Symptom Clusters in Patients With Advanced Cancer: A Prospective Longitudinal Cohort Study to Examine Their Stability and Prognostic Significance.

This study's purpose was to assess symptom cluster (SC) stability during disease progression and determine their strength of association with survival in patients with advanced cancer . Consecutively eligible patients with advanced cancer not receiving cancer-specific treatment and referred to a Tertiary Palliative Care Clinic were enrolled in a prospective cohort study. At first consultation (D0) and in subsequent consultations at day 15 (D15) and day 30 (D30), patients rated 9 symptoms through the Edmonton Symptom Assessment System scale (0-10) and 10 others using a Likert scale (1-5). Principal components factor analysis with varimax rotation was used to determine SCs at each consultation. Of 318 patients with advanced cancer, 301 met eligibility criteria with a median age of 69 years (range 37-94). Three SCs were identified: neuro-psycho-metabolic (NPM), gastrointestinal, and sleep impairment, with some variations in their constitution over time. Exploratory factor analysis accounted for 40% of variance of observed variables in all SCs. Shorter median survival was observed continuously for NPM cluster (D0 23 vs. 58 days, P < .001; D15 41 vs. 104 days, P=.004; D30 46 vs. 114 days, P = .002), although the presence of 2 or more SCs on D0 and D15 also had prognostic significance (D0: 21 vs. 45 days, P = .005; D30: 50 vs. 96 days, P = .040). In a multivariable model, NPM cluster (D0 hazard ratio estimate: HR 1.64; 95%CI, 1.17-2.31; P = .005; D15 HR: 2.51; 95%CI, 1.25-5.05; P = .009; D30 HR: 3.9; 95%CI, 1.54-9.86; P = .004) and hospitalization (D0 HR: 2.27; 95%CI, 1.47-3.51; P < .001; D15 HR: 2.43; 95%CI, 1.18-5.01; P = .016; D30 HR: 3.41; 95%CI, 1.35-8.62; P = .009) were independently and significantly associated with worse survival. Three clinically relevant SCs were identified, and their constitution had small variations, maintaining a stable set of nuclear symptoms through disease progression. Presence of the NPM cluster and hospitalization maintained their prognostic value over time.

First-trimester serum biomarkers in twin pregnancies and adverse obstetric outcomes-a single center cohort study.

PURPOSE: This study aimed to determine the association of first-trimester maternal serum biomarkers with preterm birth (PTB), fetal growth restriction (FGR) and hypertensive disorders of pregnancy (HDP) in twin pregnancies. METHODS: This is a retrospective cohort study of twin pregnancies followed at Maternidade Dr. Alfredo da Costa, Lisbon, Portugal, between January 2010 and December 2022. We included women who completed first-trimester screening in our unit and had ongoing pregnancies with two live fetuses, and delivered after 24 weeks. Maternal characteristics, pregnancy-associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG) levels were analyzed for different outcomes: small for gestational age (SGA), gestational hypertension (GH), early and late-onset pre-eclampsia (PE), as well as the composite outcome of PTB associated with FGR and/or HDP. Univariable, multivariable logistic regression analyses and receiver-operating characteristic curve were used. RESULTS: 466 twin pregnancies met the inclusion criteria. Overall, 185 (39.7%) pregnancies were affected by SGA < 5th percentile and/or HDP. PAPP-A demonstrated a linear association with gestational age at birth and mean birth weight. PAPP-A proved to be an independent risk factor for SGA and PTB (< 34 and < 36 weeks) related to FGR and/or HDP. None of the women with PAPP-A MoM > 90th percentile developed early-onset PE or PTB < 34 weeks. CONCLUSION: A high serum PAPP-A (> 90th percentile) ruled out early-onset PE and PTB < 34 weeks. Unless other major risk factors for hypertensive disorders are present, these women should not be considered candidates for aspirin prophylaxis. Nevertheless, close monitoring of all TwP for adverse obstetric outcomes is still recommended.

Does Fetal Growth Adequacy Affect the Nutritional Composition of Mothers' Milk?: A Historical Cohort Study.

OBJECTIVE: The study aimed to assess the association between intrauterine growth of preterm infants and energy and macronutrient contents in their mothers' milk. STUDY DESIGN: A historical cohort of mothers of preterm infants was assessed according to offspring's intrauterine growth. Fetal growth restriction (FGR) was defined as small-for-gestational age or appropriate for gestational age with fetal growth deceleration. During the first 4 weeks after delivery, the composition of daily pool samples of mothers' milk was measured by using a mid-infrared human milk analyzer. Explanatory models for milk energy, true protein, total carbohydrate, and fat contents were obtained by generalized additive mixed effects regression models. RESULTS: In total, 127 milk samples were analyzed from 73 mothers who delivered 92 neonates. Energy content was significantly higher in mothers with chronic hypertension (average: +6.28 kcal/dL; 95% confidence interval [CI]: 0.54-12.01; p = 0.034) and for extremely preterm compared with very preterm infants (average: +5.95 kcal/dL; 95% CI: 2.16-9.73; p = 0.003), and weakly associated with single pregnancies (average: +3.38 kcal/dL; 95% CI: 0.07-6.83; p = 0.057). True protein content was significantly higher in mothers with chronic hypertension (average: +0.91 g/dL; 95% CI: 0.63-1.19; p < 0.001) and with hypertension induced by pregnancy (average: +0.25 g/dL, 95% CI: 0.07-0.44; p = 0.007), and for extremely preterm compared with very and moderate preterm infants (average: +0.19; 95% CI: 0.01-0.38; p = 0.043 and +0.28 g/dL; 95% CI: 0.05-0.51; p = 0.017, respectively). Fat content was weakly and negatively associated with FGR, both in SGA infants and AGA infants with fetal growth deceleration (average: -0.44 g/dL; 95% CI: -0.92 to -0.05; p = 0.079 and average: -0.36 g/dL; 95% CI: -0.74 to -0.02; p = 0.066, respectively). CONCLUSION: Energy and macronutrient contents in mothers' milk of preterm infants was significantly and positively associated with the degree of prematurity and hypertension. The hypothesis that the composition of milk is associated with FGR was not demonstrated. KEY POINTS: · Energy and protein are higher for more immature infants.. · Energy and/or protein is higher in hypertension.. · Fat may be lower for infants with intrauterine growth restriction..

Optimism and fear of COVID-19 in higher education students: the mediating role of general anxiety.

Higher education students have faced several changes in their lives due to the COVID-19 pandemic. This study aims to explore the effect of dispositional optimism in students' fear of COVID-19 and to test the mediating role of general anxiety in the relationship between optimism and fear. Using an online survey, data were collected during the second wave of the pandemic in Portugal. The sample included 312 higher education students (76% females) aged 18-25 years old, who completed measures of dispositional optimism, general anxiety and fear of COVID-19. The results showed that higher optimism and lower general anxiety reduce fear of COVID-19. Moreover, the link between optimism and fear is fully mediated by general anxiety, showing that optimism reduces fear of COVID-19 indirectly through the reduction of students' anxiety. The role of optimism, anxiety and fear in higher education students is discussed and topics for further research are presented.

Predictors of anaphylaxis to peanut and tree nuts in a Mediterranean population.

Background: Peanuts (PN) and tree nuts (TN) are major causes of anaphylaxis worldwide. We aimed to determine the clinical and demographic characteristics associated with anaphylaxis in patients sensitized to PN and/or TN in a Mediterranean population. Methods: We conducted a retrospective study, which included 198 patients allergic to PN and/or TN (allergy symptoms plus specific immunoglobulin E [sIgE] sensitization), evaluated in consultations from January 2015 to December 2020. Univariate analysis and multivariate logistic regression models were developed, including demographic, clinical, and laboratory data as independent variables, and anaphylaxis to each PN and/or TN as a dependent variables. Results: Anaphylaxis was associated with an earlier age of onset of allergy to PN, cashew and/or pistachio, and pine nut allergy but not to other TN allergies. Gender, atopic comorbidities, and cofactors were not associated with PN and/or TN anaphylaxis. Anaphylaxis to PN, cashew and/or pistachio, and pine nut were associated with reactivity to a fewer number of PN and/or TN foods. Although sIgE sensitization to lipid transfer proteins (LTP) was highly prevalent in our population, only seed storage protein (SSP) positivity was associated with anaphylaxis in PN allergy. The absence of pathogenesis-related protein family 10 sensitization correlated with PN and hazelnut anaphylaxis. A higher level of sIgE to almond extract predicted anaphylaxis but the level of sIgE to other PN and/or TN extracts did not predict it. Conclusion: The high prevalence of sensitization to the pan-allergen LTP did not seem to have a significant impact in PN and/or TN allergy severity in our study. Instead, other factors, such as early age of onset and positivity for SSPs, seem to strongly associate with anaphylaxis to specific PN and/or TN. These findings may contribute to individual risk assessment in these populations.

Previous Disability and Benefit of Acute Phase Therapy in Functional Prognosis of Selected Patients with Ischemic Stroke.

OBJECTIVES: Patients' previous disability (PD) is a key factor when considering acute stroke therapy. PD's exact impact on functional prognosis of patients with acute ischemic stroke remains not entirely clarified. We aimed to analyze PD's influence on functional outcome three months after ischemic stroke. MATERIALS AND METHODS: Retrospective analysis of prospectively collected data concerning patients with acute ischemic stroke admitted to Stroke Unit of a tertiary center who underwent acute phase therapy between 2017 and 2019. Modified Rankin Scale (mRS) was used to define PD (with previous mRS≥3). Patients with PD were selected for treatment based on similar baseline characteristics to patients without PD. Patients were classified into two groups according to previous mRS: mRS<3 and mRS≥3. We defined bad outcome at three months after stroke as mRS≥3 for patients with previous mRS<3, and as a higher score than baseline mRS for patients with previous mRS≥3. RESULTS: We identified 1169 eligible patients - 1016 patients with previous mRS<3 and 153 patients with previous mRS≥3. Most baseline characteristics did not differ significantly between them. For patients ≤75 years old, PD was associated with worse outcome (odds ratio estimate [OR] 4.50, p < 0.001). For patients >75 years old, PD was protective against worse outcome (OR 0.42, p < 0.001). In patients with previous mRS≥3 and >75 years old, there was a higher proportion of women (p = 0.005). CONCLUSIONS: PD might not be a relevant factor when considering acute stroke therapy in selected patients >75 years old, especially women. Further studies are needed to clarify these findings.

Acute Treatment of Isolated Posterior Cerebral Artery Occlusion: Single Center Experience.

BACKGROUND AND OBJECTIVES: Randomized trials for mechanical thrombectomy (MT) excluded patients with ischemic strokes due to isolated posterior cerebral artery occlusion (IPCAO), and there is no evidence for best acute treatment strategy in these patients. We aimed to assess the effectiveness and safety of MT in acute IPCAO. METHODS: We retrospectively analyzed consecutive patients with acute stroke due to IPCAO submitted to MT and/or intravenous thrombolysis (IVT), between 2015-2019. Effectiveness outcomes (recanalization rate, first-pass effect, NIHSS 24h improvement and 3-month Modified Ranking Scale - mRS) and safety outcomes (complications, symptomatic intracranial hemorrhage (SICH) and 3-month mortality) were described and compared between groups. RESULTS: A total of 38 patients were included, 25 underwent MT and 13 had IVT alone. Successful and complete recanalization were achieved in 68% and 52% of MT patients, respectively. NIHSS improvement at 24h was found in 56% of MT patients versus 30.8% of patients submitted to IVT alone (OR [95% CI]=2.86 [0.69-11.82]) and excellent functional outcome at 3 months (mRS≤1) was achieved in 54.2% of MT patients versus 38.5% in the IVT group (OR [95% CI]=1.60 [0.41-6.32]). Complications occurred in 3 (12%) procedures and there were no SICH. Mortality at 3 months was 20% in the MT group and 15.4% in patients submitted to IVT alone. CONCLUSIONS: Our results reflect a real-world scenario in a single center and seem to support the recently growing literature showing that MT is a feasible and safe treatment in IPCAO, with favorable effectiveness.

Retinal structural changes in preterm children without retinopathy of prematurity.

PURPOSE: The aim of this study was to compare all retinal layers' thickness in full-term and preterm children without retinopathy of prematurity (ROP). METHODS: Cross-sectional study including two groups of patients: group 1 children with history of preterm gestation without ROP (gestational age < 37 weeks) and group 2 healthy children with history of full-term gestation. All subjects underwent an ophthalmic examination including spectral domain-optical coherence tomography. After automatic retinal segmentation, each retinal layer thickness (eight separate layers and overall thickness) was calculated in all nine Early Treatment Diabetic Retinopathy Study areas. Demographic, systemic, gestational, and birth data were collected. Generalized additive regression models were used to analyze the data. RESULTS: Fifty-one children (51 eyes) were recruited, 19 full-term and 32 preterm children, mean age at ophthalmic examination of 10.58 (4.21) and 14.13 (3.16), respectively. In multivariable analysis, the preterm group's retinal thickness was significantly decreased in total retina nasal outer sector, ganglion cell layer (GCL), and inner plexiform layer (IPL), specifically GCL temporal outer (p = 0.010), GCL superior outer (p = 0.009), IPL temporal outer (p = 0.022), and IPL superior outer (p = 0.004), when compared with full-term group. From the variables compared only with birth head circumference that influenced the models, a non-linear association was identified and consequently modeled with splines through a generalized additive model. CONCLUSION: This study suggests that preterm children without ROP have structural retinal alterations, mostly in GCL and IPL in outer areas of the macula. Therefore, it is crucial to question gestational history since these retinal changes may be found later in life leading to useless investigation.

Better balance: a randomised controlled trial of oculomotor and gaze stability exercises to reduce risk of falling after stroke.

OBJECTIVE: To assess the effect of a domiciliary program of oculomotor and gaze stability exercises on the incidence of falls and risk of fall in stroke survivors. DESIGN: Two-arm, non-blinded parallel randomized controlled trial. SUBJECTS: Stroke survivors older than 60 years, with positive Romberg test and autonomous gait after the stroke. SETTING: Physiotherapy outpatient clinic of a tertiary care hospital. INTERVENTIONS: Every participant accomplished the current rehabilitation program; the intervention group was randomly allocated into an additional three weeks intervention with a domiciliary program of oculomotor and gaze stability exercises. MAIN MEASURES: Primary outcome was the incidence of falls through the three weeks after the intervention started; in addition, the variation of the estimated risk for falling assessed by both Berg Balance Scale (four points) and Timed Up and Go Test (four seconds) was the secondary outcome. RESULTS: 79 patients were recruited and 68 completed the protocol (control group 35; intervention group 33). During the follow up, falls were registered in 4/35 participants in the control group and no event occurred in the intervention group (P = 0.064). The estimated risk for falling decreased in 11/35 control group participants and in 28/33 intervention group participants (RR 0.37; 95%CI 0.22-0.62; P < 0.001). CONCLUSION: After three weeks of a domiciliary program of oculomotor and gaze stability exercises, the estimated risk of falling significantly diminished and no falls occurred among the intervention group. These findings encourage further exploration of this promising intervention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02280980.

Functional Outcome After Mechanical Thrombectomy with or without Previous Thrombolysis.

INTRODUCTION: Combined intravenous therapy (IVT) and mechanical thrombectomy (MT) is the standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO). However, the use of  IVT before MT is recently being questioned. OBJECTIVES: To compare patients treated with IVT before MT with those treated with MT alone, in a real-world scenario. METHODS: Retrospective analysis of AIS patients with LVO of the anterior circulation who underwent MT, with or without previous IVT, between 2016 and 2018. RESULTS: A total of 524 patients were included (347 submitted to IVT+MT; 177 to MT alone). No differences between groups were found except for a higher time from stroke onset to CT and to groin puncture in the MT group (297.5 min vs 115.0 min and 394.0 min vs 250.0 min respectively, p < 0.001). Multivariable analysis showed that age<75 years (OR 2.65, 95% CI 1.71-4.07, p < 0.001), not using antiplatelet therapy (OR 1.93, 95% CI 1.21-3.08, p = 0.006), low prestroke mRS (OR 4.33, 95% CI 1.89-9.89, p < 0.001), initial NIHSS (OR 0.89, 95% CI 0.86-0.93, p < 0.001), absent cerebral edema (OR 7.83, 95% CI 3.31-18.51, p < 0.001), and mTICI 2b/3 (OR 4.56, 95% CI 2.17-9.59, p < 0.001) were independently associated with good outcome (mRS 0-2). CONCLUSIONS: Our findings support the idea that IVT before MT does not influence prognosis, in a real-world setting.

Self-Assembly Nanoparticles of Natural Bioactive Abietane Diterpenes.

Different approaches have been reported to enhance penetration of small drugs through physiological barriers; among them is the self-assembly drug conjugates preparation that shows to be a promising approach to improve activity and penetration, as well as to reduce side effects. In recent years, the use of drug-conjugates, usually obtained by covalent coupling of a drug with biocompatible lipid moieties to form nanoparticles, has gained considerable attention. Natural products isolated from plants have been a successful source of potential drug leads with unique structural diversity. In the present work three molecules derived from natural products were employed as lead molecules for the synthesis of self-assembled nanoparticles. The first molecule is the cytotoxic royleanone 7α-acetoxy-6ß-hydroxyroyleanone (Roy, 1) that has been isolated from hairy coleus (Plectranthus hadiensis (Forssk.) Schweinf). ex Sprenger leaves in a large amount. This royleanone, its hemisynthetic derivative 7α-acetoxy-6ß-hydroxy-12-benzoyloxyroyleanone (12BzRoy, 2) and 6,7-dehydroroyleanone (DHR, 3), isolated from the essential oil of thicket coleus (P. madagascariensis (Pers.) Benth.) were employed in this study. The royleanones were conjugated with squalene (sq), oleic acid (OA), and/or 1-bromododecane (BD) self-assembly inducers. Roy-OA, DHR-sq, and 12BzRoy-sq conjugates were successfully synthesized and characterized. The cytotoxic effect of DHR-sq was previously assessed on three human cell lines: NCI-H460 (IC50 74.0 ± 2.2 µM), NCI-H460/R (IC50 147.3 ± 3.7 µM), and MRC-5 (IC50 127.3 ± 7.3 µM), and in this work Roy-OA NPs was assayed against Vero-E6 cells at different concentrations (0.05, 0.1, and 0.2 mg/mL). The cytotoxicity of DHR-sq NPs was lower when compared with DHR alone in these cell lines: NCI-H460 (IC50 10.3 ± 0.5 µM), NCI-H460/R (IC50 10.6 ± 0.4 µM), and MRC-5 (IC5016.9 ± 0.5 µM). The same results were observed with Roy-OA NPs against Vero-E6 cells as was found to be less cytotoxic than Roy alone in all the concentrations tested. From the obtained DLS results, 12BzRoy-sq assemblies were not in the nano range, although Roy-OA NP assemblies show a promising size (509.33 nm), Pdl (0.249), zeta potential (-46.2 mV), and spherical morphology from SEM. In addition, these NPs had a low release of Roy at physiological pH 7.4 after 24 h. These results suggest the nano assemblies can act as prodrugs for the release of cytotoxic lead molecules.

Study of the activity of Punica granatum-mediated silver nanoparticles against Candida albicans and Candida glabrata, alone or in combination with azoles or polyenes.

The continuous emergence of Candida strains resistant to currently used antifungals demands the development of new alternatives that could reduce the burden of candidiasis. In this work silver nanoparticles synthesized using a green route are efficiently used, alone or in combination with fluconazole, amphotericin B or nystatine, to inhibit growth of C. albicans and C. glabrata oral clinical strains, including in strains showing resistance to fluconazole. A potent inhibitory effect over biofilm formation prompted by the two Candida species was also observed, including in mature biofilm cells. These results foster the use of phytotherapeutics as effective treatments in oral candidiasis.

Mechanical thrombectomy in stroke in nonagenarians: useful or futile?

BACKGROUND: Mechanical thrombectomy is the standard treatment in acute ischemic stroke due to large vessel occlusion, but there is limited evidence about its efficacy in very old patients. We sought to analyse safety and effectiveness of mechanical thrombectomy in nonagenarian versus octagenarian patients. METHODS: We included consecutive patients with acute ischemic stroke due to large vessel occlusion subjected to mechanical thrombectomy, during 29 months in a tertiary center. Patients were divided into two sub-groups, according to age: 80-89 and >90 years old. Recanalization, complications, functional outcome and mortality at discharge and at 3 months were compared. Multivariable analysis was performed to identify independent predictors of functional outcome at 3 months of follow-up, assessed by the modified Rankin Scale. RESULTS: A total of 128 octogenarians (88.9%) and 16 nonagenarians (11.1%) met the inclusion criteria. Successful revascularization was achieved in 87.5% of octagenarians and in 81.3% of nonagenarians (p = 0.486). Symptomatic hemorrhage occurred in 3.1% and 6.3% of younger and older patients, respectively (p = 0.520). Cerebral edema occured in 35.2% of octagenarians versus 25.0% of nonagenarians (p = 0.419). Functional independence (mRS ≤ 2) at 3 months was achieved in 28 (22.6%) and 5 (31.3%) of octagenarians and nonagenarians, respectively (p = 0.445). Mortality at 3 months was not significantly higher in nonagenarians (37.5%) versus octagenarians (33.9%, p = 0.773). CONCLUSIONS: No significant diferences were found in functional outcome, mortality, recanalization and complication rates between octagenarians and nonagenarians submitted to mechanical thrombectomy, underlining that patients should not be excluded from mechanical thrombectomy based on age alone.

Economic losses caused by the use of low-efficacy anthelmintic drugs in growing heifers.

The aim of this study was to compare the economic revenue related to the use of low- or high-efficacy anthelmintic drugs within suppressive or strategic schemes of treatment in growing heifers. Heifers raised in a semi-intensive grazing system in southern Brazil were used. Levamisole and ivermectin were selected as the high- and the low-efficacy drugs, respectively, based on a previous efficacy test. Subsequently, these drugs were used within strategic (Strat; four times per year) or suppressive (Supp; once a month) treatment regimens in the heifers, and their liveweight and eggs per gram of feces counts were monthly evaluated during a 13-month period. The total costs of the treatments and their cost-benefit ratio in regard to liveweight gain were calculated. Final mean liveweight gains (kg) observed were 126.7 (Strat-Low), 133.6 (Supp-Low), 141.3 (Strat-High), 142.9 (Supp-High), and 125.8 (Control). Treatments with a high-efficacy drug resulted in monetary gains of US$ 19.56 (Strat-High) and US$ 14.98 (Supp-High), but Supp-Low and Strat-Low treatments caused economic losses. Total cost of the efficacy test (US$ 374.79) could be paid by the additional liveweight gain of 20 heifers from the Strat-High group. These results showed that it would be preferable not to treat the heifers against GIN if compared with treating them with a low-efficacy drug. In addition, we showed that the use of four treatments per year with a high-efficacy drug-selected by efficacy test-resulted in a profitable management to control GIN in growing heifers raised in a semi-intensive gazing system in southern Brazil.

Biofluid quantification of TWEAK/Fn14 axis in combination with a selected biomarker panel improves assessment of prostate cancer aggressiveness.

BACKGROUND: Conventional clinical biomarkers cannot accurately differentiate indolent from aggressive prostate cancer (PCa). We investigated the usefulness of a biomarker panel measured exclusively in biofluids for assessment of PCa aggressiveness. METHODS: We collected biofluid samples (plasma/serum/semen/post-prostatic massage urine) from 98 patients that had undergone radical prostatectomy. Clinical biochemistry was performed and several cytokines/chemokines including soluble(s) TWEAK, sFn14, sCD163, sCXCL5 and sCCL7 were quantified by ELISA in selected biofluids. Also, the expression of KLK2, KLK3, Fn14, CD163, CXCR2 and CCR3 was quantified by real-time PCR in semen cell sediment. Univariate, logistic regression, and receiver operating characteristic (ROC) analyses were used to assess the predictive ability of the selected biomarker panel in conjunction with clinical and metabolic variables for the evaluation of PCa aggressiveness. RESULTS: Total serum levels of prostate-specific antigen (PSA), semen levels of sTWEAK, fasting glycemia and mRNA levels of Fn14, KLK2, CXCR2 and CCR3 in semen cell sediment constituted a panel of markers that was significantly different between patients with less aggressive tumors [International Society of Urological Pathology (ISUP) grade I and II] and those with more aggressive tumors (ISUP grade III, IV and V). ROC curve analysis showed that this panel could be used to correctly classify tumor aggressiveness in 90.9% of patients. Area under the curve (AUC) analysis revealed that this combination was more accurate [AUC = 0.913 95% confidence interval (CI) 0.782-1] than a classical non-invasive selected clinical panel comprising age, tumor clinical stage (T-classification) and total serum PSA (AUC = 0.721 95% CI 0.613-0.830). CONCLUSIONS: TWEAK/Fn14 axis in combination with a selected non-invasive biomarker panel, including conventional clinical biochemistry, can improve the predictive power of serum PSA levels and could be used to classify PCa aggressiveness.

The impact of antibiotic exposure in water and zebrafish gut microbiomes: A 16S rRNA gene-based metagenomic analysis.

In order to supply human demand for food, the aquaculture industry has been growing fast in the last years, being fish usually cultivated in overcrowded conditions. Hence, to prevent the rapidly disease spreading, antibiotics may be applied to both sick and healthy animals. Due to its broad spectrum, oxytetracycline (OTC) is one of the most used antibiotics in food-production. Yet, although useful to prevent infections, antibiotics may reshape aquatic animals' microbiome, disturbing hosts' welfare. However, the impact of this exposure to the organism microbiome and its surrounding environment is poorly understood. Then, the objective of this study was to analyze in detail the long-term effect of OTC in both zebrafish gut and water microbiomes. Zebrafish adults were exposed, via water, for two months to three concentrations of OTC (0, 10 and 10000 µg/L). Total DNA was extracted from gut and water samples and the V3-V4 region of the bacterial 16 S rRNA gene was sequenced using Illumina technology. Results of alpha and beta-diversity analyses revealed that long-term exposure to OTC impacted both zebrafish gut and water microbiomes. In water samples, effects were observed even at the lowest (10 µg/L) OTC concentration tested resulting in an increase in Deltaproteobacteria, namely the Myxococcales and Bdellovibrionales orders. On the other hand, effects on zebrafish gut were only observed at the highest concentration with the selection of Alphaproteobacteria and Actinobacteria classes. Although these classes are common in fish gut, the increase of Actinobacteria may represent a health problem since some genera like Gordonia are linked to some human infection disease. Nevertheless, in both gut and water, it was observed a decrease in Gamaproteobacteria, probably due to OTC mode of action. In silico functional metagenomic analysis revealed that OTC exposure selected general detoxification mechanisms. In addition, the abundance of functional genes involved in Quorum Sensing (QS) increased under OTC exposure suggesting that QS may help bacteria to survive OTC stress. Thus, future studies should consider post-exposure scenarios for a deeper analysis of the water and zebrafish gut resistome, since bacteria may react differently after exposure ceased.

Association between glycated haemoglobin, glycated albumin and fructosamine with neonatal birthweight and large-for-date status infants in gestational diabetes mellitus: a prospective cohort study.

This study aims to investigate associations between glycated haemoglobin (HbA1c), glycated albumin (GA) and fructosamine with neonatal birthweight in gestational diabetes mellitus (GDM). The prospective cohort consisted of 82 women with GDM and their newborns, enrolled between November 2016 and September 2017. Considering neonatal birthweight and birthweights ≥90th percentile for gestational age as outcomes, linear and logistic regression models were used, respectively. Fructosamine (R2=0.62) and GA (R2=0.61) performed very similarly between them and best than HbA1c (R2=0.58). The added value of GA or fructosamine to HbA1c resulted in increase in models' performances. GA attained the best discriminative ability regarding large-for-date status babies (AUC = 0.80, OR-estimate 1.58, p=.001) followed by fructosamine (AUC = 0.78, OR-estimate 1.42, p=.001) and HbA1c (AUC = 0.69, OR-estimate 3.09, p=.070). GA and fructosamine, besides from providing additional information to HbA1c, when used separately perform better than the traditional biomarker in predicting neonatal birthweight and large-for-date babies in pregnant women with GDM. Impact statement What is already known on this subject? HbA1c is the standard glycaemic indicator used in GDM. Its association with birthweight and large-for-date status has been previously reported. However, it has become increasingly questionable whether it is a suitable glycaemic marker in pregnancy. There is a growing interest in other non-traditional shorter-term glycaemic indicators, such as GA and fructosamine. Nevertheless, few studies exist and almost all are retrospective and with ethnically homogeneous study populations composed by pregnant women not only with GDM but also type 1 and type 2 diabetes mellitus. What do the results of this study add? Our prospective multi-ethnic cohort composed solely on pregnant women with GDM and their infants show that even though all of the aforementioned biomarkers are associated with birthweight and large-for-date status in GDM when used separately, GA and fructosamine seem to perform better than HbA1c. When used with HbA1c, they improve the predicting performance of the traditional marker. What are the implications of these findings for future clinical practice and/or further research? These findings suggest that GA and fructosamine can provide important additional or substitute information to HbA1c in GDM, namely in predicting birthweight and large-for-date status babies. Larger studies are needed to confirm if this non-traditional biomarkers can change clinical practice.

The impact of indoor air quality on respiratory health of older people living in nursing homes: spirometric and exhaled breath condensate assessments.

In the Portuguese Geriatric Study of the Health Effects of Indoor Air Quality in Senior Nursing Homes, we aimed to evaluate the impact of indoor air contaminants on the respiratory symptoms and biomarkers in a sample of elderly living in nursing homes. A total of 269 elderly answered a health questionnaire, performed a spirometry and 150 out of these collected an exhaled breath condensate sample for pH and nitrites analysis. The study included the evaluation of indoor chemical and microbiological contaminants. The median age of the participants was 84 (78-87) years and 70.6% were women. The spirometric data indicated the presence of airway obstruction in 14.5% of the sample. Median concentrations of air pollutants did not exceed the existing standards, although increased peak values were observed. In the multivariable analysis, each increment of 100 µg/m3 of total volatile organic compounds was associated with the odds of respiratory infection in the previous three months ( OR̂ =1.05; 95% CI: 1.00-1.09). PM2.5 concentrations were inversely associated with pH values ( ß̂ = -0.04, 95%: -0.06 to -0.01, for each increment of 10 µg/m3). Additionally, a direct and an inverse association were found between total bacteria and FEV1/FVC and FVC, respectively.

CHOROIDAL THICKNESS IN DIABETIC PATIENTS WITHOUT DIABETIC RETINOPATHY.

PURPOSE: To compare choroidal thickness (CT) between diabetic patients without diabetic retinopathy and a nondiabetic group. To explore how CT relates to disease duration, mean arterial pressure, glycemia, glycosylated hemoglobin, intraocular pressure, and ocular pulse amplitude. METHODS: Choroidal thickness was assessed using a spectral-domain optical coherence tomography and enhanced depth mode at 13 locations (subfoveal and 3 measurements 500 µm apart in 4 directions-nasal, temporal, superior, and inferior). Linear regression models were used. RESULTS: One hundred seventy-five patients were recruited (125 diabetic patients without diabetic retinopathy and 50 nondiabetic patients). In diabetic patients, although without statistical significance, CT showed a trend to be thicker in all locations (6.16-24.27 µm). Choroidal thickness was negatively associated with age (P < 0.001) in both groups, but only in the diabetic group, it was positively associated to ocular pulse amplitude (with a mean increase between 8.5 µm and 11.6 µm for each millimeter of mercury increase in ocular pulse amplitude). Diabetic patients' CT seems to stabilize after 150 months of diabetes, increase with higher glycemia levels (>160 mg/dL) while showing no fluctuation with glycosylated hemoglobin and mean arterial pressure. CONCLUSION: There seems to be a thickening of the choroid in diabetic patients without diabetic retinopathy. Moreover, this tissue may be functionally different in diabetes, as the pattern of associations seems to differ between groups.

Good agreement between echocardiography and impedance cardiography in the assessment of left ventricular performance in hypertensive patients.

BACKGROUND: Impedance cardiography (ICG) is a noninvasive hemodynamic monitoring tool which can define hypertensive patients' hemodynamic profiles and help to tailor antihypertensive therapy. This study assesses the concordance between ICG-derived indexes used to evaluate left ventricular performance and transthoracic echocardiography (TTE) in hypertensive patients. METHODS: In this IMPEDDANS post-hoc analysis, the ICG-derived indexes are compared with TTE by Bland-Altman method. Statistical significance of the relationship between the values obtained was assessed by generalized linear mixed-effects models. RESULTS: In supine position, Bland-Altman analysis showed good concordance for cardiac output (CO) (mean difference of 0.006 mL/min [-0.120; 0.133]), cardiac index (CI) (mean difference of 0.016 mL/min/m2 [-0.471; 0.504]), pre-ejection period (PEP) (mean difference of -0.216 ms [-4.510; 4.077]), left ventricular ejection time (LVET) (mean difference of -0.140 ms [-6.573; 6.293]), and systolic time ratio (STR) (mean difference of -0.00004 [-0.008; 0.008]). In orthostatic position, good concordance was found for CO (mean difference 0.028 mL/min [-2.036; 1.980]), CI (mean difference -0.012 mL/min/m2 [-1.063; 1.039]), and STR (mean difference -0.101 [0.296; 0.094]). No significant difference between methods was identified by the linear mixed-effects models. CONCLUSION: The ICG-derived indexes CO, CI, PEP, LVET, and STR in supine position have good agreement with TTE. Therefore, ICG can be used to accurately evaluate left ventricular performance.