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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]

Blood stream infections rank among the top seven causes of death of the general population. The aim of our study was to better understand the epidemiology of BSI in order to improve diagnostics and patient outcome. We used retrospective aggregated laboratory data of blood samples received from all public hospitals in Tyrol, Austria between 2006 and 2015. Microorganisms were categorized into obligatory, facultative, unusual pathogens and contaminants. The distribution, the cumulative incidence and antimicrobial susceptibility patterns were compared between the tertiary (TH) and regional peripheral hospitals (PH). Among 256,364 blood samples, 76.1% were from the TH The incidence of obligatory pathogens was 1.7 fold, and up to 3 times higher for facultative, unusual pathogens and contaminants in the TH and increased mainly due to an increase of E.coli, which was the most common isolated pathogen (n = 2,869), followed by Staphylococcus aureus (n = 1,439), Enterococcus sp. (n = 953) and Klebsiella sp. (n = 816). The distribution of obligatory pathogens differed between the hospital settings: In the TH Enterococcus sp. accounted for 40.8% and E.coli for 70.4%, respectively, whereas in the PH for 25.4% (p<0.0001) and 57.8%, respectively (p<0.0001) Antibiotic resistance of Gram negative bacteria and Staphylococcus aureus did not change during the observation period. Carbapenem resistance of Klebsiella sp. and vancomycin and linezolid resistance of Enterococcus faecium showed a non-significant increase since 2010 in the TH setting. We concluded that the incidence of BSI in TH was higher compared to PH. We observed higher contamination rates in the TH. We could not interpret the data of coagulase negative staphylococci due to lack of clinical data. We strongly recommend enhancement of training on blood culture sampling to decrease the rate of contamination. Due to differences in pathogen distribution and antimicrobial resistance between different hospital settings we recommend separate treatment guidelines for BSI by hospital setting. [ABSTRACT FROM AUTHOR]

Introduction: While extracorporeal membrane oxygenation (ECMO) is effective in preventing further hypoxemia and maintains blood flow in endotoxin-induced shock, ECMO alone does not reverse the hypotension. In this study, we tested whether concurrent vasopressor use with ECMO would provide increased circulatory support and blood flow, and characterized regional blood flow distribution to vital organs. Methods: Endotoxic shock was induced in piglets to achieve a 30% decrease in mean arterial pressure (MAP). Measurements of untreated pigs were compared to pigs treated with ECMO alone or ECMO and vasopressors. Results: ECMO provided cardiac support during vasodilatory endotoxic shock and improved oxygen delivery, but vasopressor therapy was required to return MAP to normotensive levels. Increased blood pressure with vasopressors did not alter oxygen consumption or extraction compared to ECMO alone. Regional microcirculatory blood flow (RBF) to the brain, kidney, and liver were maintained or increased during ECMO with and without vasopressors. Conclusion: ECMO support and concurrent vasopressor use improve regional blood flow and oxygen delivery even in the absence of full blood pressure restoration. Vasopressor-induced selective distribution of blood flow to vital organs is retained when vasopressors are administered with ECMO. [ABSTRACT FROM AUTHOR]

Background: The function of the pelvic bones is to transfer load generated by body weight. Proper function of the pelvic bones can be disturbed by alignment changes that occur during pregnancy. Further, misalignment of the pelvic bones can lead to pain, urinary incontinence, and other complications. An understanding of the timing and nature of pelvic alignment changes during pregnancy may aid in preventing and treating these complications. Objective: To investigate the changes in pelvic alignment during pregnancy and one month after childbirth. Methods: This is a prospective, longitudinal cohort study. Pelvic measurements were obtained for 201 women at 12, 24, 30, and 36 weeks of pregnancy, and 1 month after childbirth. The anterior and posterior width of the pelvis (the distance between the bilateral anterior superior iliac spines and the bilateral posterior superior iliac spines), the anterior pelvic tilt, and pelvic asymmetry (the mean left and right pelvic tilt degrees and the bilateral difference of the anterior pelvic tilt) were measured. For the change in pelvic alignment, a Friedman test was conducted to determine any significant difference in the measurements over time. Results: The anterior and posterior width of the pelvis became significantly wider with pregnancy progress and the anterior width of the pelvis at 1 month after childbirth remained wider than that at 12 weeks of pregnancy (p < 0.001). The anterior pelvic tilt increased during pregnancy and decreased after childbirth (p < 0.05). Conclusion: Some changes in pelvic alignment occur continuously during the perinatal period. Changes in the anterior width of the pelvis are not recovered at one month post-childbirth. Understanding these perinatal changes may help clinicians avert complications due to pelvic misalignment. [ABSTRACT FROM AUTHOR]

Cells damaged by mechanical or infectious injury release proinflammatory mitochondrial DNA (mtDNA) fragments into the circulation. We evaluated the relation between plasma levels of mtDNA fragments in obese type 2 diabetes mellitus (T2DM) patients and measures of chronic inflammation and insulin resistance. In 10 obese T2DM patients and 12 healthy control (HC) subjects, we measured levels of plasma cell-free mtDNA with quantitative real-time polymerase chain reaction, and mtDNA damage in skeletal muscle with quantitative alkaline Southern blot. Also, markers of systemic inflammation and oxidative stress in skeletal muscle were measured. Plasma levels of mtDNA fragments, mtDNA damage in skeletal muscle and plasma tumor necrosis factor α levels were greater in obese T2DM patients than HC subjects. Also, the abundance of plasma mtDNA fragments in obese T2DM patients levels positively correlated with insulin resistance. To the best of our knowledge, this is the first published evidence that elevated level of plasma mtDNA fragments is associated with mtDNA damage and oxidative stress in skeletal muscle and correlates with insulin resistance in obese T2DM patients. Plasma mtDNA may be a useful biomarker for predicting and monitoring insulin resistance in obese patients. [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]

Several models for the long-term development of T2DM already exist, focusing on the dynamics of the interaction between glycemia, insulinemia and β-cell mass. Current models consider representative (fasting or daily average) glycemia and insulinemia as characterizing the compensation state of the subject at some instant in slow time. This implies that only these representative levels can be followed through time and that the role of fast glycemic oscillations is neglected. An improved model (DPM15) for the long-term progression of T2DM is proposed, introducing separate peripheral and hepatic (liver and kidney) insulin actions. The DPM15 model no longer uses near-equilibrium approximation to separate fast and slow time scales, but rather describes, at each step in slow time, a complete day in the life of the virtual subject in fast time. The model can thus represent both fasting and postprandial glycemic levels and describe the effect of interventions acting on insulin-enhanced tissue glucose disposal or on insulin-inhibited hepatic glucose output, as well as on insulin secretion and β-cell replicating ability. The model can simulate long-term variations of commonly used clinical indices (HOMA-B, HOMA-IR, insulinogenic index) as well as of Oral Glucose Tolerance or Euglycemic Hyperinsulinemic Clamp test results. The model has been calibrated against observational data from the Diabetes Prevention Program study: it shows good adaptation to observations as a function of very plausible values of the parameters describing the effect of such interventions as Placebo, Intensive LifeStyle and Metformin administration. [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]

Objectives: Aging is associated with low muscle mass and has been linked to adverse health outcomes. The objectives of this cross-sectional study were: (1) to describe anthropometry, body composition, appendicular skeletal muscle mass index (ASMI; appendicular skeletal muscle mass/height2), and prevalence of low ASMI in older people with normal nutritional status (Malnutrition Universal Screening Tool score = 0); (2) to determine factors associated with ASMI, and odds ratios of having low ASMI. Methods: SHIELD is a study of community-dwelling older people aged 65 years and above in Singapore. ASMI was determined using bioelectrical impedance analysis and low ASMI was defined as <7.0 kg/m2 for males and <5.7 kg/m2 for females (Asian Working Group for Sarcopenia, 2014). Results: A total of 400 older people (183 males and 217 females) took part in this study. The overall prevalence of low ASMI was 20.6% (15.5% in males and 24.9% in females). Females had significantly lower ASMI than males (P < 0.0001), age was inversely associated with ASMI (P = 0.0024) while BMI and calf circumference were positively associated with ASMI (both P < 0.0001) in the total cohort. In addition, ASMI was positively associated with bone mass in both genders (both P < 0.0001). After adjusting for covariates, the odds ratios of having low ASMI with every 1 year and 10 years increase in age were 1.13 (95% CI: 1.06, 1.20) and 3.36 (95% CI: 1.82, 6.21) respectively. Conclusions: The high prevalence of low ASMI in community-dwelling older people with normal nutritional status highlights the need for early screening. There was a strong inverse association between age and ASMI while BMI, calf circumference and bone mass were positively associated with ASMI. These findings will give further weight to the importance and development of public health strategies in maintaining and improving muscle health in this population group. [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]

Purpose: Decreasing the risk of catheter related bloodstream infections (CRBSIs) remains a key focus for improving outcomes and reducing cost of care for hemodialysis (HD) patients. Recent studies demonstrate CRBSI rates can be improved by managing bacterial colonization at the catheter exit site. Herein we present the results of a study documenting the clinical performance of the NexSite HD catheter, a new tunneled central venous catheter which incorporates Exit Site Management (ESM) technology. Methods: We conducted an observational study using a prospective, multi-center registry of HD patients implanted with the NexSite HD catheter. The primary endpoint for the study was CRBSI rate for a period up to 180-days following catheter placement. Secondary endpoints included device placement success rate, exit site healing, development of an exit site or tunnel infection, and early or late non-infectious catheter-related complications. All reasons for early non-elective catheter removal were recorded. Results: A total of 115 HD patients at 6 sites were included in the final analysis. Cumulative catheter use was 10,924 days with a mean duration of 95 days. Seven patients experienced CRBSIs during the study period resulting in a CRBSI rate of 0.64 per 1,000 catheter-days. Seventy-four patients (64.3%) had either elective catheter removal (n = 56) or utilized the catheter for the entire 180-day observation period (n = 18). Thirty-five patients (30%) underwent non-elective device removal either due to CRBSI (n = 5), low flow (n = 16), exit site issues (n = 7), or for other causes (n = 7). Six patients died during the observation period with 1 death due to CRBSI-associated complications and the remaining 5 deaths attributed to non-device related causes. Conclusion: Our findings demonstrate that the NexSite HD catheter equipped with ESM technology can achieve a CRBSI rate in compliance with the NKF KDOQI (National Kidney Foundation Kidney Disease Outcome Quality Initiatives) Clinical Performance Guidelines stated goal of less than 1.0/1,000 catheter-days when used in hemodialysis patients using current standard of care nursing protocols. [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]

Introduction: In addition to their role in facilitating leukocyte-mediated inflammation, platelets can dampen leukocyte pro-inflammatory responses in some contexts. Consequently, platelets are increasingly appreciated as regulators of inflammation. Together, platelets and neutrophils play a role in inflammation through Toll-like receptor (TLR) expression, although we do not fully understand how platelets shape neutrophil responses to TLR stimulation. Here, we aimed to determine the extent to which platelets can modulate neutrophil function in response to in vitro stimulation with TLR4, TLR2/1, and TLR2/6 agonists. Methods: Neutrophils from 10 healthy individuals were cultured alone or with autologous platelets. Neutrophils ± platelets were left unstimulated or were stimulated with 1 or 100 ng/mL lipopolysaccharide (LPS; a TLR4 agonist), Pam3CSK4 (a TLR2/1 agonist) and fibroblast-stimulating lipopeptide (FSL)-1 (a TLR2/6 agonist). Neutrophil activation and phagocytic activity were assessed by flow cytometry, and elastase and interleukin-8 secretion were assessed by ELISA. Results: The addition of platelets attenuated neutrophil CD66b and CD11b expression in response to various doses of Pam3CSK4 and FSL-1. Furthermore, platelet co-culture was associated with higher CD62L expression (indicating reduced CD62L shedding) in response to these TLR agonists. Platelets also reduced elastase secretion in unstimulated cultures and in response to low-dose TLR stimulation. Conversely, platelet co-culture increased neutrophil phagocytosis in unstimulated cultures and in response to low-dose Pam3CSK4 and FSL-1. Platelets also increased IL-8 secretion in response to low-dose LPS. Conclusion: Platelets are complex immunomodulators that can attenuate some, and simultaneously augment other, neutrophil functions. This modulation can occur both in the absence and presence of TLR stimulation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to produce two statistical survival models in those with cirrhosis utilising only routine parameters, including non-liver-related clinical factors that influence survival. The first model identified and utilised factors impacting short-term survival to 90-days post incident diagnosis, and a further model characterised factors that impacted survival following this acute phase. Data were from the Clinical Practice Research Datalink linked with Hospital Episode Statistics. Incident cases in patients ≥18 years were identified between 1998 and 2014. Patients that had prior history of cancer or had received liver transplants prior were excluded. Model-1 used a logistic regression model to predict mortality. Model-2 used data from those patients who survived 90 days, and used an extension of the Cox regression model, adjusting for time-dependent covariables. At 90 days, 23% of patients had died. Overall median survival was 3.7 years. Model-1: numerous predictors, prior comorbidities and decompensating events were incorporated. All comorbidities contributed to increased odds of death, with renal disease having the largest adjusted odds ratio (OR = 3.35, 95%CI 2.97–3.77). Model-2: covariables included cumulative admissions for liver disease-related events and admissions for infections. Significant covariates were renal disease (adjusted hazard ratio (HR = 2.89, 2.47–3.38)), elevated bilirubin levels (aHR = 1.38, 1.26–1.51) and low sodium levels (aHR = 2.26, 1.84–2.78). An internal validation demonstrated reliability of both models. In conclusion: two survival models that included parameters commonly recorded in routine clinical practice were generated that reliably forecast the risk of death in patients with cirrhosis: in the acute, post diagnosis phase, and following this critical, 90 day phase. This has implications for practice and helps better forecast the risk of mortality from cirrhosis using routinely recorded parameters without inputs from specialists. [ABSTRACT FROM AUTHOR]

Trauma and hemorrhagic shock can lead to acute traumatic coagulopathy (ATC) that is not fully reversed by prehospital resuscitation as simulated with a limited volume of fresh whole blood (FWB) in a rat model. Tranexamic Acid (TXA) is used as an anti-fibrinolytic agent to reduce surgical bleeding if administered prior to or during surgery, and to improve survival in trauma if given early after trauma. It is not clear from the existing clinical literature whether TXA has the same mechanism of action in both settings. This study sought to explore the molecular mechanisms of TXA activity in trauma and determine whether administration of TXA as a supplement to FWB resuscitation could attenuate the established ATC in a rat model simulating prehospital resuscitation of polytrauma and hemorrhagic shock. In a parallel in-vitro study, the effects on clotting assays of adding plasmin at varying doses along with either simultaneous addition of TXA or pre-incubation with TXA were measured, and the results suggested that maximum anti-fibrinolytic effect of TXA on plasmin-induced fibrinolysis required pre-incubation of TXA and plasmin prior to clot initiation. In the rat model, ATC was induced by polytrauma followed by 40% hemorrhage. One hour after trauma, the rats were resuscitated with FWB collected from donor rats. Vehicle or TXA (10mg/kg) was given as bolus either before trauma (TXA-BT), or 45min after trauma prior to resuscitation (TXA-AT). The TXA-BT group was included to contrast the coagulation effects of TXA when used as it is in elective surgery vs. what is actually feasible in real trauma patients (TXA-AT group). A single dose of TXA prior to trauma significantly delayed the onset of ATC from 30min to 120min after trauma as measured by a rise in prothrombin time (PT). The plasma d-dimer as well as plasminogen/fibrinogen ratio in traumatized liver of TXA-BT were significantly lower as compared to vehicle and TXA-AT. Wet/dry weight ratio and leukocytes infiltration of lungs were significantly decreased only if TXA was administrated later, prior to resuscitation (TXA-AT). In conclusion: Limited prehospital trauma resuscitation that includes FWB and TXA may not correct established systemic ATC, but rather may improve overall outcomes of resuscitation by attenuation of acute lung injury. By contrast, TXA given prior to trauma reduced levels of fibrinolysis at the site of tissue injury and circulatory d-dimer, and delayed development of coagulopathy independent of reduction of fibrinogen levels following trauma. These findings highlight the importance of early administration of TXA in trauma, and suggest that further optimization of dosing protocols in trauma to exploit TXA’s various sites and modes of action may further improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Linezolid has shown strong antimicrobial activity against multidrug-resistant (MDR)/rifampin-resistant strains of Mycobacterium tuberculosis. Linezolid achieves clinical efficacy mainly through area under the concentration time curve/minimum inhibitory concentration ratio in the infected lesion site. Previous studies mainly focused on the relationship between linezolid concentrations in the blood and infected bone tissue when the blood drug concentration reached the peak 2 h after administration. However, we do not know whether linezolid can maintain the same bone/plasma ratio in infected bone tissue when the blood concentration reaches the trough level. Therefore, this study aimed to evaluate the penetrability of linezolid into bone tissue 24 h after administration in patients with MDR spinal tuberculosis (TB). Methods: Nine MDR spinal TB patients, who received a treatment regimen including linezolid and underwent surgery, were enrolled prospectively from April 2017 to March 2019. Blood and diseased bone tissue specimens were collected simultaneously during operations 24 h after taking 600 mg of linezolid orally. Linezolid concentrations in plasma and diseased bone tissue specimens were determined by high-performance liquid chromatography–tandem mass spectrometry. Results: Following a 600 mg oral administration of linezolid 24 h before surgery, median concentrations of linezolid in plasma and diseased bone tissue for the 9 patients were 1.98 mg/L (range 0.30–3.44 mg/L) and 0.60 mg/L (range 0.18–2.13 mg/L), respectively, at resection time. The median diseased bone/plasma linezolid concentration ratio was 0.48 (range 0.30–0.67). Pearson’s correlation analysis showed that linezolid concentrations in the plasma were positively related to those in diseased bone tissue (r = 0.949, p < 0.001). Conclusions: After 24 h of medication, linezolid still had good penetrability into diseased bone tissue in patients with MDR spinal TB. [ABSTRACT FROM AUTHOR]

Oral herpes is a highly prevalent infection caused by herpes simplex virus 1 (HSV-1). After an initial infection of the oral cavity, HSV-1 remains latent in sensory neurons of the trigeminal ganglia. Episodic reactivation of the virus leads to the formation of mucocutaneous lesions (cold sores), but asymptomatic reactivation accompanied by viral shedding is more frequent and allows virus spread to new hosts. HSV-1 DNA has been detected in many oral tissues. In particular, HSV-1 can be found in periodontal lesions and several studies associated its presence with more severe periodontitis pathologies. Since gingival fibroblasts may become exposed to salivary components in periodontitis lesions, we analyzed the effect of saliva on HSV-1 and -2 infection of these cells. We observed that human gingival fibroblasts can be infected by HSV-1. However, pre-treatment of these cells with saliva extracts from some but not all individuals led to an increased susceptibility to infection. Furthermore, the active saliva could expand HSV-1 tropism to cells that are normally resistant to infection due to the absence of HSV entry receptors. The active factor in saliva was partially purified and comprised high molecular weight complexes of glycoproteins that included secretory Immunoglobulin A. Interestingly, we observed a broad variation in the activity of saliva between donors suggesting that this activity is selectively present in the population. The active saliva factor, has not been isolated, but may lead to the identification of a relevant biomarker for susceptibility to oral herpes. The presence of a salivary factor that enhances HSV-1 infection may influence the risk of oral herpes and/or the severity of associated oral pathologies. [ABSTRACT FROM AUTHOR]

The development of ICU-acquired sodium disturbances is not fully understood. Alterations in non-osmotic skin sodium storage, hypothetically inflammation-driven, could play a role. To investigate this in critically ill patients we conducted a patient-control study with skin punch biopsies in patients with sepsis (n = 15), after coronary artery bypass grafting (CABG, n = 15) and undergoing total hip arthroplasty (THA-controls, n = 15) respectively, together representing a range in severity of systemic inflammation. Biopsies were taken within 24 hours (sepsis) and within 2 hours (CABG) after ICU-admission, and prior to arthroplasty. Biopsies were analysed for sodium content. In addition immunostainings and quantitative real time PCR were performed. The primary aim of this study was to detect possible differences in amounts of cutaneous sodium. The secondary aims were to quantify inflammation and lymphangiogenesis with concomitant markers. The highest amounts of both water and sodium were found in patients with sepsis, with slightly lower values after CABG and the lowest amounts in THA-controls. Correlation between water and sodium was 0.5 (p<0.01). In skin biopsies in all groups comparable amounts of macrophages, T-cells and lymph vessels were found. In all groups comparable expression of inflammation markers were found. However, higher mRNA transcript expression levels of markers of lymphangiogenesis were found in patients with sepsis and after CABG. The conjoint accumulation of water and sodium points towards oedema formation. However, the correlation coefficient of 0.5 leaves room for alternative explanations, including non-osmotic sodium storage. No signs of dermal inflammation were found, but upregulation of markers of lymphangiogenesis could indicate future lymphangiogenesis. [ABSTRACT FROM AUTHOR]

Background: Approximately 40,000 newborns die each year in Tanzania. Regional differences in outcome are common. Reviewing current local data, as well as defining potential causal pathways leading to death are urgently needed, before targeted interventions can be implemented Objective: To describe the clinical characteristics and potential causal pathways contributing to newborn death and determine the presumed causes of newborn mortality within seven days, in a rural hospital setting. Methods: Prospective observational study of admitted newborns born October 2014–July 2017. Information about labour/delivery and newborn management/care were recorded on data collection forms. Causes of deaths were predominantly based on clinical diagnosis. Results: 671 were admitted to a neonatal area. Reasons included prematurity n = 213 (32%), respiratory issues n = 209 (31%), meconium stained amniotic fluid with respiratory issues n = 115 (17%) and observation for < 24 hours n = 97 (14%). Death occurred in 124 infants. Presumed causes were birth asphyxia (BA) n = 59 (48%), prematurity n = 19 (15%), presumed sepsis n = 19 (15%), meconium aspiration syndrome (MAS) n = 13 (10%) and congenital abnormalities n = 14 (11%). More newborns who died versus survivors had oxygen saturation <60% on admission (37/113 vs 32/258; p≤0.001) respectively. Moderate hypothermia on admission was common i.e. deaths 35.1 (34.6–36.0) vs survivors 35.5 (35.0–36.0)°C (p≤0.001). Term newborns who died versus survivors were fourfold more likely to have received positive pressure ventilation after birth i.e. 4.57 (1.22–17.03) (p<0.02). Conclusion: Intrapartum-related complications (BA, MAS), prematurity, and presumed sepsis were the leading causes of death. Intrapartum hypoxia, prematurity and attendant complications and presumed sepsis, are major pathways leading to death. Severe hypoxia and hypothermia upon admission are additional contributing factors. Strategies to identify fetuses at risk during labour e.g. improved fetal heart rate monitoring, coupled with timely interventions, and implementation of WHO interventions for preterm newborns, may reduce mortality in this low resource setting. [ABSTRACT FROM AUTHOR]

Background: TB/HIV coinfection is a serious public health issue in Brazil, and patients with coinfection have difficulty adhering to treatments. Directly observed treatment (DOT) has been recommended by the World Health Organization, considering the vulnerability of those affected. The purpose is to investigate the occurrence of DOT and associated factors compared to conventional treatment in Porto Alegre, Brazil. Methods: A retrospective cohort study was carried out with all patients with coinfection from 2009 to 2013 in the city of Porto Alegre, Brazil, the state capital with the highest rate of coinfection in Brazil. The data came from national health information systems. The dependent variable was the performance of DOT. Bivariate and multivariable models were used to determine factors associated with DOT. The percentage of cure and death was verified in a period of two years, comparing patients who received and did not receive DOT. Results: 2,400 cases of coinfection were reported, with 1,574 males and 826 females and a mean age of 38 years ± 9.91 years. The occurrence of DOT was 16.9%. In the multivariable analysis, factors independently associated to DOT were the year (with greater chances of being received in 2012 and 2013), place of origin, non-white race (OR = 1.29, 95% CI = 1.08–1.54), cases of relapse (OR = 1.33; 95% CI = 1.03–1.73), readmission after abandonment (OR = 1.48, 95% CI = 1.20–1.83), transfer (OR = 2.04; 95% CI = 1.40–2.98), acid-fast bacilli (AFB) test with positive result in first sample (OR = 1.73, 95% CI = 1.24–2.42), alcohol abuse (OR = 1.39; 95% CI = 1.16–1.67), and mental disorders (OR = 1.83; 95% CI = 1.38–2.44.) Of the 532 cases of death, occurring in two years, 10.2% were in patients who underwent DOT and 89.8% in patients who did not undergo DOT (p<0.001). O percentual de óbitos em pessoas que receberam DOT foi de 13% e o percentual de óbitos para pessoas que receberam tratamento convencional foi de 24%. Conclusions: There was an increase in the percentage of DOT over the years in the scenario studied, and the predictors for DOT were related to social vulnerability. In relation to death within two years, a lower proportion was found in patients who underwent DOT, suggesting a protective effect of the strategy. [ABSTRACT FROM AUTHOR]

Objective: Although previous studies have reported a negative relationship between serum bilirubin concentration and the development of diabetes mellitus (DM), the relationship between bilirubin and insulin resistance has not been thoroughly assessed. This study was designed to determine the relationships between bilirubin, body fat distribution, and adipose tissue inflammation in patients with type 2 DM and the effect of bilirubin in an obese animal model. Method: Body fat distribution was measured using an abdominal dual bioelectrical impedance analyzer in patients with type 2 DM. We also measured glycemic control, lipid profile, serum bilirubin concentration and other clinical characteristics, and determined their relationships with body fat distribution. In the animal study, biliverdin (20 mg/kg daily) was orally administered to high-fat diet (HFD)-induced obese (DIO) mice for 2 weeks, after which intraperitoneal insulin tolerance testing was performed. Then, adipocyte area, adipocytokine expression, and macrophage polarization were evaluated in epididymal adipose tissues. Results: In the clinical study, univariate analysis showed that a lower bilirubin concentration was significantly correlated with higher body mass index, waist circumference, triglyceride, uric acid, creatinine, visceral fat area and lower HDL-C. In multivariate analyses, bilirubin concentration significantly correlated with diastolic blood pressure, creatinine, and visceral fat area. However, there was no association between bilirubin concentration and subcutaneous fat area. In the animal study, DIO mice treated with biliverdin had smaller adipocytes than untreated DIO mice and biliverdin improved HFD-induced insulin resistance. Biliverdin treatment reversed the higher gene expression of Cd11c, encoding an M1 macrophage marker, and Tnfa, encoding the proinflammatory cytokine tumor necrosis factor-α, in the adipose tissues of DIO mice. These data suggest biliverdin administration alleviates insulin resistance by ameliorating inflammation and the dysregulation of adipocytokine expression in adipose tissues of DIO mice. Conclusions: Bilirubin may protect against insulin resistance by ameliorating visceral obesity and adipose tissue inflammation. [ABSTRACT FROM AUTHOR]

Background: Cinobufacini, the sterilized hot water extraction of dried toad skin, has been widely used in the treatment of inflammation and cancers. Recently we found cinobufacini could ameliorate dextran sulfate sodium (DSS)-induced colitis in mice, but the underlying mechanism was not fully understood. In current study, we explored the effect of cinobufacini on gut microbiota in DSS-induced acute colitic mouse model by pyrosequencing of colonic contents. Methods: C57BL/6 mice were supplied with normal or 3.0% DSS containing drinking water. DSS-treat mice were gavaged daily either with vehicle (water) or cinobufacini (10.0 or 30.0 mg/kg) for 7 days. The composition of the gut microbiota was assessed by analyzing 16S rRNA gene sequences. Results: Our data indicated that cinobufacini reversed DSS-induced gut dysbiosis and enhanced intestinal barrier integrity. Moreover, changing of some specific microbial groups such as Proteobacteria and Bacteroides was closely correlated with the re-establishment of intestinal equilibrium and the recovery of intestinal function. Conclusion: Cinobufacini prevents colitis in mice by modifying the composition and function of gut microbiota. The current study provides additional mechanistic insight in the therapeutic effect of cinobufacini treatment and may pave the way for clinical application of cinobufacini in colitis therapy. [ABSTRACT FROM AUTHOR]

Aims: Alcohol use is associated with both positive and negative effects on individual cardiovascular risk factors, depending upon which risk factor is assessed. The present analysis uses a summative multisystem index of biologic risk, known as allostatic load (AL), to evaluate whether the overall balance of alcohol-associated positive and negative cardiovascular risk factors may be favorable or unfavorable. Methods: This analysis included 1255 adults from the Midlife in the United States (MIDUS) biomarker substudy. Participants, average age 54.5 (±11) years, were divided into 6 alcohol-use categories based on self-reported drinking habits. Current non-drinkers were classified as lifelong abstainers and former light drinkers, former moderate drinkers, or former heavy drinkers. Current alcohol users were classified as light, moderate, or heavy drinkers. A total AL score was calculated using 24 biomarkers grouped into 7 physiologic systems including cardiovascular, inflammation, glucose metabolism, lipid metabolism, sympathetic and parasympathetic nervous systems, and the hypothalamic-pituitary-adrenal axis. Mixed-effects regression models were fit to determine the relationship between alcohol use categories and AL with controls for covariates that may influence the relationship between alcohol use and AL. Results: 468 (37.6%) individuals were current non-drinkers while 776 (62.4%) were current drinkers. In adjusted mixed-effects regression models, all 3 groups of current drinkers had significantly lower average AL scores than the lifelong abstainer/former light drinker group (light: -0.23, 95% CI -0.40, -0.07, p < 0.01; moderate: -0.20, 95% CI -0.38, -0.02, p < 0.05; heavy: -0.30, 95% CI -0.57, -0.04, p < 0.05), while the average AL scores of former moderate and former heavy drinkers did not differ from the lifelong abstainer/former light drinker group. Conclusions: Current alcohol use is associated cross-sectionally with a favorable multisystem physiologic score known to be associated with better long-term health outcomes, providing evidence in support of long-term health benefits related to alcohol consumption. [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]

Objective: The purpose of this study was the assessment of volumetric CT-perfusion (CTP) of the lower leg musculature in patients with symptomatic peripheral arterial disease (PAD) of the lower extremities, comparing it with established angiographic and hemodynamic parameters. Materials and methods: Thirty-five consecutive patients with symptomatic PAD of the lower extremities requiring interventional revascularization were assessed prospectively. All patients underwent a CTP scan of the lower leg, and hemodynamic and angiographic assessment. Hemodynamic parameters, specifically ankle-brachial pressure index (ABI), ankle blood pressure (ABP), peak systolic velocity (PSV), and segmental pulse oscillography (SPO) level, were determined. Lesion length and degree of collateralization were assessed by interventional angiography. CTP parameters were calculated with a perfusion software, acting on a no outflow assumption. A sequential two-compartment model was used. Differences in CTP parameters and correlations between CTP, hemodynamic and angiographic parameters were assessed with non-parametric tests. Results: The cohort consisted of 27 subjects with an occlusion, and eight with a high-grade stenosis. The mean blood flow (BF) was 7.71 ± 2.96 ml/100ml*min-1, mean blood volume (BV) 0.71 ± 0.33 ml/100ml, and mean mean transit time (MTT) 7.22 ± 2.66 s. BF and BV were higher in subjects with longer lesions, and BV was higher in subjects with lower ABI. Significant correlations were found between lesion length and BV (r = 0.65) and BF (r = 0.52). Significant inverse correlations were found between BV and ABI and between BV and ABP (r = -0.56, for both correlations). Conclusions: In our study, we have shown the feasibility of CTP for the assessment of PAD. In the future, this quantitative method might serve as a non-invasive method, possibly complementing the diagnostic workup of patients with peripheral arterial disease. [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]

Variceal hemorrhage may cause high rebleeding and mortality rates. Preventing the first episode of variceal bleeding is mandatory in patients with high-risk esophageal varices (EV). This study aimed to identify factors that predict the recurrence of EV after endoscopic treatment (ET), and to develop a reasonable therapeutic strategy for EV in cirrhosis. From January 2012 to December 2014, 45 patients with cirrhosis and high-risk EV underwent ET, including sclerotherapy and/or ligation. Statistical analyses identified factors associated with the recurrence of EV after ET, and the Kaplan-Meier method determined the cumulative variceal recurrence rates. The 1-, 2-, and 3-year cumulative posttreatment recurrence rates for EV were 13.3%, 29.5%, and 32.2%, respectively. No significant differences were evident between the patients with and without variceal recurrences at 1-year posttreatment. The multivariate regression analyses identified a history of partial splenic embolization (PSE) and the pretreatment Child-Pugh classification as independent predictors of variceal recurrences at 2 years (p < 0.05) and 3 years (p < 0.05) posttreatment. While EV did not recur after ET and splenic artery embolization in cases with Child-Pugh class A, the overall posttreatment variceal recurrence rates were 0% and 66.7% when PSE was performed before and after ET, respectively, in those with Child-Pugh class B or C. Splenic artery embolization significantly reduced the hepatic venous pressure gradient and markedly lowered the Child-Pugh score in 15 patients. Adjunctive PSE and pretreatment Child-Pugh class A could be independently associated with reduced cumulative recurrence rates of EV post-ET. From the perspectives of portal hemodynamics and hepatic function, splenic artery embolization before or after ET could prevent posttreatment variceal recurrence in patients with Child-Pugh class A, and PSE before ET could achieve the long-term eradication of EV following ET in those with Child-Pugh class B or C. [ABSTRACT FROM AUTHOR]

Background: The emergence of multidrug-resistance (MDR), production of extended-spectrum β-lactamases, and carbapenemase in members of fermentative gram-negative bacilli are a serious threat to public health. Objective: The aim of this study was to determine the burden of multi-drug resistance, the production of extended-spectrum β-lactamases (ESBLs), and carbapenemase in fermentative Gram-negative bacilli in Ethiopian Public Health Institute. Materials and methods: A cross-sectional study was carried out from December 2017 to June 2018. Different clinical samples were collected, inoculated, and incubated according to standard protocols related to each sample. Bacterial identification was performed by using the VITEKR 2 compact system using the GNR card. Antimicrobial susceptibility testing was carried out by the Kirby-Bauer disc diffusion method. Production of ESBL and carbapenemase were confirmed by combination disc and modified Hodge Test method respectively. Results: A total of 238 fermentative Gram-negative bacilli were recovered during the study period, among which E.coli were the predominant isolates followed by K. pneumoniae. The highest percentage of antibiotic resistance was noted against ampicillin (100%) followed by trimethoprim/sulfamethoxazole (81.9%). The isolates showed better sensitivity towards carbapenem drugs. Out of 238 isolates, 94.5% were MDR and of which 8.8% and 0.8% were extensively and pan drug resistant, respectively. Nearly 67% and 2% of isolates were producers of ESBL and carbapenemase, respectively. The isolation rates of MDR, ESBL, and carbapenemase producing stains of the isolates were ≥70% in intensive care unit while the isolation rates in other wards were ≤25%. Conclusions: The findings of this study revealed that the burden of MDR and ESBL was high and carbapenemase producing isolates were also identified which is concerning. This situation warrants a consistent surveillance of antimicrobial resistance of fermentative Gram-negative bacilli and implementation of an efficient infection control program. [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]

Objective: Pakistan has a high pediatric burden of tuberculosis, but few studies describe the treatment experience of children with tuberculosis in Pakistan. We sought to identify risk factors for unsuccessful treatment outcomes in children with drug-susceptible tuberculosis identified in eight hospitals in Karachi, Pakistan. Design: We conducted a retrospective cohort study among children (<15 years old) treated with first-line anti-tuberculosis drugs for presumed or confirmed drug-susceptible tuberculosis between 2016 and 2017. We assessed risk factors for experiencing an unsuccessful treatment outcome through multivariable logistic regression analysis. Results: In total, 1,665 children initiated tuberculosis treatment, including 916 (55.0%) identified through intensified case finding. Unsuccessful treatment outcomes were experienced by 197 (11.8%) children, comprising 27 (1.6%) deaths, 16 (1.0%) treatment failures, and 154 (9.3%) lost to follow-up. An additional 47 (2.8%) children had outcomes not evaluable. In multivariable analysis, children 0–4 years old (OR: 1.80, 95% CI: 1.07–3.04), males (OR: 1.48, 95% CI: 1.04, 2.11), and those with bacteriologic confirmation of disease (OR: 3.39, 95% CI: 1.98, 5.80) had increased odds of experiencing an unsuccessful treatment outcome. Conclusion: Our findings suggest a need to deploy strategies to identify children earlier in the disease process and point to the need for interventions tailored for young children once treatment is initiated. [ABSTRACT FROM AUTHOR]

The evidence that exposure to ozone air pollution causes acute cardiovascular effects is mixed. We postulated that exposure to ambient levels of ozone would increase blood markers of systemic inflammation, prothrombotic state, oxidative stress, and vascular dysfunction in healthy older subjects, and that absence of the glutathione S-transferase Mu 1 (GSTM1) gene would confer increased susceptibility. This double-blind, randomized, crossover study of 87 healthy volunteers 55–70 years of age was conducted at three sites using a common protocol. Subjects were exposed for 3 h in random order to 0 parts per billion (ppb) (filtered air), 70 ppb, and 120 ppb ozone, alternating 15 min of moderate exercise and rest. Blood was obtained the day before, approximately 4 h after, and approximately 22 h after each exposure. Linear mixed effect and logistic regression models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. The definition of statistical significance was p<0.01. There were no effects of ozone on the three primary markers of systemic inflammation and a prothrombotic state: C-reactive protein, monocyte-platelet conjugates, and microparticle-associated tissue factor activity. However, among the secondary endpoints, endothelin-1, a potent vasoconstrictor, increased from pre- to post-exposure with ozone concentration (120 vs 0 ppb: 0.07 pg/mL, 95% confidence interval [CI] 0.01, 0.14; 70 vs 0 ppb: -0.03 pg/mL, CI -0.09, 0.04; p = 0.008). Nitrotyrosine, a marker of oxidative and nitrosative stress, decreased with increasing ozone concentrations, with marginal significance (120 vs 0 ppb: -41.5, CI -70.1, -12.8; 70 vs 0 ppb: -14.2, CI -42.7, 14.2; p = 0.017). GSTM1 status did not modify the effect of ozone exposure on any of the outcomes. These findings from healthy older adults fail to identify any mechanistic basis for the epidemiologically described cardiovascular effects of exposure to ozone. The findings, however, may not be applicable to adults with cardiovascular disease. [ABSTRACT FROM AUTHOR]

Introduction: Studying the role of the immune system in the interaction between mental and physical health is challenging. To study individuals with an intensive, longitudinal study design that requires repetitive sampling in their daily life, non-invasive sampling techniques are a necessity. Urine can be collected in a non-invasive way, but this may be demanding for participants and little is known about fluctuation of inflammatory markers in urine over time. The aim of this study was to investigate the feasibility of non-invasive sampling, and to explore intra-individual differences in inflammatory markers in urine. Materials & methods: Ten healthy individuals collected 24-hour urine for 63 consecutive days. In a pilot analysis, 39 inflammatory markers were examined for detectability in urine, stability over time and under storage conditions, and daily fluctuations. Multiplex analyses were used to quantify levels of eight selected markers: C-reactive protein (CRP), Fractalkine, Interleukin-1 receptor-antagonist (IL-1RA), interferon-α (IFNα), interferon-γ (IFNγ), Interferon gamma-induced protein 10 (IP10), Macrophage inflammatory protein-1β (MIP-1β), and Vascular Endothelial Growth Factor (VEGF). Cross-correlations were calculated between the overnight and 24-hour samples were calculated, to examine whether 24-hour urine could be replaced by the overnight portion for better feasibility. We examined intra- and interindividual differences in the levels of inflammatory markers in urine and the fluctuations thereof. Results: This study showed that levels of selected inflammatory markers can be detected in urine. Cross-correlation analyses showed that correlations between levels of inflammatory markers in the night portion and the 24-hour urine sample varied widely between individuals. In addition, analyses of time series revealed striking inter- and intra-individual variation in levels of inflammatory markers and their fluctuations. Conclusion: We show that the assessment of urinary inflammatory markers is feasible in an intensive day-to-day study in healthy individuals. However, 24-hour urine cannot be replaced by an overnight portion to alleviate the protocol burden. Levels of inflammatory markers show substantial variation between and within persons. [ABSTRACT FROM AUTHOR]

Objectives: Traits of metabolic syndrome (MetS) and biomarkers of inflammation and endothelial dysfunction were examined. We investigated the differences of various biomarkers among individuals with or without Mets in a gender-specific manner. The gender-specific associations between E-selectin and MetS were further evaluated. Methods: A total of 205 patients were recruited from the outpatient clinics of Tri-Service General Hospital, Taipei, Taiwan. Inclusion criteria were age between 20–75 years and BMI < 35 kg/m2. Demographic, anthropometric and MetS index data were compared between genders. Markers of inflammation and endothelial dysfunction were compared between individuals with or without MetS by gender. Results: Age-adjusted E-selectin values showed significant positive correlations with BMI, waist-hip ratio, fasting plasma glucose, systolic and diastolic blood pressure, triglycerides, TNF-α, hsCRP and ICAM-1, and inverse correlation with HDL cholesterol. E-selectin levels were positively correlated with numbers of MetS components in females (P < 0.001) but not in males (P = 0.125). Conclusions: Increased E-selectin levels are significantly associated with increased MetS risk in females, but not in males. [ABSTRACT FROM AUTHOR]

This study investigated the effect of open-placebo on cycling time-trial (TT) performance. Twenty-eight trained female cyclists completed a 1-km cycling TT following a control session or an open-placebo intervention. The intervention consisted of an individual presentation, provided by a medic, in which the concept of open-placebo was explained to the participant, before she ingested two red and white capsules containing flour; 15 min later, they performed the TT. In the control session, the participant sat quietly for 20 min. Heart rate and ratings of perceived exertion (RPE) were monitored throughout exercise, while blood lactate was determined pre- and post-exercise. Post-exercise questionnaires were employed to gain insight into the perceived influence of the supplement on performance. Open-placebo improved time-to-completion (P = 0.039, 103.6±5.0 vs. 104.4±5.1 s, -0.7±1.8 s, -0.7±1.7%) and mean power output (P = 0.01, 244.8±34.7 vs. 239.7±33.2, +5.1±9.5 W) during the TT. Individual data analysis showed that 11 individuals improved, 13 remained unchanged and 4 worsened their performance with open-placebo. Heart rate, RPE and blood lactate were not different between sessions (all P>0.05). Positive expectation did not appear necessary to induce performance improvements, suggesting unconscious processes occurred, although a lack of an improvement appeared to be associated with a lack of belief. Open-placebo improved 1-km cycling TT performance in trained female cyclists. Although the intervention was successful for some individuals, individual variation was high, and some athletes did not respond or even performed worse. Thus, open-placebo interventions should be carefully considered by coaches and practitioners, while further studies are warranted. [ABSTRACT FROM AUTHOR]

To evaluate the association between alcohol intake and incident chronic kidney disease measures as well as the sex differences in this association, we analyzed health screening data of 14,190,878 adults who underwent health screening ≥3 times and had glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and normal proteinuria at baseline. eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration equation. Proteinuria was defined as ≥1+ dipstick proteinuria and low eGFR as <60 mL/min/1.73 m2. The risk of incident proteinuria and low eGFR was analyzed with an extended Cox model with alcohol intake level as a time-varying determinant and the annual change of eGFR with generalized linear model. A J-shape association of alcohol intake with the incident proteinuria was observed in men (adjusted hazard ratio [aHR], 0.961, 95% confidence interval [CI], 0.953–0.970 in men drinking alcohol <10 g/day; aHR 1.139, 95% CI, 1.123–1.154 in men drinking alcohol ≥40 g/day, compared with non-drinking men), and a positive association was seen in women (aHR, 1.034, 95% CI, 1.023–1.044 in women drinking alcohol <10 g/day; aHR, 1.094, 95% CI, 1.034–1.158 in women drinking alcohol ≥40 g/day, compared with non-drinking women). In both sexes, an inverse association of alcohol intake with the annual eGFR decline and incident low eGFR was observed. This study observed a beneficial effect of moderate alcohol intake on incident proteinuria in men and a protective effect of alcohol intake of any amount on the annual eGFR decline and incident low eGFR in both sexes. The long-term implications of these observations need to be elucidated with future studies. [ABSTRACT FROM AUTHOR]

Aeromonas bacteria can cause an infection characterized by septicemia and is one of the most common pathogens in tropical fish. This disease is responsible for high morbidity and mortality rates, causing considerable losses in aquaculture. Thus, the understanding of its pathophysiology is crucial to develop control strategies of this bacterial infection in farmed fish. This study aimed to characterize early pathological aspects of acute sepsis in pacu (Piaractus mesopotamicus) experimentally infected with Aeromonas hydrophila. A total of 160 juvenile pacus were inoculated intraperitoneally with A. hydrophila (1.78 x 109 CFU/mL) and at 0 (control), 1, 3, 6, and 9 hours post-inoculation (hpi), animals were anesthetized and samples were collected for microbiological, light microscopy and transmission electron microscopy (TEM) analyzes. The results showed the occurrence of hemodynamic alterations, such as hemorrhage and congestion, which were observed mainly after 6 and 9 hpi. It was possible to re-isolate Aeromonas at all sampling times except in control group. However, just after 9 hpi it was possible to find the bacteria in all fish and tissues. Light microscopy analyses revealed a degenerative process, necrosis and vascular damage mainly at 6 and 9 hpi. According to the ultrastructural examination, areas of cellular death were identified in all examined tissues, especially at 6 and 9 hpi. However, the most severe, related to necrosis, were observed after 6 and 9 hpi. The findings suggested that this bacterium spreads in the first hpi through the fish organs, mainly affecting spleen, liver and kidney, causing irreversible lesions at the molecular level. [ABSTRACT FROM AUTHOR]

Immune responses have been mostly studied at a specific time in anuran species. However, time-changes related to immunomodulation associated with glucocorticoid (GC) alterations following stressors and GC treatment are complex. The present study describes time-related changes in immune response and corticosterone (CORT) plasma levels following restraint challenge, short, mid and long-term captivity, and CORT exogenous administration by transdermal application (TA) in Rhinella ornata toads. We observed increased neutrophil: lymphocyte ratios after restraint challenge and CORT TA, without changes following short and mid-term captivity. Plasma bacterial killing ability was sustained in all treatments, except long-term captivity, with decreased values after 90 days under such conditions. Phagocytic activity of peritoneal cells increased after mid-term captivity, and the phytohemagglutinin swelling response was impaired in those animals treated with CORT TA for 20 consecutive days. Plasma CORT levels increased or were sustained after restraint challenge (depending on initial values), decreased following mid and long-term captivity (for those animals showing high CORT in the field) and increased after 20 days of CORT TA. By performing assessments of time-changes in immune processes and CORT plasma levels in R. ornata, we demonstrate immuno-enhancing effects following restraint, short and mid-term stressors, while long-term stressors and CORT TA promoted immunosuppression in these toads. [ABSTRACT FROM AUTHOR]

Inflammatory immune responses induced by lipopolysaccharides (LPS) of gram-negative bacteria play an important role in the pathogenesis of preterm labor and delivery, and in neonatal disorders. To better characterize LPS-induced inflammatory response, we determined the cytokine profile of umbilical cord blood mononuclear cells (UBMC) stimulated with LPS of seven vaginal gram-negative bacteria commonly found in pregnant women with preterm labor and preterm rupture of membrane. UBMC from ten newborns of healthy volunteer mothers were stimulated with purified LPS of Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Proteus mirabilis, Acinetobacter calcoaceticus, Citrobacter freundii, and Pseudomonas aeruginosa. UBMC supernatants were tested for the presence of secreted pro-inflammatory cytokines (IL-6, IL-1β, TNF), anti-inflammatory cytokine (IL-10), TH1-type cytokines (IL-12, IFN-γ), and chemokines (IL-8, MIP-1α, MIP-1β, MCP-1) by Luminex technology. The ten cytokines were differentially induced by the LPS variants. LPS of E. coli and E. aerogenes showed the strongest stimulatory activity and P. aeruginosa the lowest. Interestingly, the ability of UBMC to respond to LPS varied greatly among donors, suggesting a strong individual heterogeneity in LPS-triggered inflammatory response. [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: Blood transfusion is the most frequently used and life-saving therapeutic procedure today. Transmission of virus, bacteria and parasitic microorganisms may occur due to transfusion (Transfusion transmitted infections-TTIs). Hepatitis B and C, human immunodeficiency virus (HIV) and syphilis (Treponema pallidum) bear the risk of transmission by transfusion. Hepatitis B surface antigen (HBsAg), anti-HCV, anti-HIV½ and syphilis antibody (VDRL: Venereal Disease Research Laboratory) are routinely controlled in all donated blood samples. The aim of the present study was to analyze the seroprevalence rates of blood donors through screening test results according to duration, age range and gender. Material and methods: Data of all blood donors obtained from blood Centre of Marmara University Pendik Training and Research Hospital between January 2013 and October 2018 were analyzed retrospectively. Serum samples of the donors were analyzed for HBsAg, anti-HCV, anti-HIV½ and VDRL. Test results of 114.240 donors were scanned. Gender, age range and distribution by years of these donors were analyzed. According to age distribution of donors were divided into 4 groups. Results: There were 114.240 participants including 106.153 (92.9%) males and 8.087 (7.1%) females. The positivity rate of HBsAg was detected 0.4% (36/8087) in females and 0.5% (500/106.153) in males. The positivity rate of anti-HCV was detected 0.4% (32/8.087) in females and 0.3% (344/106.153) in males. The positivity rate of anti HIV½ was 0.1% (9/8.087) in females and 0.1% (92/106.153) in males whereas the positivity rate of VDRL was 0.5% (41/8.087) in females and 0.3% (362/ 106.153) in males. Positivity rate for HBsAg and HCV were lower in the cases between 18 and 30 years of age. The positivity rates for anti-HIV½ was not significantly different according to the age range. Positivity rate for VDRL was higher in the cases at 51 years of age and older. Conclusion: No difference was found between men and women in terms of HBsAg, anti-HCV and anti-HIV½positivity. However, VDRL test positivity was significantly higher in female participants. Furthermore, HBsAg, anti-HCV and VDRL positivity rates increased by age. [ABSTRACT FROM AUTHOR]

The bovine dry period is a non-lactating period between consecutive lactations characterized by mammary gland involution and redevelopment phases to replace senescent mammary epithelial cells with active cells primed for the next lactation. Dairy cows exposed to heat stress during the dry period experience milk yield reductions between 3–7.5 kg/d in the next lactation, partially attributed to processes associated with mammary cell growth and turnover during the dry period. However, the carry-over impact of dry period heat stress on mammary morphology during lactation has yet to be determined. In the current study, we hypothesized that exposure to heat stress during the dry period would alter alveolar microstructure and cellular turnover (i.e. proliferation and apoptosis) during lactation. Cows were either subjected to heat stress (HT, access to shade; n = 12) or cooling (CL, access to shade, fans, and soakers; n = 12) for a 46 d dry period. Upon calving, all cows were treated similarly with access to cooling for their entire lactation. Six cows per treatment were randomly selected for mammary gland biopsies at 14, 42, and 84 days in milk. Tissues were sectioned and stained for histological analysis. During lactation, HT cows produced 4 kg less colostrum and 3.7 kg less milk compared with CL cows. Lactating mammary gland microstructure was impacted after exposure to dry period heat stress; HT cows had fewer alveoli and a higher proportion of connective tissue in the mammary gland relative to CL cows, however alveolar area was similar between treatments. Rates of mammary epithelial cell proliferation and apoptosis were similar between treatment groups. This suggests that heat stress exposure during the dry period leads to reductions in milk yield that could be caused, in part, by a reduction in alveoli number in the lactating mammary gland but not to dynamic alterations in cellular turnover once lactation is established. [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]

There are different views on which of the two forms of viral spread is more efficient in vivo between cell-free and cell-associated virus. In this study, discrete time human immunodeficiency virus models are formulated and analysed with the goal of determining the form of viral spread that is more efficient in vivo. It is shown that on its own, cell-free viral spread cannot sustain an infection owing to the low infectivity of cell-free virus and cell-associated virus can sustain an infection because of the high infectivity of cell-associated virus. When acting concurrently, cell-associated virus is more efficient in spreading the infection upon exposure to the virus. However, in the long term, the two forms of viral spread contribute almost equally. Both forms of viral spread are shown to be able to initiate an infection. [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]

Introduction: The success of antiretroviral treatment (ART) programs can be compromised by high rates of patient loss to follow-up (LTFU). We assessed the incidence and risk factors of LTFU in a large cohort of HIV-infected children receiving ART in Thailand. Methods: All children participating in a multicenter cohort (NCT00433030) between 1999 and 2014 were included. The date of LTFU was 9 months after the last contact date. ART interruption was defined as ART discontinuation for more than 7 days followed by resumption of treatment. Baseline and time-dependent risk factors associated with LTFU were identified using Fine and Gray competing risk regression models with death or referral to another hospital as competing events. Results: Of 873 children who were followed during a median of 8.6 years (interquartile range 4.5–10.6), 196 were LTFU, 73 died, and 195 referred. The cumulative incidence of LTFU was 2.9% at 1 year, 7.3% at 5 years and 22.2% at 10 years. Children aged 13 years and more had a 3-fold higher risk (95% confidence interval 2.06–4.78) of LTFU than those younger. Children who had interrupted ART within the previous year had a 2.5-fold higher risk (1.12–5.91) than those who had not. The risk of LTFU was lower in children stunted (height-for-age Z-scores <-2 SD) (0.42–0.96) or underweight (weight-for-age Z-scores <-2 SD) (0.24–0.97). Conclusion: Adolescence, ART interruption and absence of growth deficit were associated with LTFU. These may be warnings that should draw clinicians’ attention and possibly trigger specific interventions. Children with no significant growth retardation may also be at risk of LTFU. [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]

Laboratory assays for identifying recent HIV-1 infections are widely used for estimating incidence in cross-sectional population-level surveys in global HIV-1surveillance. Adequate assay and laboratory performance are required to ensure accurate incidence estimates. The NIAID-supported External Quality Assurance Program Oversight Laboratory (EQAPOL) established a proficiency testing program for the most widely-used incidence assay, the HIV-1 Limiting Antigen Avidity EIA (LAg), with US Centers for Disease Control and Prevention (CDC)-approved kits manufactured by Sedia Biosciences Corporation and Maxim Biomedical. The objective of this program is to monitor the performance of participating laboratories. Four rounds of blinded external proficiency (EP) panels were distributed to up to twenty testing sites (7 North American, 5 African, 4 Asian, 2 South American and 2 European). These panels consisted of ten plasma samples: three blinded well-characterized HIV-1-seropositive samples that were included as replicates and an HIV-negative control. The seropositive samples spanned the dynamic range of the assay and are categorized as either recent or long-term infection. Participating sites performed the assay according to manufacturers’ instructions and completed an online survey to gather information on kit manufacturer, lot of kit used, laboratory procedures and the experience of technicians. On average, fifteen sites participated in each round of testing, with an average of four sites testing with only the Maxim assay, seven testing with only the Sedia assay and five sites utilizing both assays. Overall, the Sedia and Maxim assays yielded similar infection status categorization across the laboratories; however, for most of the nine HIV+ samples tested, there were significant differences in the optical density readouts, ODn (N = 8) and OD (N = 7), between LAg kit manufacturers (p < 0.05 based on mixed effects models. The EQAPOL LAg program is important for monitoring laboratory performance as well as detecting variations between manufacturers of HIV-1incidence assays. [ABSTRACT FROM AUTHOR]

The present study investigates the wound healing potential of three chitosan-based topical preparations loaded with either tea tree essential oil, rosemary essential oil or a mixture of both oils in vivo. Essential oils of M. alternifolia and R. officinalis were analyzed using GC/MS. Essential oil-loaded chitosan topical preparations were formulated. Wound healing potential was evaluated in vivo using an excision wound model in rats. GC/MS analysis of M. alternifolia and R. officinalis essential oils revealed richness in oxygenated monoterpenes, representing 51.06% and 69.61% of the total oil composition, respectively. Topical application of chitosan-based formulation loaded with a mixture of tea tree and rosemary oils resulted in a significant increase in wound contraction percentage compared to either group treated with individual essential oils and the untreated group. Histopathological examination revealed that topical application of tea tree and rosemary oil combination demonstrated complete re-epithelialization associated with activated hair follicles. The high percentage of oxygenated monoterpenes in both essential oils play an important role in the antioxidant and wound healing potential observed herein. Incorporation of tea tree and rosemary essential oils in chitosan-based preparations in appropriate combination could efficiently promote different stages of wound healing. [ABSTRACT FROM AUTHOR]