The Impact of Crohn's Perianal Fistula on Quality of Life: Results of an International Patient Survey

Lay Summary Results from an online survey completed by patients with Crohn's disease (CD) and perianal fistulas showed the presence of perianal fistulae has a greater negative impact as compared to CD-only patients. These results may help practitioners address patient burden.Background Crohn's perianal fistula is a disabling manifestation of Crohn's disease. However, the additional burden of perianal fistula on patients with only Crohn's disease remains to be addressed. This patient-reported survey considered outcomes of two domains: "diagnosis" (eg, symptoms) and "living with the disease" (eg, quality of life, well-being, and relationships). Methods Patients with perianal fistula and Crohn's disease completed an online, self-selective, anonymous, 46-item survey available in 11 languages hosted on the European Federation of Crohn's & Ulcerative Colitis Associations and national patient association websites. The survey was conducted between July and December 2019 in Europe and other regions. Likert scales and closed questions were used to assess outcomes. Results Of the 820 respondents with Crohn's disease (67.2% women; median age, 40.0 years), 532 (64.9%) reported the presence of perianal fistula. Patients with perianal fistula reported a greater impact on overall quality of life (P < .001), well-being (P < .001), relationships (P < .001), social life (P = .001), and work life (P = .012) than patients with only Crohn's disease. Conclusions Perianal fistulas impact several domains of the life of patients with Crohn's disease. These results may help healthcare practitioners plan therapeutic strategies that address the symptomatic and psychological burden experienced by patients with perianal fistulizing Crohn's disease

Observing conversational laughter in frontotemporal dementia.

BackgroundWe performed an observational study of laughter during seminaturalistic conversations between patients with dementia and familial caregivers. Patients were diagnosed with (1) behavioural variant frontotemporal dementia (bvFTD), (2) right temporal variant frontotemporal dementia (rtFTD), (3) semantic variant of primary progressive aphasia (svPPA), (4) non-fluent variant primary progressive aphasia (nfvPPA) or (5) early onset Alzheimer's disease (eoAD). We hypothesised that those with bvFTD would laugh less in response to their own speech than other dementia groups or controls, while those with rtFTD would laugh less regardless of who was speaking.MethodsPatients with bvFTD (n=39), svPPA (n=19), rtFTD (n=14), nfvPPA (n=16), eoAD (n=17) and healthy controls (n=156) were recorded (video and audio) while discussing a problem in their relationship with a healthy control companion. Using the audio track only, laughs were identified by trained coders and then further classed by an automated algorithm as occurring during or shortly after the participant's own vocalisation ('self' context) or during or shortly after the partner's vocalisation ('partner' context).ResultsIndividuals with bvFTD, eoAD or rtFTD laughed less across both contexts of self and partner than the other groups. Those with bvFTD laughed less relative to their own speech comparedwith healthy controls. Those with nfvPPA laughed more in the partner context compared with healthy controls.ConclusionsLaughter in response to one's own vocalisations or those of a conversational partner may be a clinically useful measure in dementia diagnosis

Phenol-Rich Food Acceptability: The Influence of Variations in Sweetness Optima and Sensory-Liking Patterns

12openInternationalItalian coauthor/editorThe consumption of phenol-rich foods is limited by their prominent bitterness and astringency. This issue has been addressed by adding sweet tastes, which suppress bitterness, but this is not a complete solution since individuals also differ in their preference for sweetness. In this study, we aimed at identifying groups of consumers differing in sweetness optima and sensory-liking patterns. To this end, increasing concentrations of sucrose were added to a chocolate pudding base. This allowed us to (1) investigate if individual differences in sensory responses are associated with different sweet liking optima in a product context, (2) define the psychological and oro-sensory profile of sweet liker phenotypes derived using a product context, and (3) assess if individuals differing in sweet liking optima differ also in consumption and liking of phenol-rich foods and beverages as a function of their sensory properties (e.g., sweeter vs. more bitter and astringent products). Individuals (1208; 58.4% women, 18–69 years) were characterised for demographics, responsiveness to 6-n-propylthiouracil (PROP), personality traits and attitudes toward foods. Three clusters were identified based on correlations between sensory responses (sweetness, bitterness and astringency) and liking of the samples: liking was positively related to sweetness and negatively to bitterness and astringency in High and Moderate Sweet Likers, and the opposite in Inverted U-Shaped. Differences between clusters were found in age, gender and personality. Furthermore, the Inverted-U Shaped cluster was found to have overall healthier food behaviours and preferences, with higher liking and consumption of phenol-rich vegetables and beverages without added sugar. These findings point out the importance of identifying the individual sensory-liking patterns in order to develop more effective strategies to promote the acceptability of healthy phenol-rich foods.openSpinelli, Sara; Prescott, John; Pierguidi, Lapo; Dinnella, Caterina; Arena, Elena; Braghieri, Ada; Di Monaco, Rossella; Gallina Toschi, Tullia; Endrizzi, Isabella; Proserpio, Cristina; Torri, Luisa; Monteleone, ErminioSpinelli, S.; Prescott, J.; Pierguidi, L.; Dinnella, C.; Arena, E.; Braghieri, A.; Di Monaco, R.; Gallina Toschi, T.; Endrizzi, I.; Proserpio, C.; Torri, L.; Monteleone, E

A multimodal neuroimaging study of a case of crossed nonfluent/agrammatic primary progressive aphasia

Crossed aphasia has been reported mainly as post-stroke aphasia resulting from brain damage ipsilateral to the dominant right hand. Here, we described a case of a crossed nonfluent/agrammatic primary progressive aphasia (nfvPPA), who developed a corticobasal syndrome (CBS). We collected clinical, cognitive, and neuroimaging data for four consecutive years from a 55-year-old right-handed lady (JV) presenting with speech disturbances. 18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) and DaT-scan with (123)I-Ioflupane were obtained. Functional MRI (fMRI) during a verb naming task was acquired to characterize patterns of language lateralization. Diffusion tensor MRI was used to evaluate white matter damage within the language network. At onset, JV presented with prominent speech output impairment and right frontal atrophy. After 3 years, language deficits worsened, with the occurrence of a mild agrammatism. The patient also developed a left-sided mild extrapyramidal bradykinetic-rigid syndrome. The clinical picture was suggestive of nfvPPA with mild left-sided extrapyramidal syndrome. At this time, voxel-wise SPM analyses of (18)F-FDG PET and structural MRI showed right greater than left frontal hypometabolism and damage, which included the Broca's area. DaT-scan showed a reduced uptake in the right striatum. FMRI during naming task demonstrated bilateral language activations, and tractography showed right superior longitudinal fasciculus (SLF) involvement. Over the following year, JV became mute and developed frank left-sided motor signs and symptoms, evolving into a CBS clinical picture. Brain atrophy worsened in frontal areas bilaterally, and extended to temporo-parietal regions, still with a right-sided asymmetry. Tractography showed an extension of damage to the left SLF and right inferior longitudinal fasciculus. We report a case of crossed nfvPPA followed longitudinally and studied with advanced neuroimaging techniques. The results highlight a complex interaction between individual premorbid developmental differences and the clinical phenotype

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Correction: Endrizzi et al. Relationships between Intensity and Liking for Chemosensory Stimuli in Food Models: A Large-Scale Consumer Segmentation (Foods 2022, 11, 5)

This study, which was conducted as part of the Italian Taste project, was aimed at exploring the relationship between actual liking and sensory perception in four food models. Each food model was spiked with four levels of prototypical tastant (i.e., citric acid, sucrose, sodium chloride, capsaicin) to elicit a target sensation (TS) at an increasing perceived intensity. Participants (N = 2258; 59% women, aged 18–60) provided demographic information, a stated liking for 40 different foods/beverages, and their responsiveness to tastants in water. A food-specific Pearson’s coefficient was calculated individually to estimate the relationship between actual liking and TS responsiveness. Considering the relationship magnitude, consumers were grouped into four food-specific clusters, depending on whether they showed a strong negative (SNC), a weak negative (WNC), a weak positive (WPC), or a strong positive correlation (SPC). Overall, the degree of liking raised in parallel with sweetness responsiveness, fell as sourness and pungency perception increased, and showed an inverted U-shape relationship with saltiness. The SNC clusters generally perceived TSs at higher intensities, except for sourness. Clusters were validated by associating the level of stated liking towards food/beverages; however, some unexpected indications emerged: adding sugar to coffee or preferring spicy foods differentiated those presenting positive correlations from those showing negative correlations. Our findings constitute a step towards a more comprehensive understanding of food preference

Core sampling test in large-scale compost cells for microorganism isolation

Composting is a process by which organic wastes are transformed into fertilizer, preventing excess organic matter accumulation. Microbes that carry out this transformation have application in biotechnology. Composting cell assembling is a complex process, it can reach several m(3) of diverse materials. It is desirable a sampling methodology that allows the microbial analysis, however, this matter has not yet been approached by other researchers. In this work we tested soil auger to probe large-scale compost piles at the Sao Paulo Zoo, in Sao Paulo, Brazil. The criterion for auger selection was percentage loss of material and microbe isolation from samples.Tortuga Cia Zootecnica AgrariaConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo, BrazilFAPESP: 2009/52030-5FAPESP: 2007/50536-3Web of Scienc

Theranostic Role of (32)P-ATP as Radiopharmaceutical for the Induction of Massive Cell Death within Avascular Tumor Core

Drug inaccessibility to vast areas of the tumor parenchyma is amongst the major hurdles for conventional therapies. Treatment efficacy rapidly decreases with distance from vessels and most of the tumor cells survive therapy. Also, between subsequent cycles of treatment, spared cancer cells replace those killed near the vessels, improving their access to nutrients, boosting their proliferation rate, and thus enabling tumor repopulation. Because of their property of "acting at a distance," radioisotopes are believed to overcome the physical barrier of vascular inaccessibility. Methods: A novel molecular imaging tool called Cerenkov Luminescence Imaging (CLI) was employed for the detection of Cerenkov radiation emitted by beta particles, allowing in vivo tracking of beta-emitters. More precisely we investigated using a xenograft model of colon carcinoma the potential use of 32P-ATP as a novel theranostic radiopharmaceutical for tracing tumor lesions while simultaneously hampering their growth. Results: Our analyses demonstrated that 32P-ATP injected into tumor-bearing mice reaches tumor lesions and persists for days and weeks within the tumor parenchyma. Also, the high-penetrating beta particles of 32P-ATP exert a "cross-fire" effect that induces massive cell death throughout the entire tumor parenchyma including core regions. Conclusion: Our findings suggest 32P-ATP treatment as a potential approach to complement conventional therapies that fail to reach the tumor core and to prevent tumor repopulation

Rates Of Amyloid Imaging Positivity In Patients With Primary Progressive Aphasia

IMPORTANCE The ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies. OBJECTIVE To determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of primary progressive aphasia (PPA). DESIGN, SETTING, AND PARTICIPANTS This prospective clinical-pathologic case series was conducted at a tertiary research clinic specialized in cognitive disorders. Patients were evaluated as part of a prospective, longitudinal research study between January 2002 and December 2015. Inclusion criteria included clinical diagnosis of PPA; availability of complete speech, language, and cognitive testing; magnetic resonance imaging performed within 6 months of the cognitive evaluation; and PET carbon 11-labeled Pittsburgh Compound-B or florbetapir F 18 brain scan results. Of 109 patients referred for evaluation of language symptoms who underwent amyloid brain imaging, 3 were excluded because of incomplete language evaluations, 5 for absence of significant aphasia, and 12 for presenting with significant initial symptoms outside of the language domain, leaving a cohort of 89 patients with PPA. MAIN OUTCOMES AND MEASURES Clinical, cognitive, neuroimaging, and pathology results. RESULTS Twenty-eight cases were classified as imaging-supported semantic variant PPA (11 women [39.3%]; mean [SD] age, 64 [7] years), 31 nonfluent/agrammatic variant PPA (22 women [71.0%]; mean [SD] age, 68 [7] years), 26 logopenic variant PPA (17 women [65.4%]; mean [SD] age, 63 [8] years), and 4 mixed PPA cases. Twenty-four of 28 patients with semantic variant PPA (86%) and 28 of 31 patients with nonfluent/agrammatic variant PPA (90%) had negative amyloid PET scan results, while 25 of 26 patients with logopenic variant PPA (96%) and 3 of 4 mixed PPA cases (75%) had positive scan results. The amyloid positive semantic variant PPA and nonfluent/agrammatic variant PPA cases with available autopsy data (2 of 4 and 2 of 3, respectively) all had a primary frontotemporal lobar degeneration and secondary Alzheimer disease pathologic diagnoses, whereas autopsy of 2 patients with amyloid PET-positive logopenic variant PPA confirmed Alzheimer disease. One mixed PPA patient with a negative amyloid PET scan had Pick disease at autopsy. CONCLUSIONS AND RELEVANCE Primary progressive aphasia variant diagnosis according to the current classification scheme is associated with Alzheimer disease biomarker status, with the logopenic variant being associated with carbon 11-labeled Pittsburgh Compound-B positivity in more than 95% of cases. Furthermore, in the presence of a clinical syndrome highly predictive of frontotemporal lobar degeneration pathology, biomarker positivity for Alzheimer disease may be associated more with mixed pathology rather than primary Alzheimer disease