Future Tail Tales: A Forward-Looking, Integrative Perspective on Tail Research.

Synopsis Tails are a defining characteristic of chordates and show enormous diversity in function and shape. Although chordate tails share a common evolutionary and genetic-developmental origin, tails are extremely versatile in morphology and function. For example, tails can be short or long, thin or thick, and feathered or spiked, and they can be used for propulsion, communication, or balancing, and they mediate in predator-prey outcomes. Depending on the species of animal the tail is attached to, it can have extraordinarily multi-functional purposes. Despite its morphological diversity and broad functional roles, tails have not received similar scientific attention as, for example, the paired appendages such as legs or fins. This forward-looking review article is a first step toward interdisciplinary scientific synthesis in tail research. We discuss the importance of tail research in relation to five topics: (1) evolution and development, (2) regeneration, (3) functional morphology, (4) sensorimotor control, and (5) computational and physical models. Within each of these areas, we highlight areas of research and combinations of long-standing and new experimental approaches to move the field of tail research forward. To best advance a holistic understanding of tail evolution and function, it is imperative to embrace an interdisciplinary approach, re-integrating traditionally siloed fields around discussions on tail-related research.

'TB or not TB': the conundrum of pre-European contact tuberculosis in the Pacific.

Tuberculosis (TB) is a major global health threat, infecting one-third of the world's population. Despite this prominence, the age, origin and spread of the disease have been topics of contentious debate. Molecular studies suggest that Mycobacterium tuberculosis 'sensu stricto', the most common strain of TB infecting humans today, originated in Africa and from there spread into Europe and Asia. The M. tuberculosis strains most commonly found across the Pacific and the Americas today are most closely related to European strains, supporting a hypothesis that the disease only reached these regions relatively recently via European sailors or settlers. However, this hypothesis is inconsistent with palaeopathological evidence of TB-like lesions in human remains from across the Pacific that predate European contact. Similarly, genetic evidence from pre-European South American mummies challenges the notion of a European introduction of the disease into the Pacific. Here, we review the complex evidence for the age and origin of TB in the Pacific, and discuss key gaps in our knowledge and how these may be addressed. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.

Impact of Next-generation Sequencing Defined Human Immunodeficiency Virus Pretreatment Drug Resistance on Virological Outcomes in the ANRS 12249 Treatment-as-Prevention Trial.

BACKGROUND: Previous studies in human immunodeficiency virus (HIV)-positive individuals on thymidine analogue backbone antiretroviral therapy (ART) with either nevirapine or efavirenz have suggested poorer virological outcomes in the presence of pretreatment drug resistance (PDR). We assessed the impact of PDR on virological suppression (VS; <50 copies/mL) in individuals prescribed primarily tenofovir/emtricitabine/efavirenz in rural KwaZulu-Natal within a treatment-as-prevention trial. METHODS: Among 1557 HIV-positive individuals who reported no prior ART at study entry and provided plasma samples, 1328 individuals with entry viral load (VL) >1000 copies/mL had next-generation sequencing (NGS) of the HIV pol gene with MiSeq technology. Results were obtained for 1148 individuals, and the presence of PDR was assessed at 5% and 20% detection thresholds. Virological outcome was assessed using Cox regression in 837 of 920 ART initiators with at least 1 follow-up VL after ART initiation. RESULTS: PDR prevalence was 9.5% (109/1148) and 12.8% (147/1148) at 20% and 5% thresholds, respectively. After a median of 1.36 years (interquartile range, 0.91-2.13), mostly on fixed-dose combination tenofovir/emtricitabine/efavirenz, presence of both nonnucleoside reverse transcriptase inhibitor (NNRTI)/nucleoside reverse transcriptase inhibitor PDR vs no PDR was associated with longer time to VS (adjusted hazard ratio [aHR], 0.32; 95% confidence interval [CI], 0.12-0.86), while there was no difference between those with only NNRTI PDR vs no PDR (aHR, 1.05; 95% CI, 0.82-1.34) at the 5% threshold. Similar differences were observed for mutations detected at the 20% threshold, although without statistical significance. CONCLUSIONS: NGS uncovered a high prevalence of PDR among participants enrolled in trial clinics in rural KwaZulu-Natal. Dual-class PDR to a mainly tenofovir/emtricitabine/efavirenz regimen was associated with poorer VS. However, there was no impact of NNRTI PDR alone. CLINICAL TRIALS TEGISTRATION: NCT01509508; South African National Clinical Trials Register: DOH-27-0512-3974.

A systematic review and meta-analysis of nutrition interventions for chronic noncancer pain.

BACKGROUND: This systematic review aimed to evaluate the impact of nutrition interventions on participant reported pain severity and intensity in populations with chronic pain. METHODS: Eight databases were systematically searched for studies that included adult populations with a chronic pain condition, a nutrition intervention and a measure of pain. Where possible, data were pooled using meta-analysis. Seventy-one studies were included, with 23 being eligible for meta-analysis. RESULTS: Studies were categorised into four groups: (i) altered overall diet with 12 of 16 studies finding a significant reduction in participant reported pain; (ii) altered specific nutrients with two of five studies reporting a significant reduction in participant reported pain; (iii) supplement-based interventions with 11 of 46 studies showing a significant reduction in pain; and (iv) fasting therapy with one of four studies reporting a significant reduction in pain. The meta-analysis found that, overall, nutrition interventions had a significant effect on pain reduction with studies testing an altered overall diet or just one nutrient having the greatest effect. CONCLUSIONS: This review highlights the importance and effectiveness of nutrition interventions for people who experience chronic pain.

Putting patients at the center of kidney care transitions: PREPARE NOW, a cluster randomized controlled trial.

Care for patients transitioning from chronic kidney disease to kidney failure often falls short of meeting patients' needs. The PREPARE NOW study is a cluster randomized controlled trial studying the effectiveness of a pragmatic health system intervention, 'Patient Centered Kidney Transition Care,' a multi-component health system intervention designed to improve patients' preparation for kidney failure treatment. Patient-Centered Kidney Transition Care provides a suite of new electronic health information tools (including a disease registry and risk prediction tools) to help providers recognize patients in need of Kidney Transitions Care and focus their attention on patients' values and treatment preferences. Patient-Centered Kidney Transition Care also adds a 'Kidney Transitions Specialist' to the nephrology health care team to facilitate patients' self-management empowerment, shared-decision making, psychosocial support, care navigation, and health care team communication. The PREPARE NOW study is conducted among eight [8] outpatient nephrology clinics at Geisinger, a large integrated health system in rural Pennsylvania. Four randomly selected nephrology clinics employ the Patient Centered Kidney Transitions Care intervention while four clinics employ usual nephrology care. To assess intervention effectiveness, patient reported, biomedical, and health system outcomes are collected annually over a period of 36 months via telephone questionnaires and electronic health records. The PREPARE NOW Study may provide needed evidence on the effectiveness of patient-centered health system interventions to improve nephrology patients' experiences, capabilities, and clinical outcomes, and it will guide the implementation of similar interventions elsewhere. TRIAL REGISTRATION: NCT02722382.

Disparities exist between the dietary intake of Indigenous Australian women during pregnancy and the Australian dietary guidelines: the Gomeroi gaaynggal study.

BACKGROUND: Little is known about the adequacy of nutrient intakes and the overall diet quality of Indigenous Australian pregnant women. The aim of this cross-sectional study was to assess nutrient sufficiency and diet quality, as measured using the Australian Recommended Food Score (ARFS), in pregnant women from the Gomeroi gaaynggal cohort (n = 58). METHODS: Maternal dietary intake during pregnancy was assessed using the Australian Eating Survey Food Frequency Questionnaire, which was self-administered in the third trimester. Diet quality was determined using the ARFS. Food group servings and nutrient intakes were compared to the Australian Guide to Health Eating (AGHE) and Australian Nutrient Reference Values (NRVs). The current analysis examined the adequacy of usual intakes from food sources only, excluding supplements. RESULTS: None of the women met all AGHE daily food group serving recommendations. The highest alignment rates were for dairy (33%), meat/alternatives (31%) and vegetables (29.3%). Almost 93% of participants exceeded the recommended intake of energy-dense, nutrient-poor foods and percentage energy from saturated fat was high (15%). Of the five key nutrients for optimal reproductive health (folate, iron, calcium, zinc and fibre), the nutrients with the highest percentage of pregnant women achieving the NRVs were zinc (77.6%) and folate (68.9%), whereas iron was the lowest. Only one person achieved all NRVs (folate, iron, calcium, zinc and fibre) important in pregnancy. The median ARFS was 28 points (maximum of 73). CONCLUSIONS: Although the small cohort limits the generalisability of the findings of the present study, the data obtained indicate that the diets of these Indigenous pregnant women are inadequate. Therefore, strategies aiming to optimise nutrient intakes of Indigenous pregnant women are needed urgently.

Ancient mitogenomes of Phoenicians from Sardinia and Lebanon: A story of settlement, integration, and female mobility.

The Phoenicians emerged in the Northern Levant around 1800 BCE and by the 9th century BCE had spread their culture across the Mediterranean Basin, establishing trading posts, and settlements in various European Mediterranean and North African locations. Despite their widespread influence, what is known of the Phoenicians comes from what was written about them by the Greeks and Egyptians. In this study, we investigate the extent of Phoenician integration with the Sardinian communities they settled. We present 14 new ancient mitogenome sequences from pre-Phoenician (~1800 BCE) and Phoenician (~700-400 BCE) samples from Lebanon (n = 4) and Sardinia (n = 10) and compare these with 87 new complete mitogenomes from modern Lebanese and 21 recently published pre-Phoenician ancient mitogenomes from Sardinia to investigate the population dynamics of the Phoenician (Punic) site of Monte Sirai, in southern Sardinia. Our results indicate evidence of continuity of some lineages from pre-Phoenician populations suggesting integration of indigenous Sardinians in the Monte Sirai Phoenician community. We also find evidence of the arrival of new, unique mitochondrial lineages, indicating the movement of women from sites in the Near East or North Africa to Sardinia, but also possibly from non-Mediterranean populations and the likely movement of women from Europe to Phoenician sites in Lebanon. Combined, this evidence suggests female mobility and genetic diversity in Phoenician communities, reflecting the inclusive and multicultural nature of Phoenician society.

A dose response randomised controlled trial of docosahexaenoic acid (DHA) in preterm infants.

Thirty one infants born less than 30 weeks׳ gestational age were randomised to receive either 40 (n=11), 80 (n=9) or 120 (n=11) mg/kg/day of docosahexaenoic acid (DHA) respectively as an emulsion, via the feeding tube, commenced within 4 days of the first enteral feed. Twenty three infants were enroled in non-randomised reference groups; n=11 who had no supplementary DHA and n=12 who had maternal DHA supplementation. All levels of DHA in the emulsion were well tolerated with no effect on number of days of interrupted feeds or days to full enteral feeds. DHA levels in diets were directly related to blood DHA levels but were unrelated to arachidonic acid (AA) levels. All randomised groups and the maternal supplementation reference group prevented the drop in DHA levels at study end that was evident in infants not receiving supplementation. Australian New Zealand Clinical Trials Registry: ACTRN12610000382077.

Dietary lecithin improves dressing percentage and decreases chewiness in the longissimus muscle in finisher gilts.

The influence of dietary lecithin at doses of 0, 4, 20 or 80 g/kg fed to finisher gilts for six weeks prior to slaughter on growth performance, carcass quality and pork quality was investigated. M. longissimus lumborum (loin) was removed from 36 pig carcasses at 24h post-mortem for Warner-Bratzler shear force, compression, collagen content and colour analyses. Dietary lecithin increased dressing percentage (P=0.009). Pork chewiness and collagen content were decreased by dietary lecithin (P<0.05, respectively), suggesting that improved chewiness may be due to decreased collagen content. However, dietary lecithin had no effect on shear force, cohesiveness or hardness (P>0.05, respectively). Dietary lecithin reduced loin muscle L* values and increased a* values (P<0.05, respectively) but no changes on b* values (P=0.56). The data showed that dietary lecithin improved dressing percentage and resulted in less chewy and less pale pork.

Suppression of lipopolysaccharide-stimulated cytokine/chemokine production in skin cells by sandalwood oils and purified α-santalol and ß-santalol.

Medicinally, sandalwood oil (SO) has been attributed with antiinflammatory properties; however, mechanism(s) for this activity have not been elucidated. To examine how SOs affect inflammation, cytokine antibody arrays and enzyme-linked immunosorbent assays were used to assess changes in production of cytokines and chemokines by co-cultured human dermal fibroblasts and neo-epidermal keratinocytes exposed to lipopolysaccharides and SOs from Western Australian and East Indian sandalwood trees or to the primary SO components, α-santalol and ß-santalol. Lipopolysaccharides stimulated the release of 26 cytokines and chemokines, 20 of which were substantially suppressed by simultaneous exposure to either of the two sandalwood essential oils and to ibuprofen. The increased activity of East Indian SO correlated with increased santalol concentrations. Purified α-santalol and ß-santalol equivalently suppressed production of five indicator cytokines/chemokines at concentrations proportional to the santalol concentrations of the oils. Purified α-santalol and ß-santalol also suppressed lipopolysaccharide-induced production of the arachidonic acid metabolites, prostaglandin E2, and thromboxane B2, by the skin cell co-cultures. The ability of SOs to mimic ibuprofen non-steroidal antiinflammatory drugs that act by inhibiting cyclooxygenases suggests a possible mechanism for the observed antiinflammatory properties of topically applied SOs and provides a rationale for use in products requiring antiinflammatory effects.

A comparative validation of a child food frequency questionnaire using red blood cell membrane fatty acids.

BACKGROUND/OBJECTIVES: There are limited validated tools available for the assessment of dietary intake in pediatric populations. This report describes a comparative validation study of selected fatty acid intakes in children assessed by food frequency questionnaire (FFQ), compared with erythrocyte membrane fatty acids. SUBJECTS/METHODS: Overall, 46 overweight and 47 healthy-weight children aged 5-12 years (mean±SD, 9.1±1.3years, body mass index 20.5±4.0) were recruited; dietary fatty acid intakes assessed by parent report using a 135-item semi-quantitative FFQ, were compared with selected child erythrocyte membrane fatty acids assessed from fasting samples using gas chromatography. Spearman's rank correlation coefficients were calculated between fatty acid intake estimates (% of energy) and erythrocyte membrane concentrations (%mol/mol). RESULTS: Significant correlations were found between dietary and erythrocyte eicosapentanoic acid (EPA) concentration (r=0.24, P<0.05) with a statistical trend for total omega three (∑n-3) fatty acids (r=0.22, P=0.06) and linoleic acid (r=0.32, P=0.07) in the healthy-weight children only. CONCLUSION: Parental report of selected child fatty acid intakes using an FFQ can be used to provide an estimate of child intake of EPA, but further work is required to quantify this relationship for other fatty acids and in other populations.

Effects of dietary ß-glucans supplementation on cytokine expression in porcine liver.

As dietary supplementation with ß-glucans can stimulate the innate immune response in the porcine gastrointestinal system (GIT), the aim of this study was to determine if the effects of ß-glucan supplementation extend beyond the GIT to systemic levels. Hence, the effects of dietary supplementation of ß-glucans derived from Laminara digitata, Laminara hyperborea, and Sacharomyces cerevisiae on cytokine expression in the porcine liver with or without ex vivo lipopolysaccharide (LPS) challenge were examined. No significant differences in gene expression were observed in the unchallenged liver tissue, but differences were observed in all supplementation groups in the LPS challenged tissue. Relative to the basal diet, IL-6 (P < 0.05) was less expressed in the S. cerevisiae supplementation group, IL-6 (P < 0.05) and TLR-4 (P < 0.05) were less expressed in the L. digitata supplementation group, and IL-10 (P = 0.06) and IL-1α (P = 0.02) were more expressed in the L. hyperborea supplementation group. There was a ≈ 3-fold increase in both IL-10 and IL-1α in the liver samples of L. hyperborea relative to the L. digitata supplementation groups (P < 0.01). The results indicate that supplementation with ß-glucans from both yeast and seaweed sources have systemic effects evidenced by changes in cytokine expression in the liver in response to LPS challenge; however, the cytokines affected varied according to the source of the ß-glucan.

Effects of dietary supplementation with Laminaria hyperborea, Laminaria digitata, and Saccharomyces cerevisiae on the IL-17 pathway in the porcine colon.

An unregulated T(h)17 inflammatory response has been highlighted as a major contributor to the underlying pathology of inflammatory bowel diseases (IBD) whereas regulatory T (T(REG)) cells) have been highlighted as pivotal in suppressing autoimmune and inflammatory responses in the gut. Following dietary supplementation, ß-glucans have been shown to reduce the T(h)17 signature molecule IL-17a in the porcine colon. To expand this observation we examined the effects of supplementing feeds with ß-glucans derived from seaweeds Laminaria hyperborea and Laminaria digitata and the yeast Saccharomyces cerevisiae on gene expression of a range of cytokines, receptors, and signal transducing molecules relevant to the T(h)17 and T(REG) pathways in the porcine colon. All sources of ß-glucans significantly decreased the expression of T(h)17-related cytokines (IL-17a, IL-17F, and IL-22), receptor IL23R, and IL-6. There was no alteration to the T(REG)-related target, Foxp3, or to TGF-ß, although a significant reduction in IL-10 was observed in the L. digitata supplementation group.

Omega-3 index, obesity and insulin resistance in children.

OBJECTIVES: Recent studies in adults have suggested that the plasma level of omega-3 fatty acids may be associated with weight status and abdominal adiposity, limited studies exist in paediatric populations. The present study examined the relationship between the omega-3 index, weight status and insulin resistance in children. METHODS: School-age children between 5-12 years, classified as non-obese or obese on the basis of body mass index (BMI) z-scores, were examined. Fat intake was assessed using a parent reported 135-item semi-quantitative food frequency questionnaire. Erythrocyte fatty acid composition was determined using gas chromatography. The Omega-3 index (O3I) was calculated by adding eicosapentaenoic and docosahexaenoic acid % (weight/weight) values. RESULTS: Obese children had altered erythrocyte fatty acid composition unrelated to reported dietary intake. A greater proportion of obese (BMI z-score > 2.25) children (33%) had an omega-3 index of < 4.0 (high risk) compared with non-obese children (BMI z-score < 2.25) (17%). Simultaneously, the number of children with a higher omega-3 index (6.0-8.0 lower risk) was lower in the obese (13%) versus non-obese children (25%, respectively). A moderate, but statistically significant correlation was found between O3I and fasting insulin level (r = -0.3, P = 0.03) and with homeostatic model assessment (HOMA) scores (r = -0.3, P = 0.04). CONCLUSION; The observed association between the omega-3 index, weight status and insulin resistance in children highlights the importance of omega-3 fatty acids in the prevention of obesity-related chronic diseases in later life. The results presented merits confirmation in a larger sample of obese children.

Republished review. [corrected] Late-onset retinal macular degeneration: clinical insights into an inherited retinal degeneration.

AIM: This study describes, in detail, the phenotype of late-onset retinal macular degeneration (L-ORMD) an inherited condition affecting both the retina and anterior segment. A staging based on clinical characteristics is proposed, and the relevance of this condition to current understanding of age-related macular degeneration is discussed. METHODS: A systematic review of the literature regarding this condition supports a detailed description of the natural history. Clinical experiences in identifying, monitoring and managing patients are also presented. RESULTS: L-ORMD is a rare fully penetrant autosomal dominant condition resulting from a mutation in the C1QTNF5 gene on chromosome 11. Affected individuals develop bilateral loss of vision, dark-adaptation abnormalities, fundus drusen-like yellow spots, midperipheral pigmentation, choroidal neovascularisation, chorioretinal atrophy and long anteriorly inserted lens zonules. Patients may benefit from treatment with high-dose vitamin A. CONCLUSIONS: Raised awareness of L-ORMD should lead to earlier diagnosis and improved care for patients. New antivascular endothelial growth factor treatment may provide a new possibility for management. A deeper insight into molecular and genetic mechanisms of L-ORMD may suggest avenues to explore new treatments of this disorder.

Late-onset retinal macular degeneration: clinical insights into an inherited retinal degeneration.

AIM: This study describes, in detail, the phenotype of late-onset retinal macular degeneration (L-ORMD) an inherited condition affecting both the retina and anterior segment. A staging based on clinical characteristics is proposed, and the relevance of this condition to current understanding of age-related macular degeneration is discussed. METHODS: A systematic review of the literature regarding this condition supports a detailed description of the natural history. Clinical experiences in identifying, monitoring and managing patients are also presented. RESULTS: L-ORMD is a rare fully penetrant autosomal dominant condition resulting from a mutation in the C1QTNF5 gene on chromosome 11. Affected individuals develop bilateral loss of vision, dark-adaptation abnormalities, fundus drusen-like yellow spots, midperipheral pigmentation, choroidal neovascularisation, chorioretinal atrophy and long anteriorly inserted lens zonules. Patients may benefit from treatment with high-dose vitamin A. CONCLUSIONS: Raised awareness of L-ORMD should lead to earlier diagnosis and improved care for patients. New antivascular endothelial growth factor treatment may provide a new possibility for management. A deeper insight into molecular and genetic mechanisms of L-ORMD may suggest avenues to explore new treatments of this disorder.

Progress curve analysis of CYP1A2 inhibition: a more informative approach to the assessment of mechanism-based inactivation?

Mechanism-based cytochrome P450 inactivation is defined as a time- and NADPH-dependent inactivation that is not reversible upon extensive dialysis. Current methodologies use dilution approaches to estimate the rate of inactivation and offer limited mechanistic insight and are significantly influenced by experimental conditions. We investigated the potential of progress curve analysis because this experimental design allows investigation of both the reversible (K(iapp)) and irreversible (K(i), K(inact)) components of the reaction mechanism. The human liver microsomal CYP1A2 inactivation kinetics of resveratrol, oltipraz, furafylline, and dihydralazine (Fig. 2) were evaluated. The inactivation results for furafylline (K(i), 0.8 microM; K(inact), 0.16 min(-1)) are within 2-fold to published data (K(i), 1.6 microM; K(inact), 0.19 min(-1)). Resveratrol and dihydralazine results are within a 4.3-fold range of published data, which compares well with ranges of estimates of these parameters across publications (e.g., furafylline has estimates ranging of K(i) from 1.6 to 22.3 microM and K(inact) from 0.19 to 0.87 min(-1)). This range of estimates highlights the potential caveats surrounding the existing methodologies that have been previously discussed in depth. In addition to these inactivation parameters, we have been able to demonstrate a variation in balance of reversible versus irreversible inhibition within these inactivators. Oltipraz and resveratrol have K(iapp) values similar to their K(i), indicating a significant early onset reversible inhibition, whereas furafylline and dihydralazine are dominated by irreversible inactivation. This approach allows a more mechanistic investigation of an inactivator and in the future may improve the prediction of clinical drug-drug interactions.

Maternal folate status and neural tube defects in Ireland: the need for a national food fortification program.

To determine the present risk of a Neural Tube Defect [NTD] pregnancy in the caucasian primigravid population in Dublin by comparing the serum folate and red cell folate status of primigravid patients attending the first prenatal booking clinic with data from the late 80's. This Cross-sectional population study looking at blood folate status of over 400 sequential primigravid caucasian women with a singleton pregnancy, booking at less than or equal to 20 weeks gestation. All patients were attending a prenatal booking clinic at the Rotunda Hospital in Dublin during 2003-2004. Comparing serum and red cell folate values in 454 primigravid patients in 2003-4 to values to in a large case-control study based on over 56,000 women attending maternity hospitals in Dublin from 1986 to 1990. Just 13.9% of our patients took periconceptual folate, 33.5% of patients took folate in the first 20 weeks of pregnancy and 58.8% of mothers were taking no folate supplement. Overall, 30% of mothers had RCF levels below 400 ug/L--a level recommended as the minimum value required for protection. NTD risk occurred most frequently amongst patients with RCF levels between 300 and 400 ng/mL.

Blood transfusion requirement prediction in patients undergoing primary total hip and knee arthroplasty.

The aim of this study was to identify the clinical factors associated with the need for peri-operative blood transfusion in non-anaemic patients undergoing hip or knee arthroplasty. We prospectively evaluated 162 consecutive patients who underwent total hip or knee arthroplasty. Analysis was performed to establish the relationship between all independent variables and the need for postoperative transfusion. Univariate analysis revealed a significant relationship between the need for postoperative blood transfusion and the pre-operative haemoglobin levels (P= 0.001), weight (P= 0.019) and age (P= 0.018). Multivariate analysis identified a significant relationship only between the need for transfusion and the pre-operative haemoglobin level (P= 0.0001). The pre-operative haemoglobin level of the patient was the only variable to independently predict the need for blood transfusion after primary hip or knee arthroplasty.