title: Comparing the estimates of effect obtained from statistical causal inference methods: An example using bovine respiratory disease in feedlot cattle

text: The causal effect of an exposure on an outcome of interest in an observational study cannot be estimated directly if the confounding variables are not controlled. Many approaches are available for estimating the causal effect of an exposure. In this manuscript, we demonstrate the advantages associated with using inverse probability weighting (IPW) and doubly robust estimation of the odds ratio in terms of reduced bias. IPW approach can be used to adjust for confounding variables and provide unbiased estimates of the exposure’s causal effect. For cluster-structured data, as is common in animal populations, inverse conditional probability weighting (ICPW) approach can provide a robust estimation of the causal effect. Doubly robust estimation can provide a robust method even when the specification of the model form is uncertain. In this paper, the usage of IPW, ICPW, and doubly robust approaches are illustrated with a subset of data with complete covariates from the Australian-based National Bovine Respiratory Disease Initiative as well as simulated data. We evaluate the causal effect of prior bovine viral diarrhea exposure on bovine respiratory disease in feedlot cattle. The results show that the IPW, ICPW and doubly robust approaches would provide a more accurate estimation of the exposure effect than the traditional outcome regression model, and doubly robust approaches are the most preferable overall.


Outbreaks Associated with Untreated Recreational Water — California, Maine, and Minnesota, 2018–2019


title: On some factors determining the pressure drop across tracheal tubes during high-frequency percussive ventilation: a flow-independent model

text: To provide an in vitro estimation of the pressure drop across tracheal tubes (ΔP(TT)) in the face of given pulsatile frequencies and peak pressures (P(work)) delivered by a high-frequency percussive ventilator (HFPV) applied to a lung model. Tracheal tubes (TT) 6.5, 7.5 and 8.0 were connected to a test lung simulating the respiratory system resistive (R = 5, 20, 50 cmH(2)O/L/s) and elastic (C = 10, 20, and 50 mL/cmH(2)O) loads. The model was ventilated by HFPV with a pulse inspiratory peak pressure (work pressure P(work)) augmented in 5-cmH(2)O steps from 20 to 45 cmH(2)O, yielding 6 diverse airflows. The percussive frequency (f) was set to 300, 500 and 700 cycles/min, respectively. Pressure (Paw and Ptr) and flow (V’) measurements were performed for all 162 possible combinations of loads, frequencies, and work pressures for each TT size, thus yielding 486 determinations. For each respiratory cycle ΔP(TT) was calculated by subtracting each peak Ptr from its corresponding peak Paw. A non-linear model was constructed to assess the relationships between single parameters. Performance of the produced model was measured in terms of root mean square error (RMSE) and the coefficient of determination (r(2)). ΔP(TT) was predicted by P(work) (exponential Gaussian relationship), resistance (quadratic and linear terms), frequency (quadratic and linear terms) and tube diameter (linear term), but not by compliance. RMSE of the model on the testing dataset was 1.17 cmH(2)O, r(2) was 0.79 and estimation error was lower than 1 cmH(2)O in 68% of cases. As a result, even without a flow value, the physician would be able to evaluate ΔP(TT) pressure. If the present results of our bench study could be clinically confirmed, the use of a nonconventional ventilatory strategy as HFPV, would be safer and easier.


docid: alijioub

title: Specific labeling of synaptic schwann cells reveals unique cellular and molecular features

text: Perisynaptic Schwann cells (PSCs) are specialized, non-myelinating, synaptic glia of the neuromuscular junction (NMJ), that participate in synapse development, function, maintenance, and repair. The study of PSCs has relied on an anatomy-based approach, as the identities of cell-specific PSC molecular markers have remained elusive. This limited approach has precluded our ability to isolate and genetically manipulate PSCs in a cell specific manner. We have identified neuron-glia antigen 2 (NG2) as a unique molecular marker of S100β+ PSCs in skeletal muscle. NG2 is expressed in Schwann cells already associated with the NMJ, indicating that it is a marker of differentiated PSCs. Using a newly generated transgenic mouse in which PSCs are specifically labeled, we show that PSCs have a unique molecular signature that includes genes known to play critical roles in PSCs and synapses. These findings will serve as a springboard for revealing drivers of PSC differentiation and function.


title: Development of a TB vaccine trial site in Africa and lessons from the Ebola experience

text: Tuberculosis is the deadliest infection of our time. In contrast, about 11,000 people died of Ebola between 2014 and 2016. Despite this manifest difference in mortality, there is now a vaccine licensed in the United States and by the European Medicines Agency, with up to 100% efficacy against Ebola. The developments that led to the trialing of the Ebola vaccine were historic and unprecedented. The single licensed TB vaccine (BCG) has limited efficacy. There is a dire need for a more efficacious TB vaccine. To deploy such vaccines, trials are needed in sites that combine high disease incidence and research infrastructure. We describe our twelve-year experience building a TB vaccine trial site in contrast to the process in the recent Ebola outbreak. There are additional differences. Relative to the Ebola pipeline, TB vaccines have fewer trials and a paucity of government and industry led trials. While pathogens have varying levels of difficulty in the development of new vaccine candidates, there yet appears to be greater interest in funding and coordinating Ebola interventions. TB is a global threat that requires similar concerted effort for elimination.


title: Usefulness of point-of-care multiplex PCR to rapidly identify pathogens responsible for ventilator-associated pneumonia and their resistance to antibiotics: an observational study

text: BACKGROUND: The use of multiplex PCR to shorten time to identification of pathogens and their resistance mechanisms for patients with ventilator-associated pneumonia (VAP) is attractive, but poorly studied. The multiplex PCR–based Unyvero pneumonia cartridge assay can directly identify 20 bacteria and one fungus, amongst the most frequently causing VAP, and 19 of their resistance markers in clinical specimens (bronchoalveolar lavage or tracheal aspirate), with a turnaround time of 4–5 h. We performed this study to evaluate the concordance between the multiplex PCR–based Unyvero pneumonia cartridge assay and conventional microbiological techniques to identify pathogens and their resistance mechanisms in patients with VAP. METHODS: All patients suspected of having VAP (January 2016 to January 2019), who underwent fiberoptic bronchoscopy with bronchoalveolar lavage fluid (BALF) and whose BALF microscopy examination revealed intracellular bacteria, were included. BALF conventional cultures (gold standard), antimicrobial susceptibility testing and processing for the Unyvero pneumonia cartridge were done. Culture and Unyvero results were compared. RESULTS: Compared to cultures of the 93 samples processed for both techniques, Unyvero correctly identified pathogens in 68 (73%) proven VAP episodes, was discordant for 25 (27%), detected no pathogen in 11 and overdetected a not otherwise found pathogen in six. For the eight remaining discordant results, the pathogen responsible for VAP was not included in the Unyvero cartridge panel or it grew at a non-significant level in culture. Amongst the 31 (33%) resistance mechanism discordances observed, 22 were resistance detection failures and 24 concerned Pseudomonas aeruginosa. CONCLUSIONS: Compared to conventional microbiological cultures, the Unyvero pneumonia cartridge had poor diagnostic performance: it correctly identified pathogens and their resistance mechanisms in 73% and 67% of VAP cases, respectively. The lack of performance on the resistance mechanism was more pronounced when the pathogen detected was a Pseudomonas aeruginosa.


title: Tick-borne encephalitis (TBE) cases are not random: explaining trend, low- and high-frequency oscillations based on the Austrian TBE time series

text: BACKGROUND: Why human tick-borne encephalitis (TBE) cases differ from year to year, in some years more 100%, has not been clarified, yet. The cause of the increasing or decreasing trends is also controversial. Austria is the only country in Europe where a 40-year TBE time series and an official vaccine coverage time series are available to investigate these open questions. METHODS: A series of generalized linear models (GLMs) has been developed to identify demographic and environmental factors associated with the trend and the oscillations of the TBE time series. Both the observed and the predicted TBE time series were subjected to spectral analysis. The resulting power spectra indicate which predictors are responsible for the trend, the high-frequency and the low-frequency oscillations, and with which explained variance they contribute to the TBE oscillations. RESULTS: The increasing trend can be associated with the demography of the increasing human population. The responsible GLM explains 12% of the variance of the TBE time series. The low-frequency oscillations (10 years) are associated with the decadal changes of the large-scale climate in Central Europe. These are well described by the so-called Scandinavian index. This 10-year oscillation cycle is reinforced by the socio-economic predictor net migration. Considering the net migration and the Scandinavian index increases the explained variance of the GLM to 44%. The high-frequency oscillations (2–3 years) are associated with fluctuations of the natural TBE transmission cycle between small mammals and ticks, which are driven by beech fructification. Considering also fructification 2 years prior explains 64% of the variance of the TBE time series. Additionally, annual sunshine duration as predictor for the human outdoor activity increases the explained variance to 70%. CONCLUSIONS: The GLMs presented here provide the basis for annual TBE forecasts, which were mainly determined by beech fructification. A total of 3 of the 5 years with full fructification, resulting in high TBE case numbers 2 years later, occurred after 2010. The effects of climate change are therefore not visible through a direct correlation of the TBE cases with rising temperatures, but indirectly via the increased frequency of mast seeding.


Challenges of “Return to Work” in an Ongoing Pandemic


Oncology patient support


UDC highs and lows in Cornwall


docid: yjtwuaht

title: Back to work


docid: awatrhbk

title: New video will promote silver diamine fluoride to children


Paediatric emergencies


A new era for dental education


Coronamolars?


Working through it


BDA updates its returning to work toolkit for members


Chlorhexidine has an antiviral effect against viruses


Virucidal activity


title: Comparison of reduced-toxicity conditioning protocols using fludarabine, melphalan combined with thiotepa or carmustine in allogeneic hematopoietic cell transplantation

text: The age of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) has increased during the last decades, mainly due to improved reduced-intensity/toxicity conditioning protocols. A reduced-intensity conditioning based on fludarabin, carmustin/BCNU and melphalan (FBM) has been previously developed at our institution. Since we observed detrimental effects in individual patients with compromised lung function, efforts have been made in order to replace BCNU by thiotepa (FTM) to reduce toxicity. In this study, we retrospectively analyzed the outcome, GvHD incidence, lung function and organ toxicity of patients with a median age of 62 years (range 21–79) transplanted for malignant disease (96.7%, 62.3% in intermediate/advanced disease stage) at our institution after conditioning with FBM (n = 136) or FTM (n = 105) between 2013 and 2017. Median follow-up was 868 days (range 0–2615). In multivariate analysis for overall survival, no difference was detected between both conditioning protocols in the presence of impaired lung function, age, lower performance, and liver disease previous allo-HCT. In the subgroup analysis, FTM was not inferior to FBM in patients with pulmonary disease prior allo-HCT, lymphoid malignancies, and higher comorbidity index. In conclusion, the reduced-intensity FBM and FTM conditioning protocols show adequate antineoplastic efficacy and are suitable for patients with impaired lung function.


' My training prepared me for far more than just clinical dentistry'


title: Cobalt-catalyzed highly enantioselective hydrogenation of α,β-unsaturated carboxylic acids

text: Asymmetric hydrogenation of α,β-unsaturated acids catalyzed by noble metals has been well established, whereas, the asymmetric hydrogenation with earth-abundant-metal was rarely reported. Here, we describe a cobalt-catalyzed asymmetric hydrogenation of α,β-unsaturated carboxylic acids. By using chiral cobalt catalyst bearing electron-donating diphosphine ligand, high activity (up to 1860 TON) and excellent enantioselectivity (up to >99% ee) are observed. Furthermore, the cobalt-catalyzed asymmetric hydrogenation is successfully applied to a broad spectrum of α,β-unsaturated carboxylic acids, such as various α-aryl and α-alkyl cinnamic acid derivatives, α-oxy-functionalized α,β-unsaturated acids, α-substituted acrylic acids and heterocyclic α,β-unsaturated acids (30 examples). The synthetic utility of the protocol is highlighted by the synthesis of key intermediates for chiral drugs (6 cases). Preliminary mechanistic studies reveal that the carboxy group may be involved in the control of the reactivity and enantioselectivity through an interaction with the metal centre.


title: Changes in pulmonary oxygen content are detectable with laser absorption spectroscopy: proof of concept in newborn piglets

text: BACKGROUND: Using an optical method based on tunable diode laser absorption spectroscopy, we previously assessed oxygen (O(2)) and water vapor (H(2)O) content in a tissue phantom of the preterm infant lung. Here we applied this method on newborn piglets with induced lung complications. METHODS: Five mechanically ventilated piglets were subjected to stepwise increased and decreased fraction of inspired oxygen (FiO(2)), to atelectasis using a balloon catheter in the right bronchus, and to pneumothorax by injecting air in the pleural cavity. Two diode lasers (764 nm for O(2) gas absorption and 820 nm for H(2)O absorption) were combined in a probe delivering light either externally, on the skin, or internally, through the esophagus. The detector probe was placed dermally. RESULTS: Calculated O(2) concentrations increased from 20% (IQR 17−23%) when ventilated with room air to 97% (88−108%) at FiO(2) 1.0. H(2)O was only detectable with the internal light source. Specific light absorption and transmission patterns were identified in response to atelectasis and pneumothorax, respectively. CONCLUSIONS: The optical method detected FiO(2) variations and discriminated the two induced lung pathologies, providing a rationale for further development into a minimally invasive device for real-time monitoring gas changes in the lungs of sick newborn infants. IMPACT: Optical spectroscopy can detect pulmonary complications in an animal model. Oxygen concentrations can be evaluated in the lungs. Presents a novel minimally invasive method to detect lung oxygenation and complications. Potential to be developed into a lung monitoring method in newborn infants. Potential for bed-side detection of pulmonary complications in newborn infants.


Addressing a rare cause of paediatric stridor: subglottic cyst


Occupational therapy has gone online: What will remain beyond COVID‐19?


title: Status of Editing and Publishing of Scholarly Journals by Academic Societies of Science and Technology in Korea

text: BACKGROUND: The present study analyzed publishing data of scholarly journals which were published in 2018 by academic societies of science and technology in Korea to observe journal editing and publishing status. METHODS: A total of 346 regional journals (59 natural science, 118 engineering, 44 agriculture, fisheries, and oceanography, and 125 medical and pharmacy) and 141 international journals (32 natural science, 43 engineering, 12 agriculture, fisheries, and oceanography, 54 medical and pharmacy) were included in this analysis, which applied the journal review by the Korea Federation of Science and Technology. Websites of the journals and the submitted publication data in 2019 were reviewed. RESULTS: Except for a few journals, all of the journals were published by academic societies. Basic information of journals was well displayed by both offline and online. Most of the 346 regional journals were published in Korean language or mixed with English but 77 (22.3%), mostly medical, were in English. One-third (n = 104) journals published less than 40 articles while 9 published over 200, and 261 journals (75.4%) received less than 100 submissions in 2018. Most (n = 298, 86.1%) of them were enlisted in the Korean Citation Index (KCI). Editorial board members performed manuscript editing in 171 (49.4%) journals, and most of the journals paid < 50,000,000 won for publishing costs. Of 141 international journals, 138 (97.9%) were published in English and all of them published overseas submissions. Forty-one (29.1%) journals accepted < 20% of submissions but 58 (41.1%) accepted 100%. Of them, 124 (87.9%) were indexed in the KCI, 93 (66.0%) in the Web of Science, 120 in Scopus, and 62 in PubMed. Editorial board members in 38 (27.0%) journals took responsibility of manuscript editing. Publishing cost of 79 (56.0%) journals was < 50,000,000 won. Only 157 (32.2%) of total 487 journals, mostly medical, documented gendered innovation in their instruction to authors. CONCLUSION: Most of the Korean science and technology journals keep global standard of editing and publishing. Their offline and online visibility is acceptable but most regional journals are small and of low academic impact while international journals are globally indexed and acknowledged. Korean scholarly journals should invite more and better articles to keep quality publication.


title: Molecular detection of canine respiratory pathogens between 2017 and 2018 in Japan

text: A molecular survey was conducted to understand recent distribution of pathogens associated with canine infectious respiratory disease (CIRD) in Japan. Nasal and/or pharyngeal swabs were collected from asymptomatic dogs and those with CIRD, living in private house or in kennels. PCR-based examination was conducted for detecting nine pathogens. Among private household dogs, 50.8% with CIRD, 11.1% with respiratory disease other than CIRD, and 4.3% asymptomatic were positive for more than one pathogen, whereas in kennel-housed dogs, 42.9% with CIRD and 27.3% asymptomatic were positive. Bordetella bronchiseptica was most frequently detected, followed by canine herpesvirus 1, canine parainfluenza virus, canine pneumovirus, Mycoplasma cynos, and canine adenovirus type 2. In kennel environment, asymptomatic dogs might act as reservoirs carrying the respiratory pathogens.


title: Evaluating Safety and Efficacy of Follow-up for Patients With Abdominal Pain Using Video Consultation (SAVED Study): Randomized Controlled Trial

text: BACKGROUND: The benefits of telemedicine include cost savings and decentralized care. Video consultation is one form that enables early detection of deteriorating patients and promotion of self-efficacy in patients who are well but anxious. Abdominal pain is a common symptom presented by patients in emergency departments. These patients could benefit from video consultation, as it enables remote follow-up of patients who do not require admission and facilitates early discharge of patients from overcrowded hospitals. OBJECTIVE: The study aimed to evaluate the safety and efficacy of the use of digital telereview in patients presenting with undifferentiated acute abdominal pain. METHODS: The SAVED study was a prospective randomized controlled trial in which follow-up using existing telephone-based telereview (control) was compared with digital telereview (intervention). Patients with undifferentiated acute abdominal pain discharged from the emergency department observation ward were studied based on intention-to-treat. The control arm received routine, provider-scheduled telereview with missed reviews actively coordinated and rescheduled by emergency department staff. The intervention arm received access to a platform for digital telereview (asynchronous and synchronous format) that enabled patient-led appointment rescheduling. Patients were followed-up for 2 weeks for outcomes of service utilization, efficacy (compliance with their disposition plan), and safety (re-presentation for the same condition). RESULTS: A total of 70 patients participated, with patients randomly assigned to each arm (1:1 ratio). Patients were a mean age of 40.0 (SD 13.8; range 22-71) years, predominantly female (47/70, 67%), and predominantly of Chinese ethnicity (39/70, 56%). The telereview service was used by 32 patients in the control arm (32/35, 91%) and 18 patients in the intervention arm (18/35, 51%). Most patients in control (33/35, 94%; 95% CI 79.5%-99.0%) and intervention (34/35, 97%; 95% CI 83.4%-99.9%) arms were compliant with their final disposition. There was a low rate of re-presentation at 72 hours and 2 weeks for both control (72 hours: 2/35, 6%; 95% CI 1.0%-20.5%; 2 weeks: 2/35, 6%, 95% CI 1.0%-20.5%) and intervention (72 hours: 2/35, 6%; 95% CI 1.0%-20.5%; 2 weeks: 3/35, 9%, 95% CI 2.2%-24.2%) arms. There were no significant differences in safety (P>.99) and efficacy (P>.99) between the two groups. CONCLUSIONS: The application of digital telereview for the follow-up of patients with abdominal pain may be safe and effective. Future studies are needed to evaluate its cost-effectiveness and usefulness for broader clinical application. TRIAL REGISTRATION: ISRCTN Registry ISRCTN28468556; http://www.isrctn.com/ISRCTN28468556.


title: Generation of inner ear hair cells by direct lineage conversion of primary somatic cells

text: The mechanoreceptive sensory hair cells in the inner ear are selectively vulnerable to numerous genetic and environmental insults. In mammals, hair cells lack regenerative capacity, and their death leads to permanent hearing loss and vestibular dysfunction. Their paucity and inaccessibility has limited the search for otoprotective and regenerative strategies. Growing hair cells in vitro would provide a route to overcome this experimental bottleneck. We report a combination of four transcription factors (Six1, Atoh1, Pou4f3, and Gfi1) that can convert mouse embryonic fibroblasts, adult tail-tip fibroblasts and postnatal supporting cells into induced hair cell-like cells (iHCs). iHCs exhibit hair cell-like morphology, transcriptomic and epigenetic profiles, electrophysiological properties, mechanosensory channel expression, and vulnerability to ototoxin in a high-content phenotypic screening system. Thus, direct reprogramming provides a platform to identify causes and treatments for hair cell loss, and may help identify future gene therapy approaches for restoring hearing.


title: Case Studies in Neuroscience: The electrophysiology of a human obsession in nucleus accumbens

text: Microelectrode recordings were performed during awake deep brain stimulation surgery for obsessive-compulsive disorder, revealing robust brain oscillations that were plainly visible throughout the ventral striatum. There was an elegant topological correspondence between each oscillation and the underlying brain anatomy, most prominently a ~35-Hz gamma-oscillation specific to the nucleus accumbens. Direct provocation of the patient’s contamination obsession modulated both firing rate and gamma-oscillation amplitude within the nucleus accumbens. NEW & NOTEWORTHY Surgical implantation of deep brain stimulating electrodes (DBS) to treat obsessive-compulsive disorder (OCD) is an option for patients who have not fully responded to medical intervention or cognitive behavioral therapy. We measured the electrophysiology of a collection of deep brain structures during awake DBS surgery for an OCD patient with an obsession about cleanliness and contamination. The anatomic delineation of these deep brain structures was revealed by distinct brain rhythms, most notably a ~35 Hz oscillation specific to the nucleus accumbens. In the first ever measurement of a human obsessive thought, we found that this ~35-Hz biomarker, as well as the local neuronal action potential rate, were modulated by handing the patient a toothbrush to bring to his face and instructing him to “imagine brushing your teeth with this dirty toothbrush.”


title: Implementing the chick embryo model to study vestibular developmental disorders

text: Children with congenital vestibular disorders show delayed motor development and challenges in maintaining posture and balance. Computed tomography images reveal that these children have abnormal inner ears in the form of a sac, with the semicircular canals missing or truncated. Little is known about how this inner ear abnormality affects central vestibular development. At present, mice with the chromodomain helicase DNA-binding protein 7 mutation are the most common model for studying congenital vestibular disorders, despite forming multiple diverse inner ear phenotypes and inducing abnormal cerebellar and visual system development. To identify the effects of a sac-like inner ear on central vestibular development, we have designed and implemented a new model, the anterior-posterior axis rotated otocyst (ARO) chick, which forms a sac-like inner ear in 85% of cases. The ARO chick is produced by anterior-posterior rotation of the otocyst at embryonic day 2. Here, we describe for the first time the 15% of ARO chicks that form three small semicircular canals and rename the ARO chicks forming sacs (ARO/s chicks). The basic features of the vestibular sensory organs in ARO/s chicks are similar to those found in patients’ sacs, and ARO/s hatchlings experience balance and walking problems like patients. Thus, ARO/s chicks have a reproducible inner ear phenotype without abnormalities in vestibular-related structures, making the model a relatively simple one to evaluate the relationship between the sac-like inner ear pathology and formation of the central vestibular neural circuitry. Here, we describe unpublished details on the surgical approaches to produce ARO chicks, including pitfalls and difficulties to avoid. NEW & NOTEWORTHY This paper describes simple techniques for chick otocyst rotation resulting in a sac-like inner ear (85%), the common phenotype in congenital vestibular disorders. We now describe anterior-posterior axis rotated otocyst chicks, which form three small canals (15%), and rename chicks forming a sac (ARO/s chicks). Basic protocols and potential complications of otocyst rotation are described. With the use of ARO/s chicks, it will be possible to determine how the vestibular neural circuit is modified by sac-like inner ear formation.


title: Differences in pulmonary arterial flow hemodynamics between children and adults with pulmonary arterial hypertension as assessed by 4D-flow CMR studies

text: Despite different developmental and pathological processes affecting lung vascular remodeling in both patient populations, differences in 4D MRI findings between children and adults with PAH have not been studied. The purpose of this study was to compare flow hemodynamic state, including flow-mediated shear forces, between pediatric and adult patients with PAH matched by severity of pulmonary vascular resistance index (PVRi). Adults (n = 10) and children (n = 10) with PAH matched by pulmonary vascular resistance index (PVRi) and healthy adult (n = 10) and pediatric (n = 10) subjects underwent comprehensive 4D-flow MRI to assess peak systolic wall shear stress (WSS(max)) measured in the main (MPA), right (RPA), and left pulmonary arteries (LPA), viscous energy loss (E(L)) along the MPA-RPA and MPA-LPA tract, and qualitative analysis of secondary flow hemodynamics. WSS(max) was decreased in all pulmonary vessels in children with PAH when compared with the same age group (all P < 0.05). Similarly, WSS(max) was decreased in all pulmonary vessels in adult PAH patients when compared with healthy adult subjects (all P < 0.01). Average E(L) was increased in adult patients with PAH when compared with the same age group along both MPA-RPA (P = 0.020) and MPA-LPA (P = 0.025) tracts. There were no differences in E(L) indices between adults and pediatric patients. Children and adult patients with PAH have decreased shear hemodynamic forces. However, pathological flow hemodynamic formations appear to be more consistent in adult patients, whereas flow hemodynamic abnormalities appear to be more variable in children with PAH for comparable severity of PVRi. NEW & NOTEWORTHY Both children and adult patients with PAH have decreased shear hemodynamic forces inside the pulmonary arteries associated with the degree of vessel dilation and stiffness. These differences also exist between healthy normotensive children and adults. However, pathological flow hemodynamic formations appear to more uniform in adult patients, whereas in children with PAH flow, hemodynamic abnormalities appear to be more variable. Pathological flow formations appear not to have a major effect on viscous energy loss associated with the flow conduction through proximal pulmonary arteries.


CORRIGENDUM


title: The Physiology of the Gastric Parietal Cell

text: Parietal cells are responsible for gastric acid secretion, which aids in the digestion of food, absorption of minerals, and control of harmful bacteria. However, a fine balance of activators and inhibitors of parietal cell-mediated acid secretion is required to ensure proper digestion of food, while preventing damage to the gastric and duodenal mucosa. As a result, parietal cell secretion is highly regulated through numerous mechanisms including the vagus nerve, gastrin, histamine, ghrelin, somatostatin, glucagon-like peptide 1, and other agonists and antagonists. The tight regulation of parietal cells ensures the proper secretion of HCl. The H(+)-K(+)-ATPase enzyme expressed in parietal cells regulates the exchange of cytoplasmic H(+) for extracellular K(+). The H(+) secreted into the gastric lumen by the H(+)-K(+)-ATPase combines with luminal Cl(−) to form gastric acid, HCl. Inhibition of the H(+)-K(+)-ATPase is the most efficacious method of preventing harmful gastric acid secretion. Proton pump inhibitors and potassium competitive acid blockers are widely used therapeutically to inhibit acid secretion. Stimulated delivery of the H(+)-K(+)-ATPase to the parietal cell apical surface requires the fusion of intracellular tubulovesicles with the overlying secretory canaliculus, a process that represents the most prominent example of apical membrane recycling. In addition to their unique ability to secrete gastric acid, parietal cells also play an important role in gastric mucosal homeostasis through the secretion of multiple growth factor molecules. The gastric parietal cell therefore plays multiple roles in gastric secretion and protection as well as coordination of physiological repair.


title: mRNA Metabolism in Cardiac Development and Disease: Life After Transcription

text: The central dogma of molecular biology illustrates the importance of mRNAs as critical mediators between genetic information encoded at the DNA level and proteomes/metabolomes that determine the diverse functional outcome at the cellular and organ levels. Although the total number of protein-producing (coding) genes in the mammalian genome is ~20,000, it is evident that the intricate processes of cardiac development and the highly regulated physiological regulation in the normal heart, as well as the complex manifestation of pathological remodeling in a diseased heart, would require a much higher degree of complexity at the transcriptome level and beyond. Indeed, in addition to an extensive regulatory scheme implemented at the level of transcription, the complexity of transcript processing following transcription is dramatically increased. RNA processing includes post-transcriptional modification, alternative splicing, editing and transportation, ribosomal loading, and degradation. While transcriptional control of cardiac genes has been a major focus of investigation in recent decades, a great deal of progress has recently been made in our understanding of how post-transcriptional regulation of mRNA contributes to transcriptome complexity. In this review, we highlight some of the key molecular processes and major players in RNA maturation and post-transcriptional regulation. In addition, we provide an update to the recent progress made in the discovery of RNA processing regulators implicated in cardiac development and disease. While post-transcriptional modulation is a complex and challenging problem to study, recent technological advancements are paving the way for a new era of exciting discoveries and potential clinical translation in the context of cardiac biology and heart disease.


Extracorporeal Membrane Oxygenation Resource Planning in the Setting of Pandemic Respiratory Illness


Reply: E-Cigarette, or Vaping, Product Use–associated Lung Injury: A Response to Perez and Crotty Alexander


In Defense of Evidence-based Medicine for the Treatment of COVID-19 Acute Respiratory Distress Syndrome


docid: rvryiuwj

title: Interventions to reduce burnout of physicians and nurses: An overview of systematic reviews and meta-analyses

text: OBJECTIVE: Numerous systematic reviews and meta-analyses on the interventions to reduce burnout of physicians and nurses have been published nowadays. This study aimed to summarize the evidence and clarify a bundled strategy to reduce burnout of physicians and nurses. METHODS: Researches have been conducted within Cochrane Library, PubMed, Ovid, Scopus, EBSCO, and CINAHL published from inception to 2019. In addition, a manual search for relevant articles was also conducted using Google Scholar and ancestral searches through the reference lists from articles included in the final review. Two reviewers independently selected and assessed, and any disagreements were resolved through a larger team discussion. A data extraction spreadsheet was developed and initially piloted in 3 randomly selected studies. Data from each study were extracted independently using a pre-standardized data abstraction form. The the Risk of Bias in Systematic reviews and assessment of multiple systematic reviews (AMSTAR) 2 tool were used to evaluate risk of bias and quality of included articles. RESULTS: A total of 22 studies published from 2014 to 2019 were eligible for analysis. Previous studies have examined burnout among physicians (n = 9), nurses (n = 6) and healthcare providers (n = 7). The MBI was used by majority of studies to assess burnout. The included studies evaluated a wide range of interventions, individual-focused (emotion regulation, self-care workshop, yoga, massage, mindfulness, meditation, stress management skills and communication skills training), structural or organizational (workload or schedule-rotation, stress management training program, group face-to-face delivery, teamwork/transitions, Balint training, debriefing sessions and a focus group) and combine interventions (snoezelen, stress management and resiliency training, stress management workshop and improving interaction with colleagues through personal training). Based on the Risk of Bias in Systematic reviews and AMSTAR 2 criteria, the risk of bias and methodological quality included studies was from moderate to high. CONCLUSIONS: Burnout is a complicated problem and should be dealt with by using bundled strategy. The existing overview clarified evidence to reduce burnout of physicians and nurses, which provided a basis for health policy makers or clinical managers to design simple and feasible strategies to reduce the burnout of physicians and nurses, and to ensure clinical safety.


docid: ejoufvvj

title: Isolation and characterization of new Puumala orthohantavirus strains from Germany

text: Orthohantaviruses are re-emerging rodent-borne pathogens distributed all over the world. Here, we report the isolation of a Puumala orthohantavirus (PUUV) strain from bank voles caught in a highly endemic region around the city Osnabrück, north-west Germany. Coding and non-coding sequences of all three segments (S, M, and L) were determined from original lung tissue, after isolation and after additional passaging in VeroE6 cells and a bank vole-derived kidney cell line. Different single amino acid substitutions were observed in the RNA-dependent RNA polymerase (RdRP) of the two stable PUUV isolates. The PUUV strain from VeroE6 cells showed a lower titer when propagated on bank vole cells compared to VeroE6 cells. Additionally, glycoprotein precursor (GPC)-derived virus-like particles of a German PUUV sequence allowed the generation of monoclonal antibodies that allowed the reliable detection of the isolated PUUV strain in the immunofluorescence assay. In conclusion, this is the first isolation of a PUUV strain from Central Europe and the generation of glycoprotein-specific monoclonal antibodies for this PUUV isolate. The obtained virus isolate and GPC-specific antibodies are instrumental tools for future reservoir host studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11262-020-01755-3) contains supplementary material, which is available to authorized users.


Virtual reality device training for extracorporeal membrane oxygenation


docid: algpmftj

title: Outbreak of KPC-2 Carbapenem-resistant Klebsiella pneumoniae ST76 and Carbapenem-resistant K2 Hypervirulent Klebsiella pneumoniae ST375 strains in Northeast China: molecular and virulent characteristics

text: BACKGROUND: Carbapenem-resistant hypervirulent Klebsiella pneumoniae strains have recently come into existence worldwide; however, researchers in northeast China are not aware of their clinical features and molecular characteristics. METHODS: Here, the molecular and virulent characteristics of 44 carbapenem-resistant K. pneumoniae (CRKP) isolates collected from January 2015 to December 2017 were studied. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were carried out to define the clonal relatedness among the isolates. PCR and capsular serotyping of the virulence-associated genes, as well as biofilm formation and serum complement-mediated killing assays, were employed to determine the virulent potential. The genomic features and associated mobile genetic elements of JmsCRE57 were detected by whole genome sequencing. RESULTS: The only positive isolate was JmsCRE57, which belonged to the ST375 serotype K2 that expressed uge, mrkD, fimH, kpn, aerobactin and rmpA virulence-associated genes and showed strong biofilm formation and serum sensitivity. Sequencing results showed that the JmsCRE57 genome mainly consisted of a circular chromosome, three antimicrobial resistant plasmids and a virulent plasmid. The antimicrobial resistant plasmid expressing bla(KPC-2), bla(CTX-M-15), aph(3″)-Ib, aph(6)-Id, qnrB1, aac(3)-IIa, aac(6′)-Ib-cr, bla(OXA-1), bla(TEM-1B), catB4, sul2, dfrA14 and bla(SHV-99). The virulent plasmid belonged to the IncHI1B group, which is mainly composed of mucoid phenotype genes and siderophore-associated genes. The remaining CRKP strains that expressed uge, fimH, mrkD and kpn virulence-associated genes were not successfully typed. CONCLUSION: Our results provide new insights on the epidemiology of carbapenem-resistant K2 hypervirulent K. pneumoniae ST375 and CRKP ST76 strains in northeast China, which may help control their future outbreaks.


title: Bariatric Surgery in Prior Solid Organ Transplantation Patients: Is Race a Predictor of Adverse Outcomes?

text: PURPOSE: Metabolic and bariatric surgery (MBS) is increasingly performed in patients with previous solid organ transplantation (PSOT). In addition, controversy remains about whether racial disparity in outcomes following MBS exists. Therefore, the aim of this analysis was to determine if race independently predicts outcomes in MBS patients with PSOT. MATERIALS AND METHODS: Patients with PSOT undergoing sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) were identified in the 2017 Metabolic and Bariatric Surgery Accreditation Quality and Improvement Project (MBSAQIP) database. Patients were stratified by race (Black and White). Propensity score matching was utilized to adjust for multiple demographic variables. Multivariable logistic regression analyses were performed for overall and bariatric-related morbidity. RESULTS: Of 335 MBS patients with PSOT, 250 (75%) were white and 85 (25%) were black patents. Procedure-type and surgical approach (p > 0.1) were similarly distributed. Black patients were more likely (p < 0.05) to have hypertension dialysis-dependent chronic kidney disease, and be on chronic steroids). Mortality and morbidity were similar. Black patients had significantly (p < 0.05) higher rates of renal failure, pulmonary complications, and emergency department visits in unmatched analysis. After propensity score matching, 82 patients in each cohort were identified and were similar at baseline (p > 0.5). In the matched analysis, black patients had higher overall (17% vs. 10%, p = 0.12) and bariatric-related morbidity (14% vs. 7.2%, p = 0.05). In addition, black patients had significantly (p < 0.05) higher rates of postoperative pneumonias, progressive renal insufficiency, and emergency department visits. On multivariable regression analysis, black race did not independently predict overall or bariatric-related morbidity. CONCLUSION: MBS in racial cohorts with PSOT is safe, with very low rates of overall morbidity and mortality. Black race trended toward increased postoperative morbidity. Larger cohort studies are needed to validate our findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11695-020-04813-9) contains supplementary material, which is available to authorized users.


docid: tyexaefg

title: The Risk of Respiratory Tract Infections in Psoriasis Patients Treated With IL-23-pathway Inhibiting Biologics: A Meta-Estimate of Pivotal Trials Relevant to Decision-Making During the COVID-19 Pandemic


A New Challenge For La Presse Médicale


How systems engineering can improve care in the ICU


title: Intellectual capital and the efficiency of SMEs in the transition economy China; Do financial resources strengthen the routes?

text: Intellectual capital has been grabbed the attention of researchers due to its momentous role in sustainable competitive advantage and organizational success. There is a growing catalog of related assessments, publications and reviews that display the direct and indirect role of intellectual capital in business success and profitability. Despite the bourgeoning literature, studies have not yet unleashed the influence of each dimension of intellectual capital; human capital, structural capital and customer capital on SMEs' efficiency with financial resources as a moderator. The present study fills the gap and assesses if financial resources strengthen the paths between the dimensions of intellectual capital and SMEs' efficiency. A survey method was used and collected evidence from 264 Chinese SMEs. The findings exhibit that human capital directly enhances SMEs' efficiency but the presence of financial resources as a moderator weakens the influence. However, social capital and customer capital do not directly improve SMEs' efficiency but financial resources reinforce the paths social and customer capital and SMEs efficiency. This research recommends that owners and managers of SMEs need to use their financial resources complementary with structural and customer capital while human capital should be used exclusively.


title: Does relational mobility vary across national regions? A within-country examination

text: Relational mobility is a socio-ecological construct quantifying how much freedom and opportunity a society affords individuals to choose and dispose of interpersonal relationships. Past research has confirmed that relational mobility varies across nations, but no large-scale study has examined the degree to which relational mobility may vary within a single nation. We report two studies (Study 1, N = 647; Study 2, N = 7343) exploring within-country similarity or variability in relational mobility across all 27 states and five geo-socio-political regions in the continent-size country of Brazil. Results confirmed the measurement equivalence of the Relational Mobility Scale across respondents from all Brazilian states. Notably, relational mobility scores were uniform across Brazilian regions and states, indicating a common national culture regarding the amount of opportunities Brazilians have in selecting new relationship partners within their social context. Replicating existing findings, relational mobility was positively associated with pro-active tendencies that help people retain relationships—levels of intimacy and self-disclosure toward a close friend—indicating that friends tend to feel closer intimacy to their close friends, and reveal serious personal information to a larger degree in social contexts where opportunities to find and retain relationships with like-minded others are greater.


Investing in surgery: a value proposition for African leaders


Collaborating on kidneys: Haiti's transplantation ambitions


Methodology in the GBD study of China


Salome Maswime: dynamic leader in global surgery


Giants in Chest Medicine: Professor Nan-shan Zhong, MD


Policies Should be Based on Data Not Dogma in Medicine and Government


Nucleic Acid Approaches to Antibody-based Therapeutics for COVID-19: A Perspective


Tip of the Iceberg


docid: wdblfant

title: Adjuvant and neoadjuvant therapies in melanoma


title: The RNA quality control pathway nonsense-mediated mRNA decay targets cellular and viral RNAs to restrict KSHV

text: Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved RNA decay mechanism that has emerged as a potent cell-intrinsic restriction mechanism of retroviruses and positive-strand RNA viruses. However, whether NMD is capable of restricting DNA viruses is not known. The DNA virus Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma and primary effusion lymphoma (PEL). Here, we demonstrate that NMD restricts KSHV lytic reactivation. Leveraging high-throughput transcriptomics we identify NMD targets transcriptome-wide in PEL cells and identify host and viral RNAs as substrates. Moreover, we identified an NMD-regulated link between activation of the unfolded protein response and transcriptional activation of the main KSHV transcription factor RTA, itself an NMD target. Collectively, our study describes an intricate relationship between cellular targets of an RNA quality control pathway and KSHV lytic gene expression, and demonstrates that NMD can function as a cell intrinsic restriction mechanism acting upon DNA viruses.


The power of cooperation


docid: zxvzswpy

title: Reply: Vitamin C as a Possible Therapy for COVID-19


ApoE e4e4 genotype and mortality with COVID-19 in UK Biobank


Increased Burn Center Admissions During COVID 19 Pandemic


ARTP statement on pulmonary function testing


title: Google Trends-based non-English language query data and epidemic diseases: a cross-sectional study of the popular search behaviour in Taiwan

text: OBJECTIVE: This study developed a surveillance system suitable for monitoring epidemic outbreaks and assessing public opinion in non-English-speaking countries. We evaluated whether social media reflects social uneasiness and fear during epidemic outbreaks and natural catastrophes. DESIGN: Cross-sectional study. SETTING: Freely available epidemic data in Taiwan. MAIN OUTCOME MEASURE: We used weekly epidemic incidence data obtained from the Taiwan Centers for Disease Control and online search query data obtained from Google Trends between 4 October 2015 and 2 April 2016. To validate whether non-English query keywords were useful surveillance tools, we estimated the correlation between online query data and epidemic incidence in Taiwan. RESULTS: With our approach, we noted that keywords 感冒 (‘common cold’), 發燒 (‘fever’) and 咳嗽 (‘cough’) exhibited good to excellent correlation between Google Trends query data and influenza incidence (r=0.898, p<0.001; r=0.773, p<0.001; r=0.796, p<0.001, respectively). They also displayed high correlation with influenza-like illness emergencies (r=0.900, p<0.001; r=0.802, p<0.001; r=0.886, p<0.001, respectively) and outpatient visits (r=0.889, p<0.001; r=0.791, p<0.001; r=0.870, p<0.001, respectively). We noted that the query 腸病毒 (‘enterovirus’) exhibited excellent correlation with the number of enterovirus-infected patients in emergency departments (r=0.914, p<0.001). CONCLUSIONS: These results suggested that Google Trends can be a good surveillance tool for epidemic outbreaks, even in Taiwan, the non-English-speaking country. Online search activity indicates that people are concerned about epidemic diseases, even if they do not visit hospitals. This prompted us to develop useful tools to monitor social media during an epidemic because such media usage reflects infectious disease trends more quickly than does traditional reporting.


Response to Letter to the Editor


title: A Champion of Host Defense: A Generic Large-Scale Cause for Platelet Dysfunction and Depletion in Infection

text: Thrombocytopenia is commonly associated with sepsis and infections, which in turn are characterized by a profound immune reaction to the invading pathogen. Platelets are one of the cellular entities that exert considerable immune, antibacterial, and antiviral actions, and are therefore active participants in the host response. Platelets are sensitive to surrounding inflammatory stimuli and contribute to the immune response by multiple mechanisms, including endowing the endothelium with a proinflammatory phenotype, enhancing and amplifying leukocyte recruitment and inflammation, promoting the effector functions of immune cells, and ensuring an optimal adaptive immune response. During infection, pathogens and their products influence the platelet response and can even be toxic. However, platelets are able to sense and engage bacteria and viruses to assist in their removal and destruction. Platelets greatly contribute to host defense by multiple mechanisms, including forming immune complexes and aggregates, shedding their granular content, and internalizing pathogens and subsequently being marked for removal. These processes, and the nature of platelet function in general, cause the platelet to be irreversibly consumed in the execution of its duty. An exaggerated systemic inflammatory response to infection can drive platelet dysfunction, where platelets are inappropriately activated and face immunological destruction. While thrombocytopenia may arise by condition-specific mechanisms that cause an imbalance between platelet production and removal, this review evaluates a generic large-scale mechanism for platelet depletion as a repercussion of its involvement at the nexus of responses to infection.


There Is No Place Like Home: Rethinking Away Rotations


Reply to the Letter to the Editor: Can Sural Fasciocutaneous Flaps Be Effective in Patients Older Than 65?


Enhancing science preparedness for health emergencies in Africa through research capacity building


Recurring Themes


title: Perioperative Bluttransfusion: Nutzen, Risiken und Richtlinien

text: Surgical blood loss and trauma are the major causes of allogeneic blood transfusions, which still bear considerable risks. After the correction of hypovolemia, the anesthesiologist often has to deal with normovolemic anemia. The clinical relevance of this isolated decrease in hemoglobin concentration consists in an eventually compromised global or regional oxygen supply with the development of tissue hypoxia below a critical threshold. This is an individual threshold for each patient and depends on his or her capacity to compensate the decrease in blood oxygen content. Therefore, physiologic transfusion triggers should primarily be applied and not rigid numeric transfusion triggers, such as hemoglobin concentration, which do not take into account each patient’s individual reserve.


title: Benefits of Physical Activity and Its Associations with Resilience, Emotional Intelligence, and Psychological Distress in University Students from Southern Spain

text: This is a descriptive and cross-sectional study in a sample of 1095 university students from southern Spain. The aim was to identify the frequency of health-fulfilling physical activity engagement reported by participants. Sufficient physical activity was categorized according to whether participants ‘achieved minimum recommendations’ (≥150 min of moderate physical activity) or ‘did not achieve minimum recommendations’ (≤150 min of moderate physical activity). Participants were further categorized as: inactive (does not engage in physical activity or sport), engaging in physical activity that is not beneficial to health (≤300 min of moderate physical activity per week) and engaging in physical activity that is beneficial to health (≥300 min of moderate physical activity per week). Possible relationships with psychosocial factors and perceived psychological distress were explored. An ad hoc questionnaire was used to record the time in minutes of physical activity engagement per week. The Connor–Davidson Resilience Scale, the Trait Meta-mood Scale, and Kessler Psychological Distress Scale were also administered. Statically significant differences are shown between the three examined groups: physical inactivity and non-beneficial physical activity; physical inactivity and beneficial physical activity, and; non-beneficial physical activity and beneficial physical activity. Positive and direct correlations were seen with respect to resilience and understanding, and emotional regulation, in addition to negative associations with respect to psychological distress. In conclusion, the more individuals engage in beneficial physical activity, the greater their resilience and emotional management, and the lower their rates of psychological distress.


The 14th of April, Past and Present


docid: bpiapfsf

title: 3D Printed Monolithic Microreactors for Real-Time Detection of Klebsiella pneumoniae and the Resistance Gene bla(NDM-1) by Recombinase Polymerase Amplification

text: We investigate the compatibility of three 3D printing materials towards real-time recombinase polymerase amplification (rtRPA). Both the general ability of the rtRPA reaction to occur while in contact with the cured 3D printing materials as well as the residual autofluorescence and fluorescence drift in dependence on post curing of the materials is characterized. We 3D printed monolithic rtRPA microreactors and subjected the devices to different post curing protocols. Residual autofluorescence and drift, as well as rtRPA kinetics, were then measured in a custom-made mobile temperature-controlled fluorescence reader (mTFR). Furthermore, we investigated the effects of storage on the devices over a 30-day period. Finally, we present the single- and duplex rtRPA detection of both the organism-specific Klebsiella haemolysin (khe) gene and the New Delhi metallo-β-lactamase 1 (bla(NDM-1)) gene from Klebsiella pneumoniae. Results: No combination of 3D printing resin and post curing protocol completely inhibited the rtRPA reaction. The autofluorescence and fluorescence drift measured were found to be highly dependent on printing material and wavelength. Storage had the effect of decreasing the autofluorescence of the investigated materials. Both khe and bla(NDM-1) were successfully detected by single- and duplex-rtRPA inside monolithic rtRPA microreactors printed from NextDent Ortho Clear (NXOC). The reaction kinetics were found to be close to those observed for rtRPA performed in a microcentrifuge tube without the need for mixing during amplification. Singleplex assays for both khe and bla(NDM-1) achieved a limit of detection of 2.5 × 10(1) DNA copies while the duplex assay achieved 2.5 × 10(1) DNA copies for khe and 2.5 × 10(2) DNA copies for bla(NDM-1). Impact: We expand on the state of the art by demonstrating a technology that can manufacture monolithic microfluidic devices that are readily suitable for rtRPA. The devices exhibit very low autofluorescence and fluorescence drift and are compatible with RPA chemistry without the need for any surface pre-treatment such as blocking with, e.g., BSA or PEG.


title: Association between Health Problems and Turnover Intention in Shift Work Nurses: Health Problem Clustering

text: Shift work nurses experience multiple health problems due to irregular shifts and heavy job demands. However, the comorbidity patterns of nurses’ health problems and the association between health problems and turnover intention have rarely been studied. This study aimed to identify and cluster shift work nurses’ health problems and to reveal the associations between health problems and turnover intention. In this cross-sectional study, we analyzed data from 500 nurses who worked at two tertiary hospitals in Seoul, South Korea. Data, including turnover intention and nine types of health issues, were collected between March 2018 and April 2019. Hierarchical clustering and multiple ordinal logistic regressions were used for the data analysis. Among the participants, 22.2% expressed turnover intention and the mean number of health problems was 4.5 (range 0–9). Using multiple ordinal logistic regressions analysis, it was shown that sleep disturbance, depression, fatigue, a gastrointestinal disorder, and leg or foot discomfort as a single health problem significantly increased turnover intention. After clustering the health problems, four clusters were identified and only the neuropsychological cluster—sleep disturbance, fatigue, and depression—significantly increased turnover intention. We propose that health problems within the neuropsychological cluster must receive close attention and be addressed simultaneously to decrease nurse’s turnover intentions.


Childhood Multisystem Inflammatory Syndrome — A New Challenge in the Pandemic


title: Molecular detection of Rickettsia species and host associations of Laelaps mites (Acari: Laelapidae) in Taiwan

text: Various rickettsiae have recently been detected in Laelaps mites (Acari: Laelapidae), which are common ectoparasites of rodents; however, investigations on this topic remain very scarce, particularly in Asia. In the present study, shrews and rodents were trapped from 2006 to 2010 in eight lowland regions of Taiwan (< 500 m in elevation) to collect associated Laelaps mites, from which Rickettsia—a group of emerging pathogens—were detected and identified by assaying the gltA and ompB genes. A total of 853 Laelaps mites of at least four species were collected from a sample of 1004 small mammals that included one shrew and 10 rodent species. Rattus losea was the most common species (44.9% of total hosts) and hosted the highest percentage of mites (76.6% of total mites). Laelaps nuttalli was the most abundant mite species (51.7% of total mites), followed by Laelaps echidninus (24.2%), Laelaps sedlaceki (23.1%), and Laelaps myonyssognathus (0.2%). Notably, Rickettsia species with the highest similarity to spotted fever group (SFG) rickettsiae were identified from seven of the 72 pools of Laelaps mites. The presence of SFG rickettsiae in hematophagous Laelaps mites, particularly including species that are closely associated with commensal rodents in frequent contact with humans, calls for further investigation on the competence of Laelaps mites in transmitting rickettsiae.


Implications of CRISPR/Cas9 system in Hypertension and its related diseases


title: Whole-organism behavioral profiling reveals a role for dopamine in state-dependent motor program coupling in C. elegans

text: Animal behaviors are commonly organized into long-lasting states that coordinately impact the generation of diverse motor outputs such as feeding, locomotion, and grooming. However, the neural mechanisms that coordinate these distinct motor programs remain poorly understood. Here, we examine how the distinct motor programs of the nematode C. elegans are coupled together across behavioral states. We describe a new imaging platform that permits automated, simultaneous quantification of each of the main C. elegans motor programs over hours or days. Analysis of these whole-organism behavioral profiles shows that the motor programs coordinately change as animals switch behavioral states. Utilizing genetics, optogenetics, and calcium imaging, we identify a new role for dopamine in coupling locomotion and egg-laying together across states. These results provide new insights into how the diverse motor programs throughout an organism are coordinated and suggest that neuromodulators like dopamine can couple motor circuits together in a state-dependent manner.


title: Quantifying the annual incidence and underestimation of seasonal influenza: A modelling approach

text: BACKGROUND: Seasonal influenza poses a significant public health and economic burden, associated with the outcome of infection and resulting complications. The true burden of the disease is difficult to capture due to the wide range of presentation, from asymptomatic cases to non-respiratory complications such as cardiovascular events, and its seasonal variability. An understanding of the magnitude of the true annual incidence of influenza is important to support prevention and control policy development and to evaluate the impact of preventative measures such as vaccination. METHODS: We use a dynamic disease transmission model, laboratory-confirmed influenza surveillance data, and randomized-controlled trial (RCT) data to quantify the underestimation factor, expansion factor, and symptomatic influenza illnesses in the US and Canada during the 2011-2012 and 2012-2013 influenza seasons. RESULTS: Based on 2 case definitions, we estimate between 0.42−3.2% and 0.33−1.2% of symptomatic influenza illnesses were laboratory-confirmed in Canada during the 2011-2012 and 2012-2013 seasons, respectively. In the US, we estimate between 0.08−0.61% and 0.07−0.33% of symptomatic influenza illnesses were laboratory-confirmed in the 2011-2012 and 2012-2013 seasons, respectively. We estimated the symptomatic influenza illnesses in Canada to be 0.32−2.4 million in 2011-2012 and 1.8−8.2 million in 2012-2013. In the US, we estimate the number of symptomatic influenza illnesses to be 4.4−34 million in 2011-2012 and 23−102 million in 2012-2013. CONCLUSIONS: We illustrate that monitoring a representative group within a population may aid in effectively modelling the transmission of infectious diseases such as influenza. In particular, the utilization of RCTs in models may enhance the accuracy of epidemiological parameter estimation.


title: Macrophage polarization and its role in the pathogenesis of acute lung injury/acute respiratory distress syndrome

text: PURPOSE: Macrophages are highly plastic cells. Under different stimuli, macrophages can be polarized into several different subsets. Two main macrophage subsets have been suggested: classically activated or inflammatory (M1) macrophages and alternatively activated or anti-inflammatory (M2) macrophages. Macrophage polarization is governed by a highly complex set of regulatory networks. Many recent studies have shown that macrophages are key orchestrators in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and that regulation of macrophage polarization may improve the prognosis of ALI/ARDS. A further understanding of the mechanisms of macrophage polarization is expected to be helpful in the development of novel therapeutic targets to treat ALI/ARDS. Therefore, we performed a literature review to summarize the regulatory mechanisms of macrophage polarization and its role in the pathogenesis of ALI/ARDS. METHODS: A computer-based online search was performed using the PubMed database and Web of Science database for published articles concerning macrophages, macrophage polarization, and ALI/ARDS. RESULTS: In this review, we discuss the origin, polarization, and polarization regulation of macrophages as well as the role of macrophage polarization in various stages of ARDS. According to the current literature, regulating the polarized state of macrophages might be a potential therapeutic strategy against ALI/ARDS.


title: Amplified Concern for Social Risk in Adolescence: Development and Validation of a New Measure

text: In adolescence, there is a heightened propensity to take health risks such as smoking, drinking or driving too fast. Another facet of risk taking, social risk, has largely been neglected. A social risk can be defined as any decision or action that could lead to an individual being excluded by their peers, such as appearing different to one’s friends. In the current study, we developed and validated a measure of concern for health and social risk for use in individuals of 11 years and over (N = 1399). Concerns for both health and social risk declined with age, challenging the commonly held stereotype that adolescents are less worried about engaging in risk behaviours, compared with adults. The rate of decline was steeper for social versus health risk behaviours, suggesting that adolescence is a period of heightened concern for social risk. We validated our measure against measures of rejection sensitivity, depression and risk-taking behaviour. Greater concern for social risk was associated with increased sensitivity to rejection and greater depressed mood, and this association was stronger for adolescents compared with adults. We conclude that social risks should be incorporated into future models of risk-taking behaviour, especially when they are pitted against health risks.


title: Human Parvoviruses May Affect the Development and Clinical Course of Meningitis and Meningoencephalitis

text: Meningitis and meningoencephalitis are neurological inflammatory diseases, and although routine diagnostics include testing of a wide range of pathogens, still in many cases, no causative agent is detected. Human parvovirus B19 (B19V), human bocaviruses 1–4 (HBoV1–4), and human parvovirus 4 (hPARV4) are members of the Parvoviridae family and are associated with a wide range of clinical manifestations including neurological disorders. The main aim of this study was to determine whether human parvoviruses infection markers are present among patients with meningitis/meningoencephalitis in Latvia as well as to clarify the role of these viruses on the clinical course of the mentioned diseases. Our study revealed HBoV1–4 and B19V genomic sequences in 52.38% and 16.67% of patients, respectively. Furthermore, symptoms such as the presence of a headache and its severity, fatigue, disorientation, and difficulties to concentrate were significantly frequently present in patients with active parvovirus infection in comparison with parvoviruses negative patients, therefore we suggest that HBoV1–4 and B19V infection should be included in the diagnostics to reduce the number of meningitis/meningoencephalitis with unknown/unexplained etiology.


title: Preclinical Efficacy of a Trivalent Human FcγRI-Targeted Adjuvant-Free Subunit Mucosal Vaccine against Pulmonary Pneumococcal Infection

text: Lack of safe and effective mucosal adjuvants has severely hampered the development of mucosal subunit vaccines. In this regard, we have previously shown that immunogenicity of vaccine antigens can be improved by targeting the antigens to the antigen-presenting cells. Specifically, groups of mice immunized intranasally with a fusion protein (Bivalent-FP) containing a fragment of pneumococcal-surface-protein-A (PspA) as antigen and a single-chain bivalent antibody raised against the anti-human Fc-gamma-receptor-I (hFcγRI) elicited protective immunity to pulmonary Streptococcus pneumoniae infection. In order to further enhance the immunogenicity, an additional hFcγRI-binding moiety of the single chain antibody was incorporated. The modified vaccine (Trivalent-FP) induced significantly improved protection against lethal pulmonary S. pneumoniae challenge compared to Bivalent-FP. In addition, the modified vaccine exhibited over 85% protection with only two immunizations. Trivalent-FP also induced S. pneumoniae-specific systemic and mucosal antibodies. Moreover, Trivalent-FP also induced IL-17- and IL-22-producing CD4(+) T cells. Furthermore, it was found that the hFcγRI facilitated uptake and presentation of Trivalent-FP. In addition, Trivalent-FP also induced IL-1α, MIP-1α, and TNF-α; modulated recruitment of dendritic cells and macrophages; and induced CD80/86 and MHC-II expression on antigen presenting cells.


docid: wpmmipnm

title: Herpes Simplex Viruses Whose Replication Can Be Deliberately Controlled as Candidate Vaccines

text: Over the last few years, we have been evaluating a novel paradigm for immunization using viruses or virus-based vectors. Safety is provided not by attenuation or inactivation of vaccine viruses, but by the introduction into the viral genomes of genetic mechanisms that allow for stringent, deliberate spatial and temporal control of virus replication. The resulting replication-competent controlled viruses (RCCVs) can be activated to undergo one or, if desired, several rounds of efficient replication at the inoculation site, but are nonreplicating in the absence of activation. Extrapolating from observations that attenuated replicating viruses are better immunogens than replication-defective or inactivated viruses, it was hypothesized that RCCVs that replicate with wild-type-like efficiency when activated will be even better immunogens. The vigorous replication of the RCCVs should also render heterologous antigens expressed from them highly immunogenic. RCCVs for administration to skin sites or mucosal membranes were constructed using a virulent wild-type HSV-1 strain as the backbone. The recombinants are activated by a localized heat treatment to the inoculation site in the presence of a small-molecule regulator (SMR). Derivatives expressing influenza virus antigens were also prepared. Immunization/challenge experiments in mouse models revealed that the activated RCCVs induced far better protective immune responses against themselves as well as against the heterologous antigens they express than unactivated RCCVs or a replication-defective HSV-1 strain. Neutralizing antibody and proliferation responses mirrored these findings. We believe that the data obtained so far warrant further research to explore the possibility of developing effective RCCV-based vaccines directed to herpetic diseases and/or diseases caused by other pathogens.


title: Serodynamic Analysis of the Piglets Born from Sows Vaccinated with Modified Live Vaccine or E2 Subunit Vaccine for Classical Swine Fever

text: Classical swine fever (CSF) caused by the CSF virus (CSFV) is one of the most important swine diseases, resulting in huge economic losses to the pig industry worldwide. Systematic vaccination is one of the most effective strategies for the prevention and control of this disease. Two main CSFV vaccines, the modified live vaccine (MLV) and the subunit E2 vaccine, are recommended. In Taiwan, CSF cases have not been reported since 2006, although systemic vaccination has been practiced for 70 years. Here, we examined the sero-dynamics of the piglets born from sows that received either the CSFV MLV or the E2 vaccine and investigated in the field the correlation between the porcine reproductive and respiratory syndrome virus (PRRSV) loads and levels of CSFV antibody. A total of 1398 serum samples from 42 PRRSV-positive farms were evaluated to determine the PRRSV loads by real-time PCR and to detect CSFV antibody levels by commercial ELISA. Upon comparing the two sow vaccination protocols (CSFV MLV vaccination at 4 weeks post-farrowing versus E2 vaccination at 4–5 weeks pre-farrowing), the lowest levels of CSFV antibody were found in piglets at 5–8 and 9–12 weeks of age for the MLV and E2 groups, respectively. Meanwhile, the appropriate time window for CSFV vaccination of offspring was at 5–8 and 9–12 weeks of age in the MLV and E2 groups, respectively. There was a very highly significant negative correlation between the PRRSV load and the level of CSFV antibody in the CSFV MLV vaccination group (P < 0.0001). The PRRSV detection rate in the pigs from the MLV group (27.78%) was significantly higher than that in pigs from the E2 group (21.32%) (P = 0.011). In addition, there was a significant difference (P = 0.019) in the PRRSV detection rate at 5–8 weeks of age between the MLV (42.15%) and E2 groups (29.79%). Our findings indicate that the vaccination of CSFV MLV in piglets during the PRRSV susceptibility period at 5–8 weeks of age may be overloading the piglet’s immune system and should be a critical concern for industrial pork production in the field.


title: Prospects of and Barriers to the Development of Epitope-Based Vaccines against Human Metapneumovirus

text: Human metapneumovirus (HMPV) is a major cause of respiratory illnesses in children, the elderly and immunocompromised patients. Although this pathogen was only discovered in 2001, an enormous amount of research has been conducted in order to develop safe and effective vaccines to prevent people from contracting the disease. In this review, we summarize current knowledge about the most promising experimental B- and T-cell epitopes of human metapneumovirus for the rational design of HMPV vaccines using vector delivery systems, paying special attention to the conservation of these epitopes among different lineages/genotypes of HMPV. The prospects of the successful development of an epitope-based HMPV vaccine are discussed in the context of recent findings regarding HMPV’s ability to modulate host immunity. In particular, we discuss the lack of data on experimental human CD4 T-cell epitopes for HMPV despite the role of CD4 lymphocytes in both the induction of higher neutralizing antibody titers and the establishment of CD8 memory T-cell responses. We conclude that current research should be focused on searching for human CD4 T-cell epitopes of HMPV that can help us to design a safe and cross-protective epitope-based HMPV vaccine.


title: Development and Challenges in Animal Tuberculosis Vaccination

text: Vaccination with Bacillus Calmette–Guérin (BCG) constituted a major advance in the prevention of human tuberculosis (TB) in the beginning of the past century. BCG has also a clear potential for use in animals and, in particular, in the main domestic species subjected to TB control programs, cattle. Nowadays, the use of BCG vaccination against TB in cattle is not permitted by European Union legislation because BCG can induce a cellular immune response producing diagnostic interference in the eradication programs based on tuberculin single and comparative intradermal tests imposed worldwide. In this review, we recall the history of TB vaccination as well as different vaccine trials and the response to vaccination in both domestic and wild animals. Promising potential inactivated vaccines are also reviewed. Research studies are mainly focused to improve vaccine efficacy, and at the same time to ensure its easy administration, safety and stability in the environment. Great challenges remain, particularly in terms of vaccine candidates and also in the acceptance of vaccination. Vaccination should be included in a strategic plan for integrated control of TB under a “one health” perspective, which also includes other measures such as improved biosafety on farms to avoid or decrease contact between domestic and wild animals or control of wildlife reservoirs to avoid overabundance that may favor infection maintenance.


Prepare or perish - Readiness is the key to reopen for routine eye care


Survival tool kit for ophthalmic practices during difficult times: Build your resilience in the face of crisis


miRNA nanotherapeutics: potential and challenges in respiratory disorders


title: Droplet-based high-throughput cultivation for accurate screening of antibiotic resistant gut microbes

text: Traditional cultivation approaches in microbiology are labor-intensive, low-throughput, and yield biased sampling of environmental microbes due to ecological and evolutionary factors. New strategies are needed for ample representation of rare taxa and slow-growers that are often outcompeted by fast-growers in cultivation experiments. Here we describe a microfluidic platform that anaerobically isolates and cultivates microbial cells in millions of picoliter droplets and automatically sorts them based on colony density to enhance slow-growing organisms. We applied our strategy to a fecal microbiota transplant (FMT) donor stool using multiple growth media, and found significant increase in taxonomic richness and larger representation of rare and clinically relevant taxa among droplet-grown cells compared to conventional plates. Furthermore, screening the FMT donor stool for antibiotic resistance revealed 21 populations that evaded detection in plate-based assessment of antibiotic resistance. Our method improves cultivation-based surveys of diverse microbiomes to gain deeper insights into microbial functioning and lifestyles.


title: Interactions between Borrelia burgdorferi and ticks

text: Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to vertebrate hosts by Ixodes spp. ticks. The spirochaete relies heavily on its arthropod host for basic metabolic functions and has developed complex interactions with ticks to successfully colonize, persist and, at the optimal time, exit the tick. For example, proteins shield spirochaetes from immune factors in the bloodmeal and facilitate the transition between vertebrate and arthropod environments. On infection, B. burgdorferi induces selected tick proteins that modulate the vector gut microbiota towards an environment that favours colonization by the spirochaete. Additionally, the recent sequencing of the Ixodes scapularis genome and characterization of tick immune defence pathways, such as the JAK–STAT, immune deficiency and cross-species interferon-γ pathways, have advanced our understanding of factors that are important for B. burgdorferi persistence in the tick. In this Review, we summarize interactions between B. burgdorferi and I. scapularis during infection, as well as interactions with tick gut and salivary gland proteins important for establishing infection and transmission to the vertebrate host.


title: History of the Pan African Paediatric Surgery Association (PAPSA)

text: The Pan African Paediatric Surgery Association (PAPSA) was formed in 1994. The need for an organisation in Africa to voice children’s surgery and the trials and tribulations in forming this organisation was covered in this journal 2 years ago (Heinz R, Kyambi J, Lakhoo K. Surg Int 34(5):499–504, 2018). This article covers the history of the organisation post inception in 1994 to date. The near disbanding of the organisation due to political unrest and wars in Africa, to its success in the recent decade is highlighted in this manuscript.


title: Reconstructing family doctors’ psychological well-being and motivation for effective performance in China: the intervening role of psychological capital

text: BACKGROUND: Family practice and family doctors are critical part of China’s primary healthcare delivery in a constantly evolving society. As the first point of contact with the medical system, family practices require physically and psychologically sound and a well-motivated family doctors at all times. This is because an error can lead to loss of lives as gatekeepers of the medical system. Our study explored the extent to which positive psychological capital promotes higher performance among family doctors. METHODS: A questionnaire was used to collect data from family doctors in Shanghai, Nanjing, and Beijing. We applied a structural equation analysis to analyze the causal relationship among the variables. RESULTS: We found out that psychological well-being and job involvement significantly influences the performance of family doctors in China. The study also noted that psychological capital moderates the relationship between psychological well-being attainment, job involvement, and performance. CONCLUSIONS: Studies have shown that these pressures affect their well-being considerably. For this reason, a healthcare professional who experiences positive emotions affects the total behavior which culminates into performance.


title: Renin-Angiotensin System in Lung Tumor and Microenvironment Interactions

text: The mechanistic involvement of the renin-angiotensin system (RAS) reaches beyond cardiovascular physiopathology. Recent knowledge pinpoints a pleiotropic role for this system, particularly in the lung, and mainly through locally regulated alternative molecules and secondary pathways. Angiotensin peptides play a role in cell proliferation, immunoinflammatory response, hypoxia and angiogenesis, which are critical biological processes in lung cancer. This manuscript reviews the literature supporting a role for the renin-angiotensin system in the lung tumor microenvironment and discusses whether blockade of this pathway in clinical settings may serve as an adjuvant therapy in lung cancer.


title: Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005–2016 NHANES

text: A well-functioning immune system is essential for human health and well-being. Micronutrients such as vitamins A, C, D, E, and zinc have several functions throughout the immune system, yet inadequate nutrient intakes are pervasive in the US population. A large body of research shows that nutrient inadequacies can impair immune function and weaken the immune response. Here, we present a new analysis of micronutrient usual intake estimates based on nationally representative data in 26,282 adults (>19 years) from the 2005–2016 National Health and Nutrition Examination Surveys (NHANES). Overall, the prevalence of inadequacy (% of population below estimated average requirement [EAR]) in four out of five key immune nutrients is substantial. Specifically, 45% of the U.S. population had a prevalence of inadequacy for vitamin A, 46% for vitamin C, 95% for vitamin D, 84% for vitamin E, and 15% for zinc. Dietary supplements can help address nutrient inadequacy for these immune-support nutrients, demonstrated by a lower prevalence of individuals below the EAR. Given the long-term presence and widening of nutrient gaps in the U.S.—specifically in critical nutrients that support immune health—public health measures should adopt guidelines to ensure an adequate intake of these micronutrients. Future research is needed to better understand the interactions and complexities of multiple nutrient shortfalls on immune health and assess and identify optimal levels of intake in at-risk populations.


title: Assessing Advantages and Drawbacks of Rapidly Generated Ultra-Large 3D Breast Cancer Spheroids: Studies with Chemotherapeutics and Nanoparticles

text: Traditionally, two-dimensional (2D) monolayer cell culture models have been used to study in vitro conditions for their ease of use, simplicity and low cost. However, recently, three-dimensional (3D) cell culture models have been heavily investigated as they provide better physiological relevance for studying various disease behaviors, cellular activity and pharmaceutical interactions. Typically, small-sized tumor spheroid models (100–500 μm) are used to study various biological and physicochemical activities. Larger, millimetric spheroid models are becoming more desirable for simulating native tumor microenvironments (TMEs). Here, we assess the use of ultra-large spheroid models (~2000 μm) generated from scaffolds made from a nozzle-free, ultra-high resolution printer; these models are explored for assessing chemotherapeutic responses with molecular doxorubicin (DOX) and two analogues of Doxil(Ⓡ) (Dox-NP(Ⓡ), Doxoves(TM)) on MDA-MB-231 and MCF-7 breast cancer cell lines. To provide a comparative baseline, small spheroid models (~500 μm) were developed using a self-aggregation method of MCF-7 breast cancer cell lines, and underwent similar drug treatments. Analysis of both large and small MCF-7 spheroids revealed that Dox-NP tends to have the highest level of inhibition, followed by molecular doxorubicin and then Doxoves. The experimental advantages and drawbacks of using these types of ultra-large spheroids for cancer research are discussed.


title: Pilot Multi-Omic Analysis of Human Bile from Benign and Malignant Biliary Strictures: A Machine-Learning Approach

text: Cholangiocarcinoma (CCA) and pancreatic adenocarcinoma (PDAC) may lead to the development of extrahepatic obstructive cholestasis. However, biliary stenoses can also be caused by benign conditions, and the identification of their etiology still remains a clinical challenge. We performed metabolomic and proteomic analyses of bile from patients with benign (n = 36) and malignant conditions, CCA (n = 36) or PDAC (n = 57), undergoing endoscopic retrograde cholangiopancreatography with the aim of characterizing bile composition in biliopancreatic disease and identifying biomarkers for the differential diagnosis of biliary strictures. Comprehensive analyses of lipids, bile acids and small molecules were carried out using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy ((1)H-NMR) in all patients. MS analysis of bile proteome was performed in five patients per group. We implemented artificial intelligence tools for the selection of biomarkers and algorithms with predictive capacity. Our machine-learning pipeline included the generation of synthetic data with properties of real data, the selection of potential biomarkers (metabolites or proteins) and their analysis with neural networks (NN). Selected biomarkers were then validated with real data. We identified panels of lipids (n = 10) and proteins (n = 5) that when analyzed with NN algorithms discriminated between patients with and without cancer with an unprecedented accuracy.


title: Strategies to Improve Health Communication: Can Health Professionals Be Heroes?

text: Communicating evidence-based nutrition messages to the public is challenging and is often in conflict with popular opinions, particularly from social media influencers (SMIs). In order to increase engagement with nutrition professionals (NPs) on social media, we aimed to explore young adults’ perceptions of the authenticity and trustworthiness of SMIs and NPs Instagram posts. A cross-sectional questionnaire was administered to students (n = 149) from an Australian University. Participants viewed a real-life Instagram profile and one post from both a NP and a SMI. Main outcomes were post authenticity and trustworthiness, and emotional message appeals measured on five-point Likert scales. Regression models were developed to assess whose post (the NP or SMI) was perceived to be more authentic and trustworthy. Participants were young adults (median age (25th, 75th percentiles): 20 (19,21)), with approximately half identifying as female. A high heroic message appeal (+1SD above mean) significantly increased the perceived authenticity of the NPs post only (p = 0.01). Post authenticity enhanced post trustworthiness, but only when a heroic message appeal was used by the NP. When appropriate, NPs should convey positive emotions such as bravery and success to enhance the authenticity and trustworthiness of their posts.


title: The Central Role of Iron in Human Nutrition: From Folk to Contemporary Medicine

text: Iron is a fundamental element in human history, from the dawn of civilization to contemporary days. The ancients used the metal to shape tools, to forge weapons, and even as a dietary supplement. This last indication has been handed down until today, when martial therapy is considered fundamental to correct deficiency states of anemia. The improvement of the martial status is mainly targeted with dietary supplements that often couple diverse co-factors, but other methods are available, such as parenteral preparations, dietary interventions, or real-world approaches. The oral absorption of this metal occurs in the duodenum and is highly dependent upon its oxidation state, with many absorption influencers possibly interfering with the intestinal uptake. Bone marrow and spleen represent the initial and ultimate step of iron metabolism, respectively, and the most part of body iron circulates bound to specific proteins and mainly serves to synthesize hemoglobin for new red blood cells. Whatever the martial status is, today’s knowledge about iron biochemistry allows us to embrace exceedingly personalized interventions, which however owe their success to the mythical and historical events that always accompanied this metal.


title: Modeling the Effect of the Oxidation Status of the Ingredient Oil on Stability and Shelf Life of Low-Moisture Bakery Products: The Case Study of Crackers

text: In packed low-moisture foods such as crackers, oxidation is generally the main cause of quality depletion during storage. It is commonly believed, but scarcely investigated, that product shelf life depends on the oxidative status of the lipid ingredients. In this study, the influence of oxidation degree of the ingredient sunflower oil on cracker oxidative stability and hence shelf life was investigated. To this aim, oil with increasing peroxide values (PVs) (5, 11, and 25 mEqO(2)/kg(oil)) was used to prepare crackers. Just after production, crackers presented similar peroxide and rancid odor intensity, probably due to the interactive pathways of oxidative and Maillard reactions. Crackers were packed and analyzed for PV and rancid odor during storage at 20, 40, and 60 °C. Rancid odor well discriminated cracker oxidative status. Relevant oxidation rates were used to develop a shelf life predictive model based on the peroxide value of the ingredient oil. It was estimated that an oil PV from 5 to 15 mEqO(2)/kg(oil) shortens cracker Shelf Life (SL) by 50%, independently of storage temperature. These results demonstrate the critical impact of ingredient quality on product performance on the market.


docid: neowfhwg

title: Development of a sensitive monoclonal antibody-based sandwich ELISA to detect Vip3Aa in genetically modified crops

text: OBJECTIVES: To develop a sensitive monoclonal antibody-based sandwich enzyme-linked immunosorbent assay (ELISA) to detect Vip3Aa in genetically modified (GM) crops and their products. RESULTS: Vegetative insecticidal proteins (Vips) are secreted by Bacillus thuringiensis (Bt) and are known to be toxic to Lepidoptera species. Vip3Aa family proteins, Vip3Aa19 and Vip3Aa20, were successfully applied in GM crops to confer an effective and persistent insecticidal resistance. A sensitive monoclonal antibody-based sandwich ELISA was developed to detect Vip3Aa in GM crops and their products. Two monoclonal antibodies were raised against the overexpressed and purified His-Vip3Aa20, were purified from mouse ascites and characterized. A sandwich ELISA method was developed using the 2G3-1D7 monoclonal antibody for capture and the biotin-labeled 1F9-1F5 monoclonal antibody for detection of Vip3Aa20. The linear detection range of the method was found to be approximately 31.25–500 pg/ml, with a sensitivity of 10.24 pg/ml. CONCLUSIONS: The established ELISA was effective for detecting Vip3Aa family proteins other than Vip3Aa8, and was successfully applied in the detection of Vip3Aa20 and Vip3Aa19 expressed in transgenic maize and cotton.


docid: gfadjjmc

title: Kontaktallergie auf FFP2-Maske in der COVID-19-Pandemie


docid: bgopkwij

title: Assigning mitochondrial localization of dual localized proteins using a yeast Bi-Genomic Mitochondrial-Split-GFP

text: A single nuclear gene can be translated into a dual localized protein that distributes between the cytosol and mitochondria. Accumulating evidences show that mitoproteomes contain lots of these dual localized proteins termed echoforms. Unraveling the existence of mitochondrial echoforms using current GFP (Green Fluorescent Protein) fusion microscopy approaches is extremely difficult because the GFP signal of the cytosolic echoform will almost inevitably mask that of the mitochondrial echoform. We therefore engineered a yeast strain expressing a new type of Split-GFP that we termed Bi-Genomic Mitochondrial-Split-GFP (BiG Mito-Split-GFP). Because one moiety of the GFP is translated from the mitochondrial machinery while the other is fused to the nuclear-encoded protein of interest translated in the cytosol, the self-reassembly of this Bi-Genomic-encoded Split-GFP is confined to mitochondria. We could authenticate the mitochondrial importability of any protein or echoform from yeast, but also from other organisms such as the human Argonaute 2 mitochondrial echoform.


title: The Respiratory Specimen Collection Trial (ReSpeCT): A Randomized Controlled Trial to Compare Quality and Timeliness of Respiratory Sample Collection in the Home by Parents and Healthcare Workers From Children Aged <2 Years

text: BACKGROUND: Most acute respiratory infection (ARI) research focuses on severe disease and overlooks the burden of community-managed illness. For community-based studies, home-based specimen collection by parents could be a resource-saving alternative to collection by healthcare workers (HCWs). In this study, we compared parent and HCW groups for their likelihood to collect specimens and the timeliness and quality of such collection. METHODS: In this unblinded randomized controlled trial, parents from Brisbane, Australia, were taught to identify new ARI episodes in their children aged <2 years. When their child had a new ARI, parents either collected a nasal swab from the child (P group) or contacted an HCW who visited to obtain a nasopharyngeal swab (HCW group). We compared the likelihood and timeliness of specimen collection and respiratory pathogen detection. A nested diagnostic study compared paired specimen collections from children in the HCW group. RESULTS: Included were 76 incident ARI episodes from 31 children and 102 episodes from 33 children in the P and HCW groups, respectively. The proportions of ARIs for which a specimen was collected were similar (P group, 69.7%; HCW group, 72.5%; P = .77), and pathogens were detected in 93.8% and 77.5% of the specimens, respectively (P = .03). The period between ARI onset and specimen collection was shorter in the P group than in the HCW group (mean difference, 1.9 days [95% confidence interval, 0.7–3.0 days]; P < .001). For the 69 paired specimens, viral loads were lower in the parent-collected swabs (mean cycle threshold difference, 4.5 [95% confidence interval, 3.1–5.9]; P < .001). CONCLUSIONS: Parents and HCWs obtained samples in similar proportions of ARI episodes, but the parents collected the samples fewer days after ARI onset and with a resulting higher likelihood of pathogen identification. This method can be used in population-based epidemiological studies of ARI as a resource-saving alternative. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00966069.


title: Golgi compartments enable controlled biomolecular assembly using promiscuous enzymes

text: The synthesis of eukaryotic glycans – branched sugar oligomers attached to cell-surface proteins and lipids – is organized like a factory assembly line. Specific enzymes within successive compartments of the Golgi apparatus determine where new monomer building blocks are linked to the growing oligomer. These enzymes act promiscuously and stochastically, causing microheterogeneity (molecule-to-molecule variability) in the final oligomer products. However, this variability is tightly controlled: a given eukaryotic protein type is typically associated with a narrow, specific glycan oligomer profile. Here, we use ideas from the mathematical theory of self-assembly to enumerate the enzymatic causes of oligomer variability and show how to eliminate each cause. We rigorously demonstrate that cells can specifically synthesize a larger repertoire of glycan oligomers by partitioning promiscuous enzymes across multiple Golgi compartments. This places limits on biomolecular assembly: glycan microheterogeneity becomes unavoidable when the number of compartments is limited, or enzymes are excessively promiscuous.


The Fuzzy Connection between SARS-CoV-2 Infection and Loss of Renal Function


docid: eplgwnem

title: The Case Is Much More Baffling than We Think


Letter to the Editor regarding the Article “Impact of Anterior Kidney Calyx Involvement of Complex Stones on Outcomes for Patients Undergoing Percutaneous Nephrolithotomy”


The silent danger of social distancing


How do we reopen our motility laboratory safely and efficiently?


title: Genetic code expansion strategies for vaccine development

text: By providing long‐term protection against infectious diseases vaccinations have significantly reduced death and morbidity world‐wide. In the 21 st century, (bio)technological advances have paved the way for developing prophylactic vaccines that are safer and more effective as well as enabled the use of vaccines as therapeutics to treat human diseases. Here, we provide a focused review on the utility of genetic code expansion as an emerging tool for the development of vaccines. Specifically, we discuss how the incorporation of immunogenic non‐canonical amino acids can aid in eliciting immune responses against adverse self‐proteins and highlight the potential of an expanded genetic code for the construction of replication‐incompetent viruses. We close the review by discussing future prospects and remaining challenges for the application of these approaches in the development of both prophylactic and therapeutic vaccines in the near future.