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Background: The presence of infections is one of the main factors that leads to delays in healing or non-closure of cutaneous wounds. Although the goal of antibiotic use is to treat or prevent infection, there is currently no agreement on the effectiveness of these products. Aim: The aim of this study was to evaluate the efficacy of antibiotic use during the healing process of skin wounds in animal models not intentionally infected, as well as to analyze the advances and limitations of the studies carried out in this field. Main methods: This systematic review was performed according to the PRISMA guidelines, using a structured search on the MedLine (PubMed) and Scopus platforms to retrieve studies published until August 29, 2018, 13:35p.m. The studies included were limited to those that used excision or incision wound models and that were not intentionally infected. The data for the animal models, antibiotic used, and the main results of the studies were extracted, and compared where possible. Bias analysis and methodological quality assessments were examined through the SYRCLE's Risk of Bias tool. Key findings: Twenty-seven studies were selected. Overall, the effects of the antibiotic on the wound decreased inflammatory cell infiltration and promoted an increased number of fibroblasts, extracellular matrix constituents, re-epithelialization and tissue strength. A great deal of important information about the methodology was not presented, such as: the statistical analysis used, the animal model (sex and age), antibiotic dosage, blinding and randomization of the animals chosen. Significance: Based on the results found, we believe that antibiotic therapy can be considered a viable alternative for the treatment of cutaneous wounds. However, current evidence obtained from the methodological quality analysis points towards a high risk of bias. This is due to the incomplete characterization of the experimental design and treatment protocol, which compromises the reproducibility of the studies. [ABSTRACT FROM AUTHOR]

In the present study, antibiotic residues were detected in milk samples collected from the dairy herds located in Karnataka, India, by microbiological assay. Subsequently, the detected antibiotics were identified as azithromycin and tetracycline, by high-performance liquid chromatography, further both the antibiotics detected in the cow milk samples were found to be at high concentration (9708.7 and 5460 μg kg-1, respectively). We then investigated the effects of temperature and pH on the stabilities of azithromycin and tetracycline to determine the degradation rate constant k using first-order kinetic equation. Results indicated that significant reduction in stability and antibacterial activity of azithromycin solution when subjected to 70 and 100°C for 24 h. While stability of tetracycline was significantly reduced when subjected to 70 and 100°C for 24 h. However no significant reduction in antibacterial activity of tetracycline was observed at respective temperatures when compared with that of control. In addition, the stabilities of azithromycin and tetracycline were found to be decreased in acidic pH 4–5. The results of the present study revealed the high risk of contamination of milk sample with veterinary antibiotics and also demonstrated the effect of temperature and pH on stability of antibiotics. Therefore the study suggest that the qualitative and quantitative screening of milk for the presence of antibiotics need to be strictly performed to ensure safe drinking milk for consumers. [ABSTRACT FROM AUTHOR]

Malignant gliomas remain incurable with a poor prognosis despite of aggressive treatment. We have been studying the development of brain tumors in a glioma rat model, where rats develop brain tumors after prenatal exposure to ethylnitrosourea (ENU), and there is a sizable interval between when the first pathological changes are noted and tumors become detectable with MRI. Our aim to define a molecular timeline through proteomic profiling of the cerebrospinal fluid (CSF) such that brain tumor commitment can be revealed earlier than at the presymptomatic stage. A comparative proteomic approach was applied to profile CSF collected serially either before, at and after the time MRI becomes positive. Elastic net (EN) based models were developed to infer the timeline of normal or tumor development respectively, mirroring a chronology of precisely timed, "clocked", adaptations. These CSF changes were later quantified by longitudinal entropy analyses of the EN predictive metric. False discovery rates (FDR) were computed to control the expected proportion of the EN models that are due to multiple hypothesis testing. Our ENU rat brain tumor dating EN model indicated that protein content in CSF is programmed even before tumor MRI detection. The findings of the precisely timed CSF tumor microenvironment changes at presymptomatic stages, deviation from the normal development timeline, may provide the groundwork for the understanding of adaptation of the brain environment in tumorigenesis to devise effective brain tumor management strategies. [ABSTRACT FROM AUTHOR]

Sepsis can be caused by malaria infection, but little is known about the utility of the quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) and SOFA score in malaria. We conducted a prospective observational study from March 2013 to February 2017 to examine adults admitted with community-acquired infection in a tertiary-care hospital in Ubon Ratchathani, Northeast Thailand (Ubon-sepsis). Subjects were classified as having sepsis if they had a modified SOFA score ≥2 within 24 hours of admission. Serum was stored and later tested for malaria parasites using a nested PCR assay. Presence of severe malaria was defined using modified World Health Organization criteria. Of 4,989 patients enrolled, 153 patients (3%) were PCR positive for either Plasmodium falciparum (74 [48%]), P. vivax (69 [45%]), or both organisms (10 [7%]). Of 153 malaria patients, 80 were severe malaria patients presenting with sepsis, 70 were non-severe malaria patients presenting with sepsis, and three were non-severe malaria patients presenting without sepsis. The modified SOFA score (median 5; IQR 4–6; range 1–18) was strongly correlated with malaria severity determined by the number of World Health Organization severity criteria satisfied by the patient (Spearman’s rho = 0.61, p<0.001). Of 80 severe malaria patients, 2 (2.5%), 11 (14%), 62 (77.5%) and 5 (6%), presented with qSOFA scores of 0, 1, 2 and 3, respectively. Twenty eight-day mortality was 1.3% (2/153). In conclusion, qSOFA and SOFA can serve as markers of disease severity in adults with malarial sepsis. Patients presenting with a qSOFA score of 1 may also require careful evaluation for sepsis; including diagnosis of cause of infection, initiation of medical intervention, and consideration for referral as appropriate. [ABSTRACT FROM AUTHOR]

Background: Postural orthostatic tachycardia syndrome is a disorder of the autonomic nervous system. Approximately 30% of patients experience orthostatic headaches. Orthostatic headaches also are a hallmark symptom in spontaneous intracranial hypotension. While the cause of orthostatic headaches in spontaneous intracranial hypotension can be linked to the cerebrospinal fluid loss at the spinal level and consecutively reduced intracranial pressure in the upright position, the cause of orthostatic headaches in postural orthostatic tachycardia syndrome still remains unknown. The present study examined orthostatic changes of intracranial pressure using dynamic ultrasound of the optic nerve and optic nerve sheath diameter in postural orthostatic tachycardia syndrome, spontaneous intracranial hypotension and healthy subjects. Methods: Data was obtained from postural orthostatic tachycardia syndrome patients with (n = 7) and without orthostatic headaches (n = 7), spontaneous intracranial hypotension patients (n = 5) and healthy subjects (n = 8). All participants underwent high-resolution transorbital ultrasound in the supine and upright position to assess optic nerve and optic nerve sheath diameter. Results: Group differences were found in percentage deviations when changing position of optic nerve sheath diameter (p < 0.01), but not regarding the optic nerve diameter. Pairwise comparisons indicated differences in optic nerve sheath diameter only between spontaneous intracranial hypotension and the other groups. No differences were found between postural orthostatic tachycardia syndrome patients with and without orthostatic headaches. Conclusion: This study shows that the size of the optic nerve sheath diameter dynamically decreases during orthostatic stress in spontaneous intracranial hypotension, but not in postural orthostatic tachycardia syndrome with or without orthostatic headaches, which indicates different underlying causes. [ABSTRACT FROM AUTHOR]

Background: This study investigated the incidence and predictors of retreatment after discontinuation of either entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment in Taiwan. Methods: A total of 535 non-cirrhotic chronic hepatitis B (CHB) patients undergoing either ETV (n = 358) or TDF (n = 177) treatment were enrolled. Patients were followed for at least 12 months after stopping ETV or TDF treatment. Most patients (86.3%) fulfilled the retreatment criteria of Taiwan's National Health Plan. Results: The 5-year cumulative rates of clinical relapse and retreatment were 52.1% and 47%, respectively, in 160 hepatitis B e antigen (HBeAg)-positive patients, and were 62% and 54.8%, respectively, in 375 HBeAg-negative patients. The median duration from the end of treatment until clinical relapse and retreatment was 40 and 57 weeks, respectively, for all patients. Multivariate Cox regression analysis revealed that discontinuing TDF treatment, old age, male gender, and higher baseline HBsAg levels were independent factors of retreatment in HBeAg-positive patients; old age, HBV genotype B, and higher baseline and end-of-treatment HBsAg levels were independent factors in HBeAg-negative patients. A total of 18.8% of retreated patients satisfied the retreatment criteria of hepatic decompensation according to Taiwan's National Health Plan. Of the 64 patients who had clinical relapse without retreatment, 17 achieved sustained virological remission and 26 did not experience clinical relapse until their last visit after clinical relapse. Four patients developed HBsAg loss. Conclusions: The 5-year retreatment rate was about 50% in HBeAg-positive and HBeAg-negative patients. Discontinuing TDF treatment was an independent factor of retreatment in HBeAg-positive patients. [ABSTRACT FROM AUTHOR]

Purpose: To provide population-based reference values for cervical spinal canal parameters and vertebral body (VB) width and to study their associations with sex, age, body height, body weight and body mass index (BMI) using MRI. Methods: Cross-sectional analyses included data from 2,453 participants, aged 21–89 years, of the population-based Study of Health in Pomerania (SHIP) who underwent whole-body MRI at 1.5 Tesla between July 2008 and March 2011. A standardised reading was performed for the C2-C7 cervical spine levels at sagittal T2 TSE weighted sequences. Results: Reference intervals for spinal canal parameters were similar in males and females, while VB width was on average 2.1–2.2 mm larger in males. Age effects were only substantial regarding VB width with a 0.5 mm per ten-year age increase. Body height effects were only substantial regarding the osseous spinal canal and VB width. Body weight and BMI effects are mostly not substantial. Conclusions: Our study provides MRI-based reference values for the cervical spinal canal parameters in an adult Caucasian population. Except for VB width, associations with sex, age and somatometric measures are mostly small and thus have only limited clinical implications. Some available cut-off values may need a revision because they likely overestimate risks. [ABSTRACT FROM AUTHOR]

Objectives: Bloodstream infections in critically ill require a speeded-up microbiological diagnosis to improve clinical outcomes. In this pre-post intervention study, we evaluated how a molecular identification test directly performed on positive blood cultures of critically ill improves patient’s therapeutic management. Methods: All adult patients staying at the intensive care unit (ICU) at the time of positive blood culture detection were study-eligible. In the 8-month pre-intervention period (P0), standard positive blood culture management was performed. In the 10-month intervention period (P1), a BioFire® FilmArray® blood culture identification (FA-BCID) test (bioMérieux) was additionally performed 24/7 at detection. The evaluated clinical outcome was time to optimal antimicrobial treatment of the bloodstream infection. FA-BCID microbiological test performances were also analysed. Results: 163 positive blood culture episodes were allocated to P0 and 166 to P1. After the withdrawal of episodes in accordance with defined exclusion criteria, outcome analysis was performed on 110 bloodstream infections both in P0 and P1. Time to optimal antimicrobial treatment in P0 was 14h41 compared to 4h39 in P1. FA-BCID test results led to a treatment adjustment in 35/110 (31.8%) P1 episodes including 26 where the adjustment was the optimal antimicrobial treatment. FA-BCID testing identified 96.2% of the on-panel microorganisms thereby covering 85.2% of our ICU-strain epidemiology. Time to identification with FA-BCID testing was calculated at 1h35. Resistance detection was in complete concordance with routine results. Considering 150 FA-BCID tests were initially performed in P1, 4,3 tests were required to have 1 test leading to an improved therapeutic outcome. Conclusions: FA-BCID testing drastically reduced time to optimal antimicrobial treatment in critically ill with bloodstream infections. [ABSTRACT FROM AUTHOR]

Acute appendicitis is one of the major causes for emergency surgery in childhood and adolescence. Appendectomy is still the therapy of choice, but conservative strategies are increasingly being studied for uncomplicated inflammation. Diagnosis of acute appendicitis remains challenging, especially due to the frequently unspecific clinical picture. Inflammatory blood markers and imaging methods like ultrasound are limited as they have to be interpreted by experts and still do not offer sufficient diagnostic certainty. This study presents a method for automatic diagnosis of appendicitis as well as the differentiation between complicated and uncomplicated inflammation using values/parameters which are routinely and unbiasedly obtained for each patient with suspected appendicitis. We analyzed full blood counts, c-reactive protein (CRP) and appendiceal diameters in ultrasound investigations corresponding to children and adolescents aged 0–17 years from a hospital based population in Berlin, Germany. A total of 590 patients (473 patients with appendicitis in histopathology and 117 with negative histopathological findings) were analyzed retrospectively with modern algorithms from machine learning (ML) and artificial intelligence (AI). The discovery of informative parameters (biomarker signatures) and training of the classification model were done with a maximum of 35% of the patients. The remaining minimum 65% of patients were used for validation. At clinical relevant cut-off points the accuracy of the biomarker signature for diagnosis of appendicitis was 90% (93% sensitivity, 67% specificity), while the accuracy to correctly identify complicated inflammation was 51% (95% sensitivity, 33% specificity) on validation data. Such a test would be capable to prevent two out of three patients without appendicitis from useless surgery as well as one out of three patients with uncomplicated appendicitis. The presented method has the potential to change today’s therapeutic approach for appendicitis and demonstrates the capability of algorithms from AI and ML to significantly improve diagnostics even based on routine diagnostic parameters. [ABSTRACT FROM AUTHOR]

The survey described in this research paper aimed to investigate the economic and health impacts of birds on dairies. Birds are common pests on dairies, consuming and contaminating feed intended for cattle. As a result, dairy operators experience increased feed costs and increased pathogen and disease risk. We surveyed dairy operators attending the 2017 Washington Dairy Conference to examine the impact of birds on dairies in Washington State. Dairy operators reported feed losses valued at $55 per cow resulting in annual losses totaling $5.5 million in the Western region of the state and $9.2 million in the Eastern region of the state. Shooting was the most commonly used bird management method and European starlings (Sternus vulgaris) were the most frequently implicated species statewide. Bird abundance greater than 10,000 birds per day was associated with larger herd size and with self-reported presence of Johne’s disease and Salmonella. [ABSTRACT FROM AUTHOR]

Albeit differences in climbing-specific strength of the forearms have been demonstrated between lead and boulder climbers, little is known about the potential differences in force and power output of the upper body pulling-apparatus between disciplines. The aim of this study was to compare the climbing-specific upper-body strength and finger flexor endurance between lead and boulder climbers, as well as to examine the relative utilization of force when testing on a ledge hold compared to a jug hold. Sixteen boulder climbers (red-point climbing grade 17.9 ± 3.3) and fifteen lead climbers (red-point climbing grade 20.5 ± 3.5) performing on an advanced level volunteered for the study. Peak force, average force and rate of force development (RFD) were measured during an isometric pull-up, average velocity in dynamic pull-up, and finger flexor endurance in an intermittent test to fatigue. The isometric pull-up was performed on a ledge hold (high finger strength requirements) and on a jug hold (very low finger strength requirements). Boulder climbers demonstrated a higher maximal and explosive strength in all strength and power measurements (26.2–52.9%, ES = 0.90–1.12, p = 0.006–0.023), whereas the finger flexor endurance test showed no significant difference between the groups (p = 0.088). Both groups were able to utilize 57–69% of peak force, average force and RFD in the ledge condition compared to the jug condition, but the relative utilization was not different between the groups (p = 0.290–0.996). In conclusion, boulder climbers were stronger and more explosive compared to lead climbers, whereas no differences in finger flexor endurance were observed. Performing climbing-specific tests on a smaller hold appears to limit the force and power output equally between the two groups. [ABSTRACT FROM AUTHOR]

Objective: To explore clinical factors associated with bacterial translocation in Japanese patients with type 2 diabetes mellitus (T2DM). Methods: The data of 118 patients with T2DM were obtained from two previous clinical studies, and were retrospectively analyzed regarding the clinical parameters associated with bacterial translocation defined as detection of bacteremia and levels of plasma lipopolysaccharide binding protein (LBP), the latter of which is thought to reflect inflammation caused by endotoxemia. Results: LBP level was not significantly different between patients with and without bacteremia. No clinical factors were significantly correlated with the detection of bacteremia. On the other hand, plasma LBP level was significantly correlated with HbA1c (r = 0.312), fasting blood glucose (r = 0.279), fasting C-peptide (r = 0.265), body mass index (r = 0.371), high-density lipoprotein cholesterol (r = -0.241), and inflammatory markers (high-sensitivity C-reactive protein, r = 0.543; and interleukin-6, r = 0.456). Multiple regression analysis identified body mass index, HbA1c, high-sensitivity C-reactive protein, and interleukin-6 as independent determinants of plasma LBP level. Conclusion: The plasma LBP level was similar in patients with and without bacteremia. While both bacteremia and LBP are theoretically associated with bacterial translocation, the detection of bacteremia was not associated with LBP level in T2DM. [ABSTRACT FROM AUTHOR]

Second-generation mammalian target of rapamycin (mTOR) inhibitors such as CC-223 may have theoretical advantages over first-generation drugs by inhibiting TOR kinase in mTOR complex 1 (mTORC1) and 2 (mTORC2), potentially improving clinical efficacy for well-differentiated neuroendocrine tumors (NET).Enrolled patients had metastatic, well-differentiated NET of non-pancreatic gastrointestinal or unknown origin, with/without carcinoid symptoms, had failed ≥1 systemic chemotherapy, and were taking a somatostatin analog (SSA). Oral once-daily CC-223 was administered in 28-day cycles starting at 45 mg (n = 24), with a subsequent cohort starting at 30 mg (n = 23). Objectives were to evaluate tolerability, preliminary efficacy, and pharmacokinetic and biomarker profiles of CC-223. Forty-seven patients completed the study, with mean treatment duration of 378 days and mean dose of 26 mg; 26% of patients remained on the starting dose. Most frequent grade ≥3 toxicities were diarrhea (38%), fatigue (21%), and stomatitis (11%). By investigator, 3 of 41 evaluable patients (7%) showed partial response (PR) and 34 (83%) had stable disease (SD) for a disease control rate (DCR) of 90% (95% confidence interval [CI] 76.9–97.3%). Duration of PR was 125–401 days; median SD duration was 297 days (min–max, 50–1519 days). Median progression-free survival was 19.5 months (95% CI 10.4–28.5 months). Carcinoid symptoms of flushing, diarrhea, or both improved in 50%, 41%, and 39% of affected patients, respectively. For the first time, this study describes that a second-generation mTOR pathway inhibitor can result in highly durable tumor regression and control of NET carcinoid symptoms. The manageable safety profile, high DCR, and durable response, coupled with reduction in carcinoid symptoms refractory to SSA, make CC-223 a promising agent for further development. [ABSTRACT FROM AUTHOR]

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are debilitating events and spur disease progression. Infectious causes are frequent; however, it is unknown to what extent exacerbations are caused by larger shifts in the airways’ microbiota. The aim of the current study was to analyse the changes in microbial composition between stable state and during exacerbations, and the corresponding immune response. Methods: The study sample included 36 COPD patients examined at stable state and exacerbation from the Bergen COPD Cohort and Exacerbations studies, and one patient who delivered sputum on 13 different occasions during the three-year study period. A physician examined the patients at all time points, and sputum induction was performed by stringent protocol. Only induced sputum samples were used in the current study, not spontaneously expectorated sputum. Sputum inflammatory markers (IL-6, IL-8, IL-18, IP-10, MIG, TNF-α) and antimicrobial peptides (AMPs, i.e. LL-37/hCAP-18, SLPI) were measured in supernatants, whereas target gene sequencing (16S rRNA) was performed on corresponding cell pellets. The microbiome bioinformatics platform QIIME2TM and the statistics environment R were applied for bioinformatics analyses. Results: Levels of IP-10, MIG, TNF-α and AMPs were significantly different between the two disease states. Of 36 sample pairs, 24 had significant differences in the 12 most abundant genera between disease states. The diversity was significantly different in several individuals, but not when data was analysed on a group level. The one patient case study showed longitudinal dynamics in microbiota unrelated to disease state. Conclusion: Changes in the sputum microbiota with changing COPD disease states are common, and are accompanied by changes in inflammatory markers. However, the changes are highly individual and heterogeneous events. [ABSTRACT FROM AUTHOR]

Background: This paper is aimed to (i) develop an innovative classification of COPD, multi-dimensional phenotype, based on a multidimensional assessment; (ii) describe the identified multi-dimensional phenotypes. Methods: An exploratory factor analysis to identify the main classificatory variables and, then, a cluster analysis based on these variables were run to classify the COPD-diagnosed 514 patients enrolled in the STORICO (trial registration number: NCT03105999) study into multi-dimensional phenotypes. Results: The circadian rhythm of symptoms and health-related quality of life, but neither comorbidity nor respiratory function, qualified as primary classificatory variables. Five multidimensional phenotypes were identified: the MILD COPD characterized by no night-time symptoms and the best health status in terms of quality of life, quality of sleep, level of depression and anxiety, the MILD EMPHYSEMATOUS with prevalent dyspnea in the early-morning and day-time, the SEVERE BRONCHITIC with nocturnal and diurnal cough and phlegm, the SEVERE EMPHYSEMATOUS with nocturnal and diurnal dyspnea and the SEVERE MIXED COPD distinguished by higher frequency of symptoms during 24h and worst quality of life, of sleep and highest levels of depression and anxiety. Conclusions: Our results showed that properly collected respiratory symptoms play a primary classificatory role of COPD patients. The longitudinal observation will disclose the discriminative and prognostic potential of the proposed multidimensional phenotype. Trial registration: Trial registration number: , date of registration: 10th April 2017. [ABSTRACT FROM AUTHOR]

Congenital cytomegalovirus (CMV) infection is a major cause of birth defects ranging from developmental disorders to stillbirth. Most newborns affected by CMV do not present with symptoms at birth but are at risk of sequelae at later stages of their childhood. Stored dried blood spots (DBS) taken at birth can be used for retrospective diagnosis of hereditary diseases, but detection of pathogens is challenged by potentially low pathogen concentrations in the small blood volume available in a DBS. Here we test four different extraction methods for optimal recovery of CMV DNA from DBS at low to high CMV titers. The recovery efficiencies varied widely between the different extractions (from 3% to 100%) with the most efficient method extracting up to 113-fold more CMV DNA than the least efficient and 8-fold more than the reference protocol. Furthermore, we amplified four immunomodulatory CMV genes from the extracted DNA: the UL40 and UL111A genes which occur as functional knockouts in some circulating CMV strains, and the highly variable UL146 and US28 genes. The PCRs specifically amplified the CMV genes at all tested titers with sufficient quality for sequencing and genotyping. In summary, we here report an extraction method for optimal recovery of CMV DNA from DBSs that can be used for both detection of CMV and for genotyping of polymorphic CMV genes in congenital CMV infection. [ABSTRACT FROM AUTHOR]

Bloodstream infections (BSI) are associated with high mortality. Therefore, reliable methods of detection are of paramount importance. Efficient strategies to improve diagnostic yield of bacteraemia within the emergency department (ED) are needed. We conducted a retrospective analysis of all ED encounters in a high-volume, city-centre university hospital within Germany during a five-year study period from October 2013 to September 2018. A time-series analysis was conducted for all ED encounters in which blood cultures (BCs) were collected. BC detection rates and diagnostic yield of community-onset bacteraemia were compared during the study period (which included 45 months prior to the start of a new diagnostic Antibiotic Stewardship (ABS) bundle and 15 months following its implementation). BCs were obtained from 5,191 out of 66,879 ED admissions (7.8%). Bacteraemia was detected in 1,013 encounters (19.5% of encounters where BCs were obtained). The overall yield of true bacteraemia (defined as yielding clinically relevant pathogens) was 14.4%. The new ABS-related diagnostic protocol resulted in an increased number of hospitalised patients with BCs collected in the ED (18% compared to 12.3%) and a significant increase in patients with two or more BC sets taken (59% compared to 25.4%), which resulted in an improved detection rate of true bacteraemia (2.5% versus 1.8% of hospital admissions) without any decrease in diagnostic yield. This simultaneous increase in BC rates without degradation of yield was a valuable finding that indicated success of this strategy. Thus, implementation of the new diagnostic ABS bundle within the ED, which included the presence of a skilled infectious disease (ID) team focused on obtaining BCs, appeared to be a valuable tool for the accurate and timely detection of community-onset bacteraemia. [ABSTRACT FROM AUTHOR]

Sexually transmitted infections (STIs) remain a worldwide problem and a severe threat to public health. The purpose of this study was to compare Aptima® Assays (Hologic®) and the Allplex™ STI Essential Assay (Seegene®) for the simultaneous detection of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and Mycoplasma genitalium in clinical practice. The Aptima® assays (Hologic®) are based on a transcription-mediated amplification (TMA) method. The Allplex™ STI Essential assay (Seegene®) is based on a multiplex Real-Time PCR (RT-PCR) method. A total of 622 clinical samples from different anatomical sites were tested using both methods. A total of 88 (14.1%) and 66 (10.6%) positive samples were found for any of the TMA assays used and for the RT-PCR assay, respectively. Aptima® assays showed a slightly higher rate of positive results for all pathogens except for T. vaginalis, the results of which were similar to those obtained with Allplex™. The most commonly detected pathogen was C. trachomatis (37 samples; 5.9% using TMA assays) and the anatomical site with the highest prevalence of microorganisms was a non-urogenital site, the pharynx (27 positive samples; 4.3%). Using the Aptima® assays as reference method, the comparison showed that the average specificity of multiplex RT-PCR was 100.0% for the four pathogens. However an average sensitivity of 74.5% was observed, showing 95.2% (CI95%; 93.6–96.9) of overall concordance (κ = 0.80). In conclusion, the Aptima® assays show a higher sensitivity on a wide range of sample types compared to the Allplex™ assay. [ABSTRACT FROM AUTHOR]

In the last decade a growing HIV/AIDS epidemic with increased incidence and AIDS-related mortality has been reported in Northern Brazil from which molecular data are scarce. Also, apparently healthy, adult blood donors, recently diagnosed with HIV-1 represent important sentinel populations for molecular studies. This cross-sectional study describes HIV-1 subtypes in blood donors from three reference public blood centers located in three States in Northern Brazil. HIV-1 pol sequencing (protease/PR, reverse transcriptase/RT) was performed on plasma samples of HIV-1 positive donors from HEMOAM, Manaus, Amazonas (n = 198), HEMERON, Porto Velho, Rondônia (n = 20) and HEMORAIMA, Boa Vista, Roraima (n = 9) collected from 2011–2017. HIV-1 subtypes were identified by REGA, phylogenetic inference; recombinant viruses were characterized by SIMPLOT. Young, single, males predominated, around half was first-time donors. Syphilis co-infection was detected in 17% (39 out of 227), 8% (18 out of 227) was anti-HBc positive. Subtype B represented ≥ 90% in Amazonas, Rondônia and Roraima, subtype C (3.1%) was found in Amazonas and Rondônia; subtype F1 (0.9%) and BF1 recombinants (5.3%) were only detected in Amazonas. Subtype B sequences from Amazonas (n = 179), Rondônia (n = 18) and Roraima (n = 9) were combined with viral strains representative of the BPANDEMIC (n = 300) and BCARIBBEAN/BCAR (n = 200) lineages. The BPANDEMIC lineage predominated (78%) although BCAR lineages were frequent in Roraima (56%) and Amazonas (22%). Subtype C and subtype F1 sequences identified here clustered within Brazilian CBR and F1BR lineages, respectively. Twelve BF1 mosaics showed 11 different recombination profiles: six were singleton unique-recombinant-forms/URFs, one displays a CRF28/29_BF-like recombinant pattern and the remaining four BF1 isolates branched with other Brazilian BF1 viruses previously described and may represent putative new CRF_BF1 from Northern Brazil. Our study shows a highly homogeneous molecular pattern with prevalent subtype B, followed by BF1, and sporadic subtype C and F1 in blood donors from the Northern region. Surveillance studies are important to monitor HIV-1 diversity which can reveal patterns of viral dissemination, especially in a highly endemic, remote and geographically isolated region as Northern Brazil. [ABSTRACT FROM AUTHOR]

Background: Cachexia occurs in individuals affected by chronic diseases in which systemic inflammation leads to fatigue, debilitation, decreased physical activity and sarcopenia. The pathogenesis of cachexia-associated sarcopenia is not fully understood. Objectives: The aim of this systematic review is to summarize the current evidence on genes expressed in the skeletal muscles of humans with chronic disease-associated cachexia and/or sarcopenia (cases) compared to controls and to assess the strength of such evidence. Methods: We searched PubMed, EMBASE and CINAHL using three concepts: cachexia/sarcopenia and associated symptoms, gene expression, and skeletal muscle. Results: Eighteen genes were studied in at least three research articles, for a total of 27 articles analyzed in this review. Participants were approximately 60 years of age and majority male; sample size was highly variable. Use of comparison groups, matching criteria, muscle biopsy location, and definitions of cachexia and sarcopenia were not homogenous. None of the studies fulfilled all four criteria used to assess the quality of molecular analysis, with only one study powered on the outcome of gene expression. FOXO1 was the only gene significantly increased in cases versus healthy controls. No study found a significant decrease in expression of genes involved in autophagy, apoptosis or inflammation in cases versus controls. Inconsistent or non-significant findings were reported for genes involved in protein degradation, muscle differentiation/growth, insulin/insulin growth factor-1 or mitochondrial transcription. Conclusion: Currently available evidence on gene expression in the skeletal muscles of humans with chronic disease-associated cachexia and/or sarcopenia is not powered appropriately and is not homogenous; therefore, it is difficult to compare results across studies and diseases. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) expressed on the surface of Gram-negative bacteria activates pro-inflammatory pathways, dys-regulates the function of endometrial cells and is a key player in the mechanisms involved in endometritis. This study aimed to investigate the effects of LPS on bovine endometrial epithelial cells (bEEC) from whole transcriptome with a special focus on genes involved in embryo-maternal interactions. Following in vitro culture, bEEC from three cows were exposed to 0, 2, and 8 μg/mL LPS for 24h. RNA samples extracted at 0 and 24 hours were analyzed by RNA sequencing (RNA-seq). At 24h, 2035 differentially expressed genes (DEGs) were identified between controls and samples treated with 2 μg/mL LPS. Gene ontology analysis showed that over-expressed DEGs were associated to immune response, response to stress and external stimuli, catalytic activity, and cell cycle. Genes associated with cell membrane and cell adhesion pathways were under-expressed. LPS induced changes in expression of specific genes related to embryo-maternal interactions including under-expression of eight members of the cadherin superfamily, over-expression of six members of the mucin family, and differential expression of a large set of genes binding the above molecules and of more than 20 transcripts coding for cytokines and their receptors. Type I interferon-τ dependent genes were also over-expressed. From a sub-set of 19 genes, (biological replicates of bEEC from cows taken at time 6 (n = 3), 24 (n = 6) and 48 hours (n = 3), and 2 technical replicates per sample) differential gene expression was confirmed by RT2-qPCR (r2 between fold changes at 24 hours by RT2-qPCR and RNA-seq = 0.97). These results indicate that LPS affects the function of bEEC in many ways by differential transcription, glycolytic metabolism and oxidative stress. Many transcriptomic signatures related to implantation and embryo maternal interactions were strongly affected by LPS. These results pave the way for further studies to investigate the duration of these changes and their possible impact on endometrial function and fertility. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) has high rates of mortality and multisystem morbidity. Pre-clinical data suggest that fibroblast growth factor 23 (FGF23) may contribute to pulmonary pathology, and FGF23 is associated with mortality and morbidity, including acute kidney injury (AKI), in non-ARDS cohorts. Here, we assess whether FGF23 is associated with AKI and/or mortality in a cohort of 161 pediatric ARDS patients. Plasma total (intact + C-terminal) FGF23 and intact FGF23 concentrations were measured within 24 hours of ARDS diagnosis (Day 1), and associations with Day 3 AKI and 60-day mortality were evaluated. 35 patients (22%) developed AKI by 3 days post-ARDS diagnosis, and 25 (16%) died by 60 days post-ARDS diagnosis. In unadjusted models, higher Day 1 total FGF23 was associated with Day 3 AKI (odds ratio (OR) 2.22 [95% confidence interval (CI) 1.62, 3.03], p<0.001), but Day 1 intact FGF23 was not. In a model adjusted for demographics and disease severity, total FGF23 remained associated with AKI (OR 1.52 [95% CI 1.02, 2.26], p = 0.039). In unadjusted models, both higher Day 1 total and intact FGF23 were associated with 60-day mortality (OR 1.43 [95% CI 1.07, 1.91], p = 0.014; and OR 1.44 [95% CI 1.02, 2.05], p = 0.039, respectively). In the adjusted model, only total FGF23 remained associated with 60-day mortality (OR 1.62 [95% CI 1.07, 2.45], p = 0.023). In a subgroup analysis of patients with Day 1 plasma IL-6 concentrations available, inflammation partially mediated the association between total FGF23 and AKI. Our data suggest both inflammation-dependent and inflammation-independent associations between total FGF23 and clinical outcomes in pediatric ARDS patients. [ABSTRACT FROM AUTHOR]

Inherited bleeding disorders including abnormalities of platelet number and function rarely occur in a variety of dog breeds, but are probably underdiagnosed. Genetically characterized canine forms of platelet disorders provide valuable large animal models for understanding similar platelet disorders in people. Breed-specific disease associated genetic variants in only eight different genes are known to cause intrinsic platelet disorders in dogs. However, the causative genetic variant in many dog breeds has until now remained unknown. Four cases of a mild to severe bleeding disorder in Cocker Spaniel dogs are herein presented. The affected dogs showed a platelet adhesion defect characterized by macrothrombocytopenia with variable platelet counts resembling human Bernard-Soulier syndrome (BSS). Furthermore, the lack of functional GPIb-IX-V was demonstrated by immunocytochemistry. Whole genome sequencing of one affected dog and visual inspection of the candidate genes identified a deletion in the glycoprotein IX platelet (GP9) gene. The GP9 gene encodes a subunit of a platelet surface membrane glycoprotein complex; this functions as a receptor for von Willebrand factor, which initiates the maintenance of hemostasis after injury. Variants in human GP9 are associated with Bernard-Soulier syndrome, type C. The deletion spanned 2460 bp, and included a significant part of the single coding exon of the canine GP9 gene on dog chromosome 20. The variant results in a frameshift and premature stop codon which is predicted to truncate almost two-thirds of the encoded protein. PCR-based genotyping confirmed recessive inheritance. The homozygous variant genotype seen in affected dogs did not occur in 98 control Cocker Spaniels. Thus, it was concluded that the structural variant identified in the GP9 gene was most likely causative for the BSS-phenotype in the dogs examined. These findings provide the first large animal GP9 model for this group of inherited platelet disorders and greatly facilitate the diagnosis and identification of affected and/or normal carriers in Cocker Spaniels. [ABSTRACT FROM AUTHOR]

Intrarenal Doppler ultrasonography is a non-invasive method to evaluate the renal blood flow in patients with renal arterial stenosis as well as chronic kidney diseases (CKD). Until recently, the relationship between ultrasonography findings and CKD stage has not been fully understood. Overall, 162 patients with CKD without apparent renal arterial stenosis were included in this study, and the pulsed-wave Doppler ultrasonography findings were evaluated in terms of the following parameters: peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) at the renal arterial trunk, hilum, segmental, and interlobar regions. Age showed a significant negative correlation with the estimated glomerular filtration rate (eGFR), kidney size, and aortic PSV. Additionally, age showed a significant positive correlation with RI in all 4 regions. The eGFR showed a positive correlation with the aortic PSV and kidney size, but a negative correlation with RI. Both age and eGFR were found to be independently associated with aortic blood flow. On the intrarenal ultrasound, EDV and RI showed stronger correlations with eGFR than PSV, suggesting that the former indices would be better markers of renal function. In particular, the interlobar EDV was found to be the best index that reflects renal function. Although the RI is also a good marker of renal function, it is confounded by age; thus, its utility would be weaker than that of the EDV. In conclusion, intrarenal pulsed-wave Doppler ultrasonography is a useful tool to estimate and evaluate the renal function; the interlobar EDV may be the best index to estimate the effective perfusion and filtration of the kidneys. [ABSTRACT FROM AUTHOR]

Objectives: To assess awareness of cytomegalovirus (CMV); attitudes towards screening; and frequency of behaviors that could increase the risk of prenatal infection. Methods: We conducted a survey among 726 women at the 2017 Minnesota State Fair. Minnesota residents aged 18–44 were eligible if they had never been pregnant or had been pregnant within the past 10 years. We compared responses between never-pregnant and recently-pregnant women. Results: Only 20% of study participants had previously heard of CMV. Remarkably, recently-pregnant women were no more likely to be aware of CMV than never-pregnant women after adjusting for potential confounders. After receiving information about CMV, nearly all participants indicated they believed prenatal (96%) or newborn (96%) screening should be offered. Conclusions: Although baseline awareness of CMV was low (even among recently-pregnant women), after learning more about the risks, women supported screening. Several states have passed or proposed legislation promoting CMV education and/or screening programs. We identified important gaps in knowledge about CMV among women who may benefit from education about how to reduce their risk of exposure and who may need to decide whether they would be willing to screen for CMV in the future. [ABSTRACT FROM AUTHOR]

Objective: To explore the use of Contrast-enhanced Ultrasound (CEUS) in evaluating angiogenesis in a xenograft nasopharyngeal carcinoma (NPC) model in nude mice and the evolution of CEUS parameters according to the growth of NPC. Methods: Nude mice were divided into three groups according to experiments conducted at various times from tumor implantation (8 mice/group; group A: 4 weeks from implantation; group B:6 weeks from implantation; group C:8 weeks from implantation). CNE-2 cells were transplanted in 24 nude mice and CEUS evaluations of the tumors were performed at 4, 6 or 8 weeks from implantation. CEUS parametric perfusion images and pathological findings were recorded. R version 3.4.4 software was used to analyze the CEUS parameters and pathological findings. Results: One-way anova analysis indicated statistically significant differences among the three groups with the parameters of peak intensity (PI) (p<0.001), area wash in (AWI) (p<0.001), area wash out (AWO) (p<0.001) and tumor volumes (p<0.001).Pearson correlation coefficient analysis indicated that microvessel density (MVD) was correlated with tumor volume (r = 0.644, p = 0.001), PI (r = 0.904, p<0.0001), AWI (r = 0.547, p = 0.008) and AWO (r = 0.744, P<0.0001). Tumor volume was correlated with MVD (r = 0.644, p = 0.001), PI (r = 0.625, p = 0.002), AWI (r = 0.528, p = 0.012) and AWO (r = 0.784, p<0.001). The percentage of necrosis in histological sections was correlated with the percentage of CEUS unperfused area (r = 0.446,p = 0.038). Spearman rank correlation coefficient analysis indicated that vascular endothelial growth factor (VEGF) was correlated with PI (r = 0.462, P = 0.032). Welch t test indicated PI, AWI and AWO parameters were significantly lower than that of kidneys (p<0.001, p = 0.009, p = 0.005). Conclusions: The CEUS parameters PI, AWI and AWO indirectly reflect the MVD and the tumor volume in our model of subcutaneous transplanted NPC in nude mice, providing precious information on angiogenesis and tumor growth. VEGF may play a role in promoting angiogenesis of NPC. [ABSTRACT FROM AUTHOR]

The anticariogenic activity of the extract of Glycyrrhiza uralensis (licorice) has been well documented. We recently developed an herbal lollipop containing licorice extracts with Glycyrrhizol A, the compound displaying strong antimicrobial activity against Streptococcus mutans. Preliminary testing showed that the herbal lollipop reduced salivary S. mutans counts in vivo. In this study, we aimed to further test the efficacy of this herbal lollipop for reducing salivary S. mutans levels, and investigate its impact on salivary microbiome. Using a well-established in vitro oral microbiome model, we showed that licorice extract displays targeted killing against S. mutans without affecting the biodiversity of the community. In vivo study corroborated in vitro findings, showing for high caries-risk children aged 3–6 with salivary S. mutans levels >5x105 cells/ml, daily use of 2 licorice-containing lollipops for 3 weeks significantly reduced salivary S. mutans levels compared to the control group. Salivary microbiome analysis showed either no change or even increase in phylogenetic diversity of the oral community following herbal lollipop usage. Although further study with longer term observation is needed, these results suggest that use of licorice extract-containing lollipops can be as a simple and effective way to reduce the risk of dental caries in children. [ABSTRACT FROM AUTHOR]

Candidemia has been considered a persistent public health problem with great impact on hospital costs and high mortality. We aimed to evaluate the epidemiology and prognostic factors of candidemia in a tertiary hospital in Northeast Brazil from January 2011 to December 2016. Demographic and clinical data of patients were retrospectively obtained from medical records and antifungal susceptibility profiling was performed using the broth microdilution method. A total of 68 episodes of candidemia were evaluated. We found an average incidence of 2.23 episodes /1000 admissions and a 30-day mortality rate of 55.9%. The most prevalent species were Candida albicans (35.3%), Candida tropicalis (27.4%), Candida parapsilosis (21.6%) and Candida glabrata (11.8%). Higher mortality rates were observed in cases of candidemia due to C. albicans (61.1%) and C. glabrata (100%), especially when compared to C. parapsilosis (27.3%). Univariate analysis revealed some variables which significantly increased the probability of death: older age (P = 0.022; odds ratio [OR] = 1.041), severe sepsis (P < 0.001; OR = 8.571), septic shock (P = 0.035; OR = 3.792), hypotension (P = 0.003; OR = 9.120), neutrophilia (P = 0.046; OR = 3.080), thrombocytopenia (P = 0.002; OR = 6.800), mechanical ventilation (P = 0.009; OR = 8.167) and greater number of surgeries (P = 0.037; OR = 1.920). Multivariate analysis showed that older age (P = 0.040; OR = 1.055), severe sepsis (P = 0.009; OR = 9.872) and hypotension (P = 0.031; OR = 21.042) were independently associated with worse prognosis. There was no resistance to amphotericin B, micafungin or itraconazole and a low rate of resistance to fluconazole (5.1%). However, 20.5% of the Candida isolates were susceptible dose-dependent (SDD) to fluconazole and 7.7% to itraconazole. In conclusion, our results could assist in the adoption of strategies to stratify patients at higher risk for developing candidemia and worse prognosis, in addition to improve antifungal management. [ABSTRACT FROM AUTHOR]

Background and aims: The revised Atlanta classification is widely used for the evaluation of acute pancreatitis (AP) severity. However, this classification cannot be used within 48 hours of AP onset. The aim of this study was to investigate the predictive factors of mortality in patients with AP on admission. Methods: We evaluated the association between AP mortality and clinical parameters at the time of admission in patients with AP from April 2013 to December 2017 at one university hospital and one tertiary care referral center. Results: A total of 203 consecutive patients were enrolled. Nine patients (4.4%) died despite multidisciplinary treatment. In a multivariable analysis, hematocrit ≥ 40% (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.01–1.13; P = 0.021), blood urea nitrogen (BUN) ≥ 40 mg/dL (OR, 1.26; 95% CI, 1.11–1.42; P < 0.001), base excess < -3.0 mmol/L (OR, 1.15; 95% CI, 1.04–1.26; P = 0.004), and inflammation extending to the rectovesical excavation (OR, 1.19; 95% CI, 1.10–1.30; P < 0.001) on admission were significantly associated with mortality. Conclusion: Among the imaging findings, inflammation extending to the rectovesical excavation was the only independent predictive factor for mortality in AP. This simple finding, obtained on computed tomography without contrast agent on admission, might be a promising prognostic factor for AP. [ABSTRACT FROM AUTHOR]

This study investigated the prevalence of Orientia tsutsugamushi, Anaplasma phagocytophilum, and Leptospira interrogans in wild rodents through molecular detection using organ samples and through serological assay using blood samples of mice collected from two distinct sites in Gwangju Metropolitan City, Republic of Korea (ROK). A total of 47 wild rodents, identified as Apodemus agrarius (A. agrarius), were captured from June to August 2016. The seroprevalence of antibodies against bacterial pathogens in A. agrarius sera was analyzed; 17.4% (8/46) were identified as O. tsutsugamushi through indirect immunofluorescence assay and 2.2% (1/46) were identified as Leptospira species through passive hemagglutination assay. Using polymerase chain reaction, the spleen, kidney and blood samples were investigated for the presence of O. tsutsugamushi, A. phagocytophilum, and L. interrogans. Out of the 47 A. agrarius, 19.1% (9/47) were positive for A. phagocytophilum and 6.4% (3/47) were positive for L. interrogans, while none were positive for O. tsutsugamushi. Four out of 46 (8.7%) blood samples, six out of 45 (13.3%) spleen samples, and one out of 47 (2.1%) kidney samples were positive for A. phagocytophilum. Three out of 47 (6.4%) kidney samples were positive for L. interrogans. The sequencing results of PCR positive samples demonstrated > 99% similarity with A. phagocytophilum and L. interrogans sequences. A. phagocytophilum was mostly detected in the spleen, whereas L. interrogans was mostly detected in the kidneys. Notably, A. phagocytophilum and L. interrogans were detected in A. agrarius living in close proximity to humans in the metropolitan suburban areas. The results of this study indicate that rodent-borne bacteria may be present in wild rodents in the metropolitan suburban areas of ROK. [ABSTRACT FROM AUTHOR]

Batroxobin, isolated from Bothrops moojeni, is a defibrinogenating agent used as a thrombin-like serine protease against fibrinogen for improving microcirculation. Here, we investigated whether, and if so, how batroxobin restores ischemic tissue injury in terms of anti-inflammatory effects. In an in vitro flow cytometry assay for human neutrophil extracellular traps (NETs), batroxobin (DF-521; Defibrase) inhibited human NETs induced by tumor necrosis factor-α (TNF-α) in the presence of human fibrinogen. Next, the effect of batroxobin was investigated by immunohistochemistry of the anterior tibial muscle (ATM) in an ischemic hindlimb model using C57BL/6J mice intraperitoneally injected with DF-521 versus the saline control. NETs and fibrinogen deposition in the ischemic ATM decreased in DF-521-treated mice on day 2 after ischemia. Meanwhile, reverse transcription-quantitative PCR assay of the ischemic ATM unveiled continuous downregulation in the expression of the genes; Tnf-α and nitric oxide synthase2 (Nos2) with hypoxia-inducible factor-1α (Hif-1α) and vascular endothelial growth factor-a (Vegf-a) from day 3 to day 7, but the upregulation of arginase-1 (Arg-1) and placental growth factor (Plgf) with myogenin (Myog) on day 7. Daily intraperitoneal DF-521 injection for the initial 7 days into mice with ischemic hindlimbs promoted angiogenesis and arteriogenesis on day 14. Moreover, DF-521 injection accelerated myofiber maturation after day 14. Laser doppler imaging analysis revealed that blood perfusion in DF-521-injected mice significantly improved on day 14 versus the saline control. Thus, DF-521 improves microcirculation by protecting NETs with tissue defibrinogenation, thereby protecting against severe ischemic tissue injury and accelerating vascular and skeletal muscular regeneration. To our knowledge, batroxobin might be the first clinically applicable NET inhibitor against ischemic diseases. [ABSTRACT FROM AUTHOR]

Measles virus is highly infectious and remains a leading cause of vaccine preventable deaths in children. Neutralizing antibody responses elicited by measles virus infection or immunization are a serological correlate of protection. We describe a high-throughput neutralization assay to improve surveillance for measles immunity. Measles virus-antibody mixtures were incubated on Vero cell monolayers and 24 hours later cell-lysates harvested and subjected to one-step SYBR green RT-qPCR to amplify a target sequence within the measles virus nucleoprotein gene. Neutralization endpoint titers were interpolated to determine the dilution that inhibited the relative amplicon copy number by at least 90% compared to the mean signal obtained in virus control wells in the absence of serum. Anti-measles virus and anti-measles hemagglutinin antisera specifically neutralized measles virus in the microneutralization RT-qPCR assay while pre-immune sera and sera raised against other viruses did not. The microneutralization RT-qPCR assay obeyed the Percentage Law for measles virus inputs ranging from 100–5000 TCID50/well. The linear range of the assay corresponds to measles antibody concentrations of 30 to 3000 mIU/mL. Bland-Altman analysis and two-way analysis of variance demonstrated that results obtained using the microneutralization RT-qPCR assay were comparable to those obtained using a plaque reduction neutralization test and correctly identified human serum samples that were seropositive (95% and 100%, sensitivity and specificity, respectively). Furthermore, these comparisons suggest that a concentration of 300 mIU/mL may be a conservative cut-point to use to identify individuals likely to be protected against severe measles disease when the endpoint is based on 90% inhibition of virus replication. Measles virus microneutralization RT-qPCR is a rapid, sensitive, specific, and robust assay for detecting measles neutralizing antibodies that may help to improve immunization strategies nationally and achieve measles elimination globally. [ABSTRACT FROM AUTHOR]

Interleukin-11 (IL-11) is an interleukin-6 (IL-6) family cytokine shown to play a protective role in acute inflammatory settings including systemic infection. In this study we addressed the role of IL-11 in acute bacterial pneumonia using a mouse model of E. coli pneumonia. Compared with other related cytokines, IL-11 protein was maintained at high levels in the lung at baseline, with only mild alterations in whole lung and BALF levels during acute infection. The primary source of IL-11 in the lung was the epithelium, but steady state production was not dependent on the inflammatory transcription factor nuclear factor kappa B in cells of either myeloid or epithelial lineage. Blockade of IL-11 with neutralizing antibodies resulted in a mild but significant decrease in neutrophil recruitment and increase in pulmonary edema during pneumonia, without detectable alterations in bacterial clearance. Exogenous IL-11 administration, however, had no effect at baseline or during infection. Overall, we conclude that maintenance of lung IL-11 concentrations may influence acute pulmonary inflammation during infection, albeit modestly. [ABSTRACT FROM AUTHOR]

Background: Transcranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS) have been described as promising alternatives to treat different pain syndromes. This study evaluated the effects of TMS and tDCS in the treatment of chronic orofacial pain, through a systematic review. Methods: An electronic search was performed in major databases: MEDLINE, Scopus, Web of Science, Cochrane, Embase, LILACS, BBO, Open Gray and CINAHL. The eligibility criteria comprised randomized clinical trials (RCTs) that applied TMS or tDCS to treat chronic orofacial pain. The variables analyzed were pain, functional limitation, quality of life, tolerance to treatment, somatosensory changes, and adverse effects. The risk of bias was assessed through the Cochrane Collaboration tool, and the certainty of evidence was evaluated through GRADE. The protocol was registered in the PROSPERO database (CRD42018090774). Results: The electronic search resulted in 636 studies. Thereafter, the eligibility criteria were applied and the duplicates removed, resulting in eight RCTs (four TMS and four tDCS). The findings of these studies suggest that rTMS applied to the Motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC) and the secondary somatosensory cortex (S2) provide adequate orofacial pain relief. Two studies reported significant pain improvement with tDCS applied over M1 while the other two failed to demonstrate significant effects compared to placebo. Conclusions: rTMS, applied to M1, DLPFC or S2, is a promising approach for the treatment of chronic orofacial pain. Moreover, tDCS targeting M1 seems to be also effective in chronic orofacial pain treatment. The included studies used a wide variety of therapeutic protocols. In addition, most of them used small sample sizes, with a high risk of biases in their methodologies, thus producing a low quality of evidence. The results indicate that further research should be carried out with caution and with better-standardized therapeutic protocols. [ABSTRACT FROM AUTHOR]

Acute Promyelocytic Leukemia (APL) is a rare and potentially lethal condition in which risk-based therapy often leads to better outcomes. Because of its rarity and relatively high overall survival rate, prospective randomized trials to investigate alternative APL treatment schedules are challenging. Mathematical models may provide useful information in this regard. We collected clinical data from 38 patients treated for APL under the International Consortium on Acute Leukemia (ICAL) protocol and laboratory data during induction therapy. We propose a mathematical model that represents the dynamics of leukocytes in peripheral blood and the effect of ICAL treatment on the disease’s dynamics. We observe that our cohort presents demographic characteristics and clinical outcomes similar to previous clinical trials on APL. Over a follow-up period of 41.8 months, the relapse-free survival and overall survival at two years are both found to be 78.7%. For two selected patients, the model produces a good fit to the clinical data. Information such as the response to treatment and risk of relapse can be derived from the model, and this may assist in clinical practice and the design of clinical trials. [ABSTRACT FROM AUTHOR]

Proteasome primarily degrades the unneeded or damaged proteins by proteolysis. Disruption of the brain barrier and its resulting meningoencephalitis caused by Angiostrongylus cantonensis are important pathological events in non-permissive hosts. In this study, the results showed upregulated proteasome during A. cantonensis infection. Occludin degradation and matrix metalloproteinase-9 (MMP-9) activity were significantly increased in infected mice than in uninfected mice. Moreover, confocal immunoflourescence microscopy showed that occludin was co-localized with MMP-9. The infected-mice were treated with proteasomal activity inhibitor MG132 by 1.5 and 3.0 mg/kg/day, which resulted in significantly reduced protein levels of phosphorylated IκBα (P<0.05) compared with the untreated control. The phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) showed similar result. In addition, MMP-9 activity and occludin degradation were reduced because of MG132 treatment. These results suggested that the proteasome in A. cantonensis infection degraded phosphorylated IκBα, modulated phosphorylated NF-κB, and then regulated the activation of MMP-9 and occludin degradation. Proteasome alterations were presented in eosinophilic meningitis of BALB/c mice and may contribute to the pathophysiology of eosinophilic meningitis by increasing occludin degradation. This molecule would serve as pivotal regulator in A. cantonensis-induced eosinophilic meningoencephalitis. [ABSTRACT FROM AUTHOR]

Chronic neck pain (CNP), a global health problem, involves a large amount of psychological and socioeconomic burdens. Not only physical causes but also behavioral disorders such as a fear-avoidance belief (FAB) can associate with the chronicity of neck pain. However, functional brain mechanisms underlying CNP and its related behavioral disorders remain unknown. The aim of the current resting-state functional magnetic resonance imaging (fMRI) study was to explore how the functional brain networks differed between CNP patients and age- and sex-matched healthy, pain-free controls (HCs). We also investigated whether these possible brain network changes in CNP patients were associated with fear avoidance belief (FAB) and the intensity of pain. We analyzed the resting-state fMRI data of 20 CNP patients and 20 HCs. FAB and the intensity of pain were assessed by Tampa Scale for Kinesiophobia (TSK) and Visual Analog Scale (VAS) of pain. The whole brain analysis showed that CNP patients had significant different functional connectivity (FC) compared with HCs, and the right dorsolateral prefrontal cortex (DLPFC) was a core hub of these altered functional networks. Furthermore, general linear model analyses showed that, in CNP patients, the increased FC between the right DLPFC and the right anterior insular cortex (aIC) significantly associated with increased TSK (p = 0.01, statistical significance after Bonferroni correction: p<0.025), and the FC between the right DLPFC and dorsal posterior cingulate cortex had a trend of inverse association with VAS (p = 0.04). Our findings suggest that aberrant FCs between the right DLPFC and aIC associated with CNP and its related FAB. [ABSTRACT FROM AUTHOR]

Objectives: To apply the MB (multiband) excitation and blipped-CAIPI (blipped-controlled aliasing in parallel imaging) techniques in a spin and gradient-echo (SAGE) EPI sequence to improve the slice coverage for vessel architecture imaging (VAI). Materials and methods: Both MB excitation and blipped-CAIPI with in-plane parallel imaging were incorporated into a gradient-echo (GE)/spin-echo (SE) EPI sequence for simultaneous tracking of the dynamic MR signal changes in both GE and SE contrasts after the injection of contrast agent. MB and singleband (SB) excitation were compared using a 20-channel head coil at 3 Tesla, and high-resolution MB VAI could be performed in 32 glioma patients. Results: Whole-brain covered high resolution VAI can be achieved after applying multiband excitation with a factor of 2 and in-plane parallel imaging with a factor of 3. The quality of the images resulting from MB acceleration was comparable to those from the SB method: images were reconstructed without any loss of spatial resolution or severe distortions. In addition, MB and SB signal-to-noise ratios (SNR) were similar. A relative low g-factor induced from the MB acceleration method was achieved after using a blipped-CAIPI technique (1.35 for GE and 1.33 for SE imaging). Performing quantitative VAI, we found that, among all VAI parametric maps, microvessel type indicator (MTI), distance map (I) and vascular-induced bolus peak-time shift (VIPS) were highly correlated. Likewise, VAI parametric maps of slope, slope length and short axis were highly correlated. Conclusions: Multiband accelerated SAGE successfully doubles the number of readout slices in the same measurement time when compared to conventional readout sequences. The corresponding VAI parametric maps provide insights into the complexity and heterogeneity of vascular changes in glioma. [ABSTRACT FROM AUTHOR]

Dipeptidyl amino-peptidase 3 (DPP3) is an aminopeptidase involved in peptide degradation, including hormone peptides as angiotensin II and enkephalins. DPP3 plasma activity increases in septic patients and correlates with mortality risk. However, the exact physiological role of DPP3 remains unclear and animal studies are necessary to reveal the function of DPP3 in vivo. To this demand, we developed a two-step purification procedure for isolation of native human DPP3 from blood cell lysate (BCL) that is suitable for in vivo applications. With the use of monoclonal antibodies coupled to beads in combination with an ion-exchange chromatography, we recovered 68% of human DPP3 activity from BCL with a purity of ≥ 95%. Purified human DPP3 was assayed for activity and protein concentration using recently published DPP3-activity- and immunoassays. Additionally, protein stability and storage in relevant buffers were tested. Our results provide a promising strategy for fast and efficient isolation of human DPP3. The purified human DPP3 represents the native state of DPP3, suitable for future in vivo applications to investigate the physiological role of DPP3 and its involvement in pathophysiological conditions. [ABSTRACT FROM AUTHOR]

Bone remodeling is an essential physiological process in growth and healing. In modern systems deviations from normal bone physiology in the form of pathologies aid in the understanding of normal bone metabolism. Here we use external morphology and X-ray microtomography to diagnose and describe a metabolic bone disease in an amniote from the early Permian. The specimen consists of two fused tail vertebrae of a small varanopid from early Permian (289 million years old) cave deposits near Richards Spur, Oklahoma, USA. Inspection of the outer morphology reveals that the fusion encompasses the vertebral centra, zygopophyses and haemal arches, with the fusion zones distinctly swollen on the left side of the specimen. With visualization of its internal structure by microCT, this specimen is diagnosed as a complex metabolic bone disease. The radiological imaging suggests a pathologically high bone turnover rate, as shown by abnormal bone formation in some areas and increased bone resorption in others. This supports that the varanopid suffered from a metabolic bone disease similar to Paget’s disease of bone as seen in humans today, which is linked to both genetic and viral factors. This finding extends the occurrence of Paget-like disease to the early Permian, and–provided a viral component was present–would also be by far the oldest evidence of viral infection in the fossil record. [ABSTRACT FROM AUTHOR]

Men tend to dehydrate more than women after prolonged exercise, possibly due to lower water intake and higher perspiration rate. Women are prone to exercise-associated hyponatremia, primarily attributed to the higher water consumption causing hypervolemia. Since aquaporin-2 (AQP2) water channels in the kidney collecting duct (CD) principal cells (PCs) are involved in maintaining water balance, we investigated their role in sex-dependent water homeostasis in wild-type (WT) C57BL/6 mice. Because CD intercalated cells (ICs) may also be involved in water balance, we also assessed the urine concentrating ability of V-ATPase B1 subunit-deficient (Atp6v1b1-/-) mice. Upon 12-hour water deprivation, urine osmolality increased by 59% in WT female mice and by only 28% in males. This difference was abolished in Atp6v1b1-/- mice, in which dehydration induced a ~30% increase in urine osmolarity in both sexes. AQP2 levels were highest in WT females; female Atp6v1b1-/- mice had substantially lower AQP2 expression than WT females, comparable to the low AQP2 levels seen in both Atp6v1b1-/- and WT males. After dehydration, AQP2 relocates towards the PC apical pole, especially in the inner stripe and inner medulla, and to a greater extent in WT females than in WT males. This apparent sex-dependent concentrating advantage was absent in Atp6v1b1-/- females, whose reduced AQP2 apical relocation was similar to WT males. Accordingly, female mice concentrate urine better than males upon dehydration due to increased AQP2 expression and mobilization. Moreover, our data support the involvement of ICs in water homeostasis, at least partly mediated by V-ATPase, in a sex-dependent manner. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the levels of plasma neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP)-9, high-sensitivity C-reactive protein (hs-CRP), and interleukin (IL)-1β across different clinical presentations of coronary artery disease and to evaluate the relationship between those biomarkers and the severity of coronary artery lesions in patients without kidney disease. Methods: We examined 365 eligible patients who underwent coronary angiography. A total of 124 ST-segment elevation myocardial infarction (STEMI) patients, 117 stable angina pectoris (SAP) patients and 124 patients without atherosclerotic plaques were enrolled in the study. Plasma NGAL, MMP-9, hs-CRP, and IL-1β were measured in all patients using the enzyme-linked immunosorbent assay (ELISA) method. According to the SYNTAX score, the STEMI patients and SAP patients were divided into another set of 2 groups: a high score group (≥ 33, n = 29) and a low score group (<33, n = 212). The relationship between those biomarkers and the severity of coronary stenosis was examined by Spearman correlation analysis; the ability for NGAL to discriminate severe coronary stenosis was examined by receiver operating characteristic (ROC) curve; the influencing factors for the SYNTAX score were determined by logistic regression analysis. Results: Plasma NGAL, MMP-9, and hs-CRP levels in STEMI patients were higher than in the SAP patients and control subjects (P<0.05, respectively), and plasma NGAL and hs-CRP levels were significantly higher in the SAP patients than in control subjects (P<0.05, respectively), while plasma IL-1β was similar among the 3 groups (P>0.05, respectively). The SYNTAX score was positively related to NGAL (r = 0.363, P<0.001), MMP-9 (r = 0.377, P<0.001), and hs-CRP (r = 0.163, P<0.011); the SYNTAX score was not related to IL-1β (r = -0.043, P = 0.510). Plasma NGAL was positively related to MMP-9 (r = 0.601, P<0.001) and IL-1β (r = 0.159, P = 0.014). The area under the ROC curve for NGAL discriminating severe coronary stenosis was 0.838 (95% CI: 0.752–0.923, P<0.001), which was greater than that for MMP-9 [0.818, (95% CI: 0.724–0.912, P<0.001)], IL-1β [0.485, (95% CI: 0.369–0.601, P = 0.791)], and hs-CRP [0.607, (95% CI: 0.492–0.722, P = 0.061)]. Multivariate regression analysis showed that plasma NGAL levels were independently related to high SYNTAX scores [OR = 1.109, (95% CI: 1.104–1.114), P<0.001]. Conclusion: Plasma NGAL, MMP-9, and hs-CRP levels in STEMI patients were higher than those in the SAP patients and control subjects. NGAL had a better ability to discriminate severe coronary stenosis than MMP-9, IL-1β, and hs-CRP. NGAL may be a novel biomarker to aid in risk stratification in coronary heart disease patients. [ABSTRACT FROM AUTHOR]

Human mesenchymal stem cells (hMSCs) have the potential to differentiate into hepatocyte-like cells, indicating that these cells may be the new target cell of interest to produce biopharmaceuticals. Our group recently established a hMSC-derived immortalized hepatocyte-like cell line (imHC) that demonstrates several liver-specific phenotypes. However, the ability of imHC to produce coagulation factors has not been characterized. Here, we examined the potential for imHC as a source of coagulation protein production by investigating the ability of imHC to produce human factor VII (FVII) using a lentiviral transduction system. Our results showed that imHC secreted a low amount of FVII (~22 ng/mL) into culture supernatant. Moreover, FVII from the transduced imHC (0.11 ± 0.005 IU/mL) demonstrated a similar coagulant activity compared with FVII from transduced HEK293T cells (0.12 ± 0.004 IU/mL) as determined by chromogenic assay. We demonstrate for the first time, to the best of our knowledge, that imHC produced FVII, albeit at a low level, indicating the unique characteristic of hepatocytes. Our study suggests the possibility of using imHC for the production of coagulation proteins. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is currently under investigation as a promising technique for enhancement of athletic performance through modulating cortical excitability. Through consecutive randomization, 12 experienced bodybuilders were randomly assigned to two arms receiving either sham or real tDCS over the primary motor cortex (leg area) and left temporal cortex (T3) for 13 minutes in the first session. After 72 hours, both groups received the inverse stimulation. After the brain stimulation, cerebral hemodynamic response (using frontopolar hemoencephalography) was examined upon taking three computer-based cognitive tasks i.e. reasoning, memory and verbal ability using the Cambridge Brain Science-Cognitive Platform. Subsequently, the bodybuilders performed knee extension exercise while performance indicators including one-repetition maximum (1RM), muscular endurance (SEI), heart rate (ECG), motivation (VAS), surface electromyography over quadriceps femoris muscle (sEMG) and perceived exertion (RPE) were evaluated. The real tDCS vs. sham group showed decreased RPE and HR mean scores by 14.2% and 4.9%, respectively. Regarding muscular strength, endurance, and electrical activity, the 1RM, SEI, and sEMG factors improved by 4.4%, 16.9%, and % 5.8, respectively. Meanwhile, compared to sham, real tDCS did not affect the athletes’ motivation. Incidentally, it turned out that subjects who underwent T3 anodal stimulation outperformed in memory (p = 0.02) and verbal functions (0.02) as well as their corresponding frontopolar hemodynamic response [(memory HEG (p = 0.001) and verbal HEG (p = 0.003)]. Our findings suggest that simultaneous tDCS-induced excitation over the M1 leg area and left temporal area may potentially improve the overall athletic performance in experienced bodybuilders (Trial registration: IRCT20181104041543N1, Registered on 4 Nov. 2018, retrospectively registered). [ABSTRACT FROM AUTHOR]

Background: Maximal inspiratory pressure (PImax) and 6-minutes walk distance test (6MWD) may be more available and feasible alternatives for prognostic assessment than cardiopulmonary testing. We hypothesized that the PImax and 6MWD combination could improve their individual accuracy as risk predictors. We aimed to evaluate PImax ability as a mortality predictor in HF and whether the combination to 6MWD could improve risk stratification. Methods: Prospective cohort from HF Clinics of three University Hospitals. PImax, 6MWD and pVO2 were obtained at baseline. The end point was all cause mortality. Results: Consecutive 256 individuals (50% woman, 57.4±10.4years) with low ejection fraction (LVEF) (31.8±8.6%) were followed up to 10years. During a median follow-up of 34.7 (IQR 37) months, 110 participants died. Mean±SD values were: pVO2 14.9±5.1mL/kg/min, PImax 5.5±1.3kPa and 6MWD 372±118m. In multivariate Cox regression, pVO2, PImax, 6MWD and LVEF were independent mortality predictors. The pVO2 showed gold standard accuracy, followed by PImax (AUC = 0.84) and 6MWD (AUC = 0.74). Kaplan-Meier mean survival time (MST±SE) for lower (≤5.0kPa) and higher (>6.0kPa) PImax tertiles, were 37.9±2.8months and 105.0±5.2months respectively, and addition of 6MWD did not restratified risk. For intermediate PImax tertile, MST was 81.5±5.5months, but adding 6MWD, MST was lower (53.3±7.6months) if distance was ≤350m and higher (103.1±5.7months) for longer distances. Conclusion: PImax is an independent mortality predictor in HF, more accurate than 6MWD and LVEF. Addition of 6MWD empowers risk stratification only for intermediate PImax tertile. Although less accurate than pVO2, this simpler approach could be a feasible alternative as a prognostic assessment. [ABSTRACT FROM AUTHOR]

Neisserial Heparin Binding Antigen (NHBA) is a surface-exposed lipoprotein of Neisseria meningitidis and a component of the Bexsero vaccine. NHBA is characterized by the presence of a highly conserved Arg-rich region involved in binding to heparin and heparan sulphate proteoglycans present on the surface of host epithelial cells, suggesting a possible role of NHBA during N. meningitidis colonization. NHBA has been shown to be cleaved by the meningococcal protease NalP and by human lactoferrin (hLF), a host protease presents in different body fluids (saliva, breast milk and serum). Cleavage occurs upstream or downstream the Arg-rich region. Since the human nasopharynx is the only known reservoir of infection, we further investigated the susceptibility of NHBA to human proteases present in the saliva to assess whether proteolytic cleavage could happen during the initial steps of colonization. Here we show that human saliva proteolytically cleaves NHBA, and identified human kallikrein 1 (hK1), a serine protease, as responsible for this cleavage. Kallikrein-related peptidases (KLKs) have a distinct domain structure and exist as a family of 15 genes which are differentially expressed in many tissues and in the central nervous system. They are present in plasma, lymph, urine, saliva, pancreatic juices, and other body fluids where they catalyze the proteolysis of several human proteins. Here we report the characterization of NHBA cleavage by the tissue kallikrein, expressed in saliva and the identification of the cleavage site on NHBA both, as recombinant protein or as native protein, when expressed on live bacteria. Overall, these findings provide new insights on NHBA as target of host proteases, highlights thepotential role of NHBA in the Neisseria meningitidis nasopharyngeal colonization, and of kallikrein as a defensive agent against meningococcal infection. [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the regulation of the immune response and inflammation. In this study, we investigated effect of the proinflammatory cytokine interleukin-1β (IL-1β) on IL-6 expression in canine dermal fibroblasts. IL-1β induced IL-6 mRNA expression and protein release in a time- and dose-dependent manner. When cells were treated with inhibitors of mitogen-activated protein kinases (MAPKs), the extracellular signal-regulated kinase (ERK) inhibitor FR180240 inhibited IL-1β-induced IL-6 mRNA expression, but not SP600125 or SKF86002, which are c-Jun N-terminal kinase (JNK) and p38 MAPK inhibitors, respectively. In cells treated with U0126, an inhibitor of MAPK/ERK kinase (MEK), which activates ERK, IL-1β-induced IL-6 mRNA expression was also inhibited. IL-1β stimulated ERK1/2 phosphorylation. In cells transfected with ERK1 and ERK2 isoform siRNAs, IL-1β-induced IL-6 mRNA expression was reduced. These observations suggest that IL-1β induces IL-6 expression via ERK1/2 signaling pathway in canine dermal fibroblasts. [ABSTRACT FROM AUTHOR]

Resistance of pathogenic bacteria to standard antibiotics is an issue of great concern, and new treatments for bacterial infections are needed. Antimicrobial peptides (AMPs) are small, cationic, and amphipathic molecules expressed by metazoans that kill pathogens. They are a key part of the innate immune system in both vertebrates and invertebrates. Due to their low toxicity and broad antimicrobial activities, there has been increasing attention to their therapeutic usage. Our previous research demonstrated that four peptides—DAN1, DAN2, HOLO1 and LOUDEF1—derived from recently sequenced arthropod genomes exhibited potent antimicrobial effects in-vitro. In this study, we show that DAN2 protected 100% of mice when it was administered at a concentration of 20 mg/kg thirty minutes after the inoculation of a lethal dose of E. coli intraperitoneally. Lower concentrations of DAN2—10mg/kg and 5mg/kg protected more than 2/3s of the mice. All three dose levels reduced bacterial loads in blood and peritoneal fluid by 10-fold or more when counted six hours after bacterial challenge. We determined that DAN2 acts by compromising the integrity of the E. coli membrane. This study supports the potential of DAN2 peptide as a therapeutic agent for treating antibiotic resistant Gram-negative bacterial infections. [ABSTRACT FROM AUTHOR]

Background: The underlying pathophysiology of dysphagia is multifactorial and evidence clarifying the precise mechanisms are scarce. Dysfunction in dopamine-related and non-dopamine-related pathways, changes in cortical networks related with swallowing and peripheral mechanisms have been implicated in the pathogenesis of dysphagia. We aimed at investigating whether dysphagia is associated with presynaptic dopaminergic deficits, faster motor symptom progression and cognitive decline in a population of early drug-naïve patients with Parkinson’s disease. Methods: By exploring the database of Parkinson’s Progression Markers Initiative we identified forty-nine early drug-naïve Parkinson’s disease patients with dysphagia. Dysphagia was identified with SCOPA-AUT question 1 (answer regularly) and was assessed with MDS-UPDRS Part-II, Item 2.3 (Chewing and Swallowing). We compared Parkinson’s disease patients with dysphagia to Parkinson’s disease patients without dysphagia, and investigated differences in striatal [123I]FP-CIT single photon emission computed tomography levels. Using Cox proportional hazards analyses, we also evaluated whether dysphagia can predict motor deterioration and cognitive dysfunction. Results: Parkinson’s disease patients with dysphagia, harbored a greater deterioration regarding motor and non-motor symptoms and decreased [123I]FP-CIT binding when compared with patients without dysphagia. Higher burden of dysphagia (MDS-UPDRS-II, item 2.3) was correlated with lower [123I]FP-CIT uptakes within the striatum (rs = −0.157; P = 0.002) and the caudate (rs = −0.156; P = 0.002). The presence of dysphagia was not a predictor of motor progression (Hazard ratio [HR]: 1.143, 95% confidence interval [CI]: 0.848–1.541; P = 0.379) or cognitive decline (HR: 1.294, 95% CI: 0.616–2.719; P = 0.496). Conclusions: Dysphagia is associated with decreased presynaptic dopaminergic integrity within caudate and greater motor and non-motor symptoms burden in early drug-naïve PD. [ABSTRACT FROM AUTHOR]

Late-onset sepsis is frequently seen in preterm infants and is associated with poor neurodevelopmental outcome. White matter damage is proposed as substrate of poor outcome, with contributing factors as regional hypoxia and effects of cytokines on oligodendrocytes. We investigated the relation between cerebral oxygenation during (suspected) late-onset sepsis and neurodevelopmental outcome. Prospective cohort study, including preterm infants (gestational age <32 weeks and/or birthweight <1500 grams) with (suspected) late-onset sepsis underwent NIRS registration during the first 72 hours of suspected late-onset sepsis. At two years corrected age neurodevelopment was scored using the Bayley Scales of Infant Development-II. Thirty-two infants were included. Twenty-seven infants were identified with proven late-onset sepsis and five infants had clinical sepsis without positive blood culture. In this study, late-onset sepsis was predominantly caused by coagulase negative staphylococci (CoNS) (72%). All NIRS values were within normal limits. No association was found between NIRS and impaired neurodevelopmental outcome (n = 4) at corrected age two years: composite cognitive score 105 (80–115), composite motor score 103 (82–118) (median and range). In this pilot study, late-onset sepsis (predominantly caused by CoNS with a relatively mild clinical course), was not associated with aberrant NIRS values, nor with impaired neurodevelopmental outcome. Further research might establish our findings and elucidate effects of other micro-organisms on cerebral perfusion. [ABSTRACT FROM AUTHOR]