title: Influenza Vaccination and Healthcare Personnel Compliance

text: PURPOSE OF REVIEW: We reviewed the benefit of influenza vaccination in healthcare personnel (HCP), rates of vaccine coverage, and practices used to try to boost vaccine coverage among HCP. RECENT FINDINGS: Influenza vaccination in HCP provides benefits to both HCP and patients, including reductions in patient morbidity and mortality and decreases in HCP absenteeism. Despite these benefits, influenza vaccine coverage among HCP still falls short of the Healthy People 2020 goal of 90%. As a result, healthcare institutions have used various practices to boost vaccination, including mandatory vaccine policies and requiring non-immunized HCP to wear masks during the influenza season. All of these efforts have been successful at increasing vaccination rates, and employer vaccination requirements have led to rates that meet the Healthy People 2020 goal. Rates of mandatory vaccine policies have increased over time, and several states now have influenza vaccine requirements. However, additional study into how these policies improve patient outcomes is needed. SUMMARY: Continued effort is needed to boost influenza vaccination rates among HCP, and mandatory vaccine policies may be used if other methods have not been effective in adequately raising vaccination rates. Future research should focus on how mandatory vaccine policies can improve patient outcomes.


title: Choosing the best supraglottic airway for ophthalmic general anaesthesia: a manikin study

text: General anaesthesia is sometimes favoured over regional anaesthesia in ophthalmic surgery. The use of supraglottic airway (SGA) or laryngeal mask airway (LMA) as the primary airway device is increasing due to numerous advantages over tracheal intubation. Compared with 1st generation SGAs, 2nd generation SGAs have an added benefit of isolating the airway from the alimentary tract. However, the vertical profile of SGAs may encroach into the surgical field and hence interfere with surgery. We investigated the vertical projections of 1st generation SGAs (LMA Classic, Ambu AuraFlex) and commonly used 2nd generation SGAs in our institution (LMA ProSeal, LMA Supreme, LMA Protector, Ambu AuraGain and I-gel) in a manikin model. Each device was connected to a corrugated catheter mount or angled connector following insertion as per usual clinical practice in our institutions. Vertical projections of all devices were measured from the chin using a centimetre ruler. Securing of airway device to the chin with an adhesive tape was possible for the LMA Classic and Ambu AuraFlex with straight corrugated connector, whereas the stiffer 2nd generations SGAs required the addition of an angled connector or straight corrugated tubing to direct the airway tube caudally, away from the surgical field. The LMA ProSeal had the lowest vertical projection amongst the 2nd generation SGAs and may be the suitable choice for ophthalmic surgery. We also describe a novel technique of utilising a 1st generation SGA with placement of an orogastric tube, although with some reservations. This study has several limitations and transferability of our findings into clinical practice is questionable as the use of a manikin may not fully imitate the real condition of the patient. Our study is the first study comparing vertical projected height of different SGAs in manikin, but future studies should investigate the use of SGA in the clinical setting during ophthalmic surgery.


title: Early changes in diaphragmatic function evaluated using ultrasound in cardiac surgery patients: a cohort study

text: Little is known about the evolution of diaphragmatic function in the early post-cardiac surgery period. The main purpose of this work is to describe its evolution using ultrasound measurements of muscular excursion and thickening fraction (TF). Single-center prospective study of 79 consecutive uncomplicated elective cardiac surgery patients, using motion-mode during quiet unassisted breathing. Excursion and TF were measured sequentially for each patient [pre-operative (D1), 1 day (D2) and 5 days (D3) after surgery]. Pre-operative median for right and left hemidiaphragmatic excursions were 1.8 (IQR 1.6 to 2.1) cm and 1.7 (1.4 to 2.0) cm, respectively. Pre-operative median right and left thickening fractions were 28 (19 to 36) % and 33 (22 to 51) %, respectively. At D2, there was a reduction in both excursion (right: 1.5 (1.1 to 1.8) cm, p < 0.001, left: 1.5 (1.1 to 1.8), p = 0.003) and thickening fractions (right: 20 (15 to 34) %, p = 0.021, left: 24 (17 to 39) %, p = 0.002), followed by a return to pre-operative values at D3. A positive moderate correlation was found between excursion and thickening fraction (Spearman’s rho 0.518 for right and 0.548 for left hemidiaphragm, p < 0.001). Interobserver reliability yielded a bias below 0.1 cm with limits of agreement (LOA) of ± 0.3 cm for excursion and − 2% with LOA of ± 21% for thickening fractions. After cardiac surgery, the evolution of diaphragmatic function is characterized by a transient impairment followed by a quick recovery. Although ultrasound diaphragmatic excursion and thickening fraction are correlated, excursion seems to be a more feasible and reproducible method in this population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10877-019-00350-8) contains supplementary material, which is available to authorized users.


title: Neonatal transport in California: findings from a qualitative investigation

text: OBJECTIVE: To identify characteristics of neonatal transport in California and which factors influence team performance. STUDY DESIGN: We led focus group discussions with 19 transport teams operating in California, interviewing 158 neonatal transport team members. Transcripts were analyzed using a thematic analysis approach. RESULT: The composition of transport teams varied widely. There was strong thematic resonance to suggest that the nature of emergent neonatal transports is unpredictable and poses several significant challenges including staffing, ambulance availability, and administrative support. Teams reported dealing with this unpredictability by engaging in teamwork, gathering experience with staff at referral hospitals, planning for a wide variety of circumstances, specialized training, debriefing after events, and implementing quality improvement strategies. CONCLUSION: Our findings suggest potential opportunities for improvement in neonatal transport. Future research can explore the cost and benefits of strategies such as dedicated transport services, transfer centers, and telemedicine.


title: Diaphragm and Lung Ultrasound Indices in Prediction of Outcome of Weaning from Mechanical Ventilation in Pediatric Intensive Care Unit

text: OBJECTIVE: To predict the added value of diaphragmatic and lung ultrasound indices (US) in anticipation of the outcome of mechanical ventilation of pediatric patients in the intensive care unit. METHODS: This prospective study was conducted in Zagazig University, Pediatric Hospitals, PICU; Egypt. One hundred six mechanically ventilated children aged between 1 mo to 170 mo were included in the study. All patients were candidates for weaning and have been given a chance for spontaneous breathing trial (SBT), during which diaphragmatic and lung US was performed for them. The diaphragm thickening fraction (DTF), the diaphragmatic excursion and the lung US score (LUS), that included 4 US aeration forms, were assessed. RESULTS: There were statistically significant differences between patients with failed weaning and those with successful weaning regarding DTF, diaphragmatic excursion and LUS (p < 0.001). The best cut-off value of DTF, diaphragmatic excursion, and LUS for predicting weaning failure was ≥23.175%, ≥ 6.2 mm, and ≥ 12 with an AUC (area under curve) of 0.932, 0.876, and 0.934, respectively. CONCLUSIONS: Diaphragmatic and lung US add a quick, accurate and non-invasive indices to the weaning readiness parameters compared to the other standard parameters alone. So, it is recommended to be added to the predictive parameters of weaning outcome.


title: Clinical decision-making on spinal cord injury-associated pneumonia: a nationwide survey in Germany

text: STUDY DESIGN: Survey study. OBJECTIVES: Spinal cord injury (SCI)-associated pneumonia (SCI-AP) is associated with poor functional recovery and a major cause of death after SCI. Better tackling SCI-AP requires a common understanding on how SCI-AP is defined. This survey examines clinical algorithms relevant for diagnosis and treatment of SCI-AP. SETTING: All departments for SCI-care in Germany. METHODS: The clinical decision-making on SCI-AP and the utility of the Centers for Disease Control and Prevention (CDC) criteria for diagnosis of ‘clinically defined pneumonia’ were assessed by means of a standardized questionnaire including eight case vignettes of suspected SCI-AP. The diagnostic decisions based on the case information were analysed using classification and regression trees (CART). RESULTS: The majority of responding departments were aware of the CDC-criteria (88%). In the clinical vignettes, 38–81% of the departments diagnosed SCI-AP in accordance with the CDC-criteria and 7–41% diagnosed SCI-AP in deviation from the CDC-criteria. The diagnostic agreement was not associated with the availability of standard operating procedures for SCI-AP management in the departments. CART analysis identified radiological findings, fever, and worsened gas exchange as most important for the decision on SCI-AP. Frequently requested supplementary diagnostics were microbiological analyses, C-reactive protein, and procalcitonin. For empirical antibiotic therapy, the departments used (acyl-)aminopenicillins/β-lactamase inhibitors, cephalosporins, or combinations of (acyl-)aminopenicillins/β-lactamase inhibitors with fluoroquinolones or carbapenems. CONCLUSIONS: This survey reveals a diagnostic ambiguity regarding SCI-AP despite the awareness of CDC-criteria and established SOPs. Heterogeneous clinical practice is encouraging the development of disease-specific guidelines for diagnosis and management of SCI-AP.


title: Octogenarians with blunt splenic injury: not all geriatrics are the same

text: Geriatric trauma patients (GTP) (age ≥ 65 years) with blunt splenic injury (BSI) have up to a 6% failure rate of non-operative management (NOM). GTPs failing NOM have a similar mortality rate compared to GTPs managed successfully with NOM. However, it is unclear if this remains true in octogenarians (aged 80–89 years). We hypothesized that the failure rate for NOM in octogenarians would be similar to their younger geriatric cohort, patients aged 65–79 years; however risk of mortality in octogenarians who fail NOM would be higher than that of octogenarians managed successfully with NOM. The Trauma Quality Improvement Program (2010–2016) was queried for patients with BSI. Those undergoing splenectomy within 6 h were excluded to select for patients undergoing NOM. Patients aged 65–79 years (young GTPs) were compared to octogenarians. A multivariable logistic regression model was used to determine the risk for failed NOM and mortality. From 43,041 BSI patients undergoing NOM, 3660 (8.5%) were aged 65–79 years and 1236 (2.9%) were octogenarians. Both groups had a similar median Injury Severity Score (ISS) (p = 0.10) and failure rate of NOM (6.6% young GTPs vs. 6.8% octogenarians p = 0.82). From those failing NOM, octogenarians had similar units of blood products transfused (p > 0.05) and a higher mortality rate (40.5% vs. 18.2%, p < 0.001), compared to young GTPs. Independent risk factors for failing NOM in octogenarians included ≥ 1 unit of packed red blood cells (PRBC) (p = 0.039) within 24 h of admission. Octogenarians who failed NOM had a higher mortality rate compared to octogenarians managed successfully with NOM (40.5% vs 23.6% p = 0.001), which persisted in a multivariable logistic regression analysis (OR 2.25, CI 1.37–3.70, p < 0.001). Late failure of NOM ≥ 24 h (vs. early failure) was not associated with increased risk of mortality (p = 0.88), but ≥ 1 unit of PRBC transfused had higher risk (OR 1.88, CI 1.20–2.95, p = 0.006). Compared to young GTPs with BSI, octogenarians have a similar rate of failed NOM. Octogenarians with BSI who fail NOM have over a twofold higher risk of mortality compared to those managed successfully with NOM. PRBC transfusion increases risk for mortality. Therefore, clinicians should consider failure of NOM earlier in the octogenarian population to mitigate the risk of increased mortality.


title: Systemic lupus erythematosus presenting with status epilepticus and acute cardiomyopathy with acute heart failure: case report

text: INTRODUCTION: Systemic lupus erythematosus is a connective tissue disorder, which causes complex multi organ involvement. Neurological and cardiac manifestations have been well noted but complications such as status epilepticus and acute myocarditis with heart failure at presentation remains uncommon. CASE DESCRIPTION: A 15-year-old, previously healthy, South Asian, Sri Lankan female presented with status epilepticus and the seizures only responded to intravenous midazolam and thiopentone sodium. On the fourth day, she developed tachycardia and shortness of breath and was found to have cardiomyopathy with heart failure with an ejection fraction 40%. Along with a positive urinary sediment, a positive ANA with a very high level of ds-DNA and low C3 and C4 levels confirmed our suspicion of systemic lupus erythematosus. DISCUSSION AND EVALUATION: Systemic lupus erythematosus presents in a variety of clinical presentations and the spectrum may range from unique to ubiquitous. Clinicians should have a high index of suspicion specially when encountering atypical presentations with multi-organ involvement, especially when patients tend to be young females. Status epilepticus and myocarditis are uncommon manifestations of systemic lupus erythematosus, and should be appreciated early, as if inappropriately managed would have a deleterious impact on mortality and morbidity.


title: Questioning dogma: does a GCS of 8 require intubation?

text: BACKGROUND: There is no evidence supporting intubation for a Glasgow Coma Scale (GCS) of 8. We investigated the effect of intubation in trauma patients with a GCS 6–8, with the hypothesis that intubation would increase mortality and length of stay. METHODS: We studied adult patients with GCS 6–8 from the 2016 National Trauma Data Bank. Intubated and non-intubated patients were compared using inverse probability weighted regression adjustment (IPWRA) to control for injury severity and patient characteristics. Outcomes were mortality, intensive care unit length of stay (ICU LOS), and total LOS. Stratified analysis was performed to investigate the effect in patients with and without head injuries. RESULTS: Among 6676 patients with a GCS between 6 and 84,078 were intubated within 1 h of arrival to the emergency department. The overall mortality rate was 15.1%. IPWRA revealed an increase in mortality associated with intubation (OR 1.05, 95% CI 1.03, 1.06). The results were similar in patients with head injuries (OR 1.04, 95% CI 1.02, 1.06) and without (OR 1.06, 95% CI 1.03, 1.10). Among the 5,742 patients admitted to the ICU, intubation was associated with a 14% increase in ICU LOS (95% CI 8–20%; 5.5 vs. 4.8 days; p < 0.001). The overall length of stay was 27% longer (95% CI 19.8–34.3%) among intubated patients (mean 7.7 vs 6.0 days; p < 0.001). CONCLUSION: Among patients with GCS of 6 to 8, intubation on arrival was associated with an increase in mortality and with longer ICU and overall length of stay. The use of a strict threshold GCS to mandate intubation should be revisited.


title: Screening of compound libraries for inhibitors of Toxoplasma growth and invasion

text: Toxoplasma gondii can infect virtually all warm-blooded animals, including humans. It can differentiate between rapidly replicating tachyzoites that cause acute infection and slowly growing bradyzoites in tissue cysts. Treatment options for toxoplasmosis are challenging because current therapies cannot eradicate the latent T. gondii infection that is mainly caused by the bradyzoite forms. Accordingly, recurrence of infection is a problem for immunocompromised patients and congenitally infected patients. Protein kinases have been widely studied in eukaryotic cells, and while little is known about signaling in Toxoplasma infection, it is likely that protein kinases play a key role in parasite proliferation, differentiation, and probably invasion. To identify optimized new kinase inhibitors for drug development against T. gondii, we screened a library of kinase inhibitor compounds for anti-Toxoplasma activity and host cell cytotoxicity. Pyrimethamine served as a positive control and 0.5% DMSO was used as a negative control. Among the 80 compounds screened, 6 compounds demonstrated ≥ 80% parasite growth inhibition at concentrations at which 5 compounds did not suppress host cell viability, while 3 kinase inhibitors (Bay 11-7082, Tyrphostin AG 1295 and PD-98059) had suppressive effects individually on parasite growth and host cell invasion, but did not strongly induce bradyzoite formation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00436-020-06673-9) contains supplementary material, which is available to authorized users.


Abstracts zum 126. Kongress der Deutschen Gesellschaft für Innere Medizin e.V.


title: Vascular compression of the left bronchus in a patient with funnel chest

text: We present a case of 5 year-old female with funnel chest, by which cardiovascular structures were displaced into the left chest cavity. This caused left bronchial compression by the pulmonary artery and the descending aorta, for which an external stenting was successfully performed. The patient had features suggestive of skeletal dysplasia with tracheobronchial malacia. One possible mechanism of vascular compression could be an association of fragility of the thoracic cavity and inspiratory dyspnea, causing thoracic deformity.


title: Influence of ZnO, SiO(2) and TiO(2) on the aging process of PLA fibers produced by electrospinning method

text: The aim of this work was to study the effect of ceramics particles addition (SiO(2), ZnO, TiO(2)) on the ultraviolet (UV) aging of poly(lactic acid) nonwovens fabricated using electrospinning method. The resistance to aging is a key factor for outdoor and medical applications (UV light sterilization). Nonwovens were placed in special chamber with UV light. Changes of physicochemical properties were recorded using differential scanning calorimetry and attenuated total reflection Fourier-transform infrared spectroscopy. The fibers’ morphology was studied by using scanning electron microscopy. Obtained results clearly showed that only PLA fibers with ZnO particles gained an increase in UV resistance. The paper presents a description of structural changes taking place under the influence of UV aging processes and describes the mechanisms of this process and the effect of ceramic addition on the lifetime of such materials.


title: How to ventilate preterm infants with lung compliance close to circuit compliance: real-time simulations on an infant hybrid respiratory simulator

text: Circuit compliance close to lung compliance can create serious problems in effective and safe mechanical ventilation of preterm infants. We considered what ventilation technique is the most beneficial in this case. A hybrid (numerical–physical) simulator of infant respiratory system mechanics, the Bennett Ventilator and NICO apparatus were used to simulate pressure-controlled ventilation (PC) and volume-controlled ventilation with constant flow (VCV(CF)) and descending flow (VCV(DF)), under permissive hypercapnia (PHC) (6 ml kg(−1)) and normocapnia (SV) (8 ml kg(−1)) conditions. Respiratory rate (RR) was 36 or 48 min(−1) and PEEP was 0.3 or 0.6 kPa. Peak inspiratory pressure (PIP), mean airway pressure (MAP), and work of breathing by the ventilator (WOB) were lower (P < 0.01, 1 − β = 0.9) using the PHC strategy compared to the SV strategy. The WOB increased (P < 0.01; 1 − β = 0.9) when the RR increased. The PC, VCV(CF), and VCV(DF) modes did not differ in minute ventilation produced by the ventilator (MV(V)), but the PC mode delivered the highest minute ventilation to the patient (MV(T)) (P < 0.01; 1 − β = 0.9) at the same PIP, MAP, and WOB. The most beneficial ventilation technique appeared to be PC ventilation with the PHC strategy, with lower RR (36 min(−1)). [Figure: see text]


title: Influence of cellular lipid content on influenza A virus replication

text: Influenza A virus (IAV) depends on the metabolism of its cellular host to provide energy and essential factors, including lipids, for viral replication. Previous studies have shown that fatty acids (FAs) play an important role in IAV replication and that inhibition of FA biosynthesis can diminish viral replication. However, cellular lipids can either be synthesized intracellularly or be imported from the extracellular environment. Interfering with FA import mechanisms may reduce the cellular lipid content and inhibit IAV replication. To test this hypothesis, MDCK and Detroit 562 cells were infected with IAV followed by exposure to palmitic acid and inhibitors of FA import. Replication of IAV significantly increased when infected cells were supplied with palmitic acid. This enhancement could be reduced by adding an FA import inhibitor. The addition of palmitic acid significantly increased the cellular lipid content, and this increased level was reduced by treatment with an FA import inhibitor. These results show that reducing the cellular lipid level might be an approach for IAV therapy.


title: Steering Efficacy of Nano Molybdenum Towards Cancer: Mechanism of Action

text: Conventional cancer therapies possess a plethora of limitations which led to the awakening of nanotechnology and nanomedicine. However, technological success is widely dependent on complete understanding of the complexity and heterogeneity of tumor biology on one hand and nanobiointeractions associated with challenges of synthesis, translation, and commercialization on the other. The present study therefore deals with one such targeted approach aiming at synthesizing, characterizing, and understanding the efficacy of molybdenum oxide nanoparticles. The phase structure, morphology, and elemental composition of the synthesized nanoparticles were characterized using Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The cytotoxicity studies revealed that the IC(50) vales of molybdenum trioxide (MoO(3)) particles against skin cancer cells (melanoma and non-melanoma) were around 200–300 μg. The nanoparticles were found to induce mitochondrial-mediated apoptosis driven by the apoptotic genes such as BAX and Bcl(2). Molybdenum being a cofactor for the majority of metabolic enzymes could have triggered the selective internalization of the nanoparticles which in turn could have modified the granularity of the cytoplasm and subsequently lead to mitochondrial-mediated apoptosis. Further, the anti-angiogenic property of MoO(3) nanoparticles was corroborated using Chick chorioallantoic membrane (CAM) assay and aortic ring assay. Taken together , unraveling the role of MoO(3) nanoparticles in cancer and angiogenesis opens up venues for nano biological intervention of selective cancer cell targeting with minimal damage to the normal cells using natural trace elements that are generally known to influence various metabolic enzymes.


title: Conservative oxygen therapy for mechanically ventilated adults with sepsis: a post hoc analysis of data from the intensive care unit randomized trial comparing two approaches to oxygen therapy (ICU-ROX)

text: PURPOSE: Sepsis is a common reason for intensive care unit (ICU) admission and mortality in ICU patients. Despite increasing interest in treatment strategies limiting oxygen exposure in ICU patients, no trials have compared conservative vs. usual oxygen in patients with sepsis. METHODS: We undertook a post hoc analysis of the 251 patients with sepsis enrolled in a trial that compared conservative oxygen therapy with usual oxygen therapy in 1000 mechanically ventilated ICU patients. The primary end point for the current analysis was 90-day mortality. Key secondary outcomes were cause-specific mortality, ICU and hospital length of stay, ventilator-free days, vasopressor-free days, and the proportion of patients receiving renal replacement therapy in the ICU. RESULTS: Patients with sepsis allocated to conservative oxygen therapy spent less time in the ICU with an SpO(2) ≥ 97% (23.5 h [interquartile range (IQR) 8–70] vs. 47 h [IQR 11–93], absolute difference, 23 h; 95% CI 8–38), and more time receiving an FiO(2) of 0.21 than patients allocated to usual oxygen therapy (20.5 h [IQR 1–79] vs. 0 h [IQR 0–10], absolute difference, 20 h; 95% CI 14–26). At 90-days, 47 of 130 patients (36.2%) assigned to conservative oxygen and 35 of 120 patients (29.2%) assigned to usual oxygen had died (absolute difference, 7 percentage points; 95% CI − 4.6 to 18.6% points; P = 0.24; interaction P = 0.35 for sepsis vs. non-sepsis). There were no statistically significant differences between groups for secondary outcomes but point estimates of treatment effects consistently favored usual oxygen therapy. CONCLUSIONS: Point estimates for the treatment effect of conservative oxygen therapy on 90-day mortality raise the possibility of clinically important harm with this intervention in patients with sepsis; however, our post hoc analysis was not powered to detect the effects suggested and our data do not exclude clinically important benefit or harm from conservative oxygen therapy in this patient group. CLINICAL TRIALS REGISTRY: ICU-ROX Australian and New Zealand Clinical Trials Registry number ACTRN12615000957594. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05857-x) contains supplementary material, which is available to authorized users.


title: Clinical deterioration during neonatal transport in California

text: OBJECTIVE: Identify clinical factors, transport characteristics and transport time intervals associated with clinical deterioration during neonatal transport in California. STUDY DESIGN: Population-based database was used to evaluate 47,794 infants transported before 7 days after birth from 2007 to 2016. Log binomial regression was used to estimate relative risks. RESULTS: 30.8% of infants had clinical deterioration. Clinical deterioration was associated with prematurity, delivery room resuscitation, severe birth defects, emergent transports, transports by helicopter and requests for delivery room attendance. When evaluating transport time intervals, time required for evaluation by the transport team was associated with increased risk of clinical deterioration. Modifiable transport intervals were not associated with increased risk. CONCLUSION: Our results suggest that high-risk infants are more likely to be unstable during transport. Coordination and timing of neonatal transport in California appears to be effective and does not seem to contribute to clinical deterioration despite variation in the duration of these processes.


title: Oral delivery of Bacillus subtilis spores expressing Clonorchis sinensis paramyosin protects grass carp from cercaria infection

text: Clonorchis sinensis (C. sinensis), an important fishborne zoonotic parasite threatening public health, is of major socioeconomic importance in epidemic areas. Effective strategies are still urgently expected to prevent against C. sinensis infection. In the present study, paramyosin of C. sinensis (CsPmy) was stably and abundantly expressed on the surface of Bacillus subtilis spores. The recombinant spores (B.s-CotC-CsPmy) were incorporated in the basal pellets diet in three different dosages (1 × 10(5), 1 × 10(8), 1 × 10(11) CFU/g pellets) and orally administrated to grass carp (Ctenopharyngodon idella). The immune responses and intestinal microbiota in the treated grass carp were investigated. Results showed that specific anti-CsPmy IgM levels in sera, skin mucus, bile, and intestinal mucus, as well as mRNA levels of IgM and IgZ in the spleen and head kidney, were significantly increased in B.s-CotC-CsPmy-10(11) group. Besides, transcripts levels of IL-8 and TNF-αin the spleen and head kidney were also significantly elevated than the control groups. Moreover, mRNA levels of tight junction proteins in the intestines of B.s-CotC-CsPmy-10(11) group increased. Potential pathogenetic bacteria with lower abundance and higher abundances of candidate probiotics and bacteria associated with digestion in 1 × 10(11) CFU/g B.s-CotC-CsPmy spores administrated fishes could be detected compared with control group. The amount of metacercaria in per gram fish flesh was statistically decreased in 1 × 10(11) CFU/g B.s-CotC-CsPmy spores orally immunized group. Our work demonstrated that B. subtilis spores presenting CsPmy on the surface could be a promising effective, safe, and needle-free candidate vaccine against C. sinensis infection for grass carp. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-019-10316-0) contains supplementary material, which is available to authorized users.


title: Mathematical analysis for a new nonlinear measles epidemiological system using real incidence data from Pakistan

text: Modeling of infectious diseases is essential to comprehend dynamic behavior for the transmission of an epidemic. This research study consists of a newly proposed mathematical system for transmission dynamics of the measles epidemic. The measles system is based upon mass action principle wherein human population is divided into five mutually disjoint compartments: susceptible S(t)—vaccinated V(t)—exposed E(t)—infectious I(t)—recovered R(t). Using real measles cases reported from January 2019 to October 2019 in Pakistan, the system has been validated. Two unique equilibria called measles-free and endemic (measles-present) are shown to be locally asymptotically stable for basic reproductive number [Formula: see text] and [Formula: see text] , respectively. While using Lyapunov functions, the equilibria are found to be globally asymptotically stable under the former conditions on [Formula: see text] . However, backward bifurcation shows coexistence of stable endemic equilibrium with a stable measles-free equilibrium for [Formula: see text] . A strategy for measles control based on herd immunity is presented. The forward sensitivity indices for [Formula: see text] are also computed with respect to the estimated and fitted biological parameters. Finally, numerical simulations exhibit dynamical behavior of the measles system under influence of its parameters which further suggest improvement in both the vaccine efficacy and its coverage rate for substantial reduction in the measles epidemic.


title: Chest Trauma: Current Recommendations for Rib Fractures, Pneumothorax, and Other Injuries

text: PURPOSE OF REVIEW: This article provides an overview of the common and important chest injuries that the anesthesiologist may encounter in patients following trauma including blunt injury, pneumothorax, hemothorax, blunt aortic injury, and blunt cardiac injury. RECENT FINDINGS: Rib fractures are frequently associated with chest injury and are associated with significant pain and other complications. Regional anesthesia techniques combined with a multimodal analgesic strategy can improve patient outcomes and reduce complications. There is increasing evidence for paravertebral blocks for this indication, and the myofascial plane blocks are a popular emerging technique. Recent changes to recommended management of tension pneumothorax are also described. SUMMARY: Chest trauma is commonly encountered, and anesthesiologists have the potential to significantly improve morbidity and mortality in this group of patients.


title: Impact of multiple placental pathologies on neonatal death, bronchopulmonary dysplasia, and neurodevelopmental impairment in preterm infants

text: BACKGROUND: To determine the association of placental pathology, including multiple placental lesions, with the occurrence and severity of bronchopulmonary dysplasia (BPD), death, and neurodevelopmental impairment (NDI) in preterm infants. METHOD: A retrospective cohort study of neonates <29 weeks gestational age (GA) born at Parkland Hospital from 08/2009 to 08/2012. Infants were stratified as follows: Group 1: no significant placental pathology; Group 2: single significant placental lesion; and Group 3: ≥2 placental lesions (multiple lesions). Primary outcome was death and/or BPD. Two-year neurodevelopmental follow-up was compared. RESULTS: In all, 42% (100/241) of infants had one placental lesion, and 34% (82/241) ≥2 lesions. As the number of the pathologic lesions increased (no lesions vs. 1 vs. ≥2), the occurrence of death or BPD increased (25%, 37%, and 52%, respectively; P = 0.004). Moreover, infants with multiple pathologic lesions were more likely to have NDI (29%, 29%, and 46%, respectively; P = 0.03). After logistic regression, infants with multiple pathologic lesions were more likely to develop moderate-to-severe BPD [P < 0.01; OR 3.9 (1.5–10.1)] but not NDI. CONCLUSION(S): Neonates <29 weeks GA with multiple placental pathologic lesions have an increased risk for developing BPD, suggesting an interaction between placental inflammation and vascular pathology and the pathogenesis of BPD; however, the risk of NDI is not increased.


title: Peanut Oral Immunotherapy: a Current Perspective

text: PURPOSE OF THE REVIEW: Peanut oral immunotherapy (OIT) is one of the most studied experimental therapies for food allergy. With the recently FDA-approved peanut product, Palforzia, the goal of this article is to review the most recent data from clinical trials, discuss recent trends, and anticipate future developments. RECENT FINDINGS: The latest research suggests that peanut OIT could be a promising option for peanut-allergic patients, with the majority of participants in research studies achieving the primary efficacy endpoint of desensitization, as well as sustained unresponsiveness in select populations. Some studies also showed improvements in food allergy-related quality of life. However, peanut OIT is not without risk or side effects, including potentially serious allergic reactions. SUMMARY: Future research will need to evaluate the short- and long-term effectiveness of the therapy in the real-world setting, predictors of important treatment outcomes, and the use of adjunctive therapies that may mitigate some of these allergic reactions.


title: Low-temperature laminar flow ward for the treatment of multidrug resistance Acinetobacter baumannii pneumonia

text: This study was designed to investigate the effect of low-temperature laminar flow ward (LTLFW) on the Acinetobacter baumannii pneumonia (MDR-ABP) in neurosurgical intensive care unit (NICU) patients. We evaluated whether patients in a LTLFW had significantly improved clinical outcomes as compared to those in nonconstant-temperature NICU (room temperature). The association of temperature with the prevalence of ABP and A. baumannii isolates (ABI) found in NICU patients was specifically investigated. In vitro microbiological experiments were conducted to measure the proliferation, antibiotic sensitivity, and genomic profiles of A. baumannii (AB) that grew in variable temperatures. MDR-ABP patients in LTLFW had significantly improved outcomes than those in the room temperature NICU. In addition, the numbers of ABI were positively associated with mean ambient outdoor temperatures (P = 0.002), with the incidence of ABP and average numbers of ABI among NICU patients being substantially lower in the winter as compared to other seasons. However, there were no significant seasonal variations in the other strains of the top five bacteria. Consistent with these clinical observations, AB growing at 20°C and 25°C had significantly reduced viability and antibiotic resistance compared to those growing at 35°C. The expression of genes related to AB survival ability, drug resistance, and virulence also differed between AB growing at 20°C and those at 35°C. LTLFW is effective in promoting the recovery of MDR-ABP patients because low temperatures reduced the density and virulence of AB and enhanced the efficacy of antibiotics, likely at the genetic level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-019-03790-x) contains supplementary material, which is available to authorized users.


title: Effective Catheter Manoeuvre for the Removal of Phlegm by Suctioning: A Biomechanical Analysis of Experts and Novices

text: PURPOSE: The aim of this study was to determine the effective biomechanical technique for suctioning phlegm. METHODS: A novel tracheal suctioning simulator combined with a motion capture system was used to calculate the amount of simulated phlegm suctioned and the biomechanical parameters of the associated suctioning manoeuvre. A laboratory study, including 12 nurses with > 3 years of suctioning experience and 12 nursing students without any clinical suctioning experience, was conducted. The amount of phlegm suctioned, the maximum length of catheter insertion, and the biomechanical parameters of hand movement were calculated. RESULTS: The mean amount of phlegm suctioned per second was significantly larger in the experienced group than in the non-experienced group. The amount of phlegm suctioned correlated positively with the length of the vertical path of motion of the wrist and forearm, and with the angular velocity of thumb rotation in both the groups. CONCLUSION: Greater vertical motion of the wrist and thumb rotation improved the effectiveness of phlegm suctioning and prevented the need for deep suctioning, which is unsafe.


title: Long-Term Outcomes After Open Repair for Ruptured Abdominal Aortic Aneurysm

text: BACKGROUND: Early mortality in ruptured abdominal aneurysm (rAAA) is high, but data on long-term outcome are scarce. The aim of this study was to investigate the long-term outcome in survivors after open surgery for rAAA in well-defined population. METHODS: This is a population-based, observational long-term follow-up (beyond 30-day mortality) study of patients surgically treated for rAAA from 2000 through 2014. Long-term survival was analysed using Kaplan–Meier estimates and compared to the general population by analyses of relative survival. RESULTS: Out of 178 patients operated for rAAA, 95 patients (55%) either died in the perioperative period, were referred from other hospitals or were lost to follow-up (two patients). Altogether 83 patients were eligible for long-term outcomes: 72 men and 11 women. Estimated median crude survival time was 6.5 years [95% confidence interval (CI) 4.8–8.2]. Men had a median survival of 7.3 years (95% CI 5.1–9.4) versus 5.4 years in females (95% CI 3.5–7.3) (P = 0.082). Reinterventions during follow-up occurred in 31 (37%). Relative survival demonstrated a slightly higher risk of death in the rAAA population compared to the general age- and gender-matched population. Age, but not comorbidities, had a significant influence on long-term survival. CONCLUSION: For survivors beyond 30 days after surgery for rAAA, long-term survival compares well to that of an age- and sex-matched population. A high frequency of cardiovascular comorbidities did not seem to affect long-term survival.


title: Interventions to Improve Antiretroviral Therapy Adherence Among Adolescents and Youth in Low- and Middle-Income Countries: A Systematic Review 2015–2019

text: Adolescents and youth living with HIV have poorer antiretroviral treatment (ART) adherence and viral suppression outcomes than all other age groups. Effective interventions promoting adherence are urgently needed. We reviewed and synthesized recent literature on interventions to improve ART adherence among this vulnerable population. We focus on studies conducted in low- and middle-income countries (LMIC) where the adolescent and youth HIV burden is greatest. Articles published between September 2015 and January 2019 were identified through PubMed. Inclusion criteria were: [1] included participants ages 10–24 years; [2] assessed the efficacy of an intervention to improve ART adherence; [3] reported an ART adherence measurement or viral load; [4] conducted in a LMIC. Articles were reviewed for study population characteristics, intervention type, study design, outcomes measured, and intervention effect. Strength of each study’s evidence was evaluated according to an adapted World Health Organization GRADE system. Articles meeting all inclusion criteria except being conducted in an LMIC were reviewed for results and potential transportability to a LMIC setting. Of 108 articles identified, 7 met criteria for inclusion. Three evaluated patient-level interventions and four evaluated health services interventions. Of the patient-level interventions, two were experimental designs and one was a retrospective cohort study. None of these interventions improved ART adherence or viral suppression. Of the four health services interventions, two targeted stable patients and reduced the amount of time spent in the clinic or grouped patients together for bi-monthly meetings, and two targeted patients newly diagnosed with HIV or not yet deemed clinically stable and augmented clinical care with home-based case-management. The two studies targeting stable patients used retrospective cohort designs and found that adolescents and youth were less likely to maintain viral suppression than children or adults. The two studies targeting patients not yet deemed clinically stable included one experimental and one retrospective cohort design and showed improved ART adherence and viral suppression outcomes. ART adherence and viral suppression outcomes remain a major challenge among adolescents and youth. Intensive home-based case management models of care hold promise for improving outcomes in this population and warrant further research.


title: The contribution of frailty, cognition, activity of daily life and comorbidities on outcome in acutely admitted patients over 80 years in European ICUs: the VIP2 study

text: PURPOSE: Premorbid conditions affect prognosis of acutely-ill aged patients. Several lines of evidence suggest geriatric syndromes need to be assessed but little is known on their relative effect on the 30-day survival after ICU admission. The primary aim of this study was to describe the prevalence of frailty, cognition decline and activity of daily life in addition to the presence of comorbidity and polypharmacy and to assess their influence on 30-day survival. METHODS: Prospective cohort study with 242 ICUs from 22 countries. Patients 80 years or above acutely admitted over a six months period to an ICU between May 2018 and May 2019 were included. In addition to common patients’ characteristics and disease severity, we collected information on specific geriatric syndromes as potential predictive factors for 30-day survival, frailty (Clinical Frailty scale) with a CFS > 4 defining frail patients, cognitive impairment (informant questionnaire on cognitive decline in the elderly (IQCODE) with IQCODE ≥ 3.5 defining cognitive decline, and disability (measured the activity of daily life with the Katz index) with ADL ≤ 4 defining disability. A Principal Component Analysis to identify co-linearity between geriatric syndromes was performed and from this a multivariable model was built with all geriatric information or only one: CFS, IQCODE or ADL. Akaike’s information criterion across imputations was used to evaluate the goodness of fit of our models. RESULTS: We included 3920 patients with a median age of 84 years (IQR: 81–87), 53.3% males). 80% received at least one organ support. The median ICU length of stay was 3.88 days (IQR: 1.83–8). The ICU and 30-day survival were 72.5% and 61.2% respectively. The geriatric conditions were median (IQR): CFS: 4 (3–6); IQCODE: 3.19 (3–3.69); ADL: 6 (4–6); Comorbidity and Polypharmacy score (CPS): 10 (7–14). CFS, ADL and IQCODE were closely correlated. The multivariable analysis identified predictors of 1-month mortality (HR; 95% CI): Age (per 1 year increase): 1.02 (1.–1.03, p = 0.01), ICU admission diagnosis, sequential organ failure assessment score (SOFA) (per point): 1.15 (1.14–1.17, p < 0.0001) and CFS (per point): 1.1 (1.05–1.15, p < 0.001). CFS remained an independent factor after inclusion of life-sustaining treatment limitation in the model. CONCLUSION: We confirm that frailty assessment using the CFS is able to predict short-term mortality in elderly patients admitted to ICU. Other geriatric syndromes do not add improvement to the prediction model. Since CFS is easy to measure, it should be routinely collected for all elderly ICU patients in particular in connection to advance care plans, and should be used in decision making. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05853-1) contains supplementary material, which is available to authorized users.


title: Dietary supplementation with Withania somnifera root powder ameliorates experimentally induced Infectious Bursal Disease in chicken

text: Infectious Bursal Disease (IBD) is an economically important, immunosuppressive viral disease of chicken. Withania somnifera, a well-known Indian medicinal plant and functional food, finds extensive ethnomedicinal and ethnoveterinary use in the subcontinent. Root extracts of Withania somnifera have been shown to inhibit IBD virus (IBDV) in vitro. The effect of dietary supplementation with whole root powder of Withania somnifera was studied in chicken experimentally infected with IBDV. Dietary supplementation with the root powder improved erythrocytic indices, biochemical parameters, bursal weight index, and lymphocyte stimulation indices, and reduced histopathological insult in the infected birds. Viral load decreased to less than one-fourth in the birds receiving dietary supplementation with Withania somnifera root powder. It could be concluded that continued supplementation of IBDV-infected chicken with Withania somnifera root powder alleviated virus-induced stress and histological and immunological alterations and reduced viral persistence in the host.


title: Dual-targeting nanoparticle vaccine elicits a therapeutic antibody response against chronic hepatitis B

text: Chronic hepatitis B is caused by prolonged infection with the hepatitis B virus (HBV), which can substantially increase the risk of developing liver disease. Despite the development of preventive vaccines against HBV, a therapeutic vaccine inducing an effective antibody response still remains elusive. The preS1 domain of the large HBV surface protein is the major viral attachment site on hepatocytes and thus offers a therapeutic target; however, its poor immunogenicity limits clinical translation. Here, we design a ferritin nanoparticle vaccine that can deliver preS1 to specific myeloid cells, including SIGNR1(+) dendritic cells (which activate T follicular helper cells) and lymphatic sinus-associated SIGNR1(+) macrophages (which can activate B cells). This nanoparticle vaccine induces a high-level and persistent anti-preS1 response that results in efficient viral clearance and partial serological conversion in a chronic HBV mouse model, offering a promising translatable vaccination strategy for the functional cure of chronic hepatitis B.


title: Benefit-to-risk balance of bronchoalveolar lavage in the critically ill. A prospective, multicenter cohort study

text: PURPOSE: To assess the benefit-to-risk balance of bronchoalveolar lavage (BAL) in intensive care unit (ICU) patients. METHODS: In 16 ICUs, we prospectively collected adverse events during or within 24 h after BAL and assessed the BAL input for decision making in consecutive adult patients. The occurrence of a clinical adverse event at least of grade 3, i.e., sufficiently severe to need therapeutic action(s), including modification(s) in respiratory support, defined poor BAL tolerance. The BAL input for decision making was declared satisfactory if it allowed to interrupt or initiate one or several treatments. RESULTS: We included 483 BAL in 483 patients [age 63 years (interquartile range (IQR) 53–72); female gender: 162 (33.5%); simplified acute physiology score II: 48 (IQR 37-61); immunosuppression 244 (50.5%)]. BAL was begun in non-intubated patients in 105 (21.7%) cases. Sixty-seven (13.9%) patients reached the grade 3 of adverse event or higher. Logistic regression showed that a BAL performed by a non-experienced physician (non-pulmonologist, or intensivist with less than 10 years in the specialty or less than 50 BAL performed) was the main predictor of poor BAL tolerance in non-intubated patients [OR: 3.57 (95% confidence interval 1.04–12.35); P = 0.04]. A satisfactory BAL input for decision making was observed in 227 (47.0%) cases and was not predictable using logistic regression. CONCLUSIONS: Adverse events related to BAL in ICU patients are not infrequent nor necessarily benign. Our findings call for an extreme caution, when envisaging a BAL in ICU patients and for a mandatory accompaniment of the less experienced physicians. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05896-4) contains supplementary material, which is available to authorized users.


title: Lung-ultrasound objective structured assessment of technical skills (LUS-OSAUS): utility in the assessment of lung-ultrasound trained medical undergraduates

text: PURPOSE: Recently, some attempts have been made to integrate lung ultrasound (LUS) teaching into medical curricula. However, current education studies of LUS are extremely heterogeneous due to the lack of evidence-based guidelines on LUS education. In particular, the assessment of competencies is poorly standardized and mostly relies on non-validated scales. A new validated tool, the objective structured assessment of lung ultrasound skills (LUS-OSAUS), has the potential to overcome these limitations. Therefore, we adopted the LUS-OSAUS tool to assess the competencies of a group of LUS-trained undergraduates. Existing no prior practical applications of the LUS-OSAUS, our aim was to investigate the practical utility of this tool and its applicability in the evaluation of US-trained medical students. METHODS: Eight undergraduates (two males, six females) were enrolled on a voluntary basis to receive a theoretical and practical training in LUS. Once completed their training, each student performed an LUS examination on a different patient hospitalized for respiratory symptoms. The same eight patients were also scanned by a senior resident in emergency medicine for a comparison with students’ results. Students and the senior resident were tested by an examiner using the LUS-OSAUS tool. We compared the scores obtained by operators in all areas of competence of the LUS-OSAUS, the total scores, and the time needed to complete the sonographic task. RESULTS: Median students’ score in the single items of the scale was significantly lower than the ones obtained by the senior resident (4.0 [3.3–5.0] vs. 5.0 [5.0–5.0]; p < 0.0001). Students scored significantly lower than the senior resident in each item, except for B-line identification, choice of the correct transducer, and suggested focused questions. Median total score was also lower for students compared to the senior resident (70.5 [61.0–74.8] vs. 84.0 [83.5–84.3] (p = 0.0116). Median time required to complete the examination was significantly higher for students (14.1 [12.8–16.1] vs. 4.7 [3.9–5.2] min, p = 0.0117). CONCLUSIONS: The LUS-OSAUS tool allowed for a standardized and comprehensive assessment of student’s competencies in lung ultrasound, and helped to discriminate their level of expertise from that of a more experienced operator. The scale also specifically tests the theoretical knowledge of trainees, thus making redundant the use of questionnaires designed for this purpose. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40477-020-00454-x) contains supplementary material, which is available to authorized users.


title: The CTA1-DD adjuvant strongly potentiates follicular dendritic cell function and germinal center formation, which results in improved neonatal immunization

text: Vaccination of neonates and young infants is hampered by the relative immaturity of their immune systems and the lack of safe and efficacious vaccine adjuvants. Immaturity of the follicular dendritic cells (FDCs), in particular, appears to play a critical role for the inability to stimulate immune responses. Using the CD21mT/mG mouse model we found that at 7 days of life, FDCs exhibited a mature phenotype only in the Peyer´s patches (PP), but our unique adjuvant, CTA1-DD, effectively matured FDCs also in peripheral lymph nodes following systemic, as well as mucosal immunizations. This was a direct effect of complement receptor 2-binding to the FDC and a CTA1-enzyme-dependent enhancing effect on gene transcription, among which CR2, IL-6, ICAM-1, IL-1β, and CXCL13 encoding genes were upregulated. This way we achieved FDC maturation, increased germinal center B-cell- and Tfh responses, and enhanced specific antibody levels close to adult magnitudes. Oral priming immunization of neonates against influenza infection with CTA1-3M2e-DD effectively promoted anti-M2e-immunity and significantly reduced morbidity against a live virus challenge infection. To the best of our knowledge, this is the first study to demonstrate direct effects of an adjuvant on FDC gene transcriptional functions and the subsequent enhancement of neonatal immune responses.


title: Effect of corticosteroids on myocardial injury among patients hospitalized for community-acquired pneumonia: rationale and study design. The colosseum trial

text: Community-acquired pneumonia (CAP) is often complicated by elevation of cardiac troponin, a marker of myocardial injury that can be isolated or associated with myocardial infarction (MI). A retrospective study showed that corticosteroid treatment lowers the incidence of MI during the hospital stay. No data exist so far on the effect of corticosteroids on myocardial injury in CAP patients. The primary objective of the study is to evaluate if methylprednisolone is able to reduce myocardial injury, as assessed by serum high-sensitivity cardiac T Troponin (hs-cTnT), in a cohort of patients hospitalized for CAP. Secondary aims are to evaluate the potential effect of methylprednisolone on cardiovascular events during hospitalization, at 30 days from hospital admission and during 2 years’ follow-up. The trial will also examine whether the potential protective effects of methylprednisolone might be due to platelet activation down-regulation. Double-blind randomized placebo-controlled trial. One hundred twenty-two eligible patients will be randomized to a week treatment with iv methylprednisolone (20 mg b.i.d) or placebo from hospital admission. Serum hs-cTnT will be measured at admission and every day until up 3 days from admission. ECG will be monitored every day until discharge. After discharge, all patients will be followed-up 2 years. This is the first clinical trial aimed at examining whether methylprednisolone treatment may reduce myocardial injury. The results of this trial may constitute the basis for conducting a larger multicenter trial aimed to evaluate the effect of corticosteroid on cardiovascular events in this setting.


title: The implications of Neoliberalism on African economies, health outcomes and wellbeing: a conceptual argument

text: Not only did the 2015 Ebola Outbreak in West African countries leave the whole of the sub-Saharan region with a sense of uncertainty and panic, it was also a stress test to Africa’s and the wider world’s capacity to respond to and mitigate humanitarian crises in the twenty-first century. One plausible conclusion drawn from the spread and impact of the pandemic is that the pace of health infrastructure development in sub-Saharan Africa has lagged behind its population and economic growth posted in the last decade (2003–2013). An exhaustive audit of health infrastructure and remedial measures is, therefore, critical in navigating Africa to sustainable growth and development in the next decade. For the next charge of growth and development to not only be robust but also more sustainable and resilient to major emergencies (such as Ebola), there is a need to edify the state of healthcare across the continent to ensure the optimisation of the human resource and to redress the gap aggravated by loss of human-hours due to poor health.


title: Metal ions and graphene-based compounds as alternative treatment options for burn wounds infected by antibiotic-resistant Pseudomonas aeruginosa

text: Burn infections caused by Pseudomonas aeruginosa pose a major complication in wound healing. This study aimed to determine the antimicrobial effect of metal ions, graphene (Gr), and graphene oxide (GO), individually and in combination, against the planktonic and biofilm states of two antimicrobially resistant clinical strains of P. aeruginosa each with different antibiotic resistance profiles. Minimum inhibitory, minimum bactericidal, and fractional inhibitory concentrations were performed to determine the efficacy of the metal ions and graphene composites individually and their synergy in combination. Crystal violet biofilm and XTT assays measured the biofilm inhibition and metabolic activity, respectively. Molybdenum, platinum, tin, gold, and palladium ions exhibited the greatest antimicrobial activity (MIC = 7.8–26.0 mg/L), whilst GO and Gr demonstrated moderate-to-no effect against the planktonic bacterial cells, irrespective of their antibiograms. Biofilms were inhibited by zinc, palladium, silver, and graphene. In combination, silver–graphene and molybdenum–graphene inhibited both the planktonic and biofilm forms of the bacteria making them potential candidates for development into topical antimicrobials for burns patients infected with antibiotic-resistant P. aeruginosa.


title: Characteristics associated with spine injury on magnetic resonance imaging in children evaluated for abusive head trauma

text: BACKGROUND: Spine injuries are increasingly common in the evaluation for abusive head trauma (AHT), but additional information is needed to explore the utility of spine MRI in AHT evaluations and to ensure an accurate understanding of injury mechanism. OBJECTIVE: To assess the incidence of spine injury on MRI in children evaluated for AHT, and to correlate spine MRI findings with clinical characteristics. MATERIALS AND METHODS: We identified children younger than 5 years who were evaluated for AHT with spine MRI. Abuse likelihood was determined a priori by expert consensus. We blindly reviewed spine MRIs and compared spinal injury, abuse likelihood, patient demographics, severity of brain injury, presence of retinal hemorrhages, and pattern of head injury between children with and without spine injury. RESULTS: Forty-five of 76 (59.2%) children had spine injury. Spine injury was associated with more severe injury (longer intensive care stays [P<0.001], lower initial mental status [P=0.01] and longer ventilation times [P=0.001]). Overall abuse likelihood and spine injury were not associated. Spinal subdural hemorrhage was the only finding associated with a combination of retinal hemorrhages (P=0.01), noncontact head injuries (P=0.008) and a diagnosis of AHT (P<0.05). Spinal subdural hemorrhage was associated with other spine injury (P=0.004) but not with intracranial hemorrhage (P=0.28). CONCLUSION: Spinal injury is seen in most children evaluated for AHT and might be clinically and forensically valuable. Spinal subdural hemorrhage might support a mechanism of severe acceleration/deceleration head injury and a diagnosis of AHT.


title: Practical guide for safe central venous catheterization and management 2017

text: Central venous catheterization is a basic skill applicable in various medical fields. However, because it may occasionally cause lethal complications, we developed this practical guide that will help a novice operator successfully perform central venous catheterization using ultrasound guidance. The focus of this practical guide is patient safety. It details the fundamental knowledge and techniques that are indispensable for performing ultrasound-guided internal jugular vein catheterization (other choices of indwelling catheters, subclavian, axillary, and femoral venous catheter, or peripherally inserted central venous catheter are also described in alternatives).


title: The pig as a model for immunology research

text: The pig is an omnivorous, monogastric species with many advantages to serve as an animal model for human diseases. There are very high similarities to humans in anatomy and functions of the immune system, e g., the presence of tonsils, which are absent in rodents. The porcine immune system resembles man for more than 80% of analyzed parameters in contrast to the mouse with only about 10%. The pig can easily be bred, and there are less emotional problems to use them as experimental animals than dogs or monkeys. Indwelling cannulas in a vein or lymphatic vessel enable repetitive stress-free sampling. Meanwhile, there are many markers available to characterize immune cells. Lymphoid organs, their function, and their role in lymphocyte kinetics (proliferation and migration) are reviewed. For long-term experiments, minipigs (e.g., Göttingen minipig) are available. Pigs can be kept under gnotobiotic (germfree) conditions for some time after birth to study the effects of microbiota. The effects of probiotics can be tested on the gut immune system. The lung has been used for extracorporeal preservation and immune engineering. After genetic modifications are established, the pig is the best animal model for future xenotransplantation to reduce the problem of organ shortage for organ transplantation. Autotransplantation of particles of lymphnodes regenerates in the subcutaneous tissue. This is a model to treat secondary lymphedema patients. There are pigs with cystic fibrosis and severe combined immune deficiency available.


title: Entwicklung von Impfstoffen gegen Malaria – aktueller Stand

text: Globally, 3.1 billion people live in areas endemic for malaria (the tropics and subtropics). Annually, around 200 million fall ill, and around 500,000 persons die as a result of this infection. Mainly children are the victims. In order to control and eventually prevent any new infection, the development of effective vaccines is pivotal. In this review, background information about the history of vaccine development and malaria disease as well as possibilities for therapy and control is given. In the main part of the article, an update on the development of vaccines against Plasmodium falciparum is provided followed by an extensive discussion. Malaria is a parasitic infectious disease caused by the single cell organism Plasmodium. Five different Plasmodium species can induce disease in humans with P. falciparum being the origin for more than 99% of infections in Africa. The vector is the Anopheles mosquito. The life cycle of Plasmodium offers several approaches for vaccines to have an impact. Out of around 70 candidates, pre-erythrocytic vaccine candidates interfering with the liver phase of the parasite are the most developed. However, a vaccine with more than 75% efficacy, as required by the World Health Organization (WHO), is not yet in sight. Currently, for the first time, a moderately efficacious vaccine (RTS,S/AS01) is being applied in large-scale operations. But it is obvious that malaria can only be controlled in combination with concurring measures. For example, the use of impregnated mosquito nets, indoor residual spraying, elimination of vector breeding sites, rapid diagnosis, and therapy of the infection as well as a functioning health system are important elements, which can hardly be guaranteed in areas characterized by poverty.


title: Evaluation of a Loop-Mediated Isothermal Amplification Technique for the Rapid Visual Detection of Hepatozoon canis Infection

text: BACKGROUND: Laboratory diagnosis of Hepatozoon canis infection is tedious, especially in chronic and/or latent infections. PURPOSE: The study was planned to develop a simple read out loop mediated isothermal amplification (LAMP) assay targeting a partial 18S rRNA gene of H. canis with naked eye visualisation of LAMP products. METHODS: A LAMP assay was employed to assess the DNA amplification by adding SYBR Green I dye for naked eye inspection of DNA accumulating in reaction tubes. Positive amplification was read through observation of change in colour of reaction mixture following addition of dye. The visual results were further verified with those of agarose gel electrophoresis. Genomic DNA of other haemoparasites of dog viz. Babesia vogeli, B. gibsoni, Ehrlichia canis and Trypanosoma evansi along with no-template control were used to determine the specificity of assay. RESULTS: Among the 109 blood samples presented at Small Animal Clinics, Teaching Veterinary Clinical Complex, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab (India) tested, 39 revealed colour change from orange to green indicating positive reaction while 70 were negative as revealed by no colour change. The results of visual inspection were comparable to those obtained by agarose gel electrophoresis. The LAMP primers specifically amplified H. canis DNA, whereas no amplification was detected in DNA samples of other haemoparasites and no-template control revealing specificity of the assay. The diagnostic sensitivity and specificity (95% CI) of visual LAMP assay with respect to microscopy in detection of H. canis varied from 100% (15.81–100.00%) and 65.42% (55.61–74.35%), respectively. CONCLUSION: The present investigation has developed a specific and rapid LAMP assay for the detection of H. canis, using SYBR Green I dye, which has practical applications for the screening of field samples.


title: Rib fracture displacement worsens over time

text: PURPOSE: Rib fractures (RF) occur in 10% of trauma patients; associated with significant morbidity and mortality. Despite advancing technology of surgical stabilization of rib fractures (SSRF), treatment and indications remain controversial. Lack of displacement is often cited as a reason for non-operative management. The purpose was to examine RF patterns hypothesizing RF become more displaced over time. METHODS: Retrospective review of all RF patients from 2016–2017 at our institution. Patients with initial chest CT (CT1) followed by repeat CT (CT2) within 84 days were included. Basic demographics were obtained. Primary outcomes included RF displacement in millimeters (mm) between CT1 and CT2 in three planes (AP = anterior/posterior, O = overlap/gap, and SI = superior/inferior). Displacement was calculated by subtracting CT1 fracture displacement from CT2 displacement for each rib. Given anatomic and clinical characteristics, ribs were grouped (1–2, 3–6, 7–10, 11–12), averaged, and analyzed for displacement. Secondary outcome included number of missed RF on CT1. Non-parametric sign test and paired t test were used for analysis. Significance was set at p < 0.002. RESULTS: 78 of 477 patients with RF on CT1 had CT2 during the study period: primarily male (76%) and age 55.8 ± 20.1 with blunt mechanism of injury (99%). Median Injury Severity Score was 21 (IQR, 13–27) with Chest Abbreviated Injury Score of 3 (IQR, 3–4). Median time between CT1 and CT2 was 6 days (IQR, 3–12). Missed RF rate for CT1 was 10.1% (p = 0.11). Average fracture displacement was significantly increased for all rib groupings except 11–12 in all planes (p < 0.002). CONCLUSION: RF become more displaced over time. Pain regimens and SSRF considerations should be adjusted accordingly.


title: A model of respiratory syncytial virus (RSV) infection of infants in newborn lambs

text: Many animal models have been established for respiratory syncytial virus (RSV) infection of infants with the purpose of studying the pathogenesis, immunological response, and pharmaceutical testing and the objective of finding novel therapies and preventive measures. This review centers on a neonatal lamb model of RSV infection that has similarities to RSV infection of infants. It includes a comprehensive description of anatomical and immunological similarities between ovine and human lungs along with comparison of pulmonary changes and immune responses with RSV infection. These features make the newborn lamb an effective model for investigating key aspects of RSV infection in infants. The importance of RSV lamb model application in preclinical therapeutic trials and current updates on new studies with the RSV-infected neonatal lamb are also highlighted.


title: A pilot study exploring interventions for physician distress in pediatric subspecialists

text: BACKGROUND: While institution-sponsored wellness programs may be effective, little is known about their availability and utilization in pediatric subspecialists, and about programs physicians wish were available. METHODS: A survey of perceptions about, and availability and utilization of institutional wellness activities, was distributed electronically to pediatric subspecialists nationally. Bivariate analyses were performed using χ(2) tests or independent t tests. Multivariable logistic regression models for categories of institution-sponsored programming as a function of potential predictors of program utilization were performed. Qualitative content analysis was performed for free-text survey answers. RESULTS: Approximately 60% of respondents participated in institution-sponsored wellness opportunities. Debriefs, Schwartz Center Rounds, mental health services, and team building events were the most available institution-sponsored wellness activities, whereas debriefs, team building, Schwartz Center Rounds, and pet therapy were most frequently utilized. Respondents desired greater social/emotional support, improved leadership, enhanced organizational support, and modifications to the physical work environment, with no significant differences across subspecialties for “wish list” items. CONCLUSIONS: Physician wellness requires more than a “one-size-fits-all” initiative. Our data highlight the importance of encouraging and normalizing self-care practices, and of listening to what physicians articulate about their needs. Pre-implementation needs assessment allows a “bottom-up” approach where physician voices can be heard.


title: Improved MHC II epitope prediction — a step towards personalized medicine

text: Numerous neoepitope-based vaccination strategies are in testing for clinical use in the treatment of cancer. Rapid identification of immunostimulatory neoantigen targets hastens neoantigen vaccine development. Papers recently published in Nature Biotechnology describe two independent machine-learning-based algorithms that demonstrate improved identification of MHC class II-binding peptides. Herein, we outline the benefits of these algorithms and their implications for future immunotherapies.


title: A Real-World Analysis of Patient Characteristics and Predictors of Hospitalization Among US Medicare Beneficiaries with Respiratory Syncytial Virus Infection

text: INTRODUCTION: Little has been published on respiratory syncytial virus (RSV) among Medicare patients at high risk (HR) of RSV complications due to age or comorbidity. METHODS: Adult patients (at least 18 years of age) with at least 1 diagnostic code for RSV were identified using the 5% US Medicare database from 2011 through 2015. Patients were required to have continuous health plan enrollment for 180 days pre- and 180 days post-RSV diagnosis (baseline and follow-up periods, respectively). HR was defined as diagnosis of chronic lung disease, congestive heart failure, or weakened immune system for 180 days during the baseline period. Patients were categorized as initially hospitalized if hospitalized within 1 day of RSV diagnosis. Logistic regression models were developed to determine predictors of initial hospitalization. Healthcare utilization and costs for 180 days pre- and post-RSV diagnosis were compared. RESULTS: The study included 756 HR patients who were initially hospitalized with RSV diagnoses. Among these, 61.7% were diagnosed in the emergency department vs 15.3% in a physician’s office, with hypertension (76.3%), chronic obstructive pulmonary disease (COPD) (53.7%), and high cholesterol (52.0%) observed as the most prevalent comorbidities. Of these, COPD, congestive heart failure, chronic kidney disease, and previous evidence of pneumonia were significant predictors of hospitalization. Other significant predictors of hospitalization included older age, hematological malignancies, stroke, and baseline healthcare resource use. Among both HR and non-HR hospitalized patients, there was a significant increase in healthcare resource utilization following hospitalization, including the number of inpatient admissions and longer hospital stays post-RSV diagnosis. The total mean all-cause healthcare costs among HR hospitalized patients increased by $9210 per patient (p < 0.0001) post-RSV diagnosis. CONCLUSION: Hospitalized Medicare beneficiaries with RSV infections pose a significant healthcare burden as compared with non-hospitalized patients, mainly driven by higher comorbidity, higher likelihood of multiple inpatient admissions, and costly medical interventions.


title: Approaches to optimize therapeutic bacteriophage and bacteriophage-derived products to combat bacterial infections

text: The emerging occurrence of antibiotic-resistant bacterial pathogens leads to a recollection of bacteriophage as antimicrobial therapeutics. This article presents a short overview of the clinical phage application including their use in military medicine and discusses the genotypic and phenotypic properties of a potential “ideal” therapeutic phage. We describe current efforts to engineer phage for their improved usability in pathogen treatment. In addition, phage can be applied for pathogen detection, selective drug delivery, vaccine development, or food and surface decontamination. Instead of viable phage, (engineered) phage-derived enzymes, such as polysaccharide depolymerases or peptidoglycan-degrading enzymes, are considered as promising therapeutic candidates. Finally, we briefly summarize the use of phage for the detection and treatment of “Category A priority pathogens”.


title: The recurrent bleeding risk of a Forrest IIc lesion at the second-look endoscopy can be indicated by high Rockall scores ≥ 6

text: BACKGROUND: The Forrest classification is widely applied to guide endoscopic hemostasis for peptic ulcer bleeding. Accordingly, practice guidelines suggest medical treatment only for ulcer with a Forrest IIc lesion because it has low rebleeding risk even without endoscopic therapy, ranging from 0 to 13%. However, the risk ranges widely and it is unclear who is at risk of rebleeding with such a lesion. This study assessed whether the Rockall score, which evaluates patients holistically, could indicate the risk of recurrent bleeding among patients with a Forrest IIc lesion at the second-look endoscopy. METHODS: Patients who had peptic ulcer bleeding with Ia-IIb lesions received endoscopic hemostasis at the primary endoscopy, and they were enrolled if their Ia-IIb lesions had been fading to IIc at the second-look endoscopy after 48- to 72-h intravenous proton pump inhibitor (PPI) infusion. Primary outcomes were rebleeding during the 4th–14th day and 4(th)–28th day after the first bleeding episode. RESULTS: The prospective cohort study enrolled 140 patients, who were divided into a Rockall scores ≥ 6 group or a Rockall scores < 6 group. The rebleeding rates in the Rockall scores ≥ 6 group and the Rockall scores < 6 group during the 4th–14th day and the 4th–28th day were 13/70 (18.6%) versus 2/70 (2.9%), p = 0.003 and 17/70 (24.3%) versus 3/70 (4.3%), p = 0.001, respectively, based on an intention-to-treat analysis and 5/62 (8.1%) versus 0/68 (0%), p = 0.023 and 6/59 (10.2%) versus 0/67 (0%), p = 0.009, respectively, based on a per-protocol analysis. The Kaplan–Meier curves showed that the Rockall scores ≥ 6 group had a significantly lower cumulative rebleeding-free proportion than the Rockall scores < 6 group (p = 0.01). CONCLUSIONS: Combined Rockall scores ≥ 6 on arrival with a Forrest IIc lesion at the second-look endoscopy can identify patients at risk of recurrent peptic ulcer bleeding following initial endoscopic and intravenous PPI treatment. Trial registration Trial registration identifier: NCT01591083


title: In Silico Modeling of Crimean Congo Hemorrhagic Fever Virus Glycoprotein-N and Screening of Anti Viral Hits by Virtual Screening

text: Crimean-Congo hemorrhagic fever (CCHF) is a widespread zoonotic viral disease, caused by a tick-born virus Crimean-Congo hemorrhagic fever virus (CCHFV). This disease is endemic in Middle East, Asia, Africa and South-Eastern Europe with the mortality rate of 5–30%. CCHFV genome is composed of three segments: large, medium and small segments. M segment encodes a polyprotein (glycoprotein) so called glycoprotein N (Gn) which is considered as a potential druggable target for the effective therapy of CCHF. The complete structure of Gn is still not characterized. The aim of the current study is to predict the complete three-dimensional (3D-) structure of CCHFV Gn protein via threading-based modeling and investigate the residues crucial for binding with CCHFV envelop. The developed model displayed excellent stereo-chemical and geometrical properties. Subsequently structure based virtual screening (SBVS) was applied to discover novel inhibitors of Gn protein. A library of > 1300 anti-virals was selected from PubChem database and directed to the predicted binding site of Gn. The SBVS results led to the identification of thirty-seven compounds that inhibit the protein in computational analysis. Those 37 hits were subject to pharmacokinetic profiling which demonstrated that 30/37 compound possess safer pharmacokinetic properties. Thus, by specifically targeting Gn, less toxic and more potent inhibitors of CCHFV were identified in silico. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10989-020-10055-1) contains supplementary material, which is available to authorized users.


title: Outer Membrane Protein, Oma87 Prevents Acinetobacter baumannii Infection

text: Acinetobacter baumannii is one of the most problematic pathogens in clinical settings. Emerging of its antibiotic-resistant strains persuade researchers to find alternative treatment options such as immunization against the notorious nosocomial pathogen. Oma87 has been introduced as an immunogenic outer membrane protein via reverse vaccinology. However, protectivity of A. baumannii Oma87 is not well known. The current research undertakes a study on the immunogenicity of recombinant Oma87 in a murine model. Some physico-chemical properties were assessed via in silico analyses. The corresponding gene was amplified and cloned into pET28a plasmid. The recombinant protein was purified and then was administered to immunize mice. Sera obtained from the immunized mice were assessed with respect to the triggered antibodies. Challenges were performed on actively or passively immunized mice. In silico analyses revealed that this protein is the same as BamA. A high titer of specific antibody was raised against rOma87 even after the first injection. The specific antibody recognized the whole cell of A. baumannii. Both active and passive immunizations confer 100 and 50% protection, respectively against ~ 2 × lethal dose (LD) of A. baumannii in the murine sepsis model. Although none of mice received ~ 5 × LD of A. baumannii survived in passive immunization, 25% of mice challenged with ~ 7 × LD of the bacteria survived and the dead mice exhibited a delayed death. Based on these results, Oma87 is the same as BamA which could be considered as a promising vaccine candidate against A. baumannii in the sepsis model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10989-020-10056-0) contains supplementary material, which is available to authorized users.


title: Outcomes after pneumonectomy versus limited lung resection in adults with traumatic lung injury

text: Pneumonectomy after traumatic lung injury (TLI) is associated with shock, increased pulmonary vascular resistance, and eventual right ventricular failure. Historically, trauma pneumonectomy (TP) mortality rates ranged between 53 and 100%. It is unclear if contemporary mortality rates have improved. Therefore, we evaluated outcomes associated with TP and limited lung resections (LLR) (i.e., lobectomy and segmentectomy) and aimed to identify predictors of mortality, hypothesizing that TP is associated with greater mortality versus LLR. We queried the Trauma Quality Improvement Program (2010–2016) and performed a multivariable logistic regression to determine the independent predictors of mortality in TLI patients undergoing TP versus LLR. TLI occurred in 287,276 patients. Of these, 889 required lung resection with 758 (85.3%) undergoing LLR and 131 (14.7%) undergoing TP. Patients undergoing TP had a higher median injury severity score (26.0 vs. 24.5, p = 0.03) but no difference in initial median systolic blood pressure (109 vs. 107 mmHg, p = 0.92) compared to LLR. Mortality was significantly higher for TP compared to LLR (64.9% vs 27.2%, p < 0.001). The strongest independent predictor for mortality was undergoing TP versus LLR (OR 4.89, CI 3.18–7.54, p < 0.001). TP continues to be associated with a higher mortality compared to LLR. Furthermore, TP is independently associated with a fivefold increased risk of mortality compared to LLR. Future investigations should focus on identifying parameters or treatment modalities that improve survivability after TP. We recommend that surgeons reserve TP as a last-resort management given the continued high morbidity and mortality associated with this procedure.


title: Association study of genetic polymorphisms in proteins involved in oseltamivir transport, metabolism, and interactions with adverse reactions in Mexican patients with acute respiratory diseases

text: Oseltamivir, a pro-drug, is the best option for treatment and chemoprophylaxis for influenza outbreaks. However, many patients treated with oseltamivir developed adverse reactions, including hypersensitivity, gastritis, and neurological symptoms. The aim of this study was to determine the adverse drug reactions (ADRs) in Mexican patients treated with oseltamivir and whether these ADRs are associated with SNPs of the genes involved in the metabolism, transport, and interactions of oseltamivir. This study recruited 310 Mexican patients with acute respiratory diseases and treated them with oseltamivir (75 mg/day for 5 days) because they were suspected to have influenza A/H1N1 virus infection. Clinical data were obtained from medical records and interviews. Genotyping was performed using real-time polymerase chain reaction and TaqMan probes. The association was assessed under genetic models with contingency tables and logistic regression analysis. Out of 310 patients, only 38 (12.25%) presented ADRs to oseltamivir: hypersensitivity (1.9%), gastritis (10%), and depression and anxiety (0.9%). The polymorphism ABCB1-rs1045642 was associated with adverse drug reactions under the recessive model (P = 0.017); allele C was associated with no adverse drug reactions, while allele T was associated with adverse drug reactions. The polymorphisms SLC15A1-rs2297322, ABCB1-rs2032582, and CES1-rs2307243 were not consistent with Hardy–Weinberg equilibrium, and no other associations were found for the remaining polymorphisms. In conclusion, the polymorphism rs1045642 in the transporter encoded by the ABCB1 gene is a potential predictive biomarker of ADRs in oseltamivir treatment.


title: Epidemiological characteristics and early complications after spinal cord injury in Former Yugoslav Republic of Macedonia

text: STUDY DESIGN: Prospective cohort study OBJECTIVES: To describe epidemiological data and complications after acute traumatic spinal cord injury (tSCI) in Former Yugoslav Republic of Macedonia (FYROM). SETTING: University Clinic for Traumatology, Orthopedics, Anesthesia and Intensive Care Unit and Emergency Center (TOARILUC), Mother Teresa, Skopje, FYROM. METHOD: During the inclusion period March 2015 to September 2016, 38 tSCI patients were included. MRI, CT scan, and clinical examinations including International Standards for Neurological Classification of SCI were performed at admission. The information included: demographic data, transport type, date of admission and discharge, past illnesses, addiction habits, cause and type of injury, injury level, associated injuries, injury-related complications, and mortality. RESULTS: Mean age was 43 years (median 41, range 17–83). Seventeen patients had a complete and 15 an incomplete SCI, six were unknown. Most frequent causes for tSCI were traffic accidents (42%) and falls (40%), 24% of the accidents were contracted at work. Sixteen patients were ventilator dependent at some point during the acute period. Common complications were pressure ulcers, gastrointestinal-related, and infections. Hospital length of stay (LOS) ranged from 1 to 73 days. The in-hospital mortality rate was 32%. CONCLUSION: The annual incidence of tSCI in FYROM was in 2015–16 13 persons/million inhabitants per year. The epidemiological profile of tSCI in FYROM implies that preventive measures should be taken to reduce incidence of accidents in traffic and at work places. The high mortality rate and complications underline further actions to improve the acute care of tSCI in FYROM.


title: Bioinformatics Analysis of Domain 1 of HCV-Core Protein: Iran

text: Hepatitis C virus (HCV) infection is a serious global health problem and a cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Bioinformatics software has been an effective tool to study the HCV genome as well as core domains. Our research was based on employing several bioinformatics software applications to find important mutations in domain 1 of core protein in Iranian HCV infected samples from 2006 to 2017, and an investigation of general properties, B-cell and T-cell epitopes, modification sites, and structure of domain 1. Domain 1 sequences of 188 HCV samples isolated from 2006 to 2017, Iran, were retrieved from NCBI gene bank. Using several tools, all sequences were analyzed for determination of mutations, physicochemical analysis, B-cell epitopes prediction, T-cell and CTL epitopes prediction, post modification, secondary and tertiary structure prediction. Our analysis determined several mutations in some special positions (70, 90, 91, and 110) that are associated with HCC and hepatocarcinogenesis, efficacy of triple therapy and sustained virological response, and interaction between core and CCR6. Several B-cell, T-cell, and CTL epitopes were recognized. Secondary and tertiary structures were mapped fordomain1 and core proteins. Our study, as a first report, offered inclusive data about frequent mutation in HCV-core gene domain 1 in Iranian sequences that can provide helpful analysis on structure and function of domain 1 of the core gene.


title: Induction of Rabies Virus Infection in Mice Brain may Up and Down Regulate Type II Interferon gamma via epigenetic modifications

text: As feared and deadly human diseases globally, Rabies virus contrived mechanisms to escape early immune recognition via suppression of the interferon response. This study, preliminarily investigated whether Rabies virus employs epigenetic mechanism for the suppression of the interferon using the Challenge virus standard (CVS) strain and Nigerian street Rabies virus (SRV) strain. Mice were challenged with Rabies virus (RABV) infection, and presence of RABV antigen was assessed by direct fluorescent antibody test (DFAT). A real time quantitative Polymerase chain reaction (qRT-PCR) was used to measure the expression of type II interferon gamma (IFNG) and methylation specific quantitative PCR for methylation analysis of 1FNG promoter region. Accordingly, DNA methyltransferase (DNMT) and histone acetyltransferase (HAT) enzymes activities were determined. RABV antigen was detected in all infected samples. A statistically significant increase (p < 0.05) in mRNA level of IFNG was observed at the onset of the disease and a decrease as the disease progressed. An increase in methylation in the test groups from the control group was observed, with a fluctuation in methylation as the disease progressed. DNMT and HAT activities also agree with methylation as there was an observed increase activity in test group compared with control group. Similar fluctuation pattern was observed in both CVS and SRV groups as the disease progressed with HAT, being the most active proportionally. This study suggests that epigenetic modification via DNA methylation and histone acetylation may have played a role in the expression of type II interferon gamma in Rabies virus infection. [Figure: see text]


title: Plant-Derived Bioactive Peptides: A Treatment to Cure Diabetes

text: ABSTRACT: Recent advances in analytical techniques have opened new opportunities for plant-based drug discovery in the field of peptide and proteins. Enzymatic hydrolysis of plant parent proteins forms bioactive peptides which are explored in the treatment of various diseases. In this review, we will discuss the identified plant-based bioactive proteins and peptides and the in vitro, in vivo results for the treatment of diabetes. Extraction, isolation, characterization and commercial utilization of plant proteins is a challenge for the pharmaceutical industry as plants contain several interfering secondary metabolites. The market of peptide drugs for the treatment of diabetes is growing at a fast rate. Plant-based bioactive peptides might open up new opportunities to discover economic lead for the management of various diseases. GRAPHIC ABSTRACT: [Image: see text]


title: The effect of balneotherapy on body mass index, adipokine levels, sleep disturbances, and quality of life of women with morbid obesity

text: To investigate the effect of balneotherapy on body mass index, adipokine levels, sleep disturbances, and quality of life in women with morbid obesity. Fifty-four women with morbid obesity were included in the study. The body mass indexes (BMI) and waist/hip ratios (WHR) of the women were calculated. Subcutaneous fat thickness was measured using a *skinfold meter, and the percentage of adipose tissue was calculated. The *Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality, and the Nottingham Health Profile (NHP) was used to assess quality of life. In addition to routine biochemical tests, leptin, adipokine, visfatin from blood, and cortisol from saliva samples were studied. Participants were given 15 sessions of balneotherapy for 20 min each. After treatment, the laboratory and clinical parameters of the participants were *reevaluated. There was no statistically significant difference of BMI, WHR, and percentage of adipose tissue between before and after treatment measurements (p ˃ 0.05).There was a statistically significant improvement in PSQI and NSP scores (p ˂ 0.001). The levels of blood glucose, leptin, and visfatin were significantly decreased, and adiponectin was significantly increased after treatment (p = 0.047, p ˂ 0.001, p ˂ 0.001, and p ˂ 0.001, respectively).There was no statistically significant changes in salivary cortisol levels (p = 0.848). Patients with diabetes showed a statistically significant decrease in glucose levels after treatment (p = 0.017).There was a statistically significant decrease in low-density lipoprotein cholesterol levels in patients with dyslipidemia compared with pre-treatment (p = 0.018). Balneotherapy improves sleep and quality of life of women with morbid obesity. After balneotherapy, glucose, leptin, adiponectin, and visfatin levels may change positively.


title: Successful implementation of a Fracture Liaison Service through effective change management: a qualitative study

text: SUMMARY: We assessed the context in which a hip Fracture Liaison Service was implemented. We conducted semi-structured interviews with 21 key informants at two time points to understand organizational readiness, facilitators, and barriers to change. We identified strategies important to successful implementation, particularly in the context of change fatigue. PURPOSE: Fracture Liaison Service (FLS) is effective for secondary fracture prevention. Two hospital sites implemented FLS for hip fracture patients, 50 + years, in Alberta, Canada. We assessed organizational readiness, facilitators, and barriers to change to better understand the context in which the FLS was implemented to inform its potential spread provincially. METHODS: We recruited individuals involved in FLS implementation at provincial and site levels to participate in telephone interviews at baseline and 16 months post-implementation. Interviews were transcribed and analyzed using thematic content analysis. In addition, site-level participants were invited to complete the Organizational Readiness to Implement Change tool at baseline. RESULTS: We conducted 33 semi-structured interviews (20 at baseline; 13 at post-implementation) with 21 key informants. Participants included managers (24%), FLS physicians/clinical nurses (19%), operational/leadership roles (19%), physicians/surgeons (14%), pharmacists (10%), nurse practitioners (10%), and social work (5%). Seventeen site-level participants completed the ORIC tool at baseline; all participants scored high (71%) or neutral (29%). We found that the use of several strategies, including demonstrating value, providing resources, and selecting appropriate sites, were important to implementation, particularly in the context of change fatigue. Participants perceived the FLS as acceptable and there was evidence of facilitated learning rather than simply monitoring implementation as intended. CONCLUSIONS: An effective change management approach neutralized change fatigue. This approach, if maintained, bodes well for the potential spread of the FLS provincially if proven effective and cost effective. Change readiness assessment tools could be used strategically to inform the spread of the FLS to early adopter sites. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11657-020-0692-0) contains supplementary material, which is available to authorized users.


title: An experience with a bubble CPAP bundle: is chronic lung disease preventable?

text: BACKGROUND: Continuous positive airway pressure (CPAP) is associated with marginal decrease in chronic lung disease (CLD). This study aims to report outcomes, with focus on CLD, of preterm infants managed with a bubble CPAP (b-CPAP) bundle of care. METHODS: Infants <1500 g were stratified into four groups depending on intubation status through first 3 days of life. The incidence of mortality, CLD and other morbidities were compared over four chronological epochs. Outcomes of the most recent epoch were compared to contemporaneous benchmarks from Vermont Oxford Network (VON). RESULTS: Of 773 infants (median GA = 28 weeks, average BW = 995 g), 24.5% were intubated in DR and 11.7% in the first day of life. Mechanical ventilation, bCPAP and oxygen days in survivors were 1.5, 29 and 14, respectively. Overall incidence of CLD was 6.4% that remained consistent in the four epochs (7.6%, 7.5%, 5.8% and 5%), respectively. In comparison to VON, CLD was significantly less (p < 0.001). Initial DR intubation was not associated with increased CLD compared to initial management with CPAP that required subsequent intubation. CONCLUSION: It is feasible and sustainable to administer a b-CPAP bundle of care to decrease CLD. Cluster randomized trials are needed to validate the reproducibility of this approach.


title: A Pot Ignored Boils On: Sustained Calls for Explicit Consent of Intimate Medical Exams

text: Unconsented intimate exams (UIEs) on men and women are known to occur for training purposes and diagnostic reasons, mostly during gynecological surgeries but also during prostate examinations and abdominal surgeries. UIEs most often occur on anesthetized patients but have also been reported on conscious patients. Over the last 30 years, several parties—both within and external to medicine—have increasingly voiced opposition to these exams. Arguments from medical associations, legal scholars, ethicists, nurses, and some physicians have not compelled meaningful institutional change. Opposition is escalating in the form of legislative bans and whistleblower reports. Aspiring to professional and scientific detachment, institutional consent policies make no distinction between intimate exams and exams on any other body part, but patients do not think of their intimate regions in a detached or neutral way and believe intimate exams call for special protections. UIEs are found to contribute to moral erosion and moral distress of medical students and compromise the sacred trust between the medical community and the general public. This paper refutes the main arguments in favor of the status quo, identifies a series of harms related to continuing the current practice, and proposes an explicit consent policy for intimate exams along with specific changes to medical school curriculum and institutional culture. Because patients are the rights-holders of their bodies, consent practices should reflect and uphold patient values which call for explicit consent for intimate exams.


Less empiric broad-spectrum antibiotics is more in the ICU


title: Delphine Parrott, a pioneer of T cell biology

text: The first article in our Women in Immunology series pays tribute to Delphine Parrott, who conducted pioneering work in the fields of T cell biology, lymphoid tissue anatomy, lymphocyte trafficking and mucosal immunology.