On the dialectics of power and revolution: a few reflections on the work of John Holloway "Change the World Without Taking Power"

This study consists in a critical approach to Holloway’s ‘Open Marxism’, as presented in his Change the world without taking power. In defense of the so-called revolutionary Marxist tradition, represented by radical Marxist thinkers as Lenin, Trotsky, Luxemburg, Gramsci and Lukács, the author strongly opposes Holloway’s argument that scientific Marxism in toto succumbed actually to the bourgeois ideology of science, state, power etc. Consequently, this analysis focuses on how Holloway himself mistreats crucial concepts such as ‘science’, ‘state’, ‘party’ and ‘power’. Victim and fanatic of a theology of Negation, Holloway follows an abstract ‘either-or’ mode of thinking and arguing, and fails to treat dialectically critical relations as those among science and ideology, state and revolution, movement and party. According to this study, Holloway’s anti-capitalistic rhetoric and post-modernist methodology are nothing more than expressions of an old-fashioned anarchist ideology, against which classical Marxism, adapted to contemporary needs and conditions, can function as a radical critique. As the author suggests, searching for the meaning of the revolution nowadays, Holloway confuses the Marxist concept of science with the positivistic one and fatally mistakes a political caricature of Marxism, i.e. a Blanquist or/ and a Stalinist misinterpretation of the Marxist theory of revolution, for revolutionary Marxism itself

Pathologic findings in reduction mammaplasty specimens: a South African perspective

Background Preoperative, intraoperative and follow-up guidelines for managing occult carcinoma in reduction mammoplasty specimens are scant. Methods We retrospectively analysed the records and pathology reports of 200 patients who had undergone reduction mammoplasty at two major public hospitals in Johannesburg, South Africa, during 2009 - 2014. Demographic data, their history of breast cancer and preoperative screening, and the surgical techniques used and pathological reports were included. In all cases, preoperative screening for breast cancer had been negative. Results All the patients were female, mean age 37.1 years, range 20 - 84 (standard deviation 11.9). All reductions were performed using standard techniques. Benign pathology was observed in 98 patients (49%) and malignant pathology in four (2%). The most common benign pathology observed was fibrocystic disease, and the most common malignant pathology ductal carcinoma in situ. Patient age correlated significantly with benign or malignant disease. Conclusions Reduction mammoplasty produces tissue that should always be sent for pathological assessment. Patients should be stratified by risk, as doing so helps in selecting both the surgical setting and the approach to pathological analysis of the specimen. While the Pathologic findings in reduction mammaplasty specimens: A South African perspective incidence of occult carcinoma in reduction mammoplasty specimens is low, all patients undergoing the procedure should be informed that tissue will be sent for pathological examination, allowing them to prepare to receive possible news of breast cancer and be adequately equipped for subsequent decision-making.LG201

Co-creating high-value hospitality services in the tourism ecosystem: Towards a paradigm shift?

Purpose: Adopting the service-ecosystem perspective, this is the first empirical study conceptualising tourism as an ecosystem. Based on the institutional theory and focusing on high-value hospitality services, it aims to unveil the components of the multilayer tourism ecosystem that enable stakeholders’ interactions at and between different levels. Methods: Applying a qualitative research design in Rhodes, the study focuses on value co-creation to explore the structure of the tourism ecosystem and its underlying mechanisms. Triangulation and bracketing were employed to ensure the reliability of the data collected through ten semi-structured interviews with high-ranking tourism policy-makers and hotel/restaurant managers. Results: The results led to the identification of the three-level service ecosystem (micro, meso, macro) that incorporates myriads of actions and interactions shaping tourism activity in order to provide high-value hospitality services. The analysis also revealed the institutional logic that permeates all levels (rules, norms, practices, meanings and symbols). Implications: The study goes beyond the destination-visitor and firm-guest interactions to incorporate multiple stakeholders co-creating value in the tourism ecosystem, including tourists, locals and employees, hotels and restaurants, DMOs and other organisations supporting the tourism value chain. It sheds light on the new paradigm shift from the notion of tourism industry to the concept of an inclusive tourism ecosystem, paving the way for future research to address global challenges in the COVID-19 era

Ablation of the Pro-Apoptotic Protein Bax Protects Mice from Glucocorticoid-Induced Bone Growth Impairment

Dexamethasone (Dexa) is a widely used glucocorticoid to treat inflammatory diseases; however, a multitude of undesired effects have been reported to arise from this treatment including osteoporosis, obesity, and in children decreased longitudinal bone growth. We and others have previously shown that glucocorticoids induce apoptosis in growth plate chondrocytes. Here, we hypothesized that Bax, a pro-apoptotic member of the Bcl-2 family, plays a key role in Dexa-induced chondrocyte apoptosis and bone growth impairment. Indeed, experiments in the human HCS-2/8 chondrocytic cell line demonstrated that silencing of Bax expression using small-interfering (si) RNA efficiently blocked Dexa-induced apoptosis. Furthermore, ablation of Bax in female mice protected against Dexa-induced bone growth impairment. Finally, Bax activation by Dexa was confirmed in human growth plate cartilage specimens cultured ex vivo. Our findings could therefore open the door for new therapeutic approaches to prevent glucocorticoid-induced bone growth impairment through specific targeting of Bax

Dexamethasone stimulates expression of C-type Natriuretic Peptide in chondrocytes

BACKGROUND: Growth of endochondral bones is regulated through the activity of cartilaginous growth plates. Disruption of the physiological patterns of chondrocyte proliferation and differentiation – such as in endocrine disorders or in many different genetic diseases (e.g. chondrodysplasias) – generally results in dwarfism and skeletal defects. For example, glucocorticoid administration in children inhibits endochondral bone growth, but the molecular targets of these hormones in chondrocytes remain largely unknown. In contrast, recent studies have shown that C-type Natriuretic Peptide (CNP) is an important anabolic regulator of cartilage growth, and loss-of-function mutations in the human CNP receptor gene cause dwarfism. We asked whether glucocorticoids could exert their activities by interfering with the expression of CNP or its downstream signaling components. METHODS: Primary mouse chondrocytes in monolayer where incubated with the synthetic glucocorticoid Dexamethasone (DEX) for 12 to 72 hours. Cell numbers were determined by counting, and real-time PCR was performed to examine regulation of genes in the CNP signaling pathway by DEX. RESULTS: We show that DEX does influence expression of key genes in the CNP pathway. Most importantly, DEX significantly increases RNA expression of the gene encoding CNP itself (Nppc). In addition, DEX stimulates expression of Prkg2 (encoding cGMP-dependent protein kinase II) and Npr3 (natriuretic peptide decoy receptor) genes. Conversely, DEX was found to down-regulate the expression of the gene encoding its receptor, Nr3c1 (glucocorticoid receptor), as well as the Npr2 gene (encoding the CNP receptor). CONCLUSION: Our data suggest that the growth-suppressive activities of DEX are not due to blockade of CNP signaling. This study reveals a novel, unanticipated relationship between glucocorticoid and CNP signaling and provides the first evidence that CNP expression in chondrocytes is regulated by endocrine factors

Anemia in Patients With Resistance to Thyroid Hormone α: A Role for Thyroid Hormone Receptor α in Human Erythropoiesis

Context: Patients with resistance to thyroid hormone (TH) α (RTHα) are characterized by growth retardation, macrocephaly, constipation, and abnormal thyroid function tests. In addition, almost all RTHα patients have mild anemia, the pathogenesis of which is unknown. Animal studies suggest an important role for TH and TH receptor (TR)α in erythropoiesis.Objective: To investigate whether a defect in TRα affects the maturation of red blood cells in RTHα patients.Design, Setting, and Patients: Cultures of primary human erythroid progenitor cells (HEPs), from peripheral blood of RTHα patients (n = 11) harboring different inactivating mutations in TRα (P398R, F397fs406X, C392X, R384H, A382fs388X, A263V, A263S), were compared with healthy controls (n = 11). During differentiation, erythroid cells become smaller, accumulate hemoglobin, and express different cell surface markers. We assessed cell number and cell size, and used cell staining and fluorescence-activated cell sorter analysis to monitor maturation at different time points.Results: After ∼14 days of ex vivo expansion, both control and patient-derived progenitors differentiated spontaneously. However, RTHα-derived cells differentiated more slowly. During spontaneous differentiation, RTHα-derived HEPs were larger, more positive for c-Kit (a proliferation marker), and less positive for glycophorin A (a differentiation marker). The degree of abnormal spontaneous maturation of RTHα-derived progenitors did not correlate with severity of underlying TRα defect. Both control and RTHα-derived progenitors responded similarly when differentiation was induced. T3 exposure accelerated differentiation of both control- and RTHα patient-derived HEPs.Conclusions: Inactivating mutations in human TRα affect the balance between proliferation and differentiation of progenitor cells d

TSH elevations as the first laboratory evidence for pseudohypoparathyroidism type Ib (PHP-Ib).

Hypocalcemia and hyperphosphatemia because of resistance toward parathyroid hormone (PTH) in the proximal renal tubules are the most prominent abnormalities in patients affected by pseudohypoparathyroidism type Ib (PHP-Ib). In this rare disorder, which is caused by GNAS methylation changes, resistance can occur toward other hormones, such as thyroid-stimulating hormone (TSH), that mediate their actions through G protein-coupled receptors. However, these additional laboratory abnormalities are usually not recognized until PTH-resistant hypocalcemia becomes clinically apparent. We now describe four pediatric patients, first diagnosed with subclinical or overt hypothyroidism between the ages of 0.2 and 15 years, who developed overt PTH-resistance 3 to 20 years later. Although anti-thyroperoxidase (anti-TPO) antibodies provided a plausible explanation for hypothyroidism in one of these patients, this and two other patients revealed broad epigenetic GNAS abnormalities, which included loss of methylation (LOM) at exons AS, XL, and A/B, and gain of methylation at exon NESP55; ie, findings consistent with PHP-Ib. LOM at GNAS exon A/B alone led in the fourth patient to the identification of a maternally inherited 3-kb STX16 deletion, a well-established cause of autosomal dominant PHP-Ib. Although GNAS methylation changes were not detected in additional pediatric and adult patients with subclinical hypothyroidism (23 pediatric and 39 adult cases), hypothyroidism can obviously be the initial finding in PHP-Ib patients. One should therefore consider measuring PTH, along with calcium and phosphate, in patients with unexplained hypothyroidism for extended periods of time to avoid hypocalcemia and associated clinical complications

Effects of insulin-like growth factor-1 and dexamethasone on cytokine-challenged cartilage: relevance to post-traumatic osteoarthritis

SummaryObjectiveInterleukin-1 is one of the inflammatory cytokines elevated after traumatic joint injury that plays a critical role in mediating cartilage tissue degradation, suppressing matrix biosynthesis, and inducing chondrocyte apoptosis, events associated with progression to post-traumatic osteoarthritis (PTOA). We studied the combined use of insulin-like growth factor-1 (IGF-1) and dexamethasone (Dex) to block these multiple degradative effects of cytokine challenge to articular cartilage.MethodsYoung bovine and adult human articular cartilage explants were treated with IL-1α in the presence or absence of IGF-1, Dex, or their combination. Loss of sulfated glycosaminoglycans (sGAG) and collagen were evaluated by the DMMB and hydroxyproline assays, respectively. Matrix biosynthesis was measured via radiolabel incorporation, chondrocyte gene expression by qRT-PCR, and cell viability by fluorescence staining.ResultsIn young bovine cartilage, the combination of IGF-1 and Dex significantly inhibited the loss of sGAG and collagen, rescued the suppression of matrix biosynthesis, and inhibited the loss of chondrocyte viability caused by IL-1α treatment. In adult human cartilage, only IGF-1 rescued matrix biosynthesis and only Dex inhibited sGAG loss and improved cell viability. Thus, the combination of IGF-1 + Dex together showed combined beneficial effects in human cartilage.ConclusionsOur findings suggest that the combination of IGF-1 and Dex has greater beneficial effects than either molecule alone in preventing cytokine-mediated cartilage degradation in adult human and young bovine cartilage. Our results support the use of such a combined approach as a potential treatment relevant to early cartilage degradative changes associated with joint injury