Intracutaneous Injection Research Articles

Herpes Zoster and Post-Herpetic Neuralgia-Diagnosis, Treatment, and Vaccination Strategies.

Herpes zoster is caused by the reactivation of latent varicella infection within the sensory ganglia, caused by the varicella-zoster virus (VZV). The disease is classically characterized by a painful unilateral vesicular eruption. Complications of the disease include herpes zoster ophthalmicus, Ramsay Hunt syndrome, acute retinal necrosis, and post-herpetic neuralgia. In this paper, we discuss the epidemiology, pathogenesis, clinical features, diagnosis, management, and vaccination strategies of herpes zoster and post-herpetic neuralgia. This paper was developed with input from specialists from Singapore's public sectors-dermatologists, family physicians, and infectious diseases specialists. The diagnosis of herpes zoster is clinical and can be aided with laboratory investigations. Early initiation of antivirals, within 72 h of onset, can reduce the severity and duration of the condition and decrease the intensity of pain. In patients with a high risk of post-herpetic neuralgia, early initiation of anticonvulsants or tricyclic antidepressants can be considered. Herpes zoster is highly preventable, with the advent of the recombinant zoster vaccine (RZV) providing an overall vaccine efficacy of 97.2%. Procedures such as epidural blocks and subcutaneous or intracutaneous injections of local anesthetics and steroids can be considered for patients with a high risk of post-herpetic neuralgia to reduce its incidence. This article serves as a guideline for clinicians in the diagnosis, investigations, management, and prevention of herpes zoster. With the majority of adults in Singapore currently at risk of developing herpes zoster due to varicella immunization being only introduced in 2020, it is important for clinicians to recognize and manage herpes zoster appropriately.

Fluorescence imaging‐guided pelvic lymph node localization and resection of bladder cancer after intracutaneous injection of indocyanine green into the lower limbs and perineum

AbstractBackgroundPelvic lymph node dissection (PLND) in radical cystectomy (RC) is of great significance, but the method and scope of PLND remain controversial. Based on the principle of indirect lymphadenography, we designed a method to localize the whole pelvic lymph nodes by intradermal injection of indocyanine green (ICG) through the lower limbs and perineum, and to evaluate the effectiveness of this method.MethodsIn a single center, 54 bladder cancer patients who underwent RC and PLND participated in a prospective clinical trial, which began on February 28, 2022 and ended on December 30, 2022. ICG solution was injected subcutaneously at the medial malleolus of both lower extremities and at both sides of the midline of the perineum. The fluorescent laparoscopy was used to trace, locate, and remove the targeted areas under the image fusion mode. The consistency of lymph node resection was determined by histopathological diagnosis. The impact of ICG guidance on the surgical time of PLND was compared with that of 11 bladder cancer patients who underwent RC and PLND without ICG injection, serving as the control group.ResultsPerineal lower limb combined injection can provide comprehensive visualization of pelvic lymph nodes. This technique reduces PLND surgical time and increases the accuracy of PLND.ConclusionIntracutaneous injection of ICG into the lower limbs and perineum can specifically mark pelvic lymph nodes. Intraoperative fluorescence imaging can accurately identify, locate, and resect lymph nodes in the pelvic region, reducing PLND surgical time and increasing the accuracy of PLND.

IL-27 disturbs lipid metabolism and restrains mitochondrial activity to inhibit γδ T17 cell-mediated skin inflammation

IL-17+ γδ T cells (γδ T17) are kick-starters of inflammation due to their strict immunosurveillance of xenobiotics or cellular damages and rapid response to pro-inflammatory stimulators. IL-27 is a well-recognized pleiotropic immune regulator with potent inhibitory effects on type 17 immune responses. However, its actions on γδ T17 mediated inflammation and the underlying mechanisms are less well understood. Here we find that IL-27 inhibits the production of IL-17 from γδ T cells. Mechanistically, IL-27 promotes lipolysis while inhibits lipogenesis, thus reduces the accumulation of lipids and subsequent membrane phospholipids, which leads to mitochondrial deactivation and ensuing reduction of IL-17. More importantly, Il27ra deficient γδ T cells are more pathogenic in an imiquimod-induced murine psoriasis model, while intracutaneous injection of rmIL-27 ameliorates psoriatic inflammation. In summary, this work uncovered the metabolic basis for the immune regulatory activity of IL-27 in restraining γδ T17 mediated inflammation, which provides novel insights into IL-27/IL-27Ra signaling, γδ T17 biology and the pathogenesis of psoriasis.

In Vivo Formation of Adrenal Organoids in a Novel Porcine Model of Adrenocortical Cell Transplantation.

Recognizing the limitations of current therapies for Addison's disease, novel treatments that replicate dynamic physiologic corticosteroid secretion, under control of ACTH, are required. The aim of these experiments was to evaluate the feasibility of adrenocortical cell transplantation (ACT) in a large animal model, adapting methods successfully used for intracutaneous pancreatic islet cell transplantation, using a fully biodegradable temporizing matrix. Autologous porcine ACT was undertaken by bilateral adrenalectomy, cell isolation, culture, and intracutaneous injection into a skin site preprepared using a biodegradable temporizing matrix (BTM) foam. Hydrocortisone support was provided during adrenocortical cell engraftment and weaned as tolerated. Blood adrenocortical hormone concentrations were monitored, and the transplant site was examined at endpoint. Outcome measures included cellular histochemistry, systemic hormone production, and hydrocortisone independence. Transplanted adrenocortical cells showed a capability to survive and proliferate within the intracutaneous site and an ability to self-organize into discrete tissue organoids with features of the normal adrenal histologic architecture. Interpretation of systemic hormone levels was confounded by the identification of accessory adrenals and regenerative cortical tissue within the adrenal bed postmortem. Corticosteroids were unable to be completely ceased. ACT in a large animal model has not previously been attempted, yet it is an important step toward clinical translation. These results demonstrate rhe potential for ACT based on the development of adrenal organoids at the BTM site. However, the inability to achieve clinically relevant systemic hormone production suggests insufficient function, likely attributable to insufficient cells through delivered dose and subsequent proliferation.

Cutibacterium acnes induces acne-like lesions in hairless mice models - A comparative study

Acne vulgaris, a chronic inflammatory skin disease with a high prevalence worldwide, necessitates reliable preclinical models for both understanding its pathogenesis and evaluating potential anti-acne therapies. This study aims to establish a robust mouse model using intracutaneous injection of Cutibacterium acnes bacterial suspension. Three hairless mouse strains (SKH-hr1, SKH-hr2 brown, and SKH-hr2 + ApoE) were systematically compared to ascertain the stains most closely resembling acne in humans. Various assessments, including photo documentation, biophysical evaluation, blood analysis, and histopathology, were conducted. Despite all strains exhibiting acne-like lesions, SKH-hr1 mice emerged as the most suitable model, demonstrating the most satisfactory results across multiple criteria. This research underscores the significance of employing hairless mice strains as models in acne studies to enhance and facilitate the development of effective therapeutic interventions.

A preliminary investigation of precise visualization, localization, and resection of pelvic lymph nodes in bladder cancer by using indocyanine green fluorescence-guided approach through intracutaneous dye injection into the lower limbs and perineum.

This study aimed to investigate the feasibility and effectiveness of using indocyanine green (ICG) injected intracutaneously through the lower limbs and perineum for visualized tracking, localization, and qualitative assessment of pelvic lymph nodes (LNs) in bladder cancer to achieve their accurate resection. First, ICG was injected into the LN metastasis model mice lower limbs, and real-time and dynamic in vivo and ex vivo imaging was conducted by using a near-infrared fluorescence imaging system. Additionally, 26 patients with bladder cancer were enrolled and divided into intracutaneous group and transurethral group. A near-infrared fluorescence imaging device with internal and external imaging probes was used to perform real-time tracking, localization, and resection of the pelvic LNs. The mice normal LNs and the metastatic LNs exhibited fluorescence. The metastatic LNs showed a significantly higher signal-to-background ratio than the normal LNs (3.9 ± 0.2 vs. 2.0 ± 0.1, p < 0.05). In the intracutaneous group, the accuracy rate of fluorescent-labeled LNs was 97.6%, with an average of 11.3 ± 2.4 LNs resected per patient. Six positive LNs were detected in three patients (18.8%). In the transurethral group, the accuracy rate of fluorescent-labeled LNs was 84.4%, with an average of 8.6 ± 2.3 LNs resected per patient. Two positive LNs were detected in one patient (12.5%). Following the intracutaneous injection of ICG into the lower limbs and perineum, the dye accumulates in pelvic LNs through lymphatic reflux. By using near-infrared fluorescence laparoscopic fusion imaging, physicians can perform real-time tracking, localization, and precise resection of pelvic LNs.

Topical Application of TT-10 Ameliorates Impaired Wound Healing.

In recent decades, chronic wounds have become an increasingly significant clinical concern due to their increasing morbidity and socioeconomic toll. However, there is currently no product available on the market that specifically targets this intricate process. One clear indicator of delayed wound repair is the inhibition of re-epithelialization. Yes-associated protein (YAP), which is a potential focal point for tissue repair and regeneration, has been shown to be prominent in several studies. In this context, we have identified the pharmacological product TT-10, which is a YAP activator, as a potential candidate for the treatment of various forms of chronic wounds. The role of TT-10 in regulating YAP activity and subcellular localization was determined by western blotting and immunofluorescence staining. The effect of TT-10 on the biological functions of keratinocytes was assessed by proliferation, wound healing, and apoptosis assays. The impairment of YAP activity in chronic wounds was measured in human and mouse tissues. The in vivo efficacy of TT-10 was examined by gross examination, H&E staining, and measuring wound areas and gaps in normal, diabetic, and ischemic wounds. Our findings suggest that TT-10 facilitates the nuclear transport of YAP, consequently increasing YAP activity, which in turn increases the proliferation and migration of keratinocytes. Moreover, we showed that intracutaneous injection of TT-10 along the wound periphery promoted re-epithelization via YAP activation in the epidermis, culminating in accelerated wound closure in several chronic wound healing models. Our research highlights the potential of TT-10 to treat chronic wounds, which is a persistent challenge in tissue repair.

Effects of Gly-His-Lys-D-Ala Peptide on Skin Wound Regeneration Processes.

We evaluated the effects of the Gly-His-Lys-D-Ala peptide in a dose 0.5 μg/kg on skin wound regeneration in male Wistar rats (n=80) after initial surgical debridement when administered intracutaneously around the site of injury. Histological (severity of the inflammatory reaction, formation of granulation tissue, and epithelialization terms) and morphometric (number of fibroblastic cells, macrophages, granulocytes, and lymphocytes) studies were performed on autopsy specimens on days 3, 7, 10, and 30 of the experiment. Daily intracutaneous injection of the peptide resulted in an increase in the number of fibroblastic cells and macrophages, as well as in a decrease in the number of granulocytes against the background of active wound contraction on day 30 of the experiment. Thus, Gly-His-Lys-D-Ala alleviated the inflammatory reaction and promoted the regenerative processes.

Intranipple injection with methylene blue for tracing axillary sentinel lymph nodes in rats: A preliminary feasibility study

Background and purpose: Investigate the feasibility of intranipple injection (INN) of methylene blue dye (MB) for tracing the axillary sentinel lymph node (SLN) in rats, to provide different injection methods for finding SLN injection tracers and offer an experimental basis for specific localization of SLN. Methods: Eleven Sprague-Dawley female rats with body masses of 150-400g. Ten rats were randomly selected to use the third pair of mammary glands as the tracer injection site, and the left side was injected with MB (0.05 mL, 1% concentration) by intracutaneous injection of areola (IAA), while the right side was injected with MB(0.05 mL, 1% concentration) by INN. After 5 minutes, the rats were dislocated and dissected, and the blue-stained SLNs were found and recorded, The effectiveness evaluation was based on the number and rate of detection of SLNs as indicators, and the differences between the indicators of the two injection methods of IAA and INN were compared and analyzed. The safety evaluation was based on whether the nipple showed blood flow disorders and necrosis after MB injection by INN in the remaining 1 rat as the criteria. The data were stored and analyzed using Microsoft Excel and SPSS 25.0 statistical software. Νon-normally distributed measurement data were expressed as M (Q1, Q3) and compared by rank sum test, and count data were expressed as cases or percentages and compared by 2 test. p &lt; 0.05 was considered a statistically significant difference. Results: (i)100% (10/10) detection rate of SLNs by applying MB to both INN and IAA modalities;(ii) median number of SLNs detection was 2.0 (1.0,2.0) vs. 1.5 (1.0,2.0) for INN and IAA, respectively (P=0.66), and the difference was not statistically significant;(iii) No nipple necrosis was observed for 4 consecutive days after INN with MB. Conclusion: Tracer detection of SLNs by INN injection in rats is feasible, and the detection rate of SLNs by INN is the same as that of IAA; there is no significant difference in the median number of detected SLNs between the two injection methods. No nipple necrosis was observed after INN with MB.

IgE and anaphylaxis specific to the carbohydrate alpha-gal depend on IL-4

Alpha-gal (Galα1-3Galβ1-4GlcNAc) is a carbohydrate with the potential to elicit fatal allergic reactions to mammalian meat and drugs of mammalian origin. This type of allergy is induced by tick bites, and therapeutic options for this skin-driven food allergy are limited to the avoidance of the allergen and treatment of symptoms. Thus, a better understanding of the immune mechanisms resulting in sensitization through the skin is crucial, especially in the case of a carbohydrate allergen for which underlying immune responses are poorly understood. We aimed to establish a mouse model of alpha-gal allergy for in-depth immunologic analyses. Alpha-galactosyltransferase 1-deficient mice devoid of alpha-gal glycosylations were sensitized with the alpha-gal-carrying self-protein mouse serum albumin by repetitive intracutaneous injections in combination with the adjuvant aluminum hydroxide. The role of basophils and IL-4 in sensitization was investigated by antibody-mediated depletion. Alpha-gal-sensitized mice displayed increased levels of alpha-gal-specific IgE and IgG1 and developed systemic anaphylaxis on challenge with both alpha-gal-containing glycoproteins and glycolipids. In accordance with alpha-gal-allergic patients, we detected elevated numbers of basophils at the site of sensitization as well as increased numbers of alpha-gal-specific B cells, germinal center B cells, and B cells of IgE and IgG1 isotypes in skin-draining lymph nodes. By depleting IL-4 during sensitization, we demonstrated for the first time that sensitization and elicitation of allergy to alpha-gal and correspondingly to a carbohydrate allergen is dependent on IL-4. These findings establish IL-4 as a potential target to interfere with alpha-gal allergy elicited by tick bites.

MiR-199a-3p Regulates the PTPRF/β-Catenin Axis in Hair Follicle Development: Insights into the Pathogenic Mechanism of Alopecia Areata.

Alopecia areata is an autoimmune disease characterized by the immune system attacking self hair follicles, mainly in the scalp. There is no complete cure, and the pathogenesis is still not fully understood. Here, sequencing of skin tissues collected from 1-month-old coarse- and fine-wool lambs identified miR-199a-3p as the only small RNA significantly overexpressed in the fine-wool group, suggesting a role in hair follicle development. MiR-199a-3p expression was concentrated in the dermal papillae cells of sheep hair follicles, along with enhanced β-catenin expression and the inhibition of PTPRF protein expression. We also successfully constructed a mouse model of alopecia areata by intracutaneous injection with an miR-199a-3p antagomir. Injection of the miR-199a-3p agomir resulted in hair growth and earlier anagen entry. Conversely, local injection with the miR-199a-3p antagomir resulted in suppressed hair growth at the injection site, upregulation of immune system-related genes, and downregulation of hair follicle development-related genes. In vivo and in vitro analyses demonstrated that miR-199a-3p regulates hair follicle development through the PTPRF/β-catenin axis. In conclusion, a mouse model of alopecia areata was successfully established by downregulation of a small RNA, suggesting the potential value of miR-199a-3p in the study of alopecia diseases. The regulatory role of miR-199a-3p in the PTPRF/β-catenin axis was confirmed, further demonstrating the link between alopecia areata and the Wnt-signaling pathway.

Neurotensin counteracts hair growth inhibition induced by chronic restraint stress.

Stress has been considered as a potential trigger for hair loss through the neuroendocrine-hair follicle (HF) axis. Neurotensin (NTS), a neuropeptide, is known to be dysregulated in the inflammatory-associated skin diseases. However, the precise role of NTS in stress-induced hair loss is unclear. To investigate the function and potential mechanisms of NTS in stress-induced hair growth inhibition, we initially detected the expression of neurotensin receptor (Ntsr) and NTS in the skin tissues of stressed mice by RNA-sequencing and ELISA. We found chronic restraint stress (CRS) significantly decreased the expression of both NTS and Ntsr in the skin tissues of mice. Intracutaneous injection of NTS effectively counteracted CRS-induced inhibition of hair growth in mice. Furthermore, NTS regulated a total of 1093 genes expression in human dermal papilla cells (HDPC), with 591 genes being up-regulated and 502 genes being down-regulated. GO analysis showed DNA replication, cell cycle, integral component of plasma membrane and angiogenesis-associated genes were significantly regulated by NTS. KEGG enrichment demonstrated that NTS also regulated genes related to the Hippo signalling pathway, axon guidance, cytokine-cytokine receptor interaction and Wnt signalling pathway in HDPC. Our results not only uncovered the potential effects of NTS on stress-induced hair growth inhibition but also provided an understanding of the mechanisms at the gene transcriptional level.

Porous NiTi Dental Implant Fabricated by a Metal Injection Molding: An in Vivo Biocompatibility Evaluation in an Animal Model.

This study assessed the corrosion resistance, intracutaneous reactivity, acute systemic toxicity, and in situ tissue effect of the implantation of porous NiTi fabricated by metal injection molding in animal models. For the intracutaneous reactivity study, five intracutaneous injections were administered per site with and without the tested extract in polar and nonpolar solutions. The extract was also delivered via intravenous and intraperitoneal routes for acute systemic toxicity. TiAl6 V4 (control) and porous NiTi were implanted in rabbit femora for a period of 13 weeks to evaluate the in situ tissue response. Corrosion was evaluated through open and cyclic polarization in PBS, while biocompatibility was investigated by assessing the general conditions, skin irritation score (edema and erythema), and histopathology. No active dissolution or hysteresis loop was observed in the corrosion study. None of the animals exhibited death, moribundity, impending death, severe pain, self-mutilation, or overgrooming. No edema was observed at injection sites. Only the positive control showed an erythematous reaction at 24, 48, and 72 h observations (p < 0.001). Porous NiTi showed a low in situ biological response for inflammation, neovascularization, and fibrosis in comparison to the control implant (p = 0.247, 0.005, and 0.011, respectively). Porous NiTi also demonstrated high pitting corrosion resistance while causing no acute hypersensitivity or acute systemic toxicity. The study concludes that porous NiTi implants were unlikely to cause local sensitization, acute systemic toxicity, or chronic inflammatory reactions in an animal model. Porous NiTi also exhibited osseointegration equivalent to Ti6AI4 V of known biocompatibility.

Intradermal Local Injection of Autologous Cell‐Free Fat Extract for the Treatment of Refractory Postinflammatory Hyperpigmentation

Current treatment modalities for postinflammatory hyperpigmentation (PIH) often fall short in delivering satisfactory results for some patients. Therefore, this study aimed to assess the efficacy and tolerability of autologous cell‐free fat extract (CEFFE) in the treatment of PIH. We enrolled 15 patients with PIH and administered them with five intracutaneous CEFFE injections, each at a two‐week interval. Evaluation included efficacy assessment using objective (standard two‐dimensional photos, VISIA®‐photos, brown spot (BS) index, lesion lightness, lesion color, and trans‐epidermal water loss) and subjective (Global Aesthetic Improvement Scale and Likert satisfaction scale) parameters and tolerance assessment. Following CEFFE treatment, significant reductions were observed in the BS index (p &lt; 0.05) and transepidermal water loss (p &lt; 0.05), while skin lightness and lesion color showed significant improvements (p &lt; 0.05) at the 12‐month follow‐up. Subjectively, 93.33% of patients reported improved or greatly improved conditions after 12 months of treatment. Transient local bruising and stinging were the only observed treatment‐related adverse events, with no serious complications reported. These findings demonstrate that intradermal injections of CEFFE are well‐tolerated and effective for the treatment of PIH. This trial is registered with ChiCTR2000039381.

Treatment of an Inguinal Lymphatic Fistula with Indocyanine Green

<h3>Study Objective</h3> To address iatrogenic lymphocele after inguinal lymphadenectomy for vulvar cancer with a minimally invasive intervention, by localizing the disrupted lymphatic duct with real-time NIR/ICG fluorescent imaging. <h3>Design</h3> Narrated video footage. <h3>Setting</h3> Department of Gynecologic Oncology, Bern University Hospital. <h3>Patients or Participants</h3> Patient A underwent hemivulvectomy with homolateral inguinal sentinel lymphadenectomy for a squamous cell carcinoma of the right vulva, FIGO Ib. Two weeks later she reported a wound dehiscence in her right groin with abundant yellowish discharges, persisting over time and leading to a remarkable progression of the dehiscence. Patient B was seen after R1 resection of a relapsing FIGO II, already treated with combined chemoradiotherapy one year before. She underwent dorsal hemivulvectomy with bilateral inguinal lymphadenectomy, complete colpectomy and coverage of tissue defects with fascio-cutaneous flaps. Two weeks later she reported a closed inguinal lymphocele. We attempted a conservative treatment with antibiotics and needle aspirations, nevertheless a multibacterial infection occurred on the right side. <h3>Interventions</h3> By failing conservative measures, surgical correction of assumed lymphatic fistulas was called for in both cases. After debridement of the inguinal wound in local anesthesia, an intracutaneous injection of 2 ml ICG was carried out between the 1st and 2nd ipsilateral toe. <h3>Measurements and Main Results</h3> After 7 minutes a fluorescent effusion from the site of the fistula was identified in real-time NIR imaging, performed with an optic device (VITOM® ICG) installed on the operating table for the extracorporeal detection of the fluorescence produced by ICG. The disrupted lymphatic duct could be ligated. The absence of further fluorescent effusion confirmed the successful repair. The wound was closed and healed well in the follow-up. No recurrence or exacerbation of the lymphedema occurred. <h3>Conclusion</h3> Intraoperative NIR/ICG fluorescence lymphatic imaging with an exoscope enables a highly sensitive detection of lymphatic structures and a tailored curative intervention, with a safe toxicological profile and without radiation exposure.

Sentinel lymph node mapping with superparamagnetic iron oxide for melanoma: a pilot study in healthy participants to establish an optimal MRI workflow protocol

BackgroundCurrent pre-operative Sentinel Lymph Node (SLN) mapping using dual tracing is associated with drawbacks (radiation exposure, logistic challenges). Superparamagnetic iron oxide (SPIO) is a non-inferior alternative for SLN mapping in breast cancer patients. Limited research has been performed on SPIO use and pre-operative MRI in melanoma patients to identify SLNs. MethodsHealthy participants underwent MRI-scanning pre- and post SPIO-injection during 20 min. Workflow protocols varied in dosage, massage duration, route of administration and injection sites. The first lymph node showing a susceptibility artefact caused by SPIO accumulation was considered as SLN.ResultsArtefacts were identified in 5/6 participants. Two participants received a 0.5 ml subcutaneous injection and 30-s massage, of which one showed an artefact after one hour. Four participants received a 1.0 ml intracutaneous injection and two-minute massage, leading to artefacts in all participants. All SLNs were observed within five minutes, except after lower limb injection (30 min).ConclusionSPIO and pre-operative MRI-scanning seems to be a promising alternative for SLN visualization in melanoma patients. An intracutaneous injection of 1.0 ml SPIO tracer, followed by a two-minute massage seems to be the most effective technique, simplifying the pre-operative pathway. Result will be used in a larger prospective study with melanoma patients.Trial registrationClinicalTrials.gov (NCT05054062) – September 9, 2021.

0750 Performance Testing of a Novel Oral Appliance Material; A New Standard for OAT

Abstract Introduction Traditionally, oral appliances for treating obstructive sleep apnea have borrowed from the disciplines of removable prosthetics and orthodontics. The materials, design and manufacturing have evolved little. Today, precision milled devices using innovative materials and designs have leapt past artisanal legacy devices. The use of artificial intelligent design to accurately replicate tooth surface anatomy and robotic manufacturing to insure precision are requiring higher table stakes to ‘get in the game’. Mill-able polymethylmethacrylate, MG6™ Technology materials and printed nylons have replaced cold cured acrylics, Thermacryl, soft liners and suck down platforms. The testing and material standards should also evolve as well. Methods Typically, no specific ISO testing is performed on legacy device compositions. This new medical grade class VI (the highest category) material promised to be more robust, safer and to have the highest biocompatibility. ISO testing was performed in the following arenas: ISO tests 10993-4 Hemolysis, 10993-4 in vitro hemocompatibility, 10993-5 cytotoxicity, 10993-6 short-term intramuscular implantation, 10993-10 intracutaneous injection, 10993-11 system toxicity and USP 38 physiochemical testing.Similarly, no specific durability testing is done beyond the safety requirement designs set by the FDA. This material was exposed to all the tradition stress, bend and compression testing as well as the MIL-STD-810H Military Free Fall Drop Test. Finally, stain, biogunk and the ease of keeping a device clean are always a concern with legacy device materials. Milled PMMA has been shown previously to be nearly impervious to stain and bioburden uptake. This material was tested along with predicates and PAP mask materials for comparison. Results ISO TestingThe Material passed all the tests as indicated in reports nos. BIO-ATX 1856,1857,1858, and BIO-GNT 8321. 832, 833. Military Drop TestThis material passed the military drop test (40 cases, each dropped 6 times). Method Test 810H section 4.6.5 Procedure IV Table 516.8-X Unpackaged handling. Stain TestingMilled Iterative PMMA DE = 3.06Milled Iterative EVO material DE = 3.20CPAP Mask plastic DE = 7.54Milled PMMA w/ soft Liner/Fulcrum Strap DE = 8.27CPAP Mask silicone DE = 11.60PMMA + Liner Anterior Hook DE = 19.05PMMA with Liner Herbst DE = 32.05Nylon with Airway DE = 90.70Nylon with Straps DE = 96.99 Conclusion Medical grade class VI material sets new standard for oral appliance material performance Support (If Any) Data provided by ProSomnus, ISO.org and the DOD.

Trichoderma longibrachiatum-Associated Skin Inflammation and Atypical Hyperplasia in Mouse.

BackgroundThe relationship between infection and tumors has attracted increasing attention. Trichoderma spp. are often isolated from tumors. However, their potential role remains unclear. We recently reported the isolation of Trichoderma longibrachiatum from a patient with pulmonary spindle cell carcinoma that was confirmed as primary infection by application of laser capture microdissection and polymerase chain reaction. To explore whether the strain is pathogenic and whether it can cause atypical cell proliferation and infiltration of NK cells and T cells, we designed a mouse infection experiment.MethodsTwelve ICR mice were randomly separated into three groups. Cyclophosphamide was used to inhibit the immunity of mice. A mouse model of Trichoderma infection was successfully established by intracutaneous injection on the back skin with a suspension of strain PKUT180420015. The pathological manifestations of Trichoderma infection and the interaction between immune cells and fungi were observed by histopathology, immunohistochemistry and intensive fungal staining. Reisolation of the fungus was observed by infected tissue culture. The inoculated sites exhibited swelling 3 days after inoculation, and ulcers developed at approximately 14 days. Skin specimens were obtained and then cultured at 3, 7, and 14 days after inoculation. We selected mice 14 days after inoculation in Group 3, whose ulcers were the most typical, for histological analysis.ResultsInflammation, angioinvasion and necrosis were observed. Immunohistochemistry showed positive markers of Ki67, CD3, CD56, GZMB, and PRF. Periodic acid-Schiff staining, periodic acid-silver methenamine staining, and Calcofluor staining showed fungal spores in the vascular lumen, vascular walls and around the blood vessels.ConclusionsOur studies showed that a T. longibrachiatum strain (PKUT180420015) isolated from a biopsy specimen in a patient with pulmonary spindle cell carcinoma could induce atypical hyperplasia, with the expression of Ki67, CD3, CD56, GZMB, and PRF in mice. These data indicate that the fungus may be involved in inducing atypical hyperplasia or tumorigenesis.

Secretome – A new “Cappiler” for Compartement Syndrome

Compartment Syndrome, an orthopedic emergency, is a condition of increased perfusion pressure under closed tissue. Necrosis of the nerves and muscles, namely contracture of Volkmann and systemic complications such as acute renal failure, sepsis, ARDS, will result in compartment syndrome that is not properly treated. In children, doctors must be able to diagnose compartment syndrome in order to treat it in a timely manner. The effects of mismanagement will have an impact on the future of the child. A 5-year-old boy presented a case report with complaints of worsening wounds accompanied by loss of sensation. As the patient went to alternative medicine, the patient had to be amputated because of an error in the administration of therapy (The patient came to the “dukun tulang” for 5 months ago and received inappropriate treatment). Patients have signed an agreement to follow up on treatment by single-dose intracutaneous injection of Placental Wharton Jelly Stem Cell Secretom (SC-PWJSC). Intracutaneous injection of Secretom from Placental Wharton Jelly Stem Cell after administration of a single dose of 5cc (SC-PWJSC). The patient was advised to undergo amputation and the SC-PWJSC intracutaneous injection procedure was given to the patient. There was a significant improvement in the situation after 4 weeks of intervention.

Effect of topical local anaesthesia on injection pain associated with administration of sterile water injections - a randomized controlled trial

BackgroundSterile water injections can provide effective pain relief during childbirth, particularly for low back pain related to childbirth. However, the pain associated administering the injections can negatively impact women’s impressions of the procedure. It may discourage women from considering repeat doses despite the quality of analgesia experienced. Determining strategies to reduce the pain related to the administration of sterile water injections would improve the acceptability of the technique. Therefore, the aim of this study was to evaluate the effect of topical local anesthesia on the pain associated with administration of sterile water injections.MethodsThe study was designed as a multi-arm single-blind, randomized, controlled trial and 120 female healthy students were randomly divided according to one of four groups. The Intervention group received sterile water injections with topical local anesthesia. Control group 1 received sterile water injections without topical local anesthesia, control group 2 received injections of isotonic saline 0.9% with topical local anesthesia and control group 3 received injections of isotonic saline 0.9% without topical local anesthesia. Pain Immediately after the injections and subsidence in pain were recorded using a visual analogue scale. Sensations in the injection area were reported 15 min and the day after the injections.ResultsThe main finding of this study was that local anesthesia with EMLA® reduces the pain associated with the administration of intracutaneous sterile water injections. There was a significant difference in the self-assessed pain score immediately following the injections between the control (73.3 mm) and intervention groups (50.0 mm), p = 0.001. No adverse side effects were reported.ConclusionLocal anesthesia with EMLA® reduces the pain associated with intracutaneous administration of sterile water injections.Trial registrationThe study was registered 08/07/2014 at ClinicalTrials.gov Identifier: NCT02213185.