Understanding phycosomal dynamics to improve industrial microalgae cultivation.

Algal-bacterial interactions are ubiquitous in both natural and industrial systems, and the characterization of these interactions has been reinvigorated by potential applications in biosystem productivity. Different growth conditions can be used for operational functions, such as the use of low-quality water or high pH/alkalinity, and the altered operating conditions likely constrain microbial community structure and function in unique ways. However, research is necessary to better understand whether consortia can be designed to improve the productivity, processing, and sustainability of industrial-scale cultivations through different controls that can constrain microbial interactions for maximal light-driven outputs. The review highlights current knowledge and gaps for relevant operating conditions, as well as suggestions for near-term and longer-term improvements for large-scale cultivation and polyculture engineering.

Insulin Edema Associated With Glargine.

Insulin edema is a poorly understood complication of insulin therapy. It has been reported in patients with both type 1 and 2 diabetes mellitus and typically occurs in patients with newly diagnosed or poorly controlled diabetes mellitus either after initiation or intensification of insulin therapy. A 20-year-old man presented with anorexia, polydipsia, and weight loss. Serum glucose on admission was 824 mg/dL (45.8 mmol/L) and hemoglobin A1c was >14.0. Additional workup was notable for positive anti-IA2 antibodies and low C-peptide of 0.5 ng/mL (1.1-4.4 ng/mL). He was diagnosed with type 1 diabetes mellitus and was started on insulin therapy with glargine and lispro. Within 4 days after insulin initiation, he developed bilateral leg swelling and reported a 25-pound (11.3-kg) weight gain over the next 10 days. After excluding other systemic causes of edema such as heart failure, renal failure, and liver failure, a diagnosis of insulin edema was made. Insulin glargine was switched to insulin degludec. Complete resolution of edema occurred within 3 days of switching the insulins. Insulin edema is a diagnosis of exclusion. Insulin's role in renal sodium handling, vasodilation, and increased vascular permeability have been postulated as possible mechanisms. Clinicians should be aware of this rare complication.

Motivational characteristics of recreational drug use among emerging adults in social settings: an integrative literature review.

Introduction: Recreational drug use by emerging adults has been identified as an increasingly normalized trend in social contexts. It has been documented that the consumption of these substances regularly occurs at music festivals, raves, nightlife and party settings. While it is known that emerging adults participate in these risk-taking behaviors, what is not known is their motivational characteristics for use. The aim of this review to identify and review literature describing the motivations for recreational drug use and drug choice (excluding alcohol, cannabis and tobacco) by emerging adults in social settings to inform selection of appropriately aligned harm reduction education and health messaging interventions. Methods: Whittemore and Knafl's (2005) integrative approach was used to conduct the review. This integrative review was based on a three-step search strategy identifying 2,772 articles published between 2000 and 2022. Eleven studies were included in the review. This review explores the following areas: drug use settings, concurrent drug use, consumer drug knowledge, motives of use including likes and dislikes and peer influence. Results: A range of factors influence motivations of emerging adults to participate in recreational drug use. Similar to the consumption of alcohol, the use of recreational drugs by emerging adults is motivated by their perceived benefits and personal motivations to achieve euphoria, emotional intimacy, social benefits, peer influence, increased confidence and to decrease inhibitions. The review findings suggest that motivational factors that reinforce recreational drug use correlate with the desire to break away from the mundane by seeking pleasure and for the opportunity to create novel experiences. Beliefs about the positive and negative impacts of drug use, together with the desire to achieve emotional satisfaction influence drug taking activity. Conclusion: Recreational drug use has become an increased societal norm amongst drug using peer groups and cannot be entirely prevented. It is to be noted that emerging adults have a basic understanding concerning recreational drugs, however, consumer drug knowledge and interventions that target illicit substances is lacking and should be addressed in future research. Festivals, raves and nightlife settings provide opportunity to implement health promotion as it reaches large number of vulnerable individuals in a short period of time.

Understanding the Patient Experience of Foreign-Born Older Adults: A Scoping Review of Older Immigrants Receiving Health Care in Canada.

In Canada, foreign-born older adults (FBOAs) have a higher prevalence of chronic conditions and poorer self-reported physical and mental health than their Canadian-born peers. However, very little research has explored FBOAs' experiences of health care after immigration. This review aims to understand the patient experiences of older immigrants within the Canadian health care system. Employing Arksey and O'Malley's framework for scoping reviews, we searched six databases and identified 12 articles that discussed the patient experience of this population. Although we sought to understand patient experience, the studies largely focused on barriers to care, including: communication difficulties, lack of cultural integration, systematic barriers in health care, financial barriers, and intersecting barriers related to culture and gender.This review provides insight into new areas of research and advocates for strengthened policy and/or programming. Our review also highlights that there is a paucity of literature for an ever-growing segment of the Canadian population.

A qualitative process evaluation within a clinical trial that used healthcare technologies for children with asthma-insights and implications.

BACKGROUND: Healthcare technologies are becoming more commonplace, however clinical and patient perspectives regarding the use of technology in the management of childhood asthma have yet to be investigated. Within a clinical trial of asthma management in children, we conducted a qualitative process evaluation that provided insights into the experiences and perspectives of healthcare staff and families on (i) the use of smart inhalers to monitor medication adherence and (ii) the use of algorithm generated treatment recommendations. METHODS: We interviewed trial staff (n = 15) and families (n = 6) who were involved in the trial to gauge perspectives around the use of smart inhalers to monitor adherence and the algorithm to guide clinical decision making. FINDINGS: Staff and families indicated that there were technical issues associated with the smart inhalers. While staff suggested that the smart inhalers were good for monitoring adherence and enabling communication regarding medication use, parents and children indicated that smart inhaler use increased motivation to adhere to medication and provided the patient (child) with a sense of responsibility for the management of their asthma. Staff were open-minded about the use of the algorithm to guide treatment recommendations, but some were not familiar with its' use in clinical care. There were some concerns expressed regarding treatment step-down decisions generated by the algorithm, and some staff highlighted the importance of using clinical judgement. Families perceived the algorithm to be a useful technology, but indicated that they felt comforted by the clinicians' own judgements. CONCLUSION: The use of technology and individual data within appointments was considered useful to both staff and families: closer monitoring and the educational impacts were especially highlighted. Utilising an algorithm was broadly acceptable, with caveats around clinicians using the recommendations as a guide only and wariness around extreme step-ups/downs considering contextual factors not taken into account.

Cingulo-Opercular Subnetworks Motivate Frontoparietal Subnetworks during Distinct Cognitive Control Demands.

Cognitive control is the ability to flexibly adapt behavior in a goal-directed manner when habit will not suffice. Control can be separated into distinct forms based on the timescale (present-future) and/or medium (external-internal) over which it operates. Both the frontoparietal network (FPN) and cingulo-opercular network (CON) are engaged during control, but their respective functions and interactions remain unclear. Here, we examined activations in the FPN and CON with fMRI in humans (male and female) during a task that manipulated control across timescales/mediums. The findings show that the CON can be distinguished into the following two separable subnetworks mirroring the FPN: a rostral/ventral subnetwork sensitive to future-oriented control involving internal representations, and a caudal/dorsal subnetwork sensitive to present-oriented control involving external representations. Relative to the FPN, activation in the CON was particularly pronounced during transitions into and out of particular control demands. Moreover, the relationship of each CON subnetwork to behavior was mediated by a respective FPN subnetwork. Such data are consistent with the idea that the CON motivates the FPN, which, in turn, drives behavior. Within the CON, the dorsomedial prefrontal cortex (dmPFC) mediated the relationship between the anterior insula and FPN, suggesting that the dmPFC acts as the crux that links the CON to the FPN. Collectively, these data indicate that parallel CON-FPN subnetworks mediate controlled behaviors at distinct timescales/mediums.SIGNIFICANCE STATEMENT The cingulo-opercular network (CON) and frontoparietal network (FPN) are engaged in diverse, demanding tasks. A functional model describing how areas within these networks can be distinguished, and also interact, would facilitate understanding of how the brain adapts to demanding situations. During a comprehensive control task, fMRI data revealed that the FPN and CON can be fractionated into subnetworks based on control demands that are either externally oriented for use in the present, or control demands that operate internally to guide future behavior. Moreover, we found evidence for a chain of relationships from the CON to FPN to behavior consistent with the idea that the CON drives the FPN to adapt behavior.

Increased Prevalence of Sensory Processing Issues in Pediatric Gastrointestinal Patient Population.

Background Sensory processing dysfunction in children has been linked to attention-deficit/hyperactivity disorder, autism, feeding disorders, and functional abdominal pain. However, little is known about sensory processing in the broader pediatric gastroenterology population. Objective To characterize frequency and type of sensory processing dysfunction seen in pediatric gastroenterology compared to a general pediatric population. Methods The Short Sensory Profile 2 was administered to the parents of children ranging 3-14 years, being seen in a pediatric gastrointestinal (GI) subspecialty clinic or general pediatric clinic. Short Sensory Profile 2 scores from age- and gender-matched groups were compared with nonparametric statistics. Results Sensory processing dysfunction was increased in children seen in the GI clinic compared to children in the general pediatric clinic. Short Sensory Profile 2 quadrant analysis revealed greatest differences in avoiding, primarily in young females of the GI population. Conclusion Children presenting to a pediatric GI clinic demonstrate greater sensory processing dysfunction compared to children in a general pediatric practice.

Hippocampal activity supporting working memory is contingent upon specific task demands.

Working memory (WM) is the ability to maintain and manipulate internal representations. WM recruits varying brain regions based on task demands. Although the hippocampus has historically been associated with long-term memory (LTM), several studies provide evidence for its involvement during WM tasks. Slotnick (this issue) posits that this involvement is due to LTM processes. This argument rests on the assumption that processes are not shared among WM and LTM, and that WM processes are necessarily sustained. We argue that there are processes utilized by both WM and LTM, and that such processes need not be sustained to support WM.

Assessing the size at maturity, spawning, and condition of the truncate soft-shell clam (Mya truncata) of southern Baffin Island, Nunavut, Canada.

The truncate soft-shell clam Mya truncata is an important source of country food for Inuit communities across the territory of Nunavut, Canada. M. truncata also plays an important role in marine ecosystems, yet there is little understanding of their life history and condition in Canadian Arctic waters. To provide a foundation on which aspects of the life history and condition of M. truncata of Baffin Island can be monitored in the future with a changing climate and fishery development, this study estimated size at maturity and provides insights into the spawning cycle and weight-length condition indices of clams from inner Frobisher Bay and the north shore of the Hudson Strait. Male and female M. truncata exhibited similar lengths at 50% attainment of sexual maturity, 31 mm and 32 mm shell length (SL), respectively. Most (77%) of the sexually mature M. truncata collected from inner Frobisher Bay in late August and 35% of clams collected from the Hudson Strait in early September were in the ripe stage of gonadal development. These results lead us to suggest a spring spawning season and that M. truncata invest in gonadal development for the next year's spawning during the late summer-early autumn ice-free season while phytoplankton concentrations are high. Dry bodyweight-SL relationships were used to show that M. truncata condition can differ significantly over small and large spatial scales based on plotted 95% confidence intervals.

Reducing asthma attacks in children using exhaled nitric oxide (RAACENO) as a biomarker to inform treatment strategy: a multicentre, parallel, randomised, controlled, phase 3 trial.

BACKGROUND: The benefit of fractional exhaled nitric oxide (FeNO) in guiding asthma treatment is uncertain. We evaluated the efficacy of adding FeNO to symptom-guided treatment in children with asthma versus only symptom-guided treatment. METHODS: RAACENO was a multicentre, parallel, randomised, controlled, phase 3 trial done in 35 secondary care centres and 17 primary care recruitment sites (only seven primary care sites managed to recruit patients) in the UK. Patients with a confirmed asthma diagnosis, aged 6-15 years, prescribed inhaled corticosteroids, and who received a course of oral corticosteroids for at least one asthma exacerbation during the 12 months before recruitment were included. Participants were randomly assigned to either FeNO plus symptom-guided treatment (intervention) or symptom-guided treatment alone (standard care) using a 24 h in-house, web-based randomisation system. Participants and the clinical and research teams were not masked to the group allocation. A web-based algorithm gave treatment recommendations based on the Asthma Control Test (ACT) or Childhood ACT (CACT) score; current asthma treatment; adherence to study treatment in the past 3 months; and use of FeNO (in the intervention group). Follow-up occurred at 3-month intervals for 12 months. The primary outcome was any asthma exacerbation treated with oral corticosteroids in the 12 months after randomisation, assessed in the intention-to-treat population. This study is registered with the International Standard Randomised Controlled Trial Registry, ISRCTN67875351. FINDINGS: Between June 22, 2017, and Aug 8, 2019, 535 children were assessed for eligibility, 20 were ineligible and six were excluded post-randomisation. 509 children were recruited and at baseline, the mean age of participants was 10·1 years (SD 2·6), and 308 (60·5%) were male. The median FeNO was 21 ppb (IQR 10-48), mean predicted FEV1 was 89·6% (SD 18·0), and median daily dose of inhaled corticosteroids was 400 µg budesonide equivalent (IQR 400-1000). Asthma was partly or fully controlled in 256 (50·3%) of 509 participants. The primary outcome, which was available for 506 (99%) of 509 participants, occurred in 123 (48·2%) of 255 participants in the intervention group and 129 (51·4%) of 251 in the standard care group, the intention-to-treat adjusted odds ratio (OR) was 0·88 (95% CI 0·61 to 1·27; p=0·49). The adjusted difference in the percentage of participants who received the intervention in whom the primary outcome occurred compared with those who received standard care was -3·1% (-11·9% to 5·6%). In 377 (21·3%) of 1771 assessments, the algorithm recommendation was not followed. Adverse events were reported by 27 (5·3%) of 509 participants (15 in the standard care group and 12 in the intervention group). The most common adverse event was itch after skin prick testing (reported by eight participants in each group). INTERPRETATION: We found that the addition of FeNO to symptom-guided asthma treatment did not lead to reduced exacerbations among children prone to asthma exacerbation. Asthma symptoms remain the only tool for guiding treatment decisions. FUNDING: National Institute for Health Research.

COVID-19 Vaccine Hesitancy and Acceptance Among Individuals With Cancer, Autoimmune Diseases, or Other Serious Comorbid Conditions: Cross-sectional, Internet-Based Survey.

BACKGROUND: Individuals with comorbid conditions have been disproportionately affected by COVID-19. Since regulatory trials of COVID-19 vaccines excluded those with immunocompromising conditions, few patients with cancer and autoimmune diseases were enrolled. With limited vaccine safety data available, vulnerable populations may have conflicted vaccine attitudes. OBJECTIVE: We assessed the prevalence and independent predictors of COVID-19 vaccine hesitancy and acceptance among individuals with serious comorbidities and assessed self-reported side effects among those who had been vaccinated. METHODS: We conducted a cross-sectional, 55-item, online survey, fielded January 15, 2021 through February 22, 2021, among a random sample of members of Inspire, an online health community of over 2.2 million individuals with comorbid conditions. Multivariable regression analysis was utilized to determine factors independently associated with vaccine hesitancy and acceptance. RESULTS: Of the 996,500 members of the Inspire health community invited to participate, responses were received from 21,943 individuals (2.2%). Respondents resided in 123 countries (United States: 16,277/21,943, 74.2%), had a median age range of 56-65 years, were highly educated (college or postgraduate degree: 10,198/17,298, 58.9%), and had diverse political leanings. All respondents self-reported at least one comorbidity: cancer, 27.3% (5459/19,980); autoimmune diseases, 23.2% (4946/21,294); chronic lung diseases: 35.4% (7544/21,294). COVID-19 vaccine hesitancy was identified in 18.6% (3960/21,294), with 10.3% (2190/21,294) declaring that they would not, 3.5% (742/21,294) stating that they probably would not, and 4.8% (1028/21,294) not sure whether they would agree to be vaccinated. Hesitancy was expressed by the following patients: cancer, 13.4% (731/5459); autoimmune diseases, 19.4% (962/4947); chronic lung diseases: 17.8% (1344/7544). Positive predictors of vaccine acceptance included routine influenza vaccination (odds ratio [OR] 1.53), trust in responsible vaccine development (OR 14.04), residing in the United States (OR 1.31), and never smoked (OR 1.06). Hesitancy increased with a history of prior COVID-19 (OR 0.86), conservative political leaning (OR 0.93), younger age (OR 0.83), and lower education level (OR 0.90). One-quarter (5501/21,294, 25.8%) had received at least one COVID-19 vaccine injection, and 6.5% (1390/21,294) completed a 2-dose series. Following the first injection, 69.0% (3796/5501) self-reported local reactions, and 40.0% (2200/5501) self-reported systemic reactions, which increased following the second injection to 77.0% (1070/1390) and 67.0% (931/1390), respectively. CONCLUSIONS: In this survey of individuals with serious comorbid conditions, significant vaccine hesitancy remained. Assumptions that the most vulnerable would automatically accept COVID-19 vaccination are erroneous and thus call for health care team members to initiate discussions focusing on the impact of the vaccine on an individual's underlying condition. Early self-reported side effect experiences among those who had already been vaccinated, as expressed by our population, should be reassuring and might be utilized to alleviate vaccine fears. Health care-related social media forums that rapidly disseminate accurate information about the COVID-19 vaccine may play an important role.

The relative importance of information items and preferred mode of delivery when disseminating results from trials to participants: A mixed-methods study.

BACKGROUND: Participants want to receive the results of trials that they have participated in. Dissemination practices are disparate, and there is limited guidance available on what information to provide to participants and how to deliver it. OBJECTIVES: This study aimed to establish what trial participants believe should be included in a results summary and how this information should be delivered. METHODS: A mixed-methods design was used with focus groups and interviews involving women convenience-sampled from two host randomized-controlled trials. Participants ranked information items in order of their importance for inclusion in a trial results summary and potential modes of delivery by preference. All participants provided written informed consent. RESULTS: Sixteen women (mean age [SD] = 71.6 [9.7] years) participated. Participants ranked 'individual results from the study' and 'summary of overall trial results' as most important. Themes such as reassurance and setting results in context were identified as contributing to participants' decisions around ranking. 'A thank you for your contribution to the study' was ranked the least important. Delivery by post was the preferred mode of receiving results, with receiving a hard copy of results cited as helpful to refer back to. CONCLUSION: Our findings provide insight into what information trial participants deem as important when receiving trial results and how they would like results delivered. Involving patients during development of trial results to be communicated to participants could help to ensure that the right information is delivered in the right way. PATIENT OR PUBLIC CONTRIBUTION: Public partners were involved in focussed aspects of study conduct.

Literature Review to create Evidence Based Care Pathway for Isolated Adult Orbital Blowout Fractures.

This review aims to develop an evidence-based pathway for isolated adult orbital blowout fractures. Evaluation of assessment methods, outcome measures, imaging modalities, and crucially, the optimal timing of surgical intervention was critically examined to develop a clinically applicable care pathway. A literature search was carried out using Scopus, PubMed and Web of Knowledge. The literature favors the use of HAR% ratio, Field of Binocular Single Vision (FOBSV) and Exophthalmometer as the core tests that should form part of the standardized assessment for blow-out fractures (BOFs). CT imaging remains gold standard, particularly to identify 'red-flags' warranting early intervention. There was some disagreement in relation to timing of intervention in adult fractures who continue to be symptomatic without initial extraocular muscle (EOM) entrapment and enophthalmos >3 mm, where early intervention within two weeks is not indicated. The limited literature available agreed that successful functional and radiological outcomes can be achieved with conservative or late surgical management following an extended observational period of four weeks, opposed to the conventional two weeks. An evidence-based care pathway has been created, confidently including the initial assessment methods, imaging modality, and the criteria for observation. A four-week observational period has been advocated due to evidence suggesting that there is no significant difference in outcomes from two-week observation, plus with careful functional evaluation, surgery may be avoided in some cases.

Motivations for Engaging in Consensually Non-Monogamous Relationships.

Sexual, romantic, and intimate relationships provide opportunities for individual and interpersonal fulfillment and the enhancement of well-being. Though research has identified that consensual non-monogamy (CNM) offers unique relational benefits, little work has examined why individuals pursue CNM relationships. Both self-determination theory and self-expansion theory provide frameworks for understanding the range of intra- and interpersonal motives for choosing or negotiating a multipartnered relationship. We explored the reasons for which people engage in CNM and discuss how motivations for CNM might be linked to well-being and need fulfillment. Our study used a qualitative approach to examine the motivations individuals report for engaging in CNM relationships. As part of a larger online survey, participants completed open-ended questions examining motivations for, and experiences of, CNM relationships. Data from participants who indicated that they were currently in a CNM partnership was selected for the analyses (n = 540). Data were analyzed using thematic analysis, within a critical realist framework. Motivations were organized into six interconnected themes: reasons related to autonomy, beliefs and value systems, relationality, sexuality, growth and expansion, and pragmatism. Individuals reported diverse reasons for engaging in CNM relationships; reasons addressed both individual and relational needs and well-being. Findings contrast with stereotypic views of CNM relationships as unstable/unfulfilling or that individuals engage in CNM because of relationship problems. The findings may facilitate therapeutic interventions for counselors working with individuals who are in the process of negotiating or re-negotiating relationship boundaries.

A dyadic examination of self-determined sexual motives, need fulfillment, and relational outcomes among consensually non-monogamous partners.

Intimate and sexual relationships provide opportunity for emotional and sexual fulfillment. In consensually non-monogamous (CNM) relationships, needs are dispersed among multiple partners. Using Self-Determination Theory (SDT) and dyadic data from 56 CNM partnerships (112 individuals), we tested how sexual motives and need fulfillment were linked to relational outcomes. We drew from models of need fulfillment to explore how sexual motives with a second partner were associated with satisfaction in the primary relationship. In a cross-sectional and daily experience study we demonstrated that self-determined reasons for sex were positively associated with sexual satisfaction and indirectly linked through sexual need fulfillment. Self-determined reasons for sex predicted need fulfillment for both partners at a three-month follow up. The association between sexual motives and need fulfillment was stronger on days when participants engaged in sex with an additional partner, though this was not related to satisfaction in the primary relationship. Implications for need fulfillment are discussed.

Impact of internal and external factors on prosocial choices in rhesus macaques.

While traditional economic models assume that agents are self-interested, humans and most non-human primates are social species. Therefore, many of decisions they make require the integration of information about other social agents. This study asks to what extent information about social status and the social context in which decisions are taken impact on reward-guided decisions in rhesus macaques. We tested 12 monkeys of varying dominance status in several experimental versions of a two-choice task in which reward could be delivered to self only, only another monkey, both the self and another monkey, or neither. Results showed dominant animals were more prone to make prosocial choices than subordinates, but only when the decision was between a reward for self only and a reward for both self and other. If the choice was between a reward for self only and a reward for other only, no animal expressed altruistic behaviour. Finally, prosocial choices were true social decisions as they were strikingly reduced when the social partner was replaced by a non-social object. These results showed that as in humans, rhesus macaques' social decisions are adaptive and modulated by social status and the cost associated with being prosocial. This article is part of the theme issue 'Existence and prevalence of economic behaviours among non-human primates'.

Sameness and Difference in Psychological Research on Consensually Non-Monogamous Relationships: The Need for Invariance and Equivalence Testing.

Comparative research involving consensually non-monogamous (CNM) relationships and outcomes related to well-being continues to grow as an area of interest within sexual science. However, claims of sameness and/or difference between groups rely on two critical, yet widely under-appreciated assumptions: that the concepts being compared between groups are the same (i.e., measurement invariance), and that logically and statistically coherent procedures are used for evaluating sameness (i.e., equivalence testing). We evaluated the state of measurement invariance and equivalence across three studies, involving different types of CNM comparisons (i.e., relationship types, partner types) and designs (analysis of primary individual data, primary dyadic data, and secondary data). Our invariance tests of CNM compared to monogamous individuals (Study 1) and "primary" compared to "secondary" partners in dyadic appraisal of CNM individuals (Study 2) revealed that many measures of well-being failed to replicate their measurement models and were not generalizable across relationship types or partner types. Our reanalyses of existing comparative CNM effects using individual and meta-analyzed equivalence tests (Study 3), meanwhile, indicated that this literature requires more consistent reporting practices and larger samples, as most studies produced uninformative tests of equivalence. Our results illustrate the importance of auxiliary hypothesis evaluation and statistical procedure selection for generating informative comparative tests. Our findings also highlight potential divergences in social construction of well-being. We offer suggestions for researchers, reviewers, and editors in terms of needed methodological reforms for future comparative CNM research.

The Role of Epidemiological Evidence from Prospective Population Studies in Shaping Dietary Approaches to Therapy in Crohn's Disease.

SCOPE: The concept that dietary factors are key risk and preventive agents in the development of Crohn's disease (CD), while widely believed and supported by epidemiological evidence, has yet to lead to clear identification of those factors through clinical trials. The aims are to examine the strength of the epidemiological evidence of diet and its association with CD, examine how interpretation of mostly epidemiological data has shaped ideas for potential dietary therapies, and to explore other factors that have driven the design of dietary clinical trials in CD. METHODS: A literature search is performed in PubMed, Medline, EMBASE, and Google Scholar for prospective cohort studies and randomized clinical trials (RCTs) using search terms-"Crohn's disease," "diet," "risk," "remission," "treat," "cohort," "randomised." RESULTS: Only four prospective cohort studies examine the relationship of diet and CD development, but these trials have been largely ignored by dietary RCTs in CD, which have used predominantly exclusion diets in small populations without objective endpoint assessment. Only one demonstrated clinical benefit to intestinal inflammation. CONCLUSION: Investment in large multicenter dietary clinical trials that focus on dietary inclusions with objective endpoint assessment are needed to provide safe, sustainable dietary therapy to patients with CD.

Familial language network vulnerability in primary progressive aphasia.

OBJECTIVE: To investigate evidence of the potential role of early cortical vulnerability in the development of primary progressive aphasia (PPA). METHOD: A woman with a diagnosis of PPA and her 9 adult siblings, 7 with developmental language disabilities, underwent neuropsychological testing, structural MRI, and resting-state fMRI. Whole-exome sequencing was conducted for genes associated with dyslexia or with neurodegenerative dementia. RESULTS: The siblings demonstrated lower verbal than nonverbal cognitive test scores in a developmental dyslexia pattern. On structural MRI, although the siblings did not differ from controls in total brain volume, the left hemisphere language area volume was significantly smaller than the right. Furthermore, cortical connectivity between the left superior temporal area, previously identified as the region of peak atrophy in the proband early in the course of illness, and adjacent language network components, including the planum temporale, was decreased in the siblings. No distinctive genetic signatures were identified. CONCLUSION: This report further supports the hypothesis that at least some cases of PPA may be based on a familial language network vulnerability that interferes with the acquisition of language in some members and that makes the language network a locus of least resistance to the effects of an independently late-arising neurodegenerative disease in others. This association offers a conceptual model to explain why identical neurodegenerative diseases may selectively target the language network in some individuals while targeting networks that regulate memory or behavior in others. The genetic basis for this vulnerability remains to be determined.