Using feasibility dose-volume histograms to reduce intercampus plan quality variability for head-and-neck cancer.

The purpose of this work is to objectively assess variability of intercampus plan quality for head-and-neck (HN) cancer and to test utility of a priori feasibility dose-volume histograms (FDVHs) as planning dose goals. In this study, 109 plans treated from 2017 to 2019 were selected, with 52 from the main campus and 57 from various regional centers. For each patient, the planning computed tomography images and contours were imported into a commercial program to generate FDVHs with a feasibility value (f-value) ranging from 0.0 to 0.5. For 10 selected organs-at-risk (OARs), we used the Dice similarity coefficient (DSC) to quantify the overlaps between FDVH and clinically achieved DVH of each OAR and determined the f-value associated with the maximum DSC (labeled as f-max). Subsequently, 10 HN plans from the regional centers were replanned with planning dose goals guided by FDVHs. The clinical and feasibility-guided auto-planning (FgAP) plans were evaluated using our institutional criteria. Among plans from the main campus and regional centers, the median f-max values were statistically significantly different (p < 0.05) for all OARs except for the left parotid (p = 0.622), oral cavity (p = 0.057), and mandible (p = 0.237). For the 10 FgAP plans, the median values of f-max were 0.21, compared to 0.37 from the clinical plans. With comparable dose coverage to the tumor volumes, the significant differences (p < 0.05) in the median f-max and corresponding dose reduction (shown in parenthesis) for the spinal cord, larynx, supraglottis, trachea, and esophagus were 0.27 (8.5 Gy), 0.3 (7.6 Gy), 0.19 (5.9 Gy), 0.19 (8.9 Gy), and 0.12 (4.0 Gy), respectively. In conclusion, the FDVH prediction is an objective quality assurance tool to evaluate the intercampus plan variability. This tool can also provide guideline in planning dose goals to further improve plan quality.

Research progress on antimicrobial materials for food packaging.

Microbial contamination is an utmost cause of food spoilage. Antimicrobial agents are used to treat microbial diseases in food. They also serve food packaging industry, as they are used for the formation of antimicrobial packaging films which maintain the structure, texture, color, and nutrition value of food. Due to ever growing population, the demands of food are also rising. There is need to stop food wastage and to prevent spoilage. Most of the food is spoiled during harvesting, transportation, and distribution. This is a serious problem to overcome. Adding antibacterial agents is the most convenient way to reduce food spoilage and contamination. To support the characteristics and properties of antibacterial materials, different modifications are performed in the field of food packaging, which is one of the most demanding techniques for food preservation. This review will summarize the research about antimicrobial agents, with an emphasis on recent findings, to highlight the importance of new developments in this field. Concepts of antimicrobial packaging with a focus on antibiotics and antibacterial agents are discussed briefly in this review, along with the different types of food packaging and applications of antimicrobial packaging. Synthetic and natural antimicrobial materials are described. In summary, this article will explain the importance of antibacterial agents and their use in food packaging industry. Furthermore, readers will get good information about natural antibacterial polymers which were extensively used in past few decades. Subsequently, different innovations should be done to control food spoilage and wastage to ensure food safety. Food packaging is a sole element that helps to provide safe and secure food for all.

Electrospun nanofibers food packaging: trends and applications in food systems.

Food safety is a bottleneck problem. In order to provide information about advanced and unique food packaging technique, this study summarized the advancements of electrospinning technique. Food packaging is a multidisciplinary area involving food science, food engineering, food chemistry, and food microbiology, and the interest in maintaining the freshness and quality of foods has grown considerably. For this purpose, electrospinning technology has gained much attention due to its unique functions and superior processing. Sudden advancements of electrospinning have been rapidly incorporated into research. This review summarized some latest information about food packaging and different materials used for the packaging of various foods such as fruits, vegetables, meat, and processed items. Also, the use of electrospinning and materials used for the formation of nanofibers are discussed in detail. However, in food industry, the application of electrospun nanofibers is still in its infancy. In this study, different parameters, structures of nanofibers, features and fundamental properties are described briefly, while polymers fabricated through electrospinning with advances in food packaging films are described in detail. Moreover, this comprehensive review focuses on the polymers used for the electrospinning of nanofibers as packaging films and their applications for variety of foods. This will be a valuable source of information for researchers studying various polymers for electrospinning for application in the food packaging industry.

Effect of Sonication Duration in the Performance of Polyvinyl Alcohol/Chitosan Bilayer Films and Their Effect on Strawberry Preservation.

In this study, we fabricated polyvinyl alcohol (PVA)/chitosan (CS) bilayer films by casting and investigated the effects of preparation conditions and CS content (2, 2.5, or 3 wt.%) on the ability of these films to preserve packaged strawberries. The best performance was achieved at a CS loading of 2.5 wt.% (ultrasound time, 25 min); the strain and stress values were 143.15 ± 6.43% and 70.67 ± 0.85 MPa, respectively, oxygen permeability was 0.16 ± 0.08 cm²·m²·day-1·MPa-1, water vapor permeability was 14.93 ± 4.09 g·cm-1·s-1·Pa-1, and the shelf life of fresh strawberries packaged in the PVA/CS 2.5 wt.% bilayer film was determined to be 21 days at 5 ± 2 °C and a relative humidity of 60 ± 5%. Treatment with PVA/CS bilayer films prevented the decrease in the firmness of strawberries during storage (21 days). The evaluated physicochemical parameters (weight loss, decay, firmness, titratable acidity, soluble solid content, ascorbic acid content, and color) indicated that treatment with PVA/CS bilayer films led to better maintenance of the fruit quality. We believe that our study makes a significant contribution to literature because it paves the way to the fabrication of smart packaging materials and facilitates the commercialization of fresh strawberries as an important health food.

Effect of Potassium Sorbate and Ultrasonic Treatment on the Properties of Fish Scale Collagen/Polyvinyl Alcohol Composite Film.

Composite films containing different amounts of potassium sorbate (KS) were prepared by using fish scale collagen (Col) and polyvinyl alcohol (PVA). Fourier transform infrared spectroscopy (FTIR), light transmittance, mechanical, water vapor transmission rate (WVTR), and the antibacterial properties of the composite films were analyzed. The results showed that the addition of Col significantly reduced the light transmittance of the composite film, but KS had no significant effect on the light transmission. The tensile strength decreased first and then increased with the addition of KS, while the WVTR increased first and then decreased. The composite film exhibited a certain degree of antibacterial properties against E. coli and S. aureus. In addition, we found that ultrasonic treatment reduced the WVTR, and also improved tensile strength and elongation at break of the composite films, but had no significant effect on other properties. The KS/Col/PVA films have the potential to be used as antimicrobial food packaging.

Effect of PLA/PBAT Antibacterial Film on Storage Quality of Passion Fruit during the Shelf-Life.

In this experiment, we studied the effect of poly(lactic acid)/poly(butylene adipate-co-terephthalate) (PLA/PBAT) blend films on the efficiency of passion fruit preservation at 20 °C. The weight loss, shrinkage index, firmness, and total sugar of passion fruit packaged with PLA/PBAT films had no significant differences compared with PE films during 21 days (p > 0.05). PLA/PBAT films can more effectively reduce the rising of ethanol content and delay the total acid, ascorbic acid, and sensory evaluation. Compared with unpackaged (CK) and polyethylene (PE) films, PLA/PBAT films are more conducive to preserve the overall flavor of passion fruit during storage time, in agreement with sensory evaluation, tested by E-nose, E-tongue, and GC-MS, which also proved that it can effectively maintain the edible quality of passion fruit during storage time. We believe that our study makes a significant contribution to literature because it paves the way to the generalization and application of packaging films based on composite antibacterial polymers and facilitates the commercialization of fresh passion fruit as an important health food.

Electrospun Polyvinyl Alcohol/d-Limonene Fibers Prepared by Ultrasonic Processing for Antibacterial Active Packaging Material.

Novel fibers containing different ratios of PVA and d-limonene were fabricated using electrospinning for antibacterial active packaging applications. The PVA/d-limonene fibers were thoroughly characterized using a scanning electron microscope, fourier-transform infrared spectrometry, thermal gravimetry, differential scanning calorimetry, tensile tests, and oxygen permeability tests. The results of these analyses showed that the highest tensile strength and elongation at break values of 3.87 ± 0.25 MPa and 55.62 ± 2.93%, respectively, were achieved for a PVA/d-limonene ratio of 7:3 (v/v) and an ultrasonication time of 15 min during processing. This material also showed the lowest oxygen permeation and the best degradability and bacteriostatic properties of all samples.

Thrombotic Microangiopathy in Inverted Formin 2-Mediated Renal Disease.

The demonstration of impaired C regulation in the thrombotic microangiopathy (TMA) atypical hemolytic uremic syndrome (aHUS) resulted in the successful introduction of the C inhibitor eculizumab into clinical practice. C abnormalities account for approximately 50% of aHUS cases; however, mutations in the non-C gene diacylglycerol kinase-ε have been described recently in individuals not responsive to eculizumab. We report here a family in which the proposita presented with aHUS but did not respond to eculizumab. Her mother had previously presented with a post-renal transplant TMA. Both the proposita and her mother also had Charcot-Marie-Tooth disease. Using whole-exome sequencing, we identified a mutation in the inverted formin 2 gene (INF2) in the mutational hotspot for FSGS. Subsequent analysis of the Newcastle aHUS cohort identified another family with a functionally-significant mutation in INF2 In this family, renal transplantation was associated with post-transplant TMA. All individuals with INF2 mutations presenting with a TMA also had aHUS risk haplotypes, potentially accounting for the genetic pleiotropy. Identifying individuals with TMAs who may not respond to eculizumab will avoid prolonged exposure of such individuals to the infectious complications of terminal pathway C blockade.

Medieval DNA from Soqotra points to Eurasian origins of an isolated population at the crossroads of Africa and Arabia.

Soqotra, an island situated at the mouth of the Gulf of Aden in the northwest Indian Ocean between Africa and Arabia, is home to ~60,000 people subsisting through fishing and semi-nomadic pastoralism who speak a Modern South Arabian language. Most of what is known about Soqotri history derives from writings of foreign travellers who provided little detail about local people, and the geographic origins and genetic affinities of early Soqotri people has not yet been investigated directly. Here we report genome-wide data from 39 individuals who lived between ~650 and 1750 CE at six locations across the island and document strong genetic connections between Soqotra and the similarly isolated Hadramawt region of coastal South Arabia that likely reflects a source for the peopling of Soqotra. Medieval Soqotri can be modelled as deriving ~86% of their ancestry from a population such as that found in the Hadramawt today, with the remaining ~14% best proxied by an Iranian-related source with up to 2% ancestry from the Indian sub-continent, possibly reflecting genetic exchanges that occurred along with archaeologically documented trade from these regions. In contrast to all other genotyped populations of the Arabian Peninsula, genome-level analysis of the medieval Soqotri is consistent with no sub-Saharan African admixture dating to the Holocene. The deep ancestry of people from medieval Soqotra and the Hadramawt is also unique in deriving less from early Holocene Levantine farmers and more from groups such as Late Pleistocene hunter-gatherers from the Levant (Natufians) than other mainland Arabians. This attests to migrations by early farmers having less impact in southernmost Arabia and Soqotra and provides compelling evidence that there has not been complete population replacement between the Pleistocene and Holocene throughout the Arabian Peninsula. Medieval Soqotra harboured a small population that showed qualitatively different marriage practices from modern Soqotri, with first-cousin unions occurring significantly less frequently than today.

Clinical Response of Nuberol Forte® for Pain Management With Musculoskeletal Conditions in Routine Pakistani Practice (NFORTE-EFFECT).

Background Musculoskeletal pain is the most common complaint presented to the health practitioner. It is well-known that untreated or under-treated pain can have a significant negative impact on an individual's quality of life (QoL). Objectives The current study aimed to assess the clinical response of Nuberol Forte® (paracetamol 650 mg + orphenadrine 50 mg) to musculoskeletal pain in routine Pakistani practice and its impact on improving the patient's QoL. Methods A prospective, observational multicenter study (NFORT-EFFECT: Safety & Efficacy of Nuberol Forte in Pain Management). Three hundred ninety-nine patients with known prescreened musculoskeletal pain were recruited from 10 major healthcare facilities across six (6) major cities of Pakistan, as per the inclusion/exclusion criteria. After the baseline visit (Visit 1), the patients were followed up one to two weeks (Visit 2) after the treatment as per the physician's discretion. Data were collected using the Case Report Form (CRF) designed for the study, and adverse events (AEs) were also monitored to assess drug safety. Pain intensity was assessed through a visual analog scale (VAS), and QoL was assessed using the Muscle and Joint Measure (MJM) scale. Results Out of 399 enrolled patients, 49.4% were males and 50.6% were females with a mean age of 47.24 ± 14.20 years. Most patients were presented with knee osteoarthritis (OA), i.e., 148 (38%), followed by backache 70 (18.2%). A significant reduction in the mean pain score was observed after treatment with the combination of paracetamol and orphenadrine (p<0.05). Furthermore, an overall improvement in the patient's QoL was also observed. During the study, only 10 patients reported mild adverse events (AEs), namely, dryness of the mouth, dizziness, gastric irritation, tachycardia, restlessness, etc. Conclusion The combination of paracetamol and orphenadrine (Nuberol Forte) exhibited effective pain management among patients with musculoskeletal conditions and improved their QoL.

An Overview on Rumex dentatus L.: Its Functions as a Source of Nutrient and Health-Promoting Plant.

Rumex dentatus L. (Polygonaceae), also known as toothed dock or Aegean dock, is a medicinal plant with a high culinary value in addition to being used as an ethnomedicinal plant. This review focuses on the botanical, nutritional, phytochemical, and pharmacological activities of R. dentatus, as well as the future prospects for systematic investigations into these areas. R. dentatus has been subjected to scientific evaluation, which has confirmed its traditional uses and demonstrated a wide range of biological and pharmacological potentials, including antioxidant, anticancer, antifungal, antibacterial, anti-inflammatory, and other biological properties. Phytochemical analyses showed the presence of anthraquinones, chromones, flavonoids, and essential oils. As a result of this current review, the medicinal significance of R. dentatus has been confirmed, and future research on its unexplored aspects, such as the identification of pharmacologically active chemical constituents and related mechanisms and safety, may be stimulated, with the goal of developing it into a drug.

Preparation of polylactic acid/TiO2/GO nano-fibrous films and their preservation effect on green peppers.

Polylactic acid (PLA)/nano-TiO2(TiO2 NPs)/Graphene oxide (GO) nano-fibrous films were prepared by ultrasonic assisted electrostatic spinning technology, and the effects of TiO2 NPs:GO mass ratio and ultrasonic power on film morphology and mechanical, thermal, barrier and antibacterial properties were investigated. The addition of TiO2 NPs and GO can significantly increase the tensile strength and elongation at the break of PLA nano-fibrous films, and improve the water barrier properties of the nano-fibrous films. The antibacterial experiment showed that the inhibition rates of the nano-fibrous films against Escherichia coli and Staphylococcus aureus after 24 h exposure to UV irradiation reached 94.4 ± 1.8% and 92.6 ± 1.7% At the same time, the fresh-keeping packaging experiment of green peppers at room temperature, through the determination of hardness, soluble solids, chlorophyll content to determine the degree of decay of green pepper, it showed that PLA/TiO2 NPs/GO nano-fibrous films can better maintain the sensory quality of green peppers, delay the rate of spoilage of green peppers, and prolong the preservation period of green peppers.

Development and optimization of dynamic gelatin/chitosan nanoparticles incorporated with blueberry anthocyanins for milk freshness monitoring.

In this study, we prepared gelatin and chitosan as wall materials, and composites with a controlled release capability in a weak acidic environment were synthesized for loading and protecting anthocyanins. Fourier-transform infrared spectroscopy and scanning electron microscopy were used to assess the properties of the nanoparticles. The loading efficiencies and oxidation resistances of the proposed substances were measured. Under optimal conditions, the anthocyanins exhibited a loading efficiency of 83.81 %, and suitable long-term storage capacity at room temperature with a retention rate of ∼50 % after 15 d. When the nanoparticles were used for detecting the milk freshness, spoiled milk exhibited a reddish color, whereas the color of fresh milk did not change. Moreover, these nanoparticles exhibited a stable chroma in milk for 0-16 h. Therefore, the proposed pH responsive nanoparticles can provide a possibility for the dynamic monitoring of milk quality changes, or provide some reference value for future related research.

Designing, structural determination and biological effects of rifaximin loaded chitosan- carboxymethyl chitosan nanogel.

Due to the poor solubility and permeability of rifaximin (RFX), it is not effective against intracellular pathogens although it shows strong activity against most bacteria. To develop an effective mucoadhesive drug delivery system with a targeted release in bacterial infection site, RFX-loaded chitosan (CS)/carboxymethyl-chitosan (CMCS) nanogel was designed and systematically evaluated. FTIR, DSC, and XRD demonstrated that the nanogel was formed by interactions between the positively charged NH3+ on CS and CMCS, and the negatively charged COO on CMCS. RFX was encapsulated into the optimized nanogel in amorphous form. The nanogel was a uniform spherical shape with a mean diameter of 171.07 nm. It had excellent sustained release, strong mucin binding ability, and pH-responsive properties of quicker swelling and release at acidic pH. It showed low hemolytic ratio and high antioxidant activity. The present investigation indicated that the CS-nanogel could be potentially used as a promising bacterial responsiveness drug delivery system.

Current trends in polymer microneedle for transdermal drug delivery.

Transdermal drug delivery using microneedles is increasingly gaining interest due to the issues associated with oral drug delivery routes. Gastrointestinal route exposes the drug to acid and enzymes present in the stomach, leading to denaturation of the compound and resulting in poor bioavailability. Microneedle transdermal drug delivery addresses the problems linked to oral delivery and to relieves the discomfort of patients associated with injections to increase patient compliance. Microneedles can be broadly classified into five types: solid microneedles, coated microneedles, dissolving microneedles, hollow microneedles, and hydrogel-forming microneedles. The materials used for the preparation of microneedles dictate the different applications and features present in the microneedle. Polymeric microneedle arrays present an improved method for transdermal administration of drugs as they penetrate the skin stratum corneum barrier with minimal invasiveness. The review summarizes the importance of polymeric microneedle and discussed some of the most important therapeutic drugs in research, mainly protein drugs, vaccines and small molecule drugs in regenerative medicine.

Polymeric Nanoparticles for Brain Drug Delivery - A Review.

BACKGROUND: Blood-brain barrier (BBB) plays a most hindering role in drug delivery to the brain. Recent research comes out with the nanoparticles approach, is continuously working towards improving the delivery to the brain. Currently, polymeric nanoparticle is extensively involved in many therapies for spatial and temporal targeted areas delivery. METHODS: We did a non-systematic review, and the literature was searched in Google, Science Direct and PubMed. An overview is provided for the formulation of polymeric nanoparticles using different methods, effect of surface modification on the nanoparticle properties with types of polymeric nanoparticles and preparation methods. An account of different nanomedicine employed with therapeutic agent to cross the BBB alone with biodistribution of the drugs. RESULTS: We found that various types of polymeric nanoparticle systems are available and they prosper in delivering the therapeutic amount of the drug to the targeted area. The effect of physicochemical properties on nanoformulation includes change in their size, shape, elasticity, surface charge and hydrophobicity. Surface modification of polymers or nanocarriers is also vital in the formulation of nanoparticles to enhance targeting efficiency to the brain. CONCLUSION: More standardized methods for the preparation of nanoparticles and to assess the relationship of surface modification on drug delivery. While the preparation and its output like drug loading, particle size, and charge, permeation is always conflicted, so it requires more attention for the acceptance of nanoparticles for brain delivery.

Association between ENAM polymorphisms and dental caries in children.

AIM: Dental enamel, the most rigid biological tissue of the tooth known to mankind, is the most integral and fundamental part of the tooth. Enamel matrixes compile 5% of Enamelin peptides and at the time of tooth development, they are considered to effect the formation and elongation of enamel crystallites. ENAM plays critical role in enamel formation. Any changes in ENAM may affect the thickness of enamel and may lead to dental caries. The present study is aimed to evaluate the association of ENAM gene polymorphisms and susceptibility of dental caries development risk. MATERIAL AND METHODS: The present study was carried out on 168 South Indian children, children's with dental caries were included in study. Written consent was taken from their parents/guardians. Additionally 193 healthy individuals were enrolled as controls. Sampling was done after dental examination of the individuals. Three ENAM gene single nucleotide polymorphisms (SNPs) were rs7671281, rs3796704 and rs12640848 was genotyped to check their role in susceptibility of dental caries development risk. RESULTS: Out of three SNPs rs7671281 showed statistically significant risk association with dental caries susceptibility in this ethnic population at heterozygous allele CT (OR: 1.939, p = .01865) and with minor allele T (OR: 1.451, p = .001292). SNP rs3796704 showed significant protective association with dental caries in Indian population at heterozygous allele GA (OR: 0.409, p = .0192) and with minor allele A (OR: 0.645, p = .00875). SNP rs12640848 showed significant protective association with dental caries in Indian population at heterozygous allele AG (OR: 3.041, p = .00642) and with minor allele G (OR: 1.478, p = .02184). Preliminary insilico analysis also showed that rs7671281 (Ile648Thr) amino acid change will cause the structural and functional changes in ENAM protein. CONCLUSIONS: In the present study significant association was observed between ENAM gene SNP rs7671281 and dental caries susceptibility in South Indian children. These results suggested that ENAM gene variants may contribute to dental caries in children.

Carbon fiber paper@MgO films: in situ fabrication and high-performance removal capacity for phosphate anions.

Porous magnesium oxide (MgO) films on carbon fiber paper (CF) have been successfully fabricated in a hydrothermal route at different calcination temperatures. The CF@MgO samples (CF@MgO-300, -400, and -500) show different morphologies with the increasing surface area from 3 for CF to 27 m2 g-1 for CF@MgO-400. Among the four investigated samples, the CF@MgO-400 exhibits the highest phosphate removal ability (~ 1230 mg g-1) with promising applications for the large-scale utilization at low cost.

A Randomized Trial of Iloperidone for Prevention of Relapse in Schizophrenia: The REPRIEVE Study.

BACKGROUND: The purpose of this study was to evaluate the safety and effectiveness of iloperidone for the prevention of relapse in schizophrenia. METHODS: Study subjects were adults with schizophrenia who started on oral open-label iloperidone titrated to an initial target dose of 12 mg/day (6 mg twice daily) and then stabilized on a flexible-dose iloperidone regimen (range 8-24 mg/day) for up to 24 weeks. Subjects meeting stabilization criteria then entered the relapse-prevention phase and were randomized 1:1 in a double-blind fashion to continue with iloperidone or placebo withdrawal for up to 26 weeks or until meeting relapse or other withdrawal criteria. RESULTS: A total of 303 subjects were randomized to the relapse-prevention phase; 153 continued to receive iloperidone, and 150 were withdrawn to placebo. The modal total daily dose for iloperidone in all phases of the study was 12 mg/day. The pre-defined unblinded interim analysis upon reaching 68 relapse events confirmed the hypothesis that iloperidone (n = 97) was more effective than placebo (n = 96) in preventing relapse events, and the trial was stopped early. The estimated relapse rates were 63.4 % (Kaplan-Meier [KM] estimate) for placebo compared with 20.4 % (KM estimate) for those continuing to receive iloperidone (log rank test: p < 0.0001). The mean time to relapse was 71 days for placebo and 139 days for iloperidone (hazard ratio 4.7; 95 % confidence interval 2.7-8.3; p < 0.0001). The safety profile observed in previous short-term studies was also reaffirmed in this maintenance treatment setting. The most common treatment-emergent adverse events (TEAEs) in the stabilization phase were dizziness (11.6 %), somnolence (8.3 %), and dry mouth (6.8 %). Rates of reported extrapyramidal disorder or akathisia during stabilization were 2.5 and 3.7 %, respectively. CONCLUSIONS: Flexible dosing of iloperidone for maintenance-phase therapy, with a modal dose of 12 mg/day was effective in preventing relapse in subjects previously stabilized on iloperidone. The adverse event profile for iloperidone was consistent with other studies, and the low extrapyramidal symptom and akathisia burden during stabilization was sustained during the course of the study. ClinicalTrials.gov identifier: NCT01291511.

Ethyl cellulose-based solid matrix system for sustaining release of naproxen.

The present study was conducted to develop sustained release matrix tablets of naproxen with the help of a hydrophobic polymer, Ethyl Cellulose (EC). Matrix tablets were prepared by incorporating various proportions of EC in the matrix system using wet granulation technique. The rate of drug release from the matrix tablets was found to be very slow and could not produce the desired release profiles in 12 h testing time. However, the tablets prepared by slightly modifying the wet granulation method exhibited comparatively linear and desirable release rate. No significant difference in the release profiles of naproxen matrix tablets was observed at different stirring speeds and storage conditions.