To review the evidence for the role of dietary modifications in alleviating chronic fatigue syndrome symptoms.
A systematic literature review was guided by PRISMA and conducted using Scopus, CINAHL ...Plus, Web of Science and PsycINFO scientific databases (1994–2016) to identify relevant studies. Twenty‐two studies met the inclusion criteria, the quality of each paper was assessed and data extracted into a standardised tabular format.
Positive outcomes were highlighted in some included studies for polyphenol intakes in animal studies, D‐ribose supplementation in humans and aspects of symptom alleviation for one of three polynutrient supplement studies. Omega three fatty acid blood levels and supplementation with an omega three fatty acid supplement also displayed positive outcomes in relation to chronic fatigue syndrome symptom alleviation.
Limited dietary modifications were found useful in alleviating chronic fatigue syndrome symptoms, with overall evidence narrow and inconsistent across studies.
Due to the individual and community impairment chronic fatigue syndrome causes the population, it is vital that awareness and further focused research on this topic is undertaken to clarify and consolidate recommendations and ensure accurate, useful distribution of information at a population level.
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Cell-free human T-lymphotropic virus type 1 (HTLV-1) virions are poorly infectious in vitro for their primary target cells, CD4(+) T cells. Here, we show that HTLV-1 can efficiently infect myeloid ...and plasmacytoid dendritic cells (DCs). Moreover, DCs exposed to HTLV-1, both before and after being productively infected, can rapidly, efficiently and reproducibly transfer virus to autologous primary CD4(+) T cells. This DC-mediated transfer of HTLV-1 involves heparan sulfate proteoglycans and neuropilin-1 and results in long-term productive infection and interleukin-2-independent transformation of the CD4(+) T cells. These studies, along with observations of HTLV-1-infected DCs in the peripheral blood of infected individuals, indicate that DCs have a central role in HTLV-1 transmission, dissemination and persistence in vivo. In addition to altering the current paradigm concerning how HTLV-1 transmission occurs, these studies suggest that impairment of DC function after HTLV-1 infection plays a part in pathogenesis.
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This book explores the representation of Wales and ‘Welshness’ in texts by French- (including Breton) and German-speaking travellers from 1780 to the present day. Since the emergence of the travel ...narrative as a popular source of information and entertainment in the mid-18th century, writing about Wales has often been embedded and hidden in accounts of travel to ‘England’. This book locates and presents these largely forgotten texts and broadens perspectives to encompass European perceptions. Works uncovered for the first time include travelogues, private correspondences, travel diaries, articles and blogs which have Wales or Welsh culture as their focus. The ‘travellers’ analysed in this volume include those travelling for the purpose of leisure, scholarship or commerce as well as exiles and refugees. By focusing on Wales, a minoritized nation at the geographical periphery of Europe, the authors are able to problematize notions of hegemony and identity, relating to both the places encountered (the ‘travellee’ culture) and the places of origin (the travellers’ cultures). This book thereby makes an original contribution to studies in travel writing and provides an important case study of a culture often minoritized in the field, but that nevertheless provides a telling illustration of the dynamics of intercultural relations and representation.
The absence of social support, or social isolation, can be stressful, leading to a suite of physical and psychological health issues. Growing evidence suggests that disruption of the gut-immune-brain ...axis plays a crucial role in the negative outcomes seen from social isolation stress. However, the mechanisms remain largely unknown. The socially monogamous prairie vole (Microtus ochrogaster) has been validated as a useful model for studying negative effects of social isolation on the brain and behaviors, yet how the gut microbiome and central immune system are altered in isolated prairie voles are still unknown. Here, we utilized this social rodent to examine how social isolation stress alters the gut-immune-brain axis and relevant behaviors. Adult male and female prairie voles (n = 48 per sex) experienced social isolation or were cohoused with a same-sex cagemate (control) for six weeks. Thereafter, their social and anxiety-like behaviors, neuronal circuit activation, neurochemical expression, and microgliosis in key brain regions, as well as gut microbiome alterations from the isolation treatment were examined. Social isolation increased anxiety-like behaviors and impaired social affiliation. Isolation also resulted in sex- and brain region-specific alterations in neuronal activation, neurochemical expression, and microgliosis. Further, social isolation resulted in alterations to the gut microbiome that were correlated with key brain and behavioral measures. Our data suggest that social isolation alters the gut-immune-brain axis in a sex-dependent manner and that gut microbes, central glial cells, and neurochemical systems may play a critical, integrative role in mediating negative outcomes from social isolation.
•Social isolation increased anxiety-like behaviors and impaired social affiliation.•Isolation altered neuronal activation and neurochemical expression in the brain.•Isolation stress increased microgliosis in a brain region-specific manner.•Isolation stress also resulted in alterations to the gut microbiome.•Social isolation altered the gut-immune-brain axis in a sex-dependent manner.
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Chagas disease resulting from Trypanosoma cruzi infection leads to a silent, long-lasting chronic neglected tropical disease affecting the poorest and underserved populations around the world. ...Antiparasitic treatment with benznidazole does not prevent disease progression or death in patients with established cardiac disease. Our consortium is developing a therapeutic vaccine based on the T. cruzi flagellar-derived antigen Tc24-C4 formulated with a Toll-like receptor 4 agonist adjuvant, to complement existing chemotherapy and improve treatment efficacy. Here we demonstrate that therapeutic treatment of acutely infected mice with a reduced dose of benznidazole concurrently with vaccine treatment - also known as "vaccine-linked chemotherapy"-induced a T
17 like immune response, with significantly increased production of antigen specific IL-17A, IL-23 and IL-22, and CD8 + T lymphocytes, as well as significantly increased T. cruzi specific IFNγ-producing CD4 + T lymphocytes. Significantly reduced cardiac inflammation, fibrosis, and parasite burdens and improved survival were achieved by vaccine-linked chemotherapy and individual treatments. Importantly, low dose treatments were comparably efficacious to high dose treatments, demonstrating potential dose sparing effects. We conclude that through induction of T
17 immune responses vaccine-linked chemotherapeutic strategies could bridge the tolerability and efficacy gaps of current drug treatment in Chagasic patients.
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The acidic polysaccharide succinoglycan produced by the rhizobial symbiont Sinorhizobium meliloti 1021 is required for this bacterium to invade the host plant Medicago truncatula and establish a ...nitrogen-fixing symbiosis. S. meliloti mutants that cannot make succinoglycan cannot initiate invasion structures called infection threads in plant root hairs. S. meliloti exoH mutants that cannot succinylate succinoglycan are also unable to form infection threads, despite the fact that they make large quantities of succinoglycan. Succinoglycan produced by exoH mutants is refractory to cleavage by the glycanases encoded by exoK and exsH, and thus succinoglycan produced by exoH mutants is made only in the high-molecular-weight (HMW) form. One interpretation of the symbiotic defect of exoH mutants is that the low-molecular-weight (LMW) form of succinoglycan is required for infection thread formation. However, our data demonstrate that production of the HMW form of succinoglycan by S. meliloti 1021 is sufficient for invasion of the host M. truncatula and that the LMW form is not required. Here, we show that S. meliloti strains deficient in the exoK- and exsH-encoded glycanases invade M. truncatula and form a productive symbiosis, although they do this with somewhat less efficiency than the wild type. We have also characterized the polysaccharides produced by these double glycanase mutants and determined that they consist of only HMW succinoglycan and no detectable LMW succinoglycan. This demonstrates that LMW succinoglycan is not required for host invasion. These results suggest succinoglycan function is not dependent upon the presence of a small, readily diffusible form.
Sinorhizobium meliloti is a bacterium that forms a beneficial symbiosis with legume host plants. S. meliloti and other rhizobia convert atmospheric nitrogen to ammonia, a nutrient source for the host plant. To establish the symbiosis, rhizobia must invade plant roots, supplying the proper signals to prevent a plant immune response during invasion. A polysaccharide, succinoglycan, produced by S. meliloti is required for successful invasion. Here, we show that the critical feature of succinoglycan that allows infection to proceed is the attachment of a "succinyl" chemical group and that the chain length of succinoglycan is much less important for its function. We also show that none of the short-chain versions of succinoglycan is produced in the absence of two chain-cleaving enzymes.
It is crucial to include a wide range of the population in clinical trials for the outcome to be applicable in real-world settings. Existing literature indicates that under-served groups, including ...disabled people, have been excluded from participating in clinical trials without justification. Exclusion from clinical trials exacerbates disparities in healthcare and diminishes the benefits for excluded populations. Therefore, this study was conducted to investigate potential obstacles that prevent disabled people from participating in clinical trials in the United Kingdom (UK).
The study was carried out through an explanatory sequential mixed methods design. The Imperial Clinical Trials Unit devised and implemented an online questionnaire-based survey (with open/closed-ended questions) and an online focus group discussion. The target population were disabled people, family members/carers of disabled people and staff involved in clinical trials, whereupon the sample was recruited by convenience sampling methods via posters and emails through various networks. The Qualtrics XM survey system was used as the host platform for the online survey, and Microsoft Teams was used for an online focus group discussion. The focus group discussion was conducted to gain a deeper understanding of the themes identified from the survey responses. We analysed responses to the survey via descriptive analysis and used thematic analysis to synthesise the free-text answers from the survey and focus group discussion.
We received 45 responses to the survey questionnaire and 5 disabled people took part in a focus group discussion. Our findings highlighted the differences between the perspectives of researchers and those "being researched" and different types of barriers experienced by disabled people: opportunity barriers (inadequate recruitment strategy and ambiguous eligibility criteria), awareness barriers (perception of disability) and acceptance/refusal barriers (available support and adjustment, and sharing of trial results).
Our findings support perspectives drawn from the Ford Framework regarding the need to consider all barriers, not just up to the point of enrolment into trials but also beyond the point of inclusion in clinical trials. We support calls for the introduction of legislation on including disabled people in clinical trials, implementation of industry/community-wide participatory approaches and the development of guidelines, a combined public-private approach.
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Ascariasis remains the most common helminth infection in humans. As an alternative or complementary approach to global deworming, a pan-anthelminthic vaccine is under development targeting Ascaris, ...hookworm, and Trichuris infections. As16 and As14 have previously been described as two genetically related proteins from Ascaris suum that induced protective immunity in mice when formulated with cholera toxin B subunit (CTB) as an adjuvant, but the exact protective mechanism was not well understood.
As16 and As14 were highly expressed as soluble recombinant proteins (rAs16 and rAs14) in Pichia pastoris. The yeast-expressed rAs16 was highly recognized by immune sera from mice infected with A. suum eggs and elicited 99.6% protection against A. suum re-infection. Mice immunized with rAs16 formulated with ISA720 displayed significant larva reduction (36.7%) and stunted larval development against A. suum eggs challenge. The protective immunity was associated with a predominant Th2-type response characterized by high titers of serological IgG1 (IgG1/IgG2a > 2000) and high levels of IL-4 and IL-5 produced by restimulated splenocytes. A similar level of protection was observed in mice immunized with rAs16 formulated with alum (Alhydrogel), known to induce mainly a Th2-type immune response, whereas mice immunized with rAs16 formulated with MPLA or AddaVax, both known to induce a Th1-type biased response, were not significantly protected against A. suum infection. The rAs14 protein was not recognized by A. suum infected mouse sera and mice immunized with rAs14 formulated with ISA720 did not show significant protection against challenge infection, possibly due to the protein's inaccessibility to the host immune system or a Th1-type response was induced which would counter a protective Th2-type response.
Yeast-expressed rAs16 formulated with ISA720 or alum induced significant protection in mice against A. suum egg challenge that associates with a Th2-skewed immune response, suggesting that rAS16 could be a feasible vaccine candidate against ascariasis.
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Employing history of science methods, including analyses of the scientific literature, archival documents, and interviews with scientists, this paper presents a history of lampreys in neurobiology ...from the 1830s to the present. We emphasize the lamprey's roles in helping to elucidate spinal cord regeneration mechanisms. Two attributes have long perpetuated studies of lampreys in neurobiology. First, they possess large neurons, including multiple classes of stereotypically located, 'identified' giant neurons in the brain, which project their large axons into the spinal cord. These giant neurons and their axonal fibers have facilitated electrophysiological recordings and imaging across biological scales, ranging from molecular to circuit-level analyses of nervous system structures and functions and including their roles in behavioral output. Second, lampreys have long been considered amongst the most basal extant vertebrates on the planet, so they have facilitated comparative studies pointing to conserved and derived characteristics of vertebrate nervous systems. These features attracted neurologists and zoologists to studies of lampreys between the 1830s and 1930s. But, the same two attributes also facilitated the rise of the lamprey in neural regeneration research after 1959, when biologists first wrote about the spontaneous, robust regeneration of some identified CNS axons in larvae after spinal cord injuries, coupled with recovery of normal swimming. Not only did large neurons promote fresh insights in the field, enabling studies incorporating multiple scales with existing and new technologies. But investigators also were able to attach a broad scope of relevance to their studies, interpreting them as suggesting conserved features of successful, and sometimes even unsuccessful, CNS regeneration. Lamprey research demonstrated that functional recovery takes place without the reformation of the original neuronal connections, for instance, by way of imperfect axonal regrowth and compensatory plasticity. Moreover, research performed in the lamprey model revealed that factors intrinsic to neurons are integral in promoting or hindering regeneration. As this work has helped illuminate why basal vertebrates accomplish CNS regeneration so well, whereas mammals do it so poorly, this history presents a case study in how biological and medical value have been, and could continue to be, gleaned from a non-traditional model organism for which molecular tools have been developed only relatively recently.
Sinorhizobium meliloti forms symbiotic, nitrogen-fixing nodules on the roots of Medicago truncatula. The bacteria invade and colonize the roots through structures called infection threads. S. ...meliloti unable to produce the exopolysaccharide succinoglycan are unable to establish a symbiosis because they are defective in initiating the production of infection threads and in invading the plant. Here, we use microarrays representing 16,000 M. truncatula genes to compare the differential transcriptional responses of this host plant to wild-type and succinoglycan-deficient S. meliloti at the early time point of 3 days postinoculation. This report describes an early divergence in global plant gene expression responses caused by a rhizobial defect in succinoglycan production, rather than in Nod factor production. The microarray data show that M. truncatula inoculated with wild-type, succinoglycan-producing S. meliloti more strongly express genes encoding translation components, protein degradation machinery, and some nodulins than plants inoculated with succinoglycan-deficient bacteria. This finding is consistent with wild-type-inoculated plants having received a signal, distinct from the well characterized Nod factor, to alter their metabolic activity and prepare for invasion. In contrast, M. truncatula inoculated with succinoglycan-deficient S. meliloti more strongly express an unexpectedly large number of genes in two categories: plant defense responses and unknown functions. One model consistent with our results is that appropriate symbiotically active exopolysaccharides act as signals to plant hosts to initiate infection thread formation and that, in the absence of this signal, plants terminate the infection process, perhaps via a defense response.
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