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.

Rapid differentiation of cystic fibrosis-related bacteria via reagentless atmospheric pressure photoionisation mass spectrometry.

Breath analysis is an area of significant interest in medical research as it allows for non-invasive sampling with exceptional potential for disease monitoring and diagnosis. Volatile organic compounds (VOCs) found in breath can offer critical insight into a person's lifestyle and/or disease/health state. To this end, the development of a rapid, sensitive, cost-effective and potentially portable method for the detection of key compounds in breath would mark a significant advancement. Herein, we have designed, built and tested a novel reagent-less atmospheric pressure photoionisation (APPI) source, coupled with mass spectrometry (MS), utilising a bespoke bias electrode within a custom 3D printed sampling chamber for direct analysis of VOCs. Optimal APPI-MS conditions were identified, including bias voltage, cone voltage and vaporisation temperature. Calibration curves were produced for ethanol, acetone, 2-butanone, ethyl acetate and eucalyptol, yielding R2 > 0.99 and limits of detection < 10 pg. As a pre-clinical proof of concept, this method was applied to bacterial headspace samples of Escherichia coli (EC), Pseudomonas aeruginosa (PSA) and Staphylococcus aureus (SA) collected in 1 L Tedlar bags. In particular, PSA and SA are commonly associated with lung infection in cystic fibrosis patients. The headspace samples were classified using principal component analysis with 86.9% of the total variance across the first three components and yielding 100% classification in a blind-sample study. All experiments conducted with the novel APPI arrangement were carried out directly in real-time with low-resolution MS, which opens up exciting possibilities in the future for on-site (e.g., in the clinic) analysis with a portable system.

Laparoscopic magnetic sphincter augmentation device placement for patients with medically-refractory gastroesophageal reflux after sleeve gastrectomy.

BACKGROUND: The use of the magnetic sphincter augmentation (MSA) in patients with de novo or persistent gastroesophageal reflux disease (GERD) after sleeve gastrectomy has not been thoroughly investigated. OBJECTIVE: The aim of this study is to evaluate the efficacy of MSA device placement in improving GERD symptoms and reducing anti-reflux medication usage in patients with persistent or de novo GERD after sleeve gastrectomy. METHODS: This is a retrospective analysis of patients who underwent laparoscopic MSA device placement between January 2018 and July 2020 after sleeve gastrectomy. RESULTS: A total of twenty-two patients met inclusion criteria. Twenty patients were female (91%) and two patients were male (9%). All patients were taking anti-reflux medications daily to control GERD symptoms prior to MSA device placement. There was a significant improvement in the mean GERD-HRQL survey scores when comparing scores prior to (43.8) and after (16.7) MSA device placement (p < 0.0001). Majority of the patients did well without any post-operative complications (77%). Nearly 82% of patients were no longer taking any anti-acid medications after MSA device placement (p < 0.0485). There were no patients that required MSA device removals. There were no adverse events such as MSA device erosions or device-related mortalities. CONCLUSIONS: MSA device placement in patients with medically refractory GERD after sleeve gastrectomy is a safe and viable alternative to Roux-en-Y gastric bypass without conferring additional risks. We show an improvement in reflux symptoms after MSA device placement as evidenced by decreased post-operative GERD-HRQL scores, decreased anti-acid medication usage, and overall patient satisfaction with the procedure. Further prospective and comparative studies with longer term follow-up are needed to validate the use of MSA in patients who have undergone sleeve gastrectomy.

Gut Microbiota Composition and Its Metabolites in Different Stages of Chronic Kidney Disease.

A growing body of study have documented the association of gut dysbiosis or fecal metabolites with chronic kidney disease (CKD). However, it is not clear whether the phenomenon simply reflects the microenvironment changes correlated with the CKD severity or contributes to the progression of CKD. In this study, we identified the gut microbiota and metabolite in feces samples correlated with CKD severity using the Nanopore long-read sequencing platform and UPLC-coupled MS/MS approach. A cross-sectional cohort study was performed from 1 June 2020 to 31 December 2020. One hundred and fifty-six clinical participants, including 60 healthy enrollees and 96 Stage 1-5 CKD patients, were enrolled in this study. The ROC curve generated with the relative abundance of Klebsiella pneumonia or S-Adenosylhomocysteine showed a gradual increase with the CKD severity. Our results further revealed the positive correlation of increased K. pneumonia and S-Adenosylhomocysteine in gut environment, which may be of etiological importance to the deterioration of a CKD patient. In that sense, the microbiota or metabolite changes constitute potential candidates for evaluating the progression of CKD.

Differences in Specific Mass Density Between Dinoflagellate Life Stages and Relevance to Accumulation by Hydrodynamic Processes.

One previously unstudied aspect of differences between sexual and asexual life stages in large-scale transport and accumulation is density (mass per unit volume) of cells in each life stage. The specific density was determined for Scrippsiella lachrymosa cells in medium with and without nitrogen (N) enrichment through density-gradient centrifugation. Growth medium without N addition is often called "encystment medium" when used for the purpose of resting cyst formation in cyst-forming dinoflagellates; mating gametes are usually seen after 2-3 days. Significant differences in specific density were found after 2 days in encystment medium simultaneously with the observation of typical gamete swimming behavior and mating. The specific density of cells in encystment medium was 1.06 g · cm-3 ; whereas, the specific density of cells in growth medium was 1.11 g · cm-3 . Cells in encystment medium were found to have significantly increased lipid content, reduced chlorophyll content, and reduced internal complexity. The findings may explain differential transport of less dense and chemotactically aggregating gametes into surface blooms in contrast to denser vegetative cells that perform daily vertical migration and do not aggregate. Passive accumulation of non-migrating gametes into layers in stagnant water also can be explained, as well as sinking of zygotes when the storage of highly dense starch increases. Resting cysts had a density of over 1.14 g · cm-3 and would sink to become part of the silt fraction of the sediment. We suggest that differences in behavior and buoyancy between sexual and asexual life stages cause differences in cell accumulation, and therefore large-scale, environmental transport could be directly dependent upon life-cycle transitions.

Cytisine versus varenicline for smoking cessation in New Zealand indigenous Maori: a randomized controlled trial.

AIM: To determine whether cytisine was at least as effective as varenicline in supporting smoking abstinence for ≥ 6 months in New Zealand indigenous Maori or whanau (extended-family) of Maori, given the high smoking prevalence in this population. DESIGN: Pragmatic, open-label, randomized, community-based non-inferiority trial. SETTING: Bay of Plenty, Tokoroa and Lakes District Health Board regions of New Zealand. PARTICIPANTS: Adult daily smokers who identified as Maori or whanau of Maori, were motivated to quit in the next 2 weeks, were aged ≥ 18 years and were eligible for subsidized varenicline. Recruitment used multi-media advertising. INTERVENTIONS: A total of 679 people were randomly assigned (1 : 1) to receive a prescription for 12 weeks of cytisine or varenicline, plus low-intensity cessation behavioural support from the prescribing doctor and community stop-smoking services or a research assistant. Day 5 of treatment was the designated quit date. MEASUREMENTS: The primary outcome was carbon monoxide-verified continuous abstinence at 6 months, analysed as intention-to-treat (with multiple imputation for missing data). Secondary outcomes measured at 1, 3, 6 and 12 months post-quit date included: self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes per day, time to (re)lapse, adverse events, treatment adherence/compliance and acceptability, nicotine withdrawal/urge to smoke and health-care utilization/health-related quality of life. FINDINGS: Verified continuous abstinence rates at 6 months post-quit date were 12.1% (41 of 337) for cytisine versus 7.9% (27 of 342) for varenicline [risk difference 4.29%, 95% confidence interval (CI) = -0.22 to 8.79; relative risk 1.55; 95% CI = 0.97-2.46]. Sensitivity analyses confirmed that the findings were robust. Self-reported adverse events over 6 months occurred significantly more frequently in the varenicline group (cytisine: 313 events in 111 participants; varenicline: 509 events in 138 participants, incidence rate ratio 0.56, 95% CI = 0.49-0.65, P < 0.001) compared with the cytisine group. Common adverse events were headache, nausea and difficulty sleeping. CONCLUSION: A randomized controlled trial found that cytisine was at least as effective as varenicline at supporting smoking abstinence in New Zealand indigenous Maori or whanau (extended-family) of Maori, with significantly fewer adverse events.

Whole-Body Diffusion-Weighted MRI Compared to 18 FFDG PET/CT in Initial Staging and Therapy Response Assessment of Hodgkin Lymphoma in Pediatric Patients.

PURPOSE: The aim of our study was to compare whole-body diffusion-weighted MRI (WB-DWI-MRI) to fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the assessment of initial staging and treatment response in pediatric patients with Hodgkin lymphoma. MATERIALS AND METHODS: This prospective study comprised 11 children with Hodgkin lymphoma. Whole-body DWI-MRI and FDG-PET/CT were obtained at baseline and after 2 cycles of chemotherapy. Two radiologists measured the apparent diffusion coefficient (ADC) values of the sites of involvement agreed upon in consensus and 1 nuclear medicine physician assessed the PET/CT. Reliability of radiologists' ratings was assessed by intraclass correlation coefficients (ICC2,1). The sensitivity and positive predictive value (PPV) of DW-MRI relative to PET/CT were calculated for nodal and extranodal sites. The patients were staged according to both modalities. Association of treatment responses was assessed through the Pearson correlation between the ADC ratios and the change standardized uptake value (SUV) between baseline and follow-up. RESULTS: There was good agreement between the raters for nodal and extranodal ADC measurements. The sensitivity and PPV of DW-MRI relative to PET/CT of nodal disease was 0.651 and 1.0, respectively, at baseline, and 0.697 and 0.885 at follow-up. The sensitivity and PPV of extranodal disease were 0.545 and 0.6 at baseline, and 0.167 and 0.333 at follow-up. Diffusion-weighted MRI determined correct tumor stage in 8 of 11 examinations. There was poor correlation between the ADC ratios and the absolute change in SUV between baseline and follow-up (0.348). CONCLUSION: Our experience showed that WB-DWI-MRI is inferior to PET/CT for initial staging and assessment of treatment response of Hodgkin lymphoma in pediatric patients.

Cytisine versus varenicline for smoking cessation for Maori (the indigenous people of New Zealand) and their extended family: protocol for a randomized non-inferiority trial.

BACKGROUND AND AIMS: Cytisine, a nicotinic acetylcholine receptor partial agonist (like varenicline) found in some plants, is a low-cost, effective smoking cessation medication that may appeal to Maori [the indigenous people of New Zealand (NZ)]. The RAUORA trial aims to determine the effectiveness, safety and cost-effectiveness of cytisine (Tabex® ) versus varenicline (Champix® ) for smoking cessation in Maori and the whanau (extended family) of Maori. DESIGN: Pragmatic, community-based, open-label randomized non-inferiority trial. SETTING: Lakes District Health Board region, NZ. PARTICIPANTS: Daily smokers (n = 2140) who self-identify as Maori or whanau of Maori, and are: aged ≥ 18 years, motivated to quit smoking in the next 2 weeks, eligible for subsidized varenicline, able to provide verbal consent and have daily access to a mobile phone/internet. Recruitment uses multi-media advertising. INTERVENTION AND COMPARATOR: Participants are randomized (1 : 1 ratio) to receive a prescription for 12 weeks of cytisine tablets [following the manufacturer's dosing regimen for 25 days, then one 1.5-mg tablet every 6 hours (two per day) until 12 weeks] or varenicline tablets (following the manufacturer's dosing regimen). Both groups receive brief stop-smoking advice from the prescribing doctor and withdrawal-orientated behavioural support via community-based stop-smoking counselling services (frequency, duration and mode of delivery tailored for participants) or a research assistant (six weekly 10-15-minute calls). Participants are advised to reduce their smoking over the first 4 days of treatment, with day 5 as their designated quit-date. MEASUREMENTS: The primary outcome is carbon monoxide-verified continuous abstinence at 6 months post-quit date. Secondary outcomes at 1, 3, 6 and 12 months post-quit date include: self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes per day, time to (re)lapse, adverse events, treatment adherence/compliance, treatment acceptability, nicotine withdrawal/urge to smoke and health-care utilization/health-related quality of life. COMMENTS: This trial compares cytisine and varenicline when used by the indigenous people of NZ and their extended family for smoking cessation.

A four-strain probiotic exerts positive immunomodulatory effects by enhancing colonic butyrate production in vitro.

Poorly formulated probiotic supplements intended for oral administration often fail to protect bacteria from the challenges of human digestion, meaning bacteria do not reach the small intestine in a viable state. As a result, the ability of probiotics to influence the human gut microbiota has not been proven. Here we show how (i) considered formulation of an aqueous probiotic suspension can facilitate delivery of viable probiotic bacteria to the gut and (ii) quantitate the effect of colonisation and proliferation of specific probiotic species on the human gut microbiota, using an in-vitro gut model. Our data revealed immediate colonisation and growth of three probiotic species in the luminal and mucosal compartments of the proximal and distal colon, and growth of a fourth species in the luminal proximal colon, leading to higher proximal and distal colonic lactate concentrations. The lactate stimulated growth of lactate-consuming bacteria, altering the bacterial diversity of the microbiota and resulting in increased short-chain fatty acid production, especially butyrate. Additionally, an immunomodulatory effect of the probiotics was seen; production of anti-inflammatory cytokines (IL-6 and IL-10) was increased and production of inflammatory chemokines (MCP-1, CXCL 10 and IL-8.) was reduced. The results indicate that the probiotic species alone do not result in a clinical effect; rather, they facilitate modulation of the gut microbiota composition and metabolic activity thereby influencing the immune response.

MEF2 plays a significant role in the tumor inhibitory mechanism of encapsulated RENCA cells via EGF receptor signaling in target tumor cells.

BACKGROUND: Agarose encapsulated murine renal adenocarcinoma cells (RENCA macrobeads) are currently being investigated in clinical trials as a treatment for therapy-resistant metastatic colorectal cancer. We have previously demonstrated the capacity of RENCA macrobeads to produce diffusible substances that markedly inhibit the proliferation of epithelial-derived tumor cells outside the macrobead environment. This study examined the molecular mechanisms underlying the observed inhibition in targeted tumor cells exposed to RENCA macrobeads. METHODS: We evaluated changes in transcription factor responses, participating intracellular signaling pathways and the involvement of specific cellular receptors in targeted tumor cells exposed to RENCA macrobeads. RESULTS: Factors secreted by RENCA macrobeads significantly up-regulated the activity of the MEF2 transcription factor as well as altered the transcription of MEF2b and MEF2d isoforms in targeted tumor cells. Suppression of individual or multiple MEF2 isoforms in target tumor cells markedly reduced the growth inhibitory effects of RENCA macrobeads. Furthermore, these effects were linked to the activation of the EGF receptor as attenuation of EGFR resulted in a substantial reduction of the cancer cell growth-inhibitory effect. CONCLUSIONS: Since interruption of the EGFR signaling cascade did not eliminate RENCA macrobead-induced growth control, our data suggests that RENCA macrobeads exert their full growth inhibitory effects through the simultaneous activation of multiple signaling pathways. In contrast to a precision medicine approach targeting single molecular abnormalities, the RENCA macrobead functions as a biological-systems therapy to re-establish regulation in a highly dysfunctional and dysregulated cancer system.