Decreased expression of surfactant Protein-C and CD74 in alveolar epithelial cells during influenza virus A(H1N1)pdm09 and H3N2 infection.

The primary replication site of Influenza A virus (IAV) is type II alveolar epithelial cells (AECII), which are central to normal lung function and present important immune functions. Surfactant components are synthesized primarily by AECII, which play a crucial role in host defense against infection. The aim of this study was to analyze if the impact of influenza infection is differential between A(H1N1)pdm09 and A/Victoria/3/75 (H3N2) on costimulatory molecules and ProSP-C expression in AECII from BALB/c mice infected and A549 cell line infected with both strains. Pandemic A(H1N1)pdm09 and A/Victoria/3/75 (H3N2) were used to infect BALB/c mice and the A549 cell line. We evaluated the surface expression of co-stimulatory molecules (CD45/CD31/CD74/ProSP-C) in AECII and A549 cell lines. Our results showed a significant decrease in ProSP-C+ CD31- CD45- and CD74+ CD31- CD45- expression in AECII and A549 cell line with the virus strain A(H1N1)pdm09 versus A/Victoria/3/75 (H3N2) and controls (non-infection conditions). Our findings indicate that changes in the expression of ProSP-C in AECII and A549 cell lines in infection conditions could result in dysfunction leading to decreased lung compliance, increased work of breathing and increased susceptibility to injury.

Post-exposure prophylaxis following consented sexual exposure: impact of national recommendations on user profile, drug regimens and estimates of averted HIV infections.

OBJECTIVES: The aim of the study was to describe the characteristics, impact and outreach of post-exposure prophylaxis (PEP) for sexual exposure in Brazil. METHODS: We used secondary data from the Brazilian Ministry of Health to describe the impact of national guidelines on the frequency of prescription, user profile and antiretroviral regimens. We also estimated the number of potentially averted HIV infections attributable to PEP for consented sexual exposure between 2009 and 2017. RESULTS: A total of 260 457 PEP regimens were prescribed to individuals ≥ 14 years old; 104 613 (40.2%) were prescribed for consented sexual exposure, with an increasing frequency since 2011. Drugs used in PEP regimens underwent significant modifications during the period, reflecting national recommendations. We estimated that there were up to 3138 potentially averted HIV infections attributable to PEP for consented sexual exposure between 2009 and 2017. CONCLUSIONS: In the context of a combined HIV prevention strategy, PEP is still an essential tool for individuals for whom other methods are contraindicated or fail to be applied.

Perianal warts as a risk marker for anal high-risk-human papillomavirus (HPV) detection and HPV-associated diseases.

BACKGROUND: Genital warts are the most common sexually transmitted infection (STI) and are caused by human papillomavirus (HPV). Persistent anal infection by oncogenic genotypes of HPV is a determinant for anal cancer. Currently, anal cancer screening is not widely implemented. OBJECTIVES: Our aim is to evaluate the role of perianal warts as a risk marker for anal high-risk (HR) HPV detection and anal dysplasia. METHODS: In this observational, retrospective, cohort study of attendees of a STI outpatient clinic between January 2010 and June 2018, all human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) who performed anal cytology, anal HPV DNA detection and anoscopy were included. A comparison was made between patients with and without perianal warts. Primary endpoint: proportion of patients with an abnormal anal cytology. Secondary endpoints: proportion of patients with (i) anal HR-HPV detection; (ii) anal HPV 16 detection; (iii) abnormal anal biopsy; and (iv) anal high-grade squamous intraepithelial lesion (HSIL). RESULTS: Seventy-eight individuals were included: 39 with perianal warts and 39 without perianal warts. Subjects with perianal warts more frequently had an abnormal anal cytology (71.8% vs. 38.5%; P = 0.003). This group also had a higher rate of anal HPV 16 detection (38.5% vs. 12.8%; P = 0.01). No differences were detected in the proportion of patients with anal HR-HPV detection, with an abnormal anal biopsy or with anal HSIL. Perianal warts was an independent risk factor for an abnormal anal cytology (OR: 7.2) and for anal HPV 16 detection (OR: 6.7). CONCLUSION: Given the high risk of anal cancer in HIV-positive MSM, effective screening strategies are greatly needed. This study suggests that the presence of perianal warts is a suitable risk marker for anal HPV 16 detection and anal dysplasia.

Inflammatory biomarkers in infective endocarditis: machine learning to predict mortality.

Infective endocarditis (IE) is the cardiac disease with the highest rates of mortality. New biomarkers that are able to identify patients at risk for death are required to improve patient management and outcome. This study aims to investigate if cytokines, chemokines and growth factors measured at IE diagnosis can predict mortality. Patients with definite IE, according to the Duke's modified criteria, were included. Using high-performance Luminex assay, 27 different cytokines, chemokines and growth factors were analyzed. Machine learning techniques were used for the prediction of death and subsequently creating a decision tree, in which the cytokines, chemokines and growth factors were analyzed together with C-reactive protein (CRP). Sixty-nine patients were included, 41 (59%) male, median age 54 [interquartile range (IQR) = 41-65 years] and median time between onset of the symptoms and diagnosis was 12 days (IQR = 5-30 days). The in-hospital mortality was 26% (n = 18). Proinflammatory cytokines interkeukin (IL)-15 and C-C motif chemokine ligand (CCL4) were found to predict death, adding value to CRP levels. The decision tree predicted correctly the outcome of 91% of the patients at hospital admission. The high-risk group, defined as CRP ≥ 72 mg/dL, IL-15 ≥ 5·6 fg/ml and CCL4 ≥ 6·35 fg/ml had an 88% in-hospital mortality rate, whereas the patients classified as low-risk had a mortality rate of 8% (P = < 0·001). Cytokines IL-15 and CCL4 were predictors of mortality in IE, adding prognostic value beyond that provided by CRP levels. Assessment of cytokines has potential value for clinical risk stratification and monitoring in IE patients.

Correction to: Satellite Images Combined with Field Data Reveal Negative Changes in the Distribution of Babassu Palms after Clearing off Amazonian Forests.

The original article has been corrected.

Satellite Images Combined with Field Data Reveal Negative Changes in the Distribution of Babassu Palms after Clearing off Amazonian Forests.

When the Amazonian rain forest is cut to create pasture, some of the original vegetal species survive clearing, even expressing their ability to invade agro-systems. It is true of the babassu palm, which can be considered, paradoxically, a natural resource by the "Interstate Movement of Babassu Fruit Breaker Women" or as native weed by land owners-farmers. To manage potential conflict of land uses, we study here the current density of this palm tree in different habitats, based on a combination of field data and remote sensing data. Firstly, we checked that the field survey methodology (i.e., counting free-trunk palm trees over 20 cm in circumference) provides density values compatible with those stemming from satellite images interpretation. We can see then that, a PA-Benfica Brazilian territory revealed an average density of the babassu lower in pastures (2.86 ind/ha) than in the dense forest (4.72 ind/ha) from which they originate and than in fallow land (4.31 ind/ha). We analyze in detail density data repartition in three habitats and we discuss results from the literature on the density of this palm tree versus its resilience at different developmental stages after forest clearing, depending on anthropogenic-or not-factors, including solar radiation, fire, weeding, clear cutting, burying fruit, and competition with forage grass. All these results can be exploited for the design of future management plans for the babassu palm and we think that the linked methodology and interdisciplinary approach can be extended to others palms and trees species in similar problematic issues.

Outcome and risk factors assessment for adverse events in advanced esophageal cancer patients after self-expanding metal stents placement.

Self-expanding metal stents (SEMS) are the treatment of choice for advanced esophageal cancers. Literature is scarce on risk factors predictors for adverse events after SEMS placement. Assess risk factors for adverse events after SEMS placement in advanced esophageal cancer and evaluate survival after SEMS placement. Cross-sectional study of patients with advanced esophageal cancer referred for SEMS placement, during a period of 3 years. Ninety-seven patients with advanced esophageal cancer placed SEMS. Adverse events were more common when tumors were located at the level of the distal esophagus/cardia (47% vs 23%, P = 0.011, OR 3.1), with statistical significance being kept in the multivariate analysis (OR 3.1, P = 0.018). Time until adverse events was lower in the tumors located at the level of the distal esophagus/cardia (P = 0.036). Survival was higher in patients who placed SEMS with curative intent (327 days [126-528] vs. 119 days [91-147], P = 0.002) and in patients submitted subsequently to surgery compared with those who did just chemo/radiotherapy or who did not do further treatment (563 days [378-748] vs. 154 days [133-175] vs. 46 days [20-72], P < 0.001). Subsequent treatment kept statistical significance in the multivariate analysis (HR 3.4, P < 0.001). SEMS allow palliation of dysphagia in advanced esophageal cancer and are associated with an increased out-of-hospital survival, as long as there are conditions for further treatments. Tumors located at the level of the distal esophagus/cardia are associated with a greater number of adverse events, which also occur earlier.

Inflammation, neurotrophism and oxidative stress and childhood psychopathology in a large community sample.

OBJECTIVE: To investigate the association between peripheral biomarkers and child psychopathology in a large community sample. METHOD: A total of 625 aged 6- to 13-year old subjects were recruited from a community school-based study. Psychopathology was assessed using the Child Behaviour Checklist (CBCL). Psychiatric diagnosis was evaluated using the Development and Well-Being Assessment. The following biomarkers were examined in peripheral blood: brain-derived neurotrophic factor, cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-g, and TNF-α), chemokines (eotaxin/CCL11, IP-10, MCP-1), cytokine receptors (sTNFR1 and sTNFR2), and the oxidative stress marker TBARS. RESULTS: We found significant associations between sTNFR2, eotaxin/CCL11 and CBCL total score, as well as with specific dimensions of psychopathology. There were different patterns of association between these biomarkers and psychological and behavioural symptoms in children with and without a mental disorder. TBARS, IL-6 and MCP-1 were more specific to some clusters of symptoms in children with a psychiatric diagnosis. CONCLUSION: Our data support the potential use of biomarkers, especially those involved in immune-inflammatory pathways, in investigating neurodevelopmental psychopathology. Their association with different dimensions of symptoms might be of useful when analyzing illness severity and clusters of symptoms within specific disorders.

Is the tiger shark Galeocerdo cuvier a coastal species? Expanding its distribution range in the Atlantic Ocean using at-sea observer data.

The occurrence of tiger shark Galeocerdo cuvier in the Atlantic Ocean was assessed using at-sea observer data from multiple pelagic longline fisheries. Geographic positions of 2764 G. cuvier recorded between 1992 and 2013 and covering a wide area of the Atlantic Ocean were compared with the currently accepted distribution ranges of the species. Most records fell outside those ranges in both the Southern and Northern Hemispheres, which strongly suggests that the distribution range of G. cuvier in the open ocean is considerably larger than previously described.

Loss of mitochondrial SDHB expression: what is its role in diffuse thyroid lipomatosis?

Diffuse lipomatosis of the thyroid gland is a very rare disease, characterized by extensive infiltration of thyroid parenchyma by mature adipose tissue, usually not accompanied by amyloid fibrils deposition. The pathophysiology of adipose tissue infiltration in the thyroid gland remains unknown. We report a clinical case of a diffuse thyroid lipomatosis, whose immunohistochemical study of succinate dehydrogenase - subunit B (SDHB) revealed loss of expression of this protein in the follicular or adipose cells. We detected the presence of a recently described SDHB gene large deletion. Loss of mitochondrial SDHB expression may have a key role in understanding the pathophysiology of thyrolipomatosis, by regulating status of lipid metabolism.

Infliximab therapy increases the frequency of circulating CD16(+) monocytes and modifies macrophage cytokine response to bacterial infection.

Crohn's disease (CD) has been correlated with altered macrophage response to microorganisms. Considering the efficacy of infliximab treatment on CD remission, we investigated infliximab effects on circulating monocyte subsets and on macrophage cytokine response to bacteria. Human peripheral blood monocyte-derived macrophages were obtained from CD patients, treated or not with infliximab. Macrophages were infected with Escherichia coli, Enterococcus faecalis, Mycobacterium avium subsp. paratuberculosis (MAP) or M. avium subsp avium, and cytokine levels [tumour necrosis factor (TNF) and interleukin (IL)-10] were evaluated at different time-points. To evaluate infliximab-dependent effects on monocyte subsets, we studied CD14 and CD16 expression by peripheral blood monocytes before and after different infliximab administrations. We also investigated TNF secretion by macrophages obtained from CD16(+) and CD16(-) monocytes and the frequency of TNF(+) cells among CD16(+) and CD16(-) monocyte-derived macrophages from CD patients. Infliximab treatment resulted in elevated TNF and IL-10 macrophage response to bacteria. An infliximab-dependent increase in the frequency of circulating CD16(+) monocytes (particularly the CD14(++) CD16(+) subset) was also observed (before infliximab: 4·65 ± 0·58%; after three administrations: 10·68 ± 2·23%). In response to MAP infection, macrophages obtained from CD16(+) monocytes were higher TNF producers and CD16(+) macrophages from infliximab-treated CD patients showed increased frequency of TNF(+) cells. In conclusion, infliximab treatment increased the TNF production of CD macrophages in response to bacteria, which seemed to depend upon enrichment of CD16(+) circulating monocytes, particularly of the CD14(++) CD16(+) subset. Infliximab treatment of CD patients also resulted in increased macrophage IL-10 production in response to bacteria, suggesting an infliximab-induced shift to M2 macrophages.

Childhood maltreatment and inflammatory markers: a systematic review.

OBJECTIVE: Childhood maltreatment (CM) has been associated with several diseases in adult life, including diabetes, obesity and mental disorders. Inflammatory conditions have been postulated as possible mediators of this relationship. The aim was to conduct a systematic review regarding the association between CM and inflammatory markers in adulthood. METHOD: A literature search of the PubMed, ISI, EMBASE and PsychINFO databases was conducted. The key terms used were as follows: 'Child Maltreatment', 'Childhood Trauma', 'Early Life Stress', 'Psychological Stress', 'Emotional Stress', 'Child Abuse' and 'Child Neglect'. They were cross-referenced separately with the terms: 'C-reactive Protein (CRP)', 'Tumor Necrosis Factor', 'Cytokine', 'Interleukin', 'Inflammatory' and 'Inflammation'. RESULTS: Twenty articles remained in the review after exclusion criteria were applied. Studies showed that a history of CM was associated with increased levels of CRP, fibrinogen and proinflammatory cytokines. Increased levels of circulating CRP in individuals with a history of CM were the most robust finding among the studies. Data about anti-inflammatory mediators are still few and inconsistent. CONCLUSION: Childhood maltreatment is associated with a chronic inflammatory state independent of clinical comorbidities. However, studies are heterogeneous regarding CM assessment and definition. Important methodological improvements are needed to better understand the potential impact of CM on inflammatory response.

Impact of disclosure of radiographic test results on quality of life among patients with hernias: a randomized controlled trial.

PURPOSE: Hernias noted on radiographic imaging are common. We aimed to determine if informing patients of the presence of a clinically apparent or occult hernia on imaging would change their abdominal wall quality of life (AW-QOL). METHODS: This study was registered on clinicaltrials.gov (NCT04355819) in April 2020. Patients with a ventral hernia on elective CT abdomen/pelvis were enrolled. Patients underwent standardized abdominal examination by surgeons, and completed the modified Activities Assessment Scale, a validated, hernia-specific AW-QOL survey. On this scale, 1 is poor AW-QOL, 100 is perfect, and the minimally clinically important difference is five for a minor change. Patients were randomized to complete the one-year follow-up survey before or after being informed of the presence of a hernia on their imaging results. Primary outcome was follow-up AW-QOL adjusted for baseline AW-QOL. RESULTS: Of 169 patients randomized, 126 (75%) completed follow up at one-year. Among patients with occult hernias, those who completed the follow-up survey after being informed of having a hernia had a lower follow-up AW-QOL (mean difference - 7.6, 95% CI = - 20.8 to 5.7, p = 0.261) compared to those who completed the survey before being informed. Conversely, for patients with clinical hernias, those who completed the survey after being informed had higher adjusted follow-up AW-QOL (mean difference 10.3, 95% CI = - 3.0 to 23.6, p = 0.126) than those that completed it after. CONCLUSION: Conveying findings of hernias found on CT imaging can influence patients' AW-QOL. Future research should focus on identifying and addressing patients' concerns after disclosure of CT results.

Short-chain fatty acids inhibit the activation of T lymphocytes and myeloid cells and induce innate immune tolerance.

The intestinal microbiota contributes to gut immune homeostasis, where short-chain fatty acids (SCFAs) function as the major mediators. We aimed to elucidate the immunomodulatory effects of acetate, propionate, and butyrate. With that in mind, we sought to characterise the expression of SCFA receptors and transporters as well as SCFAs' impact on the activation of different immune cells. Whereas all three SCFAs decreased tumour necrosis factor (TNF)-α production in activated T cells, only butyrate and propionate inhibited interferon (IFN)-γ, interleukin (IL)-17, IL-13, and IL-10 production. Butyrate and propionate inhibited the expression of the chemokine receptors CCR9 and CCR10 in activated T- and B-cells, respectively. Similarly, butyrate and propionate were effective inhibitors of IL-1ß, IL-6, TNF-α, and IL-10 production in myeloid cells upon lipopolysaccharide and R848 stimulation. Acetate was less efficient at inhibiting cytokine production except for IFN-α. Moreover, SCFAs inhibited the production of IL-6 and TNF-α in monocytes, myeloid dendritic cells (mDC), and plasmacytoid dendritic cells (pDC), whereas acetate effects were relatively more prominent in pDCs. In monocytes and mDCs, acetate was a less efficient inhibitor, but it was equally effective in inhibiting pDCs activation. We also studied the ability of SCFAs to induce trained immunity or tolerance. Butyrate and propionate - but not acetate - prevented Toll-like receptor-mediated activation in SCFA-trained cells, as demonstrated by a reduced production of IL-6 and TNF-α. Our findings indicate that butyrate and propionate are equally efficient in inhibiting the adaptive and innate immune response and did not induce trained immunity. The findings may be explained by differential SCFA receptor and transporter expression profiles of the immune cells.

Crystallization and preliminary crystallographic studies of FoxE from Rhodobacter ferrooxidans SW2, an Fe(II) oxidoreductase involved in photoferrotrophy.

FoxE is a protein encoded by the foxEYZ operon of Rhodobacter ferrooxidans SW2 that is involved in Fe(II)-based anoxygenic photosynthesis (`photoferrotrophy'). It is thought to reside in the periplasm, where it stimulates light-dependent Fe(II) oxidation. It contains 259 residues, including two haem c-binding motifs. As no three-dimensional model is available and there is no structure with a similar sequence, crystals of FoxE were produced. They diffracted to 2.44 Å resolution using synchrotron radiation at the Fe edge. The phase problem was solved by SAD using SHELXC/D/E and the experimental maps confirmed the presence of two haems per molecule.

High-grade anal intraepithelial neoplasia treated with endoscopic submucosal dissection: a case report.

Anal intraepithelial neoplasia is a premalignant lesion for anal squamous cell carcinoma. Current treatment options, consisting of topical therapy and local ablative procedures with electrocautery or radiofrequency ablation, are effective although recurrence rates are high. Experience with endoscopic submucosal dissection for anal lesions is limited, with only a few cases of anal intraepithelial neoplasia and early anal squamous cell carcinoma. We present a 65-year-old woman with high-grade anal intraepithelial neoplasia successfully removed by endoscopic submucosal dissection with no complications or signs of recurrence after 5 months, suggesting that this technique could be a safe and effective approach for management of anal premalignant lesions.

Risk factors and clinical outcomes of acute esophageal necrosis: retrospective case series of a rare disease with "black" prognosis.

Acute esophageal necrosis is a rare syndrome classically characterized by black distal esophagus with a complex pathophysiology that usually involves a combination of esophageal ischemia, gastroesophageal reflux and impaired mucosal reparative mechanisms. We retrospectively analyzed the main risk factors, clinical characteristics and outcome in all patients diagnosed with acute esophageal necrosis between January 2015 and December 2020 at our center. Ten patients were identified in a total of 26854 upper digestive endoscopies (0.04%). Most patients were male (8/10) and the mean age of presentation was 71.1 years. The most common presenting symptoms were melena and hematemesis and half the patients required red blood cell transfusion. The most common risk factors were hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, peripheral artery disease, coronary artery disease, cerebrovascular disease, heart failure and malignancy. Compromised hemodynamic state was the most common precipitating event in four patients. Other recognized precipitating events included surgical interventions, decompensated heart failure, gastrointestinal bleeding from gastric malignancy and methotrexate. Endoscopic findings revealed diffuse and circumferential black distal esophagus with abrupt transition at gastroesophageal junction and variable proximal extension at presentation. The 1-month mortality rate was 30%, mostly from severe underlying illness. In conclusion, acute esophageal necrosis is a rare cause of upper gastrointestinal bleeding that should be suspected in older patients with multiple comorbidities. Although associated with a high mortality rate, appropriate treatment may result in favorable outcome in most patients.

Exosomal glypican-1 discriminates pancreatic ductal adenocarcinoma from chronic pancreatitis.

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) diagnosis can be difficult in a chronic pancreatitis (CP) background, especially in its mass forming presentation. We aimed to assess the accuracy of glypican-1-positive circulating exosomes (GPC1+crExos) to distinguish PDAC from CP versus the state-of-the-art CA 19-9 biomarker. METHODS: This was a unicentric prospective cohort. Endoscopic ultrasound with fine-needle aspiration or biopsy and blood tests (GPC1+crExos and serum CA 19-9) were performed. RESULTS: The cohort comprised 60 PDAC and 29 CP (7 of which mass forming - MF) patients. Median levels of GPC1+crExos were significantly higher in PDAC (99.7%) versus CP (28.4%; p<0.0001) with an AUROC of 0.96 with 98.3% sensitivity and 86.2% specificity for a cut-off of 45.0% (p<0.0001); this outperforms CA 19-9 AUROC of 0.82 with 78.3% sensitivity and 65.5% specificity at a cut-off of 37 U/mL (p<0.0001). The superiority of% GPC1+crExos over CA 19-99 in differentiating PDAC from CP was observed in both early (stage I) and advanced tumors (stages II-IV). CONCLUSION: Levels of GPC1+crExos coupled to beads enable differential diagnosis between PDAC and CP including its mass-forming presentation.