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Background: The benefits of caffeine to physical performance have been extensively demonstrated, however, it has recently been speculated that there is an effect of the administration route on its effectiveness. Purpose: The current study investigated the effect of caffeine mouth rinse in isolation or combined with ingestion on performance in a 30-minute constant-load exercise followed by a 10-km cycling time trial. Methods: Ten physically active men performed a 30-minute constant-load exercise at 50% of the graded test Wmax, followed by a 10-km cycling time trial. Before and at the middle points of the constant-load exercise and 10-km cycling time trial, the following conditions were administered: PLA (cellulose ingestion plus mouth rinsing with magnesium sulfate), ING (5 mg.kg -1 of caffeine ingestion plus mouth rinsing with magnesium sulfate), MR (cellulose ingestion plus mouth rinsing with 1.2% caffeine), and COMB (5 mg.kg -1 of caffeine ingestion plus mouth rinsing with 1.2% caffeine). Results: During the 30-minute constant-load exercise, COMB presented a lower rating of perceived exertion (RPE) than MR ( p  = .04). For the 10-km time trial, the COMB was faster than MR (MR = 1363 ± 345 vs. COMB = 1291 ± 308s, Δ% = 5.57, p  = .05). Mean power output was higher in COMB than PLA, ING, and MR (234 ± 15 vs. 169 ± 29, 148 ± 11, and 145 ± 12 W, respectively). There were no differences between conditions for heart rate and RPE during the 10-km time trial. Conclusion: In summary, caffeine mouth rinsing potentiated the effects of caffeine ingestion during the 10-km time trial compared to caffeine mouth rinsing alone.

Tobacco stalk is a cellulose-rich material and a sustainable alternative to be applied as a plant-based nanofibrillated cellulose (NFC) source. NFC use has garnered attention in the development of oral pharmaceutical forms, despite concerns about its safety due to the adverse effects of nicotine on health. Therefore, we aimed at establishing the safety of NFC derived from tobacco stalk for its potential use as a novel pharmaceutical excipient, exploring its potential functions for tablet production. We conducted acute and subchronic oral toxicity tests in adult female Wistar rats. Initially, individual animals received sequential doses (175-5,000 mg·kg -1 ) for 24 hours followed by a careful observation of any toxic effects. Subsequently, 20 rats were divided into four groups for a subchronic assay, evaluating toxicity signs, body weight changes, hematological, biochemical, and histopathological parameters. No deaths or other clinical toxicity signs were observed in either the acute or the subchronic assays. We noticed a significant reduction in body weight gain (p < 0.05) after 14 days. We found statistical differences for hematological and biochemical parameters, unrelated to dosage. There were no observed toxic effects, and tobacco stalk ingestion did not adversely affect organ morphology in the histopathological evaluation. The oral administration of NFC at 5,000 mg·kg -1 per day for 28 days was well-tolerated by treated rats, with no reported deaths. In conclusion, NFC derived from tobacco stalk has shown to be a sustainable and safe alternative for use as an excipient at experimental doses, demonstrating compatibility with its proposed applications.

Purpose: To evaluate using a biocellulose-based hydrogel as an adjuvant in the healing process of arterial ulcers., Methods: A prospective single group quasi-experimental study was carried out with chronic lower limb arterial ulcer patients. These patients received biocellulose-based hydrogel dressings and outpatient guidance on dressing and periodic reassessments. The primary outcomes were the ulcer-healing rate and product safety, which were assessed by ulcer area measured in photographic records of pre-treatment and posttreatment after 7, 30, and 60 days. Secondary outcomes were related to clinical assessment by the quality-of-life scores (SF-36 and EQ-5D) and pain, evaluated by the visual analogue scale (VAS)., Results: Seventeen participants were included, and one of them was excluded. Six patients (37%) had complete wound healing, and all patients had a significant reduction in the ulcer area during follow-up (233.6mm2 versus 2.7mm2) and reduction on the score PUSH 3.0 (p < 0.0001). The analysis of the SF-36 and EQ-5D questionnaires showed a statistically significant improvement in almost all parameters analyzed and with a reduction of pain assessed by the VAS., Conclusions: The biocellulose-based hydrogel was safe and showed a good perspective to promoting the necessary conditions to facilitate partial or complete healing of chronic arterial ulcers within a 60-day follow-up. Quality of life and pain were positively affected by the treatment.

Chronic dietary protein-restriction can create essential amino acid deficiencies and induce metabolic adaptation through the hepatic FGF21 pathway which serves to maintain host fitness during prolonged states of nutritional imbalance. Similarly, the gut microbiome undergoes metabolic adaptations when dietary nutrients are added or withdrawn. Here we confirm previous reports that dietary protein-restriction triggers the hepatic FGF21 adaptive metabolic pathway and further demonstrate that this response is mediated by the gut microbiome and can be tuned through dietary supplementation of fibers that alter the gut microbiome. In the absence of a gut microbiome, we discover that FGF21 is de-sensitized to the effect of protein-restriction. These data suggest that host-intrinsic adaptive pathways to chronic dietary protein-restriction, such as the hepatic FGF21 pathway, may in-fact be responding first to adaptive metabolic changes in the gut microbiome.

Background: The objective of the present study was co-delivery of venlafaxin (VEN) and doxycycline (DOX), a matrix metalloproteinase inhibitor drug, for alleviating inflammation and neuropathy in diabetic foot ulcer (DFU)., Methods: Bacterial cellulose nanofiber sheets (BCNS) were loaded with DOX and VEN and categorized by their loading efficiency, release profiles and ex vivo permeation throughrat skin. The optimized nanofibers were used in patients with DFU to compare with the standard wound care regimen during a 12-week trial. Wound area was measured every 2 weeks. Biochemical parameters and microscopic studies of the skin were examined prior and at the end of the treatment. The Michigan Neuropathy Screening Instrument (MNSI) questionnaire was utilized to assess diabetic neuropathy., Results: The optimum formulation showed loading efficiency of 37.8 ± 1.6% for DOX and 48 ± 1.9% for VEN. Rat skin permeation was 40% for DOX after 7-29 h and 83% for VEN during 105 h. Patients treated with BCNS showed no significant difference in their biochemical parameters before and after intervention. The ulcer size showed faster reduction after 12 weeks in the treatment group compared to the control group. The abnormal responses in the MNSI questionnaire decreased and pain-free walking distance increased significantly in the treatment group compared with the control group (p < 0.001). Microscopic studies of the skin after using nanofibers showed a large number of polymorphonuclear chronic inflammatory cells and formation of new capillary beds., Conclusions: The BCNS loaded with DOX and VEN may expedite healing and reduce neuropathy in the DFU of diabetic patients.

Background: In facial contour surgery, due to the narrow field of vision in the oral approach and the abundant blood supply to the maxillofacial area, hemostasis is not easy. The purpose of this study was to evaluate the hemostatic effect of soluble hemostatic gauze., Methods: We organized a prospective randomized study of 282 patients receiving facial contouring surgery (4 types of procedures in total) during 2016.1.1 to 2018.12.30. For each type of procedure, patients were randomly divided into study group (received hemostatic gauze) and control group (received sterile gauze). Two groups were compared for each type of procedure regarding 5 major perioperative variables: intraoperative blood loss, operation time, 24-hour postoperative drainage volume, total postoperative drainage volume, and postoperative drainage time. Correlation between variables was analyzed., Results: Compared with control group, the study group had higher amount of intraoperative blood loss in mandibular angle ostectomy (MAO) (P < .01) and mandibular angle-body-chin curved ostectomy procedures (P < .05), less total postoperative drainage volume in MAO (P < .01) but not in malarplasty with MAO and partial masseter muscle resection along with MAO procedures. No significant difference was observed between respective study and control groups regarding operation time, 24-hour postoperative drainage volume, and postoperative drainage time in any of the 4 types of surgery. In all 4 types of procedures, a strongly positive correlation was observed between total drainage volume and 24-hour drainage volume in both the study and control groups (r: 0.88-0.97, P < .01)., Conclusion: The effect of hydroxyethyl cellulose soluble hemostatic gauze on hemostasis in facial contouring surgery is associated with the type of surgery, which can reduce the risk of postoperative bleeding in MAO. However, for surgery with relatively large amount of intraoperative and postoperative bleeding, the hemostatic gauze had a limited postoperative hemostasis efficacy, which needs further evaluation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Poly-l-lactic acid (PLLA) is an injectable volumizer with biostimulatory properties used for volumetric structural rejuvenation in patients with facial fat volume loss but has increasingly been utilized for off-face applications., Objective: The objectives of this randomized, double-blind, placebo-controlled single center study was to assess the safety and effectiveness of PLLA for the treatment of lower extremity cellulite in adult women., Methods: 31 healthy women were enrolled in the study. Eligible subjects received 3 treatments every 4 weeks with either PLLA (treatment group) or saline (control group) injections combined with subcision, into each of the glutes or thighs. Follow-up visits were at 1, 3, and 6 months after treatment. Assessments included live ratings, rating of standardized pictures by a blinded evaluator, patient questionnaires, safety, and tolerability ratings., Results: At the 3 and 6-month follow-up, there was a statistically significant change in the global aesthetic improvement scale (GAIS) compared to baseline as assessed by blinded investigators. Significant improvements were shown in the cellulite severity scale (CSS) as well as in the subject satisfaction questionnaires. Treatments were found to be tolerable, and no severe treatment-related adverse events occurred., Conclusion: Repeated PLLA treatments combined with subcision are effective and safe in improving the appearance of cellulite. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5380.

The effects of arabinoxylan (AX)-rich rye bran based diet (RB) and antibiotics on digestion, fermentation and short-chain fatty acids (SCFA) absorption were studied compared with an iso-dietary fibre (DF) cellulose based diet (CEL). Thirty female pigs (body weight 72.5 ± 3.9 kg) were fed a standard swine diet in week 1, CEL as wash-out for bran-associated bioactive components in week 2 and then divided into 3 groups fed either the CEL (n = 10) or RB (n = 20) for 2 weeks, where 10 pigs from RB had daily intramuscular antibiotic injections (RB+) and the other 10 pigs were untreated (RB-) in week 4. In RB, the degradation of AX mainly occurred in caecum and proximal colon (P < 0.01) and to a higher extent than cellulose, which on the other hand, irrespective of antibiotic treatment, was less degraded in the RB groups than in the CEL (P < 0.01). The apparent digestibility of fat and protein in the distal small intestine was lower for RB than CEL (P < 0.05), the protein digestibility remained lower in most of the colon, and the digestibility was not affected by treatment with antibiotics. The colonic concentrations of SCFA, acetate and propionate as well as the butyrate concentration in the distal colon were lower with the RB treatments compared with CEL (P < 0.01). Caecal butyrate concentrations were on the other hand higher, and a significant reduction was seen with antibiotic treatment (P < 0.001). The daily net absorption of SCFA and acetate was lower with RB than with CEL (P < 0.01). In conclusion, RB resulted in different DF degradation processes and SCFA production compared with CEL, whereas antibiotic treatment had marginal effects on the intestinal DF degradation but hampered butyrate production.

Background: This is a updated version of our Cochrane Review published in Issue 6, 2012. Sexually-transmitted infections (STIs) continue to rise worldwide, imposing an enormous morbidity and mortality burden. Effective prevention strategies, including microbicides, are needed to achieve the goals of the World Heath Organization (WHO) global strategy for the prevention and control of these infections., Objectives: To determine the effectiveness and safety of topical microbicides for preventing acquisition of STIs, including HIV., Search Methods: We undertook a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CLIB, Web of Science, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and reference lists of relevant articles up to August 2020. In addition, we contacted relevant organisations and experts., Selection Criteria: We included randomised controlled trials of vaginal microbicides compared to placebo (except for nonoxynol-9 because it is covered in related Cochrane Reviews). Eligible participants were sexually-active non-pregnant, WSM and MSM, who had no laboratory confirmed STIs., Data Collection and Analysis: Two review authors independently screened and selected studies, extracted data, and assessed risks of bias in duplicate, resolving differences by consensus. We conducted a fixed-effect meta-analysis, stratified by type of microbicide, and assessed the certainty of the evidence using the GRADE approach., Main Results: We included eight trials from the earlier version of the review and four new trials, i.e. a total of 12 trials with 32,464 participants (all WSM). We did not find any eligible study that enrolled MSM or reported fungal STI as an outcome. We have no study awaiting assessment. All 12 trials were conducted in sub-Saharan Africa, with one having a study site in the USA, and another having a site in India. Vaginal microbicides tested were BufferGel and PRO 2000 (1 trial, 3101 women), Carraguard (1 trial, 6202 women), cellulose sulphate (2 trials, 3069 women), dapivirine (2 trials, 4588 women), PRO 2000 (1 trial, 9385 women), C31G (SAVVY) (2 trials, 4295 women), and tenofovir (3 trials, 4958 women). All microbicides were compared to placebo and all trials had low risk of bias. Dapivirine probably reduces the risk of acquiring HIV infection: risk ratio (RR) 0.71, (95% confidence interval (CI) 0.57 to 0.89, I 2 = 0%, 2 trials, 4588 women; moderate-certainty evidence). The other microbicides may result in little to no difference in the risk of acquiring HIV (low-certainty evidence); including tenofovir (RR 0.83, 95% CI 0.68 to 1.02, cellulose sulphate (RR 1.20, 95% CI 0.74 to 1.95, BufferGel (RR 1.05, 95% CI 0.73 to 1.52), Carraguard (RR 0.89, 95% CI 0.71 to 1.11), PRO 2000 (RR 0.93, 95% CI 0.77 to 1.14), and SAVVY (RR 1.38, 95% CI 0.79 to 2.41). Existing evidence suggests that cellulose sulphate (RR 0.99, 95% CI 0.37 to 2.62, 1 trial, 1425 women), and PRO 2000 (RR 0.95, 95% CI 0.73 to 1.23) may result in little to no difference in the risk of getting herpes simplex virus type 2 infection (low-certainty evidence). Two studies reported data on tenofovir's effect on this virus. One suggested that tenofovir may reduce the risk (RR 0.55, 95% CI 0.36 to 0.82; 224 participants) while the other did not find evidence of an effect (RR 0.94, 95% CI 0.85 to 1.03; 1003 participants). We have not reported the pooled result because of substantial heterogeneity of effect between the two studies (l 2 = 85%). The evidence also suggests that dapivirine (RR 1.70, 95% CI 0.63 to 4.59), tenofovir (RR 1.27, 95% CI 0.58 to 2.78), cellulose sulphate (RR 0.69, 95% CI 0.26 to 1.81), and (Carraguard (RR 1.07, 95% CI 0.75 to 1.52) may have little or no effect on the risk of acquiring syphilis (low-certainty evidence). In addition, dapivirine (RR 0.97, 95% CI 0.89 to 1.07), tenofovir (RR 0.90, 95% CI 0.71 to 1.13), cellulose sulphate (RR 0.70, 95% CI 0.49 to 0.99), BufferGel (RR 0.97, 95% CI 0.65 to 1.45), Carraguard (RR 0.96, 95% CI 0.83 to 1.12), and PRO 2000 (RR 1.01, 95% CI 0.84 to 1.22) may result in little to no difference in the risk of acquiring chlamydia infection (low-certainty evidence). The evidence also suggests that current topical microbicides may not have an effect on the risk of acquiring gonorrhoea, condyloma acuminatum, trichomoniasis, or human papillomavirus infection (low-certainty evidence). Microbicide use in the 12 trials, compared to placebo, did not lead to any difference in adverse event rates. No study reported on acceptability of the intervention.  AUTHORS' CONCLUSIONS: Current evidence shows that vaginal dapivirine microbicide probably reduces HIV acquisition in women who have sex with men. Other types of vaginal microbicides have not shown evidence of an effect on acquisition of STIs, including HIV. Further research should continue on the development and testing of new microbicides., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Chitosan-based hydrogels have received significant interest in tissue engineering and regenerative medicine applications owing to their superior biocompatibility. However, their applications are restricted owing to their weak mechanical strength. Cellulose nanocrystals (CNCs) are often explored as reinforcing agents to improve the native properties of polymers owing to their superior physicochemical properties. We fabricated a multi-functional hydrogel scaffold of chitosan/CNCs by incorporating different amounts of CNCs into a chitosan (CH) hydrogel. Significant enhancement in the mechanical strength was noted in the CH/CNCs as compared to that in pure CH hydrogel scaffolds. The cytocompatibility of the fabricated scaffolds was monitored in the presence of bone-marrow-derived mesenchymal stem cells (BMSCs). Improved cell viability and mineralization were observed with CH/CNC hydrogel scaffolds than those with pure CH hydrogel scaffolds. Enhanced osteogenic-related gene expression was observed in the CH/CNC hydrogel scaffold environment than that in the control, indicating their osteogenic potential, in addition to enhanced antibacterial activity. Developed composite scaffolds exhibited improved sustained drug release compared to that by pure polymer scaffolds, and this was more sustained in the scaffolds with higher CNC content. Therefore, the fabricated scaffolds may have been used in tissue engineering for osteogenesis, as antibacterial agents, and in sustained drug delivery., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier B.V.)

This study targets to develop curcumin-loaded polyvinyl alcohol/cellulose nanocrystals (PVA/CNCs) membrane as localized delivery system for breast/liver cancer. A novel strategy was developed for enhancing encapsulation capacity and maximizing therapeutic efficiency of curcumin-loaded PVA/CNCs membranes. Membranes were prepared by solution-casting method using citric acid as crosslinker. SEM revealed that PVA/CNCs ratio (80:20) was chosen as the optimum for loading curcumin. FT-IR indicated that, curcumin was incorporated into PVA/CNCs in amorphous-phase via intermolecular hydrogen bond between curcumin and membrane components. Curcumin showed biphasic-release through burst-release of 41% of curcumin during the first hour, followed by sustained-release of 70% and 94% during 24 h and 48 h, respectively. In vitro cytotoxicity of PVA/CNCs/Curcumin membrane exhibited a selective inhibition proliferation of breast and liver cancer cells in a concentration-dependent without any toxic effect on normal cells. At high concentration (8 mg/ml) of PVA/CNCs/Curcumin, reduced viability to 35% and 7% of MCF-7 and Huh-7 cells, respectively; meanwhile high HFB-4 normal cell viability ≥80% was investigated. Antimicrobial activity of PVA/CNCs/Curcumin was investigated by multi-drug-resistant strains, and MIC values. PVA/CNCs/Curcumin membranes with concentration (40 mg/ml) showed broad-spectrum antimicrobial activities, thus inhibited ~96-99% of microbial growth. PVA/CNCs/Curcumin membranes could be as promised anti-infective biomaterials for breast and liver cancer wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Cellulose nanocrystals (CNC) are linear organic nanomaterials derived from an abundant naturally occurring biopolymer resource. Strategic modification of the primary and secondary hydroxyl groups on the CNC introduces amine and iodine group substitution, respectively. The amine groups (0.285 mmol of amine per gram of functionalized CNC (fCNC)) are further reacted with radiometal loaded-chelates or fluorescent dyes as tracers to evaluate the pharmacokinetic profile of the fCNC in vivo. In this way, these nanoscale macromolecules can be covalently functionalized and yield water-soluble and biocompatible fibrillar nanoplatforms for gene, drug and radionuclide delivery in vivo. Transmission electron microscopy of fCNC reveals a length of 162.4 ± 16.3 nm, diameter of 11.2 ± 1.52 nm and aspect ratio of 16.4 ± 1.94 per particle (mean ± SEM) and is confirmed using atomic force microscopy. Size exclusion chromatography of macromolecular fCNC describes a fibrillar molecular behavior as evidenced by retention times typical of late eluting small molecules and functionalized carbon nanotubes. In vivo, greater than 50% of intravenously injected radiolabeled fCNC is excreted in the urine within 1 h post administration and is consistent with the pharmacological profile observed for other rigid, high aspect ratio macromolecules. Tissue distribution of fCNC shows accumulation in kidneys, liver, and spleen (14.6 ± 6.0; 6.1 ± 2.6; and 7.7 ± 1.4% of the injected activity per gram of tissue, respectively) at 72 h post-administration. Confocal fluorescence microscopy reveals cell-specific accumulation in these target tissue sinks. In summary, our findings suggest that functionalized nanocellulose can be used as a potential drug delivery platform for the kidneys.

Previous data suggested the potential treatment effect of a proprietary quail eggs-based blend on allergic rhinitis (AR) symptoms, induced by allergen challenge. We herein aimed to investigate the efficacy and safety of a similar dietary supplement, comprising the bioactive ingredients of quail eggs and the zinc mineral, in the setting of active AR. Adult patients ( n  = 77), aged 18- 60 years, with mild, intermittent AR were enrolled in this single-arm, open-label trial. Patients' responses were assessed based on peak nasal inspiratory flow (PNIF) measurements at two visits (Day 1/Visit 1 and Day 7/Visit 2) and self-rating of AR-associated symptoms on a Visual Analog Scale (VAS) throughout the entire 7-day study period. PNIF values at 15, 30, 60, 90 and 120 min (Visit 1) following administration of an oral dose of the study product were the primary efficacy endpoint. PNIF values (Visit 1) gradually increased from baseline (pre-treatment), with statistical significance first reached 30 min later ( p  = 0.002). VAS scores (Visit 1) for all AR symptoms gradually decreased with statistical significance first reached at 15 min (rhinorrhea, p  = 0.042; itchy nose, p  = 0.001; sneezing p  < 0.001), 30 min (nasal congestion, p  < 0.001; itchy eyes, p  = 0.003) or 60 min (watery eyes, p  = 0.04). PNIF improvement and decline of VAS scores were significantly more apparent at Visit one vs. Visit 2. Treatment-emergent adverse events were limited to cough and muscle strain (one patient each). Our results support the efficacy, rapid mode of action and tolerability of the investigated product for symptomatic treatment of mild intermittent AR.

Background: Since the approval of Sculptra Aesthetic, the amount of sterile water used to reconstitute the product has gradually increased in clinical practice. A retrospective chart review was conducted to evaluate patient safety associated with a larger reconstitution volume, and to investigate specific parameters for how Sculptra Aesthetic is used in a real-world clinical setting., Objective: The primary objective of the study was to evaluate the safety of Sculptra Aesthetic when using a reconstitution volume of 7 to 10 mL, via collection of adverse events related to the product or injection procedure reported in medical records., Methods: This was a multi-center, retrospective chart review conducted in the US. Medical records for subjects treated in the facial area with Sculptra Aesthetic reconstituted to 7&ndash;10 mL were reviewed to obtain information about demographics, treatment data, and adverse events. Each injector completed a questionnaire regarding reconstitution and injection procedures generally used., Results: There were 4483 treatments performed in 1002 subjects; nearly half (48%) had 3 or 4 treatments during the studied period. Subjects most commonly received treatment in the midface/cheek area (97%), temple (94%), and jawline (54%). All injectors indicated adding lidocaine to the solution, resulting in total volumes of 8&ndash;10 mL. Adverse events were reported by 3.6% of subjects, all mild in intensity. Nodules were reported by 4 subjects (0.4%)., Conclusion: The low number of AEs reported in this retrospective chart review suggests that facial aesthetic treatment with PLLA reconstituted to a final volume of 8&ndash;10 mL, including anesthetics, is associated with a favorable risk benefit ratio. J Drugs Dermatol. 2021;20(1):18-22. doi:10.36849/JDD.5631.

Background: Poly-L-lactic acid (PLLA) is a biodegradable, synthetic polymer that stimulates collagen production and can improve skin quality, volume, and thickness. The current reconstitution procedure for Sculptra, a PLLA-containing injectable device involves 2 hours standing time before use., Objective: To evaluate and validate an immediate-use procedure for reconstituting a PLLA-containing injectable device., Methods and Materials: Three batches of the product were shaken for 1 minute immediately after reconstitution with 8 mL of sterile water. Different physicochemical tests including viscosity, concentration of excipients (sodium carboxymethylcellulose and mannitol), pH, and particle size distribution were performed for standing times 0, 2, 24, and 72 hours after immediate shaking, and compared with the standard 2 hours standing time before shaking. The recovery and stability of optional addition of 1 mL of 2% lidocaine hydrochloride was also assessed., Results: All physiochemical parameters evaluated were equivalent, regardless of reconstitution procedure, showing that shaking vigorously for 1 minute dissolves the excipients of the product properly without a required standing time and with no impact to the PLLA particles. There were no differences in lidocaine hydrochloride content of suspensions after 0 and 72 hours., Conclusion: The PLLA-containing product can be used immediately after reconstitution including vigorous shaking, as shown from physicochemical analyses. Optional addition of lidocaine hydrochloride is feasible. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5228.

A Western diet comprising high fat, high carbohydrate, and low fiber content has been suggested to contribute to an increased prevalence of colitis. To clarify the effect of dietary cellulose (an insoluble fiber) on gut homeostasis, for 3 months mice were fed a high-cellulose diet (HCD) or a low-cellulose diet (LCD) based on the AIN-93G formulation. Histologic evaluation showed crypt atrophy and goblet cell depletion in the colons of LCD-fed mice. RNA-sequencing analysis showed a higher expression of genes associated with immune system processes, especially those of chemokines and their receptors, in the colon tissues of LCD-fed mice than in those of HCD-fed mice. The HCD was protective against dextran sodium sulfate-induced colitis in mice, while LCD exacerbated gut inflammation; however, the depletion of gut microbiota by antibiotic treatment diminished both beneficial and non-beneficial effects of the HCD and LCD on colitis, respectively. A comparative analysis of the cecal contents of mice fed the HCD or the LCD showed that the LCD did not influence the diversity of gut microbiota, but it resulted in a higher and lower abundance of Oscillibacter and Akkermansia organisms, respectively. Additionally, linoleic acid, nicotinate, and nicotinamide pathways were most affected by cellulose intake, while the levels of short-chain fatty acids were comparable in HCD- and LCD-fed mice. Finally, oral administration of Akkermansia muciniphila to LCD-fed mice elevated crypt length, increased goblet cells, and ameliorated colitis. These results suggest that dietary cellulose plays a beneficial role in maintaining gut homeostasis through the alteration of gut microbiota and metabolites.

The surface chemistry of cellulose nanocrystals was engineered to show variable sulfation degrees, which was exploited to modulate platelet lysate-derived biomolecule sequestration and presentation. The protein coronas developed on CNC surfaces were characterized and it was demonstrated how they promote different signaling effects on human adipose-derived stem cell behavior.

The use of transabdominal color Doppler ultrasound after oral administration of an oral cellulose-based contrast agent (TUS-OCCA) in depicting varices at the cardia and fundus was explored. Both gastroscopy and transabdominal color Doppler ultrasound (TUS) were performed for this purpose, with gastroscopy serving as the gold standard. Patients were assigned by TUS protocol to one of three groups: TUS + empty stomach (TUS-ES); TUS + oral water intake (TUS-OW); and TUS-OCCA. TUS-based grading of varices reflected venous diameters and blood flow velocities, designated as follows: Ux = difficulty discerning gastric fundus and cardia or delineating varices; U0 = no detectable varices; U1 = diameter <5 mm, flow rate <10 cm/s; U2 = diameter <5 mm, flow rate ≥10 cm/s; U3 = diameter 5-10 mm, flow rate <10 cm/s; U4 = diameter 5-10 mm, flow rate ≥10 cm/s; and U5 = diameter >10 mm, any flow rate. Between August 2016 and August 2019, 239 patients with cirrhosis were enrolled prospectively, including bleeding (n = 71) and non-bleeding (n = 168) groups. Varices were directly observed in 10.5% (25/239) of TUS-ES group members, compared with 59.2% (58/98) of the TUS-OW group and 89.6% (104/116) of the TUS-OCCA group; all detection rates differed significantly (TUS-OCCA > TUS-OW > TUS-ES, p < 0.05). TUS-based grading (as defined) revealed the following patient distribution: Ux, n = 34; U0, n = 18; U1, n = 50; U2, n = 41; U3, n = 16; U4, n = 46; U5, n = 34. In grading by variceal diameter, overall correspondence between TUS and gastroscopy was 93% (174/187). TUS-OCCA greatly improved rates of detection of varices at the cardia and fundus, offering a new method by which diagnosis and quantitative grading may be achieved and affording an excellent, non-invasive approach to dynamic follow-up., Competing Interests: Conflict of interest disclosure The authors declare no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Ternary composite films containing bulk chitosan (CS) and chitosan nanoparticles (CSNPs) with different concentrations were prepared using bacterial cellulose/poly(vinyl alcohol) as the base film and the composites films were compared. The micromorphology and mechanical, physical, chemical, antibacterial, and optical barrier properties of the composite films were compared. CS incorporation improved the mechanical properties, as the maximum tensile strength was increased to 130.55 ± 9.42 MPa. The dense structure of CSNPs prevented water diffusion and lessened the water content of the composite membranes. The inclusion of CS and CSNPs both reduced the water solubility and water vapor permeability. CS-doped films possessed good transparency, while CSNPs had better ultraviolet-barrier properties (3.84 % of transmittance at 200-280 nm). In addition, CSNPs-embedded membranes exhibited prominent antibacterial properties against Escherichia coli and Staphylococcus aureus, which were much greater than those of CS composite membranes with a maximum bacteriostatic diameter of 10.33 ± 1.55 mm., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: There is a growing demand for procedures to treat cellulite. Subcision™ is widely used for cellulite correction, and injectable poly-L-lactic acid (PLLA) has been shown to be an effective option for various body conditions., Aims: Present the results of combining Subcision™ plus PLLA, in the same session, in patients with cellulite and flaccidity., Patients/methods: Twenty-four women underwent Subcision™ followed by PLLA injections. An expert panel of dermatologists evaluated before and after photographs according to Global Aesthetic Improvement Scale (GAIS). Patients also answered a satisfaction questionnaire., Results: The author describes the results, as well as number of sessions and dose used. The most frequent GAIS score was "great improvement." No nodules or granulomas appeared in the treated areas., Conclusion: The combination of Subcision™ plus PLLA, in the same treatment session, promotes safe and desirable results for cellulite associated with flaccidity., (© 2020 Wiley Periodicals, Inc.)

Development of high responsive photocatalysts for the degradation of dye from water is a significance method to solve the difficulties of water contamination. In the present project, Cr 2 O 3 nanoparticles were decorated onto cellulose through a facile synthesis method, which was exposed to characterization by XRD, FESEM, DLS, PL, and UV-vis spectroscopy. The structural attributes confirmed the presence of rhombohedral phase of Cr 2 O 3 nanoparticles. The mean crystal size of Cr 2 O 3 , and Cr 2 O 3 /cellulose nanocomposites were 38.50 nm, and 50.11 nm, respectively. The band gap values (Eg) of Cr 2 O 3 , and Cr 2 O 3 /cellulose nanocomposites were was found 3.00, and 2.53 eV, respectively. Moreover, the morphological and optical studies have been showed the impressive photocatalytic properties of the prepared Cr 2 O 3 /cellulose nanocomposites. The photocatalytic efficiency of Cr 2 O 3 , and Cr 2 O 3 /cellulose nanocomposites has been investigated for the photo-degradation of crystal violet in the ultraviolet light region. The Cr 2 O 3 /cellulose indicated promising photocatalytic performance and up to 99.65% of the crystal violet was photo-degraded in 40 min. The obtained crystal violet degradation results were fitted onto a Langmuir-Hinshelwood (L-H) plot. The antioxidant performances of Cr 2 O 3 , and Cr 2 O 3 /cellulose were analyzed. The beneficial antibacterial performance of the Cr 2 O 3 /cellulose nanocomposites was tested by various bacteria as Escherichia coli, Pseudomonas aeruginosa, staphylococcus aurous, and Streptococcus pyogenes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Chronic wasting disease (CWD) is a prion disease of free-ranging and farmed cervids that is highly contagious because of extensive prion shedding and prion persistence in the environment. Previously, cellulose ether compounds (CEs) have been shown to significantly extend the survival of mice inoculated with mouse-adapted prion strains. In this study, we used CEs, TC-5RW, and 60SH-50, in vitro and in vivo to assess their efficacy to interfere with CWD prion propagation. In vitro, CEs inhibited CWD prion amplification in a dose-dependent manner. Transgenic mice over-expressing elk PrP C (tgElk) were injected subcutaneously with a single dose of either of the CEs, followed by intracerebral inoculation with different CWD isolates from white tailed deer, mule deer, or elk. All treated groups showed a prolonged survival of up to more than 30 % when compared to the control group regardless of the CWD isolate used for infection. The extended survival in the treated groups correlated with reduced proteinase K resistance of prions. Remarkably, passage of brain homogenates from treated or untreated animals in tgElk mice resulted in a prolonged life span of mice inoculated with homogenates from CE-treated mice (of + 17%) even in the absence of further treatment. Besides the delayed disease onset upon passage in TgElk mice, the reduced proteinase K resistance was maintained but less pronounced. Therefore, these compounds can be very useful in limiting the spread of CWD in captive and wild-ranging cervids., (© 2019 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Drug crystallization in transdermal patches is still a major challenge, confronting the formulation development of topical drug delivery systems. Encapsulation of drugs into nanoparticles is proposed here as a promising tool for regulating drug crystallization in transdermal patches. The degree of recrystallization and transdermal permeation of ibuprofen and hydrocortisone loaded in polymeric and lipid nanoparticles from matrix-type transdermal patches were investigated. Ethyl cellulose (EC4), poly (lactide-co-glycolic acid) (PLGA) and polycaprolactone (PCL) were employed for polymeric nanoparticle preparations; while medium chain triglyceride (MCT) and witepsol were used for the preparation of MCT nanoemulsion and solid lipid nanoparticles (SLNs), respectively. As control, similar patches were prepared containing the free form of the investigated model drugs. All nanoparticle-containing transdermal patches exhibited less degree of drug recrystallization after 4 weeks compared to the control groups. Among the investigated nanocarriers, transdermal patches formulated with drug-loaded lipid nanoparticles showed the lowermost degree of recrystallization. Drug encapsulation into SLNs succeeded to reduce the degree of ibuprofen and hydrocortisone recrystallization from 23.3 ± 0.9 and 21.9 ± 1.2% to 0.2 ± 0.1 and 1.8 ± 0.1%, respectively. Additionally, the decreased crystalline fraction was accompanied by a corresponding increase in the drug flux through excised pig skin, which was found to be correlated to the hydrophobicity of the different nanocarriers. In conclusion, polymeric and lipid nanoparticles proved to be effective tools for the preparation of transdermal patches with on-demand drug loadings, while lowering the recrystallization risks. Moreover, the results of this study can be a valuable guidance for the design of effective transdermal patches by controlling the crystallization of various drugs through fine tuning of the carrier hydrophobicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Multifunctional bioplastics have been prepared by amorphous reassembly of cellulose, hemicelluloses (xylan), and hydrolyzed lignin. For this, the biopolymers were dissolved in a trifluoroacetic acid-trifluoroacetic anhydride mixture and blended in different percentages, simulating those found in natural woods. Free-standing and flexible films were obtained after the complete evaporation of the solvents. By varying xylan and hydrolyzed lignin contents, the physical properties were easily tuned. In particular, higher proportions of hydrolyzed lignin improved hydrodynamics, oxygen barrier, grease resistance, antioxidant, and antibacterial properties, whereas a higher xylan content was related to more ductile mechanical behavior, comparable to synthetic and bio-based polymers commonly used for packaging applications. In addition, these bioplastics showed high biodegradation rates in seawater. Such new polymeric materials are presented as alternatives to common man-made petroleum-based plastics used for food packaging.

There is a current interest from the food packaging, biomedical and agricultural sectors in hybrid materials formed from clays and natural polymeric compounds. However, research investigating the toxicity of vermiculite-cellulose nanocrystal (VERN) hybrid on the testes of Wistar rats is rare. Twenty rats, divided into control and treatment groups, were orally administered distilled water, 5, 10, and 20 mg/kg bw VERN daily for two consecutive weeks. At the termination of experiments, the testicular organo-somatic index, superoxide dismutase, catalase, and gamma-glutamyl transferase activities were not significantly changed by VERN relative to the controls. Contrarily, myeloperoxidase, glutathione peroxidase, and malondialdehyde levels were depleted in the testes of treated rats. Moreso, VERN increased follicle-stimulating and luteinizing hormones, and decreased testosterone levels at the 20 mg/kg dose. Histology of the testes revealed healthy looking Leydig cells at the doses of 5 and 10 mg/kg VERN. Overall, these results indicate that oral exposure of VERN was not overly deleterious to the redox and structural histoarchitecture in the testes of rats., (© 2019 Blackwell Verlag GmbH.)

The development of biodegradable and antibacterial hemostatic materials with high blood absorption to halt the internal hemorrhage of deep noncompressible wounds remains a challenge. In this study, a novel hemostatic nanocomposite (OBC/COL/CS) was fabricated by coupling oxidized bacterial cellulose (OBC) and chitosan (CS) with collagen (COL), that is, during the electrostatic self-assembly of OBC with CS (OBC/CS), COL was ingeniously attached as a functional component by the electrostatic attraction of cationic CS and anionic OBC. The introduction of collagen was anticipated to provide functional properties such as enhanced hemostasis and promotion of wound healing so as to achieve a new functional composite. This study is the first to evaluate the performance of OBC, OBC/CS, and the OBC/COL/CS composite for rapid internal hemostasis using a rat liver injury model. To our knowledge, this is also the first study to report that OBC has a faster biodegradability in vivo than commercial hemostatic oxidized regenerated plant cellulose (ORC). The OBC/COL/CS nanocomposite exhibited appropriate mechanical strength, broad spectrum antimicrobial properties, and excellent biodegradation in vivo. Furthermore, excellent hemostatic efficacy of the composite was confirmed in vivo. OBC/COL/CS exhibited greater procoagulant properties and blood-clotting capability, higher adhesion of erythrocytes and platelets with concomitant lower blood loss, in addition to ultrafast cessation of bleeding, superior to the commercial hemostatic ORC product Surgicel gauze. The results suggest that the OBC/COL/CS is a fast and efficient procoagulant agent with good antibacterial properties and great potential for use as an absorbable hemostat for control of internal bleeding.

Release of Zn 2+ ions from zinc oxide nanoparticles (ZnO NPs) is a major mechanism for oligodynamic activities of these metal oxide NPs against eukaryotic and prokaryotic microorganisms. In addition to this mechanism, ZnO NPs can form reactive oxygen species (ROSs) resulted from electron-hole formation under certain light wavelength. These properties with suitable biocompatibility and biodegradability of ZnO NPs compared to other metal NPs have caused higher applications of these nanomaterials in therapeutic and cosmetic fields. Recently, natural polymers including cellulose, chitosan, and alginate polymers have gained more attention as safe and cost-effective scaffold for wound healing. Both ZnO NPs and these polymers have not been able to satisfy related patients. In this way, the coupling of these materials and nanomaterials as nanocomposites (NCs) is an alternative way to increase the mechanical and antibacterial properties of wound-healing tissue scaffolds. Controllable release of Zn 2+ ions in physiological medium should be considered as an indispensable factor to obtain appropriate industrial formulation. Therefore, in this review, attempts were made to highlight particularly important antibacterial results of these NCs in recent investigations., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Obesity is a risk factor for asthma, especially nonatopic asthma, and attenuates the efficacy of standard asthma therapeutics. Obesity also augments pulmonary responses to ozone, a nonatopic asthma trigger. The purpose of this study was to determine whether obesity-related alterations in gut microbiota contribute to these augmented responses to ozone. Ozone-induced increases in airway responsiveness, a canonical feature of asthma, were greater in obese db/db mice than in lean wild-type control mice. Depletion of gut microbiota with a cocktail of antibiotics attenuated obesity-related increases in the response to ozone, indicating a role for microbiota. Moreover, ozone-induced airway hyperresponsiveness was greater in germ-free mice that had been reconstituted with colonic contents of db /db than in wild-type mice. In addition, compared with dietary supplementation with the nonfermentable fiber cellulose, dietary supplementation with the fermentable fiber pectin attenuated obesity-related increases in the pulmonary response to ozone, likely by reducing ozone-induced release of IL-17A. Our data indicate a role for microbiota in obesity-related increases in the response to an asthma trigger and suggest that microbiome-based therapies such as prebiotics may provide an alternative therapeutic strategy for obese patients with asthma.

The addition of fiber in chick feeds is known to dilute nutrients; as a result, this may reduce nutrient digestibility and performance. However, recent studies suggest that moderate inclusion of insoluble fibers (2 to 3%) may stimulate gizzard development, which could result in better nutrient utilization and chick growth. The previous fiber sources evaluated were subject to wide fluctuation in their nutritional and chemical composition due to variation in processing. Miscanthus giganteus is a C4 grass purposefully grown for its fiber content which has a consistent fiber composition compared to food process residues. The objectives of this study were to determine the effect of dietary fiber source and particle size on day-old chick performance and nutrient digestibility. Day-old chicks (8 chicks per cage, 5 cages per treatment) were fed diets containing 3% of either sepiolite (SEP), cellulose (CEL), coarse beet pulp (BP), fine BP, coarse Miscanthus grass (MG), and fine MG. At the end of days 7, 14, and 21, chicks and experimental diets were weighed to compute average daily gain and feed intake. In addition, excreta from the previous 48 h of each data capture point was collected to determine nutrient digestibility. In general, chicks fed diets containing fiber consumed more feed, gained more weight, and had better feed conversion rate than birds fed the SEP diet. Particle size of the fiber had no effect on chick performance; however, nutrient utilization was higher (P < 0.05) for chicks fed coarse fiber particles compared to these fed fine fiber particles. Birds fed diets containing MG performed similar to chicks fed CEL (P > 0.05), but digestibility coefficients of birds fed BP diets were generally higher than chicks fed MG diets. In conclusion, chicks performed better with fiber in their diet and MG was comparable to CEL., (© 2019 Poultry Science Association Inc.)

Introduction: Efficacy and safety are critical concerns when designing drug carriers. Nanoparticles are a particular type of carrier that has gained recent attention in cancer therapeutics., Methods: In this study, we assess the safety profile of IT-101, a nanoparticle formed by self-assembly of camptothecin (CPT) conjugated cyclodextrin-based polymers. IT-101 delivers CPT to target cancer cells in animal models of numerous human cancers and in humans. Previous data from preclinical and clinical trials indicate that IT-101 has no notable immunological side effects. However, there have been no published studies focused on evaluating the effects of IT-101 on host immune systems., Results: In this work, we demonstrate that IT-101 diminished initial host immune response following first injection of the nanopharmaceutical and induced NK cell activation and T cell proliferation upon further IT-101 exposure. Additionally, IT-101 could attenuate tumor growth more efficiently than CPT treatment only., Conclusions: Drugs administration in whole-body circulation may lead to poorly bioavailable in central nervous system and often has toxic effects on peripheral tissues. Conjugated with cyclodextrin-based polymers not only reduce adverse effects but also modulate the immune responses to elevate drug efficacy. These immune responses may potentially facilitate actions of immune blockage, such as PD1/PDL1 in cancer treatment.

The current conventional injectable vaccines face several drawbacks such as inconvenience and ineffectiveness in mucosal immunization. Therefore, the current development of effective oral vaccines is vital to enable the generation of dual systemic and mucosal immunity. In the present study, we examine the potential of pH-responsive bacterial nanocellulose/polyacrylic acid (BNC/PAA) hydrogel microparticles (MPs) as an oral vaccine carrier. In-vitro entrapment efficiency and release study of Ovalbumin (Ova) demonstrated that as high as 72% of Ova were entrapped in the hydrogel, and the release of loaded Ova was pH-dependent. The released Ova remained structurally conserved as evident by Western blot and circular dichroism. Hydrogel MPs reduced the TEER measurement of HT29MTX/Caco2/Raji B triple co-culture monolayer by reversibly opening the tight junctions (TJs) as shown in the TEM images. The ligated ileal loop assay revealed that hydrogel MPs could facilitate the penetration of FITC-Ova into the Peyer's patches in small intestine. Ova and cholera toxin B (CTB) were utilized in in-vivo oral immunization as model antigen and mucosal adjuvant. The in-vivo immunization revealed mice orally administered with Ova and CTB-loaded hydrogel MPs generated significantly higher level of serum anti-Ova IgG and mucosal anti-Ova IgA in the intestinal washes, compared to intramuscular administrated Ova. These results conclude that BNC/PAA hydrogel MPs is a potential oral vaccine carrier for effective oral immunization., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study was performed to achieve two primary goals: First, a microemulsion containing betamethasone dipropionate was optimized using the quality by design approach. Second, a hydrogel-containing microemulsion was developed using cellulose derivatives, and its anti-inflammatory and skin irritation effects were evaluated. Face-centered central composite design was used to investigate the impacts of two independent variables (oleic acid and ratio of surfactant to cosolvent, S/CoS) on three dependent variables (skin deposition, flux of BMD, and microemulsion droplet size). The microemulsion including oleic acid at a low level (coded with -1) and S/CoS at a high level (coded with +1) was considered optimal since it was the most effective in terms of skin deposition and flux of BMD. Different cellulose derivatives (HPMC E6, HEC, NaCMC, and CMC) were screened to prepare a hydrogel-containing microemulsion based on four properties: flux and skin deposition of BMD, hydration of stratum corneum, and rheological properties of hydrogel-containing microemulsion (ME-hydrogel). The anti-inflammatory effect and flux of BMD from optimal ME-hydrogel with carboxymethyl cellulose as the hydrogel-forming agent were then compared to those of the hydrogel-containing solid lipid nanoparticles (SLN-hydrogel) and nanostructure lipid carriers (NLC-hydrogel). The percentage of edema inhibition declined proportionally with flux of BMD in the following order: ME-hydrogel (44.56 ± 8.08%) > NLC-hydrogel (35.93 ± 7.22%) > SLN-hydrogel (25.68 ± 9.05%)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Injectable poly-L-lactic acid (PLLA) is a biodegradable synthetic polymer that stimulates collagen production, leading to gradual volume restoration. The treatment of sagging skin in body areas is still a big challenge, as there are few aesthetic procedures aiming to improve it. This article provides recommendations on the use of PLLA in the treatment of skin laxity in off-face areas, as the neck, décolletage, arms, abdomen, buttocks, and thighs, including the patient selection, product preparation, and injection techniques. The use of PLLA is a promising method for the treatment of skin laxity in corporal areas, improving body contour and appearance. Further investigation is needed to better understand the efficacy and durability of PLLA in non-facial indications and to provide the best evidence for optimal patient outcomes. J Drugs Dermatol. 2019;18(9):929-935.

The grains that form the basis of most commercial chicken diets are rich in cellulose, an unbranched β-1,4-linked D-glucopyranose polymer, used as a structural molecule in plants. Although it is a predominant polysaccharide in cereal hulls, it is considered an inert non-fermentable fiber. The aim of the current study was to analyze the effect of in-feed supplementation of cellulose on the gut microbiota composition of broilers. Administration of cellulose to chickens, on top of a wheat-based diet, changed the caecal microbiota composition, as determined using pyrosequencing of the 16S rRNA gene. At day 26, a significantly (P < 0.01) higher relative abundance of the Alistipes genus was observed in the caeca of broilers fed the cellulose-supplemented diet, compared to animals fed the control diet. An in vitro batch fermentation assay showed a significant (P < 0.01) growth stimulation of Alistipes finegoldii in the presence of cellulose. In conclusion, in-feed supplementation of cellulose alters the microbiota composition at the level of the phylum Bacteroidetes, specifically the Alistipes genus. This suggests that cellulose is not essentially inert but can alter the gut micro-environment., (© 2019 Poultry Science Association Inc.)

Background: We previously demonstrated that lubrication of an endotracheal tube (ETT) cuff with K-Y™ jelly strongly and significantly inhibited the increase in cuff pressure during nitrous oxide (N 2 O) exposure in vitro. However, in our previous study, we identified critical differences between some influential factors, such as the amount of lubricant retained on the cuff, and studied temperature differences between laboratory and clinical conditions. Therefore, it remained unclear whether this effect holds true in clinical settings., Methods: We first sought to study how changes in the amount of K-Y™ jelly and temperature influence the inhibitory effects of the lubricant on the increase in N 2 O-induced cuff pressure in vitro. Furthermore, we aimed to determine whether the application of K-Y™ jelly inhibits the increase in ETT cuff pressure during general anesthesia using N 2 O in adult patients., Results: In the laboratory studies, we found that K-Y™ jelly inhibited the cuff pressure increase dose-dependently when the dose of K-Y™ jelly was varied (P = 0.02), and that such an inhibitory effect decreased with an increase in the studied temperature (P = 0.019). In the clinical study, lubrication with K-Y™ jelly slightly, but significantly, delayed the increase in ETT cuff pressure during general anesthesia with N 2 O (P = 0.029). However, the inhibitory effect in the clinical settings was smaller than that in vitro., Conclusions: Lubrication of the ETT cuff with K-Y™ jelly may delay the increase in cuff pressure during general anaesthesia with N 2 O. However, the clinical significance of this effect may be limited., Trial Registration: UMIN Clinical Trials Registry: UMIN000031377 on March 1, 2019.

Polymeric cyclodextrin-based nanoparticles are currently undergoing clinical trials as nanotherapeutics. Using a non-covalent approach, we decorated two cross-linked cyclodextrin polymers of different molecular weights with an RGD peptide derivative to construct a novel carrier for the targeted delivery of doxorubicin. RGD is the binding sequence for the integrin receptor family that is highly expressed in tumour tissues. The assembled host-guest systems were investigated using NMR and DLS techniques. We found that, in comparison with free doxorubicin or the binary complex doxorubicin/cyclodextrin polymer, the RGD units decorating the cyclodextrin-based nanosystems improved the selectivity and cytotoxicity of the complexed doxorubicin towards cultured human tumour cell lines. Our results suggest that the nanocarriers under study may contribute to the development of new platforms for cancer therapy.

Prion accumulation in the brain and lymphoreticular system causes fatal neurodegenerative diseases. Our previous study revealed that cellulose ethers (CE) have anti-prion activities in vivo and in prion-infected cells when administered at high doses. This study aims to improve the bioavailability of a representative CE using a liposomal formulation and characterized CE-loaded liposomes in cultured cells. The liposomal formulation reduced the EC 50 dose of CE by <1/200-fold in prion-infected cells. Compared to empty liposomes, CE-loaded liposomes were taken up much more highly by prion-infected cells and less by macrophage-like cells. Phosphatidylserine modification reduced the uptake of CE-loaded liposomes in prion-infected cells and did not change the anti-prion activity, whereas increased the uptake in macrophage-like cells. Polyethylene glycol modification reduced the uptake of CE-loaded liposomes in both types of cells and reduced the anti-prion activity in prion-infected cells. These results suggest that a liposomal formulation of CE is more practical than unformulated CE and showed that the CE-loaded liposome uptake levels in prion-infected cells were not associated with anti-prion activity. Although further improvement of the stealth function against phagocytic cells is needed, the liposomal formulation is useful to improve CE efficacy and elucidate the mechanism of CE action., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: We describe the management and control of an outbreak of mediastinitis in a cardiac surgery department. Method: We performed a retrospective cohort study of 87 patients who underwent coronary artery bypass grafting (CABG), valve replacement, or both during a five-month period with a higher than normal number of cases of post-operative mediastinitis. In addition to medical records review, a survey was conducted among surgeons to estimate the frequency of cellulose-derived absorbable hemostatic (CDAH) use. Results: Eleven patients (12.5%) developed mediastinitis during the period. None of them died, and the course of the infections was benign. No differences were found between the infected and non-infected patients regarding clinical or demographic characteristics. The rate of infection by surgeon ranged from 0 to 21.4%. (p = 0.38). We found a significant linear relation between the frequency of CDAH use and the risk of infection, from 3.3% to 22.6% (p = 0.024). Cultures of unused CDAHs were negative. Cessation of product use led to no new cases for the following year and to a mediastinitis rate <1% for the following 24 months. Conclusion: We identified a cluster of undesired clinical outcomes compatible with mediastinitis that added morbidity and associated cost, but not deaths, related to the use of CDAH as a hemostatic. These data suggest keeping the use of CDAH in cardiothoracic surgery to a minimum.

The control of the glycemic level among diabetes/T2 patients is very important for their long term survival and avoiding further complexities including micro/macrovascular diseases as well as diabetic neuropathy. Vildagliptin (VD) is a drug that has addressed these issues successfully with the desired safety portfolio. We used DNA-nanocubes for initial nano-encapsulation of VD followed by HPMC/EC coating. The results revealed the stable, smooth, spherical and nano-sized nanoparticles with improved size uniformity (from 100 to 400 nm in diameter) and encapsulation-efficiency (E.E.%) than previously reported (500-2000 nm) with the chemical compatibility evident in ATR/FTIR and DSC results. Animal experiments results revealed the improvement of incretin level in the serums due to potent DPP-4 inhibition compared to the free-VD/solution with better maintenance of glycemic levels after feeding. The safety of these HPMC/EC-DNA-VD nanoparticles was assessed through the histological-examination after completion of the treatment turn. The solvent evaporation technique provided the better coating of HPMC around DNA-core with gastro-resistant and effervescent property due to presence of NaHCO 3 (0.01%) in the formulations that caused delayed delivery of VD as well as nanoparticles to the intestine, increasing the availability time of the drug and nanospheres at the target sites (intestine and blood) where DPP-4 enzyme is most abundant (to degrade the GLP-1 and GIP causing loss of control of the postprandial glycemic levels. So the availability of sustained release nanospheres near the target sites and prolonged DPP-4 inhibition improved the outcomes of the therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Since early times, propolis has been used in folk medicine. The red propolis, collected in the northeast region of Brazil has been highlighted due to its popular use as an antimicrobial, with anti-inflammatory and healing properties, which are associated with its chemical composition. Here, we combine a bacterial membrane with red propolis to treat wounds of diabetic mice. This work aims to evaluate a biocurative from bacterial cellulose associated with red propolis in diabetic mice as wound healing model. Biocuratives from bacterial cellulose membrane and different extracts of red propolis were produced. The qualification and quantification of the presence of propolis chemical compounds in the membrane were investigated through high-resolution mass spectrometry (HRMS). Tests in vivo with biocuratives were performed on Swiss male diabetic mice induced by estroptozotocin. The animals were submitted to a surgical procedure and a single lesion was produced in the dorsal region, which was treated with the biocuratives. Macroscopic assessments were performed at 2, 7 and 14 postoperative days, and biopsies were collected on days 0, 7 and 14 for histological analysis, myeloperoxidase enzyme activity (MPO) and cytokines (TNF-α, IL-1β, and TGF-β). Altogether, ten compounds were identified in membranes and five were further quantified. The ethyl acetate extract showed more red propolis markers, and the most prevalent compound was Formononetin with 4423.00-2907.00 μg.g -1 . Macroscopic analyses demonstrated that the two groups treated with red propolis (GMEBT and GMEAE) showed significantly greater healing capabilities compared to the control groups (GS and GMS). An increase in leukocyte recruitment was observed, confirmed by the activity of the enzyme myeloperoxidase (MPO) in GMEBT and GMEAE groups. The levels of TNF-α were significantly higher in wounds stimulated with red propolis, as well as in TGF-β (GMEBT and GMEAE) on day 7. This was different from the IL-1β levels that were higher in the control groups (GS and GMS). In summary, the biocuratives produced in this work were able to accelerate the wound healing process in a diabetic mouse model. In this way, the traditional knowledge of red propolis activity helped to create a biotechnological product, which can be used for diabetic wound healing purpose., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The healing of wounds, including those from burns, currently exerts a burden on healthcare systems worldwide. Hydrogels are widely used as wound dressings and in the field of tissue engineering. The popularity of bacterial cellulose-based hydrogels has increased owing to their biocompatibility. Previous study demonstrated that bacterial cellulose/acrylic acid (BC/AA) hydrogel increased the healing rate of burn wound. This in vivo study using athymic mice has extended the use of BC/AA hydrogel by the addition of human epidermal keratinocytes and human dermal fibroblasts. The results showed that hydrogel loaded with cells produces the greatest acceleration on burn wound healing, followed by treatment with hydrogel alone, compared with the untreated group. The percentage wound reduction on day 13 in the mice treated with hydrogel loaded with cells (77.34 ± 6.21%) was significantly higher than that in the control-treated mice (64.79 ± 6.84%). Histological analysis, the expression of collagen type I via immunohistochemistry, and transmission electron microscopy indicated a greater deposition of collagen in the mice treated with hydrogel loaded with cells than in the mice administered other treatments. Therefore, the BC/AA hydrogel has promising application as a wound dressing and a cell carrier.

Cellulose acetate phthalate-based pH-responsive hydrogel was synthesized for fabrication of polymeric matrix tablets for gastro-protective delivery of loxoprofen sodium. Cellulose acetate phthalate (CAP) was cross-linked with methacrylic acid (MAA) using free radical polymerization technique. Fourier transform infrared (FTIR) spectra confirmed the formation of cross-linked structure of CAP-co-poly(methacrylic acid). Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the thermal stability of polymeric networks, and scanning electron microscopy (SEM) and energy-dispersive X-ray spectrum (EDS) images unveiled that the prepared formulations were porous in nature and thus the developed formulations had shown better diffusibility. Swelling and in vitro drug release was performed at various pHs and maximum swelling and release was obtained at pH 7.4, while swelling and release rate was very low at pH 1.2 which confirmed the pH-responsive behavior of CAP-co-poly(MAA). CAP-co-poly(MAA) copolymer prevents the release of loxoprofen sodium into the stomach due to reduced swelling at gastric pH while showing significant swelling and drug release in the colon. Cytotoxicity studies revealed higher biocompatibility of fabricated hydrogel. Acute oral toxicity studies were performed for the evaluation and preliminary screening of safety profile of the developed hydrogels. Matrix tablets were evaluated for release behavior at simulated body pH. The investigations performed for analysis of hydrogels and fabricated matrix tablets indicated the controlled drug release and gastro-protective drug delivery of CAP-co-poly(MAA) hydrogels and pH-sensitive matrix tablets for targeted delivery of gastro-sensitive/irritative agents. Graphical abstract.

An injectable bone may serve as a minimally invasive therapy for large orthopedic defects and osteoporosis and an alternative to allografting and surgical treatment. However, conventional bone substitutes lack the desirable biodegradability, bioresponsibility, and functionality to regulate the bone regeneration process. Here, we report an injectable, bioresponsive bone composed of bisphosphonate-modified nanocellulose (pNC) as a bone substitute for bone regeneration. Composites composed of nanofibrillated cellulose and β-tricalcium phosphate (β-TCP) mimic bone structures in which apatite reinforces collagen fibrils. Bisphosphonate groups on nanocellulose provide reversible, physical cross-linking with β-TCP, apatite formation, binding property to bone, and pH responsiveness. When the pH drops to ∼4.5, which corresponds to an osteoclast-induced pH decrease, pNC-β-TCP composite degrades and releases pNC. pNC suppresses osteoclast formation and pit formation. This osteoclast-responsive property allows for controlling the degradation rate of the composite. Moreover, the composite of pNC, α-tricalcium phosphate (α-TCP), and β-TCP enhances osteoblast differentiation. This injectable bone substitute of pNC that regulates osteoclast/osteoblast activity has enormous potential for the treatment of bone diseases and prevention of locomotive syndrome.

Object: To compare between results of bacterial cellulose graft myringoplasty and fat graft myingoplasty in patients had mild or moderate size safe perforation., Methods: 120 patients undergoing myringoplasty due to mild or moderate size perforation were divided into 3 groups: group I: 40 patients undergoing myringoplasty with use of bacterial cellulose graft, group II: 40 patients undergoing myringoplasty with use of fat graft, group III: 40 patients undergoing usual myringoplasty with use of temporalis fascia graft (control group)., Results: Healing in 20 patients with small perforation and 17 patients with moderate perforation in Group I, Healing in 15 patients with small perforation and 10 patients with moderate perforation in Group II, Healing in 18 patients with small perforation and 12 patients with moderate perforation in Group III., Conclusion: Bacterial cellulose graft myringoplasty would be a good, simple, rapid and safe surgery that could be done under local anesthesia in outpatient clinic with shorter time of surgery than fat graft myringoplasty and temporalis fascia graft myringoplasty, with better hearing and healing., Summary at Glance: 120 patients undergoing myringoplasty were divided into 3 groups to compare between results of bacterial cellulose graft myringoplasty, fat graft myringoplasty and temporalis fascia graft myringoplasty., (Copyright © 2018. Published by Elsevier Inc.)

Background: Perennial allergic rhinitis (PAR) often coexists in asthmatic patients. Intranasal cellulose powder (ICP) was reportedly effective in ameliorating PAR., Objective: We investigated whether ICP is equally effective compared with intranasal corticosteroids in improving asthma control as well as nasal symptoms among children with PAR and allergic asthma (AA)., Methods: Between July 2015 and September 2016, we did a single-center, randomized, placebo-controlled trial. Asthmatic children aged 6 to 11 years with mild-to-moderate PAR were randomly assigned to formoterol/budesonide inhalation (4·5 µg/80 µg, twice daily) plus intranasal budesonide 64 µg twice daily (group A), ICP 250 µg thrice daily (group B), or intranasal placebo 250 µg thrice daily (group C) for 8 weeks. The primary outcome was change in asthma control test for children (C-ACT) score from baseline to week 8 posttreatment. Changes in spirometry, peak expiratory flow (PEF), fractional exhaled nitric oxide (FeNO), and visual analog scale (VAS) for nasal and ocular symptoms were detected as secondary outcomes., Results: We included 121 patients (38 in group A, 41 in group B, and 42 in group C) in full-analysis set. C-ACT score was markedly higher at week 8 compared with baseline (mean difference: 5.11, 6.05, and 4.85 points in groups A, B, and C, respectively; P < .05). There were interactions between baseline and treatment in C-ACT scores ( P < .05). Group B demonstrated greater improvement in C-ACT score than group C among children with baseline C-ACT score of 6 to 18. 95% confidence intervals of group A at baseline overlapped with those of groups B and C. The treatment achieved reduced VAS symptoms in groups A and B but not in group C. Incidence of adverse events was comparable. No serious adverse event was reported., Conclusions: ICP could be recommended for children with PAR and AA who have poorer asthma control.

Soybean hulls (SBH) are a fiber-rich co-product of the soybean oil extraction process that corresponds to 8% of the soybean seed. Despite being readily available and priced competitively, SBH are underutilized in monogastric nutrition. Thus, the objective of this study was to evaluate SBH as a dietary fiber in canine diets. Four diets were formulated with either SBH, beet pulp (BP), or cellulose (CL) as the main source of dietary fiber (15% total dietary fiber [TDF]), with the control diet formulated with no supplemental fiber (NF). Animal procedures were approved by the University of Illinois Institutional Animal Care and Use Committee. Eight adult female Beagle (mean age = 4.6 ± 0.6 yr; mean BW = 12.8 ± 1.7 kg) were used in a replicated 4 × 4 Latin square design. Each period consisted of 14 d, with 10 d of diet adaptation followed by 4 d of total fecal and urine collections. At the end of each period, a blood sample was collected and analyzed for serum chemistry. Food was offered twice daily and fed to maintain body weight. Food intake (g/d) on a dry matter basis (DMB) did not differ among treatments. Fecal score was lower (P < 0.05) for dogs fed CL (2.0) in contrast with other dietary treatments (2.3), using a 5-point scale (1 = hard, dry pellets; 5 = diarrhea). Fecal as-is and DM output did not differ for dogs fed BP, CL, or SBH, and were approximately 50% greater (P < 0.05) than dogs fed NF. Apparent total tract digestibility (ATTD) of dry matter, organic matter, and gross energy were greater (P < 0.05) for dogs fed NF when compared with dogs fed BP, CL, or SBH. Dogs fed CL had greater (P < 0.05) AHF ATTD (94%) compared with all other treatments (mean = 91%). Dogs fed CL and NF had greater (P < 0.05) CP ATTD, 87% and 86%, respectively, while dogs fed SBH were intermediate (83%) and dogs fed BP were lowest (79%). Total short-chain fatty acid (SCFA) concentration was greatest in dogs fed BP (582.5 μmol/g) and SBH (479.7 μmol/g) when compared with NF and CL (267.0 and 251.1 μmol/g, respectively). Serum metabolites were within-reference ranges and dogs remained healthy throughout the study. In conclusion, SBH resulted in similar macronutrient ATTD when compared with BP and CL. Dogs fed SBH were also observed to have an increase in fecal SCFA concentration. In general, high level addition of SBH were well-utilized by the dog, resulting in no untoward effects on dog health, nutrient digestibility, or fecal characteristics., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dietary fibers have gained renewed interest in companion animal nutrition as a means to manage pet obesity and improve gut and host health. Soybean hulls (SBH), a coproduct of the soybean oil extraction process, is an accessible and economical fiber source. However, limited research is available on the use of SBH in feline nutrition. Thus, the aim of this study was to determine the effects of a high SBH inclusion level on daily food intake, apparent total tract (ATT) macronutrient digestibility, fecal quality, and fecal fermentative end products in diets of adult cats. Four diets were formulated with either SBH, beet pulp (BP), or cellulose (CL) as the main source of dietary fiber, with the control diet formulated with no added fiber (NF). The fiber treatments were formulated to achieve approximately 15% total dietary fiber (TDF). Eight adult male cats (mean age = 10.5 yr ± 0.1; mean BW = 6.1 ± 0.8 kg) were used in a replicated 4 × 4 Latin square design. Each period consisted of 14 d, with 10 d of diet adaptation followed by 4 d of total fecal and urine collections. Food was offered twice daily and cats were fed to maintain BW. Food intake on a DM basis (DMB) was lower (P < 0.05) in cats fed BP (55.2 g/d) when compared with SBH (70.8 g/d). As-is fecal output did not differ in cats fed BP or SBH, and when expressed on a DMB, fecal output did not differ among fiber treatments. The ATT digestibility of DM, OM, and GE was greater (P < 0.05) in cats fed NF when compared with those fed BP, CL, or SBH. Cats fed CL had the greatest (P < 0.05) ATT CP digestibility (88.5%), followed by cats fed NF (84.9) and SBH (81.7%) with the lowest values (77%) noted for cats fed BP. Acid-hydrolyzed fat (AHF) digestibility was greater for cats fed CL (92.9%) than for cats fed BP (86.9%) and SBH (88.6%). The TDF ATT digestibility was lowest for cats fed NF and CL (8.5% and 15.1%, respectively), followed by SBH (18.0%), with BP having the highest digestibility (33.7%). Total short-chain fatty acid concentration was greatest (P < 0.05) in cats fed BP (699.7 μmole/g) when compared with the other 3 treatments, whereas phenol and indole concentrations did not differ among treatments. In conclusion, a high inclusion level (15% TDF) of SBH appears acceptable in diets for adult cats, resulting in no negative effects on daily food intake, fecal scores, and similar ATT digestibility for most macronutrients when compared with BP and CL., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ascites syndrome (AS) is a harmful disease in fast-growing broilers characterized by heart failure and serious fluid accumulation in the abdominal cavity. One of the known functions of zinc transporter ZIP12 is an important regulator in pulmonary hypertension (PH) in rat. Whether chicken ZIP12 is involved in the process of AS need to be explored. Here, chicken ZIP12 was sequenced and expression pattern and histological distribution were detected in broilers of AS induced by intravenous cellulose microparticle injection. Phylogenetic analysis showed that ZIP12 was significantly different between chicken and mammalian. The relative mRNA expression level of ZIP12 in the liver and lung in AS and pre-ascites (PAS) groups were significantly higher (P < 0.01) than that in control. The immunohistological staining using rabbit anti-chicken ZIP12 IgG and integrated optical density analysis showed the positive cells of ZIP12 distributed in detected tissues and the expression level of ZIP12 protein increased in AS and PAS groups compared to control. The results will provide the basic data of ZIP12 in the pathological process of AS in broiler chickens and offer an important reference for prevention and control of the disease.

The recent decade has witnessed a growing demand to substitute synthetic materials with naturally-derived platforms for minimizing their undesirable footprints in biomedicine, environment, and ecosystems. Among the natural materials, cellulose, the most abundant biopolymer in the world with key properties, such as biocompatibility, biorenewability, and sustainability has drawn significant attention. The hierarchical structure of cellulose fibers, one of the main constituents of plant cell walls, has been nanoengineered and broken down to nanoscale building blocks, providing an infrastructure for nanomedicine. Microorganisms, such as certain types of bacteria, are another source of nanocelluloses known as bacterial nanocellulose (BNC), which benefit from high purity and crystallinity. Chemical and mechanical treatments of cellulose fibrils made up of alternating crystalline and amorphous regions have yielded cellulose nanocrystals (CNC), hairy CNC (HCNC), and cellulose nanofibrils (CNF) with dimensions spanning from a few nanometers up to several microns. Cellulose nanocrystals and nanofibrils may readily bind drugs, proteins, and nanoparticles through physical interactions or be chemically modified to covalently accommodate cargos. Engineering surface properties, such as chemical functionality, charge, area, crystallinity, and hydrophilicity, plays a pivotal role in controlling the cargo loading/releasing capacity and rate, stability, toxicity, immunogenicity, and biodegradation of nanocellulose-based delivery platforms. This review provides insights into the recent advances in nanoengineering cellulose crystals and fibrils to develop vehicles, encompassing colloidal nanoparticles, hydrogels, aerogels, films, coatings, capsules, and membranes, for the delivery of a broad range of bioactive cargos, such as chemotherapeutic drugs, anti-inflammatory agents, antibacterial compounds, and probiotics. SYNOPSIS: Engineering certain types of microorganisms as well as the hierarchical structure of cellulose fibers, one of the main building blocks of plant cell walls, has yielded unique families of cellulose-based nanomaterials, which have leveraged the effective delivery of bioactive molecules., (Copyright © 2018 Elsevier B.V. All rights reserved.)