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This essay offers a detailed description of the contours and political stakes of the debate around working-class dealignment from the Democratic Party. It shows that the phenomenon is real and explains why it matters, surveys prominent accounts of how working-class drift can be addressed, and offers a set of tentative paths forward., A battle is raging among US progressives over how to understand the political attitudes and strategic significance of the working class in American politics. Have workers really abandoned the Democratic [...]

Despite participatory institutions' increasing ubiquity, we know little about their effects on governance and well-being. What we do know comes largely from Brazil, where positive outcomes have been attributed to civil society's role in implementation. Often, however, participatory institutions are imposed by national governments, with little civil society engagement. In these cases, scholars have argued, participatory institutions are unlikely to improve governance and well-being, as civil society is not present to unlock the institutions' potential. We test this proposition in Peru, the first country featuring government mandated participatory institutions for all subnational governments. We find, surprisingly, that Peru's participatory budgeting process increased pro-poor spending and improved citizen's quality of life. We attribute these outcomes to reduced information asymmetries, made possible by the central role played by an influential and autonomous government agency. We employ a unique panel dataset, as well as an original survey and extensive interviews with government and civil society actors. [ABSTRACT FROM AUTHOR]

How does the structure of democratic institutions affect citizen engagement? This study employs conjoint analysis to assess the effects of institutional design on political participation in participatory budgeting (PB) programs. We find evidence that PB program design strongly affects citizens' interest in participation. Participation appeals more to citizens when PB programs offer participants meaningful control over decision‐making outcomes, when barriers to participation are low, and when resources allocated through PB are targeted diffusely to communities rather than individual beneficiaries. We also find that focusing PB on issues specific to marginalized communities does not necessarily boost interest in participation among members of those communities. Finally, we observe few systematic differences in preferences for participation between demographic groups traditionally associated with low rates of civic engagement compared to other groups. We then use the results surrounding PB to discuss broad implications for citizen participation in participatory institutions and democratic governance. [ABSTRACT FROM AUTHOR]

Research has been conducted on the gamma-glutamylcysteine synthetase which catalyzes ATP-dependent L-Glu and L-Cys ligation. The role of the amino acid residues in the kinetic properties of the substrates in the reaction catalyzed by Trypanosoma brucei gamma-glutamylcysteine synthetase has been examined and discussed.

Seth Masket's book Learning From Loss: The Democrats, 2016-2020 draws important lessons from Democrats' postmortem of their 2016 electoral defeat. Chief among these is that, given the party's dependence on white suburban voters and the threat of resurgent Trumpism, they will most likely double down on their risk-averse 2020 strategy, thereby inviting further working-class defections. [ABSTRACT FROM AUTHOR]

The article focuses on practical proposal for a viable socialist electoral strategy and popular control, the Left has never found a way of sustained electoral success. It mentions obvious choice is to abandon the electoral arena altogether and to opt for a permanent "movementism" and constraints that have thus far derailed all attempts to forge an electoral vehicle for the Left. It also mentions first step toward building a socialist party, distinct from workplace organizing.

Research was conducted to examine the mechanistic role of the Lys-69 residue in catalysis by Trypanosoma brucei ornithine decarboxylase (ODC) via an analysis of the mutant enzymes. It was found that the enzyme copurified with amines hat were tightly bound to the active site through a Schiff base with pyridoxal-5'-phosphate-dependent. A kinetic analysis of the binding of a series of diamines and amino acids to Arg ODC indicates that noncovalent interactions in the active site of Arg ODC promote selective ligand biding during Schiff base formation.

Objective: To identify correlations between clinical presentation, specific histopathologic findings, and subsequent disease course in patients with necrobiotic xanthogranuloma (NXG). Design: Retrospective review of medical records and histopathologic examination of fixed tissue samples. Setting: Tertiary care medical center. Patients: Seventeen patients with a diagnosis of NXG established between January 1, 1994, and December 31, 2007. Main Outcome Measures: Description and distribution of clinical lesions, presence of monoclonal gammopathy, multiple myeloma, and correlation with microscopic patterns of skin lesions. Results:: Eleven patients (65%) showed involvement of the periorbital area, and the trunk was affected in 8 patients (47%). Twelve patients (71%) had a monoclonal gammopathy; of these, 3 (18%) had multiple myeloma. Histopathologic examination of 12 patients showed findings consistent with NXG, including a band like pattern of necrobiotic granulomatous inflammation, atypical giant cells, cholesterol clefts, and plasma cells. No correlations were identified between clinical presentation and specific histopathologic findings. Although most patients had a serum monoclonal gammopathy, staining with antibodies to CD3, CD20, k light chains, and k light chains showed polytypic lymphocytes and plasma cells in all cases. Conclusions: The association between NXG and paraproteinemia is well documented and corroborated by this study. However, the skin lesions in NXG represent reactive inflammation and are not associated with the presence of monoclonal plasma cells or multiple myeloma. [ABSTRACT FROM AUTHOR]

Determines the substrate binding determinants of trypanosoma brucei γ-glutamylcysteine synthetase. Consideration of R366 and R491 as determinants of L-glu binding; Mechanism of substrate binding; Impact of the mutation of residues on the substrates.

Background: Extramammary Paget disease (EMPD) is categorized into 2 groups: primary EMPD or EMPD secondary to underlying malignancy. Primary EMPD has a better prognosis, and the ability to distinguish between the 2 subsets has clinical relevance. Recent studies have suggested that immunostains, including cytokeratin (CK) 7, CK20, and BRST-2, distinguish between the 2 groups. We analyzed a large series of EMPD with an expanded immunohistochemical panel to assess its value in distinguishing primary from secondary disease., Design: Formalin-fixed, paraffin-embedded sections of 98 EMPD specimens from 61 patients (45 primary and 16 secondary) were immunostained with CK7, CK20, HER-2/neu, BRST-2, CDX2, androgen receptor (AR), and cyclin D1. The study included 44 women and 17 men (median age: 73 years). Median follow-up time was 47 months., Results: All EMPD specimens were vibrantly positive for CK7. The frequency of positivity for all EMPD samples was CK20 (28%), BRST-2 (40%), HER-2/neu (64%), CDX2 (10%), AR (16%), and cyclin D1 (76%). For primary EMPD, the frequency of positivity was CK20 (22%), BRST-2 (48%), HER-2/neu (65%), CDX2 (2%), AR (21%), and cyclin D1 (84%). For secondary EMPD, the frequency of positivity was CK20 (50%), BRST-2 (25%), HER-2/neu (60%), CDX2 (33%), AR (0%), and cyclin D1 (53%). Notably, all 6 of 7 cases of EMPD secondary to an anorectal adenocarcinoma tested were HER-2/neu negative and 5 of those 6 cases (80%) were CDX2 positive., Conclusions: The role of CK7, CK20, and BRST-2 in distinguishing primary and secondary EMPD is limited because CK20 and BRST-2 were positive in large subsets of both groups. An expanded immunohistochemical panel, including HER-2/neu and CDX2, may be useful in discriminating primary EMPD from EMPD secondary to anorectal adenocarcinoma but fails to distinguish primary EMPD from EMPD secondary to urothelial or prostatic malignancy. The consistent overexpression of HER-2/neu in primary EMPD suggests a role for trastuzumab therapy in patients with recurrent disease.

The morphological features of epithelioid sarcoma may closely mimic those of epithelial neoplasms, such as squamous cell carcinoma, mesenchymal tumors, such as benign fibrous histiocytoma, and nonneoplastic lesions, such as granuloma annulare. Immunohistochemistry, particularly for epithelial markers and CD34, thus plays a valuable role in the differential diagnosis of epithelioid sarcoma. However, some epithelioid sarcomas may show very focal or even absent expression of such markers and may be difficult to distinguish from various morphological mimics. There is therefore continued interest in the development of new immunohistochemical markers of epithelioid sarcoma. Recently, loss of expression of INI1, a tumor suppressor gene/protein, and expression of GLUT-1, a glucose transporter protein, have been described in epithelioid sarcoma. We examined the utility of immunohistochemistry for INI1 and GLUT-1 in the diagnosis of epithelioid sarcoma and various cutaneous mimics. Twenty-four cases of epithelioid sarcoma, 13 cases of granuloma annulare, 10 cases of rheumatoid nodule, 19 cases of cutaneous squamous cell carcinoma, 7 cases of atypical fibroxanthoma, 9 cases of benign fibrous histiocytoma (dermatofibroma), and 3 cases of nodular fasciitis were immunostained for GLUT-1 and INI1 using commercially available antibodies, heat-induced epitope retrieval, and the Dako Envision detection system. Total or near-total loss of normal constitutive expression of INI1 protein was noted in more than 85% of epithelioid sarcomas, with 19 of 24 cases (79%) showing complete loss of INI1 expression. In contrast, all other cases studied showed uniformly retained expression of INI1. GLUT-1 was positive in 40%-50% of epithelioid sarcomas, all cases of granuloma annulare and rheumatoid nodules, 67% of benign fibrous histiocytomas, and in all squamous cell carcinomas. In contrast, atypical fibroxanthomas and cases of nodular fasciitis were consistently GLUT-1 negative. We conclude that immunohistochemistry for INI1 expression should be included as part of the routine immunohistochemical panel for the diagnosis of epithelioid sarcoma, along with established markers such as wide-spectrum cytokeratins, cytokeratin 5/6, p63, and CD34. In this clinical context, loss of INI1 expression seems to be an entirely specific marker of epithelioid sarcoma and this finding may be of great value in distinguishing CD34-negative epithelioid sarcoma from squamous cell carcinoma and in the distinction of rare cytokeratin-negative epithelioid sarcomas from necrobiotic processes, nodular fasciitis, and benign fibrous histiocytomas. In contrast, there does not seem to be a role for GLUT-1 immunohistochemistry in this differential diagnosis.

Mammary-like glands are a poorly recognized structure of normal vulvar skin. Adenocarcinomas arising from these glands are rare and represent a distinct clinicopathologic entity that must be distinguished from metastatic tumors. We reviewed 19 cases reported in the literature and describe a 51-year-old patient with a long-standing nodule on her right interlabial sulcus. Excisional biopsy and Mohs micrographic surgery demonstrated an infiltrating adenocarcinoma of the mammary-like glands involving the dermis and subcutis. On review of all 20 cases, the mean age at diagnosis was 59.6 years, the labia majora were involved in 13 cases (65%), and the mean lesional size was 2.5 cm. The tumor's histologic patterns varied greatly, although the histomorphologic similarity among this neoplasm, sweat gland carcinomas, and invasive extramammary Paget disease suggested a morphologic spectrum among these tumors. Criteria for establishing the diagnosis of adenocarcinoma of mammary-like glands include identifying transition zones between normal mammary-like glands and adenocarcinomatous areas. This tumor is best categorized as a locally aggressive neoplasm with a low risk for widespread metastasis. Use of aggressive surgical therapeutic regimens, particularly in the case of tumors localized to the skin, must be reassessed, especially given the likelihood of long-term morbidity with such regimens. In our patient, successful Mohs micrographic surgery suggests that alternate management may be adopted for tumors localized to the skin, especially in elderly patients.

Dermatofibrosarcoma protuberans (DFSP) is a superficial tumor characterized by high rates of local recurrence and a small risk of metastasis. Fibrosarcomatous (FS) areas rarely arise in DFSP, and considerable controversy exists as to whether these tumors have a higher risk of metastasis than the typical DFSP. The aim of this study was to reappraise the prognostic significance of FS changes in DFSP by analyzing 41 patients from the consultation files of our institution. The study included 23 females and 18 males, with a median age of 48 years (range, 16-100 years). Eighteen lesions were located on the trunk, 16 on the extremities, and 7 on the head/neck region. All tumors were treated with local excision, and the surgical margins were considered positive for tumor in 22 of 39 cases (56%). Fibrosarcomas arose de novo in 38 cases and as a recurrence in 3 cases. All tumors involved the dermis and subcutis, and the FS component comprised 5% to 95% of the tumor area (median, 60%). Mitotic rates of the FS component (median, 20 mitoses/10 high-power fields [HPFs]; range, 5-48/10 HPFs) were considerably higher than those of the neighboring DFSP component (0-2 mitoses/10 HPFs). Immunohistochemical analyses showed that CD34 expression was stronger and more extensive in the DFSP component (97% positive; median intensity, 3+) than in the FS component (81% positive; median intensity, 2+). The MIB-1 labeling index was higher in the FS areas (median, 20%; range, 5%-45%) than in the DFSP areas (<3%). Expression of p53 was present in 92% of the FS areas and in only 3% of adjacent DFSP areas. Follow-up data revealed that 8 patients had local recurrences, 4 patients (10%) had metastases, and 2 patients died of disease. None of the variables evaluated, including margin status, FS proportion, and mitotic count, correlated with disease progression. We demonstrate that FS change in DFSP is a form of tumor progression that carries an increased risk of metastasis over classic DFSP and is associated with gains of p53 mutations and increased proliferative activity.