Mild Irritation Research Articles

Design, fabrication, and evaluation of antimicrobial sponge microneedles for the transdermal delivery of insulin

Transdermal drug delivery systems hold promise, but their effectiveness is often constrained by the skin’s barrier. Microneedles (MNs) improve drug permeability by creating micro-channels in the skin, yet they continue to face challenges such as infection risks and safety concerns. To overcome these challenges, a novel antimicrobial sponge MNs (ASMNs@PVP-INS) modified with polyvinylpyrrolidone (PVP) for insulin (INS) delivery was designed. Mechanical testing demonstrated that these MNs possess excellent mechanical strength, capable of withstanding at least 0.11 N per needle without rupture. In vitro drug penetration tests revealed that the MNs consistently released over 75 % of INS within a 6 h. In an animal model, ASMNs@PVP-INS reduced initial blood glucose levels from 22.4 to 5.72 mmol/L, effectively maintaining glucose control for more than 6 h without inducing hypoglycemia. Additionally, agar diffusion assays indicated that INS loading did not compromise the antimicrobial properties of antimicrobial sponge MNs (ASMNs). Skin irritation tests showed that ASMNs@PVP-INS exhibited mild irritation (PII < 0.6), with skin damage fully recovering within 8 h. Safety assessments indicated no significant toxicity to mice, with biochemical markers remaining within normal ranges, thereby confirming their good biocompatibility. In conclusion, ASMNs@PVP-INS hold promise as a novel drug delivery vehicle.

Ayurvedic Management of Subconjunctival Haemorrhage: A Single Case Report

Subconjunctival haemorrhage is a very common phenomenon that may result from surgery, conjunctivitis and trauma (from minor unnoticed to severe skull base), but is often idiopathic and apparently spontaneous, particularly in older patients. The bleed is usually asymptomatic until noticed by the patient . It gets absorbed by itself within 2 or 3 weeks considering cold compression in the initial stages, artificial tears- if mild ocular irritation is present and by avoiding aspirin and NSAIDs . According to Ayurveda, the disease Arjuna, one among the Suklagata Roga is presented as Neeruk (without pain), Slekshna (slimy) and Sasalohita Lohita Bindu (reddish spot as blood of rabbit). The symptoms of both Arjuna and subconjunctival haemorrhage appears to be similar. Pittahara is the line of management of Arjuna. This case report discusses ayurvedic management of subconjunctival haemorrhage with Kumari Pindi, and Yastimadhu-Lodra Netrapariseka. Kumari, Yastimadhu and Lodra being Chakshushya and with Pittasamana property helped out in complete resolution of subconjunctival haemorrhage with 5 days of Netrakriyakalpa Pindi and Seka giving significant result.

Preclinical safety assessment in rats after dermal exposure to acetylcarvacrol, a potential acaricide against the brown dog tick

Carvacrol, a phenolic monoterpene found in essential oils of plants of the Lamiaceae family, emerges as an alternative acaricide of plant origin. Its acetylation was proposed to obtain a derivative compound with a better pharmacological profile and lower toxicity to non-target organisms. The present study aimed to assess the preclinical safety of acetylcarvacrol after dermal application in Wistar rats, through the examination of hematological and biochemical parameters, as well as histopathological analysis of the skin, liver and kidney. For this, twenty rats were distributed into four groups with five animals each. Three groups received treatment with different concentrations of the substance (26, 52, and 104 µL/mL) based on the lethal concentration for Rhipicephalus sanguineus ticks, and one group (Control) received only the vehicle. Acetylcarvacrol was applied daily to a trichotomized skin area for 21 days. No changes in hematological parameters were observed. Regarding biochemical analysis, a slight increase in urea and alanine transaminase levels was noted. No significant changes were observed in the kidney and liver, although the rats had developed cumulative irritant contact dermatitis at the application site, as corroborated by the histopathological analysis of the skin. In general, the results showed that the dermal application of acetylcarvacrol in the experimental conditions described here is safe. However, it can cause signs of mild systemic toxicity and skin irritation at high concentrations, suggesting that this product should be used in lower therapeutic doses and that the development of less aggressive formulations, including the combination with other acaricides, is desirable.

Resveratrol plus carboxymethyl-β-glucan for children with respiratory diseases.

Respiratory infections in children, ranging from mild to severe, are a leading cause of school absences and medical visits, creating significant socio-economic burdens for families. Recent interest has focused on resveratrol, a natural polyphenol known for its antioxidant, anti-inflammatory, and antiviral properties. When combined with carboxymethyl-β-glucan (CM-glucan), a modified polysaccharide with immunostimulatory effects, this formulation has shown potential benefits in managing respiratory diseases.Our research examines five randomized clinical trials investigating the efficacy of resveratrol and CM-glucan nasal solutions in children. The trials included children with recurrent respiratory infections (RRIs) and allergic rhinitis. The results demonstrate significant reductions in key respiratory symptoms, including nasal congestion, sneezing, coughing, and fever. In addition to symptomatic relief, the treatment was associated with fewer medical visits, decreased medication use, and reduced school absences. Importantly, the combination also showed efficacy in decreasing wheezing episodes in non-atopic children with RRIs and improving symptoms of allergic rhinitis. While these findings are promising, the studies are limited by small sample sizes and short-term follow-up periods, raising questions about the long-term efficacy and safety of the treatment. Mild and transient nasal irritation was the only reported side effect. Based on these concepts, the combination of resveratrol and carboxymethyl-β-glucan could be considered a valuable add-on strategy, complementing standard pharmacological treatments for pediatric respiratory infections and allergic conditions.

Intravesical Therapies for Recurrent Urinary Tract Infections: A Systematic Review.

Recurrent urinary tract infections (rUTIs) present a significant clinical challenge, particularly due to the associated overuse of antibiotics and the rise in antimicrobial resistance. This systematic review evaluates the current literature on the use of intravesical therapies as an alternative treatment for rUTIs. Two established primary therapies are reviewed: glycosaminoglycan (GAG) instillations and intravesical antibiotic instillations. Both therapies offer localised treatment, reducing systemic antibiotic exposure and targeting infection sites more directly. A literature search was conducted using PubMed and Cochrane Controlled Register of Trials (CENTRAL), yielding 5,963 relevant articles, of which seven studies met the inclusion criteria. The review indicates that both GAG and antibiotic instillations significantly reduce UTI recurrence rates and improve symptoms such as pain and urinary urgency. However, significant variations in treatment schedules and dosages exist, and no direct comparative studies between GAG instillations and intravesical antibiotics were found. Moreover, intravesical antibiotics show great potential in minimising antimicrobial resistance, though further large-scale studies are needed to confirm these findings. While intravesical therapies are generally well-tolerated, GAG instillations can cause mild irritation. Further research is required to optimise therapy regimens and to perform cost-benefit analyses, particularly considering the high costs of these therapies compared to traditional antibiotic prophylaxis. Randomised controlled trials comparing different intravesical treatments are crucial to inform future clinical practice.

Histopathological changes in the human tissues in various types of poisoning: A cross-sectional autopsy study

BackgroundPoisoning is a critical health issue caused by exposure to harmful substances, leading to a range of biological effects from mild irritation to severe organ damage and death. Acute poisoning is particularly prevalent in developing countries reliant on agriculture, where agricultural poisons such as organophosphates, carbamates, pyrethroids, and aluminum/zinc phosphide are common. This study aims to analyze the histopathological changes in various organs in autopsy of poisoning cases to understand the extent and nature of organ damage. MethodsAutopsies were performed on cases with an established or suspected history of poison ingestion. Tissue samples from the stomach, intestine, liver, spleen, kidneys, brain, and lungs were examined for histopathological changes. ResultsOut of 52 cases analyzed, aluminum phosphide was the predominant poison, accounting for 76.92 % of cases. Histopathological findings in poisoning cases included significant pulmonary edema (55.77 %), intra-alveolar hemorrhage (48.08 %), liver ballooning degeneration (48.08 %), acute tubular necrosis (51.92 %) in kidney, and universal brain and spleen congestion (100 %). Stomach findings showed partial loss of rugosity (80.77 %), congestion (51.92 %), necrosis of the mucosa (30.77 %), congestion (71.15 %), denudation of the epithelium (48.08 %), and mucosal inflammation (48.08 %) as predominant findings. Aluminum phosphide caused severe histopathological changes across all examined organs. ConclusionThe study highlights the critical role of histopathological examination in diagnosing and understanding organ damage in poisoning cases. Forensic pathologists can use these histopathological patterns as reference points to differentiate poisoning from other causes of death, aiding in accurate diagnosis and targeted treatment.

Dermal toxicity studies of 1,2-benzisothiazolin-3-one (CAS number: 2634-33-5) in Sprague-Dawley rats

Biocides are used as preservatives in various household products, and 1,2-benzisothiazolin-3-one (BIT) is one of the popular chemicals. Therefore, BIT is highly likely to be exposed to human skin, necessitating dermal toxicity evaluation. In this study, we aimed to investigate dermal toxicity, eyes and skin irritation, and skin sensitization of BIT. All studies were conducted according to the Organisation for Economic Co-operation and Development testing guidelines. In acute dermal toxicity using rats, no treatment-related responses were observed at the highest dose (2000 mg/kg). A 28-day repeated dermal toxicity study at 1, 4, and 12 mg/kg/day showed transient local skin irritation lesions, including erythema, exfoliation, and crust formation. Based on no systemic effects, the no observed adverse effect level (NOAEL) of BIT of the 28-day repeated dermal toxicity study was determined to be 12 mg/kg/day. Eye and skin irritation tests showed that BIT is a strong irritant and corrosive to the eyes and a mild irritant to the skin. However, BIT showed no skin sensitization reactions in a local lymph node assay. These dermal toxicity studies can provide valuable information for the risk assessment of BIT.

Use of growth factor concentrate using derma roller in treatment of androgenetic alopecia: A literature review

Androgenetic alopecia (AGA) is a common cause of hair loss in both men and women. Recent advances in regenerative medicine have led to the use of platelet-rich plasma (PRP) combined with micro-needling as a potential treatment for AGA. However, the clinical effectiveness of this combination therapy remains unclear. To evaluate the efficacy and safety of platelet-rich plasma (PRP) combined with micro-needling for the treatment of androgenetic alopecia through a systematic review and meta-analysis of available clinical studies. A systematic search was conducted in PubMed, Embase, and the Cochrane Library for studies published up to January 2024. Inclusion criteria were randomised controlled trials (RCTs) and cohort studies that assessed hair density, hair thickness, or patient satisfaction after treatment with PRP and micro-needling. Data were extracted and pooled using a random-effects model, and heterogeneity was assessed with the I² statistic. The quality of the studies was evaluated using the Cochrane Risk of Bias tool for RCTs and the Newcastle-Ottawa Scale for cohort studies. A total of 12 studies involving 546 participants were included. Meta-analysis showed that the combination of PRP and micro-needling significantly increased hair density (mean difference: 18.9 hairs/cm², 95% CI: 15.3-22.5, p &amp;#60; 0.001) and hair thickness (mean difference: 0.4 mm, 95% CI: 0.3-0.5, p &amp;#60; 0.01) compared to controls. Patient satisfaction was also higher in the treatment group. The most commonly reported adverse effects were mild scalp irritation and transient erythema, with no serious adverse events. Moderate heterogeneity was observed among the studies (I² = 42%). The combination of PRP and micro-needling is an effective and well-tolerated treatment for androgenetic alopecia, resulting in significant improvements in hair density and thickness. Further large-scale, high-quality trials are needed to confirm these findings and standardize treatment protocols.

Assessing Barrier Function in Psoriasis and Cornification Models of Artificial Skin Using Non-Invasive Impedance Spectroscopy.

Reconstructed epidermal equivalents (REEs) consist of two distinct cell layers - the stratum corneum (SC) and the keratinocyte layer (KL). The interplay of these layers is particularly crucial in pruritic inflammatory disorders, like psoriasis, where a defective SC barrier is associated with immune dysregulation. However, independent evaluation of the skin barrier function of the SC and KL in REEs is highly challenging because of the lack of quantitative methodologies that do not disrupt the counter layer. Here, a non-invasive impedance spectroscopy technique is introduced for dissecting the distinct contributions of the SC and KL to overall skin barrier function without disrupting the structure. These findings, inferred from the impedance spectra, highlight the individual barrier resistances and maturation levels of each layer. Using an equivalent circuit model, a correlation between impedance parameters and specific skin layers, offering insights beyond traditional impedance methods that address full-thickness skin only is established. This approach successfully detects subtle changes, such as increased paracellular permeability due to mild irritants and the characterization of an immature SC in psoriatic models. This research has significant implications, paving the way for detailed mechanistic investigations and fostering the development of therapies for skin irritation and inflammatory disorders.

2250 A mixed-method feasibility study of an intervention to reduce sedentary behaviour in community-dwelling older adults aged ≥ 75 years

Abstract Introduction Older adults are the fastest growing and most sedentary group in society. With sedentary behaviour associated with negative health outcomes, reducing sedentary time may improve overall wellbeing. This single-arm mixed-method feasibility study explored the acceptability of an intervention to reduce sedentary behaviour in community-dwelling older adults aged ≥75 years. Methods Participants were recruited from the Community Ageing Research 75+ Study (CARE75+) cohort, with factors such as age, frailty status, living arrangements and levels of sedentariness being considered. The intervention consisted of an educational booklet including advice on how to reduce sedentary behaviour, a smartwatch with a sedentary reminder function, educational group sessions and follow up phone calls. The 9-week intervention was conducted from June–August 2023. Reach, uptake, adherence, and adverse events were recorded, and the acceptability of the intervention was explored through semi-structured exit interviews. Results Of the 39 eligible participants, 10 consented (5 M:5F) and had a mean age 84.3 years. The intervention had an uptake and reach of 25.6%, and retention of 100%. No falls, hospitalisations or deaths occurred, and three cases of mild irritation were reported which resolved during the study. 100% adherence was observed for the group sessions and follow-up phone calls, and 65% for self-monitoring. Qualitative data suggests that participants were receptive of the intervention according to the domains of the Theoretical Framework of Acceptability, and suggestions were provided on refining the intervention components. Conclusion Strategies to reduce sedentary behaviour were tested on a diverse sample of community-dwelling older adults in the oldest old age group, with varying levels of sedentary behaviour and frailty status. The presented strategies appear to be acceptable, appropriate, safe, and high levels of adherence were observed. Participant feedback will be used to refine the intervention.

Kaempferia galanga L. alleviates the expression of COX-2 and NF-kappaB-p65 in the oral mucosa ulcer of Wistar rats and exhibits no irritation toward the vascular membrane of chicken eggs and the skin of albino rabbits

The global incidence of recurrent aphthous stomatitis in 2018 reached 5–66 % of the population, while in Indonesia 8 %. Moreover, the prevalence of oral mucosal fibrosis and recurrent aphthous stomatitis among male doctors and nurses in China was 21.24 % and 24.27 %, respectively. Our previous study has shown that the ethanol extract of Kaempferia galanga L. rhizome (EKGR) revealed an accelerated wound-healing effect in the oral mucosa ulcer of Wistar rats. This study aims to explore the effects of EKGR on the expression of NF-kappaB-p65 and COX-2 in the tongue tissue of male Wistar rats by Western blot analysis and immunohistochemistry technique, its safety towards the vascular membrane of the egg chorioallantoic membrane, and its single-dose application on the skin of male rabbits. The rats were randomly assigned into 7 groups: the normal control; the negative control; the positive control (treated with triamcinolone acetonide); and 4 treatment groups of EKGR (0.5 %; 1 %; 2 %; 4 %). Western blot and immunohistochemistry methods were used to measure the expression of NF-kappaB-p65 and COX-2. The hen's egg test-chorioallantoic membrane assay was employed to predict the safety of EKGR towards the vascular membrane. Moreover, the effect of 200 mg/kg BW EKGR application on the dorsal skin of male albino rabbits was also evaluated. EKGR inhibits the expression of NF-kappaB-p65 and COX-2 as proven by WB and IHC results. In the HET-CAM assay, all concentrations of EKGR do not induce irritation responses, which elicits the safety of EKGR. The administration of EKGR causes mild irritation to the dorsal skin of male rabbits but does not induce erythema and edema, no significant changes in BW, no toxic effects on organ macroscopic examination or histopathology, and does not induce abnormalities in the hematological profile of male albino rabbits. EKGR has confirmed its anti-inflammatory activity by suppressing the expression of COX-2 and NF-kappaB-p65 in the oral mucosa ulcer of Wistar rats. EKGR is safe as it does not exhibit irritating potential and harmful effects.

Evaluation of eye irritation potential of experimental cosmetic formulations containing glycolic acid, salicylic acid and ethanol using the Bovine Corneal Opacity and Permeability Assay

Objective Prototype cosmetic formulations containing short-chain acids and alcohols intended to be applied in the proximity of the eyes are sometimes evaluated for ocular irritation potential using the validated Bovine Corneal Opacity and Permeability Assay (OECD TG 437). We evaluated the eye irritation potential of nine experimental cosmetic formulations designed and prepared by Avon Global Reserach and Development to differ only in the concentrations of Ethanol, Glycolic Acid and Salicylic Acid. Methods We analysed the data generated using the BCOP assay. The opacity and permeability values obtained following the exposure of bovine corneas to experimental cosmetic formulations were combined into a single In Vitro Irritancy Score used to rank eye irritation potential. Histopathological examination of treated corneas was used to provide additional information about the depth and degree of the injury and to support the prediction of eye irritation potential of each experimental cosmetic formulation. Results The In Vitro Irritancy Scores and histopathological analysis showed that experimental formulations containing only Ethanol, Glycolic Acid, or Salicylic Acid alone had, at most, a mild ocular irritation potential. The experimental formulations containing both Ethanol and Glycolic Acid had a mild ocular irritation potential, while the experimental formulations containing both Ethanol and Salicylic Acid had a moderate ocular irritation potential. Severe ocular irritation potential was induced by an experimental formulation containing a combination of Glycolic Acid and Salicylic Acid and it was further accentuated by the addition of Ethanol to the formulation. Our data indicate a possible synergistic effect on eye irritation potential of Ethanol, Glycolic Acid and Salicylic Acid in at least some experimental cosmetic formulations. Further, our results provide insight on an apparent concentration-dependent ocular irritation potential effect of combinations of Glycolic Acid, Salicylic Acid and Ethanol in at least one experimental cosmetic formulation. Conclusions The results presented herein emphasise the need to consider in vitro testing of prototype cosmetic formulations containing combinations of Ethanol, Glycolic Acid and Salicylic Acid rather than relying on any predicted additive effect on ocular irritation based solely on previously generated results of similar formulations containing Ethanol, Glycolic Acid or Salicylic Acid alone. Further work is required to understand the significance of these observations and to elucidate the mechanisms responsible for the apparent synergistic effects of Glycolic Acid, Salicylic Acid and Ethanol and eye irritation potential suggested by our results.

Trends in acupuncture for infertility: a scoping review with bibliometric and visual analysis.

Unexplained recurrent implantation failure and the high cost of assisted reproductive techniques for those experiencing infertility have increasingly resulted in the use of acupuncture. However, the trends and research status of acupuncture on infertility resulting in natural conception have not been systematically summarized. This scoping review and knowledge graph analysis aimed to summarize existing clinical studies on acupuncture for infertility that resulted in natural conception. Seven databases, namely, PubMed, Embase, the Cochrane Library, CNKI, VIP, Wanfang Data, and SinoMed, were searched up to August 2023 (updated on 1 April). Two authors independently identified related clinical studies and systematic reviews, and extracted data from included studies on acupuncture for infertility; any discrepancies were resolved by discussion or judged by a third author. A meta-analysis was conducted based on randomized controlled trials (RCTs), and data were synthesized using risk ratios with 95% confidence intervals. Of the 310 articles meeting the inclusion criteria, 274 were primary studies, 7 were systematic reviews, and 29 were case reports. Reported adverse events included mild ovarian irritation and early signs of miscarriage. Out of the 274 primary studies, there were 40 (14.60%) cases of male infertility and 234 (85.40%) cases of female infertility. Current research highlights on acupuncture for infertility focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and luteinized unruptured follicle syndrome (LUFS), while acupuncture for male infertility was a hotspot in the early research stage. The meta-analysis also suggested that acupuncture was more effective than human chorionic gonadotropin (HCG) [RR = 1.89, 95% CI (1.47, 2.42), 11 RCTs, 662 participants]. Acupuncture combined with HCG was comparable to HCG [RR = 2.33, 95% CI (1.53, 3.55), four RCTs, 259 participants]. Compared with no treatment, acupuncture resulted in a higher pregnancy rate [RR = 22.12, 95% CI (1.39, 353.09), one RCT, 47 participants]. There was no statistical difference between acupuncture combined with HCG plus letrozole and HCG plus letrozole [RR = 1.56, 95% CI (0.84, 2.89), one RCT, 84 participants]. Current research highlights on acupuncture for infertility resulting in natural conception focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and LUFS, while studies on male infertility and female infertility caused by blockage in the fallopian tube, thin endometrium, and other factors were insufficient. Well-designed confirmatory clinical studies are still needed as the research hypotheses of most studies were unclear.

Acute exposure to hydrazine reported to four United States regional poison centers: reconsidering a paradigm

Introduction Exposures to hydrazines occur during aeronautic and space operations and pose a potential risk to personnel. Historically, extensive preparatory countermeasures have been taken due to concern for severe toxicity. This study seeks to better understand manifestations of acute occupational exposures to hydrazine to guide recommendations for management. Materials and methods A retrospective database review of records from four United States regional poison centers was conducted of all human exposures to hydrazine, monomethylhydrazine, or 1,1-dimethylhydrazine over two decades. Following case abstraction, descriptive statistics were performed to characterize demographics, manifestations, treatments, and outcomes. Results One hundred and thirty-five cases were identified, and most were adult males exposed to inhaled hydrazine propellant vapors. Fifty-seven percent of patients were asymptomatic following exposure; otherwise, common symptoms were dyspnea, throat irritation, cough, ocular irritation, and headache. All patients were evacuated or received decontamination, with a few reports of symptomatic treatments, including oxygen supplementation and salbutamol (albuterol). Patients usually recovered quickly and were released after a brief healthcare facility evaluation or observed locally. No patients developed delayed symptoms. Symptoms of severe toxicity were not observed, and there were no deaths. Discussion Acute exposures to hydrazines during operations within the aerospace industry appear to be limited primarily to mucosal and mild pulmonary irritation without significant neurologic, hepatic, or hematologic toxicity. These findings are contrary to previously established expectations and may be related to low-level exposures or possibly due to current emergency countermeasures. Conclusions Care in occupational hydrazine exposure will focus on evacuation, decontamination, and symptomatic management of chemical irritant properties of hydrazines. It is reasonable to manage mild cases outside of a healthcare facility. Continued endeavors in human space exploration and habitation will increase the risk of these exposures, making it imperative that clinicians be comfortable with the care and management of these patients.

Safety of the feed additive consisting of endo-1,4-β-xylanase (produced with Trichoderma reeseiCBS 143953), subtilisin (produced with Bacillus subtilisCBS 143946) and α-amylase (produced with Bacillus amyloliquefaciensCBS 143954) (Avizyme® 1505) for all poultry species (Danisco (UK) Ltd.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety of the feed additive consisting of endo-1,4-β-xylanase (produced with Trichoderma reesei CBS 143953), subtilisin (produced with Bacillus subtilis CBS 143946) and α-amylase (produced with Bacillus amyloliquefaciens CBS 143954) (Avizyme® 1505) as a zootechnical feed additive for all poultry species. The additive is authorised in feed for chickens and turkeys for fattening, ducks and laying hens. In 2020, the FEEDAP Panel issued an opinion for the renewal of the authorisation of the additive for the species/categories for which there is an authorisation, a reduction of the minimum recommended level in turkeys for fattening and the extension of use to all poultry species. In that assessment, the Panel could not conclude on the safety of the additive due to uncertainties on the characterisation of the production strains and the possible presence of their viable cells and DNA in the final product. Moreover, limitations were identified in the xylanase specifications and xylanase method of analysis. The applicant submitted information to address the limitations previously identified. The Panel concluded that the additive is safe for the target species under the proposed conditions of use. The use of Avizyme® 1505 in animal nutrition is considered safe for the consumer and the environment. The additive is a mild irritant to skin and eyes; it is not a dermal sensitiser but should be considered a respiratory sensitiser. The additive is efficacious in ducks at 75 U endo-1,4-β-xylanase, 1000 U subtilisin and 100 U α-amylase/kg of complete feed. In other poultry species for fattening (including turkeys), reared for breeding and reared for laying, the additive is efficacious at 187.5 U endo-1,4-β-xylanase, 2500 U subtilisin and 250 U α-amylase per kg of complete feed and at 300 U endo-1,4-β-xylanase, 4000 U subtilisin and 400 U α-amylase per kg of complete feed for all poultry species for laying (except for ducks).

The Orbicularis Oculi Muscle Sparing Full-Incision Double-Eyelid Blepharoplasty.

Double-eyelid blepharoplasty was the most prevailing cosmetic procedures in China. To reduce the visible scar and unnatural crease after the removal of the OOM in the traditional full-incision double-eyelid technique. This research tried to introduce and promote the orbicularis oculi muscle sparing full-incision double-eyelid blepharoplasty with more conservative resection of upper eyelid soft tissue. The orbicularis oculi muscle sparing full-incision double-eyelid blepharoplasty was operated and evaluated in 227 patients (454 eyes), and the esthetic results, the satisfaction of patients and complications were scored and analyzed at 6-12months postoperative. Of the 227 patient, 164 (72.25%) patients were very satisfied, and 49 (21.59%) patients were satisfied, 14 (6.17%) patients were unsatisfied mainly because of the loss of palpebral fold or shallow folds. The average subjective scar score was 4.92 with 209 (92.1%) patients scored very satisfied, 18 patients scored satisfied. No patients experienced the eyelid numbness, dry eyes, and stitch abscess. 8 patients (3.52%) developed mild eye irritation in early postoperative period, however the symptoms resolved spontaneously in 2weeks. The orbiculars oculi muscle sparing full-incision double-eyelid blepharoplasty contributes to the conservation of the physiology of the eyelid structure, producing a reliable, nature, dynamic double-eyelid crease with a light scar and less complication. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Comparative toxicological-hygienic assessment, structural-morphological, physicochemical characteristics, and virucidal properties of new nanopowder materials TiO2 and TiO2@Ag

In order to address safety concerns related to the acquisition and utilization of TiO2 and TiO2@Ag nanomaterials, as well as to investigate their disinfectant and biological effects, the structural-morphological, morpho­metry, toxicological, cytotoxic, and virucidal properties of these specified nanomaterials have been studied through experiments conducted on laboratory animals and in vitro. It has been demonstrated that the TiO2@Ag nanocomposite exhibited distinct physicochemical characteristics: it consisted of TiO2 nanoparticles ranging in size from 13 nm to 20 nm and Ag nanoparticles ranging from 35 nm to 40 nm with 4.0 wt% of silver localized on the surface of titanium dioxide. The purity of the modification of synthesized nano-TiO2 and nano-TiO2@Ag has been confirmed. Acute intraperitoneal administration of nanopowders revealed LD50 values of 4783.30 mg/kg for nano-TiO2 and 724.44 mg/kg for nano-TiO2@Ag. A slight accumulation was observed upon repeated (28-fold) intragastric administration of nano-TiO2. The cumulative dose administered, which equated to 15.9 multiples of the LD50 (76040 mg/kg), did not result in animal mortality but led to retardation in body weight gain. TiO2 and TiO2@Ag nanopowders do not irritate the skin, induce mild conjunctival irritation, and may exhibit a weak sensitizing effect. Nano-TiO2 and nano-TiO2@Ag powders accumulate in the tissues of internal organs and cause damage to the liver, kidneys, and lungs of laboratory animals upon intraperitoneal administration. The most characteristic morphological signs of the toxic effect of nano-TiO2 on liver tissue were observed at a level of 67.7% (cytoplasmic vacuolization in hepatocytes), while in the case of nano-TiO2@Ag initial necrotic changes were at a level of 70.0% (hepatocytes with pyknotic nuclei). Immunoassay analysis has demonstrated that TiO2@Ag and TiO2 nanomaterials at concentrations of 30 µg/ml can enhance the functional activity of peripheral blood mononuclear cells in vitro by increasing the production of cytokines IL-1, IL-6, TNF-α, and IL-4 in donors (p&lt;0.05). This indicates the potential for chronic inflammation and allergic reactions among synthesis operators. In the study of the impact of nanomaterials on murine germ cells, it has been established that they affect the activity of mitochondrial enzymes and exert a damaging effect on mitochondrial membranes and overall cell integrity. Estimated approximate safe exposure levels in the workplace air are 0.3 mg/m3 for nano-TiO2 and 0.2 mg/m3 for nano-TiO2@Ag. Nano-TiO2@Ag and nano-TiO2 at a concentration of 100 µg/ml exhibit pronounced extracellular virucidal activity against human adenovirus serotype 2. The TiO2@Ag nanocomposite has a less damaging effect on Нер-2 cells compared to nano-TiO2.

Oral pyogenic granuloma with calcification

Rationale: Pyogenic granuloma (PG) is a commonly observed reactive soft-tissue lesion, often arising due to prolonged mild irritation or hormonal fluctuations in the oral cavity. Clinically, PG presents as a lesion with a smooth or lobulated appearance, which can be either sessile or pedunculated, and typically exhibits an hemorrhagic tendency. Very few cases of calcification in a PG have been reported in the past as these rarely exhibit ossification when viewed under a microscope. Patient Concerns: The following report is a case of a PG, that presented as a growth with occasional pain in the right upper back region of a 54 year old female. The patient reported no other concerns. Diagnosis: A provisional diagnosis of PG was given following thorough clinical and radiographic investigations. This was confirmed by a histopathological examination following an excisional biopsy. Intervention: The patient was treated with surgical excision as a part of the excisional biopsy of the lesion. Follow-up for the patient was done after 6 months, and there were no signs or indications of recurrence. Outcomes: The histopathological examination revealed regions of calcification, which are uncommon in PG, in addition to the characteristic hallmarks of proliferating endothelial cells, blood vessels, and inflammatory cells.

A rare case of conjunctival granuloma in Aurolab aqueous drainage implant (AADI) with supramid

Conjunctival granuloma (CG) can be caused by a foreign body, surgically related inflammation, an allergen, an infectious organism, or as part of a systemic disease. We are reporting the first case of CG related to 5-0 prolene as supramid, which is used as an intraluminal stent in AADI to prevent hypotony. A 70-year-old female diagnosed with POAG in both eyes with posterior PCIOL on MMT with advanced disc damage and uncontrolled IOP in the right eye underwent AADI with supramid. The patient developed mild irritation and redness in RE in the fourth month of follow-up. On slit-lamp examination, there was localized CG at the end of the supramid tip. CG resolved with the removal of the supramid suture and medical treatment. Supramid-related CG is rare and generally causes non-fatal material-related hypersensitivity reactions that can be treated well with medications and removal of inciting factors.

A Dermatological Safety Test of a Face Serum Formulation Derived from Honey and Propolis of Stingless Bee from East Kalimantan

Skincare, which is a type of cosmetics, is an essential component in the process of maintaining and caring for the skin. It is known that the skin quickly absorbs the tiny molecular structure of serum. Stingless bees, widespread in East Kalimantan and Indonesia, benefit the skin's health by producing honey and propolis. This research aims to demonstrate that a face serum derived from honey and propolis of stingless bees from East Kalimantan is safe for use on the skin using dermatological standards. Here we will see whether there are allergic reactions and irritation from using facial serum. Using the Repeated Open Application Test (ROPT) technique, 20 volunteers were subjected to applying a face serum containing honey and stingless bee propolis. The serum was given to the upper arm twice daily for seven days. As part of the test, allergic reactions were evaluated using the system developed by the International Contact Dermatitis Research Group (ICDRG), and irritating reactions were evaluated using the Primary Irritation Index (PII). The results showed that on the first day, four of the volunteers reported moderate irritation reactions. Consequently, they scored 0.7, indicating they suffered minor irritation. On the other hand, the reactions of the remaining 16 volunteers were typical. Twenty participants had normal skin from the second treatment until the seventh day. The overall findings show that the facial serum based on honey and kelulut propolis from stingless bees from East Kalimantan showed a mild irritation reaction at the beginning of use and was safe to use in subsequent uses.