Business model reinvention: Impacts of Covid-19 on the fitness gym industry

Fitness gyms are experiencing a particular turmoil due to the Covid-19 crisis. The fitness industry is at the heart of wellness and health and is one of the most affected by the pandemic since 2020 (Baron, 2021). The closure of gyms, the cancellation of memberships, and the advent of free online fitness classes are undeniable challenges to face. Fitness gyms must adapt quickly and understand the new needs of their customers. To this extent, fitness gyms need to rethink their business models to overcome this Covid-19 crisis. This research aims to understand the major impacts of Covid-19 on the fitness gyms industry, identify the main changes is and present a possible reinvention of a business model to guide fitness gyms in a post-pandemic era. A literature review has been completed, a survey conducted on social medias and in-depth interviews conducted with diverse fitness gyms professionals exclusively in France. The key findings that can be retained are that fitness gyms should now offer more flexibility, accessibility, and security to their members.Os ginásios de fitness estão a passar por um tumulto particular devido à crise do Covid-19. A indústria do fitness está no centro do bem-estar e da saúde e é uma das mais afeitadas pela pandemia desde 2020 (Baron, 2021). O encerramento de ginásios, o cancelamento de inscrições, e o advento de aulas de fitness online gratuitas são desafios inegáveis a enfrentar. As academias de fitness devem adaptar-se rapidamente e compreender as novas necessidades dos seus clientes. Nesta medida, os ginásios de fitness precisam de repensar os seus modelos de negócio para ultrapassar esta crise da Covid-19. Esta investigação visa compreender o grande impacto do Covid-19 na indústria dos ginásios de fitness, identificar as principais mudanças é e apresentar uma possível reinvenção de um modelo de negócio para orientar os ginásios de fitness numa era pós-pandémica. Foi concluída uma revisão bibliográfica, um inquérito realizado em meios sociais e entrevistas aprofundadas com diversos profissionais de ginásios exclusivamente em França. As principais conclusões que podem ser retidas são que os ginásios de fitness devem agora oferecer mais flexibilidade, acessibilidade e segurança aos seus membros

Cytoplasmic SET induces tau hyperphosphorylation through a decrease of methylated phosphatase 2A

International audienceBackground: The neuronal cytoplasmic localization of SET, an inhibitor of the phosphatase 2A (PP2A), results in tau hyperphosphorylation in the brains of Alzheimer patients through mechanisms that are still not well defined.Results: We used primary neurons and mouse brain slices to show that SET is translocated to the cytoplasm in a manner independent of both its cleavage and over-expression. The localization of SET in the cytoplasm, either by the translocation of endogenous SET or by internalization of the recombinant full-length SET protein, induced tau hyperphosphorylation. Cytoplasmic recombinant full-length SET in mouse brain slices induced a decrease of PP2A activity through a decrease of methylated PP2A levels. The levels of methylated PP2A were negatively correlated with tau hyperphosphorylation at Ser-202 but not with the abnormal phosphorylation of tau at Ser-422.Conclusions: The presence of full-length SET in the neuronal cytoplasm is sufficient to impair PP2A methylation and activity, leading to tau hyperphosphorylation. In addition, our data suggest that tau hyperphosphorylation is regulated by different mechanisms at distinct sites. The translocation of SET to the neuronal cytoplasm, the low activity of PP2A, and tau hyperphosphorylation are associated in the brains of Alzheimer patients. Our data show a link between the translocation of SET in the cytoplasm and the decrease of methylated PP2A levels leading to a decrease of PP2A activity and tau hyperphosphorylation. This chain of events may contribute to the pathogenesis of Alzheimer disease

PAT1 inversely regulates the surface Amyloid Precursor Protein level in mouse primary neurons

International audienceAbstractBackgroundThe amyloid precursor protein (APP) is a key molecule in Alzheimer disease. Its localization at the cell surface can trigger downstream signaling and APP cleavages. APP trafficking to the cell surface in neurons is not clearly understood and may be related to the interactions with its partners. In this respect, by having homologies with kinesin light chain domains and because of its capacity to bind APP, PAT1 represents a good candidate.ResultsWe observed that PAT1 binds poorly APP at the cell surface of primary cortical neurons contrary to cytoplasmic APP. Using down and up-regulation of PAT1, we observed respectively an increase and decrease of APP at the cell surface. The increase of APP at the cell surface induced by low levels of PAT1 did not trigger cell death signaling.ConclusionsThese data suggest that PAT1 slows down APP trafficking to the cell surface in primary cortical neurons. Our results contribute to the elucidation of mechanisms involved in APP trafficking in Alzheimer disease

Calcium and vitamin D have a synergistic role in a rat model of kidney stone disease

International audienceVitamin D supplementation in humans should be accompanied by calcium administration to avoid bone demineralization through vitamin D receptor signaling. Here we analyzed whether long-term exposure of rats to vitamin D supplementation, with or without a calcium-rich diet, would promote kidney stone formation. Four groups of rats received vitamin D alone (100,000 UI/kg/3 weeks), a calcium-enriched diet alone, both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Serum and urine parameters and crystalluria were monitored. Kidney stones were assessed by 3-dimensional micro-computed tomography, infrared spectroscopy, von Kossa/Yasue staining, and field emission scanning electron microscopy. Although serum calcium levels were similar in the 4 groups, rats receiving vitamin D had a progressive increase in urinary calcium excretion over time, especially those receiving both calcium and vitamin D. However, oral calcium supplementation alone did not increase urinary calcium excretion. At 6 months, rats exposed to both calcium and vitamin D, but not rats exposed to calcium or vitamin D alone, developed significant apatite kidney calcifications (mean volume, 0.121 mm3). Thus, coadministration of vitamin D and increased calcium intake had a synergistic role in tubular calcifications or kidney stone formation in this rat model. Hence, one should be cautious about the cumulative risk of kidney stone formation in humans when exposed to both vitamin D supplementation and high calcium intake

High frequency and wide range of human kidney papillary crystalline plugs

International audienceMost of kidney stones are supposed to originate from Randall's plaque at the tip of the papilla or from papillary tubular plugs. Nevertheless, the frequency and the composition of crystalline plugs remain only partly described. The objective was to assess the frequency, the composition and the topography of papillary plugs in human kidneys. A total of 76 papillae from 25 kidneys removed for cancer and without stones were analysed by immunohistochemistry combined with Yasue staining, field emission-scanning electron microscopy and Fourier transformed infrared micro-spectroscopy. Papillary tubular plugs have been observed by Yasue staining in 23/25 patients (92%) and 52/76 papillae (68%). Most of these plugs were made of calcium phosphate, mainly carbonated apatite and amorphous calcium phosphate, and rarely octacalcium phosphate pen-tahydrate. Calcium and magnesium phosphate (whitlockite) have also been observed. Based upon immunostaining coupled to Yasue coloration, most of calcium phosphate plugs were located in the deepest part of the loop of Henle. Calcium oxalate monohydrate and dihydrate tubular plugs were less frequent and stood in collecting ducts. At last, we observed calcium phosphate plugs deforming and sometimes breaking adjacent collecting ducts. Papillary tubular plugging, which may be considered as a potential first step toward kidney stone formation, is a very frequent setting, even in kidneys of non-stone formers. The variety in their composition and the distal precipitation of calcium oxalate suggest that plugs may occur in various conditions of urine supersaturation. Plugs were sometimes associated with collecting duct deformation

Urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model

Abstract Most mouse kidney stone models induce nephrocalcinosis rather than urolithiasis. The aim of our study was to find an accelerated experimental model in order to study the early events of stone formation, that is, at the time of crystal binding to intrarenal urothelium. C57B6 mice exposed to vitamin D supplements and water containing hydroxyl-L-proline, ammonium chloride and calcium chloride were studied for 42 days. A group receiving urothelial cell mitogen Fibroblast Growth Factor 7 (FGF7) was compared to control group receiving saline. Calcium oxalate monohydrate (COM) crystals were detected in urines by day 2 and within urinary spaces in specialized fornix areas in both groups as soon as day 14 with enhanced deposits in FGF7 group compared to controls at day 21. Urothelial cells proliferation, uroplakin III downregulation and de novo expression of osteopontin receptor CD44 detected in FGF7 group, were delayed in the control group (day 42). Crystal aggregates within specialized fornix areas by day 42 were located in urinary spaces but also within and under a multilayered metaplastic urothelium, simultaneous to macrophages influx. Point of note, administration of a normal diet by day 21 was responsible for a spontaneous crystal clearance. Our data show that under supersaturation conditions, urothelial cell proliferation and calcium oxalate crystal retention occur within specialized fornix areas. Enhanced crystal deposits following FGF7 administration suggest that urothelium proliferation would be a relevant trigger for renal stone formation

Topography, composition and structure of incipient Randall’s plaque at the nanoscale level

International audiencePurposeAlexander Randall identified calcium phosphate plaques in renal papillae as the origin of kidney stones. However, little is known about the early steps of Randall’s plaque formation, preceding the onset of urolithiasis. Our objectives were to characterize the composition and the initial formation site of incipient Randall’s plaque in non-stone formers living patients.Material and MethodsMedian age of the patients was 67.7 years. Fifty-four healthy papillae from kidneys removed for cancer and without stones have been analyzed by immunohistochemistry and Von Kossa staining, Field Emission-Scanning Electron Microscopy with Energy Dispersive X-ray analysis, μ-Fourier Transform Infrared Spectroscopy, Cryo-Transmission Electron Microscopy coupled to Selected-Area Electron Diffraction and Electron Energy Loss Spectroscopy.ResultsIncipient Randall’s plaque has been observed in 72.7% of kidneys. Carbonated apatite was as expected the main component of microcalcifications but amorphous calcium phosphate and whitlockite have been identified in 80% and 40% of the papillae, respectively. Incipient plaques stood in the deepest part of the papillae, around the loop of Henle tip but also around vasa recta (respectively 62.4 % and 37.2 % of microcalcifications) and rarely close to collecting ducts. At the nanoscale level, incipient calcifications were often made of several nanocrystals inside organic material looking like microvesicles.ConclusionsIncipient Randall’s plaque is frequent and appears at the extreme tip of renal papillae, around the hairpin structure of the loop of Henle but also around vasa recta. Nanoscale analyses suggest a local nucleation process promoting nanocrystal growth in a supersaturated milieu. In addition, plaques contain various calcium and magnesium phosphates and not only carbonated apatite

ABCC6 Deficiency Promotes Development of Randall Plaque

International audienceBackground: Pseudoxanthoma elasticum (PXE) is a genetic disease caused by mutations in the ABCC6 gene that result in low pyrophosphate levels and subsequent progressive soft tissue calcifications. PXE mainly affects the skin, retina, and arteries. However, many patients with PXE experience kidney stones. We determined the prevalence of this pathology in patients with PXE and examined the possible underlying mechanisms in murine models.Methods: We conducted a retrospective study in a large cohort of patients with PXE and analyzed urine samples and kidneys from Abcc6−/− mice at various ages. We used Yasue staining, scanning electron microscopy, electron microscopy coupled to electron energy loss spectroscopy, and Fourier transform infrared microspectroscopy to characterize kidney calcifications.Results: Among 113 patients with PXE, 45 (40%) had a past medical history of kidney stones. Five of six computed tomography scans performed showed evidence of massive papillary calcifications (Randall plaques). Abcc6−/− mice spontaneously developed kidney interstitial apatite calcifications with aging. These calcifications appeared specifically at the tip of the papilla and formed Randall plaques similar to those observed in human kidneys. Compared with controls, Abcc6−/− mice had low urinary excretion of pyrophosphate.Conclusions: The frequency of kidney stones and probably, Randall plaque is extremely high in patients with PXE, and Abcc6−/− mice provide a new and useful model in which to study Randall plaque formation. Our findings also suggest that pyrophosphate administration should be evaluated for the prevention of Randall plaque and kidney stones

Localization and characterization of thyroid microcalcifications: A histopathological study

International audienceThyroid calcification is frequent in thyroid nodules. The aim of our study was to evaluate the prevalence of calcifications in thyroid tissue samples of patients with various thyroid diseases , and to identify their composition according to their localization. Among 50 thyroid samples included, 56% were malignant (papillary carcinoma) and 44% were benign (ade-noma, multinodular goiter, Graves' disease, sarcoidosis). Calcifications were found in 95% of samples using polarised light microscopy, whereas only 12% were described in initial pathological reports. Three types were individualised and analyzed by infrared spectrometry (μFTIR): colloid calcifications composed of calcium oxalate, capsular calcifications and psammoma bodies, both composed of calcium phosphate. Of notice, psammoma bodies characterized by FE-SEM were composed of concentric structure suggesting a slow process for crystal deposition. Calcium phosphates were found only in malignant samples whereas calcium oxalate was not associated with a define pathology. Proliferation assessed by KI67 staining was high (33% of positive follicles), and RUNX2, OPN, and CD44 positive staining were detected in thyrocytes with a broad variation between samples. However, thyr-ocyte proliferation and differentiation markers were not associated with the number of crystals. TRPV5 and CaSR expression was also detected in thyrocytes. mRNA transcripts expression was confirmed in a subgroup of 10 patients, altogether with other calcium transporters such as PMCA1 or Cav1.3. Interestingly, TRPV5 mRNA expression was significantly associated with number of colloid calcifications (rho =-0.72; p = 0.02). The high prevalence of calcium oxalate crystals within colloid gel raises intriguing issues upon follicle physiology for calcium and oxalate transport

Stiripentol protects against calcium oxalate nephrolithiasis and ethylene glycol poisoning

International audienceIncreased urinary oxalate excretion (hyperoxaluria) promotes the formation of calcium oxalate crystals. Monogenic diseases due to hepatic enzyme deficiency result in chronic hyperoxaluria, promoting end-stage renal disease in children and young adults. Ethylene glycol poisoning also results in hyperoxaluria, promoting acute renal failure and frequently death. Stiripentol is an antiepileptic drug used to treat children affected by Dravet syndrome. It has been shown to inhibit neuronal lactate dehydrogenase 5 enzyme. As this isoenzyme is also the last step of hepatic oxalate production, we hypothesized that stiripentol would potentially reduce hepatic oxalate production and urine oxalate excretion. In vitro, stiripentol decreased the synthesis of oxalate by hepatocytes in a dose-dependent manner. In vivo, oral administration of stiripentol significantly reduced urine oxalate excretion in rats. Stiripentol protected the kidneys against calcium oxalate crystal deposits in acute ethylene glycol intoxication and chronic calcium oxalate nephropathy models. In both models, stiripentol significantly improved renal function. Patients affected by Dravet syndrome and treated with stiripentol had a lower urine oxalate excretion than control patients. A young girl affected by severe type I hyperoxaluria received stiripentol for several weeks, and urine oxalate excretion decreased by two-thirds. Stiripentol is a promising potential therapy against genetic hyperoxaluria and ethylene glycol poisoning