identify CD4+CD25+ T reg cells accurately. Using a novel real-time PCR assay, mRNA copy number of FoxP3, TGFβ1, and interleukin (IL)-10 was measured in single cells to characterize and quantify CD4+CD25+ T reg cells in the nonobese diabetic (NOD) mouse, a murine model for type 1 diabetes (T1D). The suppressor function of CD4+CD25+CD62Lhi T cells, mediated by TGFβ, declined in an age-dependent manner. This loss of function coincided with a temporal decrease in the percentage of FoxP3 and TGFβ1 coexpressing T cells within pancreatic lymph node and islet infiltrating CD4+CD25+CD62Lhi T cells, and was detected in female NOD mice but not in NOD male mice, or NOR or C57BL/6 female mice. These results demonstrate that the majority of FoxP3-positive CD4+CD25+ T reg cells in NOD mice express TGFβ1 but not IL-10, and that a defect in the maintenance and/or expansion of this pool of immunoregulatory effectors is associated with the progression of T1D

Relations of the level of morphological differentiation and metabolic activity of squamous carcinomas of oropharyngeal areas according to positron emission tomography

Today verification and grading of oropharyngeal tumors, determination of their malignant potential remain an actual problem both in diagnostics and in predicting the growth of tumors. The aim of the study was to determine the metabolic activity of the oropharyngeal tumors due to positron emission tomographic diagnosis and comparison with the morphological (histological) pattern. Materials and methods. From May 1, 2012 to January 1, 2015, on the basis of the military hospital of Bundeswehr in Ulm, we investigated 121 cases of squamous-cell carcinoma of the oropharyngeal area with preoperative use of positron emission tomographic (PET) diagnostics. We have studied the relationship between the accumulation of 2-fluoro [18F] -2-deoxy-D-glucose and certain morphological criteria. The study assessed the level of differentiation according to the method of Anneroth et al., 1987 and Bryne et al., 1992. Results. After selecting and viewing the biopsy and surgical material, depending on the level of morphological differentiation of the tumors, the patients were divided into three main groups. In the first, which includes highly differentiated – G1 tumors – 22 patients, in group 2, in contrast to G2 – 45 and in group 3, poorly differentiated G3 – 54. We have morphologically described all these groups. Later in the groups, PET results were evaluated according to the SUVmax index. Comparing the indices, a statistically significant difference was found between the groups (P < 0.001 by the Kruskal–Wallis criterion for all indicators). So, as the level of Me decreases, the differentiation of SUVmax tumors significantly (P < 0.05) increases, and the growth of SUVmax indicates an increase in the degree of malignancy of the tumors. Conclusions. On the basis of the conducted research, a statistically visible relationship between the SUVmax and the level of morphological differentiation of squamous carcinomas of the oropharyngeal area was established. The possibility of using the method of PET diagnostics as a possible criterion for assessing the level of differentiation of tumors, including complex squamous carcinomas of the oropharyngeal area, has been demonstrated

Attosecond streaking of photoelectron emission from disordered solids

Attosecond streaking of photoelectrons emitted by extreme ultraviolet light has begun to reveal how electrons behave during their transport within simple crystalline solids. Many sample types within nanoplasmonics, thin-film physics, and semiconductor physics, however, do not have a simple single crystal structure. The electron dynamics which underpin the optical response of plasmonic nanostructures and wide-bandgap semiconductors happen on an attosecond timescale. Measuring these dynamics using attosecond streaking will enable such systems to be specially tailored for applications in areas such as ultrafast opto-electronics. We show that streaking can be extended to this very general type of sample by presenting streaking measurements on an amorphous film of the wide-bandgap semiconductor tungsten trioxide, and on polycrystalline gold, a material that forms the basis of many nanoplasmonic devices. Our measurements reveal the near-field temporal structure at the sample surface, and photoelectron wavepacket temporal broadening consistent with a spread of electron transport times to the surface