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Summary: Background & aims: Olfactory disorders impact mental health, with adverse effects on quality of life, particularly in the area of eating. Despite their high prevalence in the population, olfactory disorders are poorly managed, with patients still lacking easy access to rapid diagnosis and treatment. In this context, the present study offers a new screening tool and compares the efficiency of different olfactory training protocols. Methods: A screening test was set up and different olfactory training paradigms were compared for their effect on the recovery of the sense of smell on the one hand, and quality of life on the other. The study population was composed of post-COVID-19 dysosmic patients (with a loss of more than 6 weeks). Three training protocols were used, differing in terms of number of odors and in format (either lab-supplied odorant kits, or the use of odorants found at home). All three protocols were implemented over a 12-week period. Results: The screening test distinguished dysosmics from normosmics with an accuracy of 73%. During training, 69% of patients completed the evaluation protocol and 77% of them performed more than half of the training sessions, resulting in a 53% completion rate. Olfactory performances improved significantly after training, irrespective of the training paradigm and 59% of patients displayed a clinically significant improvement of their sense of smell. These improvements were positively associated with assiduity along training. Finally, olfactory disorders negatively affected quality of life. After olfactory training, this overall negative impact on quality of life was reduced, especially with regard to the pleasure of eating. Conclusion: This study introduces a new screening tool for olfactory deficits. It also provides important insights into the optimization of olfactory training protocols and their effects on quality of life, and on eating behavior in particular.

Summary: An International Altered Taste Consortium (I-eAT) is proposed that seeks to utilise gastronomic and biopsychosocial insights to understand and help people who experience taste alterations. Altered eating experiences and a changed experience of taste is a common and disabling trans-diagnostic, multi-causal entity which has for too long been poorly understood and supported in health research and practice. The phrase Altered Taste is employed (using “taste” in its most commonly understood sense to refer to the overall multi-sensory flavour experience) to emphasise the lived sensory experience of those living with an altered relationship with food. Interdisciplinary collaboration between the domains of medicine, health care, physiology, psychology and gastronomy is considered key to understanding, working with and improving altered taste. This manifesto emerged from ongoing research and practice, and was formulated at a workshop of interdisciplinary experts and patient representatives at the Second International Altered Taste Symposium (2022). Between them they collectively agreed on 1. A shared terminology to maximise stakeholder involvement and 2. An overall research aim to better understand, manage and treat Altered Taste. This aim is implemented in 4 key research objectives.

Summary: Food liking is an essential component of the food intake experience. However, some conditions may alter the perception, thus the liking of food, leading to a reduced intake and increasing the risk of malnutrition. Particularly, in the context of cancer and related therapies, malnutrition is a major challenge with 25%–80% of cancer patients experiencing malnutrition at different degrees. The aim of the present exploratory study was to examine the effect of flavor enhancement on food liking in a group of cancer patients undergoing chemotherapy and with varying self-reported taste/smell abilities.The liking of four eggplant creams enhanced with either salt, lemon, garlic or cumin was evaluated in comparison to a reference eggplant cream by a group of 154 cancer patients. Patients were stratified in two subgroups according to their self-reported taste and smell perception abilities. Results showed that adding salt and garlic significantly increased patients' liking of the eggplant cream (P0.05), while adding lemon reduced liking compared to the reference (P

An epidermoid cyst is a slowly growing, typically benign tumour, which requires surgical treatment. It usually develops in the cerebellopontine angle or the parasellar region, and occasionally appears in the ventricular system. It is unusual for an epidermoid cyst to place itself in the fourth ventricle. There have only been few published reports on this subject in recent years, and therefore, we would like to present a comprehensive description of a fourth ventricle epidermoid cyst diagnosed in two patients in a short period of time. Optimal recovery of the patient, with a minimal risk of tumour recurrence, is best accomplished by total microscopic removal of the tumour and its capsule.

Objectives: Type 2 diabetes (T2D) is associated with chronic, low grade inflammation. Activation of the NLRP3 inflammasome and secretion of its target interleukin-1β (IL-1β) have been implicated in pancreatic β cell failure in T2D. Specific targeting of the NLRP3 inflammasome to prevent pancreatic β cell death could allow for selective T2D treatment without compromising all IL-1β-associated immune responses. We hypothesized that treating a mouse model of T2D with MCC950, a compound that specifically inhibits NLRP3, would prevent pancreatic β cell death, thereby preventing the onset of T2D. Methods: Diabetic db/db mice were treated with MCC950 via drinking water for 8 weeks from 6 to 14 weeks of age, a period over which they developed pancreatic β cell failure. We assessed metabolic parameters such as body composition, glucose tolerance, or insulin secretion over the course of the intervention. Results: MCC950 was a potent inhibitor of NLRP3-induced IL-1β in vitro and was detected at high levels in the plasma of treated db/db mice. Treatment of pre-diabetic db/db mice with MCC950, however, did not prevent pancreatic dysfunction and full onset of the T2D pathology. When examining the NLRP3 pathway in the pancreas of db/db mice, we could not detect an activation of this pathway nor increased levels of its target IL-1β. Conclusions: NLRP3 driven-pancreatic IL-1β inflammation does not play a key role in the pathogenesis of the db/db murine model of T2D. Keywords: Type 2 diabetes, Inflammasome, Interleukin-1β, MCC950, db/db mice

Titanium dioxide was synthesized by the sol–gel method and platinum supported on titanium dioxide were prepared by a wet impregnation chemical process at different platinum contents. The prepared samples were dried over night at 110 °C and then calcined at 500 °C for 4 h. Structural and morphological characterization has been carried out by means of X-ray diffraction (XRD), differential scanning calorimetry–thermogravimetric analysis (DSC–TGA), Raman spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), Brunauer–Emmett–Teller surface area measurement (BET) and transmission electron microscopy coupled to the energy dispersive spectroscopy (TEM/EDX). The adsorption performance and photocatalytic activity of the samples were investigated using two chlorophenoxy herbicides: 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-(2,4-dichlorophenoxy) propionic acid (2,4-DP) as models of organic pollutants in water. The obtained results show that Pt/TiO2 exhibited higher photocatalytic activity than TiO2 particles for the degradation of the two selected herbicides. The photocatalytic activity increases by increasing the platinum yield in the catalyst.

A series of mixed oxide catalysts CexZr1−xO2 with different compositions (x = 0.93, 0.80, 0.75, 0.60, 0.55, and 0.50) were synthesized by co-precipitation technique using ammonia as the precipitant agent. Textural and structural properties of calcined ceria–zirconia oxides were characterized by nitrogen adsorption, X-ray diffraction and Raman spectroscopy. The redox properties were investigated by temperature-programmed reduction measurement using H2. The procedure of preparation as well as the composition has a great influence on the structural and textural properties of mixed oxides. Fluorite type oxides were shown to be a very interesting support for the total oxidation, since these materials led to the complete decomposition of ethyl acetate at rather low temperatures. Of the synthesized materials, Ce0.5Zr0.5O2 showed the best catalytic activity.

Full factorial experimental design technique was used to study the main effects and the interaction effects between operational parameters in the photocatalytic degradation of oxalic acid in a batch photo-reactor using TiO2 aqueous suspension. The important parameters which affect the removal efficiency of oxalic acid such as agitation, initial concentration, volume of the solution and TiO2 dosage were investigated. The parameters were coded as X1, X2, X3 and X4, consecutively, and were investigated at two levels (−1 and +1). The effects of individual variables and their interaction effects for dependent variables, namely, photocatalytic degradation efficiency (%) were determined. From the statistical analysis, the most effective parameters in the photocatalytic degradation efficiency were initial concentration and volume of solution. The interaction between initial concentration, volume of solution and TiO2 dosage was the most influencing interaction. However, the interaction between agitation, initial concentration and volume of solution was the least influencing parameter.

Titanium dioxide was synthesized by the sol–gel method and titanium pillared purified clay was prepared with two titanium contents: 1.15 and 10.5 mmol of Ti per gram of clay. The composites were synthesized by immobilizing TiO2 onto surfactant-pillared clay via ion exchange reaction between clay with cation surfactant, cetyl-trimethyl ammonium bromide (CTMABr). The composition and texture of the prepared photocatalysts were characterized with X-ray powder diffraction (XRD), FT-IR spectroscopy, transmission electron microscopy (TEM) and energy-dispersive spectroscopy (EDX). The adsorption performance and photocatalytic activities of the prepared samples were investigated using 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4-dichlorophenoxypropionic acid (2,4-DP) as models of organic pollutants. The results were obtained that these photocatalysts can effectively degrade selected pesticides. The removal efficiency increases with the Ti content in the pillared clay.

A prospective study in healthy infants predefining both diet fatty acid and cholesterol, from birth to age 1 year, compared response of cholesterol fractions in three groups: random assignment to 1) monounsaturated-(Hi-Mono) (n = 20), or 2) polyunsaturated-(Hi-Poly) (n = 22) fatty acid-enriched diets, or 3) non-randomized selection to breast feeding (Human Milk) (n = 25). In each group, designated weaning foods and supplements maintained fatty acid and cholesterol intake similar to that of each group's defined formulas, with long-term compliance confirmed by plasma phospholipid fatty acid concentrations. By 12 months, total cholesterol was significantly lower in the Hi-Poly group compared to either of the other groups (P < 0.05). Low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol concentrations were significantly lower by 12 months in the Hi-Poly group, compared to the Hi-Mono groups. However, at the earlier 4-month interval, total cholesterol and LDL-cholesterol in both Hi-Mono and Hi-Poly groups were not different from each other, although each was significantly lower than the parallel Human Milk-group (P < 0.05). The Hi-Mono group increased gradually in total and LDL-cholesterol such that, after 12 months' feedings, all lipid fractions of this Hi-Mono group were no different from those of the Human Milk group. In independent group comparisons, there were no significant differences in HDL-cholesterol concentrations after 4 and 9 months on these diets. Independent of diet, HDL-cholesterol showed a falling trend as an overall time-effect across all groups (P < 0.001). These data suggest that prolonged feeding of a diet enriched in polyunsaturated acids in early infancy has a significant cholesterol-lowering effect compared to monounsaturates. These differences in total, LDL-, and HDL-cholesterol plasma concentrations between polyunsaturates and monounsaturates were not significantly evident until feedings had continued for a year.

Background: Cyclosporine (CsA) has been shown to alter the activity of plasma membrane transporters in kidney epithelial cells. In this study, we have investigated the effects of CsA on Na+,K+-ATPase and Na+-K+-Cl- cotransport activities in cultured cells derived from microdissected mouse medullary thick ascending limb (mTAL) cells., Methods: Experiments were carried out on subcultured confluent mouse TAL cells. Reverse transcription-polymerase chain reaction experiments showed that they expressed the mNKCC2 electroneutral Na+-K+-Cl- cotransporter and ROM-K1 and ROMK2 potassium channel mRNA. Western blotting also revealed the presence of the 40 kD ROMK protein using an anti-ROMK antibody. The effect of CsA (100 ng/mL) on ion transport was assessed by measuring the influx and efflux of rubidium (86Rb+) and 36Cl-, used as tracers of K+ and Cl- movements, on cells grown on Petri dishes or permeable filters., Results: CsA inhibited by 38% the ouabain-sensitive component of 86Rb+ influx mediated by the Na+,K+-ATPase pumps. CsA also increased by 38% the ouabain-resistant furosemide-sensitive component (Or-Fs) of 86Rb+ influx, reflecting the Na+-K+-Cl- cotransport activity and stimulated the basolateral efflux of 36Cl- from mTAL cells grown on filters. The CsA-stimulated basal efflux of Cl- was prevented by the basal addition of the Cl- channel blocker 5-nitro-2-(3-phenylpropylamino) benzoate (NPPB, 10-4 mol/L). Apical addition of the K+ channel blocking agent Ba2+ (10-4 mol/L) partially prevented the CsA-stimulated basal efflux of Cl-. Adding Ba2+ to the luminal side of cells grown on Petri dishes also prevented the rise in apical 86Rb+ efflux and the increased Or-Fs component of 86Rb+ influx caused by CsA., Conclusion: These results indicated that CsA may stimulate the Na+-K+-Cl- cotransport activity and also suggested that this immunosuppressive agent may interfere in the recycling of apical K+ in this model of cultured mouse TAL cells.

We have investigated CFTR specific intestinal expression by transfection assays in mouse cultured fibroblasts and transimmortalized intestinal crypt m-ICc12 cells using the beta-galactosidase gene linked to rat CFTR non-coding regions. Two constructs were studied, one encompassing a 5.3 kb region 5' to the gene where numerous duodenum-specific DNase I hypersensitive sites (DHSs) were previously mapped and the other including a 1.3 kb 3' region in which novel DHSs had been identified. In transient transfection assays, transgenes were expressed in m-ICc12 cells but not in fibroblasts. In m-ICc12 cells, the pattern of expression of the chromosomally integrated transgenes paralleled the endogenous expression of CFTR and beta-galactosidase activity was detected in cells containing villin and forming domes. Thus, a 6.6 kb region encompassing 5' and 3' non-coding parts of rat CFTR is able to drive specific expression of a reporter gene in cultured mouse intestinal cells having kept a crypt phenotype.

Dihydrotestosterone (DHT) binding studies and the effects of DHT on the expression of beta-glucuronidase (Gus) and kidney androgen-regulated protein (KAP) genes and cell growth were investigated in immortalized early PKSV-PCT and late PKSV-PR proximal tubule cells, derived from transgenic mice carrying the L-pyruvate kinase/SV40 hybrid gene. [3H]DHT binding studies indicated that both cell lines have conserved substantial amounts of androgen receptors. The levels of KAP and Gus transcripts in PKSV-PCT cells, and those of KAP transcripts in PKSV-PR cells, decreased when cells were shifted from a serum-supplemented to a steroid-free medium. The addition of 30 nM DHT to the steroid-free medium resulted in a slight increase in Gus and in a more marked increase in KAP transcripts in both cell lines. Dihydrotestosterone also affected the growth of PKSV-PCT and PKSV-PR cells, since this hormone added to the steroid-free medium stimulated the incorporation of [3H]thymidine in a dose-dependent manner and induced the formation of domes, which represent indicators of ionic transport processes. Thus, because these early and late mouse proximal tubule cells have conserved androgen receptors, they represent attractive cell systems to analyze the action of androgens on specific functions of the mouse proximal tubule.

N-Acetyl-beta-D-glucosaminidase (NAG) isoenzyme profile in primary cultures of rabbit kidney proximal tubule cells was studied. Confluent cells had high levels of NAG activity, but ion exchange chromatography showed that the NAG isoenzyme profile in cultured cells was different from that of rabbit renal cortex homogenates and freshly isolated cells. Confluent cultured cells contained an atypical acidic isoform, absent in homogenates and freshly isolated cells in which the predominant isoform is NAG-A (a heterodimer alpha beta). The fact that this atypical isoform was able to hydrolyse the synthetic substrate 4-methylumbelliferyl-beta-N-acetylglucosaminide-6-sulphate indicated that it probably was an alpha-subunit homodimer. These results suggest subunit rearrangement within NAG polypeptide chains linked to down-regulation of beta-subunit production in cultured rabbit proximal cells. The change in isoenzyme profile in cultured cells may make it difficult to use primary cultures of rabbit proximal tubule cells to establish correlations between in vitro and in vivo studies using NAG isoenzymes as a nephrotoxicity index, as illustrated by the effects of gentamicin.

The effects of gentamicin on N-acetyl-beta-D-glucosaminidase (NAG) and acid phosphatase (AcP), two lysosomal enzymes present in proximal renal tubule cells, were studied in the PKSV-PCT cell line derived from proximal convoluted tubules from the kidney of a transgenic mouse carrying SV40 large T antigen under the control of the L-type pyruvate kinase gene. Gentamicin (400 micrograms/ml for 72 hr) did not alter cell viability, but significantly reduced cell growth and favored the formation of myeloid bodies. Gentamicin (50 to 800 micrograms/ml for 72 hr) decreased in a dose-dependent manner the cellular NAG in PKSV-PCT cells and stimulated its secretion by 20 to 60%. Chloroquine (50 to 100 microns) and ammonium chloride (NH4Cl, 30mM), two lysosomotropic amines known to stimulate the secretion of lysosomal enzymes in fibroblasts and macrophages, also stimulated secreted NAG in PKSV-PCT cells. However, the effect of chloroquine was less marked in PKSV-PCT cells than in cultured mouse 3T3 fibroblasts. Gentamicin induced lysosomal alkalinization but, in contrast to chloroquine and NH4Cl, the aminoside strongly stimulated the secretion of AcP. The secretion induced by gentamicin was nonpolarized, since the percentage of secreted NAG significantly increased from both the apical and basal sides of PKSV-PCT cells grown on permeable filters. Thus, these data suggest that gentamicin alters the secretion of NAG and AcP by a non-specific pathway and indicate that the PKSV-PCT cell line is a suitable system to examine the cellular action of drugs in kidney proximal tubule cells.

We have investigated whether or not tissue factor (TF) which is present in the supernatant of isolated glomeruli, is responsible for the stimulatory activity of TXB2 production by isolated human platelets. Reconstituted TF stimulated TXB2 synthesis in platelets in a dose-dependent manner. This effect was potentiated in the presence of a mixture of the major fatty acids found in glomerular supernatants. Addition of a neutralizing anti-TF monoclonal antibody abolished both the procoagulant activity and the platelet-TXB2 stimulatory activity of reconstituted TF and of glomerular supernatants. Anti-factor VII/VIIa (F VII/VIIa) Fab inhibited in a dose-dependent manner the platelet-TXB2 stimulatory activity of an identical dilution of reconstituted TF and of glomerular supernatants, providing evidence that the functional complex TF. VIIa and not TF itself was the active agent. Pretreatment of platelets, TF or glomerular supernatant by hirudin, an inhibitor of thrombin, as well as by antithrombin III heparin, which inhibits both activated factor X and thrombin also markedly inhibited the synthesis of TXB2 by platelets in the presence of either TF or glomerular supernatant. Taken together, these results demonstrate that the stimulatory activity for TXB2 production by platelets which is released by the glomerular cells is attributable to TF. TF does not act directly. Its effect is mediated by thrombin which is formed de novo at the platelet surface in the presence of even traces of the plasma coagulation proteins associated with platelets. TXB2 formation in platelets correlates well with TF concentration in the glomerular supernatant. The possibility of a similar set of mechanisms associated with glomerular injury may require consideration.

Tumor necrosis factor (TNF) is a cytokine which is produced by mononuclear phagocytes upon activation by bacterial lipopolysaccharide (LPS) and various other stimuli. In immune-mediated glomerulonephritis, infiltration of glomeruli by monocytes-macrophages is associated with production of TNF. The purpose of the present experiments was to determine whether mesangial cells could also contribute to glomerular TNF synthesis. TNF activity has been determined in the culture medium of rat mesangial cells using a L-929 fibroblast lytic assay. This activity was detectable only when the cells were exposed to LPS (0.1 to 10 micrograms/ml) and for periods longer than one hour. The cytotoxic factor was identified as TNF since: (1) the lytic activity was completely inhibited by an anti-mouse TNF polyclonal antibody and was associated with suppression of lipoprotein lipase activity in adipocytes; (2) its molecular weight (110,000 daltons) corresponded to that observed for murine TNF under non-denaturing conditions; and (3) mRNA encoding TNF was expressed by mesangial cells two hours after addition of LPS. To assess the mechanisms whereby TNF production was regulated, the role of prostaglandin E2 (PGE2) was determined. LPS caused a dose-dependent increase of PGE2 synthesis by mesangial cells. Treatment by indomethacin promoted a suppression of PGE2 production together with an increase of TNF synthesis, indicating that PGE2 acted in a negative feedback manner to regulate the production of TNF. Addition of PGE2 (0.1 to 300 nM) or 8-bromo cyclic AMP (0.1 to 100 microM) induced similar dose-dependent reductions of TNF synthesis. Thus the inhibitory effect of PGE2 probably required in part cyclic AMP accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

The cell-free medium of isolated human glomeruli exhibited a procoagulant activity and stimulated thromboxane (TXB2) synthesis in human platelets in a dose-dependent manner. The amount of TXB2 measured was 16-fold higher than what could have been predicted (TXB2 synthesized by the platelets under control conditions plus TXB2 present in the glomerular supernatant). The lipid extract of the glomerular supernatant and its purified fraction including the fatty acids was still able to stimulate--although at a lesser degree--TXB2 synthesis in platelets. Stimulation was abolished after treatment of this fraction by charcoal or albumin. Gas chromatography/mass spectrometry analysis demonstrated the presence in the purified glomerular fraction of several long-chain saturated or monoenoic fatty acids at a total concentration of 80 microM with the following order of abundance: stearic, palmitic, myristic and oleic acids. Addition to human platelets of these same exogenous synthetic acids resulted in a dose-dependent stimulation of TX synthesis. It was maximum with three or four fatty acids tested in combination, but still present with myristic acid used separately. Arachidonic acid was absent in the glomerular supernatant. Thus the stimulation observed could not be related to a greater availability of substrate. Fatty acids did not act on platelets through a non-specific detergent effect since addition of high doses of detergents inhibited TXB2 formation in platelets. The combination of fatty acids from glomerular origin identified in the present study represents a novel factor involved in the control of intracapillary hemostasis, but different from the procoagulant activity common to many tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Because there is an accumulation of macrophages in the Bowman's space during human and experimental glomerulonephritis, we have studied the binding of [3H]-uridine labeled macrophages to isolated glomeruli. Binding was related to the glomerular protein and macrophage concentrations, temperature, time of incubation, and was a saturable process. Macrophage adherence depended on glomerular lipoxygenase activity but not on glomerular cyclooxygenase activity since preincubation of glomeruli with nordihydroguaiaretic acid (NDGA) inhibited this phenomenon whereas preincubation with indomethacin was ineffective. Glomeruli interacted with macrophages in converting arachidonic acid (C20:4) to prostaglandins (PG) since productions of 6 keto-PGF1 alpha, TXB2, and PGD2 by glomeruli and macrophages incubated in combination were much greater than the sums of their respective productions by glomeruli and macrophages incubated separately. Macrophages were the source of the supplementary synthesis of PG which was abolished when these cells were pretreated with aspirin. Stimulation of macrophages by glomeruli was blunted by pretreatment of glomeruli with NDGA. Production of PG and of 12-HETE by macrophages was stimulated by a lipid extract of glomeruli containing the oxygenated metabolites of C20:4. Direct addition of 12-HPETE also stimulated macrophage functions. These data suggest that macrophage attachment to glomeruli and macrophage stimulation in the presence of glomeruli depend on glomerular lipoxygenase activity.