Intrathecal Vector Delivery in Juvenile Rats via Lumbar Cistern Injection.

Gene therapy is a powerful technology to deliver new genes to a patient for the treatment of disease, be it to introduce a functional gene, inactivate a toxic gene, or provide a gene whose product can modulate the biology of the disease. The delivery method for the therapeutic vector can take many forms, ranging from intravenous infusion for systemic delivery to direct injection into the target tissue. For neurodegenerative disorders, it is often desirable to skew transduction towards the brain and/or spinal cord. The least invasive approach to target the entire central nervous system involves injection into the cerebrospinal fluid (CSF), allowing the therapeutic to reach a large fraction of the central nervous system. The safest approach to deliver a vector into the CSF is the lumbar intrathecal injection, where a needle is introduced into the lumbar cistern of the spinal cord. This technique, also known as a lumbar puncture, has been widely used in neonatal and adult rodents and in large animal models. While the technique is similar across species and developmental stages, subtle differences in size, structure, and elasticity of tissues surrounding the intrathecal space require accommodations in the approach. This article describes a method for performing lumbar puncture in juvenile rats to deliver an adeno-associated serotype 9 vector. Here, 25-35 µL of vector were injected into the lumbar cistern, and a green fluorescent protein (GFP) reporter was used to evaluate the transduction profile resulting from each injection. The benefits and challenges of this approach are discussed.

An Intraperitoneal Injection Technique in Adult Zebrafish that Minimizes Body Damage and Associated Mortality.

The adult zebrafish (Danio rerio), which is genetically accessible, is being employed as a valuable vertebrate model to study human disorders such as cardiomyopathy. Intraperitoneal (IP) injection is an important method that delivers compounds to the body for either testing therapeutic effects or generating disease models such as doxorubicin-induced cardiomyopathy (DIC). Currently, there are two methods of IP injection. Both methods have limitations when handling toxic compounds such as doxorubicin, which result in side effects manifesting as severe damage to the body shape and fish death. While these shortcomings could be overcome by extensive investigator training, a new IP injection method that has minimal side effects is desirable. Here, a unique IP injection method that is able to handle toxic compounds is reported. Consistently reduced cardiac function can result without incurring significant fish death. The technique can be easily mastered by researchers who have minimal experience with adult zebrafish.

Consideration of the diameter of superficial temporal arteries related to filler injections in the temporal region.

BACKGROUND: The concavity of the temple due to adipose tissue atrophy from aging accentuates the zygomatic arch and lateral orbital rim, leading to an aged appearance. The use of hyaluronic acid filler in the temporal region has gained popularity due to its procedural simplicity and consistent outcomes. OBJECTIVE: To evaluate the safety of administering hyaluronic acid filler in the temporal region concerning the frontal branch of the superficial temporal artery, which is at risk of injury. METHODS: Empirical observations were conducted on the internal diameter of the frontal branch of the superficial temporal artery, a critical anatomical site for potential injury. RESULTS: A significant proportion of the artery segments exhibited an internal diameter below 1 mm. Given that the outer diameter of an 18-gauge cannula is 1.27 mm, this method can be considered a relatively secure approach for enhancing the temporal region. CONCLUSION: The use of an 18-gauge cannula for hyaluronic acid filler administration in the temporal region appears to be a safe and effective method, with the potential risk to the frontal branch of the superficial temporal artery being minimal.

Effects of in ovo injection of organic selenium on the hatchability of broiler breeder hen eggs and resulting chick physiology and performance.

BACKGROUND: Selenium is an essential mineral for poultry. The conflicting reports about its in ovo injection are the justification for the more detailed investigation. OBJECTIVES: The aim of this study was to investigate the effects of in ovo injection of organic selenium on the hatching traits of broiler chickens and their performance. METHODS: Three hundred and twenty eggs of Ross 308 strain with an average weight of 65 g and 160 chicks were randomly divided into 4 treatment groups (each with 8 replicates of 10 eggs each for hatching parameters and 4 replicates of 10 chicks for broiler farming parameters): negative control (no injection), positive control (in ovo injection of 0.272 mL of normal saline solution) and 2 selenium treatments (in ovo injection of 2.72 or 5.44 µg of organic selenium). Injection was into the amniotic sac on the 10th day of incubation. Effects of in ovo injection on hatching and performance traits, blood parameters, immune responses, carcass characteristics, meat fatty acid profile, cecal microbial population and selenium consternation in the tibia were measured. RESULTS: Fewer chicks from the injected treatments hatched than from the negative control group (p < 0.01). However, the injection of selenium increased feed intake and the final weight of the birds (p < 0.01). Blood parameters were also affected. Glucose and cholesterol in experimental treatment chicks was lower than those of the controls (p < 0.01), whereas blood lipoproteins (VLDL, LDL and HDL) and the ratio of cholesterol to HDL was significantly increased in the treatments injected with selenium (p < 0.01). There was no significant difference in the immune response or microbial population between the experimental groups, but carcass components, such as thigh, breast, wing and abdominal fat weight, were significantly greater in the selenium treatments. CONCLUSIONS: Intra-egg injection of organic selenium produced favourable effects on performance of broiler chickens, although it had no effect on immune response or microbial population. However, the negative effect on hatching of chickens needs to be prevented to result in an acceptable economic return for the producer.

A systematic review and meta-analysis on sodium tanshinone IIA sulfonate injection for the adjunctive therapy of pulmonary heart disease.

AIMS: Sodium tanshinone IIA sulfonate (STS) injection has been widely used as adjunctive therapy for pulmonary heart disease (PHD) in China. Nevertheless, the efficacy of STS injection has not been systematically evaluated so far. Hence, the efficacy of STS injection as adjunctive therapy for PHD was explored in this study. METHODS: Randomized controlled trials (RCTs) were screened from China Science and Technology Journal Database, China National Knowledge Infrastructure, Wanfang Database, PubMed, Sino-Med, Google Scholar, Medline, Chinese Biomedical Literature Database, Cochrane Library, Embase and Chinese Science Citation Database until 20 January 2024. Literature searching, data collection and quality assessment were independently performed by two investigators. The extracted data was analyzed with RevMan 5.4 and STATA 14.0. Basing on the methodological quality, dosage of STS injection, control group measures and intervention time, sensitivity analysis and subgroup analysis were performed. RESULTS: 19 RCTs with 1739 patients were included in this study. Results showed that as adjunctive therapy, STS injection combined with Western medicine showed better therapeutic efficacy than Western medicine alone for PHD by increasing the clinical effective rate (RR = 1.22; 95% CI, 1.17 to 1.27; p < 0.001), partial pressure of oxygen (MD = 10.16; 95% CI, 5.07 to 15.24; p < 0.001), left ventricular ejection fraction (MD = 8.66; 95% CI, 6.14 to 11.18; p < 0.001) and stroke volume (MD = 13.10; 95% CI, 11.83 to 14.38; p < 0.001), meanwhile decreasing the low shear blood viscosity (MD = -1.16; 95% CI, -1.57 to -0.74; p < 0.001), high shear blood viscosity (MD = -0.64; 95% CI, -0.86 to -0.42; p < 0.001), plasma viscosity (MD = -0.23; 95% CI, -0.30 to -0.17; p < 0.001), hematokrit (MD = -8.52; 95% CI, -11.06 to -5.98; p < 0.001), fibrinogen (MD = -0.62; 95% CI, -0.87 to -0.37; p < 0.001) and partial pressure of carbon dioxide (MD = -8.56; 95% CI, -12.09 to -5.02; p < 0.001). CONCLUSION: STS injection as adjunctive therapy seemed to be more effective than Western medicine alone for PHD. However, due to low quality of the included RCTs, more well-designed RCTs were necessary to verify the efficacy of STS injection.

Effectiveness and Safety of a New Hyaluronic Acid Injectable for Augmentation and Correction of Chin Retrusion.

BACKGROUND: A hyaluronic acid (HA) filler intended for non-surgical improvement of chin appearance should ideally be of high strength/firmness (high G') to allow for deep injections on the bone. HASHA (Restylane Shaype) is a new hyaluronic acid (HA) injectable with high G' and high HA concentration (25 mg/mL), engineered by the new NASHA-HD (High Definition) technology. HASHA is suitable to be placed periosteally, aiming to mimic the natural shape of the bony chin. This pivotal clinical investigation evaluated effectiveness and safety of HASHA for augmentation and correction of chin retrusion.  Methods: Subjects 18 years or older with mild or moderate chin retrusion by the Galderma Chin Retrusion Scale (GCRS), were randomized 3:1 to HASHA (n=103) or no treatment (n=37). Assessments included GCRS (blinded evaluator), aesthetic improvement (Global Aesthetic Improvement Scale [GAIS]), subject satisfaction, and safety.  Results: GCRS responder rate (1-grade or greater improvement from baseline) was significantly higher for HASHA (83.3%) versus controls (10.8%) at month 3 (P<0.001) and maintained through month 12 (P<0.001). Aesthetic improvement was high throughout the study in the HASHA group, according to investigators (97% or greater) and subjects (89% or greater). Overall, subject satisfaction was high at month 3 and maintained at month 12. Product- or injection-related adverse events were mostly mild or moderate and transient. No product- or injection-related serious adverse events were reported. CONCLUSIONS: HASHA, a new NASHA-HD injectable with extra strength/firmness, was safe and effective for chin augmentation and correction of chin retrusion, with high aesthetic improvement and subject satisfaction throughout 12 months. J Drugs Dermatol. 2024;23(4):255-261.     doi:10.36849/JDD.8145.

Smart distribution network voltage estimation using PMU technology considering zero injection constraints.

To properly control the network of the power system and ensure its protection, Phasor measurement units (PMUs) must be used to monitor the network's operation. PMUs can provide synchronized real-time measurements. These measurements can be used for state estimation, fault detection and diagnosis, and other grid control applications. Conventional state estimation methods use weighting factors to balance the different types of measurements, and zero injection measurements can lead to large weighting factors that can introduce computational errors. The offered methods are designed to ensure that these zero injection criteria can be strictly satisfied while calculating the voltage profile and observability of the various distribution networks without sacrificing computing efficiency. The proposed method's viability is assessed using standard IEEE distribution networks. MATLAB coding is used to simulate the case analyses. Overall, the study provides a valuable contribution to the field of power distribution system monitoring and control by simplifying the process of determining the optimal locations for PMUs in a distribution network and assessing the impact of ZI buses on the voltage profile of the system.

The Effect of a Combination of Vibration and External Cold on Pain Caused during Vaccine Injection in Infants: A Randomized Clinical Trial.

Aim: This study was conducted to determine the effect of combining vibration and external cold on pain caused by vaccine injection among six-month-old infants. Design: Randomized controlled trial. Methods: In this clinical trial, 80 eligible infants were selected from the infants referred to a health center as per the inclusion criteria. The infants were assigned to either a control group or an intervention group by block randomization. In the intervention group, a vibrating and cold device was placed above the injection site from one minute before to 15 seconds after the pentavalent vaccine injection. In the control group, no intervention was performed, and they were vaccinated according to the routine procedure. The pain status in the two groups was measured using the Modified Behavioral Pain Scale (MBPS) 15 seconds after the injection, and the crying duration was assessed from the injection of the vaccine till the end of it. Data were analyzed in SPSS 23 software using Mann-Whitney, t, Spearman, and chi-square tests. The level of significance was set to p < 0.05. Results: Most participants in the control (55%) and intervention (55%) groups were girls. Statistical data analysis of 80 infants showed that the mean pain intensity (p = 0.032) and duration of crying (p = 0.0001) in the intervention group (6.1 ± 1.8, 32.47 ± 16.78) were lower than those of the control group (7.2 ± 0.1, 51.02 ± 25.9), respectively. Conclusion: Because the intensity of pain, especially the duration of crying, was lower in the intervention group than in the control group, we may suggest that nurses use simple pain relief solutions in vaccination centers, such as a combination of vibration and cold. This trial is registered with IRCT201207157130N2.

Africa may lead rollout of long-lasting HIV drug.

U.S. agency plans to make inexpensive prevention shots widely available for people at risk.

Recurrent inferior oblique myositis and its outcomes.

This report presents a unique case of recurrent idiopathic inferior oblique myositis (IOM) with a focus on clinico-radiological characteristics and histological features. A woman in her early 40s presented with a third episode of IOM following a 12-year period of quiescence. The first two episodes were characterised by unilateral IOM with rapid resolution following oral prednisone treatment. MRI revealed anterior focal enlargement of the left inferior oblique muscle with ipsilateral lacrimal gland enlargement. An inferior oblique muscle and lacrimal gland biopsy demonstrated significant inflammatory infiltrate. An intraorbital injection of triamcinolone acetonide was administered with complete resolution of symptoms within 1 week.

Evidence-Based Use of Bevacizumab in the Management of Neovascular Age-Related Macular Degeneration.

Indicated for colorectal cancer for decades, bevacizumab has been widely used off label to treat retinal diseases, and the benefits of its use, specifically in neovascular age-related macular degeneration, have been demonstrated in multiple clinical trials. The intravitreal delivery of bevacizumab requires it to be aseptically repackaged into individual syringes by compounding pharmacies for use in the eye. Although the repackaging process is permitted by the US Food and Drug Administration, the resultant product does not meet the specific standards of products approved for use as ophthalmic injectables nor is the parenteral innovator solution compliant with ophthalmic standards. Studies have also demonstrated variability in the quality and quantity of repackaged bevacizumab. This narrative review summarizes the evidence and discusses the role of off-label bevacizumab in the treatment and management of retinal diseases, its mechanism of action, current challenges and provides a critical appraisal of current evidence, clinical implications, and future directions. [Ophthalmic Surg Lasers Imaging Retina 2024;55:155-162.].

[Rehabilitation of patients with facial nerve neuropathy in cases of increased muscle tone on the healthy side of the face]. / Reabilitatsiya patsientov s neiropatiei litsevogo nerva pri povyshenii tonusa myshts na zdorovoi storone litsa.

OBJECTIVE: To evaluate the effectiveness of physical rehabilitation (PR) and injections of botulinum toxin type A (BTA) in the correction of muscles hypertonicity ty of the healthy side of the face or its prevention in patients with facial nerve neuropathy (FNN). MATERIAL AND METHODS: One hundred and forty-six patients with FNN of various etiologies with muscles hypertonicity of the healthy side or the risk of its development were studied. The term of treatment was 33 [10; 99] days. There are 88 women and 58 men aged 42 [34; 56] years. Diagnosis included clinical examination and stimulation electroneuromyography (ENMG, n=113; 77.4%) with assessment of M-wave amplitude asymmetry. All patients were prescribed a standard PR complex, in addition - relaxation of the muscles of the healthy side by injections of BTA (Incobotulinumtoxin A) - BTA group (n=38) or by special PR techniques - physiotherapy group (n=108). RESULTS: In both groups, patients were comparable in age, sex and severity of FNN at clinical assessment. But objectively, in the BTA group there were more symptomatic forms (63.2% vs 43.5%; p=0.038), cases of M-wave amplitude asymmetry over 90% in ≥2 branches (52.6% vs 18.5%; p=0.032). Displacement of the face midline was a factor limiting recovery (68.4% and 62%; χ2=0.495; p=0.482) in two groups. With amplitude asymmetry of more than 90% in ≥2 branches (a predictor of the risk of unfavorable outcome), a favorable outcome occurred more often in the BTA group (80% versus 45%; χ2=5.227; p=0.023). In case of amplitude asymmetry of less than 90% in all branches, a favorable outcome was observed in two groups. CONCLUSION: Indications for botulinum therapy in patients with FNN are deep prosoparesis or prosoplegia, muscles hypertonicity of the healthy side, displacement of the face midline, ENMG predictors of the risk of unfavorable outcome. PR is an effective method of prevention in patients with a favorable prognosis of outcome or treatment of mild forms.

High-frequency Ultrasound in the Assessment before and after Applying HArmonyCa™.

AIM: To describe a clinical case of ultrasound (US) used to evaluate, before, post-immediately, and after 4 months, the facial application of a volumizing and biostimulating substance. BACKGROUND: Detecting the behavior of injected filler materials with high-frequency US-guided application is the future of natural facial rejuvenation with more predictable and satisfactory results. TECHNIQUE: A patient indicated for orofacial harmonization (OFH) procedures through volumizing and biostimulating material application was invited to participate. The technique was performed by applying HArmonyCa™ (Allergan Aesthetics, Irvine, CA, USA) in the gonial, preauricular, and bilateral lateral zygomatic angle regions. The first evaluations used the US images before and after product application with a Logiq e® high-frequency US device (GE Healthcare, Chicago, IL, USA) with a probe/linear transducer of 18 MHz. About 4 months after the procedure, a new assessment with the same initial acquisition pattern was performed. The first evaluation showed normal-looking anatomical structures without the esthetic material. Immediately after the procedure and 4 months later, the assessments presented semi-permanent esthetic fillers as dispersed lobulated hyperechogenic areas with a cloud aspect. CONCLUSION: High-frequency US was efficient in the static evaluation of HArmonyCa™ behavior on the facial skin. CLINICAL SIGNIFICANCE: The US-guided application of injectable products in specific areas has minimal side effects and contributes to more predictable and satisfactory results. How to cite this article: Gouveia RSA, Tostes LLL, Bezerra FV, et al. High-frequency Ultrasound in the Assessment before and after Applying HArmonyCa™. J Contemp Dent Pract 2024;25(1):10-14.

Backflow reduction in local injection therapy with gelatin formulations.

The local injection of therapeutic drugs, including cells, oncolytic viruses and nucleic acids, into different organs is an administrative route used to achieve high drug exposure at the site of action. However, after local injection, material backflow and side effect reactions can occur. Hence, this study was carried out to investigate the effect of gelatin on backflow reduction in local injection. Gelatin particles (GPs) and hydrolyzed gelatin (HG) were injected into tissue models, including versatile training tissue (VTT), versatile training tissue tumor-in type (VTT-T), and broiler chicken muscles (BCM), using needle gauges between 23 G and 33 G. The backflow material fluid was collected with filter paper, and the backflow fluid rate was determined. The backflow rate was significantly reduced with 35 µm GPs (p value < .0001) at different concentrations up to 5% and with 75 µm GPs (p value < .01) up to 2% in the tissue models. The reduction in backflow with HG of different molecular weights showed that lower-molecular-weight HG required a higher-concentration dose (5% to 30%) and that higher-molecular-weight HG required a lower-concentration dose (7% to 8%). The backflow rate was significantly reduced with the gelatin-based formulation, in regard to the injection volumes, which varied from 10 µL to 100 µL with VTT or VTT-T and from 10 µL to 200 µL with BCM. The 35 µm GPs were injectable with needles of small gauges, which included 33 G, and the 75 µm GPs and HG were injectable with 27 G needles. The backflow rate was dependent on an optimal viscosity of the gelatin solutions. An optimal concentration of GPs or HG can prevent material backflow in local injection, and further studies with active drugs are necessary to investigate the applicability in tumor and organ injections.

El reposicionamiento malar. Presentación de una técnica original: punto MM / Malar repositioning. Presentation of an original technique: point MM

El envejecimiento facial es una sinergia compleja de cambios texturales de la piel, hiper- o hipoactividad muscular, reabsorción del tejido graso y resorción ósea. El déficit de volumen resultante, la deflación y la posterior caída del tercio medio facial produce una cara menos atractiva y juvenil. Los procedimientos inyectables en región malar son cada vez más populares y solicitados por los pacientes. El conocimiento de la anatomía de la cara media es fundamental para el inyector. La comprensión de la irrigación facial puede ayudar a disminuir la exposición a la aparición de hematomas y complicaciones vasculares severas. Existen múltiples técnicas de inyección propuestas para el tercio medio, en este artículo presentamos una técnica original, simple, segura y eficaz con resultados satisfactorios y riesgo reducido

Facial aging is a complex synergy of textural skin changes, muscle hyperactivity, fat dysmorphism, bone resorption. The resulting volume deficit and deflation of the mid face produces a less attractive and youthful face. Injectable midface procedures are becoming increasingly popular and requested by patients. Knowledge of the anatomy of the midface is critical for the injector. Understanding the irrigation of the face can help decrease the risk of hematoma and severe vascular complications. There are multiple injection techniques proposed for the middle third, in this article we present a simple, safe and effective technique with satisfactory results and lower risk

Construction of an Injectable Composite Double-Network Hydrogel as a Liquid Embolic Agent.

Conventional embolists disreputably tend to recanalization arising from the low filling ratio due to their rigidity or instability. As a result, intelligent hydrogels with a tunable modulus may meaningfully improve the therapeutic efficacy. Herein, an injectable composite double-network (CDN) hydrogel with high shear responsibility was prepared as a liquid embolic agent by cross-linking poly(vinyl alcohol) (PVA) and carboxymethyl chitosan (CMC) via dynamic covalent bonding of borate ester and benzoic-imine. A two-dimensional nanosheet, i.e., layered double hydroxide (LDH), was incorporated into the network through physical interactions which led to serious reduction of yield stress for the injection of the hydrogel and the capacity for loading therapeutic agents like indocyanine green (ICG) and doxorubicin (DOX) for the functions of photothermal therapy (PTT) and chemotherapy. The CDN hydrogel could thus be transported through a thin catheter and further in situ strengthened under physiological conditions, like in blood, by secondarily cross-linking with phosphate ions for longer degradation duration and better mechanical property. These characteristics met the requirements of arterial interventional embolization, which was demonstrated by renal embolism operation on rabbits, and meanwhile favored the inhibition of subcutaneous tumor growth on an animal model. Therefore, this work makes a breakthrough in the case of largely reducing the embolism risks, thus affording a novel generation for interventional embolization.