A transporter's doom or destiny: SLC6A1 in health and disease, novel molecular targets and emerging therapeutic prospects.

As the first member of the solute carrier 6 (SLC6) protein family, the γ-aminobutyric acid (GABA) transporter 1 (GAT1, SLC6A1), plays a pivotal role in the uptake of GABA from the synaptic cleft into neurons and astrocytes. This process facilitates the subsequent storage of GABA in presynaptic vesicles. The human SLC6A1 gene is highly susceptible to missense mutations, leading to severe clinical outcomes, such as epilepsy, in the afflicted patients. The molecular mechanisms of SLC6A1-associated disorders are discerned to some degree; many SLC6A1 mutations are now known to impair protein folding, and consequently fail to reach the plasma membrane. Inherently, once inside the endoplasmic reticulum (ER), GAT1 abides by a complex cascade of events that enable efficient intracellular trafficking. This involves association with specialized molecular chaperones responsible for steering the protein folding process, oligomerization, sorting through the Golgi apparatus, and ultimately delivery to the cell surface. The entire process is subject to stringent quality control mechanisms at multiple checkpoints. While the majority of the existing loss-of-function SLC6A1 variants interfere with folding and membrane targeting, certain mutants retain abundant surface expression. In either scenario, suppressed GAT1 activity disrupts GABAergic neurotransmission, preceding the disease manifestation in individuals harboring these mutations. The nervous system is enthralling and calls for systematic, groundbreaking research efforts to dissect the precise molecular factors associated with the onset of complex neurological disorders, and uncover additional non-canonical therapeutic targets. Recent research has given hope for some of the misfolded SLC6A1 variants, which can be salvaged by small molecules, i.e., chemical and pharmacological chaperones, acting on multiple upstream targets in the secretory pathway. We here highlight the significance of pharmacochaperoning as a therapeutic strategy for the treatment of SLC6A1-related disorders.

Strategies to Improve Bladder Control: A Preliminary Case Study.

Background: Lower urinary tract symptoms (LUTSs) are a common complaint in adult and elderly men with bladder outlet obstruction, and have a considerable impact on their quality of life. Symptoms affect storage, voiding and post micturition stages. Among the latter, a feeling of incomplete emptying is one of the most bothersome for the patients; a condition that in turn contributes to affect urinary urgency, nocturia and frequency. Common recommendations include self-management practices (e.g., control of fluid intake, double-voiding and distraction techniques) to relieve patients' symptoms, whose effectiveness, however, is under debate. Methods: In this report we describe two pioneering procedures to favor bladder residual content voiding in people complaining of LUTS disorders. The first is based on motor imagery and the second on the use of odors. The beneficial effects of Mental imagery techniques on various tasks (e.g., in the treatment of several pathological conditions or as valid mnemonics aids have a long tradition and have received consistently experimental support. Thus, a patient (a 68-year-old Caucasian man) complaining of LUTS was trained to use a motor imagery technique (building up a visual image comprising the bladder, the detrusor muscle and the urethra, and to imagine the detrusor muscle contracting and the flow of urine expelled) for 90 days and two odors (coffee and a lavender scented cleanser) for 10 days, as a trigger for micturition. He was asked to record-immediately after the first morning micturition-the time interval between the first (free) and the second (cued) micturition. Results: Reported data suggest the efficacy of motor imagery in favoring the bladder residual urine voiding in a few minutes (M = 4.75 min.) compared to the control condition, i.e., the baseline of the patient (M = 79.5 min.), while no differences between the odor-based procedures (M 1st odorant = 70.6 min.; M 2nd odorant = 71.1 min) and the latter were observed. Conclusions: A procedure based on an imagery technique may, therefore, be of general value-as a suggested protocol-and accordingly can be applicable to clinical settings. An olfactory bladder control hypothesis cannot, however, be ruled out and is discussed as a promising future line of research.

Four odorants for olfactory training are enough: a pilot study.

BACKGROUND:  Olfactory training (OT) is commonly used for the treatment of olfactory disorders. Nevertheless, there is an ongoing debate about the most effective OT regimen. We aimed to compare the effects of OT with 7 items (rose, lemon, eucalyptus, cloves, stewed apple, balm, mint) to 4-item-OT (rose, lemon, eucalyptus, cloves) over 3 months. Methods: Participants were 40 patients with olfactory dysfunction receiving 4-item-OT or 7-item-OT and 60 gender- and age-matched individuals with normal sense of smell receiving no OT, 4-item-OT, or 7-item-OT. Before and after the OT we assessed n-butanol odor thresholds, discrimination, and identification (TDI score), additionalthresholds for (R)-(-)-carvone, ß-damascenone, salicyclic acid benzylester, the degree of phantosmia and parosmia, cognitive function, and ratings of olfactory function. Results: In both patient groups, the TDI score increased with the use of OT, regardless of the number of odors used (p < 0.001; 3.48 ± 4.21 and lower than control groups). The clinically significant increase of 5.5 points in TDI score correlated with change of ratings of parosmia (r 0.62; p < 0.01) and with ratings of olfactory dysfunction (r = 0.51; p < 0.05). CONCLUSION:  Concluding, OT over a 3-months period with 4 or 7 odors appears to produce similar results, although the sample size has to be considered.

The olfactory test established by Henkin: is it reliable and does it correlate to established psychophysical tests?

PURPOSE: This pilot study aimed to determine whether the Henkin olfactory test discriminates between the olfactory function of patients with olfactory loss and healthy individuals, and whether the Henkin test is correlated with a validated psychophysical olfactory test. METHODS: Participants underwent olfactory testing using the modified Henkin test (including detection [DT] and recognition [RT] thresholds, magnitude estimation [ME], and hedonic ratings [H], for four different odors) and the extended "Sniffin' Sticks" test battery (odor detection, discrimination, identification). RESULTS: Forty-four individuals (28 women, aged 19-81 years, mean: 39 years) were included. Twenty-three were healthy (mean age: 38 years) and 21 had olfactory dysfunction (OD) (mean age: 40 years). OD patients had worse mean DT, lower composite RT, and lower ME ratings. Mean and individual odor H ratings were not significantly different between the groups. Most individuals were classified as hyposmic when using the prescribed classification by Henkin, with only very few satisfying the stringent criteria of anosmia and normosmia. Modified Henkin subtests were all positively correlated with each other and with the "Sniffin' Sticks", except for Unpleasant Mean H which was only correlated with Pleasant Mean H; and Pleasant mean H which was not correlated with mean DT scores. CONCLUSION: The Henkin test is able to separate between OD patients and controls. However, modifications to the conduct of this test may be required. Studies that used this test should be carefully interpreted.

Olfactory perceptual fingerprints of people with olfactory dysfunction and healthy controls.

Objectives: An olfactory perceptual fingerprint (OPF) defines one's olfactory perception using perceptual descriptor ratings (such as odor pleasantness, intensity) for a set of odors. OPFs have been shown to distinguish patients with COVID-related olfactory dysfunction (OD) and healthy controls with 86% accuracy. However, all participants rated the same odorants. With the aim to evaluate whether the OPFs are indeed odorant independent, previously published dataset by Lötsch et al. was reanalyzed. Furthermore, this independent dataset was used to check whether the OPFs separate patients with OD due to various causes from controls. Methods: The study included 104 controls and 42 patients, who were randomized into four odor sets with 10 odorants each. Odorants were presented using a computer-controlled olfactometer and evaluated on scales from 1 (not at all) to 5 (very) using perceptual descriptors pleasant, intensive, familiar, edible, irritating, cold/warm, and painful. Results: Permutational multivariate analysis of variance showed that the odor set did not have a significant effect on the OPFs, confirming that the OPFs are indeed odorant independent. On the other hand, both diagnosis and age affected the OPFs (p < .001) and explained around 11% and 5% of the variance of the OPFs, respectively. Furthermore, a supervised machine learning method, random forest classifier, showed that OPF can distinguish patients and controls with 80% accuracy. Conclusion: OPFs are odorant independent. Patients perceived odors as less familiar, less intense, and less edible than controls. Other perceptual descriptors were much less important for the separation of patients and controls. Level of evidence: 3.

Test-retest reliability and normative data for "Seven-iTT", a test for the assessment of taste and oral trigeminal function.

BACKGROUND: Assessment of taste and somatosensory perception in clinical practice lacks fast tests that are validated and reliable. Recently, a 12-item identification test for taste and oral trigeminal perception, and its shorter version, the Seven-iTT, was developed. The objectives of this study were to evaluate its test-retest reliability and establish normative data. NEW METHOD: Two-hundred participants (120 women, 80 men) with a good sense of taste performed a whole-mouth identification test using 12 filter-paper strips impregnated with low and high concentrations of sweet, sour, salty, bitter, astringency, and spiciness. Fifty of them repeated the task, with a median interval of 122 days from the first visit. Test-retest reliability was determined using Spearman correlation and the Bland-Altman plot method. RESULTS: There was a significant correlation in identification score between the first and the second session for both versions of the test (r ≥ 0.28; p ≤ 0.048). The Bland-Altman plot reflected a good congruence between the results of the two sessions. Additionally, frequencies of correct identification were consistent between sessions, with women outperforming men (p = 0.005). Hypogeusia was established at Seven-iTT score of 3 of less. COMPARISON WITH EXISTING METHODS: The identification test combines taste and somatosensory perception, thus creating a more detailed diagnosis tool. Scores were correlated with self-rated taste perception. CONCLUSION: The present results confirmed the applicability of Seven-iTT for a reliable, fast evaluation of taste and somatosensory perception in the general population, that can be extended to clinical practice.

Hot topic: Mapping of the human intranasal mucosal thermal sensitivity: A clinical study on thermal threshold and trigeminal receptors.

INTRODUCTION: The olfactory and trigeminal system are closely interlinked. Existing literature has primarily focused on characterizing trigeminal stimulation through mechanical and chemical stimulation, neglecting thermal stimulation thus far. The present study aimed to characterize the intranasal sensitivity to heat and the expression of trigeminal receptors (transient receptor potential channels, TRP). METHODS: A total of 20 healthy participants (aged 21-27 years, 11 women) were screened for olfactory function and trigeminal sensitivity using several tests. Under endoscopic control, a thermal stimulator was placed in 7 intranasal locations: anterior septum, lateral vestibulum, interior nose tip, lower turbinate, middle septum, middle turbinate, and olfactory cleft to determine the thermal threshold. Nasal swabs were obtained in 3 different locations (anterior septum, middle turbinate, olfactory cleft) to analyze the expression of trigeminal receptors TRP: TRPV1, TRPV3, TRPA1, TRPM8. RESULTS: The thermal threshold differed between locations (p = 0.018), with a trend for a higher threshold at the anterior septum (p = 0.092). There were no differences in quantitative receptor expression (p = 0.46) at the different sites. The highest overall receptor RNA expression was detected for TRPV1 over all sites (p<0.001). The expression of TRPV3 was highest at the anterior septum compared to the middle turbinate or the olfactory cleft. The thermal sensitivity correlated with olfactory sensitivity and results from tests were related to trigeminal function like intensity ratings of ammonium, a questionnaire regarding trigeminal function, nasal patency, and CO2 thresholds. However, no correlation was found between receptor expression and psychophysical measures of trigeminal function. DISCUSSION: This study provided the first insights about intranasal thermal sensitivity and suggested the presence of topographical differences in thermal thresholds. There was no correlation between thermal sensitivity and trigeminal mRNA receptor expression. However, thermal sensitivity was found to be associated with psychophysical measures of trigeminal and olfactory function.

Olfactory training: perspective from people who were disturbed by their smell problems.

PURPOSE: Olfactory training (OT) is an effective and affordable option in the treatment of olfactory dysfunction. Despite significant progress in the field in recent years, some factors influencing OT participation remain unclear. METHODS: Based on an anonymous online survey orchestrated by AbScent.org the present study enrolled 450 participants and divided them into OT (n = 161) and No OT (n = 289) groups based on their OT participation. Participants also provided information on demographics, medical history, quality of life, OT duration for those who engaged in OT, and the reasons for non-participation in OT among those who did not. RESULTS: Patients who had greater loss of quality of life participated more in OT. Similarly, more participation was observed in patients who noticed an improvement in their ability to smell. Notably, most of the sample engaged in OT trained less than four weeks (73%). In the No OT group, the primary barrier to OT participation was the unawareness of OT treatment (37%) and these barriers differed by age, where older people expressed interest but were unaware of OT treatment, while younger individuals exhibited more cautiousness about its effectiveness. CONCLUSION: Lower quality of life drives active OT participation. Limited training periods and unawareness of OT serve as potential barriers to olfactory recovery. Clinicians should actively promote the background of OT and underscore the significance of adhering to the "prescribed" training regimen.

The digital scent device 20: an automated, self-administered odor identification test.

PURPOSE: Assessing olfactory function is highly significant in clinical practice, particularly in the context of the recent COVID-19 pandemic. Recent approaches in this field emphasize the importance of reducing the time and cost devoted to olfactory testing procedures. Hence, the aim of the present study was to examine the reliability and basic characteristics of Digital Scent Device 20 (DSD-20), an innovative olfactory test consisting of 20 "universal odors", in a European population. METHODS: A total of 88 participants (mean age = 45.1, SD = 20.3) volunteered for the study. The sample consisted of 37 normosmic controls and 51 dysosmic patients. RESULTS: The correlation between DSD-20 and the total score in Sniffin' Sticks was high (TDI; R = .80, p < .001), and the test correlated with the individual components of the Sniffin' Sticks test. Furthermore, the correlation coefficient between DSD-20 test and retest was very high (R = .88, p < .001), which was additionally confirmed by a Bland-Altman plot. Essential characteristics of the DSD-20 are its simplicity in self-administration, speed of application, portability, and the fact that it can be reused. CONCLUSION: Overall, the present study confirms previous notions on DSD-20 by demonstrating its high reliability and usefulness in separating patients with hyposmia/anosmia and normosmic controls.

Human perception of Parkinson's disease body odor in comparison to the volatile organic compounds of Parkinson's disease.

INTRODUCTION: Patients with Parkinson's Disease (PD) have a distinctive body odor, which was first described by a patient's wife as musky and strong. Later analysis of sebum of patients with PD revealed four volatile organic compounds (VOC) (perillic aldehyde, hippuric acid, eicosane, octadecanal), that differed from healthy subjects, and the patient's wife confirmed that three of them smelled like patients with PD. However, it is unclear whether other people can also perceive this PD body odor and whether it can be artificially recreated. Hence, we aimed to systematically assess whether young women can perceive the PD body odor and whether they can discriminate between the PD body odor and the "artificial PD odor" composed of the four VOCs mentioned above. METHODS: T-shirts were collected from 19 people with idiopathic PD and 15 age- and gender-matched healthy participants to represent the PD body odor and the healthy body odor, respectively. The four VOCs were diluted in 1,2-propanediol to prepare the artificial PD body odor. Body odors were rated by 26 young women. RESULTS: PD body odor was perceived as more musty, strong, smelly, and unpleasant compared to healthy and artificial PD body odor. Furthermore, around 80 % of women were able to discriminate PD body odor from artificial PD body odor. CONCLUSION: Overall, this study confirmed a distinctive body odor quality of patients with PD, which can be perceived by young women. However, the four VOCs, composing the artificial PD body odor, were insufficient to reproduce the body odor from PD patients.

A novel olfactory sorting task.

BACKGROUND: This study aimed to develop a simple self-administered screening tool for odor memory, which allowed users to self-test their olfactory function repeatedly even at home. METHODS: One hundred and ten participants were recruited (30 men, age = 50.1 ± 9.9 years; 80 women, age = 47.1 ± 11.5 years); half of them were heathy volunteers, the other half were patients with olfactory dysfunction. Fifty-one healthy participants volunteered for a retest within an interval of a maximum of 14 days. Olfactory function was assessed using the extended Sniffin' Sticks test (SST) comprising tests for odor threshold, identification, and discrimination. All participants received the Novel Olfactory Sorting Task (NOST) which is based on the sorting of 12 matching pairs of odors involving olfactory and cognitive functions. After that, all participants rated questions related to their test performance and the practicability of the test. RESULTS: Consistent with the previous literature, significant effects of age were found. Results showed an acceptable test-retest reliability and a satisfactory validity of the NOST. The NOST score not only had positive correlations with SST, but also was capable of differentiating severe hyposmia/anosmia from normosmia by the score of 5.5 (sensitivity of 76.2%, specificity of 77.6%). CONCLUSION: The present study showed the good reliability, validity, and possible clinical usefulness of the NOST. As a self-performed screening test, it can be comprehended and conducted easily, which may provide a quick and simple approach to obtaining a global estimation of olfactory and cognitive functions.

Development and validation of the MultiScent-20 digital odour identification test using item response theory.

Although validated and reliable psychophysical tests of olfactory function are available, an easy-to-use and feasible test has yet to be developed. This study aimed to design a digital odour identification test, evaluate its validity, assess its reliability, establish a normative curve, and explore the impact of demographic factors. The odour identification test was presented with the Multiscent-20, a hand-held, tablet-like digital scent device that features an integrated odour digital delivery system. The identification performance on the 20 odours was assessed using item response theory (IRT). The normative curve was established by administering the test to a large sample of participants (n = 1299). The mean identification score was 17.5 (SD = 2.1). The two-parameter logistic IRT model provided the best fit, revealing variation in item discrimination and difficulty parameters. Educational attainment influenced performance, with primary education associated with lower scores. Additionally, sex was not found to be associated with performance. This study provides initial evidence supporting the validity and reliability of use of the Multiscent-20 as a digital odour identification test. The test's automation and portability enable the standardized delivery of olfactory stimuli and efficient automatic recording and scoring of responses.

Pregnant women exhibit decreased trigeminal sensitivity.

INTRODUCTION: Chemosensory function in pregnant women is far from being fully understood due to the lack of data and inconsistencies between the results of self-reports and objective studies. METHODS: In the present study in pregnant and non-pregnant women (npregnant = 14, nnon-pregnant = 13), we measured EEG-derived electrophysiological response measures supported by psychophysical olfactory and trigeminal tests. RESULTS: Results indicate that the olfactory event-related potential amplitudes or latencies of the P1, N1, and P2 components remain unchanged in pregnant women. In accordance with these findings, no difference was observed between pregnant and non-pregnant women in psychophysical olfactory tests. However, pregnant women displayed a lower degree of sensitivity to trigeminal stimuli compared to non-pregnant controls, which was also reflected in the electrophysiological responses to trigeminal stimuli. CONCLUSION: Counterintuitive as they may seem, our findings demonstrate a "flattening" of chemosomatosensory responses. Psychological processes occurring during pregnancy, such as changes in socioemotional perception of odors resulting from the diminished stress response, may provide a background to these results. Overall, the present results indicate the absence of major differences between non-pregnant and pregnant women in terms of measured olfactory function though chemosomatosensory function of the pregnant women appears to be decreased.

Smell and Taste Alterations in Patients Receiving Curative or Palliative Chemotherapy-The CONKO 021-ChemTox Trial.

Previous data regarding chemotherapy-induced olfactory and gustatory dysfunction (CIOGD) are heterogeneous due to inconsistent study designs and small numbers of patients. To provide consistent, reliable data, we conducted a cohort study using standardized testing. Patients diagnosed with lymphoma, leukemia, or gastrointestinal malignancies were examined up to five times (T1 to T5), beginning prior to chemotherapy. We examined patients receiving temporary treatment up to 12 months post-therapy. Clinical assessment included extensive questionnaires, psychophysical tests of olfactory and gustatory function, and measurement of peripheral neuropathy. Statistical analysis included non-parametric tests to evaluate the longitudinal development of CIOGD. Our data (n = 108) showed a significant decline in olfactory and gustatory testing during chemotherapy (p-values < 0.001). CIOGD appeared stronger among patients above 60 years, while sex did not matter significantly. However, we identified distinct associations between CIOGD and reported anorexia as well as with higher neuropathy scores. Self-assessment appeared less sensitive to chemosensory dysfunction than psychophysical testing. Post-therapy, olfactory and gustatory function regenerated, though baseline levels were not attained within 6 to 12 months. In conclusion, our data highlight the wide prevalence and slow recovery of CIOGD. Understanding CIOGD as a potential neurotoxic effect may disclose new therapeutic prospects.

Parosmia in patients with post-infectious olfactory dysfunction in the era of COVID-19-associated olfactory impairment.

OBJECTIVES: A large number of patients with olfactory impairment are affected by parosmia or phantosmia. This study aimed to examine the demographic and clinical characteristics of parosmia. METHODS: We performed a retrospective data analysis of patients consulting at our Smell and Taste Outpatient Clinic. A total of 297 patients were included (203 women, mean age 44.4 ± 13.7 years). Olfactory function was quantified using the "Sniffin' Sticks" composite TDI (odor threshold, determination, and identification) score. The presence of qualitative olfactory impairment was assessed trough medical history and a parosmia questionnaire. RESULTS: Most of the patients showed olfactory impairment after an infection with SARS-CoV­2 (84%) and were diagnosed with parosmia (49%). Patients with parosmia (PAR) (n = 201) were significantly younger compared to the group without parosmia (noPAR; n = 92) (PAR 43.2 ± 13 years vs. noPAR 47 ± 15.1 years, p = 0.03) and had a slightly shorter duration of disease, without reaching statistical significance (PAR 10.3 ± 4.9 months, noPAR 13.6 ± 37.6 months, p = 0.23). They also had higher TDI scores (PAR 24.3 ± 7 points, noPAR 21.4 ± 8.2 points, p = 0.003). CONCLUSIONS: Patients affected by parosmia were younger and had a better olfactory function compared to patients without parosmia.

Can immersive olfactory training serve as an alternative treatment for patients with smell dysfunction?

Objectives: Olfactory training (OT) has emerged as a first-line therapeutic approach to the management of olfactory dysfunction. Conventional OT (COT) involves the systematic home-based exposure to four distinct odors. Previous research has demonstrated that immersive OT (IOT) involving full-body exposure to dozens of distinct odors could also improve overall olfactory function. This study compared IOT and COT in terms of efficacy. Methods: A total of 60 patients were enrolled and assigned to three groups. The IOT group (n = 25) underwent immersive exposure to 64 odors once daily in a specialized theater. COT participants (n = 17) sniffed four typical odors in a set of four jars twice daily at home. A control group (n = 18) underwent passive observation. Olfactory function was assessed before and after training. Results: Significant improvements in composite threshold-discrimination-identification (TDI) scores were observed after training in both the IOT (mean difference = 2.5 ± 1.1. p = .030) and COT (mean difference = 4.2 ± 1.3, p = .002) groups. No changes were observed in the control group. A significantly higher proportion of patients in the COT group (41%) presented improvements of clinical importance (TDI ≥5.5) compared to the controls (p = .018). The improvements attained in the IOT group (20%) were less pronounced (p = .38). Conclusion: While IOT did not exhibit the same efficacy as COT in restoring olfactory function, it still demonstrated promising outcomes. Future efforts to advance olfactory recovery should focus on cross-modal integration. Level of Evidence: Level 3.

Screening for elder mistreatment in a Swiss emergency department: a prospective cohort study.

AIM OF THE STUDY: The mistreatment of older adults is a global and complex problem with varying prevalence. As there are no data on the prevalence of elder mistreatment in European emergency department populations, we aimed to translate and culturally adapt the Emergency Department Senior Abuse Identification (ED Senior AID) tool for German use, assess the positive screen rate for elder mistreatment with the German version, and compare characteristics of patients who screened positive and negative. METHODS: To assess the prevalence of elder mistreatment, we created a German version of the ED Senior AID tool. This tool identifies intentional or negligent actions by a caregiver or trusted person that cause harm or risk to an older adult. Then, the German ED Senior AID tool was applied to all consecutively presenting patients aged ≥65 years at our academic emergency department in the Northwest of Switzerland from 25 April to 30 May 2022. Usability was defined as the percentage of patients with completed assessments using the German ED Senior AID tool. RESULTS: We included 1010 patients aged ≥65 years, of whom 29 (2.9%) screened positive with the ED Senior AID tool. The patients who screened positive were older, more severely cognitively impaired, hospitalised more frequently, and presented with higher frailty scores than those who screened negative. Mortality up to 100 days after presentation was comparable in all patients (p = 0.861), regardless of their screening result. The tool showed good usability, with 73% of assessments completed. CONCLUSION: This is the first prospective investigation on the prevalence of elder mistreatment in a European emergency department setting. Overall, 2.9% of patients screened positive using a validated screening tool translated into German. TRIAL REGISTRATION: This study was registered with the National Institute of Health on ClinicalTrials.gov with the registration number NCT05400707.

Efficacy and Safety of Habitual Consumption of a Food Supplement Containing Miraculin in Malnourished Cancer Patients: The CLINMIR Pilot Study.

Taste disorders (TDs) are common among systemically treated cancer patients and negatively impact their nutritional status and quality of life. The novel food approved by the European Commission (EFSA), dried miracle berries (DMB), contains the natural taste-modifying protein miraculin. DMB, also available as a supplement, has emerged as a possible alternative treatment for TDs. The present study aimed to evaluate the efficacy and safety of habitual DMB consumption in malnourished cancer patients undergoing active treatment. An exploratory clinical trial was carried out in which 31 cancer patients were randomized into three arms [standard dose of DMB (150 mg DMB/tablet), high dose of DMB (300 mg DMB/tablet) or placebo (300 mg freeze-dried strawberry)] for three months. Patients consumed a DMB tablet or placebo daily before each main meal (breakfast, lunch, and dinner). Throughout the five main visits, electrochemical taste perception, nutritional status, dietary intake, quality of life and the fatty acid profile of erythrocytes were evaluated. Patients consuming a standard dose of DMB exhibited improved taste acuity over time (% change right/left side: -52.8 ± 38.5/-58.7 ± 69.2%) and salty taste perception (2.29 ± 1.25 vs. high dose: 2.17 ± 1.84 vs. placebo: 1.57 ± 1.51 points, p < 0.05). They also had higher energy intake (p = 0.075) and covered better energy expenditure (107 ± 19%). The quality of life evaluated by symptom scales improved in patients receiving the standard dose of DMB (constipation, p = 0.048). The levels of arachidonic (13.1 ± 1.8; 14.0 ± 2.8, 12.0 ± 2.0%; p = 0.004) and docosahexaenoic (4.4 ± 1.7; 4.1 ± 1.0; 3.9 ± 1.6%; p = 0.014) acids in erythrocytes increased over time after DMB intake. The standard dose of DMB increased fat-free mass vs. placebo (47.4 ± 9.3 vs. 44.1 ± 4.7 kg, p = 0.007). Importantly, habitual patients with DMB did not experience any adverse events, and metabolic parameters remained stable and within normal ranges. In conclusion, habitual consumption of a standard 150 mg dose of DMB improves electrochemical food perception, nutritional status (energy intake, fat quantity and quality, fat-free mass), and quality of life in malnourished cancer patients receiving antineoplastic treatment. Additionally, DMB consumption appears to be safe, with no changes in major biochemical parameters associated with health status. Clinical trial registered (NCT05486260).

Palmitoylethanolamide and Luteolin for Postinfectious Olfactory Disorders: How Clinically Meaningful Is Its Effect?

INTRODUCTION: The prevalence of post-viral olfactory dysfunction has increased significantly during the COVID-19 pandemic, posing a major challenge for patients and practitioners. While olfactory training (OT) is a common approach to therapy, there has been increasing interest in supplementing therapy with a combination of palmitoylethanolamide (PEA) and luteolin (LUT), which are known for their anti-inflammatory properties. In this study, their efficacy in the treatment of patients with olfactory loss following upper respiratory tract infections, mainly COVID-19, was investigated in an outpatient clinic. METHODS: Fifty patients with persistent olfactory dysfunction were randomized to two groups: one receiving OT and PEA-LUT, the other OT alone. Olfactory function was evaluated before and after treatment. RESULTS: The study group showed significant improvements in odor discrimination and overall olfactory function (TDI score) after treatment with PEA-LUT and OT, while the control group did not. However, when clinically meaningful improvements were considered, there was no significant difference between the groups. CONCLUSION: The present study suggests that while PEA-LUT may have the potential to improve olfactory function in post-viral dysfunction, the additional benefit over OT alone may be limited. These results contrast with some previous studies.

Identification of the needs of individuals affected by COVID-19.

BACKGROUND: The optimal management of COVID-19 symptoms and their sequelae remains an important area of clinical research. Policy makers have little scientific data regarding the effects on the daily life of affected individuals and the identification of their needs. Such data are needed to inform effective care policy. METHODS: We studied 639 people with COVID-19 resident in France via an online questionnaire. They reported their symptoms, effects on daily life, and resulting needs, with particular focus on olfaction. RESULTS: The results indicate that a majority of participants viewed their symptoms as disabling, with symptoms affecting their physical and mental health, social and professional lives. 60% of the individuals reported having unmet medical, psychological and socio-professional support needs. Finally, affected individuals were concerned about the risk and invasiveness of possible treatments as shown by a preference for non-invasive intervention over surgery to cure anosmia. CONCLUSIONS: It is important that policy makers take these needs into consideration in order to assist affected individuals to regain a normal quality of life.

The impact of COVID-19 has been substantial, both on individuals' health and on society. Information is needed to understand the biological mechanisms underlying the illness and to provide appropriate support for people affected. This study uses data from an online questionnaire of adults diagnosed with COVID-19 to characterize symptoms, understand their impact on peoples' everyday lives, and determine the support that people need. Our over-arching analysis of symptoms experienced reveals that heart- and skin-related symptoms are linked to chronic illness, and symptoms related to the sense of smell may have a different underlying disease mechanism. Most respondents had a mild initial illness, but their symptoms were long-lasting and had a severe impact. Our findings show that sufferers need different kinds of support in order to regain a normal quality of life.