Dysgeusia Research Articles

Prevalence of smell and taste dysfunction in different clinical severity groups of COVID-19 patients

BACKGROUND: Studies on the long-term prevalence of smell and taste impairment concerned with severe disease in the acute phase of COVID-19 are limited. The aim of our study was to assess and compare psychophysical testing and self-reported smell and taste disturbances and recovery between three patient groups suffering from critical, severe, or mild COVID-19 in a follow-up at six-months after the acute phase. METHODOLOGY: The prospective controlled study of 227 participants comprised 72 intensive-care-unit-treated (ICU-treated), 53 pulmonology- or infectious-diseases-ward-treated (WARD-treated), and 48 home-isolated patients (HOME) with preceding COVID-19, and 54 individuals with no history of COVID-19 (CONTROL). All participants visited a follow-up clinic for a sense-of-smell screening and underwent Magnetic Resonance Imaging (MRI) of the brain, olfactory bulbs and sinonasal area at six months after acute disease. Before the follow-up visit, the participants received a questionnaire concerning smell and taste function. We sent a supplementary questionnaire including questions about phantosmia and parosmia and taste recovery at a median of 502.5 days after the acute phase. RESULTS: We found no statistically significant differences between the groups in the incidence of smell and taste dysfunction, recovery, or the occurrence of parosmia or phantosmia. There were no statistically significant differences in semi-objective smell performance across the different study groups and controls. The olfactory bulb volume was normal in all patients and controls. Mucosal thickening in paranasal sinuses was rare. CONCLUSIONS: We found no difference in a six-month follow-up in the subjective or semi-objective senses of smell and taste between three severity groups of COVID-19 and controls.

Clinical effects of traditional Chinese herbal medicine management in patients with COVID-19 sequelae: A hospital-based retrospective cohort study in Taiwan.

Introduction: An estimated 43% of COVID-19 patients showed sequelae, including fatigue, neurocognitive impairment, respiratory symptoms, and smell or taste disorders. These sequelae significantly affect an individual's health, work capacity, healthcare systems, and socioeconomic aspects. Traditional Chinese herbal medicine (TCHM) management showed clinical benefits in treating patients with COVID-19 sequelae. This study aimed to analyze the effects of personalized TCHM management in patients with COVID-19 sequelae. Methods: After the COVID-19 outbreak in Taiwan, we recorded Chronic Obstructive Pulmonary Disease Assessment Tool (CAT), Chalder Fatigue Questionnaire (CFQ-11), and Brief Symptom Rating Scale (BSRS-5) to assess post-COVID respiratory, fatigue, and emotional distress symptoms, respectively. In this study, we retrospectively reviewed the medical records between July 2022 and March 2023. We analyzed the effects of TCHM administration after 14- and 28-days of treatment. Results: 47 patients were included in this study. The results demonstrated that personalized TCHM treatment significantly improved the CAT, CFQ-11, and BSRS-5 scores after 14 and 28 days. TCHM alleviated physical and psychological fatigue. In logistic regression analysis, there was no statistically significant differences in the severity of the baseline symptoms and TCHM administration effects concerning the duration since the initial confirmation of COVID-19, sex, age, or dietary preference (non-vegetarian or vegetarian). Conclusions: Our study suggested that personalized TCHM treatment notably reduced fatigue, respiratory and emotional distress symptoms after 14- and 28-days of treatment in patients with COVID-19 sequelae. We propose that TCHM should be considered as an effective intervention for patients with COVID-19 sequelae.

Prevalence and Factors Associated with Olfactory Dysfunction in Individuals with COVID-19 in Brazil: A Study of 20,669 Cases from 2020 to 2021

Objective: The aim of the study is to determine the prevalence and factors associated with olfactory dysfunction in individuals with COVID-19 in the first 2 years of the pandemic in Brazil. Materials and Methods: This is a prevalent study involving the confirmed cases of COVID-19 recorded in the municipality between the years 2020 and 2021. Individuals symptomatic for COVID-19, with a positive laboratory result and aged 12 or older were included in this study. Measures of central tendency and dispersion were used in the description of continuous variables and frequency was used for categorical variables. The Shapiro-Wilk test was used to evaluate data distribution. Results: Data from 20,669 individuals were analyzed. The prevalence of olfactory disorders was 17.9% and increased from 11.5% to 21.9% between 2020 and 2021. A female gender predominance was observed among individuals who reported anosmia, with 61.1% (n = 564) in 2020 and 61.7% (n = 1,713) in 2021. On the other hand, the median age of individuals with olfactory disorders was lower than that of the group without disorders (35 [IQR 27–46] vs. 39 [IQR 29–50]; p < 0.001). Smell disturbances were present in 18.2% (n = 3,634) of patients who recovered and in 7.1% (n = 38) of those who died. Furthermore, in 2021, a prevalence rate of 30.6% for olfactory disorders was linked to obesity as a comorbidity. Conclusion: The prevalence of olfactory disorders was lower compared to other studies, with cough and fever being negatively related to olfactory dysfunction and headache, coryza, and taste disorders being positively related. Obesity was the only associated comorbidity.

Efficacy and safety of alpha-pinene capsule in the management of functional dyspepsia and eradication of helicobacter pylori: a randomized clinical trial.

Our objective was to assess the efficacy and safety of adding alpha-pinene (a herbal terpenoid) to quadruple therapy compared to a placebo in improving symptoms and Helicobacter pylori (H. pylori) eradication rates in Functional dyspepsia (FD) patients. FD is a prevalent upper gastrointestinal condition, and no definitive pharmacological treatment is available for its management. We conducted a randomized, double-blinded, placebo-controlled trial on FD patients diagnosed with H. pylori infection. We collected baseline demographic data and assessed FD symptoms in the participants. Patients were randomly allocated to receive either standard quadruple therapy with α-pinene capsules (0.25 mg/day) or quadruple therapy with a placebo for two weeks. We employed a validated questionnaire, the Short Form Leeds Dyspepsia Questionnaire (SF-LDQ), to evaluate FD symptoms. The eradication rate of H. pylori was compared between the two groups one month after completing the treatment regimens. Any reported adverse drug reactions (ADRs) were documented throughout the trial. Over four months, a total of 66 patients completed the trial. Notably, there were no significant differences in baseline SF-LDQ scores between the two groups (p=0.83); however, a significant divergence emerged at the trial's conclusion (p=0.03). The H. pylori eradication rates did not show notable differences between the two treatment arms (p=0.43). Importantly, there were no dropouts from the trial due to ADRs. Among reported ADRs, participants experienced abdominal pain, headache, diarrhea, and a metallic taste, with no significant variance in incidence rates observed between the two groups (p=0.62). These findings suggest that α-pinene could be an effective and safe agent for reducing FD symptoms.

Integrating the patient's voice into the research agenda for treatment of chemosensory disorders.

World-wide some 658 million people were infected with coronavirus disease 2019 (COVID-19) and millions suffer from chemosensory impairment associated with long COVID. Current treatments for taste and smell disorders are limited. Involving patients has the potential to catalyze the dynamic exchange and development of new ideas and approaches to facilitate biomedical research and therapeutics. We assessed patients' perceptions of the efficacy of treatments for chemosensory impairment using an online questionnaire completed by 5,815 people in the US Logistic regression determined variables predictive of reported treatment efficacy for patients aged 18 to 24, 25 to 39, 40 to 60, and 60+ yrs. who were treated with nasal steroids, oral steroids, zinc, nasal rinse, smell training, theophylline, platelet-rich plasma, and Omega 3. The most consistent predictor was age, with the majority of those 40 to 60 and 60+ reporting that nasal steroids, oral steroids, zinc, nasal rinse, and smell training were only slightly effective or not effective at all. Many of these treatment strategies target regeneration and immune response, processes compromised by age. Only those under 40 reported more than slight efficacy of steroids or smell training. Findings emphasize the need to include patients of all ages in clinical trials. Older adults with olfactory impairment are at increased risk for Alzheimer's disease (AD). We speculate that olfactory impairment associated with long COVID introduces the potential for a significant rise in AD. Long COVID-associated chemosensory impairment increases the urgency for translational and clinical research on novel treatment strategies. Suggestions for high-priority areas for epidemiological, basic, and clinical research on chemosensory impairment follow.

Redefining endoscopic stapedotomy: a detailed exploration of endoscopic principles and surgical techniques

Objective: Our aim was to investigate the practicality, safety, and effectiveness of endoscopic stapedotomy (ES) for otosclerosis. To assess audiological outcomes and any complications that arose during our experience at the hospital. Methods: A Case Series of 42 patients underwent ES at our hospital between January 2021 and December 2023. Patients were carefully selected based on a confirmed diagnosis of otosclerosis, age (18 years or older), and no history of prior ear surgery or chronic middle ear issues. We diligently collected data on patient characteristics, surgical specifics, hearing outcomes, and any complications encountered and then analyzed this data to see how ES affected patients’ hearing and how safe it was. Results: Significant improvement in air conduction (AC), bone conduction (BC), and the air-bone gap (ABG) after surgery (p &lt; 0.0001 for all). On average, the surgery took 31 min to perform. Complications were rare, with only a few patients experiencing mild vertigo. Notably, we had no cases of taste disturbance (dysgeusia) or eardrum perforation. As the surgeon gained more experience with ES, we noticed a trend toward shorter operating times and fewer complications. Conclusion: Our experience with ES suggests that it is a feasible, effectual, and the safest technique for treating otosclerosis. It offers significant benefits in terms of better visualization and less invasive surgery, but it does require specialized training. It is clear that a surgeon’s experience with this technique plays a significant role in achieving the best possible outcomes for patients.

Adverse event profile differences between pralsetinib and selpercatinib: a real-world study based on the FDA adverse events reporting system.

The objective of this study is to compare the adverse events (AEs) associated with pralsetinib and selpercatinib. To evaluate the imbalance of AEs linked to pralsetinib and selpercatinib in real-world data, the reporting odds ratio (ROR) was utilized to detect potential signals of AEs. Stratified analysis was conducted to examine the differences in AEs occurring among different genders and age groups taking pralsetinib and selpercatinib. FAERS received 891 reports for pralsetinib and 569 reports for selpercatinib. Our analysis confirmed expected AEs like hypertension, fatigue, and elevated transaminase levels. Unexpected AEs such as rhabdomyolysis, myocardial injury and cognitive disorder were associated with pralsetinib, while selpercatinib was linked with pulmonary embolism, deep vein thrombosis, and pericardial effusion. The risk of AEs such as decreased platelet count, anemia, decreased white blood cell count, pneumonitis, asthenia, and edema caused by pralsetinib is significantly higher than that of selpercatinib. In contrast, the risk of AEs such as ascites, elevated alanine aminotransferase, and elevated aspartate aminotransferase caused by selpercatinib is significantly higher than that of pralsetinib. Women treated with pralsetinib experience higher rates of hypertension, pulmonary embolism, and blurred vision than men, who are more susceptible to rhabdomyolysis. Adults between 18 and 65years are more likely to experience taste disorder, edema, and pulmonary embolism than individuals older than 65, who are particularly vulnerable to hypertension. For patients treated with selpercatinib, males demonstrate a significantly higher incidence of QT prolongation, urinary tract infection, and dysphagia. Individuals aged 18 to 65 are more likely to experience pyrexia and pleural effusion than those older than 65, who are more prone to hypersensitivity. In the clinical administration of pralsetinib and selpercatinib, it is crucial to monitor the effects of gender and age on AEs and to be vigilant for unlisted AEs.

Not Every Anosmia is COVID, a Case of Nasal Mass

Smell and test problems especially anosmia is a frequent symptom for COVID infection. Anosmia was experienced by almost 53% of those affected, in some cases persisting for longer periods after resolution of respiratory symptoms. Nasal blockage is another common symptom for emergency department patients and frequently associated with allergic rhinitis. A 25-year-old male patient presented with persistent bilateral nasal blockage, blood-stained nasal discharge, anosmia, and headache since last 1 year. During the peak of the pandemic, he was diagnosed with COVID. He was complaining of anosmia and nasal blockage and was treated with antihistaminic medicine for allergic rhinitis, but his symptoms persisted. He had breathing, bleeding and smelling problems in the last 2 years and started complaining of left sided proptosis for 3-4 weeks before being admitted to our department and had computerized tomography (CT) imaging at another facility. He was referred by an ophthalmologist to our hospital for advanced imaging with magnetic resonance (MRI) with contrast. He was investigated for exophthalmos in his left eye. He denied any other prior disease or medication. On examination he has nasal voice, left side exophthalmos, no diplopia or vision problem. The right tympanic membrane (TM) was intact, left sided dull TM with effusion. Other system evaluations were unremarkable. The patient was referred to Ear Nose and Throat consultant for further examination. Nasal endoscopy revealed fungating mass with covered blood clots and engorged vessels filling both the nasal cavities. MRI report described soft tissue mass, infiltrating the nasal cavity, paranasal sinuses and clivus with intracranial extension, to involve the left sub frontal region. Also noted associated destruction of the left lamina papyracea, showing orbital extension, compressing the orbital muscle cone, and compressing the medial rectus, with consequent left sided unilateral proptosis. In addition, there was nasopharyngeal extension. The epicenter of the mass was likely to be the ethmoid sinuses. His MRI revealed complete obstruction of the osteomeatal complexes, complete obliteration of the maxillary, ethmoids and frontal sinuses, due to retention of secretions and mass infiltration. Biopsy was taken and patient was followed up for surgical intervention. The differential diagnosis included vascular tumor, meningothelial tumor, undifferentiated carcinoma, and neuroendocrine carcinoma. Smell and taste disorders emerge during COVID infection, seem to be more common than other upper respiratory tract infections. Allergic rhinitis is also common amongst emergency department patients and frequently associated with nasal blockage. Rhinitis can be differentiated from sinus problems by the increased response of nasal obstruction to treatment, clear nasal discharge, and absence of pain or fever. Rhinitis does not lead to ostial obstruction, and patients do not complain of facial pain or headache. For suspected rhinitis or acute sinusitis, routine radiographic examination is not recommended and should be limited to the diagnosis of chronic or recurrent admissions, cases of questionable diagnoses, patients with unresponsive disease, or investigation of complications. Axial and coronal CT is the imaging modality of choice. In this case the patient was investigated for sinusitis complications and additional further imaging was necessary like MRI with contrast for proper diagnosis and management of the patient. Nasal blockage and upper respiratory system findings may be overseen by the patients or even the healthcare workers. Especially repeated admissions and persistence of these symptoms should be suspicious for the emergency physicians. Additional imaging and thorough examination are crucial for differential diagnosis and proper management of these patients. Emergency physicians should be careful on their diagnoses for common symptoms like nasal blockage especially for the patient

Evaluation of Hemodialysis Complications among Children with Chronic Kidney Disease at District Head Quarter Hospital, Nankana Sahib

A patient with chronic kidney disease depends on hemodialysis to mechanically remove fluid, electrolytes, and waste products from the blood. Chronic kidney disease (CKD) is a universal matter of concern that affects around 15% of the population globally. Objective: To evaluate hemodialysis complications among children with chronic kidney disease. Methods: A cross-sectional descriptive study was carried out at the renal department of DHQ hospital. The duration of study was six months from April to September, 2023. The sample size was 45 children on hemodialysis with kidney disease. A purposive sampling technique was used. Data were gathered through self-administrated questionnaire. Data were analyzed through SPSS-25.0 and results were presented in the form of frequencies tables. Results: Majority of the participants suggested that initiation of hemodialysis lead to cardiovascular problems (72%), anemia (83%), and metallic taste (79%) in children. Moreover, majority of them complained about skin problem and itching as an adverse effect (78%). Other complications as indicated by participants are headache, restlessness, vertigo, nausea and vomiting (86%). Conversely, some subjects did not considered the hypertriglyceridemia (27%), gastric problems (31%), sleep problems (24%) and muscular pain (34%) as the result of initiation of hemodialysis procedure. Conclusions: Findings of present study suggested the most common complications of hemodialysis are hemodynamic instability, anemia and hypertension/hypotension, skin problems and itching. Other complications of hemodialysis as indicated by participants are headache, restlessness, vertigo, nausea, vomiting and decease concentration in children. However, most of the participants have limited understanding about additional complications of hemodialysis.

Chronic Kidney Disease Interplay with Comorbidities and Carbohydrate Metabolism: A Review.

Chronic kidney disease (CKD) poses a global health challenge, engendering various physiological and metabolic shifts that significantly impact health and escalate the susceptibility to severe illnesses. This comprehensive review delves into the intricate complexities of CKD, scrutinizing its influence on cellular growth homeostasis, hormonal equilibrium, wasting, malnutrition, and its interconnectedness with inflammation, oxidative stress, and cardiovascular diseases. Exploring the genetic, birth-related, and comorbidity factors associated with CKD, alongside considerations of metabolic disturbances, anemia, and malnutrition, the review elucidates how CKD orchestrates cellular growth control. A pivotal focus lies on the nexus between CKD and insulin resistance, where debates persist regarding its chronological relationship with impaired kidney function. The prevalence of insulin abnormalities in CKD is emphasized, contributing to glucose intolerance and raising questions about its role as a precursor or consequence. Moreover, the review sheds light on disruptions in the growth hormone and insulin-like growth factor axis in CKD, underscoring the heightened vulnerability to illness and mortality in cases of severe growth retardation. Wasting, a prevalent concern affecting up to 75% of end-stage renal disease (ESRD) patients, is analyzed, elucidating the manifestations of cachexia and its impact on appetite, energy expenditure, and protein reserves. Taste disturbances in CKD, affecting sour, umami, and salty tastes, are explored for their implications on food palatability and nutritional status. Independent of age and gender, these taste alterations have the potential to sway dietary choices, further complicating the management of CKD. The intricate interplay between CKD, inflammation, oxidative stress, and cardiovascular diseases is unraveled, emphasizing the profound repercussions on overall health. Additionally, the review extends its analysis to CKD's broader impact on cognitive function, emotional well-being, taste perception, and endothelial dysfunction. Concluding with an emphasis on dietary interventions as crucial components in CKD management, this comprehensive review navigates the multifaceted dimensions of CKD, providing a nuanced understanding essential for developing targeted therapeutic strategies.

Cellular mechanisms of taste disturbance induced by the non-steroidal anti-inflammatory drug, diclofenac, in mice.

Drug-induced taste disorders are a serious problem in an aging society. This study investigated the mechanisms underlying taste disturbances induced by diclofenac, a non-steroidal anti-inflammatory drug that reduces pain and inflammation by inhibiting the synthesis of prostaglandins by cyclooxygenase enzymes (COX-1 and COX-2). RT-PCR analyses demonstrated the expression of genes encoding arachidonic acid pathway components such as COX-1, COX-2 and prostaglandin synthases in a subset of mouse taste bud cells. Double-staining immunohistochemistry revealed that COX-1 and cytosolic prostaglandin E synthase (cPGES) were co-expressed with taste receptor type-1 member-3 (T1R3), a sweet/umami receptor component, or gustducin, a bitter/sweet/umami-related G protein, in a subset of taste bud cells. Long-term administration of diclofenac reduced the expression of genes encoding COX-1, gustducin and cPGES in mouse taste buds and suppressed both the behavioral and taste nerve responses to sweet and umami taste stimuli but not to other tastants. Furthermore, diclofenac also suppressed the responses of both mouse and human sweet taste receptors (T1R2/T1R3, expressed in HEK293 cells) to sweet taste stimuli. These results suggest that diclofenac may suppress the activation of sweet and umami taste cells acutely via a direct action on T1R2/T1R3 and chronically via inhibition of the COX/prostaglandin synthase pathway inducing down-regulated expression of sweet/umami responsive components. This dual inhibition mechanism may underlie diclofenac-induced taste alterations in humans.

Comparison of the incidence of smell and taste disorders between influenza and COVID-19

ObjectiveSmell and taste disorders among patients with COVID-19 has become increasingly reported in the literature, however the prevalence varies. Post-infectious respiratory dysfunction has also been linked to influenza. In this study, we aimed to compare the rates of smell and taste disorders between COVID-19 and Influenza in unvaccinated patients. Study designRetrospective cohort study. SettingTriNetX research network. MethodsTwo queries were made on 7/1/2023 to include Influenza without a diagnosis of COVID-19 and a COVID-19 without a diagnosis of Influenza. The queries included patients from January 1 to December 31, 2022 from 102 Healthcare Organizations. The resultant population of patients with ICD-10 codes for COVID-19 and Influenza were matched using demographic characteristics to evaluate the risk of smell disorders. ResultsThe overall 3-month incidence of smell and taste disorders was 0.73 % in the COVID-19 population and 0.1 % in the influenza population. The 3-month matched risk ratios were 11.1 [95 % CI (8.8,13.8)]; p < 0.001) times higher for disorders of the smell and taste secondary to COVID-19 compared to influenza. ConclusionsDisorders of the smell and taste are more common among patients with COVID-19 compared to patients with Influenza. Beyond smell loss, patients experience additional nasal and sinus-related rhinological symptoms, pointing to COVID-19's and influenza's wider impact on overall rhinological health. We believe that due to the transient nature of these disorders, they might go underreported.

The pH of Drinking Water and Its Human Health Implications: A Case of Surrounding Communities in the Dormaa Central Municipality of Ghana

Of all the things to consider about safe water, the pH of drinking water probably has been overlooked. Most spoken about, however, is alkaline water which has a host of supposed health benefits? For instance, it is known to help the body to clear toxins thereby improving metabolism. Meanwhile, research has shown that most diseases, illnesses, and bad bacteria thrive in an over-acidic environment. Additionally, the acidic water indirectly may impact on budget as this would contribute to the metallic or sour taste of drinking water, and stained laundry and provide blue-green staining of sinks and other household fixtures. Acidic water having low pH often are known to contain high amounts of heavy metals. Also, research has found that solutions with low pH are more likely to have heavy metals from the environment. Other researchers have identified that acidic water can be high in Pb, As, Cu, Ni, Cb, Cr, and Zn. All these elements fall under heavy metals and exposure to them can be dangerous, and could lead to heavy metal poisoning and toxicity. This is concerning as water is said to be life and the population within Dormaa Central Municipality is most likely to have symptoms such as diarrhoea, nausea and vomiting, abnormal pains, weakness, shortness of breath, suppression of the immune system, organ damage, and enamel wearout leading to dental cavities. Water samples and their corresponding spatial locations were collected from (how many?) communities within the Dormaa Central Municipality. The potential for hydrogen (pH) readings of the respective water samples was measured using a pH meter. The results obtained range from 0.2 mmHg to 6.5 mmHg.

Quality of Life in Adults with Chronic Cough: A Mixed Methods Study Informing the Development of a Quantitative Patient Preference Study.

This study aimed to describe quality of life for patients with chronic cough (CC) and identify meaningful attributes that affect patient treatment preferences to inform the design of a quantitative preference study. Eligible patients (≥ 18 years) with a CC (> 8 weeks) participated in qualitative interviews with two defined steps. Step one: concept elicitation and bidding games were used to collect descriptions of patient experiences with CC and identify important CC-related attributes. Step two: attributes were confirmed using concept elicitation and bidding games and prioritized using structured card sort activities. Purposive sampling ensured diversity of patient experiences. Qualitative content analysis was used to analyze participant narratives, and descriptive statistics were used to summarize card sort results. This study follows a fully mixed concurrent dominant status design, with qualitative (dominant) and quantitative components. A total of 20 participants were interviewed with a mean age of 61.4 years (range 24-79 years). Coughing episodes, described as intense consecutive coughs that made catching breath difficult, were important to most participants (n = 17). Participants emphasized the emotional impact of episodes including feelings of uncertainty, loss of control, self-consciousness, and fear. Severity of CC was most often judged by frequency (n = 11) and intensity (n = 12) of cough. Daily, physical, or social activities were impacted for most participants. Impact on sleep (n = 14) included waking during the night, difficulty falling asleep, and daytime fatigue. Medication-related taste disturbances were an important consideration for what participants were willing to accept in exchange for cough relief. This study emphasizes the importance of coughing episodes for adults with CC and provides initial evidence that taste alterations are an important component of patient treatment decisions for CC.

Druggable site near the upper vestibule determines the high affinity and P2X3 homotrimer selectivity of sivopixant/S-600918 and its analogue DDTPA.

The P2X3 receptor, a trimeric ionotropic purinergic receptor, has emerged as a potential therapeutic target for refractory chronic cough (RCC). Nevertheless, gefapixant/AF-219, the only marketed P2X3 receptor antagonist, might lead taste disorders by modulating the human P2X2/3 (hP2X2/3) heterotrimer. Hence, in RCC drug development, compounds exhibiting strong affinity for the hP2X3 homotrimer and a weak affinity for the hP2X2/3 heterotrimer hold promise. An example of such a molecule is sivopixant/S-600918, a clinical Phase II RCC candidate with a reduced incidence of taste disturbance compared to gefapixant. Sivopixant and its analogue, (3-(4-([3-chloro-4-isopropoxyphenyl]amino)-3-(4-methylbenzyl)-2,6-dioxo-3,6-dihydro-1,3,5-triazin-1(2H)-yl)propanoic acid (DDTPA), exhibit both high affinity and high selectivity for hP2X3 homotrimers, compared with hP2X2/3 heterotrimers. The mechanism underlying the druggable site and its high selectivity remains unclear. To analyse mechanisms that distinguish this drug candidate from other inhibitors of the P2X3 receptors we used a combination of chimera construction, site covalent occupation, metadynamics, mutagenesis and whole-cell recording. The high affinity and selectivity of sivopixant/DDTPA for hP2X3 receptors was determined by the tri-symmetric site located close to the upper vestibule. Substitution of only four amino acids inside the upper body domain of hP2X2 with those of hP2X3, enabled the hP2X2/3 heterotrimer to exhibit a similar level of apparent affinity for sivopixant/DDTPA as the hP2X3 homotrimer. From the receptor-ligand recognition perspective, we have elucidated the molecular basis of novel RCC clinical candidates' cough-suppressing properties and reduced side effects, offering a promising approach to the discovery of novel drugs that specifically target P2X3 receptors.

Prospective observational study of zinc deficiency symptoms during first-line chemotherapy for gastric and colorectal cancer.

Zinc deficiency during long-term chemotherapy and its related symptoms, including skin rash, taste disorders, and oral mucositis, have not been sufficiently investigated. This prospective observational study enrolled patients with gastric and colorectal cancer who underwent standard first-line chemotherapy. According to the Practice Guidelines for Zinc Deficiency, zinc deficiency is defined as a serum level of <60 µg/dL. Serum zinc levels were measured before and after (1, 3, and 6 months) chemotherapy, and symptoms were assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events version 1.0. Repeated measures were analyzed using a generalized linear mixed model. Of the 61 enrolled patients, 48 who underwent standard first-line chemotherapy with fluoropyrimidine plus oxaliplatin were analyzed. Zinc deficiency was observed in 18 patients (38%) before chemotherapy. The least-squares means of serum zinc levels significantly decreased at 3 and 6 months of chemotherapy in 30 patients without zinc deficiency at the start of chemotherapy (both P<0.01) but not in 18 with zinc deficiency at the beginning. Changes in serum zinc levels during chemotherapy negatively correlated with changes in taste, rash, and itching (all P<0.04) in patients without zinc deficiency before treatment initiation. Serum zinc levels decreased during chemotherapy in zinc-non-deficient patients at the beginning of chemotherapy and correlated with taste changes, skin rash, and itching. Therefore, investigating whether zinc supplementation ameliorates these symptoms is necessary.

Application of customisable 3D-printed bite blocks combined with nano head, neck and shoulder mask to head and neck neoplasm radiotherapy

This study investigated the effectiveness of customisable 3D-printed bite blocks combined with nano head, neck and shoulder mask in radiotherapy for head and neck neoplasms. The images of 50 patients with head and neck neoplasms treated at our hospital from 2020 to 2022 were collected using CBCT. The patients were divided into two groups: 25 in the mask group and 25 in the combination group. The mask group utilized thermoplastic polyurethane (TPU) nanofiber membrane to stabilize the position of the patients’ head, shoulder, and neck. On the other hand, the combined group added a personalized bite block produced by 3D printing technology on the basis of the mask group. Cone beam CT (CBCT) was used to calibrate any errors, and the set-up errors and number of head rotations after image calibration were analyzed between the two groups. The conformation number (CN) and heterogeneity index (HI) in the target area of the intensity-modulated radiation therapy (IMRT) plan of the two groups were calculated, and the dose-volume parameters of the tongue and other organs at risk, including Dmax and Dmean, were compared using paired tests. Follow-up observations were performed to assess the occurrence of adverse reactions to radiation damage among the patients. The findings revealed a statistically significant difference in the Y -axis set-up error between the combination group and the mask group (P &lt; 0.05). Additionally, the combination group exhibited a higher proportion of set-up errors &lt; 2 mm in both the Y -axis and Z-axis directions compared to the mask group. Significantly fewer images showed head rotation in the combination group than in the mask group. In terms of the target area, there were no significant differences observed in the conformation number (CN) and heterogeneity index (HI) between the two groups. However, wearing the personalized bite block resulted in significantly lower Dmax and Dmean values for the tongue. In contrast, the mask group experienced a higher incidence of oral mucositis and taste disorders. By utilizing customizable 3D-printed bite blocks in conjunction with a nano-mask, accurate repositioning for chemotherapy was achieved, leading to a reduction in set-up error and a significant decrease in radiation dose to the tongue and its surface oral mucosa. Consequently, the occurrence of adverse reactions such as oral mucositis and taste disorders was also reduced. The production of personalized bite blocks is simple, with accurate radiotherapy, making it a technique that should be widely adopted.

Smell and Taste Disorders Knowledge Graph: Answering Questions Using Health Data

Smell and Taste Disorders Knowledge Graph: Answering Questions Using Health Data

Immunosuppressive treatment for myasthenia gravis crises improve the taste disorder in patients with thymoma: two case reports

Immunosuppressive treatment for myasthenia gravis crises improve the taste disorder in patients with thymoma: two case reports

Changes in symptoms and characteristics of COVID-19 patients across different variants: two years study using neural network analysis

BackgroundConsidering the fact that COVID-19 has undergone various changes over time, its symptoms have also varied. The aim of this study is to describe and compare the changes in personal characteristics, symptoms, and underlying conditions of individuals infected with different strains of COVID-19.MethodsThis descriptive-analytical study was conducted on 46,747 patients who underwent PCR testing during a two-year period from February 22, 2020 to February 23, 2022, in South Khorasan province, Iran. Patient characteristics and symptoms were extracted based on self-report and the information system. The data were analyzed using logistic regression and artificial neural network approaches. The R software was used for analysis and a significance level of 0.05 was considered for the tests.ResultsAmong the 46,747 cases analyzed, 23,239 (49.7%) were male, and the mean age was 51.48 ± 21.41 years. There was a significant difference in symptoms among different variants of the disease (p < 0.001). The factors with a significant positive association were myalgia (OR: 2.04; 95% CI, 1.76 – 2.36), cough (OR: 1.93; 95% CI, 1.68—2.22), and taste or smell disorder (OR: 2.62; 95% CI, 2.1 – 3.28). Additionally, aging was found to increase the likelihood of testing positive across the six periods.ConclusionWe found that older age, myalgia, cough and taste/smell disorder are better factors compared to dyspnea or high body temperature, for identifying a COVID-19 patient. As the disease evolved, chills and diarrhea, demonstrated prognostic strength as in Omicron.