We are reporting a case of neurofibromatosis type 1 in a genotype-phenotype correlation and chromosomal microarray test revealed a submicroscopic deletion on the long arm of chromosome 17, which is associated with a more severe phenotype. The presence of a more severe phenotype warrants precise monitoring of complications.

We report the case of an 81 year old lady presenting with a left pulsatile neck mass 7 years after her initial carotid endarterectomy (CEA). We were able to employ a combined hybrid trans-cervical carotid stents followed by open excision and repair for a successful outcome

Background. Children with cancer and infection may develop glomerular hyperfiltration (GH). With the aim to determine the prevalence of GH in children and young adults with haemato-oncological disease and infection we developed population pharmacokinetic model of iohexol. We further aimed to assess the accuracy of estimated glomerular filtration rate (eGFR) equations and single- or two-point measured GFR (mGFR) formulas compared with GFR based on iohexol clearance from our population pharmacokinetic model (iGFR). Procedure. Hospitalized patients (0.5-25 years) with haemato-oncological disease and infection were included if their eGFR was ≥80 mL/min/1.73 m2 at the screening visit. Iohexol plasma concentrations were described by population pharmacokinetic model. Bias, precision and accuracy of 23 eGFR equations and 18 mGFR formulas were calculated. Results. Total of 32 iohexol administrations was performed in 28 patients. Median (range) eGFR was 136 (74-234) mL/min/1.73 m2 and age 15.1 (0.8-26.0) years. Three-compartment model with allometric scaling of central, one peripheral compartment and clearance (with power 0.75) to weight fitted the best. Median (range) iGFR was 103 (68-140) mL/min/1.73 m2. All except one eGFR equation overestimated GFR. Lund-Malmö revised eGFR equation performed the best, followed by Gao equation. Of single- or two-point mGFR formulas 15 overestimated iGFR. Modified Jacobsson formula at 5.5 h performed the best, followed by Fleming formula at 3 h. Conclusions. In children and young adults with haemato-oncological disease and infection renal function is best described by iohexol clearance from three-compartmental pharmacokinetic model, while eGFR equations and single- and two-point mGFR formulas overestimate iGFR.

Background: Therapeutic drug monitoring for busulfan is important to prevent adverse events and improve outcomes in stem cell transplantation. We investigated intravenous busulfan pharmacokinetics and evaluated the utility of limited sampling strategy (LSS) as a simple method to estimate the area under the concentration-time curve (AUC). Procedure: The study comprised 87 busulfan measurements in 54 children who received intravenous busulfan between August 2015 and May 2020. AUCs were calculated from 3–5 blood sampling points in each patient, and the correlation between AUC and plasma concentrations (ng/mL) at 1, 2, 3, 4, and 6 h after initiating busulfan infusion (C1, C2, C3, C4, and C6, respectively). Results: By one-point sampling strategy, the most accurate predicted AUC was based on C6 (r2 = 0.789; precision, 11.0%) in all patients. The predicted AUC based on C6 was highly precise (r2 = 0.937; precision, 5.9%) in adolescent patients weighing > 23 kg, but the correlation was poor in infants and young children weighing ≤23 kg (r2 = 0.782; precision, 11.4%). By two-point sampling strategy, the predicted AUC based on C3 and C6 showed the most favorable performance (r2 = 0.943; precision, 6.4%), even in infants and young children, whereas the predicted AUC based on C3 and C6 was acceptable (r2 = 0.963; precision, 5.7%). Conclusions: The AUC of busulfan can be predicted based on C6 in adolescent patients. However, there was substantial inter-individual variation in busulfan pharmacokinetics in infants and young children, in whom two-point LSS was necessary for accurate AUC prediction.

A document by Klaus Rose. Click on the document to view its contents.

Background: The prognosis of metastatic hepatoblastoma remains poor; to improve it, pulmonary metastasis must be controlled. Indocyanine green (ICG) fluorescent imaging has been used recently for lung metastasectomy. The objective of our study was to clarify the usefulness of ICG imaging for lung metastasectomy of hepatoblastoma using detailed clinicopathological analysis. Procedure: Patients with hepatoblastoma who underwent resection of pulmonary metastases with ICG fluorescent imaging were studied using retrospective analysis of clinical information, a review of their surgical records, and a histological analysis of their metastatic nodules. Results: Sixteen patients were enrolled. In total, 61 ICG-imaging-guided pulmonary metastasectomies were performed, and 350 ICG-positive and 23 ICG-negative specimens were identified. Tumors were confirmed in 250 of the ICG-positive specimens, including eight nonpalpable nodules, on microscopic examination. One hundred ICG-positive specimens and histologically tumor-negative specimens showed histological changes suggesting the regression of a tumor or bloodstream disturbance. The palpable ICG-negative tumors showed more-severe atypia than the ICG-positive tumors. Conclusions: This study demonstrates the high sensitivity of ICG imaging in detecting metastatic lesions of hepatoblastoma. Histological examinations suggested that ICG imaging detects not only tumor cells, but also nontumorous pulmonary tissues affected by bloodstream disturbance. Because a number of false-positive specimens were detected, further optimization of the dose of ICG and the timing of its administration may be required for thorough metastasectomy. Several false-negative specimens were also detected, suggesting the presence of ICG-negative metastatic tumors. Palpation during operation and imaging studies remain essential for detecting metastatic lesions, even in the era of ICG imaging.

ABSTRACT The hepatic rupture durig pregnancy is a catastrophic clinical issue associated with high fetal and maternal mortality. We describe the case of hepatic hemangioma rupture complicated by massive thrombosis of the inferior vena cava successfully treated by using AngioVac aspiration system. Although an aggressive surgical strategy is recommended, a multidisciplinary approach using modern devices can represent a new frontier in the treatment of these patients.

Background and Purpose: Many pain-triggering nociceptor neurons express TRPV1 or TRPA1, cation-selective channels with large pores that enable permeation of QX-314, a cationic analogue of lidocaine. Co-application of QX-314 with TRPV1 or TRPA1 activators can silence nociceptors. We now describe BW-031, a novel more potent cationic sodium channel inhibitor, test whether its application alone can inhibit the pain associated with tissue inflammation, and whether this strategy can also inhibit cough. Experimental Approach: We characterized BW-031 inhibition of sodium channels and tested BW-031 in three models of inflammatory pain: rat paw inflammation produced by Complete Freund’s Adjuvant injection or surgical incision and a mouse paw UV burn model. We also tested the ability of BW-031 to inhibit cough induced by inhalation of dilute citric acid in guinea pigs. Key Results: BW-031 inhibited Nav1.7 and Nav1.1 channels with ~6-fold greater potency than QX-314 when introduced inside cells and entered capsaicin-activated TRPV1 expressing sensory neurons. BW-031 inhibited inflammatory pain in all three models, producing more effective and longer-lasting inhibition of pain than QX-314 in the mouse UV burn model. BW-031 was also effective in reducing cough counts by 78-90% when applied intratracheally under isoflurane anesthesia or by aerosol inhalation in awake guinea pigs with airway inflammation produced by ovalbumin sensitization. Conclusion and Implications: BW-031 a novel cationic sodium channel inhibitor can be applied locally as a single agent to inhibit inflammatory pain and also effectively inhibits cough in a guinea pig model of nociceptor-activated cough, suggesting a new clinical approach to treating cough.

I bioreattori a membrana (MBR) uniscono nella stessa unità sia il processo biologico che la filtrazione su membrana in sostituzione dei sedimentatori secondari. Gli MBR presentano vari vantaggi rispetto all’impianto convenzionale a fanghi attivi tra cui minor ingombro, migliore qualità dell’effluente e minor produzioni di fanghi. Non mancano, però, degli svantaggi: il primo è rappresentato dai costi elevati dovuti ai consumi energetici e al costo delle membrane, il secondo, ma non meno importante è legato alla formazione del fouling, ossia dello sporcamento delle stesse, che ne riduce il flusso, limitando così l’efficienza del processo. Negli anni sono state studiate diverse tecnologie per porre rimedio a questi svantaggi. L’introduzione delle membrane dinamiche auto-formanti (SFDM) ha permesso di contrastare il problema del costo delle membrane, poiché il loro funzionamento è basato sulla deposizione delle particelle di fango su un modulo di supporto con porosità elevata e realizzato con materiali economici. Lo svantaggio principale di questa tecnologia risiede nella necessità di un tempo iniziale per la completa formazione della membrana dinamica, il quale varia a seconda delle caratteristiche del refluo o delle condizioni operative in cui avviene il processo.   Altra soluzione proposta dalla letteratura scientifica per contrastare il problema dello sporcamento della membrana è quella di accoppiare i processi elettrochimici con gli MBR, tale soluzione non solo riduce il fouling di membrana ma aumenta le performance depurative del sistema. 

The Intermediate Disturbance Hypothesis is widely considered to be wrong but is rarely tested against alternative hypotheses. It predicts that soil disturbances and herbivory have identical impacts on species richness via identical mechanisms (reduction in biomass and in competition). An alternative hypothesis is that the specific traits of disturbance agents (small mammals) and plants differentially affects richness or abundance of different plant groups. We tested these hypotheses on a degu (Octodon degus) colony in central Chile. We ask whether native and non-native forbs respond differently to degu bioturbation on runways vs. herbivory on grazing lawns. We ask whether this can explain the increase in non-native plants on degu colonies. We found that biopedturbation did not explain the locations of non-native plants. We did not find direct evidence of grazing increasing non-native herbs either, but a grazing effect appears to be mediated by grass, which is the dominant cover. Further, we provide supplementary evidence to support our interpretation that a key mechanism of non-native spread is the formation of dry soil conditions on grazing lawns. Thus ecosystem engineering (alteration of soil qualities) may be an outcome of disturbances, which each interact with specific plant traits, to create the observed pattern of non-native spread in the colony. Based on these results we propose to extend Jentsch & White’s (2019) concept of combined pulse/ disturbance events to the long-term process duality of ecosystem engineering/ disturbance.

A document by Minggang DU. Click on the document to view its contents.

Objective: The present study aimed to investigate the possible cardioprotective effects of ketotifen and to assess its activity as an iron-chelating agent in patients receiving anthracyclines for the treatment of breast cancer. Patients & Methods: This was a randomized, prospective, controlled clinical trial. One hundred eleven eligible patients with breast cancer (age range, 30-60 years) were scheduled to receive anthracyclines chemotherapy. The patients were divided into two groups: Patients (n = 56) assigned to the ketotifen group received ketotifen 1 mg three times daily for six consecutive cycles of treatment, and patients assigned to the control group (n = 55) without ketotifen treatment. The echocardiogram for each patient was recorded two times at baseline and the end of the study. As well, blood samples were collected from all patients. Results: The findings showed a statistically significant reduction in the mean serum levels of common cardiotoxicity accompanied biomarkers in the ketotifen group compared with the control group (P ≤ 0.05). The mean serum levels of total iron-binding capacity were significantly elevated in the ketotifen group (P ≤ 0.001). There was a direct correlation between the mean serum levels of iron and that of lactate dehydrogenase (LDH) (r = + 0.79). On the other hand, there were indirect correlations between mean serum levels of LDH and both the percentage of ejection fraction and the total iron-binding capacity (r = - 0.69 and -0.697, respectively). Conclusion: Oral administration of ketotifen appears to be efficient and safe as a novel cardioprotective agent for the prevention of anthracyclines induced cardiotoxicity. Additionally, ketotifen suggested a beneficial effect in iron overload inducing diseases such as COVID-19.

Background: Despite continued efforts, the majority of patients with valvular heart disease (VHD) remain undiagnosed and untreated. This study aimed to assess the adoptability and accuracy of point-of-care handheld echocardiographic assessments (POCE) in the primary care setting. Methods: Eleven previously untrained primary care providers were trained to use the Vscan Extend (GE, WI) POCE to assess VHD, left ventricular function (LVEF), and major extra-cardiac findings. Their assessments were compared to those of 3 blinded expert readers. A total of 180 assessments were evaluated using Kappa statistics (κ) together with their estimated standard error, p-value, and 95% CI bounds. Results: Identical or nearly identical agreement between previously untrained primary providers and expert readers was evident for the diagnosis of tricuspid regurgitation, mitral regurgitation, pericardial effusion, volume status. These agreements were strongest in apical long axis (κ =1, p<0.001) and parasternal long and short axis views (k>=0.82 p<0.001), though agreement remained robust in apical 4-chamber views (k>=0.76). The agreements in LVEF assessment were identical in the apical long axis view (κ =1, p<0.001) and robust in the remaining 3 views (κ>=0.66, p<0.001). The assessments of aortic stenosis (parasternal/long, κ =0.42, and parasternal/short, κ =0.47, both p<0.001) were weak in their agreement. Conclusion: Compared to expert echocardiography readers, the untrained providers’ use of POCE for VHD shows high user adoptability and diagnostic accuracies in the primary care setting.

Biliary tract cancer is the most common biliary malignant tumor, which is considered to be a high-grade malignant tumor because of its frequent recurrence / metastasis[1]. Late recurrence of gallbladder cancer after operation is rare. We presented a case of recurrent cancer after radical resection of gallbladder cancer.

From the perspective of prey, movement synchrony can represent either a potent anti-predator strategy or a dangerous liability. Prey must balance the costs and benefits of using conspecifics to mediate risk and the emergent patterns of risk-driven sociality depends on the spatial variation and trait composition of the system. Our literature review outlined the prevailing, but not universal, trend of animals using sociality as an antipredator strategy. Empirically, we then used movement synchrony as a measure of social antipredator response of two ungulates to spatial variation in predator and prey habitat domains. We demonstrated that these responses vary based on prey vulnerability and predator hunting modes. Prey favored asynchrony when calves were present and within habitat domains of ambush predators but not pursuit predators. By unifying community ecology concepts such as habitat domains with movement ecology we provided a comprehensive evaluation of factors mediating prey social response to predation risk.

Introduction: Immunotherapy has proven its efficacy in multiple randomized control trials (RCT) in treating allergic rhinitis (AR) as it induces induces long term remission after discontinuation and prevent new sensitization. Objective: Our aim is to look into earliest improvement of quality of life (QOL) in AR patient treated with Sublingual immunotherapy (SLIT). Methodology: Patients who were sensitized to dust mites (Dermatophagoides farinae, Dermatophagoides pteronyssinus and Blomia tropicalis) were enrolled into the study. All patients were treated with SLIT for 6 months. The patients were assessed using rhinoconjunctivitis quality of life questionnaires (RQLQ) and peak nasal inspiratory flow (PNIF) pre-treatment at 1, 3 and 6 months post SLIT. The usage of intranasal corticosteroids (INS) and antihistamine were documented in medication diary. The data for pre and post treatment for RQLQ results were analysed using paired T-test and medication diary were analysed using ANOVA test. Results: A total of 53 patients were enrolled in the study. The mean RQLQ score showed significant result at 3 and 6 months post SLIT (p<0.05). Significant improvement seen in the mean PNIF value pre-treatment (81.54 L/min ±29.36 ) compared to mean PNIF value at 3 months (92.0L/min ±29.03 ) and 6 months (96.13L/min ±26.67) post SLIT (p<0.05). The dependency of patients towards pharmacotherapy also showed a significant reduction at 3 and 6 months post SLIT (p<0.05). Conclusion: Our study showed a significant improvement of patients’ quality of life as early as 3 months of post SLIT treatment.

In this study, the impact of spatio-temporal accuracy of four different sea surface temperature (SST) datasets on the accuracy of the Weather Research and Forecasting (WRF)-Hydro system to simulate hydrological response during two catastrophic flood events over Eastern Black Sea (EBS) and Mediterranean (MED) regions of Turkey is investigated. Three time-varying and high spatial resolution external SST products (GHRSST, Medspiration, and NCEP-SST) and one coarse-resolution and invariable SST product (ERA5- and GFS-SST for EBS and MED regions, respectively) already embedded in the initial and boundary condition dataset of WRF model are used in deriving near-surface weather variables through WRF. After the proper event-based calibration performed to the WRF-Hydro using hourly and daily streamflow data of small catchments in both regions, uncoupled model simulations for independent SST events are conducted to assess the impact of SST-triggered precipitation on simulated extreme runoff. Some localized and temporal differences in the occurrence of the flood events with respect to observations depending on the SST representation are noticeable. SST products represented with higher temporal and spatial correlation revealed significant improvement in flood hydrographs for both regions. The higher spatial and temporal correlations of GHRSST dataset show RMSE reduction up to 20% and increase in correlation from 0.3 to 0.8 with respect to the invariable SST (ERA5) in simulated runoffs over the EBS region. The error reduction with GHRSST reached 35% after the calibration of hydrological model parameters compared to not calibrated model. The use of both GHRSST and Medspiration SST data characterized with high spatiotemporal correlation resulted in runoff simulations exactly matching the observed runoff peak of 300 m3/s by reducing the overestimation seen in not calibrated runs over the MED region.

A bendable UHF RFID tag antenna using non-uniform meandered lines for retail garments in the textile industry is presented. Based on an earlier UHF RFID tag antenna using nonuniform meandered lines, the proposed tag is fully bendable and aimed to be embedded in retail garments for long-life cycles. As a result, a relatively low cost, wide band, compactness and good conjugate matching with good dipole-like read range is presented. Results showed an antenna with a wide bandwidth of 900MHz and a long read range of 10.1m making the UHF RFID tag antenna using non-uniform meandered lines a potential candidate for retail garments in bendable applications of the textile industry. Simulations are corroborated by measurements and are in fairly agreement.

Background: Locusts as model systems are widely used in many biological laboratories worldwide. Occupational exposure to locusts induces a high prevalence of allergic sensitization. However, knowledge on occupational locust allergens remains unclear. This study aimed to identify a novel allergen from locusts that causes occupational allergies. Methods: We conducted a 20-year retrospective survey of 94 persons using questionnaires and a cross-sectional survey of 57 persons using questionnaires and immunological tests for occupational allergies in long-term locust laboratories. We identified the major allergens by immunoblotting and analysed them by LC-MS/MS. The allergenicity of the major allergen proteins was assessed by specific IgE (sIgE) detection, immunoblotting and ELISA inhibition assays. Results: The retrospective survey indicated that the frequency of occupational allergies was relatively low (13.8%), while the cross-sectional survey showed a higher frequency (40.4%). The symptoms in most allergic males were allergic rhinitis and asthma, while females showed higher prevalence of atopic dermatitis. Occupational exposure for 2-3 h per day or continuing one and half years obviously increased the allergy risk. We identified the hexamerin-2 protein as a major allergen in locusts. Purified hexamerin-2 protein achieved approximately 60% serum IgE reactivity with locust protein extract. The potential for cross-reactivity with cockroaches was indicated by sequence alignment of the hexamerin-2 protein and allergens of cockroaches. Conclusion: Occupational exposure is an important risk factor for locust allergy. The hexamerin-2 protein of locusts as a major allergen in occupational allergy was identified for the first time.

OBJECTİVE: Kidney transplant recipients (KTRs) may have increased serum uric acid (SUA) level due to presence of existing greft dysfunction and used immunosuppressives. In this retrospective study, we evaluated effect of high SUA levels and allopurinol therapy in KTRs on renal functions. PATIENTS and METHODS: 113 KTRs of 233 KTRs included, had elevated SUA level (G1). Fiftyseven of G1 received allopurinol treatment (G1A+) and 56 patients (G1A-) did not. 56 of 118 patients who were followed for five years (G5) were hyperuricemic (G5-1) and 26 of G5-1 treated with allopurinol (G5-1A+) and 30 of them did not (G5-1A-). 62 patients were normourisemic (G5-2). RESULTS: Of the 233 patients included the mean age was 42.8±11.6 (17-76), 164 were male (70.0%). In 2. year graft loss developed in 9 (7.5 %) and 18 (15.9%) of G2 and G1 respectively (p = 0.045). According to allopurinol therapy 10 of the graft loss occurred in the G1A+ and 8 in the G1A- (p=0,330). Graft loss occurred in 12 (21%) and 9 (14%) in G5-1 and G5-2 respectively (p = 0.62). Graft loss occurred in 7 (23 %) and 5 (19%) in G5-1A+ and G5-1A- respectively P = 0.71). Considering the first 2 in G5; in G5-1 graft loss was higher than in the G5-2 (p = 0.023), and higher SUA levels increased the graft loss by 3.6 times compared to normal SUA levels (95% confidence interval: 1,2-12.70). CONCLUSION: There was a significant relationship between high SUA levels and graf loss in kidney transplant recipients in 2 years and 5 years. Treatment of high SUA with alIopurinol therapy had protective effect on renal functions. So that hyperuricemia should be treated and low dose allopurinol can be option for treatment of hyperuricemia therefore prevention of loss of kidney function in kidney transplant recipients.

Aim: The aim of this study was to measure plasma midkine levels in patients with COVID-19 and to assess its clinical significance. Material and Method: 88 patients followed in our hospital with a diagnosis of COVID-19 were included in the study. Demographic characteristics, clinical and laboratory data of the patients were recorded, and the relationship between midkine level and prognosis and other parameters were investigated. Results: Of the 88 patients included in the study, 43 (48.9%) were female and 45 (51.1%) were male. 24 (27%) of our cases were died. The mean age of non-survivals was 70 ± 12.3 and the survivals were 61.9 ± 18.2 years. Mortality predictors due to COVID-19 in group 2 patients were significantly higher than those in group 2 (p <0.05). The median (IR) value of the MK level was 152.5±125 pg/ml in all patients, 143±149 pg/ml in survivors and 165.5±76 pg/ml in those who died (p= 0.546). The difference between these two groups compared according to mortality was not statistically significant The area under the ROC curve was found to be 0.542 (95% CI 0.423-0.661, p= 0.546). Conclusion: MK is not a biomarker that can reinforce known predictors of mortality in COVID-19 patients and can provide better predictions of mortality.

A physical model demonstrating critical zone structure and flow processes in headwatersXuhui Shen1,2, Jintao Liu1,2*, Wanjie Wang2, Xiaole Han1,3, Jie Zhang2, Guofang Li2, Xiaopeng Li4, and Yue Shi2___________________1 State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering, Hohai University, Nanjing 210098, China2 College of Hydrology and Water Resources, Hohai University, Nanjing 210098, China3 School of Earth Sciences and Engineering, Hohai University, Nanjing 211100, China4 Institute of Soil Science, Chinese Academy of Sciences, Nanjing, Jiangsu 210008, China___________________*Corresponding author: Jintao Liu. Tel.: +86-025-83787803; Fax: +86-025-83786606.Running head: A physical model demonstrating critical zone structure in headwaterKeywords: Physical model; Hydrologic processes; Critical zone structures; Artificial soil

Background: Rate of non-adherence to antiepileptic drugs (AEDs) in children is about 33%. Engaging clinical pharmacists in the management of patients has proved to increase adherence to medications which will improve the outcomes of treatment.Objectives: To investigate the effect of a clinical pharmacist-led educational tool on the adherence to AEDs in pediatric patients with epilepsy. Secondary outcomes include effectiveness and safety of AEDs, satisfaction with information about AEDs provided to the caregivers, and patients quality of life (QoL).Methods: This was an interventional study where pediatric patients were randomly assigned to the intervention (n=41) or the control (n=40) group. A 30-minute clinical pharmacist-led educational interview to the parent/caregiver was provided to the intervention group as add-on to standard medical care received by the control group. Outcomes were measured at baseline and after eight-week follow-up. Results: The intervention group had an increase in mean adherence score from 6 ± 1.09 at baseline to 7.6 ± 0.9 at follow up (P-value < 0.001), while the control group had no significant change (P-value > 0.05), the difference between the two groups at follow-up was significant (P-value <0.0001). No significant difference was observed between groups at follow up with regard to effectiveness (P- value > 0.05), and safety (P-value=0.08). While higher satisfaction with information (P-value <0.0001), and higher QoL (P-value <0.05) was observed in the intervention group. There was a significant positive correlation between satisfaction and adherence (r=0.682, P-value < 0.0001), adherence and QoL (r=0.323, P-value < 0.01), satisfaction and QoL (r=0.298, P-value < 0.05). While, satisfaction and safety, safety and QoL correlated significantly and negatively (r=-0.263, P-value < 0.05 and r=-0.782, P-value < 0.0001, respectively)Conclusion: Clinical pharmacist-led educational tool had a positive outcome on pediatric patients with epilepsy with regard to adherence, effectiveness, safety, satisfaction with information about AEDs, and QoL.

Title: The Effect of COVID- 19 Pandemic on Routine Adult Vaccination in Cancer PatientsRunning title: COVID-19 and Vaccination in Cancer Patients