Invasive Non-Native Species (INNS) can co-transport externally and internally other organisms including viruses, bacteria and other eukaryotes (including metazoan parasites), collectively referred to as the symbiome. These symbiotic organisms include pathogens, a small minority of which are subject to surveillance and regulatory control, but most of which are currently unscrutinised and/or unknown. The (putatively) pathogenic symbionts co-transported by an INNS host may be latent or associated with asymptomatic infection and unable to cause disease in the INNS, but may be opportunistic pathogens of other hosts, causing impact to one or more hosts in their new range. These pathogens potentially pose diverse risks to other species, with implications for increased epidemiological risk to agriculture and aquaculture, wildlife/ecosystems, and human health (zoonotic diseases). Aquatic INNS and their symbionts have many introduction pathways, including commodity and trade (releases, escapes, contaminant), transport (stowaway), and dispersal (corridor, unaided). The risks and impacts arising from co-transported pathogens, including other symbionts of unknown pathogenic virulence, remain largely unexplored, unlegislated, and difficult to identify and quantify. Here, we propose a workflow to determine any known and potential pathogens of aquatic INNS. This workflow acts as a prerequisite for assessing the nature and risk posed by co-transported symbionts of INNS. A better understanding of co-transported organisms, the risks they pose and their impact, is necessary to inform policy and INNS risk assessments. This leap in evidence will be instrumental to devise an appropriate set of statutory responsibilities with respect to these symbionts, and to underpin new and more effective legislative processes relating to the disease screening and risk assessment of INNS.

Background and Objective: The knowledge about the impact of the nonpharmacological measures to control the COVID-19 pandemic can give insight to ways in which they can also be applied for other respiratory diseases. To assess the impact of containment measures of the COVID-19 pandemic on pneumonia hospitalizations in children from 0 to 14 years of age in Brazil. Methods: Data from hospital admissions for pneumonia were obtained from the Department of Informatics of Brazilian Public Health System database in the period of 2015–2020 and analyzed by macro-regions and age groups. To evaluate the effect of containment measures, used in the pandemic, on the incidence of pneumonia, the absolute reduction and relative reduction were calculated by analyzing the subsets 2015-2019 vs 2020. Results: Comparing the subsets of April-August 2015-2019 vs April-August 2020, there was an expressive reduction in the average incidence of hospitalizations, with numbers ranging from -87% [IRR 0.12 (0.10 to 0.14)] for < 4 years, -79% [IRR 0.21 (0.07 to 0.57)] for 5-9 years, -73% [IRR 0.26 (0.05 to 1.21)] for 10-14 and -86% [IRR 0.14 (0.06 to 0.29)] for <14 years. Conclusion: We found a significant decrease in cases of pneumonia during the COVID-19 pandemic. Nonpharmacological public health interventions can contribute to the decline of other respiratory infectious diseases.

The calcium looping thermochemical thermal energy storage is one of the best high-temperature heat storage schemes for 3th concentrating solar power photothermal power, but its application is restricted by the inherent low solar absorptance and poor cyclic stability of CaCO3/CaO. Herein, the solar absorptance of CaCO3 particles is enhanced by doping Mn-Fe oxides, meanwhile, awns of setaria faberis and microcrystalline cellulose are used as bio-templates to generate pores inside the particles. The test results show that the prepared particles possess adequate anti-crushing strength, high cyclic stability, high solar absorption, and high carbonation rate. In addition, the carbonation kinetic equation of the composite porous particles is studied with the influence factors such as CO2 partial pressure, reaction temperature, and particle morphology taken into consideration. is of great significance for the design and regulation of the carbonator achieving highly stable heat output in the CaL thermochemical heat storage system.

Overview:  The process of 3D printing is essentially a manufacturing technology to create objects in three dimensions using various materials heated to a temperature that allows them to be formed into different shapes.  3D printing has gained much popularity in the past few decades due to availability of cost-effective 3D printers as well as books/knowledge source on how to use 3D printers.   It is a convenient way to create prototypes or customized items for inventors and novice who likes to create their own designs.  Prior to 3D printing, 3D model (typically in STL file format) needs to be created through software like TINKERCAD to create the design shapes ideal for printing.  The lesson here is focus on 3D modelling using TINKERCAD rather than detail 3D printing which is more hardware focus.Lesson ObjectivesStudents will explore a foundation in 3D modeling by designing simple structures.  Students will learn tips, techniques and associated best practices for exciting explorations in 3D modelling and printing.Students will create a name tag using TINKERCAD with detail step-by-step instructionStudents will work independently using TINKERCAD after completing the initial name tag design to create another design that is useful and can be apply to daily use (pencil box, soap holder, bookmark, bookend, etc..)Students are encourage to further their learning and creating design and publish it on open source such as Thingiverse.Vocabulary3D modelComputer-aided design (CAD)Additive ManufacturingExtrusionFilamentSnapGridSTL FileWorkplaneSolid / HoleSuggested time:                 240 minutes (best to break into 3 parts)Suggested age level:         8+Required and optional materials:TINKERCAD (FREE, need to create an account)Markers / Pencils / PaperScissors / Tape or glue3D Printer (Optional, only if you want to print out your designs).    A list of popular 3D printers with various price point and functionality can be found in this link.  If you are looking for specific 3D printer with enclosure as well as dual extruder (allow you to print 2 different color), we will recommend to use the FlashForge Creator Pro.  3D Printer Filament (Optional, only if you want to print out your designs).     You can find many 3D printer filament materials on the market, the dominate filament type is ABS or PLA.  We recommend to use PLA as it is the least toxic filament.  For more guidance on what filament to choose and safety tips, please read through the safety tips article here.Reflection:  *Specific printer and filament are recommendations. Feel free to use another make or model. Also, be aware that 3D printers are slow; the quality of the design also depend on the resolution of the printing.  Prior to create your design, you should consider the difficulty of the print (shapes) and the duration of the print (size).  Optional resources Amazon.com: Tinkercad For Dummies (9781119464419): Bryant, Shaun C.: Books 3D Printing and Maker Lab for Kids: Create Amazing Projects with CAD Design and STEAM Ideas (Lab for Kids, 22): Sequeira, Eldrid: 9781631597992: Amazon.com: Books 3D Printing & Sudoku Lovers Puzzle Activity Gift Book: Depot, Mega Media: 9798632850827: Amazon.com: Books 3D Printing Failures: 2020 Edition: How to Diagnose and Repair ALL Desktop 3D Printing Issues: Aranda, Sean, Feeney, David: 9781710054590: Amazon.com: Books Lesson Plan (Part 1:  60 min)Go to TINKERCAD and completed the STARTER lessons (total of 4)

Epoxy fatty acids (EFAs), which exist in the human body, are signaling molecules that maintain homeostasis. They are involved in anti-inflammation and are precursors of dihydroxy fatty acids. EFAs derived from the C20 polyunsaturated fatty acid (PUFA) arachidonic acid by lipoxygenases, such as 5,6-epoxy-7E,9E,11Z,14Z-eicosatetraenoic acid and 8,9-epoxy-5Z,10E,12E,14Z-eicosatetraenoic acid, are found in humans and mice, respectively. However, EFAs derived from C18 PUFAs by lipoxygenases have not been identified to date. In this study, the putative lipoxygenase gene of Spingopyxis macrogoltabida was cloned and expressed in Escherichia coli. The activity and catalytic efficiency (kcat/Km) of the recombinant enzyme were the highest for linoleic acid among the C18 PUFAs, including also α-linolenic acid and γ-linolenic acid. The product obtained from the conversion of linoleic acid by the putative lipoxygenase was identified as 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE) by high-performance liquid chromatography using 9-HODE and 13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE) standards. These results indicate that the enzyme is a linoleate 9-lipoxygenase. The enzyme converted linoleic acid, α-linolenic acid, and γ-linolenic acid into 9-HODE, 13-hydroxy-9Z,11E,15Z-octadecatrienoic acid, and 9-hydroxy-6Z,10E,12Z-octadecatrienoic acid, respectively. Moreover, the enzyme also converted the three C18 PUFAs into 9,10-epoxy-11E,13E-octadecadienoic acid, 12,13-epoxy-8E,10E,15Z-octadecatrienoic acid, and 9,10-epoxy-6Z,11E,13E-octadecatrienoic acid, respectively, which were identified as new EFAs by liquid chromatography-mass spectrometry/mass spectrometry. To our knowledge, this is the first report on the biosynthesis of EFAs from C18 PUFAs via a lipoxygenase.

Commonly related to abuse of alcohol or hyperemesis gravidarum, Gayet wernicke encephalopathy is neurological disorder due to a deficiency of thiamine. The diagnosis is based on a triade made of ophthalmoplegia, ataxia and mental disturbance. MRI imaging confirms the diagnosis.

Aim: In this study, we evaluated the presence of sarcopenia multidimensionally in patients with knee osteoarthritis (OA) using clinical, ultrasonographic and biochemical parameters, and in this respect, it was aimed to investigate the relation between OA and sarcopenia and to identify the most practical, easily accessible and inexpensive method for investigating sarcopenia.Materials and methods: 102 patients with clinical and radiological diagnosis of knee osteoarthritis and 33 healthy control subjects were included in the study. The detailed musculoskeletal system examination of the patients included in the study was carried out by a single physician, and blood sample tests were recorded .Dual-X-ray absorptiometry (DEXA) is used to measure Body composition parameters and muscle mass measurements, isometric muscle strength evaluations, handgrip strength and gait speeds for diagnosis of sarcopenia. Short-form -36 (SF-36) The Nutritional Assessment-short form (MNA), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the International Physical Assessment Questionnaire Short Form (IPAQ-SF) and the Center for Epidemiologic Studies Depression Scale (CES-D scale) were administered to every patient as outcome measures.Results: Body composition parameter results showed that sarcopenic patients had statistically lower values as fat mass, lean body mass and skeletal muscle index (p <0.001, p= 0.001, p <0.001, respectively) than those of non-sarcopenic and control group. It was determined that body composition values measured with DEXA, ultrasonographic measures, isokinetic muscle strength assessment, handgrip strength and gait speed had predictive values for sarcopenia. Conclusion: We found that patients with sarcopenic OA were older, weaker, undernourished, and restricted in their level of physical activity in the study in which we identified sarcopenia as approximately 12% in patients with osteoarthritis. Among the methods of determining sarcopenia, ultrasound becomes prominent with its practical, cheap and easily accessible features. We think that our results will increase the awareness of the presence of sarcopenia in OA patients.

Abstract: The Prothrombin mutation G2021 alone is considered a minor risk factor for thromboembolism, but thromboembolic events are more likely in the presence of additional risk factors. We report on a 44-year-old female with an atrial thrombus causing pulmonary embolism and transiting through a patent foramen ovale. The thrombus was extracted by open heart operation. The patient had a family history for thromboembolic events. Further diagnostic after surgery found the patient positive for the Prothrombin mutation G2021, but not for the Factor V Leiden mutation. After surgery, a permanent oral anticoagulation has been started.

Background: Limb ischemia is a major complication of femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO). Use of ankle-brachial index (ABI) to monitor limb perfusion in VA-ECMO has not been described. We report our experience monitoring femoral VA-ECMO patients with serial ABI and the relationships between ABI and near infrared spectroscopy (NIRS). Methods: This is a retrospective single-center review of consecutive adult patients placed on femoral VA-ECMO between January 2019 and October 2019. Data were collected on patients with paired ABI and NIRS values. Relationships between NIRS and ABI of the cannulated (E-NIRS and E-ABI) and non-cannulated legs (N-NIRS and N-ABI) along with the difference between legs (D-NIRS and D-ABI) were determined using Pearson correlation. Results: Overall, 22 patients (mean age 56.5±14.0 years, 72.7% male) were assessed with 295 E-ABI and E-NIRS measurements, and 273 N-ABI and N-NIRS measurements. Mean duration of ECMO support was 129.8±78.3 hours. ECMO-mortality was 13.6% and in-hospital mortality was 45.5%. N-ABI and N-NIRS were significantly higher than their ECMO counterparts (ABI mean difference 0.16, 95%CI 0.13-0.19, p<0.0001; NIRS mean difference 2.51, 95%CI 1.48-3.54, p<0.0001). There was no correlation between E-ABI vs. E-NIRS (r=0.032, p=0.59), N-ABI vs. N-NIRS (r=0.097, p=0.11), or D-NIRS vs. D-ABI (r=0.11, p=0.069). Conclusions: ABI is a quantitative metric that may be used to monitor limb perfusion and supplement clinical exams to identify limb ischemia in femorally cannulated VA-ECMO patients. More studies are needed to characterize the significance of ABI in femoral VA-ECMO and its value in identifying limb ischemia in this patient population.

Aortic dissection is an aggressive and life-threatening cardiac disease with highly challenging in surgical operation. Bentall procedure was potential complications. How to manage them would be important to improve patient outcomes. In this case, we present a 41-year-old male patient with iatrogenic aortic dissection. He had aortic valve replacement and repair of atrial septal defect in 2012. After 5 years, he suffered reoperation for aortic dissection. A year later the patient was readmitted for a voluminous pulsatile mass over the anterior thorax, confirming the presence of a huge pseudoaneurysm originating from the left coronary bottom performed during the Bentall procedure, requiring a third operation to repair the hemorrhagic site. The pseudoaneurysm was common complication after inclusion technique in Bentall procedure. How to effective hemostasis or tension-free anastomosis was important to improve patient outcomes.

Objective:To integrate the effects of duration of using intraaortic balloon pump (IABP) on renal function, major adverse cardiac events (MACEs) and all-cause mortality in patients with acute myocardial infarction (AMI) complicating pump failure. Methods:Between March 2017 and June 2018, a retrospective study enrolled 306 patients with AMI complicating pump failure who underwent coronary artery angiography (CAG) or percutaneous coronary intervention (PCI) was conducted. Patients were divided into the duration ≤4 days and the duration＞4 days in basis of median the IABP duration. We compared the renal function parameters at the three time section of IABP implantation between two groups. Analysis of factors of contrast-induced nephropathy (CIN), 12-month MACEs and all-cause mortality were also performed. Results:There were 146 patients in IABP duration ≤4 days and 92 patients in IABP duration > 4 days. Renal function was only correlated with IABP duration instead of timing of IABP implantation. On multivariate analysis, CIN risk increased by 81.2% (RR= 1.812, 95%CI, 1.167–3.763) for every 100mL increment of contrast agent. Hematocrit, blood platelet, IABP use >4 days were significantly inversely associated with CIN. Cox-regression analysis suggested that IABP duration was not significantly correlated with the incidence of 12-month MACEs and all-cause mortality. Conclusion:Longer duration of IABP implantation was beneficial to renal function, but was not significantly correlated with the incidence of 12-month MACEs and all-cause mortality in patients with AMI complicating pump failure. Patients undergoing PCI or CABG should notice that the potential damage of high dose of contrast agents on the renal function.

Background: Red blood cell (RBC) transfusion increases morbidity and mortality after cardiac surgery. Despite the use of patient blood management methods, blood transfusions may still be needed in cardiac surgery. This study aims to determine the risk factors for blood transfusions in isolated coronary bypass graft surgery with the use of a restrictive transfusion strategy along with individualized patient blood management. Methods: A total of 198 consecutive patients (28 females, 170 males; age range 38–87) who underwent isolated CABG surgery in single private hospital using a restrictive transfusion strategy between April 2015 and October 2020 were included in the study. Patients were divided into two groups: with RBC transfusion and without RBC transfusion. Preoperative, intraoperative, and postoperative values were compared between groups. The risk factors for transfusion and transfusion probability were analyzed. Results: Preoperative hematocrit level and female gender (OR: 0.752; 95% CI 0.639–0.884; p = 0.001; OR: 7.874; 95% CI 1.678–36.950; p = 0.009, respectively) were the statistically significant independent risk factors for red blood cell transfusion. In female patients, the RBC transfusion probability was 61.08% when the preoperative hematocrit was 30%. The intensive care unit and hospital stay were longer in the blood transfusion group. Conclusions: The risk factors for RBC transfusion were preoperative anemia and female gender in isolated CABG surgery with restrictive blood transfusion strategies. Keywords: anemia, blood transfusion, coronary artery bypass, patient blood management, restrictive blood transfusion

We report about a 78-year-old woman with severe aortic valve stenosis (AS). She had heavily calcified and thickened aortic valve leaflets with black pigmentation. After excision of the aortic valve leaflets, biological aortic valve replacement (AVR) was performed. Alkaptonuria was diagnosed and confirmed based on increased urinary excretion of homogentisic acid. She has had no cardiovascular system-related symptoms for 3 years and no evidence of structural valve deterioration. Data on the long-term outcomes of AVR associated with structural valve deterioration that could regulate prosthetic valve selection in alkaptonuria are limited. Therefore, further research on the natural evolution of AS and the rate of structural valve deterioration after AVR is needed to provide an optimal prosthesis for these patients.

Background: The worldwide escalation of Coronavirus Disease 2019 (COVID-19) has urgently required the development of safe and effective vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of disease. The BNT162b2 (Pfizer–BioNTech) RNA-based vaccine confers 95% protection against COVID-19 by encoding a mutated isoform of SARS-CoV-2 full-length spike (S) protein. Objective: Here, we report the antigen-specific immune profile against SARS-CoV-2 S protein after vaccination with a single dose of BNT162b2 in order to define the immunological landscape required for an efficient response to the SARS-CoV-2 vaccine. Methods: We determined the levels of antibodies and antigen-specific B, T and NK-T cells against a recombinant GFP tagged SARS-CoV-2 S protein in subjects up to 20 days after injection of a single dose of BNT162b2 vaccine using a combined approach involving serological assays and flow cytometry analyses. Former COVID-19 patients have been also included in this study to evaluate the effect of vaccine after exposition to SARS-CoV-2. Results: The level of antigen-specific helper T-cells against SARS-CoV-2 S protein was reduced in subjects, low responsive or unresponsive to vaccination with respect to the highly responsive individuals, while the numbers of antigen-specific regulatory and cytotoxic T-cells were comparable. Of interest, in former COVID-19 patients, a single dose of BNT162b2 vaccine induced a significant increase of antibody production simultaneous with an antigen-specific B and NK-T cell response. Conclusion: Taken together, these results suggest that favorable immune profiles support the progression and an effective reaction to BNT162b2 vaccination.

Leptospermum scoparium J. R. Forst et G. Forst, known as mānuka by Māori, the indigenous people of Aotearoa (New Zealand), is a culturally and economically significant shrub species, native to New Zealand and Australia. Chemical, morphological and phylogenetic studies have indicated geographical variation of mānuka across its range in New Zealand, and genetic differentiation between New Zealand and Australia. We used pooled whole genome re-sequencing of 76 L. scoparium and outgroup populations from New Zealand and Australia to compile a dataset totalling ~2.5 million SNPs. We explored the genetic structure and relatedness of L. scoparium across New Zealand, and between populations in New Zealand and Australia, as well as the complex demographic history of this species. Our population genomic investigation suggests there are five geographically distinct mānuka gene pools within New Zealand, with evidence of gene flow occurring between these pools. Demographic modelling suggests three of these gene pools have undergone expansion events, whilst the evolutionary histories of the remaining two have been subjected to contractions. Furthermore, mānuka populations in New Zealand are genetically distinct from populations in Australia, with coalescent modelling suggesting these two clades diverged ~9 –12 million years ago. We discuss the evolutionary history of this species and the benefits of using pool-seq for such studies. Our research will support the management and conservation of mānuka by landowners, particularly Māori, and the development of a provenance story for the branding of mānuka based products.

Improved global access to novel age-appropriate formulations for paediatric subsets, either of new chemical entities or existing drugs, is a priority to ensure that medicines meet the needs of these patients. However, despite regulatory incentives, the introduction to the market of paediatric formulations still lags behind adult products. This is mainly caused by additional complexities associated with the development of acceptable age-appropriate paediatric medicines. This position paper proposes the use of a paediatric Quality Target Product Profile (pQTPP) as an efficient tool to facilitate early planning and decision making during the children-centric formulation design for new chemical entities, or to repurpose/reformulate off-patent drugs. Essential key attributes of a paediatric formulation are suggested and described. Moreover, greater collaboration between formulation experts and clinical colleagues, including healthcare professionals, is advocated to lead to safe and effective, age-appropriate medicinal products. Acceptability testing should be a secondary endpoint in paediatric clinical trials to ensure post-marketing adherence is not compromised by a lack of acceptability. Not knowing the indications and the related age groups and potential dosing regimens early enough is still a major hurdle for efficient paediatric formulation development; however the proposed pQTPP could be a valuable collaborative tool for planning and decision making to expedite paediatric product development.

Objective To analyze the effect of nasopharyngeal ventilation on the detection rate of colorectal polyps in 200 middle-aged and elderly overweight patients during painless colonoscopy. Methods A total of 100 patients aged 50-75 years, body mass index (BMI) ≥24 or abdominal circumference ≥85 cm in males and ≥82 cm in females, without underlying diseases, who underwent nasopharyngeal ventilation during painless colonoscopy at physical examinations in our hospital from 2019 to 2020, were selected as the observation subjects (n = 100). The control sample area was determined by propensity matching according to the basic information characteristics presented by the observation group. 100 patients received mask oxygen at physical examinations were randomly selected in the control group (n = 100). Results The verification analysis after matching indicated that there were no intraoperative and postoperative adverse reactions, the number of intraoperative limb movements was less than 1, and the intestinal peristalsis intervals were more than 5s in both groups, without atropine intervention. Colonoscopy was performed by senior endoscopists with a withdrawal time of 6-8 min. When the intraoperative SpO2 was lower than 90% but higher than 85%, the patients in the observation group underwent nasopharyngeal ventilation while those in the control group received mask oxygen assisted chin-lift. As a result, the SpO2 was maintained higher than 90%. The detection rate of colorectal polyps was compared between the two groups. Conclusion The detection rate of colorectal polyps in the observation group was higher than that in the control group, with a statistically significant difference. It may result from the reduction of ineffective respiratory movement and intraoperative intestinal peristalsis in middle-aged and elderly overweight patients.

Reply to Betts et al. “When are hypotheses useful in ecology and conservation?”Meredith Root-Bernstein1, 2, 3UMR CESCO, CNRS, Muséum National d’Histoire Naturelle, Paris, FranceCenter of Applied Ecology and Sustainability, Santiago, ChileInstitute of Ecology and Biodiversity, Santiago, ChileWords: 2045It is difficult to disagree with Betts et al. (2021) when they claim that hypotheses are often useful but sometimes not necessary. The difficulty with Betts et al. does not lie with any of their individual points, but rather with the lack of a clear argument giving them structure. This is not just a critique of style. It is relevant because it is an example of what I think is the real problem in ecological research. In my view, the lack of hypotheses in ecology and conservation is not just about the rise of big data approaches, or the documentation of applied work. More generally, I argue that the low use of hypotheses reflects the failure of ecology and conservation to value and develop discipline-specific forms of argument, logic and reasoning. I first address the particular nature of the hypothesis as an argument form, and then the question of whether there are specifically ecological argument forms. Finally I argue that we need a broad set of arguments and logics suitable to the broad set of phenomona in ecology, and that hypotheses are usually derived from non-hypothetico-deductive reasoning and logic. If we want more or better hypotheses, we need more and better forms of non-hypothetico-deductive ecological reasoning.A hypothesis is a form of argument structured so that it can be answered in only one of two ways: rejection or non-rejection. Hypotheses are also characterized by particular ways of framing questions that are considered legitimate, interesting, or elegant, which varies by the discipline or subject matter. I will illustrate my points about the need for forms of argument that fit a subject matter with the Betts et al. paper itself. Betts et al. present their argument about why ecologists should use hypotheses in the form of a couple of hypotheses, the predictions of which they test in a hypothetico-deductive manner on quantitative data using statistical reasoning. They structure their hypothesis as though it were an evolutionary argument: they identify potential discrete individual benefits of adopting a behaviour within a specific environment.

The choice of patient for a single lung resection is challenging for the surgeon. This report is presenting our experience in surgical treatment for patient with metastatic synovial sarcoma who initially underwent total left pneumonectomy and to identify possible predictors for the selection of patients who may undergo surgical treatment.

Objective: Investigate the cardiorespiratory effects of non-invasive neurally adjusted ventilatory assist (NIV-NAVA), non-synchronized nasal intermittent positive pressure ventilation (NIPPV), and nasal continuous positive airway pressure (NCPAP) during the critical period shortly after extubation. Hypothesis: Levels of non-invasive pressure support provided and/or presence of synchronization can affect cardiorespiratory parameters. Study design: Randomized crossover trial. Patient-subject selection: Infants with birth weight (BW) ≤ 1250g undergoing their first planned extubation were randomly assigned to all 3 modes following extubation. Methodology: Electrocardiogram and electrical activity of the diaphragm (Edi) were recorded during 30min on each mode. Analysis of heart rate variability (HRV), diaphragmatic activity (Edi area, breath area, amplitude, inspiratory and expiratory times) and respiratory variability (RV) were compared between modes. Results: 23 enrolled infants had full data recordings and analysis: median [IQR] gestational age = 25.9 weeks [25.2-26.4], BW = 760g [595-900], and post-natal age 7 [4-19] days. There were no differences in HRV parameters between modes. During NIV-NAVA and NIPPV, diaphragmatic activity was significantly lower and RV higher than NCPAP. Delivered peak inflation pressures (PIPs) were lower during NIV-NAVA than NIPPV (14 cmH2O [13-16] vs cmH2O 16 [16-17]; p<0.001). However, due to a significantly higher proportion of assisted breaths (99% [92-103] vs. 51% [38-82]; p<0.001) NIV-NAVA provided a higher mean airway pressure (MAP)(9.4 cmH2O [8.2-10.0] vs. 8.2 cmH2O [7.6-9.3]; p=0.002). Conclusions: NIV-NAVA and NIPPV applied shortly after extubation were associated with positive cardiorespiratory effects. This effect was more evident during NIV-NAVA where patient-ventilator synchronization provided a higher MAP with lower PIPs.

Background: Despite a proven mortality benefit in primary prevention (PP) patients, the utilization of implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy-defibrillators (CRT-D) remains low in many geographies. Purpose: The objective of this analysis was to examine the mortality benefit in PP patients by guideline-indicated device type: implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D). Methods: Improve SCA was a prospective, non-randomized, non-blinded multicenter trial that enrolled patients from regions where ICD utilization is low. PP patient’s CRT-D or ICD eligibility was based upon the 2008 ACC/AHA/HRS and 2006 ESC guidelines. Mortality was assessed according to guideline-indicated device type comparing implanted and non-implanted patients. Cox proportional hazards methods were used, adjusting for known factors affecting mortality risk. Results: Among 2,618 PP patients followed for a mean of 20.8 ± 10.8 months, 1,073 were indicated for a CRT-D, and 1,545 were indicated for an ICD. PP CRT-D-indicated patients who received CRT-D therapy had a 58% risk reduction in mortality compared to those without implant (adjusted HR 0.42, 95% CI: 0.28-0.61, P<0.0001). PP patients with an ICD indication had a 43% risk reduction in mortality with an ICD implant compared with no implant (adjusted HR 0.57, 95% CI: 0.41-0.81, P=0.002). Conclusions: This analysis confirms the mortality benefit of adherence to guideline-indicated implantable defibrillation therapy for PP patients in geographies where ICD therapy was underutilized. These results affirm that medical practice should follow clinical guidelines when choosing therapy for PP patients who meet the respective defibrillator device implant indication.

Therapeutic drug monitoring (TDM) is a teamwork clinical pharmacokinetic services aimed to optimize pharmacotherapy of certain drugs such as those with a narrow therapeutic range, complicated pharmacokinetics. It involves the determination of drug level in blood samples taken at the appropriate time. Interpretation of results requires integration of pharmacokinetics, the pharmacodynamics of the drug and the patient’s clinical profile. To be cost-effective the service should be optimized. This review was written by experts from different developing countries to highlight the fundamentals of the service and provide suggestions for its optimization. These cover the rationale of requesting drug level, design of request form, optimal sampling, and analytical tools. guidelines for appropriate interpretation of drug levels; completeness of the roles of the qualified medical team; continuing education and skills development; involve the patients in improving the service, conducting relevant research; use PK software and integration of TDM with pharmacogenomics

- Invited Commentary –

The pathological mechanisms involved in Heart failure (HF) are complex and remain controversial. Caused by a variety of predisposing and exacerbating factors for HF development, the selection of animal models in current preclinical R&D has been a major challenge. In this review, we give a comprehensive overview of different models in various species currently used in HF research, and discuss their general applicability. In addition, we summarize the preclinical research review of approved drugs for HF, which provides theoretical and practical guidance for researchers considering preclinical studies for the treatment of HF.