Fiscal Disobedience represents a novel approach to the question of citizenship amid the changing global economy and the fiscal crisis of the nation-state. Focusing on economic practices in the Chad ...Basin of Africa, Janet Roitman combines thorough ethnographic fieldwork with sophisticated analysis of key ideas of political economy to examine the contentious nature of fiscal relationships between the state and its citizens. She argues that citizenship is being redefined through a renegotiation of the rights and obligations inherent in such economic relationships. The book centers on a civil disobedience movement that arose in Cameroon beginning in 1990 ostensibly to counter state fiscal authority--a movement dubbed Opération Villes Mortes by the opposition and incivisme fiscal by the government (which for its part was eager to suggest that participants were less than legitimate citizens, failing in their civic duties). Contrary to standard approaches, Roitman examines this conflict as a "productive moment" that, rather than involving the outright rejection of regulatory authority, questioned the intelligibility of its exercise. Although both militarized commercial networks (associated with such activities trading in contraband goods including drugs, ivory, and guns) and highly organized gang-based banditry do challenge state authority, they do not necessarily undermine state power. Contrary to depictions of the African state as "weak" or "failed," this book demonstrates how the state in Africa manages to reconstitute its authority through networks that have emerged in the interstices of the state system. It also shows how those networks partake of the same epistemological grounding as does the state. Indeed, both state and nonstate practices of governing refer to a common "ethic of illegality," which explains how illegal activities are understood as licit or reasonable conduct.
Purpose of Review
The purpose of this review is to summarize the scientific evidence on bone health in transgender and gender diverse (TGD) youth.
Recent Findings
Gender-affirming medical therapies ...may be introduced during a key window of skeletal development in TGD adolescents. Before treatment, low bone density for age is more prevalent than expected in TGD youth. Bone mineral density
Z
-scores decrease with gonadotropin-releasing hormone agonists and differentially respond to subsequent estradiol or testosterone. Risk factors for low bone density in this population include low body mass index, low physical activity, male sex designated at birth, and vitamin D deficiency. Peak bone mass attainment and implications for future fracture risk are not yet known.
Summary
TGD youth have higher than expected rates of low bone density prior to initiation of gender-affirming medical therapy. More studies are needed to understand the skeletal trajectories of TGD youth receiving medical interventions during puberty.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Coronavirus Disease 2019 (COVID-19) is caused by the betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus that can mediate asymptomatic or fatal infections ...characterized by pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. Several studies have highlighted the importance of B and T lymphocytes, given that neutralizing antibodies and T cell responses are required for an effective immunity. In addition, other reports have described myeloid cells such as macrophages and monocytes play a major role in the immunity against SARS-CoV-2 as well as dysregulated pro-inflammatory signature that characterizes severe COVID-19. During COVID-19, neutrophils have been defined as a heterogeneous group of cells, functionally linked to severe inflammation and thrombosis triggered by degranulation and NETosis, but also to suppressive phenotypes. The physiological role of suppressive neutrophils during COVID-19 and their implications in severe disease have been poorly studied and is not well understood. Here, we discuss the current evidence regarding the role of neutrophils with suppressive properties such as granulocytic myeloid-derived suppressor cells (G-MDSCs) and their possible role in suppressing CD4+ and CD8+ T lymphocytes expansion and giving rise to lymphopenia in severe COVID-19 infection.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Irreproducibility of preclinical biomedical research has gained recent attention. It is suggested that requiring authors to complete a checklist at the time of manuscript submission would improve the ...quality and transparency of scientific reporting, and ultimately enhance reproducibility. Whether a checklist enhances quality and transparency in reporting preclinical animal studies, however, has not been empirically studied. Here we searched two highly cited life science journals, one that requires a checklist at submission (Nature) and one that does not (Cell), to identify in vivo animal studies. After screening 943 articles, a total of 80 articles were identified in 2013 (pre-checklist) and 2015 (post-checklist), and included for the detailed evaluation of reporting methodological and analytical information. We compared the quality of reporting preclinical animal studies between the two journals, accounting for differences between journals and changes over time in reporting. We find that reporting of randomization, blinding, and sample-size estimation significantly improved when comparing Nature to Cell from 2013 to 2015, likely due to implementation of a checklist. Specifically, improvement in reporting of the three methodological information was at least three times greater when a mandatory checklist was implemented than when it was not. Reporting the sex of animals and the number of independent experiments performed also improved from 2013 to 2015, likely from factors not related to a checklist. Our study demonstrates that completing a checklist at manuscript submission is associated with improved reporting of key methodological information in preclinical animal studies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Obstructive sleep apnea syndrome (OSAS) is a common and underdiagnosed medical condition characterized by recurrent sleep-dependent pauses and reductions in airflow. While a narrow, collapsible ...oropharynx plays a central role in the pathophysiology of OSAS, there are other equally important nonanatomic factors including sleep-stage dependent muscle tone, arousal threshold, and loop gain that drive obstructive apneas and hypopneas. Through mechanisms of intermittent hypoxemia, arousal-related sleep fragmentation, and intrathoracic pressure changes, OSAS impacts multiple organ systems. Risk factors for OSAS include obesity, male sex, age, specific craniofacial features, and ethnicity. The prevalence of OSAS is rising due to increasing obesity rates and improved sensitivity in the tools used for diagnosis. Validated questionnaires have an important but limited role in the identification of patients that would benefit from formal testing for OSA. While an in-laboratory polysomnography remains the gold standard for diagnosis, the widespread availability and accuracy of home sleep apnea testing modalities increase access and ease of OSAS diagnosis for many patients. In adults, the most common treatment involves the application of positive airway pressure (PAP), but compliance continues to be a challenge. Alternative treatments including mandibular advancement device, hypoglossal nerve stimulator, positional therapies, and surgical options coupled with weight loss and exercise offer possibilities of an individualized personal approach to OSAS. Treatment of symptomatic patients with OSAS has been found to be beneficial with regard to sleep-related quality of life, sleepiness, and motor vehicle accidents. The benefit of treating asymptomatic OSA patients, particularly with regard to cardiovascular outcomes, is controversial and more data are needed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Serrated polyps (hyperplastic polyps, sessile or traditional serrated adenomas), which can arise in a sporadic or polyposis setting, predispose to colorectal cancer (CRC), especially those with ...microsatellite instability (MSI) due to MLH1 promoter methylation (MLH1
). We investigate genetic alterations in the serrated polyposis pathway.
We used a combination of exome sequencing and target gene Sanger sequencing to study serrated polyposis families, sporadic serrated polyps and CRCs, with validation by analysis of The Cancer Genome Atlas (TCGA) cohort, followed by organoid-based functional studies.
In one out of four serrated polyposis families, we identified a germline RNF43 mutation that displayed autosomal dominant cosegregation with the serrated polyposis phenotype, along with second-hit inactivation through loss of heterozygosity or somatic mutations in all serrated polyps (16), adenomas (5) and cancer (1) examined, as well as coincidental BRAF mutation in 62.5% of the serrated polyps. Concurrently, somatic RNF43 mutations were identified in 34% of sporadic sessile/traditional serrated adenomas, but 0% of hyperplastic polyps (p=0.013). Lastly, in MSI CRCs, we found significantly more frequent RNF43 mutations in the MLH1
(85%) versus MLH1
(33.3%) group (p<0.001). These findings were validated in the TCGA MSI CRCs (p=0.005), which further delineated a significant differential involvement of three Wnt pathway genes between these two groups (RNF43 in MLH1
; APC and CTNNB1 in MLH1
); and identified significant co-occurrence of BRAF and RNF43 mutations in the MSI (p<0.001), microsatellite stable (MSS) (p=0.002) and MLH1
MSI CRCs (p=0.042). Functionally, organoid culture of serrated adenoma or mouse colon with CRISPR-induced RNF43 mutations had reduced dependency on R-spondin1.
These results illustrate the importance of RNF43, along with BRAF mutation in the serrated neoplasia pathway (both the sporadic and familial forms), inform genetic diagnosis protocol and raise therapeutic opportunities through Wnt inhibition in different stages of evolution of serrated polyps.
Familial hypocalciuric hypercalcemia and related disorders Lee, Janet Y.; Shoback, Dolores M.
Baillière's best practice and research in clinical endocrinology and metabolism/Baillière's best practice & research. Clinical endocrinology & metabolism,
10/2018, Volume:
32, Issue:
5
Journal Article
Peer reviewed
Open access
Familial hypocalciuric hypercalcemia (FHH) causes hypercalcemia by three genetic mechanisms: inactivating mutations in the calcium-sensing receptor, the G-protein subunit α11, or adaptor-related ...protein complex 2, sigma 1 subunit. While hypercalcemia in other conditions causes significant morbidity and mortality, FHH generally follows a benign course. Failure to diagnose FHH can result in unwarranted treatment or surgery for the mistaken diagnosis of primary hyperparathyroidism (PHPT), given the significant overlap of biochemical features. Determinations of urinary calcium excretion greatly aid in distinguishing PHPT from FHH, but overlap still exists in certain cases. It is important that 24-h urine calcium and creatinine be included in the initial workup of hypercalcemia. FHH should be considered if low or even low normal urinary calcium levels are found in what is typically an asymptomatic hypercalcemic patient. The calcimimetic cinacalcet has been used to treat hypercalcemia in certain symptomatic causes of FHH.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Transgender and gender-diverse (TGD) youth may pursue gender-affirming medical therapy in the form of gonadotropin-releasing hormone analogues (GnRHa), or "puberty blockers," if pubertal changes ...result in the development or worsening of gender dysphoria. GnRHa monotherapy can allow TGD youth to explore gender without the distress of unwanted secondary sexual characteristics. However, given the potential effects of GnRHa on growth, skeletal development, neurodevelopment, fertility, and future surgical outcomes, it is critical to accurately assess pubertal status to facilitate fully informed conversations with TGD youth and families about risks, benefits, and unknown consequences of GnRHa monotherapy. The focus of this discussion will be on the approach to puberty assessment in TGD youth as well as the different effects of GnRHa monotherapy that may be important to TGD youth and their families.
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Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. ...Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.
Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7). Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro. In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy. CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression. Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1(-/-) mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.
We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo. The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tabary and Lee discuss alveolar macrophage geterogeneity. The lungs are constantly exposed to potentially harmful environmental gases, particles, toxins, allergens, and pathogens. Immune system has ...been ascribed the crucial role of protection against these insults. Alveolar macrophages (AMs) perform the duties of frontline soldiers tasked with airway surveillance, immune regulation, and surfactant homeostasis. Recent interest has focused on the heterogeneity of AMs, in which healthy individuals possess distinct subsets of resident macrophages but also monocyte-like cells.
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