A novel fatty acid analogue triggers CD36-GPR120 interaction and exerts anti-inflammatory action in endotoxemia.

Inflammation is a mediator of a number of chronic pathologies. We synthesized the diethyl (9Z,12Z)-octadeca-9,12-dien-1-ylphosphonate, called NKS3, which decreased lipopolysaccharide (LPS)-induced mRNA upregulation of proinflammatory cytokines (IL-1ß, IL-6 and TNF-α) not only in primary intraperitoneal and lung alveolar macrophages, but also in freshly isolated mice lung slices. The in-silico studies suggested that NKS3, being CD36 agonist, will bind to GPR120. Co-immunoprecipitation and proximity ligation assays demonstrated that NKS3 induced protein-protein interaction of CD36 with GPR120in RAW 264.7 macrophage cell line. Furthermore, NKS3, via GPR120, decreased LPS-induced activation of TAB1/TAK1/JNK pathway and the LPS-induced mRNA expression of inflammatory markers in RAW 264.7 cells. In the acute lung injury model, NKS3 decreased lung fibrosis and inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and nitric oxide (NO) production in broncho-alveolar lavage fluid. NKS3 exerted a protective effect on LPS-induced remodeling of kidney and liver, and reduced circulating IL-1ß, IL-6 and TNF-α concentrations. In a septic shock model, NKS3 gavage decreased significantly the LPS-induced mortality in mice. In the last, NKS3 decreased neuroinflammation in diet-induced obese mice. Altogether, these results suggest that NKS3 is a novel anti-inflammatory agent that could be used, in the future, for the treatment of inflammation-associated pathologies.

In Vitro Functional Characterization of Type-I Taste Bud Cells as Monocytes/Macrophages-like Which Secrete Proinflammatory Cytokines.

The sense of taste determines the choice of nutrients and food intake and, consequently, influences feeding behaviors. The taste papillae are primarily composed of three types of taste bud cells (TBC), i.e., type I, type II, and type III. The type I TBC, expressing GLAST (glutamate--aspartate transporter), have been termed as glial-like cells. We hypothesized that these cells could play a role in taste bud immunity as glial cells do in the brain. We purified type I TBC, expressing F4/80, a specific marker of macrophages, from mouse fungiform taste papillae. The purified cells also express CD11b, CD11c, and CD64, generally expressed by glial cells and macrophages. We further assessed whether mouse type I TBC can be polarized toward M1 or M2 macrophages in inflammatory states like lipopolysaccharide (LPS)-triggered inflammation or obesity, known to be associated with low-grade inflammation. Indeed, LPS-treatment and obesity state increased TNFα, IL-1ß, and IL-6 expression, both at mRNA and protein levels, in type I TBC. Conversely, purified type I TBC treated with IL-4 showed a significant increase in arginase 1 and IL-4. These findings provide evidence that type I gustatory cells share many features with macrophages and may be involved in oral inflammation.

Cellular and Molecular Mechanisms of Fat Taste Perception.

During the last couples of years, a number of studies have increasingly accumulated on the gustatory perception of dietary fatty acids in rodent models and human beings in health and disease. There is still a debate to coin a specific term for the gustatory perception of dietary fatty acids either as the sixth basic taste quality or as an alimentary taste. Indeed, the psycho-physical cues of orosensory detection of dietary lipids are not as distinctly perceived as other taste qualities like sweet or bitter. The cellular and molecular pharmacological mechanisms, triggered by the binding of dietary long-chain fatty acids (LCFAs) to tongue taste bud lipid receptors like CD36 and GPR120, involve Ca2+ signaling as other five basic taste qualities. We have not only elucidated the role of Ca2+ signaling but also identified different components of the second messenger cascade like STIM1 and MAP kinases, implicated in fat taste perception. We have also demonstrated the implication of Calhm1 voltage-gated channels and store-operated Ca2+ (SOC) channels like Orai1, Orai1/3, and TRPC3 in gustatory perception of dietary fatty acids. We have not only employed siRNA technology in vitro and ex vivo on tissues but also used animal models of genetic invalidation of STIM1, ERK1, Orai1, Calhm1 genes to explore their implications in fat taste signal transduction. Moreover, our laboratory has also demonstrated the importance of LCFAs detection dysfunction in obesity in animal models and human beings.

Is fat taste associated with diet quality? A cross-sectional study conducted among Tunisian adults.

The Tunisian population has experienced a nutrition transition with an increase in the incidence of obesity. As obesity has been associated with a poor orosensory detection of fat. We hypothesized that poor fat detection could be a driver of poor diet quality. This study examined the association between linoleic acid (LA) detection and adherence to a healthy diet among adult participants. A total of 104 LA taster participants were recruited for this study. Dietary assessment was conducted using the 24 h dietary recall method. Diet quality was assessed by determining the Mediterranean diet (MD) score and Health diet indicator (HDI). The relationship between diet quality and log LA detection threshold was done using adjusted linear regression for age, sex, and daily energy intake (only in the fully adjusted model). The predictive margins model (interaction: anthropometric status x LA threshold) was used to assess the difference between non-obese and subjects with obesity adherence to MD across LA detection values. We have observed that the increase in the concentration of linoleic acid detection by 1 log(mmol/L) is associated with an increase of HDI score by 0.12-point [95% CI: 0.02-0.21] and a decrease of the MD score by -0.14-point [-0.25 to -0.03] in the partially adjusted model. However, only the MD score remained negatively associated with LA detection threshold in the fully adjusted model. The subjects with obesity adherence to the Mediterranean diet was lower than subjects with normal weight for LA concentration less than 0 log(mmol/L). The present study suggests that poor orosensory detection of dietary lipids might be a driver for worsening diet quality. Hence, These subjects might be at risk for obesity and, consequently, exposed cumulatively to the harmful effects of excess adiposity and an unhealthy diet.

Antioxidant and Anti-Inflammatory Potential of Polyphenols Contained in Mediterranean Diet in Obesity: Molecular Mechanisms.

Nutrition transition can be defined as shifts in food habits, and it is characterized by high-fat (chiefly saturated animal fat), hypercaloric and salty food consumption at the expense of dietary fibers, minerals and vitamins. Western dietary patterns serve as a model for studying the impact of nutrition transition on civilization diseases, such as obesity, which is commonly associated with oxidative stress and inflammation. In fact, reactive oxygen species (ROS) overproduction can be associated with nuclear factor-κB (NF-κB)-mediated inflammation in obesity. NF-κB regulates gene expression of several oxidant-responsive adipokines including tumor necrosis factor-α (TNF-α). Moreover, AMP-activated protein kinase (AMPK), which plays a pivotal role in energy homeostasis and in modulation of metabolic inflammation, can be downregulated by IκB kinase (IKK)-dependent TNF-α activation. On the other hand, adherence to a Mediterranean-style diet is highly encouraged because of its healthy dietary pattern, which includes antioxidant nutraceuticals such as polyphenols. Indeed, hydroxycinnamic derivatives, quercetin, resveratrol, oleuropein and hydroxytyrosol, which are well known for their antioxidant and anti-inflammatory activities, exert anti-obesity proprieties. In this review, we highlight the impact of the most common polyphenols from Mediterranean foods on molecular mechanisms that mediate obesity-related oxidative stress and inflammation. Hence, we discuss the effects of these polyphenols on a number of signaling pathways. We note that Mediterranean diet (MedDiet) dietary polyphenols can de-regulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and NF-κB-mediated oxidative stress, and metabolic inflammation. MedDiet polyphenols are also effective in upregulating downstream effectors of several proteins, chiefly AMPK.

Novel GPR120 agonist TUG891 modulates fat taste perception and preference and activates tongue-brain-gut axis in mice.

GPR120 is implicated as a lipid receptor in the oro-sensory detection of dietary fatty acids. However, the effects of GPR120 activation on dietary fat intake or obesity are not clearly understood. We investigated to determine whether the binding of TUG891, a novel GPR120 agonist, to lingual GPR120 modulates fat preference in mice. We explored the effects of TUG891 on obesity-related hormones and conducted behavioral choice tests on mice to better understand the physiologic relevance of the action of TUG891. In cultured mouse and human taste bud cells (TBCs), TUG891 induced a rapid increase in Ca2+ by acting on GPR120. A long-chain dietary fatty acid, linoleic acid (LA), also recruited Ca2+ via GPR120 in human and mouse TBCs. Both TUG891 and LA induced ERK1/2 phosphorylation and enhanced in vitro release of glucagon-like peptide-1 from cultured human and mouse TBCs. In situ application of TUG891 onto the tongue of anesthetized mice triggered the secretion of pancreatobiliary juice, probably via the tongue-brain-gut axis. Furthermore, lingual application of TUG891 altered circulating concentrations of cholecystokinin and adipokines, associated with decreased circulating LDL, in conscious mice. In behavioral tests, mice exhibited a spontaneous preference for solutions containing either TUG891 or LA instead of a control. However, addition of TUG891 to a solution containing LA significantly curtailed fatty acid preference. Our study demonstrates that TUG891 binds to lingual GPR120 receptors, activates the tongue-brain-gut axis, and modulates fat preference. These findings may support the development of new fat taste analogs that can change the approach to obesity prevention and treatment.

A Half Century of Oral Rehydration Therapy in Childhood Gastroenteritis: Toward Increasing Uptake and Improving Coverage.

Termed by the Lancet, as "potentially the most important medical advance of the twentieth century," therapy with oral rehydration solutions (ORSs) has been essential to reducing mortality in children less than 5 years (under five) with infectious gastroenteritis and diarrhea. The target of the diarrhea-control programs in the 1990s was to achieve ORS use in 80% of diarrhea cases by the year 2000. Nevertheless, nearly 20 years later, global uptake remains limited to only a third of the cases. Our analysis shows that from 1990 to 2017, mean ORS coverage in Countdown countries [the 81 Countdown-to-2030 priority countries, which together account for 95% of maternal deaths and 90% of under-five deaths] increased from ~ 30% to nearly 40%. Flawed government policies, inadequate supplies, and lack of awareness among health workers and communities all contributed to this shortfall in coverage. Moreover, imperfect measurement methodology is implicated in questionable coverage data. A multipronged approach focusing on the manufacture, supply, training, and behavioral change is essential to ensure that ORS is used in all epidemic diarrhea cases globally, especially in the under-five population.

Octadecaneuropeptide (ODN) Induces N2a Cells Differentiation through a PKA/PLC/PKC/MEK/ERK-Dependent Pathway: Incidence on Peroxisome, Mitochondria, and Lipid Profiles.

Neurodegenerative diseases are characterized by oxidative stress, mitochondrial damage, and death of neuronal cells. To counteract such damage and to favor neurogenesis, neurotrophic factors could be used as therapeutic agents. Octadecaneuropeptide (ODN), produced by astrocytes, is a potent neuroprotective agent. In N2a cells, we studied the ability of ODN to promote neuronal differentiation. This parameter was evaluated by phase contrast microscopy, staining with crystal violet, cresyl blue, and Sulforhodamine 101. The effect of ODN on cell viability and mitochondrial activity was determined with fluorescein diacetate and DiOC6(3), respectively. The impact of ODN on the topography of mitochondria and peroxisomes, two tightly connected organelles involved in nerve cell functions and lipid metabolism, was evaluated by transmission electron microscopy and fluorescence microscopy: detection of mitochondria with MitoTracker Red, and peroxisome with an antibody directed against the ABCD3 peroxisomal transporter. The profiles in fatty acids, cholesterol, and cholesterol precursors were determined by gas chromatography, in some cases coupled with mass spectrometry. Treatment of N2a cells with ODN (10-14 M, 48 h) induces neurite outgrowth. ODN-induced neuronal differentiation was associated with modification of topographical distribution of mitochondria and peroxisomes throughout the neurites and did not affect cell viability and mitochondrial activity. The inhibition of ODN-induced N2a differentiation with H89, U73122, chelerythrine and U0126 supports the activation of a PKA/PLC/PKC/MEK/ERK-dependent signaling pathway. Although there is no difference in fatty acid profile between control and ODN-treated cells, the level of cholesterol and some of its precursors (lanosterol, desmosterol, lathosterol) was increased in ODN-treated cells. The ability of ODN to induce neuronal differentiation without cytotoxicity reinforces the interest for this neuropeptide with neurotrophic properties to overcome nerve cell damage in major neurodegenerative diseases.

Taste perception and its effects on oral nutritional supplements in younger life phases.

PURPOSE OF REVIEW: The current review summarizes the importance of taste perception with regard to acceptance of oral nutritional supplements (ONS) in young children. We also shed light on how basic tastes may influence the orosensory detection of ONS in the light of genetic variations, encoding for different taste modalities, particularly for sweet and bitter (and fat), in children. RECENT FINDINGS: Single nucleotide polymorphism (SNP) of bitter and sweet taste receptor genes, that is, respectively, TAS2R38 and T1R2/T1R3, may influence orosensory perception of 'bitter-made-sweet' ONS. The SNP of fat taste receptor gene, that is, CD36, might communicate with bitter taste perception. The emerging new sixth fat taste may interfere with obesity in children. SUMMARY: Sweet and bitter taste modalities are innate cues, expressed by children from birth to adolescence, either by a strong preference or by food aversion. Sweet and bitter tastes also communicate with each other as sweeteners can mask bitter phenotype. The fat preference, encoded by specific lingual taste receptors, is also modulated, via its interaction with phenotype and genotype, by bitter taste. Sodium salts might interact with bitter taste. Finally, the taste modalities will impact on the intake of ONS in children as the taste phenotype changes in this population, irrespective to genotype.

The rs1527483, but not rs3212018, CD36 polymorphism associates with linoleic acid detection and obesity in Czech young adults.

Recent evidence has raised the possibility of the existence of a sixth taste modality - that is, taste for fat - which is mediated by lingual CD36 and plays a role in obesity. Consequently, the genetic polymorphism of CD36 has been shown to be associated with altered oro-sensory detection of dietary lipids. In the present study, we investigated the relationship between oro-sensory perception of linoleic acid (LA), two CD36 polymorphisms (rs1527483 and rs3212018), obesity parameters and craving habits for dietary lipids in young Czech adults. We also sequenced 5 and 6 exons of CD36 to trace out any new mutation that might be responsible for the difference in taste perception. We observed that craving for dietary lipids was correlated with anthropometric parameters (P<0·05) and LA detection threshold (P=0·033). The participants with the CC genotype of the rs1527483 polymorphism had lower BMI (P=0·011), waist circumference (P=0·005), waist:height ratio (P=0·010) and higher sensitivity for LA (P=0·037) than the participants with the CT and TT genotypes. Interestingly, we did not observe any association between the rs3212018 polymorphism and the studied parameters. Moreover, we did not observe any mutation in exons 5 and 6 of the CD36 gene in these subjects. Finally, we can state that rs1527483, but not rs3212018, is associated with high body weight in young Czech subjects.

Promoting healthy school food environments and nutrition in Canada: a systematic review of interventions, policies, and programs.

CONTEXT: The school food environment is a critical interface for child and adolescent nutrition, and there is a need to understand existing literature on Canadian school food environments to identify equity gaps and opportunities, and empower decision-makers to plan for future action. OBJECTIVE: Literature on Canadian school food and nutrition interventions, policies, programs, and their effects on diets and nutritional status are synthesized and appraised in this systematic review. DATA SOURCES: A search strategy was developed for each database used (Medline, Embase, PsycINFO, ERIC, Cochrane Collaboration, Canadian Electronic Library, BiblioMap), with a combination of free text and controlled vocabulary, for articles published from 1990 to 2021. Unpublished data and grey literature were also searched. DATA EXTRACTION: Quantitative and qualitative studies with an observational or intervention study design, reviews, or program evaluations conducted in Canadian schools with participants aged 5-19.9 years were included. Key study characteristics and risk of bias were extracted independently by 2 investigators using a standardized tool. DATA ANALYSIS: A total of 298 articles were included (n = 192 peer reviewed and 106 from the grey literature), which were mostly conducted in Ontario (n = 52), British Columbia (n = 43), and Nova Scotia (n = 28). Twenty-four interventions, 5 nonevaluated programs, and 1 policy involved Indigenous populations. Overall, 86 articles measured and reported on effectiveness outcomes, including dietary intake; anthropometry; knowledge, attitudes, and practices; and physical activity. The literature remains largely heterogenous and primarily focused on nutrition education programs that use subjective assessments to infer changes in nutrition. A key facilitator to implementation and sustainability was community engagement, whereas key barriers were staff capacity, access to resources and funding, and consistent leadership. CONCLUSIONS: This review provides insight into Canadian school food and nutrition interventions, programs, and policies and uncovers important evidence gaps that require careful examination for future evaluations. Governments must create supportive environments that optimize nutrition for children and adolescents through equitable policies and programs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022303255.

A Low-Cost, Integrated Immunization, Health, and Nutrition Intervention in Conflict Settings in Pakistan-The Impact on Zero-Dose Children and Polio Coverage.

Pakistan is one of two countries globally still endemic for poliovirus. While increasing immunization coverage is a concern, providing equitable access to care is also a priority, especially for conflict-affected populations. Recognizing these challenges, Naunehal, an integrated model of maternal, newborn, and child health (MNCH), immunization, and nutrition services delivered through community mobilization, mobile outreach, and private-sector engagement was implemented in conflict-affected union councils (UCs) with high poliovirus transmission, including Kharotabad 1(Quetta, Balochistan) and Bakhmal Ahmedzai (Lakki Marwat, Khyber Pakhtunkhwa). A quasi-experimental pre-post-design was used to assess the impact of the interventions implemented between April 2021 and April 2022, with a baseline and an endline survey. For each of the intervention UCs, a separate, matched-control UC was identified. At endline, the proportion of fully immunized children increased significantly from 27.5% to 51.0% in intervention UCs with a difference-in-difference (DiD) estimate of 13.6%. The proportion of zero-dose children and non-recipients of routine immunization (NR-RI) children decreased from 31.6% to 0.9% and from 31.9% to 3.4%, respectively, with a significant decrease in the latter group. Scaling up and assessing the adoption and feasibility of integrated interventions to improve immunization coverage can inform policymakers of the viability of such services in such contexts.

Measuring coverage in MNCH: a prospective validation study in Pakistan and Bangladesh on measuring correct treatment of childhood pneumonia.

BACKGROUND: Antibiotic treatment for pneumonia as measured by Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) is a key indicator for tracking progress in achieving Millennium Development Goal 4. Concerns about the validity of this indicator led us to perform an evaluation in urban and rural settings in Pakistan and Bangladesh. METHODS AND FINDINGS: Caregivers of 950 children under 5 y with pneumonia and 980 with "no pneumonia" were identified in urban and rural settings and allocated for DHS/MICS questions 2 or 4 wk later. Study physicians assigned a diagnosis of pneumonia as reference standard; the predictive ability of DHS/MICS questions and additional measurement tools to identify pneumonia versus non-pneumonia cases was evaluated. Results at both sites showed suboptimal discriminative power, with no difference between 2- or 4-wk recall. Individual patterns of sensitivity and specificity varied substantially across study sites (sensitivity 66.9% and 45.5%, and specificity 68.8% and 69.5%, for DHS in Pakistan and Bangladesh, respectively). Prescribed antibiotics for pneumonia were correctly recalled by about two-thirds of caregivers using DHS questions, increasing to 72% and 82% in Pakistan and Bangladesh, respectively, using a drug chart and detailed enquiry. CONCLUSIONS: Monitoring antibiotic treatment of pneumonia is essential for national and global programs. Current (DHS/MICS questions) and proposed new (video and pneumonia score) methods of identifying pneumonia based on maternal recall discriminate poorly between pneumonia and children with cough. Furthermore, these methods have a low yield to identify children who have true pneumonia. Reported antibiotic treatment rates among these children are therefore not a valid proxy indicator of pneumonia treatment rates. These results have important implications for program monitoring and suggest that data in its current format from DHS/MICS surveys should not be used for the purpose of monitoring antibiotic treatment rates in children with pneumonia at the present time.

Determinants of suboptimal breast-feeding practices in Pakistan.

OBJECTIVE: Exclusive breast-feeding is estimated to reduce infant mortality in low-income countries by up to 13 %. The aim of the present study was to determine the risk factors associated with suboptimal breast-feeding practices in Pakistan. DESIGN: A cross-sectional study using data extracted from the multistage cluster sample survey of the Pakistan Demographic and Health Survey 2006-2007. SETTING: A nationally representative sample of households. SUBJECTS: Last-born alive children aged 0-23 months (total weighted sample size 3103). RESULTS: The prevalences of timely initiation of breast-feeding, bottle-feeding in children aged 0-23 months, exclusive breast-feeding and predominant breast-feeding in infants aged 0-5 months were 27·3 %, 32·1 %, 37·1 % and 18·7 %, respectively. Multivariate analysis indicated that working mothers (OR = 1·48, 95 % CI 1·16, 1·87; P = 0·001) and mothers who delivered by Caesarean section (OR = 1·95, 95 % CI 1·30, 2·90; P = 0·001) had significantly higher odds for no timely initiation of breast-feeding. Mothers from North West Frontier Province were significantly less likely (OR = 0·37, 95 % CI 0·23, 0·59; P < 0·001) not to breast-feed their babies exclusively. Mothers delivered by traditional birth attendants had significantly higher odds to predominantly breast-feed their babies (OR = 1·96, 95 % CI 1·18, 3·24; P = 0·009). The odds of being bottle-fed was significantly higher in infants whose mothers had four or more antenatal clinic visits (OR = 1·93, 95 % CI 1·46, 2·55; P < 0·001) and belonged to the richest wealth quintile (OR = 2·41, 95 % CI 1·62, 3·58; P < 0·001). CONCLUSIONS: The majority of Pakistani mothers have suboptimal breast-feeding practices. To gain the full benefits of breast-feeding for child health and nutrition, there is an urgent need to develop interventions to improve the rates of exclusive breast-feeding.

NAUNEHAL; Integrated immunization and MNCH interventions: A quasi-experimental study-Protocol.

INTRODUCTION: Great improvements in the health of newborns, children, and women in Pakistan are needed. A large body of literature has demonstrated that the majority of maternal, newborn, and child deaths are preventable with essential health strategies including immunization, nutrition interventions, and child health interventions. Despite the importance of these interventions for the health of women and children, access to services continues to be a barrier. Furthermore, demand for services also contributes to low coverage of essential health interventions. Given the emerging threat of COVID-19 coupled with already weak maternal and child health, delivering effective and feasible nutrition and immunization services to communities, and increasing demand and uptake of services is a pressing and important need. METHODS AND ANALYSIS: This quasi-experimental study aims to improve health service delivery and increase uptake. The study included four main intervention strategies including community mobilization, mobile health teams offering MNCH and immunization services, engagement of the private sector, and testing of a comprehensive health, nutrition, growth, and immunization app, Sehat Nishani, for a period of 12 months. The target group of the project were women of reproductive age (15-49 years) and children under-five. The project was implemented in three union councils (UCs) in Pakistan including Kharotabad-1(Quetta District, Balochistan), Bhana Mari (Peshawar District, Khyber Pakhtunkhwa) and Bakhmal Ahmedzai (Lakki Marwat district, Khyber Pakhtunkhwa). Propensity score matching based on size, location, health facilities, and key health indicators of UC was conducted to identify three matched UCs. A household baseline, midline, endline and close-out assessment will be conducted for evaluating coverage of interventions as well as the knowledge, attitude, and practices of the community in the MNCH and COVID-19 context. Descriptive and inferential statistics will be used to test hypotheses. As well, a detailed cost-effectiveness analysis will be conducted to generate costing data for these interventions to effectively inform policymakers and stakeholder on feasibility of the model. Trial registration: NCT05135637.

Loss of Sour Taste Is the Striking Feature among Four Basic Taste Qualities in Tunisian COVID-19 Patients.

BACKGROUND: Taste disorders (TDs) have been reported to be very common in patients suffering from coronavirus disease 2019 (COVID-19), which is caused by the SARS-CoV-2 virus. In most of the hitherto conducted studies, a gustatory assessment was performed on the basis of surveys or self-reports by patients. The aim of our study was to undertake an objective assessment of four basic taste qualities by conducting tasting sessions that allowed detection thresholds in COVID-19 Tunisian patients and to study their associations with inflammation. METHODS: This analytical cross-sectional study was conducted on 89 patients aged between 21 to 70 years who had been diagnosed with COVID-19. We used Burghart taste strips to assess taste perception of the four taste qualities, i.e., sour, bitter, sweet, and salty. Serum levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) were measured. RESULTS: Taste disorders were reported by 40.4% of the patients, while objective assessments revealed that 63.8% of participants were suffering from hypogeusia and/or ageusia. Sour taste was the most altered (70.8%) gustatory quality. Patients with severe COVID-19 had significantly lower sour and bitter taste scores when compared to patients with minor/moderate forms. There was no significant association between serum inflammatory markers and taste disorders. However, the relationship between bitter and sweet taste qualities and IL-1ß levels was significant (p = 0.018 and p = 0.041). CONCLUSIONS: Our results demonstrate the interest in the objective assessment of taste dysfunctions in COVID-19 patients.

The Last Mile-Community Engagement and Conditional Incentives to Accelerate Polio Eradication in Pakistan: Study Protocol for a Quasi-Experimental Trial.

Poliomyelitis is a condition of great concern and is endemic in only two countries of the world: Pakistan and Afghanistan. Community mobilization plays a vital role in raising awareness and can help reduce polio vaccine refusals. The objective of this study will be to decrease polio vaccine refusals and zero-dose vaccines by motivating behavior change through the provision of conditional-collective-community-based incentives (C3Is) based on a reduction in polio vaccine refusals. The project will adopt a pretest/post-test quasi-experimental design with two intervention high-risk union councils (HRUCs) and two control union councils (UCs) of peri-urban (Karachi) and rural (Bannu) settings in Pakistan. A participatory community engagement and demand creation strategy with trust-building community mobilization with C3Is, to reduce vaccine refusals and improve polio immunization coverage in two HRUCs, will be used. These UCs will be divided into clusters based on the polio program framework and community groups will be formed in each cluster. These community groups will carry out awareness activities and will be given serial targets to reduce vaccine refusals and those who qualify will be provided C3Is. The project intends to create a replicable model that the government can integrate within health systems for long-term sustainability until the goal of eradication of poliovirus is achieved. The evaluation will be carried out by an independent data collection and analysis team at baseline and endline (after 12 months of intervention). The trial is registered with linicalTrials.gov with number NCT05721274.

Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male Mice.

BACKGROUND & AIMS: The spontaneous preference for dietary lipids is principally regulated by 2 lingual fat taste receptors, CD36 and GPR120. Obese animals and most of human subjects exhibit low orosensory perception of dietary fat because of malfunctioning of these taste receptors. Our aim was to target the 2 fat taste receptors by newly synthesized high affinity fatty acid agonists to decrease fat-rich food intake and obesity. METHODS: We synthesized 2 fat taste receptor agonists (FTA), NKS-3 (CD36 agonist) and NKS-5 (CD36 and GPR120 agonist). We determined their molecular dynamic interactions with fat taste receptors and the effect on Ca2+ signaling in mouse and human taste bud cells (TBC). In C57Bl/6 male mice, we assessed their gustatory perception and effects of their lingual application on activation of tongue-gut loop. We elucidated their effects on obesity and its related parameters in male mice fed a high-fat diet. RESULTS: The two FTA, NKS-3 and NKS-5, triggered higher Ca2+ signaling than a dietary long-chain fatty acid in human and mouse TBC. Mice exhibited a gustatory attraction for these compounds. In conscious mice, the application of FTA onto the tongue papillae induced activation of tongue-gut loop, marked by the release of pancreato-bile juice into collecting duct and cholecystokinin and peptide YY into blood stream. Daily intake of NKS-3 or NKS-5 via feeding bottles decreased food intake and progressive weight gain in obese mice but not in control mice. CONCLUSIONS: Our results show that targeting fat sensors in the tongue by novel chemical fat taste agonists might represent a new strategy to reduce obesity.

DHA induces Jurkat T-cell arrest in G2/M phase of cell cycle and modulates the plasma membrane expression of TRPC3/6 channels.

We investigated whether docosahexaenoic acid (DHA), a dietary n-3 fatty acid, modulates calcium (Ca2+) signaling and cell cycle progression in human Jurkat T-cells. Our study demonstrates that DHA inhibited Jurkat T-cell cycle progression by blocking their passage from S phase to G2/M phase. In addition, DHA decreased the plasma membrane expression of TRPC3 and TRPC6 calcium channels during T-cell proliferation. Interestingly, this fatty acid increased plasma membrane expression of TRPC6 after 24 h of mitogenic stimulation by phorbol-13-myristate-12-acetate (PMA) and ionomycin. These variations in the membrane expression of TRPC3 and TRPC6 channels were not directly correlated with the mRNA expression, indicating that it was a post-translational phenomenon. DHA increased free intracellular calcium concentrations, [Ca2+]i, via opening TRPC3 and TRPC6 channels. We conclude that the anti-proliferative effect of DHA might involve the modulation of TRPC3 and TRPC6 channels in human T-cells.

Tongue Leptin Decreases Oro-Sensory Perception of Dietary Fatty Acids.

Leptin, an anorectic hormone, regulates food intake, energy expenditure and body weight. We assessed the implication of tongue leptin in the modulation of oro-sensory detection of dietary fatty acids in mice. The RT-PCR analysis showed that mRNA encoding leptin and leptin receptor (Ob-Rb) was expressed in mice taste bud cells (TBC). Confocal microscopic studies showed that the lipid sensor CD36 was co-expressed with leptin in mice TBC. Silencing of leptin or Ob-Rb mRNA in tongue papillae upregulated preference for a long-chain fatty acid (LCFA), i.e., linoleic acid (LA), in a two-bottle paradigm in mice. Furthermore, tongue leptin application decreased the preference for the LCFA. These results suggest that tongue leptin exerts an inhibitory action on fatty acid preference. In isolated mice TBC, leptin decreased LCFA-induced increases in free intracellular calcium concentrations, [Ca2+]i. Leptin and LCFA induced the phosphorylation of ERK1/2 and STAT-3 and there were no additive or opposite effects of the two agents on the degree of phosphorylation. However, leptin, but not the LCFA, induced phosphoinositide-3-kinase (PI-3-K)-dependent Akt phosphorylation in TBC. Furthermore, leptin induced hyperpolarization, whereas LCFA induced depolarization in TBC. Our study demonstrates that tongue leptin exerts an inhibitory action on oro-sensory detection of a dietary fatty acid by interfering with Ca2+ signaling and membrane potential in mice TBC.