Needle Length Research Articles

Insulin Injection Technique and Related Complications in Patients With Diabetes in a Northwest City of China.

Appropriate insulin injection technique can help to enhance positive clinical outcomes in insulin-treated patients. This cross-sectional survey was undertaken to assess the present state of injection technique practices of patients administering insulin and the incidence of local complications associated with insulin injection. This cross-sectional study was conducted at 11 tertiary hospitals in Xi'an City. A total of 1370 patients with diabetes were enroled in the survey. Each patient was asked questions on the Injection Technique questionnaire, demonstrated insulin injection on an injection training pad and had their injection sites inspected by a nurse. About 98% of participants were type 2 diabetic patients. The 5 mm length needles were used by 640 (46.71%) patients. Around 1286 participants reused pen needles. Only one-third of patients rotate the injection sites. Around 901 patients had ecchymosis at injection sites, 43 participants suffered rash and or pruritus and 661 patients had lipohypertrophy. About 2.99% of patients reported having infection at the injection sites. Most patients (72.55%) occasionally felt pain when injecting insulin. The results of the multivariable logistict analysis showed that gender (male), needle length, priming the pen before injections and correct site rotation were negatively associated with the incidence of injection site ecchymosis. Lower incidence of lipohypertrophy was associated with needle length 4 mm, needle length 6 mm, single use of pen needles, priming the pen before injections and correct site rotation. Higher incidence of injection site infection was related to not disinfecting injection sites before each injection. Despite some improvements detected in some aspects of patients' insulin injection practice in recent years, a large gap still exists between insulin injection guidelines and patients' actual injection behaviour. Injection-related complications at injection sites are still considerably common among our study population. Patients' education regarding insulin injection technique should be conducted repeatedly and regularly to make sure patients' compliance to injection guidelines.

Current Practice and Perspectives on Subcutaneous Immunoglobulin Replacement Therapy in Patients with Primary Antibody Deficiency Among Specialized Nurses in Poland

Background/Objectives: Inborn errors of immunity (IEI) encompass various congenital disorders, resulting in immunity defects and recurrent infections. Home-based subcutaneous immunoglobulin replacement therapy (scIgRT) is the best treatment option for those with primary antibody deficiency (PAD). However, the lack of standardized procedures in patient training remains a challenge. Our study investigates nurses’ practice and perspectives, aiming to identify areas for improvement in at-home scIgRT practice. Methods: We prepared a structured survey regarding scIgRT, including needle choice experience and perception of adverse events, and distributed it among qualified nurses involved in patient training and scIgRT supervising. Results: We included 56 nurses with a median age of 50 years. Among them, 67.9% represented adult care providers, while 32.1% supervised IgRT in children. Most respondents (83.9%) used the classic or assisted with hyaluronidase scIgRT preparations. Single-channel needles were administered most commonly (85.7%). The needle length was mostly chosen solely by a nurse (57.1%) or in cooperation with the patient (23.2%). Next, 9 mm and 12 mm needles were used most often (92.9% and 78.6%, respectively). As expected, the 6 mm needle was more frequently applied for children compared to adults (n = 16, 88.9% vs. n = 11, 28.9%, p < 0.001), while 12 mm was primarily used in adults (n = 35, 92.1% vs. n = 9, 50.0%, p < 0.001). Visual skin fold assessment was the basis for the needle selection (58.9%), followed by the injection site rule (26.8%) or a choice between two available needle types for thinner or thicker patients (25.0%). Results of this survey indicate that, according to nurses’ opinions presented in this survey, the needle length could be associated with local scIgRT adverse events, such as side needle leakage or local burning. Yet, it was likely unrelated to general adverse signs, such as headaches or dizziness. Most respondents (66.1%) indicated that, even if local adverse events occur, patients are reluctant to change scIgRT preparation or needle length. Most participants (69.6%) reported that the optimal administration technique needs to be discussed with the patient before and during scIgRT. Conclusions: This study sheds light on scIgRT practice in Poland, emphasizing deficiency in needle selection technique. Future research should focus on standardized training and advanced needle selection procedures on patient outcomes, investigating the correlation between needle strategies and adverse events, as well as the effectiveness of scIgRT.

Clinical assessment of the potential use of a novel single-dose prefilled injection device for the administration of Acthar Gel in children: a narrative review.

Acthar® Gel (repository corticotropin injection; Mallinckrodt Pharmaceuticals, NJ, USA) is indicated for the treatment of myriad inflammatory disorders and is currently administered manually via a vial and syringe. The administration of Acthar via a single-dose prefilled injector (SelfJect™) is intended to simplify its subcutaneous (SC) delivery. The purpose of this review was to determine whether SelfJect is suitable for use in pediatric patients through a literature assessment of various factors, including skin depth, needle length and gauge, dosage, force required for injection, and potential harms. Infants and young children, who commonly have skin-to-muscle distances less than the minimum depth of SelfJect administration, may have risk of unintentional intramuscular (IM) injection; however, an inadvertent IM injection poses no additional risk to children because of the bioequivalence between SC and IM administration of Acthar. The needle gauge of SelfJect is acceptable for pediatric patients and aligns with the Centers for Disease Control and Prevention recommendations for SC injections. The dosage delivered by SelfJect is only appropriate for children over 2years of age. Although adolescents would likely be able to achieve the minimum force required to remove the protective cap and deliver a full dose of Acthar with SelfJect, an adult (18years of age and older) should administer SelfJect to pediatric patients. In addition to the commonly reported postmarketing adverse events (AEs) from Acthar administration (e.g., asthenic conditions, fluid retention, insomnia, headache and increased blood glucose), injection site-related AEs common to injection devices may occur with SelfJect use. The risk of needlestick injury from SelfJect is mitigated by a needle guard. In summary, this review of injection device considerations demonstrates that SelfJect is appropriate for use in the pediatric population.

Indicators of woody plants and soil in the urbanised environment of the Southern Urals (green zone of Ufa, Russia)

ABSTRACT The study investigates biometric indicators of assimilation and reproductive organs of coniferous and deciduous trees in urban environments: leaf area, inflorescence flower count, stipule length of Tilia cordata Mill. and needle length and weight of Scots pine (Pinus sylvestris L.). Samples of wood, needles, leaves and soil from the planting sites were analysed for 17 chemical elements, including Hazard Class I elements (Arsenic, Lead, Cadmium, Mercury, Selenium) and Hazard Class II elements (Chromium, Cobalt, Nickel, Copper, Molybdenum, Antimony). Tree plantations decreased airborne dust by 30–40% compared to open areas. Concentrations of PM2.5 and PM10 particles showed a direct correlation with busy roads (p < 0.05). In instances of environmental degradation, healthy trees exhibited in needle an increase in biomass and a reduction in weight and length. Consequently, forestry measurements and the impact of the urban environment require specific and individual monitoring of trees, rather than a general assessment of plantations.

Impact of radiomics features, pulmonary emphysema score and muscle mass on the rate of pneumothorax and chest tube insertion in CT-guided lung biopsies

Iatrogenic pneumothorax is a relevant complication of computed tomography (CT)-guided percutaneous lung biopsy. The aim of the present study was to analyze the prognostic significance of texture analysis, emphysema score and muscle mass derived from CT-imaging to predict postinterventional pneumothorax after CT-guided lung biopsy. Consecutive patients undergoing CT-guided percutaneous lung biopsy between 2012 and 2021 were analyzed. Multivariate logistic regression analysis included clinical risk factors and CT-imaging features to detect associations with pneumothorax development. Overall, 479 patients (178 females, mean age 65 ± 11.7 years) underwent CT-guided percutaneous lung biopsy of which 180 patients (37.5%) developed pneumothorax including 55 patients (11.5%) requiring chest tube placement. Risk factors associated with pneumothorax were chronic-obstructive pulmonary disease (COPD) (p = 0.03), age (p = 0.02), total lung capacity (p < 0.01) and residual volume (p = 0.01) as well as interventional parameters needle length inside the lung (p < 0.001), target lesion attached to pleura (p = 0.04), and intervention duration (p < 0.001). The combined model demonstrated a prediction accuracy of the occurrence of pneumothorax with an AUC of 0.78 [95%CI: 0.70–0.86] with a resulting sensitivity 0.80 and a specificity of 0.66. In conclusion, radiomics features of the target lesion and the lung lobe CT-emphysema score are predictive for the occurrence of pneumothorax and need for chest insertion after CT-guided lung biopsy.

The variation in climate conditions and fire-related traits across Pinus (Pinaceae) species

Fire has long been recognized as a significant evolutionary factor for the genus Pinus (family Pinaceae). Many pine species have developed specific fire-adaptations, such as self-pruning, resprouting, and serotiny, to persist under various fire regimes. Fire-related traits, such as needle length, bark thickness, and plant height, also can affect the survival of pines in fire-prone environments. Investigating the climate conditions of pines and analyzing the variation in fire-adaptations and fire-related traits across pines can provide insights into the evolutionary process of the genus Pinus affected by fire. However, such studies are rare, particularly those focusing on the relationship among environmental conditions, fire-adaptations, and fire-related traits with a large number of pine species. In this study, we explored the variation in climate conditions and fire-related traits (including tree height, bark thickness, and leaf length) between fire-adapted and non-fire-adapted pines, as well as among three fire survival strategies (fire-tolerators, fire-embracers, fire avoiders). We also investigated the relationships between climatic conditions and fire-related traits/fire-adaptations (including resprouting, self-pruning, the grass stage, and serotiny) across the genus Pinus. Sixty-one out of 101 pine species were found to possess one or more fire adaptations and were classified as fire-adapted pines. We found that fire-adapted pines occupy warmer and more fire-prone habitats, and exhibit longer leaves, thicker bark, and taller habits than non-fire-adapted species. Our analysis did not indicate a significant difference between fire tolerators and embracers regarding traits and climate conditions, except that fire-tolerators have thicker bark and are more associated with wildfire-prone areas. Climate conditions appeared to significantly affect fire-related traits/fire-adaptations across the genus Pinus. These findings will facilitate our understanding the evolutionary process of fire adaptations/fire-related traits in the genus Pinus and will guide sustainable fire management in different pine forests.

Development of Norelgestromin Dissolving Bilayer Microarray Patches for Sustained Release of Hormonal Contraceptive.

Microarray patches (MAPs) offer a noninvasive and patient-friendly drug delivery method, suitable for self-administration, which is especially promising for low- and middle-income country settings. This study focuses on the development of dissolving bilayer MAPs loaded with norelgestromin (NGMN) as a first step towards developing a future potential drug delivery system for sustained hormonal contraception. The fabricated MAPs were designed with the appropriate needle lengths to penetrate the stratum corneum, while remaining minimally stimulating to dermal nociceptors. Ex vivo assessments showed that the MAPs delivered an average of 176 ± 60.9 μg of NGMN per MAP into excised neonatal porcine skin, representing 15.3 ± 5.3% of the loaded drug. In vivo pharmacokinetic analysis in Sprague Dawley rats demonstrated a Tmax of 4 h and a Cmax of 67.4 ± 20.1 ng/mL for the MAP-treated group, compared to a Tmax of 1 h and a Cmax of 700 ± 138 ng/mL for the intramuscular (IM) injection group, with a relative bioavailability of approximately 10% for the MAPs. The MAP-treated rats maintained plasma levels sufficient for therapeutic effects for up to 7 days after a single application. These results indicate the potential of NGMN-loaded dissolving bilayer MAPs, with further development focused on extending the release duration and improving bioavailability for prolonged contraceptive effects.

Comparative metabolomics and transcriptomics analyses provide insights into branching changes induced by heterografting in Pinus massoniana seedlings

The investigation of dwarfing rootstocks for the establishment of high-generation seed orchards is a prospective avenue of research. In this investigation, Pinus massoniana, Pinus yunnanensis var. pygmaea (P. pygmaea), and P. elliottii seedlings were used as rootstocks for grafting with P. massoniana scions. Grafting P. massoniana onto P. pygmaea rootstock resulted in observable phenotypic alterations in lateral branches, apical buds, and needle length. Certain characteristic metabolites of rootstocks, such as fatty acyls, pregnenolones, steroids, and steroid derivatives, were found to be highly expressed in scions after grafting. RNA-seq analysis revealed MYB-related, SBP, and bHLH demonstrating a significant positive correlation, while C2H2 and Orphans exhibited negative correlations with the differential intensity of metabolites related to lipids and lipid-like molecules. This study offers valuable insights for the establishment of rootstock breeding programs.

A temporal enhanced semi-supervised training framework for needle segmentation in 3D ultrasound images

Objective. Automated biopsy needle segmentation in 3D ultrasound images can be used for biopsy navigation, but it is quite challenging due to the low ultrasound image resolution and interference similar to the needle appearance. For 3D medical image segmentation, such deep learning networks as convolutional neural network and transformer have been investigated. However, these segmentation methods require numerous labeled data for training, have difficulty in meeting the real-time segmentation requirement and involve high memory consumption. Approach. In this paper, we have proposed the temporal information-based semi-supervised training framework for fast and accurate needle segmentation. Firstly, a novel circle transformer module based on the static and dynamic features has been designed after the encoders for extracting and fusing the temporal information. Then, the consistency constraints of the outputs before and after combining temporal information are proposed to provide the semi-supervision for the unlabeled volume. Finally, the model is trained using the loss function which combines the cross-entropy and Dice similarity coefficient (DSC) based segmentation loss with mean square error based consistency loss. The trained model with the single ultrasound volume input is applied to realize the needle segmentation in ultrasound volume. Main results. Experimental results on three needle ultrasound datasets acquired during the beagle biopsy show that our approach is superior to the most competitive mainstream temporal segmentation model and semi-supervised method by providing higher DSC (77.1% versus 76.5%), smaller needle tip position (1.28 mm versus 1.87 mm) and length (1.78 mm versus 2.19 mm) errors on the kidney dataset as well as DSC (78.5% versus 76.9%), needle tip position (0.86 mm versus 1.12 mm) and length (1.01 mm versus 1.26 mm) errors on the prostate dataset. Significance. The proposed method can significantly enhance needle segmentation accuracy by training with sequential images at no additional cost. This enhancement may further improve the effectiveness of biopsy navigation systems.

The Precision and Safety of Ultrasound-Guided versus Palpation-Guided Needle Placement on the Plantar Fascia and Flexor Digitorum Brevis Interface: An Anatomical Study.

Evidence suggests the plantar fascia and its interphase with the flexor digitorum brevis muscle can play a relevant role in plantar heel pain. Needling interventions could offer an appropriate treatment strategy to addressing this interface. We compared the accuracy and safety of ultrasound-guided versus palpation-guided procedures for the proper targeting of the interface between the plantar fascia and the flexor digitorum brevis with a solid needle. A crossover cadaveric study was conducted. Five experienced therapists performed a series of 20 needle insertions each (n = 100 in total, 10 landmark-guided and 10 ultrasound-guided) on 10 anatomical samples. The therapists were instructed to accurately place the needle on the interface between the plantar fascia and the flexor digitorum brevis muscle. The distance of the tip of the needle to the identified target (accuracy), the surrounding sensitive structures targeted (safety), the time needed for the procedure, the number of needle passes, and the needle length outside the skin were assessed. The ultrasound-guided technique was associated with a significantly higher accuracy (p < 0.001) but without differences in safety (p = 0.249) as compared to the palpation-guided procedure. Our results suggest that ultrasound-guided insertion exhibits greater accuracy but not greater safety than palpation-guided insertion when targeting the interface between the plantar fascia and the flexor digitorum brevis.

Incorporation of Finasteride-Loaded Microspheres into Personalized Microneedle for Sustained Transdermal Delivery.

Although finasteride (FNS) tablets are considered the most effective drug for the treatment of androgenetic alopecia (AGA), their clinical applications are limited due to the associated side effects including decreased libido, breast enlargement, and liver dysfunction. In this study, we have developed a personalized microneedle (PMN) with a double-layer structure that incorporates FNS-loaded microspheres (MPs) to accommodate irregular skin surfaces. This design enables the sustained release of FNS, thereby reducing potential side effects. The needle body was synthesized with high-strength hyaluronic acid (HA) as the base material substrate. The backing layer utilized methacrylate gelatin (GelMA) with specific toughness, enabling PMN to penetrate the skin while adapting to various skin environments. The length of PMN needles (10 × 10) was approximately 600 μm, with the bottom of the needles measuring about 330 μm × 330 μm. The distance between adjacent tips was around 600 μm, allowing the drug to penetrate the stratum corneum of the skin. The results of the drug release investigation indicated the sustained and regulated release of FNS from PMN, as compared to that of pure FNS and FNS-MPs. Further, the cytotoxicity assay demonstrates that PMS displays good cytocompatibility. Altogether, this mode of administration has immense potential for the development of delivery of other drugs, as well as in the medical field.

Frequencies and predictors of subcutaneous and intraosseous injection with 4 epinephrine autoinjector devices

BackgroundTo prevent anaphylaxis-associated illness, intramuscular epinephrine injection is recommended. Subcutaneous injection may reduce efficacy, and intraosseous injection promotes morbidity. A few studies suggested that commercially available thigh epinephrine autoinjectors (EAIs) may induce subcutaneous/intraosseous injection in some adults. ObjectiveTo estimate the subcutaneous/intraosseous-injection rates of 4 EAIs by comparing their needle lengths with the ultrasound-measured skin-to-muscle depth and skin-to-bone depth of the midthigh of adults with allergic diseases in a cross-sectional study and to determine patient factors that predict subcutaneous EAI injection. MethodsThigh ultrasound was conducted in a convenience-recruited cohort with minimal and maximal compression to estimate the effect of EAI-induced compression. Subcutaneous/intraosseous-injection rates were estimated for Anapen (BioProject), EpiPen (Mylan), Jext (ALK), and Emerade (Medeca). Multivariate analyses for subcutaneous-injection risk were conducted with age, male/female sex, abdominal and thigh circumferences, and upper-arm skinfold thickness. ResultsA total of 68 patients were recruited. Compression thinned the subcutaneous tissue and muscle by 1 and 9 mm, respectively, on average. Projected subcutaneous-injection rates with/without compression were high for Anapen (65%-66%), moderate for EpiPen and Jext (29%-38%), and lowest for Emerade (13%-21%). Compression introduced a small intraosseous-injection risk with Emerade (4%). Female sex predicted subcutaneous injection (odds ratio, 1.3-2.0; all P < .001). Depending on the EAI, 29% to 97% of women and 0% to 41% of men would be injected subcutaneously. Older men were at risk of intraosseous Emerade injection. Obesity-related variables predicted subcutaneous injection poorly. ConclusionAnapen was associated with high subcutaneous-injection rates. EpiPen and Jext were projected to provide intramuscular injection in all men without risk of intraosseous injection. Emerade yielded the lowest subcutaneous-injection rates in women. Compression largely affected the muscle. Trial RegistrationClinicalTrials.gov Identifier: NCT02886468

Depth of the subcutaneous tissue in the nose: Application to filler injection.

The nasal region plays a pivotal role in both facial esthetics and functionality. The use of volumizing fillers has emerged as a potential means to enhance nasal appearance. Preliminary findings from cadaveric studies have highlighted potential risks associated with deeper needle injection, leading to cartilage damage and lateral migration of filler material. Understanding the subcutaneous tissue depth is crucial to prevent such complications and ensure safe filler placement guided by anatomical knowledge. This study aimed to employ ultrasonographic assessment to precisely measure the depth of soft tissue in the nasal area. Fifty-two participants without prior nasal surgery or filler injections underwent detailed ultrasonographic evaluation, focusing on seven key anatomical points: Glabellar, Sellion, Rhinion, between Rhinion and Pronasal, Pronasal, between Pronasal and Subnasal, and Subnasal. The ultrasonographic observation revealed varying depths of subcutaneous tissue across these points: Glabellar (4.11 ± 0.79), Sellion (5.21 ± 0.97), Rhinion (2.02 ± 0.74), Rhinion to Pronasal midpoint (6.45 ± 3.1), Pronasal (9.5 ± 2.2), between Pronasal and Subnasal (8.8 ± 0.8), and Subnasal (8.5 ± 0.5). The discussion underscores the significance of understanding subcutaneous tissue depth in guiding needle length and approach angles during filler injections. This knowledge aids in achieving effective filling while ensuring safe placement within the subcutaneous tissue.

SINTERING PROCESSES, PHASE AND STRUCTURE FORMATION AND PROPERTIES OF ELECTRICAL PORCELAIN WITH THE USE OF MARSHALLIT AND WOLLASTONITE ADDITIVES

The effect of marshallite upon its complete replacement of quartz and wollastonite additions (2.0 wt.%) on the sintering and phase formation processes, as well as the structure and properties of insulation porcelain was studied. The object of study is insulation porcelain of typical component composition (kaolin, soft clay, feldspar, quartz sand). It has been established that the processes of melting and sintering at firing of the investigated porcelain compositions are not equilibrial. The formation of ternary eutectics fusions of the R2O-Al2O3-SiO2 systems at temperatures of 985 and 1050 °C in amounts of 45–60% does not occur. The formation of a fusion during firing of ceramics occurs due to partial binary eutectics “white feldspar-earth silicon” and “orthoclase feldspar-earth silicon” during the interaction of feldspar with silica-containing components (990–1060 °C). This is due to the fact that primary mullite is formed at temperatures of its stable state above 1200 °C. The actual processes of fusion formation during porcelain firing are not equilibrium. Recrystallization of mullite occurs due to the dissolution of primary mullite in the fusion, followed by crystallization of acicular mullite. Replacing of quartz sand with marshallite leads to a decrease in the temperatures of earth silicon with feldspar interaction and the formation of a primary fusion, which results in a decrease in the ceramics firing temperature by 70° from 1340 to 1270 °C. The addition of wollastonite – CaSiO3 (2 %wt.) intensifies the process of primary mullite dissolution and crystallization of acicular mullite. The length of the mullite needles increases from 2–3 μm up to 7–10 μm, the mullite needles form aggregates, which provides an increase in the bending strength of porcelain by 36% up to 80 MPa. For citation: Vereshchagin V.I., Kurbanbayev M.Ye., Yessimov B.O., Root L.O., Mogilevskaya N.V. Sintering processes, phase and structure formation and properties of electrical porcelain with the use of marshallit and wollastonite additives. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 5. P. 87-98. DOI: 10.6060/ivkkt.20246705.6960.

Investigating the Mechanisms of Intradermal Injection for Easier "Skin Booster" Treatment: A Fluid Mechanics Approach to Determine Optimal Delivery Method.

The use of "skin boosters" for rejuvenating aged skin is widely used. However, the accurate injection of the skin booster into the dermal layer remains a challenge due to the density of the dermis. The purpose of this study was to investigate the optimal mechanical variables of delivery that enabled correct targeting of the product to the dermis for optimal results. We investigated the impact of mechanical variables (syringe diameter, needle diameter and length, and viscosity of the skin booster) on the force required for intradermal injection in porcine skin. The correlation between these variables and the injection force was examined as well. The results show that smaller syringe diameters, larger needle diameters, shorter needle lengths, and lower viscosity of the skin boosters reduce the injection force needed for intradermal injections. During the administration of skin booster injections, clinicians should take into account optimal conditions that facilitate intradermal injections, thus maximizing rejuvenating outcomes. Furthermore, manufacturers of skin boosters should formulate the products with decreased viscosity and provide the product in conjunction with appropriate needles and syringes, designed to optimize ease of injection.

A Hollow Microneedle Equipped with a Micropillar for Improved Needle Insertion and Injection of Drug Solution.

Hollow-type microneedles (hMNs) are a promising device for the effective administration of drugs into intradermal sites. Complete insertion of the needle into the skin and administration of the drug solution without leakage must be achieved to obtain bioavailability or a constant effect. In the present study, several types of hMN with or without a rounded blunt tip micropillar, which suppresses skin deformation, around a hollow needle, and the effect on successful needle insertion and administration of a drug solution was investigated. Six different types of hMNs with needle lengths of 1000, 1300, and 1500µm with or without a micropillar were used. Needle insertion and the disposition of a drug in rat skin were investigated. In addition, the displacement-force profile during application of hMNs was also investigated using a texture analyzer with an artificial membrane to examine needle factors affecting successful insertion and administration of a drug solution by comparing with in vivo results. According to the results with the drug distribution of iodine, hMN1300 with a micropillar was able to successfully inject drug solution into an intradermal site with a high success rate. In addition, the results of displacement-force profiles with an artificial membrane showed that a micropillar can be effective for depth control of the injected solution as well as the prevention of contact between the hMN pedestal and the deformed membrane. In the present study, hMN1300S showed effective solution delivery into an intradermal site. In particular, a micropillar can be effective for depth control of the injected solution as well as preventing contact between the hMN pedestal and the deformed membrane. The obtained results will help in the design and development of hMNs that ensure successful injection of an administered drug.

The Needle Shield Size and Applied Force of Subcutaneous Autoinjectors Significantly Influence the Injection Depth.

This study examines how shield-triggered autoinjectors (AIs), for subcutaneous drug delivery, affect injection depth. It focuses on shield size and applied force, parameters that could potentially lead to inadvertent intramuscular (IM) injections due to tissue compression. A blinded ex-vivo study was performed to assess the impact of shield size and applied force on injection depth. Shields of 15, 20, and 30 mm diameters and forces from 2 to 10 N were investigated. The study involved 55 injections in three Landrace, Yorkshire, and Duroc (LYD) pigs, with injection depths measured with computed tomography (CT). An in-vivo study, involving 20 injections in three LYD pigs, controlled the findings, using fluoroscopy (FS) videos for depth measurement. The CT study revealed that smaller shield sizes significantly increased injection depth. With a 15 mm diameter shield, 10 N applied force, and 5 mm needle protrusion, the injection depth exceeded the needle length by over 3 mm. Injection depth increased with higher applied forces until a plateau was reached around 8 N. Both applied force and size were significant factors for injection depth (analysis of variance [ANOVA], P < .05) in the CT study. The FS study confirmed the ex-vivo findings in an in-vivo setting. The study demonstrates that shield size has a greater impact on injection depth than the applied force. While conducted in porcine tissue, the study provides useful insights into the relative effects of shield size and applied force. Further investigations in humans are needed to confirm the predicted injection depths for AIs.

Efficacy and Safety of an Autologous Micrografting Procedure for Management of Striae Distensae in Women.

Striae distensae (SD), or stretch marks, are a common skin problem having a psychological impact and cosmetic concern, especially for women, in whom the prevalence is higher than in men. This study assessed the efficacy and safety of a single autologous micrografting treatment (AMT®) using Rigenera® technology for the management of SD. This single-centre study included 10healthy women between 24 and 65years of age, with Fitzpatrick-Goldman skin typesI-IV, who had visible SD in glutes/thighs. Each subject acted as their own control. The treatment procedure (microneedling + AMT) and the control procedure (no treatment) were performed on contralateral sides of the glutes/thighs, targeting matched and paired SD. Microneedling was carried out using Dermapen®, equipped with 32 needle heads set at 1.5mm needle length. The AMT procedure involved extracting biopsies from the mastoid hair zone with a 2.5-mm dermal punch, followed by disaggregation of the biopsies in a physiological saline solution using the Rigeneracons. The disaggregated micrografts were then intradermally injected using 30G 4-mm needles, maintaining a distance of 1cm between injection points, covering the entire marked treatment region. In the treated area, at 3months post-procedure compared to pre-procedure, the following changes were observed, all with statistical significance (P ≤ 0.05): (a) significant reductions in skin roughness (Ra, - 15.9%; Rz, - 22.6%), skin luminance (- 2.0%), and blue-green color distribution (- 10.6%); (b) significant increases in skin microcirculation maximum value (+ 240.1%), skin hydration (+ 71.2%), skin elasticity (+ 216.5%), skin density (+ 34.3%), skin thickness (+ 26.0%), and hypodermis thickness (+ 29.9%). Furthermore, for each of the aforementioned parameters, there was a significantly greater improvement observed with the AMT procedure compared with microneedling at 3months (all P ≤ 0.05). The AMT procedure using Rigenera technology resulted in an noticeable improvement in the SD appearance after 3months in healthy women.

A Bilayer Microarray Patch (MAP) for HIV Pre-Exposure Prophylaxis: The Role of MAP Designs and Formulation Composition in Enhancing Long-Acting Drug Delivery.

Microarray patches (MAPs) have shown great potential for efficient and patient-friendly drug delivery through the skin; however, improving their delivery efficiency for long-acting drug release remains a significant challenge. This research provides an overview of novel strategies aimed at enhancing the efficiency of MAP delivery of micronized cabotegravir sodium (CAB Na) for HIV pre-exposure prophylaxis (PrEP). The refinement of microneedle design parameters, including needle length, shape, density, and arrangement, and the formulation properties, such as solubility, viscosity, polymer molecular weight, and stability, are crucial for improving penetration and release profiles. Additionally, a bilayer MAP optimization step was conducted by diluting the CAB Na polymeric mixture to localize the drug into the tips of the needles to enable rapid drug deposition into the skin following MAP application. Six MAP designs were analyzed and investigated with regard to delivery efficiency into the skin in ex vivo and in vivo studies. The improved MAP design and formulations were found to be robust and had more than 30% in vivo delivery efficiency, with plasma levels several-fold above the therapeutic concentration over a month. Repeated weekly dosing demonstrated the robustness of MAPs in delivering a consistent and sustained dose of CAB. In summary, CAB Na MAPs were able to deliver therapeutically relevant levels of drug.

Stochastic processes and changes in evolutionary rate are associated with diversification in a lineage of tropical hard pines (Pinus)

The study of the patterns of polymorphism and molecular evolution among closely related species is key to understanding the evolutionary forces involved in the diversification of lineages. This point is a big challenge in species with slow evolutionary rates, long life cycles, and ancient, shared polymorphisms such as conifers. Under the premise of divergence in a stepwise migration process, we expect clinal geographical patterns of purifying selection efficiency, and genetic structure related to latitude or longitude. If migration is accompanied by changes in the environment, we could further expect a role of positive selection in driving species divergence. Here, we infer patterns of polymorphism, efficiency of purifying selection, and molecular evolution using a dataset of 161 nuclear genes (∼71 Kb) in a lineage of hard pines from North America, the Caribbean, Mexico, and Central America presumed to have migrated from North America toward lower latitudes with tropical conditions. Under the premise of differences in selective pressures, we also look for possible signals of positive selection. To test our hypothesis, first we estimated different indices to infer patterns of polymorphism and efficiency of purifying selection (Ka, Ks, Ka/Ks, dN, dS, dN/dS, and dxy) and compared these metrics across five clades. Also, we investigated possible clinal patterns in these indices and morphological traits (needle length and cone length). Then we inferred genetic structure and environmental differences among species to test for possible signals of positive selection using phylogenetic methods in specific clades. We found differences among clades using Ka, Ks, and Ka/Ks with a relaxation of purifying selection, especially in the Elliotti and Patula clades. We also found environmental differences related to geographic distance, and among clades suggesting differences in selective pressures. The indices Ks, dxy, and needle length had relationships with geography but not ovulate cone length. Finally, we found that most analyzed genes are under purifying selection, but there was an exception of faster evolutionary rate in some pine species, suggesting the possible action of positive selection in divergence. Our study indicated that stochastic processes have played a key role in the diversification of the group, with a possible input of positive selection in pines from Mexico and Central America.