Injection Group Research Articles

The Tree Shrew Model of Parkinson Disease: A Cost-Effective Alternative to Nonhuman Primate Models

The surge in demand for experimental monkeys has led to a rapid increase in their costs. Consequently, there is a growing need for a cost-effective model of Parkinson disease (PD) that exhibits all core clinical and pathologic phenotypes. Evolutionarily, tree shrews (Tupaia belangeri) are closer to primates in comparison with rodents and could be an ideal species for modeling PD. To develop a tree shrew PD model, we used the 1-methyl-4-phenylpyridinium (MPP+), a metabolite derived from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, to induce lesions in dopaminergic neurons of the unilateral substantia nigra. The induced tree shrew model consistently exhibited and maintained all classic clinical manifestations of PD for a 5-month period. The symptoms included bradykinesia, rest tremor, and postural instability, and ∼50% individuals showed apomorphine-induced rotations, a classic phenotype of unilateral PD models. All these are closely resembled the ones observed in PD monkeys. Meanwhile, this model was also sensitive to L-dopa treatment in a dose-dependent manner, which suggested that the motor deficits are dopamine dependent. Immunostaining showed a significant loss of dopaminergic neurons (∼95%) in the lesioned substantia nigra, which is a crucial PD pathological marker. Moreover, a control group of nigral saline injection did not show any motor deficits and pathological changes. Cytomorphologic analysis revealed that the size of nigral dopaminergic neurons in tree shrews is much bigger than that of rodents and is close to that of macaques. The morphologic similarity may be an important structural basis for the manifestation of the highly similar phenotypes between monkey and tree shrew PD models. Collectively, in this study, we have successfully developed a PD model in a small animal species that faithfully recapitulated the classic clinical symptoms and key pathological indicators of PD monkeys, providing a novel and low-cost avenue for evaluation of PD treatments and underlying mechanisms.

Asymmetrical primary vesicoureteral reflux: Which is the best surgical strategy?

No report has been published regarding the recommended surgical treatment in patients presenting with symptomatic primary asymmetrical vesicoureteral reflux (VUR): high grade on one side and low grade on the contralateral side. The aim of this study was to evaluate the effectiveness and outcome of combined Lich-Gregoir extravesical reimplantation and subureteric Deflux® injection, of high grade and low grade VUR respectively. Non-inferiority to bilateral cross-trigonal reimplantation was investigated in terms of surgical complications, number of post-operative fUTIs and need for re-intervention. A monocentric retrospective study was undertaken of all consecutive children with primary asymmetrical VUR on MCUG treated over an 18-year period (2004-2022). Surgery was indicated following an episode of febrile urinary tract infection despite appropriate non-operative management. Demographic and clinical such as length of hospital stay for pain management, use of urinary Foley catheter and complications were analyzed. A total of 80 children met the study criteria: 40 patients underwent bilateral cross-trigonal re-implantation (Group 1) and 40 patients the combined Lich-Gregoir extra vesical reimplantation and Deflux® sub ureteric injection (Group 2). Complication and success rates were comparable in the two groups. The median hospital stay was significantly shorter for Group 2, with 50% of patients who were discharged on day 1. Moreover, the data showed a significant lesser need in number and length of bladder catheter and ureteral stents in Group 2. The technique proposed overcome the inconveniences of the other procedures that are commonly used in bilateral RVU: difficulty in retrograde catheterization or ureteroscopy after bilateral cross-trigonal reimplantation, the risk of transient bladder dysfunction after bilateral extravesical reimplantation and the low rate of success for high grade reflux of the sub ureteric Deflux® injection. The main limitation of the study lies in its retrospective nature and in the relatively short median follow-up. The combined Lich-Gregoir extra-vesical ureteral reimplantation and sub-ureteric Deflux® injection for the treatment of primary asymmetrical VUR is an effective alternative to the gold standard cross-trigonal ureteral reimplantation. Moreover, the position of the ureteric orifice is not modified in the eventuality of endourological procedures into adulthood.

Local corticosteroid injection versus surgery for carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) is a very common clinical syndrome manifested by signs and symptoms of irritation of the median nerve at the carpal tunnel in the wrist. Direct and indirect costs of CTS are substantial, with estimated costs of two billion US dollars for CTS surgery in the USA alone. Local corticosteroid injection has been used as a non-surgical treatment for CTS for many years, but its effectiveness is still debated. To evaluate the benefits and harms of corticosteroids injected in or around the carpal tunnel for the treatment of carpal tunnel syndrome (CTS) compared to surgery. We used standard, extensive Cochrane search methods. We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, and WHO ICTRP. The latest search was 26 May 2022. We included randomised controlled trials (RCTs) or quasi-randomised trials of adults with CTS that included at least one comparison group of local corticosteroid injection (LCI) into the wrist and one group of any surgical intervention. We used standard Cochrane methods. Our primary outcome was 1. improvement in symptoms at up to three months of follow-up. Our secondary outcomes were 2. functional improvement, 3. improvement in symptoms at greater than three months of follow-up, 4. improvement in neurophysiological parameters, 5. improvement in imaging parameters, 6. improvement in quality of life and 7. We used GRADE to assess the certainty of evidence for each outcome. We included seven studies involving 569 'hands' (although two studies had unusable data for quantitative analyses). All studies used a one-time LCI as a comparator, using several different types and doses of corticosteroids. In every study, for both surgery and LCI groups, all our primary and secondary outcomes showed improvement from pre- to post-treatment. However, evidence from the combined analysis was too uncertain for us to draw reliable conclusions for the comparison of surgical treatment versus LCI with respect to our primary outcome of symptom relief at up to three months' follow-up (standardised mean difference (SMD) 0.63, 95% confidence interval (CI) -0.61 to 1.88; I2 = 95%; 5 trials, 305 participants; very low-certainty evidence). Findings with respect to secondary outcome measures of symptom relief at greater than three months' follow-up (SMD 0.94, 95% CI -0.31 to 2.19; I2 = 93%; 4 trials, 235 participants), functional improvement at up to three months' follow-up (SMD -0.11, 95% CI -0.94 to 0.72; I2 = 84%; 3 trials, 215 participants) and functional improvement at greater than three months' follow-up (SMD 0.19, 95% CI -1.22 to 1.59; I2 = 93%; 3 trials, 185 participants) were also uncertain (very low-certainty evidence) and showed no clear advantage for surgery or LCI. Surgery may improve neurophysiology (median nerve distal motor latency) more than LCI (mean difference (MD) 0.87 ms, 95% CI 0.32 to 1.42; I2 = 72%; 3 trials, 162 participants; low-certainty evidence). Evidence for quality of life and adverse events was also uncertain; quality of life (EuroQol-5D-3L) may be slightly improved after LCI than after surgery (the difference may not be clinically important) (MD 0.07, 95% CI 0.02 to 0.12; 1 trial, 38 participants; very low-certainty evidence) and there may be fewer adverse events with LCI than with surgery (risk ratio (RR) 0.34, 95% CI 0.04 to 3.26; 3 trials, 112 participants; very low-certainty evidence). The evidence comparing LCI to surgery for CTS, either in the short term or up to 12 months' follow-up, is too uncertain for any reliable conclusions to be drawn.

Quantification of Cardiac Iron Overload at 3 T MRI in a Rabbit Model Utilizing ME-GRE T2* Sequence.

Myocardial iron overload can lead to myocardial dysfunction, muscle cell injury, and end-stage heart failure. The enhanced signal-to-noise ratio and technical advancements have made 3 T magnetic resonance imaging (MRI) more accessible in clinical settings. However, 3 T assessments for early diagnosis of myocardial iron overload are scarce. To evaluate the feasibility of myocardial iron quantification using 3 T MRI in a rabbit model of iron overload. Animal model. Overall, 40 male New Zealand white rabbits were categorized into control (N = 8; no treatment) and experimental (N = 32; weekly 200 mg/kg iron dextran injections) groups. 3 T MRI with multi-echo gradient echo (ME-GRE) T2* sequence. Each week, two experimental rabbits were randomly selected for blood collection to determine serum iron (SI) levels; their tissue was harvested to assess myocardial and hepatic iron deposition. Spearman's rank correlation tests were used to evaluate the correlations among R2*, cardiac iron concentration (CIC), liver iron concentration (LIC), total amount of iron injected, and SI levels. P ≤ 0.05 was considered statistically significant. The myocardial T2* value in the experimental group was significantly lower than that of the control group. An excellent correlation was observed between R2* values and CIC (r = 0.854). CIC moderately correlated with LIC (r = 0.712) and the total amount of iron injected (r = 0.698). A strong correlation was observed between the total amount of iron injected and LIC (r = 0.866). SI levels poorly correlated with the total amount of iron injected (r = 0.205, P = 0.277) and LIC (r = 0.170, P = 0.370) but fairly correlated with CIC (r = 0.415, P = 0.022). A 3 T MRI with an ME-GRE sequence may serve as a noninvasive method for evaluating cardiac iron content. N/A TECHNICAL EFFICACY: Stage 1.

Oral vs. injected: which vitamin D boost works best for low levels?

Vitamin D is essential for maintaining bone and mineral balance. This study aims to identify the most effective route for achieving optimal vitamin D levels (≥30 ng/mL) to support bone and mineral health. In this open-label randomized trial, 132 participants aged 18-60 with initial serum vitamin D levels below 30 ng/mL were divided into three intervention groups: daily 800 I.U. oral tablet (Group A), weekly 60,000 I.U. oral sachet (Group B), and monthly 300,000 I.U. intramuscular injection (Group C). The study assessed changes in their serum vitamin D levels at six and 12weeks. The monthly intramuscular (IM) group consistently had the highest mean vitamin D levels at six weeks 38.38(±9.953) (p<0.002) and 12weeks 48.15(±7.71) (p<0.001). Vitamin D insufficiency was reduced to 34.8 % at six weeks (p=0.434) and 6.8 % at 12weeks (p=0.002). Notably, 100 % of the monthly IM group achieved vitamin D sufficiency at 12weeks. The monthly IM route demonstrated superior effectiveness compared to tablets and sachets at both the 6-week and 12-week points. A significantly larger number of monthly IM participants achieved vitamin D sufficiency compared to the other groups.

Effects of in ovo supplementation of selenium (Se) and zinc (zn) on hatchability and production performance of broiler chickens.

The current research was conducted to assess the effect of in ovo feeding (IOF) of selenium (Se) and zinc (Zn) on hatchability, production performance, liver, intestinal morphology, antioxidant levels and expression levels of immune-related genes in broiler chickens. A total of 400 fertilized eggs were equally divided into four groups: control (non-injected), sham (in ovo injection of 0.75% NaCl), Se (@ 1.5µg/egg in ovo injection) and Zn (500µg/egg in ovo injection) groups respectively. On the seventeenth day of incubation, treatment solutions were administered into amniotic fluid of fertilized eggs. The results revealed that Se and Zn supplementation significantly (P < 0.05) enhanced hatchability, post-hatch growth, organ development, and liver antioxidant capability. Histopathological examination revealed a typical hepatocyte morphology, well-arranged cells, and a significant (P < 0.05) decrease in apoptosis in both selenium and zinc groups. Additionally, selenium and zinc produced auspicious effects on intestinal epithelium and villi surface area. Interestingly, our results revealed that IOF of Se and Zn modulated the expression of immune-related genes in comparison to the control and sham groups. Conclusively, IOF of Se and Zn augmented health and productivity by enhancing the cellular immunity in the broiler chickens, thus IOF can be utilized as an effective strategy to promote health and immunity in broiler chickens.

Supplemental L-arginine promotes hepatocyte proliferation and alters liver fatty acid metabolism in the late embryonic phase: an RNA-seq analysis

The in ovo feeding (IOF) of L-arginine (L-Arg) to chick embryos is a viable method for improving early intestinal development, subsequently leading to an acceleration in growth rate during the posthatch stage. However, the liver, being the pivotal organ for energy metabolism in poultry, the precise effects and mechanisms of L-Arg on the liver development and metabolism remain unclear. To elucidate these, the present study injected 2 doses of L-Arg (10 mg/egg and 15 mg/egg) into the embryos of Hongyao chickens at 17.5 d of incubation, subsequently incubating them until d 19 for further analysis. IOF of 15 mg L-Arg/egg significantly increased the organ indices of liver and small intestine, as well as the duodenal villus height/crypt depth. RNA-Seq analysis of liver tissues showed that the metabolism of xenobiotics, amino acid metabolism, and the fatty acid metabolism were significantly enriched in L-Arg injection group. The core differentially expressed genes (DEGs) were primarily involved in cell proliferation and fatty acid metabolism. The CCK8 assays revealed that supplemental L-Arg significantly enhanced the proliferation of primary embryo hepatocytes and leghorn male hepatoma (LMH) cells. Upregulation of core DEGs, including HBEGF, HES4, NEK3, EGR1, and USP2, significantly promoted the proliferation of liver cells. Additionally, analysis of triglyceride and total cholesterol content, as well as oil red O staining, indicated that supplemental L-Arg effectively reduced lipid accumulation. Overall, L-Arg supplementation in late chick embryos may promote early liver and small intestine development by reducing liver lipid deposition and enhancing energy efficiency, necessitating further experimental validation. This study provides profound insights into the molecular regulatory network of L-Arg in promoting the development of chicken embryos. The identified DEGs that promote cell proliferation and lipid metabolism can serve as novel targets for further developing methods to enhance early development of chicken embryos.

Sperm chromatin dispersion assay reliability and assisted reproductive technology outcomes: Systematic review and meta-analysis.

Elevated sperm DNA fragmentation has potential implications for semen quality and fertility. The commonly used sperm chromatin dispersion test offers an indirect estimation but has limitations in terms of bias and variability. This study aimed to assess the reliability of the sperm chromatin dispersion assay for predicting assisted reproductive technology outcomes. This systematic review included studies published until December 2023 that adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, Scopus, and Google Scholar databases were searched. Various assisted reproductive technology outcomes in patients with high (≥30%) versus low (<30%) sperm DNA fragmentation were compared using a sperm chromatin dispersion assay and including a sub-analysis of intracytoplasmic sperm injection versus in vitro fertilization. A comprehensive meta-analysis software facilitated quantitative analysis with statistical comparisons between cases and controls. Interstudy heterogeneity was assessed, and sensitivity and publication bias tests were performed. Of the 199 abstracts assessed, 64 full-text articles were screened, and 44 articles were qualitatively synthesized. Fourteen articles representing 5346 participants were quantitatively analyzed. Using the sperm chromatin dispersion assay, elevated sperm DNA fragmentation was associated with lower fertilization and embryo cleavage rates. Notably, high sperm DNA fragmentation levels did not affect the clinical pregnancy, implantation, miscarriage, or live birth outcomes. Sub-analysis revealed lower fertilization, embryo cleavage, clinical pregnancy, live birth rates, and higher miscarriage rates in the intracytoplasmic sperm injection subgroup only. The sperm chromatin dispersion assay did not show significant differences in pregnancy or live birth rates between the high- and low-sperm DNA fragmentation groups. Noteworthy, high sperm DNA fragmentation was associated with worse assisted reproductive technology outcomes in the intracytoplasmic sperm injection group. Given the current quality of the evidence, affected by the experimental design and the absence of correction for female factors of infertility, clinicians should be wary of the assay's limited predictive power for pregnancy and live birth outcomes.

The Impact of Preoperative Intra-articular Injections on Postoperative Outcomes in Hip Arthroscopy

Introduction: Hip arthroscopy is a minimally invasive procedure commonly performed to treat various hip conditions. Preoperative intra-articular injections, such as local anesthetics and corticosteroids, are frequently used to alleviate pain and as a diagnostic tool before hip arthroscopy. However, studies have shown conflicting information; some demonstrate better patient outcomes, while others have found an increased risk of complications and negative effects on postoperative recovery. This retrospective study evaluated the association between preoperative injections and postoperative outcomes in hip arthroscopy patients. Materials and Methods: A retrospective review of 1400 patients who underwent hip arthroscopy between 2014 and 2021 at our institution was performed. The patients were allocated into two cohorts based on whether they received a cortisone injection with local anesthetic within 1 year before the surgery. Outcomes during the study follow-up period (average: 437 days, max: 3018 days) were compared. Further analysis looked at subgroups at 30-day increments. Results: The results showed that 35.5% of the patients had received a preoperative injection. Although patients who received injections were more likely to be female (68.3% injected vs. 60.8% not injected, P = 0.019) and have asthma (12.5% injected vs. 7.3% not injected, P = 0.008), there were no significant differences in 90-day complications, 90-day emergency department visits, 90-day readmissions, any complications (wound infection, re-injury, recurrent pain or weakness, deep vein thrombosis, or pulmonary embolism), prolonged pain or recovery, reoperation, total hip arthroplasty, 6-month Patient-Reported Outcomes Measurement Information System Physical Function, 6-month Hip Dysfunction and Osteoarthritis Outcome Score Joint Replacement, or follow-up time between the injection and noninjection groups. There were no other differences in demographics, comorbidities, or physical function between the groups. Conclusion: Our study suggests that preoperative corticosteroid injections with local anesthetics do not significantly affect postoperative outcomes in hip arthroscopy patients or increase the risk of adverse effects. Careful evaluation of these risks and benefits is crucial to minimize potential adverse effects and maximize patient outcomes.

Rebound pain after arthroscopic cuff repair with interscalene brachial plexus block anesthesia is reduced by surgeon administered multimodal shoulder injections: A prospective randomized controlled trial.

To compare the effects of additional multimodal shoulder injections on postoperative rebound pain in patients undergoing arthroscopic rotator cuff repair (ASRCR) under interscalene brachial plexus block (ISBPB) anesthesia. A single-blind randomized controlled trial was conducted with 67 patients between April 2023 and December 2023. Patients undergoing ASRCR got an ISBPB anesthesia, not general anesthesia, were included with a minimum follow-up period of 48 h. The injection group received 40 mL of 0.75% ropivacaine, 20 mg morphine, 1:200,000 epinephrine, and saline solution, totaling 100 mL. Following surgery, the injection was administered to the subacromial space (50 ml) with blind suprascapular nerve block (25 ml) and blind axillary nerve block (25 ml). Controls received 100 mL of saline solution. Intravenous patient-controlled analgesia (IV-PCA) was used as adjuvant analgesia for all patients. The primary outcome was evaluated using the visual analog scale (VAS) pain score at 12 h after surgery, with secondary outcomes of the incidence of rebound pain and VAS pain scores at 0, 2, 4, 8, 24, 36, and 48 h postoperatively. Fentanyl in IV-PCA and rescue analgesic amounts, complications, and satisfaction were recorded. Sixty-seven patients (32 in the injection group, 35 in the control group) with a mean age of 61.1±9.0 years were included. The primary outcome assessment, VAS pain score at 12 h, significantly favored the injection group (2.7±0.93 vs. 4.1±1.70, p<0.001). The incidence of rebound pain was 18.8% and 65.7% in the injection and control groups, respectively (18.8% vs 65.7%, p<0.001). The injection group reported better VAS pain scores at 24, 36, and 48 h, and lower fentanyl use over the 48 h postoperative period (p=0.014). The use of rescue analgesics was similar between groups and no complications were associated with multimodal shoulder injections. Satisfaction levels were similar in both groups. The present study found that multimodal shoulder injections during ASRCR under ISBPB anesthesia significantly lowered VAS pain scores at 12 hours postoperatively and reduced the incidence of rebound pain compared to the control group. Pain levels were consistently lower from 12 to 48 hours postoperatively. Additionally, the injection group had reduced opioid consumption within the first 48 hours postoperatively, with no complications observed. Level I, randomized controlled trial.

Efficacy Analysis of Arthroscopic Surgery Combined with Intra-articular Chitosan Injection for Stage II-III Knee Osteoarthritis in Patients with Abnormal Body Weight.

Weight is an influential factor in knee osteoarthritis (KOA). However, the effect of abnormal body weight on chitosan's efficacy in treating KOA is unclear. This study aimed to explore the differences in the effectiveness of arthroscopic surgery combined with intra-articular chitosan injection for KOA in patients with abnormal body weight. Patients with stage II-III KOA (Kellgren-Lawrence rating, K-L) undergoing arthroscopic surgery were recruited for this clinical study from January 2020 to September 2021. Based on body mass index (BMI) and intra-articular chitosan injection, patients with KOA undergoing arthroscopic surgery (138 patients) were divided into four groups: low-weight-non-injection (Lw-N, BMI <18.5); low-weight-chitosan injection (Lw-CS, BMI <18.5); overweight-non-injection (Ow-N, BMI ≥25); overweight-chitosan injection (Ow-CS, BMI ≥25). A 2-year follow-up was conducted to evaluate various indicators, including the visual analogue scale (VAS) and the Western Ontario and McMaster Universities osteoarthritis index score (WOMAC). Statistical analyses were performed using relevant parametric or non-parametric tests. In total, 138 patients with KOA were included in this study. There were no significant differences in gender, age, and incidence of chronic residual pain after arthroscopy among the four groups (p > 0.05). The proportion of patients undergoing subsequent knee arthroplasty during the 2-year follow-up period was significantly higher in the Ow-CS group (20/35) than in the Lw-CS group (12/39) (p < 0.05). The K-L rating showed an overall increasing trend over time, with the K-L rating in the Ow-N and Ow-CS groups significantly higher than that in the Lw-CS group at the final follow-up (p < 0.05). VAS and WOMAC scores significantly decreased at 1 and 3 months post-arthroscopy and then increased. One month after arthroscopy, VAS was significantly lower (p < 0.05) in the intra-articular chitosan injection groups (Lw-CS and Ow-CS) compared with the non-injection groups (Lw-N and Ow-N). VAS was lower in the Ow-CS group than in the Lw-CS group (p < 0.05). There was no significant difference in WOMAC between the intra-articular chitosan injection and non-injection groups at each time point (Lw-N vs. Lw-CS, Ow-N vs. Ow-CS, p > 0.05). Arthroscopic surgery combined with intra-articular chitosan injection shows short-term positive effects in treating KOA. Intra-articular chitosan injection appears to have a greater short-term pain relief effect in obese patients.

Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women.

There are gaps in uptake of, adherence to, and persistence in the use of preexposure prophylaxis for human immunodeficiency virus (HIV) prevention among cisgender women. We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine-tenofovir alafenamide (F/TAF), or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo. We assessed the efficacy of lenacapavir and F/TAF by comparing the incidence of HIV infection with the estimated background incidence in the screened population and evaluated relative efficacy as compared with F/TDF. Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group (0 per 100 person-years; 95% confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAF group (2.02 per 100 person-years; 95% CI, 1.44 to 2.76), and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person-years; 95% CI, 0.96 to 2.74). Background HIV incidence in the screened population (8094 participants) was 2.41 per 100 person-years (95% CI, 1.82 to 3.19). HIV incidence with lenacapavir was significantly lower than background HIV incidence (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.04; P<0.001) and than HIV incidence with F/TDF (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.10; P<0.001). HIV incidence with F/TAF did not differ significantly from background HIV incidence (incidence rate ratio, 0.84; 95% CI, 0.55 to 1.28; P = 0.21), and no evidence of a meaningful difference in HIV incidence was observed between F/TAF and F/TDF (incidence rate ratio, 1.20; 95% CI, 0.67 to 2.14). Adherence to F/TAF and F/TDF was low. No safety concerns were found. Injection-site reactions were more common in the lenacapavir group (68.8%) than in the placebo injection group (F/TAF and F/TDF combined) (34.9%); 4 participants in the lenacapavir group (0.2%) discontinued the trial regimen owing to injection-site reactions. No participants receiving twice-yearly lenacapavir acquired HIV infection. HIV incidence with lenacapavir was significantly lower than background HIV incidence and HIV incidence with F/TDF. (Funded by Gilead Sciences; PURPOSE 1 ClinicalTrials.gov number, NCT04994509.).

Efficacy of Submucosal versus Pterygomandibular Dexamethasone Injection in Surgical Extraction of the Impacted Lower Third Molar

Objectives: This study aimed to evaluate the efficacy and postoperative complications of preoperative submucosal dexamethasone injection compared to preoperative dexamethasone injection into the pterygomandibular space for surgical extraction of the impacted lower third molar. Study design and setting: This was a quasi-experimental, cross-sectional study conducted at the Department of Oral and Maxillofacial Surgery, Dow International Dental College, Dow University of Health Sciences, Karachi, from April to July 2021. Methodology: The study sample consisted of 72 patients who reported surgical extraction of their lower wisdom teeth and consented to participate in this study. The patients were randomly divided into the submucosal injection group (SM) and the pterygomandibular space (PM) group. The injection time was recorded on the second and seventh postoperative days. Results: No significant differences in the duration of the intervention were observed between the two groups (23.08 min in PM, 23.07 min in SM). The postoperative facial swelling was significantly reduced transversely (ear lobe to the angle of the mouth) in both groups compared to their respective baselines on the first postoperative day. On the secondpostoperative day, significant changes were observed in the submucosal group in postoperative swelling. Conclusions: Using intraoral dexamethasone injections in third molar surgery significantly reduces conventional complications of surgery while avoiding the systemic side effects of steroids. Dexamethasone should be used regardless of the administration site when warranted, with less apprehension than is common in dentistry

Continuous Thymoquinone Administration Mitigates Sodium Iodate-Induced Retinal Degeneration in Rats

Purpose This study aimed to investigate the protective or therapeutic effect of thymoquinone (TQ) in a retinal degeneration rat model and its relationships with the retina ultrastructure, heme oxygenase 1 (HO-1), caspase-3, and RPE65 expressions and to determine whether TQ has a therapeutic effect at the biochemical level. Methods A total of 25 adult Wistar albino rats were divided into the following treatment groups: saline (control: CONT), CO (corn oil), sodium iodate (SI), TQ + SI, and SI + TQ injection groups. Retina morphology, RPE65, HO-1, and caspase-3 expression levels were evaluated using immunohistochemistry, and optical density was determined using ImageJ. Ultrastructural evaluations were performed with electron microscopy. Thiol-disulfide homeostatic parameters were examined in serum samples. Results Outer nuclear layer (ONL) thickness was significantly higher in the SI + TQ group compared to the SI group. The RPE65 expression significantly decreased in the SI group compared with the CONT and CO groups. A significant increase in RPE65 expression level and a significant decrease in caspase-3 expression level were found in the SI + TQ group compared with the SI group. The increase in HO-1 expression level was significantly higher in the TQ treatment groups, particularly in the SI + TQ group. In the SI and TQ + SI groups, the ONL thickness significantly decreased with a significant increase in caspase-3 expression compared to the CONT and CO groups. In the treatment groups, decreased organelle damage was observed on electron microscopy. In the SI + TQ group, the disulfide/native thiol and disulfide/total thiol ratios were significantly lower than all other groups, while the native/total thiol ratio was significantly higher than the other experimental groups. Conclusions The present study provides evidence that continuous TQ treatment can increase HO-1 and RPE65 expression and decrease apoptosis (caspase-3 levels), thereby preserving the retina at the ultrastructural level. Moreover, TQ administration can maintain thiol/disulfide homeostasis in SI-induced retinal degeneration-modelled rats.

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.

Comparison and clinical analysis of antibiotics and endoscopic injection for vesicoureteral reflux in children

PurposeThis study evaluated the outcome of pediatric patients with primary vesicoureteral reflux (VUR) and compared of the treatments between continued antibiotic prophylaxis (CAP) and endoscopic injection.MethodsThe clinical data of children diagnosed with primary vesicoureteral reflux from March 2015 to June 2020 who were treated with antibiotics or endoscopic injection were reviewed. Antibiotic was the first-chosen treatment after the diagnosis of VUR in children. Endoscopic treatment consisted of injection of dextran hyaluronic acid copolymer (DX/HA) into the ureteral opening under direct cystoscopy guidance.ResultsFifty-two children (35 males, 17 females) were included in this study, and for a total 90 ureters (14 unilateral, 38 bilateral) were diagnosed with vesicoureteral reflux by Voiding cystourethrography (VCUG). Twenty-two children were treated with antibiotics (8 unilateral, 14 bilateral), for a total of 36 ureters; thirty children were treated by endoscopic injection (6 unilateral, 24 bilateral), for a total of 54 ureters. The injection surgery took 36 ± 17 min including duration of general anesthesia and circumcision and the hospital stay was 2.3 ± 1.3 days. All male patients underwent circumcision simultaneously. There were no drug and allergic reactions in the antibiotic group, and no postoperative complications occurred in the injection group. With 23 months (13–63 months) of mean follow-up, the resolution rate, defined as radiological disappearance of VUR, was 36.1% (13/36) in the antibiotic group and 57.4% (31/54) in the injection group (P = 0.048).Two cases of bilateral reflux in the injection group required a second injection before resolution could be achieved. Thus, the overall success rate of injection was 64.8% (35/54). 9 cases (9/18, 50%) in the antibiotic group had renal scars on DMSA scans, while this was seen in 20 cases (20/23, 86.9%) in the injection group. There was a statistically significant difference between the two groups (P = 0.010).The positive rates of ultrasound between the antibiotic group and the injection group were 45.5% (10/22) and 80.0% (24/30), respectively. There was a statistically significant difference between the two groups in positive rates of ultrasound (P = 0.010).ConclusionsEndoscopic injection is easy to operate with short surgical time and hospital stay, so it is a safe and feasible treatment. For the treatment of primary vesicoureteral reflux in children, the radiological resolution rate of endoscopic injection is better than antibiotic therapy. In this study, the presence of kidney scars on DMSA and the dilated of the collecting system on ultrasound are the indications for endoscopic injection.

Ultrasound-guided Hydrogel Injection Provides Better Therapeutic Effects After Hand Tendon Surgery Than Intraoperative Injection: A Randomized Controlled Trial.

Hydrogels are used to provide a barrier against peritendinous adhesion formation, but when implanted intraoperatively, they degrade rapidly and aggravate early inflammatory pain. It is uncertain whether clinical efficacy can be improved by avoiding the inflammatory phase when hydrogels are delivered during adhesion formation. (1) Compared with intraoperative hydrogel application, does ultrasound-guided postoperative application result in better total active motion (TAM) at 12 months after tendon injury? (2) Does ultrasound-guided postoperative application of hydrogels result in lower pain, better function, and better satisfaction? This open-label, prospective, single-center, randomized controlled trial was conducted by reparative and reconstructive surgeons at the National Orthopedics Clinical Medical Center, Shanghai, People's Republic of China. Between May 2021 and December 2022, 53% (168 of 317) of patients who met our inclusion criteria were recruited, and 47% (149 of 317) of patients were excluded because of the exclusion criteria. Finally, 84 patients were randomized to the postoperative group to receive ultrasound-guided carboxymethyl chitosan (CMC) hydrogel delayed injection, and 84 patients were randomized to the intraoperative group to receive CMC hydrogel intraoperative application. Another 8% (7 of 84) of patients in the postoperative group and 10% (8 of 84) of patients in the intraoperative group were lost before the minimum study follow-up time of 1 year or had incomplete datasets, leaving 91% (153 of 168) of patients with data for analysis. Data on outcome events were analyzed according to the intention-to-treat principle, which included all patients who underwent randomization. Follow-up visits were completed at 3 weeks, 6 weeks, 3 months, 6 months, and 12 months after tendon repair. The primary outcome was TAM (ie, the sum of the degrees of active metacarpophalangeal joint, proximal interphalangeal joint, and distal interphalangeal joint flexion less the degrees from full extension; minimum clinically important difference [MCID] 20°) at 12 months. Secondary outcomes included pain (measured with a VAS; range 0 to 10, a higher score indicating worse pain; MCID 0.6), Michigan Hand Outcomes Questionnaire activities of daily living (MHQ-ADL) score (range 0 to 100, a higher score indicating better outcomes; MCID 10.1), and MHQ satisfaction (MHQ-SAT) score (range 0 to 100, a higher score indicating better outcomes; MCID 33.0). At 12 months, the ultrasound-guided postoperative injection group had improved TAM (intraoperative 189° [95% CI 179° to 199°] versus postoperative 209° [95% CI 199° to 219°], mean difference 20° [95% CI 6° to 35°]; p = 0.006; the mean difference in the primary outcome fulfilled the MCID value at all time points). At 6 weeks, we found no clinically important difference in VAS pain scores among groups (intraoperative mean ± SD 2.0 ± 1.0 versus postoperative 1.7 ± 1.0, mean difference 0.3 [95% CI 0.1 to 0.7]; p = 0.02); however, at 3 weeks, the VAS pain scores showed clinically important difference among groups (3.6 ± 1.4 versus 2.9 ± 1.2, mean difference 0.7 [95% CI 0.3 to 1.1]; p = 0.001). At 3 months, the ultrasound-guided postoperative injection group had higher MHQ-ADL scores (intraoperative 62 ± 10 versus postoperative 75 ± 10, mean difference 13 [95% CI 11 to 17]; p < 0.001), and the mean difference of MHQ-ADL scores reached the MCID value at all time points. At 3 months, there was no clinically important difference in MHQ-SAT scores between groups (intraoperative 62 ± 8 versus postoperative 70 ± 8, mean difference 8 [95% CI 6 to 11]; p < 0.001). Compared with intraoperative CMC hydrogel injection, postoperative ultrasound-guided injection improved the TAM and function of the affected limb, showed a short-term pain control effect, and did not increase the risk of complications. Clinical trials are needed to confirm the safety and efficacy of ultrasound-guided postoperative injection of CMC hydrogels and to determine the most effective dose and the health and economic benefits of treatment. Level I, therapeutic study.

Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice.

Postoperative cognitive dysfunction is a severe complication of the central nervous system that occurs after anesthesia and surgery, and has received attention for its high incidence and effect on the quality of life of patients. To date, there are no viable treatment options for postoperative cognitive dysfunction. The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research. To identify the signaling mechanisms contributing to postoperative cognitive dysfunction, we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset, which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus 3 days after tibial fracture. The dataset was enriched in genes associated with the biological process "regulation of immune cells," of which Chill was identified as a hub gene. Therefore, we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fracture surgery. Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 1 24 hours post-surgery, and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests. In addition, protein expression levels of proinflammatory factors (interleukin-1β and inducible nitric oxide synthase), M2-type macrophage markers (CD206 and arginase-1), and cognition-related proteins (brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B) were measured in hippocampus by western blotting. Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment, downregulated interleukin-1β and nducible nitric oxide synthase expression, and upregulated CD206, arginase-1, pNR2B, and brain-derived neurotropic factor expression compared with vehicle treatment. Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1. Collectively, our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus. Therefore, recombinant chitinase-3-like protein 1 may have therapeutic potential for postoperative cognitive dysfunction.

Effects of sodium lactate injection on meat quality and lactate content in broiler chickens: emphasis on injection method and dosage

This study aims to develop an experimental model of high lactate levels in broilers to mimic the condition of birds under stress or diseases and evaluate its consequent effects on meat quality. The injection sites and dosage effects were compared separately in 2 experiments. Experiment 1 includes 3 injection sites: intraperitoneal injection, intramuscular injection, and subcutaneous injection. Experiment 2 was a dosage experiment based on the results of Experiment 1: sodium lactate intraperitoneal injection group with 1.5, 3, 6 mM concentration. The results showed that injecting sodium lactate intraperitoneally, intramuscularly, or subcutaneously all significantly decreased body weight and breast muscle weight while elevating lactic acid levels in both the blood and breast muscle of broilers. Moreover, all 3 injection methods caused a significant reduction in pH24h and an increase in the shear force value of breast muscle. In addition, dose-response experiments of intraperitoneal injection showed that a concentration of 3 mM and 6 mM were significantly decreased body weight and breast muscle weight in broiler chickens, accompanied by a notable increase in breast muscle lactate content. Compared to the control group, intraperitoneal injections of 1.5 mM, 3 mM, and 6 mM sodium lactate treatments significantly reduced the yellowness values of the breast muscle. As the dose of sodium lactate increased, the shear force value of the breast meat exhibited linear and quadratic increments, while the drip loss decreased linearly. Intraperitoneal injection of 3 mM sodium lactate also significantly reduced the pH24h of broiler breast muscle. In addition, an increased dose of lactate injections up-regulated the glycolytic pathway responsible for endogenous lactate production in the breast muscle by upregulating the expression of phosphofructokinase, pyruvate kinase and lactate dehydrogenase A. In conclusion, intraperitoneal injection of sodium lactate at 3 mM directly increased breast muscle lactate levels, providing a valuable method for establishing a high-level lactate model in poultry.

Investigation of the Effect of Local and Systemic Preoperative Dexamethasone Application on Bone Tissue Healing in Mandibular Bone Defects.

The aim of this study was to investigate the effect of locally and systemically delivered single-dose corticosteroid injections on bone tissue. A total of 84 Wistar albino rats were divided into 2 groups as local and systemic injection groups, and 2 groups as control and experiment among themselves. Before the procedure, dexamethasone was given to the experimental group and physiological saline was given to the control group. A defect was created in the jawbone. It was sacrificed on the third, seventh, and 40th days. The mandible bones of the sacrificed rats were removed and the healing of the bone tissue was examined histopathologically. No significant difference was observed in the tissue sections of the subjects sacrificed after 40 days. However, the increase in fibroblastic connective tissue and the number of osteoblasts were less in the experimental local groups that were sacrificed after 7 days compared with the control groups (P=0.040 and 0.041). Again, it was determined that there was a statistically significant decrease in the experimental local group compared with the experimental systemic group (P=0.040 and 0.004). It can be said that single-dose corticosteroid applications cause a delay in bone healing in the early period.