Physical properties of cellulose nanocrystal/magnesium oxide/chitosan transparent composite films for packaging applications.

Hitherto unreported hybrid nanofillers (CNC:MgO) reinforced chitosan (CTS) based composite (CNC:MgO)/CTS films were synthesized using a solution-casting blend technique and synergistic effect of hybrid nanofiller in terms of properties enhancement were investigated. Optical microscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD) technique, fourier-transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (FESEM) were used to characterize the films. The hybrid nanofiller considerably changed the transparency and color of the CTS films. The tensile strengths of (3 wt%) CNC/CTS, (3 wt%) MgO/CTS, (1:1)(CNC:MgO)/CTS, (1:2)(CNC:MgO)/CTS and (2:1)(CNC:MgO)/CTS films were 27.49 %, 35.60 %, 91.62 %, 38.22 %, and 29.32 % higher than pristine CTS films respectively, while the water vapor permeation were 28.21 %, 30.77 %, 34.62 %, 38.46 %, and 37.44 % lower than pristine CTS film, respectively. Moreover, the CTS composite films exhibited an improvement in overall water barrier properties after incorporating hybrid nanofillers. Our observations suggest that chitosan-based hybrid nanofiller composite films are a good replacement for plastic-based packaging materials within the food industry.

Patients with Obesity Should be Recognised as a Special Patient Population During Drug Development of Antibacterial and Antifungal Agents; A Call to Action.

Individuals with obesity are at increased risk of developing infectious diseases. Timely administration of an effective dose of an antimicrobial agent is paramount to safeguard optimal therapy. For this purpose, special patient populations at risk for altered exposure such as renal or hepatic impairment are studied during drug development. Strikingly, there is no such evaluation in individuals with obesity despite a potential influence on exposure and a global obesity prevalence of 13 %. Optimal clinical decision making in patients with obesity is impossible without prior study of the drug of interest in this population. This statement is strengthened by an evaluation of 19 antimicrobial agents that showed tremendous variability in the influence of weight on clearance. In contrast to patient with renal or hepatic impairment who are mainly at risk of overexposure, individuals with obesity can be at risk of both under- and overexposure. Gaining knowledge on the influence of body weight on clearance during early phases of drug development may allow for optimisation of other phases of research, potentially increasing success rate of the drug, and can provide clinicians with vital information as soon as the drug reaches the market. Antimicrobial therapy should be tailored to obesity-related (patho)physiological changes and to reach this goal, obese individuals should be studied during drug development.

Impact of mucositis on oral bioavailability and systemic exposure of ciprofloxacin Gram-negative infection prophylaxis in patients with haematological malignancies.

BACKGROUND: Patients with haematological malignancies frequently endure neutropenia and gastrointestinal (GI)-mucositis after high-dose chemotherapy. In these patients, ciprofloxacin is used for Gram-negative infection prophylaxis. OBJECTIVES: We investigate ciprofloxacin pharmacokinetics after oral administration in patients with haematological malignancies and explore the impact of GI-mucositis on oral bioavailability and clearance in order to assure adequate systemic exposure. METHODS: Adult haematological patients from two Dutch University Medical Centres received 500 mg twice daily oral ciprofloxacin for Gram-negative prophylaxis. The ciprofloxacin plasma concentrations were collected at various timepoints after oral ciprofloxacin administration and at various days after completion of chemotherapy. Data obtained after oral and intravenous ciprofloxacin administration in 28 healthy volunteers without mucositis served as a control group (391 samples). For haematological patients the degree of GI-mucositis was assessed using the Daily Gut Score (DGS), plasma citrulline and albumin. Data were analysed by non-linear mixed-effects modelling. RESULTS: In total, 250 blood samples were collected in 47 patients with a wide variety of haematological malignancies between 0-30 days after start of chemotherapy. Mucositis was generally mild [DGS median (IQR) 1 (1-1) and citrulline 16 µmol/L (12-23)]. The time to Cmax was slower in haematological patients compared with healthy volunteers although no association with the degree of mucositis (defined as DGS or citrulline) could be identified. Ciprofloxacin bioavailability and clearance were 60% and 33.2 L/h, respectively. CONCLUSIONS: This study supports oral dosing of ciprofloxacin as Gram-negative infection prophylaxis in haematological patients with mild-to-moderate mucositis capable of oral intake.

Hydrophilicity and hydrophobicity consideration of organic surfactant compounds: Effect of alkyl chain length on corrosion protection.

Organic compounds have been recognized as one of the utmost operative corrosion protective measures. However, their usage and synthesis are allied with the consumption and release of malignant materials. More so, out of various manufactured and settled compounds, only a few are effective. Therefore, the high mandate is to design and formulate effective compounds based on literature outcomes. Literature outcomes suggest that surfactant molecules having alkyl substituent of neither too small nor too large act as effective aqueous phase corrosion inhibitors. The present review describes the effect of alkyl/hydrocarbon chain length on the corrosion inhibition potential of some series of surfactant molecules. Generally, an increase in the alkyl chain length favors inhibition performance due to enhancing the packing of surfactant molecules at the interface of metal and electrolyte, but a very high level of hydrophobicity disfavors the inhibition performance. Hydrophilicity and hydrophobicity can be suitably tailored by varying the number and size of the hydrocarbon chain. Organic compounds containing the hydrocarbon chain length of C12-C16 exhibit the best inhibition efficiency (%IE). The molecules become effective by adsorbing on the metal surface. They behave as mixed- and interface-type corrosion inhibitors.

Watson for Oncology and breast cancer treatment recommendations: agreement with an expert multidisciplinary tumor board.

Background: Breast cancer oncologists are challenged to personalize care with rapidly changing scientific evidence, drug approvals, and treatment guidelines. Artificial intelligence (AI) clinical decision-support systems (CDSSs) have the potential to help address this challenge. We report here the results of examining the level of agreement (concordance) between treatment recommendations made by the AI CDSS Watson for Oncology (WFO) and a multidisciplinary tumor board for breast cancer. Patients and methods: Treatment recommendations were provided for 638 breast cancers between 2014 and 2016 at the Manipal Comprehensive Cancer Center, Bengaluru, India. WFO provided treatment recommendations for the identical cases in 2016. A blinded second review was carried out by the center's tumor board in 2016 for all cases in which there was not agreement, to account for treatments and guidelines not available before 2016. Treatment recommendations were considered concordant if the tumor board recommendations were designated 'recommended' or 'for consideration' by WFO. Results: Treatment concordance between WFO and the multidisciplinary tumor board occurred in 93% of breast cancer cases. Subgroup analysis found that patients with stage I or IV disease were less likely to be concordant than patients with stage II or III disease. Increasing age was found to have a major impact on concordance. Concordance declined significantly (P ≤ 0.02; P < 0.001) in all age groups compared with patients <45 years of age, except for the age group 55-64 years. Receptor status was not found to affect concordance. Conclusion: Treatment recommendations made by WFO and the tumor board were highly concordant for breast cancer cases examined. Breast cancer stage and patient age had significant influence on concordance, while receptor status alone did not. This study demonstrates that the AI clinical decision-support system WFO may be a helpful tool for breast cancer treatment decision making, especially at centers where expert breast cancer resources are limited.

Prevalence of sexual dysfunctions and other sexual disorders in adults with attention-deficit/hyperactivity disorder compared to the general population.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention and/or hyperactivity and impulsivity that lead to dysfunctioning in daily life. One of the affected areas of life that has so far not been studied in ADHD is sexual functioning. The goal of this study was to assess prevalence of sexual dysfunctions and other sexual disorders among adults with ADHD. A total of n = 136 adult patients treated in a Dutch outpatient ADHD clinic filled out two questionnaires to screen for sexual dysfunctions and other sexual disorders. We compared the prevalence of sexual dysfunctions and other sexual disorders in our ADHD patient population to results from two large surveys among the general Dutch population. We found that 39% of the male and 43% of the female ADHD patients had symptoms of a sexual dysfunction, and 17% of the male and 5% of the female ADHD patients had symptoms of any other sexual disorder. Only one male patient had received a diagnosis of a sexual disorder at this clinic prior to study participation. In conclusion, sexual dysfunctions and other sexual disorders are highly prevalent in adults with ADHD. Screening for sexual disorders should be therefore standard procedure during diagnostic assessment.

[A patient with severe digoxin toxicity]. / Een patiënt met ernstige digoxine-intoxicatie.

BACKGROUND: Digoxin is a cardiac glycoside that is frequently prescribed in atrial fibrillation and heart failure. Symptoms such as nausea, hyperkalaemia, cardiac arrhythmias and cardiac arrest are seen in digoxin toxicity. The treatment focuses on reduction of digoxin absorption, prevention of hypokalaemia and hyperkalaemia, treatment of symptoms and, in severe toxicity, administration of digoxin antibodies. CASE DESCRIPTION: A 73-year-old man with a history of extensive cardiac disease was seen 45 minutes after ingesting 20 mg of digoxin. The patient developed ventricular fibrillation within 3 hours of ingestion, before arrival of the digoxin antibodies. The patient passed away despite resuscitation and administration of an insufficient amount of digoxin antibodies. CONCLUSION: The national supply of digoxin antibodies in the Netherlands proved to be too limited for the treatment of a patient with severe digoxin toxicity. An increase in the supply, and central storage, of digoxin antibodies could promote faster administration of an adequate amount of the antibodies. Timely transportation to an extra corporeal membrane oxygenation centre should also be considered.

Self-expandable metal stents for malignant esophageal obstruction: a comparative study between extrinsic and intrinsic compression.

Self-expandable metal stents (SEMSs) are effective for malignant esophageal obstruction, but usefulness of SEMSs in extrinsic lesions is yet to be elucidated. This study is aimed at evaluating the clinical usefulness of SEMSs in the extrinsic compression compared with intrinsic. A retrospective review was conducted for 105 patients (intrinsic, 85; extrinsic, 20) with malignant esophageal obstruction who underwent endoscopic SEMSs placement. Technical and clinical success rates were evaluated and clinical outcomes were compared between extrinsic and intrinsic group. Extrinsic group was mostly pulmonary origin. Overall technical and clinical success rate was 100% and 91%, respectively, without immediate complications. Extrinsic and intrinsic group did not differ significantly in clinical success rate. The median stent patency time was 131.3 ± 85.8 days in intrinsic group while that of extrinsic was 54.6 ± 45.1 due to shorter survival after stent insertion. The 4-, 8-, and 12-week patency rates were 90.5%, 78.8%, and 64.9% respectively in intrinsic group, while stents of extrinsic group remained patent until death. Uncovered, fully covered, and double-layered stent were used evenly and the types did not influence patency in both groups. In conclusion, esophageal SEMSs can safely and effectively be used for malignant extrinsic compression as well as intrinsic.

AAV-mediated and pharmacological induction of Hsp70 expression stimulates survival of retinal ganglion cells following axonal injury.

We evaluated the effect of AAV2- and 17-AAG (17-N-allylamino-17-demethoxygeldanamycin)-mediated upregulation of Hsp70 expression on the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC). AAV2-Hsp70 expression in the retina was primarily observed in the ganglion cell layer. Approximately 75% of all transfected cells were RGCs. RGC survival in AAV2-Hsp70-injected animals was increased by an average of 110% 2 weeks after the axonal injury compared with the control. The increase in cell numbers was not even across the retinas with a maximum effect of approximately 306% observed in the inferior quadrant. 17-AAG-mediated induction of Hsp70 expression has been associated with cell protection in various models of neurodegenerative diseases. We show here that a single intravitreal injection of 17-AAG (0.2 ug ul(-1)) results in an increased survival of ONC-injured RGCs by approximately 49% compared with the vehicle-treated animals. Expression of Hsp70 in retinas of 17-AAG-treated animals was upregulated approximately by twofold compared with control animals. Our data support the idea that the upregulation of Hsp70 has a beneficial effect on the survival of injured RGCs, and the induction of this protein could be viewed as a potential neuroprotective strategy for optic neuropathies.

Lactoferrin causes IgA and IgG2b isotype switching through betaglycan binding and activation of canonical TGF-ß signaling.

Lactoferrin (LF), a pleiotropic iron-binding glycoprotein, is known to modulate the humoral immune response. However, its exact role in Ig synthesis has yet to be elucidated. In this study, we investigated the effect of LF on Ig production by mouse B cells and its underlying mechanisms. LF, like transforming growth factor (TGF)-ß1, stimulated B cells to produce IgA and IgG2b, while downregulating other isotypes. Using limiting dilution analysis, LF was shown to increase the frequency of IgA-secreting B-cell clones. This was paralleled by an increase in Ig germ-line α (GLα) transcripts, indicating that LF plays a role as an IgA switch factor. Interestingly, LF directly interacted with betaglycan (TGF-ß receptor III, TßRIII) and in turn induced phosphorylation of TßRI and Smad3 through formation of the TßRIII/TßRII/TßRI complex, leading to IgA isotype switching. Peroral administration of LF increased intestinal/serum IgA production as well as number of IgA plasma cells in lamina propria. Finally, we found that LF has an adjuvant activity when nontoxigenic Salmonella typhimurium was inoculated perorally, conferring protection against intragastrical infection of toxigenic S. typhimurium. These results suggest that LF has an important effect on the mucosal/systemic IgA response and can contribute to protection against intestinal pathogens.

The hemodynamic alterations induced by the vascular angular deformation in stent-assisted coiling of bifurcation aneurysms.

The hemodynamic changes induced by stent deployment and vascular remodeling in bifurcation aneurysms were investigated using computational fluid dynamics. The stent deployment reduced the intra-aneurysmal flow activity by decreasing the mean velocity, mean kinetic energy, mean wall shear stress, and mean vorticity. These hemodynamic parameters increased with an increase in the branching angle because of the vessel deformation caused by stent straightening. The maximum wall shear stress and its spatial gradient occurred near the neck of the aneurysm in the stented left daughter vessel, whereas a maximum oscillatory shear index was detected near the neck of the right aneurysm of the right daughter vessel. Theses parameters, which might be related to the recurrence of aneurysms, were also increased by stent-induced vessel deformation.

The facile and low temperature synthesis of nanophase hydroxyapatite crystals using wet chemistry.

A simple and facile wet chemistry route was used to synthesize nanophase hydroxyapatite (HaP) crystals at low temperature. The synthesis was carried out at a pH of 11.0 and at a temperature of 37°C. The resulting samples were washed several times and subjected to further analysis. XRD studies revealed that the HaP crystals were polycrystalline in nature with a crystallite size of ~15-60 ± 5 nm. SEM-EDXA images confirmed the presence of calcium (Ca), phosphorous (P), and oxygen (O) peaks. Likewise, FTIR confirmed the presence of characteristic phosphate and hydroxyl peaks in samples. Lastly, HRTEM images clearly showed distinctive lattice fringes positioned in the 100 and 002 planes. TGA analysis shows that HaP crystals can withstand higher calcination temperatures and are thermally stable.

Effect of carbon nanotube addition on the wear behavior of basalt/epoxy woven composites.

The effect of acid-treated carbon nanotube (CNT) addition on the wear and dynamic mechanical thermal properties of basalt/epoxy woven composites was investigated in this study. Basalt/CNT/epoxy composites were fabricated by impregnating woven basalt fibers into epoxy resin mixed with 1 wt% CNTs which were acid-treated. Wear and DMA (dynamic mechanical analyzer) tests were performed on basalt/epoxy composites and basalt/CNT/epoxy composites. The results showed that the addition of the acid-treated CNTs improved the wear properties of basalt/epoxy woven composites. Specifically, the friction coefficient of the basalt/epoxy composite was stabilized in the range of 0.5-0.6 while it fell in the range of 0.3-0.4 for basalt/CNT/epoxy composites. The wear volume loss of the basalt/CNT/epoxy composites was approximately 68% lower than that of the basalt/epoxy composites. The results also showed that the glass transition temperature of basalt/CNT/epoxy composites was higher than that of basalt/epoxy composites. The improvement of wear properties of basalt/epoxy composites by the addition of acid-treated CNTs was caused by the homogeneous load transfer between basalt fibers and epoxy matrix due to the reinforcement of CNTs.

Chitosan nanocomposite films: enhanced electrical conductivity, thermal stability, and mechanical properties.

A novel, high-performance Fe(3)O(4)/MWNT/Chitosan nanocomposite has been prepared by a simple solution evaporation method. A significant synergistic effect of Fe(3)O(4) and MWNT provided enhanced electrical conductivity, mechanical properties, and thermal stability on the nanocomposites. A 5% (wt) loading of Fe(3)O(4)/MWNT in the nanocomposite increased conductivity from 5.34×10(-5) S/m to 1.49×10(-2) S/m compared to 5% (wt) MWNT loadings. The Fe(3)O(4)/MWNT/Chitosan films also exhibited increases in tensile strength and modulus of 70% and 155%, respectively. The integral procedure decomposition temperature (IPDT) was enhanced from 501 °C to 568 °C. These effects resulted from a number of factors: generation of a greater number of conductive channels through interactions between MWNT and Fe(3)O(4) surfaces, a higher relative crystallinity, the antiplasticizing effects of Fe(3)O(4), a restricted mobility and hindrance of depolymerization of the Chitosan chain segments, as well as uniform distribution, improved dispersion, and strong interfacial adhesion between the MWNT and Chitosan matrix.

Dnmt1-dependent DNA methylation is essential for photoreceptor terminal differentiation and retinal neuron survival.

Epigenetic regulation of the genome is critical for the emergence of diverse cell lineages during development. To understand the role of DNA methylation during retinal network formation, we generated a mouse retinal-specific Dnmt1 deletion mutation from the onset of neurogenesis. In the hypomethylated Dnmt1-mutant retina, neural progenitor cells continue to proliferate, however, the cell cycle progression is altered, as revealed by an increased proportion of G1 phase cells. Despite production of all major retinal neuronal cell types in the Dnmt1-mutant retina, various postmitotic neurons show defective differentiation, including ectopic cell soma and aberrant dendritic morphologies. Specifically, the commitment of Dmnt1-deficient progenitors towards the photoreceptor fate is not affected by DNA hypomethylation, yet the initiation of photoreceptor differentiation is severely hindered, resulting in reduction and mislocalization of rhodopsin-expressing cells. In addition to compromised neuronal differentiation, Dnmt1 deficiency also leads to rapid cell death of photoreceptors and other types of neurons in the postnatal retina. These results indicate that Dnmt1-dependent DNA methylation is critical for expansion of the retinal progenitor pool, as well as for maturation and survival of postmitotic neurons.

Early bloodstream infection after pediatric living donor living transplantation.

To determine the perioperative risk factors for bacterial infections after pediatric living donor liver transplantation (LDLT), we investigated the clinical profiles of 149 children who underwent pediatric LDLT between 1994 and 2008. Bacterial infections were diagnosed based on guidelines proposed by the Centers for Disease Control. We observed 36 bloodstream infections (BSIs) in 32/149 (21.5%) patients (0.24 infections per patient), which, 21 (58.3%) BSIs in 19 patients were due to gram-positive and 15 (41.7%) in 13 patients to gram-negative organisms. The most common pathogens of early BSI were coagulase-negative Staphylococcus; (n = 11; 30.6%) and Klebsiella pneumoniae (n = 8; 22.2%). The most common site of early BSI was catheter-related (n = 14; 38.9%). Multivariate analysis showed that age ≤ 1 year (P < .05; odds ratio [OR] = 3.90; 95% CI, 1.83-15.26) and bile duct complications (P < .05; OR = 6.2, 95% CI = 3.21-35.23) were significant independent risk factors for early BSIs. More cautious management of pediatric LDLTs may be necessary for younger age children particularly with postoperative biliary complications.

De novo autoimmune hepatitis in Korean children after liver transplantation: a single institution's experience.

INTRODUCTION: De novo autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLT) has been described as a new type of late graft dysfunction in children who have not undergone transplantation for previous autoimmune liver disease. The purpose of this study was to evaluate the clinical aspects of de novo AIH among children following OLT. PATIENTS AND METHODS: Between January 1994 and May 2007, 149 children underwent OLT, including 1 with recurrent AIH who was excluded from this study, whereas 4 others developed de novo AIH (2.7%; n = 4/148). We analyzed the demographics, laboratory characteristics, and response to treatment of the 4 children with de novo AIH following OLT. RESULTS: The 4 patients were all girls with a median interval after OLT to presentation of 6.5 years (range, 0.7-8.8 years). The median age when de novo AIH developed was 12.4 years (range, 8.7-17.3 years). All cases were detected by abnormal liver function tests, namely, increased aspartate aminotransferase (AST; median, 322 IU/L; range, 181-919 IU/L). One patient showed elevated immunoglobulin G. Three patients displayed positive antinuclear antibodies. All were seronegative for smooth muscle antibody and liver-kidney microsomal type 1 antibody. One patient showed anti-mitochondrial antibody. All patients were treated with steroids with or without azathioprine. The liver function tests in these 4 patients, improved by at least 50% during the first month of treatment, responding to steroid treatment with or without azathioprine. CONCLUSION: In preadolescent or adolescent female patients with unexplained graft dysfunction after OLT, it is important to recognize de novo AIH rapidly and to develop an adequate diagnostic strategy, including evaluation of serum autoantibodies, immunoglobulin G, and liver biopsy.

Comparison of transnasal small-caliber vs. peroral conventional esophagogastroduodenoscopy for evaluating varices in unsedated cirrhotic patients.

BACKGROUND AND STUDY AIMS: We aimed to evaluate the accuracy of transnasal small-caliber esophagogastroduodenoscopy (TNSC-EGD) compared with peroral conventional EGD (POC-EGD) for evaluating varices in unsedated patients with liver cirrhosis. The success rate, safety, endoscopist satisfaction, and patient tolerability of TNSC-EGD were also addressed. PATIENTS AND METHODS: One hundred patients with liver cirrhosis participated in this randomized crossover trial, and 84 subjects completed both procedures. Of the 84 patients, 28 had marked bleeding diathesis (platelet count ≤ 50000/mm (3) and/or prothrombin time ≥ 1.7 INR). Endoscopists and patients answered questionnaires using a 100-mm visual analog scale about, respectively, their satisfaction and their tolerance of the procedure. RESULTS: The success rate of TNSC-EGD was comparable to that of POC-EGD (96% vs. 99%). Nasal mucosal hemorrhages induced by TNSC-EGD occurred in 5 patients (6%), but were easily controlled. Compared to the POC-EGD reference test, diagnostic accuracies of TNSC-EGD for detecting esophageal varices, gastric varices, and red color signs were 98%, 98%, and 96%, respectively. Concordance rates on grading esophageal varices and gastric varices were excellent at 93% (κ = 0.85) and 96% (κ = 0.87). Endoscopist satisfaction was not significantly different between TNSC-EGD and POC-EGD, whereas patient tolerance of TNSC-EGD was significantly greater than that of POC-EGD (79.0 ± 14.4 vs. 69.5 ± 16.1; P = 0.001). CONCLUSION: TNSC-EGD without sedation was found to be feasible, safe, and accurate for evaluating esophageal varices, gastric varices, and red color signs in patients with cirrhosis - even in those with marked bleeding diathesis. Furthermore, it was significantly better tolerated by patients, without altering endoscopist satisfaction. Our findings indicate that TNSC-EGD without sedation might be viewed as a potential alternative to POC-EGD for evaluation of varices.

Effects of silane modification and temperature on tensile and fractural behaviors of carbon nanotube/epoxy nanocomposites.

We investigated the effects of carbon nanotube (CNT) functionalization with silanes and temperature on the tensile and fractural characteristics of CNT/epoxy nanocomposites. Three groups of nanocomposites were fabricated using unmodified, oxidized and silanized CNTs, each at 0.1 wt%. Tensile and fractural tests were performed using the three nanocomposite samples at -30 degrees C, 20 degrees C, and 45 degrees C. Results showed that the tensile strength of silanized samples at -30 degrees C was about 89% and 241% higher, respectively, than at 20 degrees C and 45 degrees C. The elastic modulus of silanized CNT nanocomposite at -30 degrees C was about 52% and 871% higher, respectively, than at 20 degrees C and 45 degrees C. The fracture toughness of silanized samples was higher than those of unmodified and oxidized samples at all temperatures. However, fracture toughness decreased with decreasing temperature. Specifically, fracture toughness of silanized nanocomposites at -30 degrees C was about 76% and 117% lower, respectively, than those at 20 degrees C and 45 degrees C.