A case of mandible Paget's disease of the bone treated with intravenous neridronate

Paget's disease of bone (PDB) is a focal disorder of osteoclasts, leading to chaotic bone remodelling, and it is characterized by the presence of focal areas of excessive bone formation alongside with areas of focal bone resorption. The typical radiographic feature is the cotton wool appearance. To date, bisphosphonates are the mainstay of the treatment. We hereby report the case of a young woman presenting with mandible PDB, with a relevant diagnostic delay and mistakenly treated for five years with chronic oral corticosteroids. After our evaluation, the patient received treatment with intravenous neridronate (an amino-bisphosphonate licensed in Italy for the treatment of this disease), with achievement of clinical remission

Insight into the WNT system and its drug related response.

The WNT signalling pathway is a complex system for transferring information for DNA expression from the cell surface receptors to cytoplasm and then to the nucleus. It is based on several proteins that work together as agonists and antagonists in order to maintain homeostasys and to promote anabolic processes. The WNT system acts on all cellular lines involved in bone resorption and formation. WNT pathway can mainly be triggered by two different signalling cascades. The first is well known and is the so-called WNT-beta catenin system (or the canonical pathway), the second is known as the non canonical WNT pathway. WNT proteins form a superfamily of secreted glycoproteins. The association with surface receptors, called Frizzled, that are members of the G protein-coupled receptors superfamily and co receptors like low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) complete the WNT system. LRP5/6 show high affinity for WNT antagonists that modulate the activity of this pathway: DKK1 and sclerostin (SCL), that play a crucial role in modulating the WNT system. The WNT-pathway and in particular its antagonists SCL and DKK1 seems to play a key role in the regulation of bone remodeling during treatment with bone active agents such as bisphosphonates, but not only. Their effects become relevant especially in the course of long-term treatments

Blind Rule-Following and the Regress of Motivations

Normativists about belief hold that belief formation is essentially rule- or norm-guided. On this view, certain norms are constitutive of or essential to belief in such a way that no mental state not guided by those norms counts as a belief, properly construed. In recent influential work, Kathrin Glüer and Åsa Wikforss develop novel arguments against normativism. According to their regress of motivations argument, not all belief formation can be rule- or norm-guided, on pain of a vicious infinite regress. I argue that the regress of motivations argument is unsuccessful: an appeal to the notion of blind rule-following, drawn from a plausible interpretation of Ludwig Wittgenstein’s remarks on rule-following, stops the regress of motivations in its tracks

Instability of Quark Matter Core in a Compact Newborn Neutron Star With Moderately Strong Magnetic Field

It is explicitly shown that if phase transition occurs at the core of a newborn neutron star with moderately strong magnetic field strength, which populates only the electron's Landau levels, then in the $\beta$-equilibrium condition, the quark core is energetically much more unstable than the neutron matter of identical physical condition.Comment: Six pages REVTEX file, one .eps file (included

Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes

Background: Several studies suggest an association between serum 25-hydroxyvitamin D (25OHD) and the outcomes of Severe Acute Respiratory Syndrome Corona-Virus-2 (SARS-CoV-2) infection, in particular Coronavirus Disease-2019 (COVID-19) related severity and mortality. The aim of the present meta-analysis was to investigate whether vitamin D status is associated with the COVID-19 severity, defined as ARDS requiring admission to intensive care unit (ICU) or mortality (primary endpoints) and with the susceptibility to SARS-CoV-2 and COVID-19-related hospitalization (secondary endpoints). Methods: A search in PubMed, ScienceDirect, Web of Science, Google Scholar, Scopus, and preprints repositories was performed until March 31th 2021 to identify all original observational studies reporting association measures, or enough data to calculate them, between Vitamin D status (insufficiency <75, deficiency <50, or severe deficiency <25 nmol/L) and risk of SARS-CoV-2 infection, COVID-19 hospitalization, ICU admission, or death during COVID-19 hospitalization. Findings: Fifty-four studies (49 as fully-printed and 5 as pre-print publications) were included for a total of 1,403,715 individuals. The association between vitamin D status and SARS-CoV2 infection, COVID-19 related hospitalization, COVID-19 related ICU admission, and COVID-19 related mortality was reported in 17, 9, 27, and 35 studies, respectively. Severe deficiency, deficiency and insufficiency of vitamin D were all associated with ICU admission (odds ratio [OR], 95% confidence intervals [95%CIs]: 2.63, 1.45–4.77; 2.16, 1.43–3.26; 2.83, 1.74–4.61, respectively), mortality (OR, 95%CIs: 2.60, 1.93–3.49; 1.84, 1.26–2.69; 4.15, 1.76–9.77, respectively), SARS-CoV-2 infection (OR, 95%CIs: 1.68, 1.32–2.13; 1.83, 1.43–2.33; 1.49, 1.16–1.91, respectively) and COVID-19 hospitalization (OR, 95%CIs 2.51, 1.63–3.85; 2.38, 1.56–3.63; 1.82, 1.43–2.33). Considering specific subgroups (i.e., Caucasian patients, high quality studies, and studies reporting adjusted association estimates) the results of primary endpoints did not change. Interpretations: Patients with low vitamin D levels present an increased risk of ARDS requiring admission to intensive care unit (ICU) or mortality due to SARS-CoV-2 infection and a higher susceptibility to SARS-CoV-2 infection and related hospitalization

Alterações químicas, bioquímicas e da qualidade do café submetido a diferentes formas de processamento de secagem.

Devido ao elevado teor de umidade em que é colhido, o café requer secagem adequada a fim de preservar sua qualidade. Nesta etapa, o teor de umidade é reduzido de aproximadamente 60% (b.u.) para 11% (b.u.), sendo que o processo de secagem em terreiros, em secadores mecânicos ou a combinação destes são os métodos mais utilizados. Pesquisas recentes têm indicado várias alterações na integridade das membranas celulares, processo de germinação, conteúdo de ácidos e açúcares, devido ao estresse provocado aos grãos, ao longo do processamento e secagem. A elevação da temperatura de secagem promove danos aos grãos, o que reduz sensivelmente a qualidade da bebida. Este trabalho teve como objetivo verificar a influência da secagem lenta e secagem rápida sobre alguns parâmetros físicoquímicos do grão e sobre a qualidade do café. Os cafés utilizados neste experimento foram da cultivar Catuaí Vermelho IAC 44 produzidos na Fazenda Experimental de Machado-FEMA, da EPAMIG. Foram avaliadas três formas de preparo: café natural, desmucilado e despolpado. Após a obtenção destas três formas de preparo os cafés foram então submetidos à secagem lenta, sendo secados em telados suspensos à sombra ou secados por meio de secagem rápida em secadores de camada fixa com controle de temperatura de secagem de 35ºC, até atingirem cerca de 11% de umidade (b.u.). Depois do processo de secagem (lenta ou rápida), os cafés foram beneficiados e submetidos às seguintes análises: condutividade elétrica, lixiviação de potássio, atividade enzimática da polifenoloxidase, acidez total titulável e análise sensorial. Por meio dos resultados observados, verificam-se menores valores de condutividade elétrica, lixiviação de potássio, acidez total titulável, maior atividade enzimática da polifenoloxidase e melhor qualidade nos cafés submetidos à secagem lenta, ou seja, secagem à sombra, independente da forma de preparo utilizada. Em relação ao tipo de preparo, observa-se que os cafés naturais apresentaram maiores valores de condutividade elétrica e lixiviação de potássio quando submetidos à secagem rápida, ou seja, em secadores mecânicos, o que denota uma maior probabilidade desses cafés de perderem qualidade

Pregnancy, Proteinuria, Plant-Based Supplemented Diets and Focal Segmental Glomerulosclerosis: A Report on Three Cases and Critical Appraisal of the Literature.

Chronic kidney disease (CKD) is increasingly recognized in pregnant patients. Three characteristics are associated with a risk of preterm delivery or small for gestational age babies; kidney function reduction, hypertension, and proteinuria. In pregnancy, the anti-proteinuric agents (ACE–angiotensin converting enzyme-inhibitors or ARBS -angiotensin receptor blockers) have to be discontinued for their potential teratogenicity, and there is no validated approach to control proteinuria. Furthermore, proteinuria usually increases as an effect of therapeutic changes and pregnancy-induced hyperfiltration. Based on a favourable effect of low-protein diets on proteinuria and advanced CKD, our group developed a moderately protein-restricted vegan-vegetarian diet tsupplemented with ketoacids and aminoacids for pregnant patients. This report describes the results obtained in three pregnant patients with normal renal function, nephrotic or sub-nephrotic proteinuria, and biopsy proven diagnosis of focal segmental glomerulosclerosis, a renal lesion in which hyperfiltration is considered of pivotal importance (case 1: GFR (glomerular filtration rate): 103 mL/min; proteinuria 2.1 g/day; albumin 3.2 g/dL; case 2: GFR 86 mL/min, proteinuria 3.03 g/day, albumin 3.4 g/dL; case 3: GFR 142 mL/min, proteinuria 6.3 g/day, albumin 3.23 g/dL). The moderately restricted diet allowed a stabilisation of proteinuria in two cases and a decrease in one. No significant changes in serum creatinine and serum albumin were observed. The three babies were born at term (38 weeks + 3 days, female, weight 3180 g-62th centile; 38 weeks + 2 days, female, weight 3300 g-75th centile; male, 38 weeks + 1 day; 2770 g-8th centile), thus reassuring us of the safety of the diet. In summary, based on these three cases studies and a review of the literature, we suggest that a moderately protein-restricted, supplemented, plant-based diet might contribute to controlling proteinuria in pregnant CKD women with focal segmental glomerulosclerosis. However further studies are warranted to confirm the potential value of such a treatment strategy