A rapidly advancing area of ecological immunology concerns the effects of diet on animals’ immunological responses to parasites and pathogens. Here, we focus on diet-mediated ecological immunology in ...herbivorous insects, in part because these organisms commonly experience nutritional limitations from their diets of plants. Nutritional immunology highlights nutrient-based trade-offs between immunological and other physiological processes as well as trade-offs among distinct immunological processes. This field reveals that nutrition influences the quality and quantity of immunological defense in herbivorous insects, and conversely that nutritional intake by herbivorous insects can be an adaptive response to the specific types of immune-challenge they face in the context of other physiological processes. Because the diets of herbivores challenge them physiologically with plants’ secondary metabolites, another area of study analyzes constraints on immunological defense imposed by secondary metabolites of plants in the diets of herbivorous insects. Alternatively, some herbivores can use secondary metabolites as medicine against parasites or pathogens. Animal-medication theory makes an important contribution to ecological immunology by distinguishing prophylactic and therapeutic mechanisms of anti-parasite defense. Integrating ideas from animal-medication and nutritional immunology, we outline a conceptual framework in which the immunological role of the diet consists of mechanisms of prophylaxis, therapy, compensation, and combinations thereof. Then, we use this framework to organize findings from our own research on diet-mediated ecological immunology of woolly bear caterpillars. We show evidence that the woolly bear caterpillar, Grammia incorrupta (Hy. Edwards) (Lepidoptera, Erebidae, and Arctiinae), can employ both diet-mediated prophylaxis and therapy. First, increased consumption of carbohydrate-biased food prior to immune-challenge increased its melanization- response. Second, increased consumption of pyrrolizidine alkaloids (PAs) more than 24 h after parasitism by tachinid flies resulted in anti-parasite resistance. Caterpillars reduced feeding on protein-biased food within 24 h after immune-challenge, showing evidence of illness-induced anorexia. We synthesize our work to generate the hypothesis that a diet-mediated defense by the host against parasites acts as a temporally explicit, multi-stage process.
Oral and oropharyngeal cancer represents the sixth more common type of cancer affecting the worldwide population. It has been estimated the number of 650,000 new cases per year globally and a greater ...prevalence has been registered among men. The main risk factors for oral cancer such as tobacco smoking and alcohol are uncontroversial and have been deeply investigated and evidenced in the scientific literature. Recently, viral infections related to Human Papilloma Virus (HPV), with the genotype 16 and 32, have shown a correlation mainly with oropharyngeal cancer (OPC) especially in the non-smoking and non-drinkers young adults. Its transmission is mainly related to sexually transmitted diseases (STDs) although its involvement in oral squamous cell carcinoma (OSCC) is still unclear. This review aims to explore the hypotheses of the OSCC etiology and other possible risk factors, such as chronic traumatisms, chronic periodontitis, and poor oral hygiene that affect directly the oral mucosa and might trigger the carcinogenesis process that should not be underestimated. Furthermore, in the last 10 years, the role of oral microbiome gained attention as a predicting biomarker, for a possible bacterial, viral, and fungal involvement in tumorigenesis.
Purpose
Hyponatremia is the most frequent electrolytic disorder in clinical practice. In addition to neurological symptoms, hyponatremia, even when mild/moderate and chronic, has been related to ...other manifestations, such as bone demineralization and increased risk of fractures. To better elucidate tissue alterations associated with reduced serum sodium concentration Na
+
, we developed an in vivo model of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis.
Methods and results
Hyponatremia was induced in Foxn1
nu/nu
mice by subcutaneous infusion of the vasopressin analog 1-deamino 8-D-arginine vasopressin (dDAVP) for 14 days via osmotic mini-pumps. Mice in the control group were infused with isotonic saline solution. Serum Na
+
progressively decreased, with a nadir of 123.4 ± 2.3 mEq/L (mean ± SD, dDAVP 0.3 ng/h) and 111.6 ± 4.7 mEq/L (mean ± SD, dDAVP 0.5 ng/h). Evident signs of liver steatofibrosis were observed at histology in hyponatremic mice. Accordingly, the expression of proteins involved in lipid metabolism (SREBP-1, PPARα and PPARγ) and in myofibroblast formation (αSMA and CTGF) significantly increased. Furthermore, heme oxygenase 1 expression was up-regulated in Kupffer and hepatic stellate cells in the liver of hyponatremic mice. Testis alterations were also observed. In particular, the thickness of the seminiferous epithelium appeared reduced. The expression levels of PCNA and PTMA, which are involved in DNA replication and germ cells maturation, were markedly reduced in the testis of hyponatremic mice.
Conclusion
Overall, these findings shed new light on the possible consequences of chronic hyponatremia and prompt a more thorough evaluation of hyponatremic patients.
Abstract
Austropuccinia psidii, originating in South America, is a globally invasive fungal plant pathogen that causes rust disease on Myrtaceae. Several biotypes are recognized, with the most widely ...distributed pandemic biotype spreading throughout the Asia-Pacific and Oceania regions over the last decade. Austropuccinia psidii has a broad host range with more than 480 myrtaceous species. Since first detected in Australia in 2010, the pathogen has caused the near extinction of at least three species and negatively affected commercial production of several Myrtaceae. To enable molecular and evolutionary studies into A. psidii pathogenicity, we assembled a highly contiguous genome for the pandemic biotype. With an estimated haploid genome size of just over 1 Gb (gigabases), it is the largest assembled fungal genome to date. The genome has undergone massive expansion via distinct transposable element (TE) bursts. Over 90% of the genome is covered by TEs predominantly belonging to the Gypsy superfamily. These TE bursts have likely been followed by deamination events of methylated cytosines to silence the repetitive elements. This in turn led to the depletion of CpG sites in TEs and a very low overall GC content of 33.8%. Compared to other Pucciniales, the intergenic distances are increased by an order of magnitude indicating a general insertion of TEs between genes. Overall, we show how TEs shaped the genome evolution of A. psidii and provide a greatly needed resource for strategic approaches to combat disease spread.
Purpose
Hyponatremia, the most frequent electrolyte alteration in clinical practice, has been associated with a worse prognosis in cancer patients. On the other hand, a better outcome has been ...related to serum sodium normalization. In vitro studies have shown that low extracellular sodium promotes cancer cells proliferation and invasiveness. Tolvaptan, a selective vasopressin receptor type 2 (V
2
) antagonist, has been effectively used in the last decade for the treatment of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis. A few in vitro data suggested a direct role of tolvaptan in counteracting cancer progression, so far. The aim of this study was to evaluate the effect and the mechanism of action of tolvaptan in cell lines from different tumours i.e. colon cancer (HCT-8), hepatocarcinoma (HepG2), neuroblastoma (SK-N-AS).
Methods and results
First, we showed that these cell lines express the V
2
receptor. Tolvaptan significantly reduced cell proliferation with an IC
50
in the micromolar range. Accordingly, reduced levels of cAMP, of the catalytic α subunit of PKA, and a reduced pAKT/AKT ratio were observed. Tolvaptan effectively inhibited cell cycle progression, whereas it induced apoptotis. Furthermore, it reduced cell invasiveness. In particular, anchorage-independent growth and the activity of collagenases type IV were blunted in the three cell lines. Accordingly, tolvaptan counteracted the RhoA/ROCK1–2 pathway, which has a pivotal role in regulating cell movement.
Conclusions
Overall, these findings indicate that tolvaptan effectively inhibits tumour progression in vitro. Further studies should clarify whether the V
2
receptor might be considered a possible target in anti-cancer strategies in the future.
•Physical activity (PA) is an important outcome in peripheral artery disease (PAD).•Invasive and noninvasive treatments are used in the management of PAD.•PA at follow-up was statistically similar ...independent of treatment.•Increased PA was associated with greater PAQ specific health status.
The association of invasive versus noninvasive treatment and physical activity level in patients with claudication remains unclear. Participants with claudication were enrolled from US vascular clinics. Treatment was categorized as invasive (surgical or endovascular treatment <3 months of initial visit) versus noninvasive. Self-reported leisure time (LTPA) and work related physical activity (WRPA) (sedentary, mild, moderate/strenuous), and health status (peripheral artery questionnaire summary score PAQ SS) was measured at baseline and 12 months. Change in PA was also categorized as increased, decreased, persistent sedentary reference and persistent active based on activity status at baseline and 12 months. Multivariable logistic regression assessed the association of treatment with 12-month LTPA and WRPA. Multivariable linear regression examined the association between 12-month change in PA with a 12-month change in PAQ. A total of 196of 656 patients (29.9%) underwent invasive treatment. There was no association between treatment and 12-month LTPA (p = 0.77) or WRPA (p = 0.26). Compared with being persistently sedentary, increased LTPA was associated with increased PAQ SS (OR 11.1 95% CI 4.4 to 17.7, p <0.01). In conclusion, there was no association between invasive treatment and physical activity at follow up despite a greater health status change in the invasive group. As increased physical activity was associated with more health status gains than remaining sedentary, additional ways to improve physical activity levels could potentially improve PAD outcomes.
Numerous studies have demonstrated that sympathetic nervous system overactivation during exercise in hypertensive rodents and humans is due, in part, to an exaggerated reflex response known as the ...exercise pressor reflex. Our prior studies have implicated a key role of mineralocorticoid receptor activation in mediating an augmented exercise pressor reflex in spontaneously hypertensive rats, which is mitigated by blockade with eplerenone. However, the effect of eplerenone on exercise pressor reflex has not been assessed in human hypertension. Accordingly, the authors performed a randomized crossover study to compare the effects of eplerenone to another antihypertensive drug from a different class amlodipine on sympathetic nerve activity (SNA) in 14 patients with uncomplicated hypertension. The authors found that amlodipine unexpectedly augmented the increase in SNA during the second minute of isometric handgrip, which persisted into the post‐exercise circulatory arrest period (∆ SNA, from rest of 15 ± 2 vs. 9 ± 2 vs. 10 ± 2 bursts/min, amlodipine vs. baseline vs. eplerenone, respectively, p < .01), suggesting an exaggerated muscle metaboreflex function. Eplerenone did not alter sympathetic responses to exercise or post‐exercise circulatory arrest in the same hypertensive individuals. In conclusions, our studies provide the first direct evidence for a potentially unfavorable potentiation of muscle metaboreflex by amlodipine during isometric handgrip exercise in hypertensive patients whereas eplerenone has no significant effect. Our study may have clinical implications in terms of selection of antihypertensive agents that have the least detrimental effects on sympathetic neural responses to isometric exercise.
Background
Excess adipose tissue has been implicated in the pathogenesis of insulin resistance and atherosclerosis and is a key risk factor for blood pressure (BP) elevation. However, circulating ...levels of adiponectin, a protein produced by adipose tissue and widely implicated in the pathogenesis of insulin resistance and atherosclerosis, are inversely proportional to adiposity. The relationship between adiponectin and incident hypertension has not been determined in the general US population.
Methods
Normotensive participants (n = 1233) enrolled in the Dallas Heart Study, a multiethnic, probability‐based population sample of Dallas County adults were followed for median of 7 years. Retroperitoneal, intraperitoneal, visceral, and subcutaneous adipose tissue were measured at baseline by magnetic resonance imaging. Liver fat content was measured by 1H‐magnetic resonance spectroscopy. Relative risk regression was used to determine the association of adiponectin with incident hypertension after adjustment for age, race, sex, BMI, smoking, diabetes, baseline systolic BP, total cholesterol, and regional fat depot.
Results
Of the 1233 study participants (median age 40 years, 40% black, and 56% women), 391 (32%) had developed hypertension over a median follow‐up of 7 years. Adiponectin levels were associated with reduced risk of incident hypertension (RR 0.81, 95% CI 0.68‐0.96) in the fully adjusted model, which included liver fat. Similar results were observed after adjustment for subcutaneous or visceral fat depots when tested individually or simultaneously in the model.
Conclusion
Our study suggested a protective role of adiponectin against incident hypertension independent of body fat distribution.
This study investigates complex effects of parasitoid infection on herbivore diet choice. Specifically, we examine how immunological resistance, parasitoid infection stage, and parasitoid taxonomic ...identity affect the pharmacophagous behavior of the polyphagous caterpillar, Grammia incorrupta (Arctiidae). Using a combination of lab and field experiments, we test the caterpillar's pharmacophagous response to pyrrolizidine alkaloids (PAs) over the course of parasitoid infection, as well as the effect of dietary PAs on the caterpillar's immunological response. Previous work from other systems gave the prediction that dietary PAs would be detrimental to the immune response and thus less acceptable to feeding early in the infection, when encapsulation of the parasitoid is most crucial. We found that the feeding acceptability of PAs was indeed low for caterpillars with early-stage parasitoid infections; however, this was not explained by PA interference with immune function. When allowed to choose among three host plant species, individuals harboring early-stage parasitoids increased their consumption of a nutritious plant containing antioxidants. This result was driven by wasp-parasitized caterpillars, whereas fly-parasitized caterpillars increased their consumption of plants containing iridoid glycosides. Individuals in the later time phase of infection exhibited an increase in PA intake that was consistent with previously reported self-medication behavior during late-stage parasitoid infection. This study reveals the depth of complexity and the dynamic nature of herbivore host plant choice, and underscores the importance of considering multitrophic interactions when studying insect diet choice.
Background
Minimally invasive Ivor Lewis esophagectomy (MIILE) provides better outcomes than open techniques, particularly in terms of post-operative recovery and pulmonary complications. However, in ...addition to requiring advanced technical skills, thoracoscopic access makes it hard to perform esophagogastric anastomosis safely, and the reported rates of anastomotic leak vary from 5 to 16%. Several minimally invasive esophago-gastric anastomotic techniques have been described, but to date strong evidence to support one technique over the others is still lacking. We herein report the technical details and preliminary results of a new robot-assisted hand-sewn esophago-gastric anastomosis technique.
Methods
From January 2018 to December 2020, 12 cases of laparoscopic/thoracoscopic Ivor Lewis esophagectomy with robot-assisted hand-sewn esophago-gastric anastomosis were performed. The gastric conduit was prepared and tailored taking care of vascularization with a complete resection of the gastric fundus. The anastomosis consisted of a robot-assisted, hand-sewn four layers of absorbable monofilament running barbed suture (V-lock). The posterior outer layer incorporated the gastric and esophageal staple lines.
Results
The post-operative course was uneventful in nine cases. Two patients developed chyloperitoneum, one patient a Sars-Cov-2 infection, and one patient a late anastomotic stricture. In all cases, there were no anastomotic leaks or delayed gastric conduit emptying. The median post-operative stay was 13 days (min 7, max 37 days); the longest in-hospital stay was recorded in patients who developed chyloperitoneum.
Conclusion
Despite the small series, we believe that our technique looks to be promising, safe, and reproducible. Some key points may be useful to guarantee a low complications rate after MIILE, particularly regarding anastomotic leaks and delayed emptying: the resection of the gastric fundus, the use of robot assistance, the incorporation of the staple lines in the posterior aspect of the anastomosis, and the use of barbed suture. Further cases are needed to validate the preliminary, but very encouraging, results.
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