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Buprenorphine, an analgesic commonly used in rodent surgery, requires repeated dosing every 4 to 6 h in order to provide adequate analgesia. However, redosing requires repeated handling, which may itself cause stress. Buprenorphine SR-LAB, which reportedly maintains serum levels of buprenorphine greater than 1 ng/mL for 48 to 72 h, is commercially available. However, the viscosity of the product and small dosing volumes make accurate dosing a challenge. Simbadol is a concentrated formulation of buprenorphine hydrochloride labeled for use in cats with recommended dosing frequency of every 24 h. We measured serum concentrations over time after a single injection of this product in C57BL/6NCrl mice and compared it to standard buprenorphine (Buprenex) and Buprenorphine SR-LAB. Male and female mice were injected subcutaneously with one of the 3 buprenorphine formulations at a dose of 1 mg/kg at time 0. Groups of mice (n = 8) were euthanized at 1, 4, 8, 12, 16 h for all groups and 24 h for the Simbadol and the Buprenorphine SR-LAB. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to determine concentrations of buprenorphine in each serum sample. High concentrations were observed in both Simbadol and standard buprenorphine groups one hour after injection (>50 ng/mL). These groups had similar buprenorphine concentration curves, including rates of decline. The standard buprenorphine group had mean concentrations less than 1 ng/mL by 12 h and the Simbadol group by 16 h. In contrast, the Buprenorphine SR-LAB group remained above the 1 ng/mL therapeutic threshold throughout the 24 h. In addition, clinical signs, including increased activity, that lasted for up to an hour after the injection in the Simbadol and standard buprenorphine groups. We conclude that Simbadol does not offer dosing advantages over the standard buprenorphine formulation when given at 1 mg/kg. Buprenorphine SR-LAB maintained a steady concentration of buprenorphine above 1 ng/mL for at least 24 h, and as such is a superior choice for providing long-term analgesia.

Cefazolin is an antibiotic recommended for infection prevention in total hip arthroplasty (THA). However, the dosing regimen necessary to achieve therapeutic concentrations in obese patients remains unclear. The aim of this study was to conduct a population analysis of cefazolin pharmacokinetics (PK) and assess whether cefazolin administration should be weight adapted in THA. Adult patients undergoing THA surgery received an injection of 2000 mg of cefazolin, doubled in the case of BMI > 35 kg/m2 and total body weight > 100 kg. A population PK study was conducted to quantify cefazolin exposure over time compared to the therapeutic concentration threshold. A total of 484 cefazolin measurements were acquired in 100 patients, of whom 29% were obese. A 2-compartment model best fitted the data, and creatinine clearance determined interpatient variability in elimination clearance. Our PK simulations using a 2000 mg cefazolin bolus showed that cefazolin concentrations remained above the threshold throughout surgery, regardless of weight or renal function. A 2000 mg cefazolin single injection without adaptation to weight or renal function and without intraoperative reinjection was efficient in maintaining therapeutic concentrations throughout surgery. The optimal target concentration and necessary duration of its maintenance remain unclear.

Background Ultrasonography is increasingly used in pediatric surgery. Intraoperatively, ultrasonography can be used to confirm the preoperative diagnosis, guide the surgical approach, and enhance decision-making. We aimed to report our experience with intraoperative ultrasonography in different neonatal and pediatric procedures. So, a retrospective study was designed. It included all pediatric patients who had intraoperative ultrasound between January 2018 and October 2020 in a single center. Results We used intraoperative ultrasonography in 208 pediatric patients for various types of surgery. The authors compared ultrasound-guided central line insertion (n = 139) to the landmark method (n = 153). The number of trials was significantly lower in the ultrasound-guided method (P < 0.001). Conversion to cut-down was significantly lower with the ultrasound-guided technique (4 (2.8%) vs. 13 (8.5%); P = 0.047) and insertion-related complications were lower with ultrasound (0 vs 13 (8.5%); P < 0.001). We used ultrasound-guided sclerotherapy for cystic hygroma in 15 patients. Nine patients had successful treatment with a single injection (60%). Conclusion The application of intraoperative ultrasound in pediatric patients is increasing in our institution. The technique is safe and could effectively reduce central line insertion complications and enhance cystic hygroma sclerotherapy’s success with a single injection. Ultrasonography should be an essential part of residents’ and fellows’ training in pediatric surgery.

OBJECTIVE To evaluate the efficacy and safety of anakinra compared to triamcinolone in the treatment of gout flares. METHODS Patients for whom nonsteroidal antiinflammatory drugs and colchicine were not suitable treatments were enrolled in this multicenter, randomized, double-blind study with follow-up for up to 2 years. The study was designed to assess superiority of anakinra (100 or 200 mg/day for 5 days) over triamcinolone (40 mg in a single injection) for the primary end point of changed patient-assessed pain intensity in the most affected joint (scored on a visual analog scale of 0-100) from baseline to 24-72 hours. Secondary outcome measures included: safety, immunogenicity, and patient- and physician-assessed global response. RESULTS One hundred sixty-five patients were randomized to receive anakinra (n = 110) or triamcinolone (n = 55). The median age was 55 years (range 25-83), 87% were men, the mean disease duration was 8.7 years, and the mean number of self-reported flares during the prior year was 4.5. A total of 301 flares were treated (214 with anakinra; 87 with triamcinolone). Anakinra in both doses and triamcinolone provided clinically meaningful reduction in patient-assessed pain intensity in the first and subsequent flares. For the first flare, the mean decline in pain intensity from baseline to 24-72 hours for total anakinra and triamcinolone was -41.2 and -39.4, respectively (P = 0.688). Anakinra performed better than triamcinolone for most secondary end points. There were no unexpected safety findings. The presence of antidrug antibodies was not associated with adverse events or altered pain reduction. CONCLUSION Anakinra was not superior to triamcinolone for the primary end point, but had comparable efficacy in pain reduction and was favored for most secondary end points. Anakinra is an effective option for gout flares when conventional therapy is unsuitable.

BACKGROUND Epidural steroid injections (ESIs) have been widely used for over 50 years in the treatment of back pain with or without radiculopathy. In this study, we intended to evaluate the effect of single caudal epidural steroid injection (CESI) in patients suffering from chronic lumbago-sciatica syndrome, resistant to conservative medical therapy. METHODS This was a retrospective study. CESI was performed on thirty-four patients suffering from chronic lumbago-sciatica syndrome, from April 2019 to March 2020. Single injection of caudal epidural steroid (40 mg Triamcinolone Acetonide) diluted with 10 ml. of sterile water was given guided by anatomic landmark, confirmed by “Whoosh” test and radiologically with dye. Patients were followed for 12 weeks using Numeric Rating Scale (NRS) for pain, Oswestry disability index (ODI) and North American spine society patient satisfaction index (NASS). Values were recorded before the injection and after the injection at 1 week, 3 week, 6 week and 12 week during follow-up. RESULTS Significant improvement in patient’s status was observed after CESI, as measured with NRS, ODI and NASS at one, three, six and twelve weeks as compared to pre injection (zero week) but no significant difference was observed at successive follow ups at first to third and third to six weeks. There was significant reversal of NRS and ODI Score from 6 week to 12 week follow-up. Sixty seven percent of patients were satisfied at the end of the follow-up and mild side-effects were reported in a few patients. CONCLUSIONS CESI is a safe, simple and cost-effective intervention procedure for the treatment of chronic lumbago-sciatica syndrome. It provides rapid pain relief and physical function improvement of the patient starting within a week. KEYWORDS Injections, Epidural, Sciatica, Low Back Pain

As veterinary practice shows, most often atopic dermatitis in animals manifests itself in the form of a rash (in the ears, muzzle, paws, etc.), which in turn is accompanied by itching. First of all, prescribe a single injection of glucocorticoids, or short-term therapy. Corticosteroid hormones (glucocorticoids) are one of the most powerful antiallergic drugs. They are effective in treating almost all types of allergic reactions. An appropriate dose of glucocorticoids is required to obtain a rapid effect, and the form of the drug should be convenient to use. The aimof the research.The aim of our study was experimentally substantiate the choice of the optimal gelling agent when developing a gel composition with hydrocortisone for use in veterinary medicine. Materials and methods.Physical, physico-chemical and pharmaco-technological methods were used during the experimental study. Studies were performed according to the method described in the SPhU. The rheological properties of the samples were determined using a rotary viscometer type Brookfield HB DV (USA) with spindle SC4-21. Results.As a result of the research, it was found that Aristoflex as a gelling agent in the development of a veterinary drug of local action will ensure the availability of appropriate extrusion properties (namely, easy and uniform application of animal skin, ease of use). Gels with hydrocortisone based on Aristoflex gave stable performance, which was confirmed by the results of mechanical and colloidal stability. Conclusions.The composition and technology of a hydrocortisone gel for local therapy of atopic dermatitis in animals has been developed. Aristoflex at a concentration of 1.5 % on the basis of a set of physicochemical, structural-mechanical and biopharmaceutical studies was selected as the optimal gelling agent in the drug

BACKGROUND This was a randomised single-blinded study. It was designed to compare the superiority of infiltration analgesia and ultrasound guided unilateral transversus abdominis plane block on pain scores, total opioid consumption, and assess the side effects of opioid after nephrectomy. METHODS This study included 56 patients aged between 18 - 50 years with American Society of Anaesthesiologists (ASA) status II - III who underwent nephrectomy. Patients were broadly placed in 2 groups, who underwent transversus abdominis plane block for postoperative analgesia as Group TAP and infiltration analgesia as Group LA. Visual analog scale was used for post-operative pain evaluation at the 0, 2, 4, 6, 8, 12, 24 hours. Patients with VAS of more than 3 were given tramadol 1 mg / Kg. In the first 24 hours postoperatively, total analgesic consumption, rate of nausea vomiting and other side effect of patients were recorded and results were evaluated statistically. RESULTS Demographic characteristics were similar in the two groups; post-operative visual analog scale (VAS) score were significantly less in the transversus abdominis plane block group at the 6th, 8th and 12th hours compared to the infiltration analgesia group. The total analgesic consumption and nausea-vomiting rates were significantly lower in the transversus abdominis plane block. CONCLUSIONS In our study transversus abdominis plane block method was found superior to infiltration analgesia method on post-operative pain management in unilateral nephrectomy. In conclusion, we recommend the transversus abdominis plane block to be effective for post-operative analgesia after unilateral nephrectomy. KEYWORDS Nephrectomy, Postoperative Pain Management, Transversus Abdominis Plane Block, Infiltration Analgesia, opioid Consumption

Ketamine has emerged as a novel treatment for common psychiatric conditions such as Major Depressive Disorder (MDD) and anxiety disorders, many of which can be initiated and exacerbated by psychological stress. Sex differences in the frequency of both anxiety and depressive disorders are well known and could be due in part to sex differences in neuroendocrine responses to stress. Ketamine is an MDD treatment and is itself known to modulate the hormonal response to stress, specifically corticosterone. Though differential behavioral responses to ketamine between the sexes have been reported in animals, it is not clear if the acute effect of ketamine on corticosterone differs by sex, or what role this could play in the subsequent behavioral response. Here we test whether a single injection of (R,S)-ketamine (30 mg/kg, i.p.), administered either with or without unpredictable chronic stress (UCS), has different sustained effects on open field (OFT), elevated zero maze (EZM) or forced swim test (FST) behavior in female versus male C57BL/6J mice. We also test whether plasma corticosterone may play a predictive role in those responses. In the OFT (24 hours post-injection), ketamine increased center square exploration in males but not females. In contrast, in the FST (72 hours post-injection), females showed a trend toward a decrease in immobility after ketamine whereas males were not strongly modulated. These behavioral effects of ketamine were stronger in the presence of UCS than in unstressed animals. UCS animals also showed lower corticosterone after injection than unstressed animals, and in the presence of UCS ketamine increased corticosterone; these effects were similar in both sexes. Corticosterone post-injection did not predict subsequent behavioral measures. These findings complement a growing preclinical literature suggesting both stress-dependency and sex differences in OFT and FST behavioral responses to ketamine, and these differences are not mediated by corticosterone.

Background: One common method of pain control for total shoulder arthroplasty is long-duration delivery of local anesthetic via interscalene brachial plexus block (ISB) with a continuous catheter. Alternatively, liposomal bupivacaine has also been administered as an ISB as a means to prolong the analgesic effect. This study was completed to measure the non-inferiority of single-injection ISB with liposomal bupivacaine compared with ISB continuous catheter for total shoulder arthroplasty. Methods: We performed a retrospective chart review of patients who underwent total shoulder arthroplasty using either an ISB continuous catheter or a single injection ISB with liposomal bupivacaine for post operative analgesia. The primary goal of this study was to determine if single-injection with liposomal bupivacaine conferred non-inferior pain scores compared to the continuous catheter. Secondary outcomes evaluated oxygen saturation as a measure of hemidiaphragmatic paresis, post operative opioid requirements, and difference in cost. Results: We identified 333 patients for the study: 126 received continuous catheter and 207 received single-injection with liposomal bupivacaine. The median length of stay was 1 day. Pain scores for those treated with single-injection with liposomal bupivacaine were non-inferior to pain scores of those treated with the continuous catheter on post-op days 0, 1 and 2. Pain scores were lower for single-injection with liposomal bupivacaine patients on days 3 and 4, however they did not reach statistical significance. There was no significant difference in oxygen saturation between the two groups. Both groups had similar daily morphine milligram equivalent requirements. Liposomal bupivacaine ISB was also found to be less expensive. Conclusion: Single-injection ISB with liposomal bupivacaine provides non-inferior analgesia at a reduced cost compared with continuous catheter ISB for total shoulder arthroplasty.

New methods have been studied in the past few decades to decrease exhaust emissions and fuel consumption of diesel engines. Using new combustion methods as low-temperature combustion (LTC) strategies and also utilizing new fuels as bio-diesel are beneficial ways to overcome diesel engine issues. This numerical study focused on the effect of split injection strategies as well as swirl ratio (SR) on the biodiesel premixed charge compression ignition (PCCI) combustion process and the related emissions. In this regard, KIVA-3V code as a CFD tool has been utilized to analyze the combustion and emission characteristics of the diesel engine. Single and split injection strategies have been executed on biodiesel PCCI combustion and have been compared in order to probe and examine the injection strategies. The results show that in both strategies, advancing the injection timing can lower the combustion emission and improve the engine performance by optimizing the start of injection (SOI) as sweet spot value. Utilizing a high swirl ratio with the split injection strategy has a negative effect on overall combustion, emission, and performance in comparison with the single injection strategy. For multi-injection scheme, SOI = −35 ATDC, SR = 1.1, and for single injection scheme, SOI = −40 ATDC, SR = 1.1 are considered as optimum cases regarding minimum total exhaust emissions and highest performance.

GM1 gangliosidosis is a rare neurodegenerative lysosomal storage disease caused by loss-of-function mutations in the gene encoding beta-galactosidase (β-gal). There are no approved treatments for GM1 gangliosidosis. Previous studies in animal models have demonstrated that adeno-associated viral (AAV) vector-mediated gene transfer to the brain can restore β-gal expression and prevent the onset of neurological signs. We developed an optimized AAV vector expressing human β-gal and evaluated the efficacy of a single intracerebroventricular injection of this vector into the cerebrospinal fluid (CSF) of a murine disease model. The AAV vector administration into the CSF increased β-gal activity in the brain, reduced neuronal lysosomal storage lesions, prevented the onset of neurological signs and gait abnormalities, and increased survival. These findings demonstrate the potential therapeutic activity of this vector and support its subsequent development for the treatment of GM1 gangliosidosis.

Aim: To assess the functional outcome of treatment of osteoarthritis knee joint by intra articular injection of platelet rich plasma.Methods: A total of 50 patients with grade 0 to grade 3 osteoarthritis knee joint were randomly selected and 2 doses of intraarticular injection of platelet rich plasma were given at interval of 1 month and the outcome was evaluated with visual analog scale (VAS) and the western Ontario and mcmaster universities arthritis index (WOMAC) at preinjection, 1,3 and 6 months interval. Results: The mean age of patients were 55.5. There were better improvements noted in VAS and WOMAC scale. Best scores were noted in 2 months interval. The scores got deteoriated over 6 months interval but the final scores were better than the pre injection scores. Two injection therapy gives better result than single injection therapy.Conclusion: Platelet rich plasma injection is effective in the treatment of osteoarthritis knee with minimum of two injections is appropriate therapies in treatment of osteoarthritis knee joint.

Purpose To compare efficacy of ultrasound (US)-guided single-injection nerve blocks (SINB) before bipolar hemiarthroplasty (BHA) of the hip in patients with femoral neck fractures. Materials and Methods Clinical outcomes of 89 patients who underwent BHA between September 2016 and February 2018 were retrospectively compared. Eight patients were excluded according to exclusion criteria and the remaining patients were divided into two groups: patients who received SINB before surgery (Group I; n=40), and patients who did not (Group II; n=41). The femoral, obturator, and lateral femoral cutaneous nerves were each blocked separately under US guidance. Pain scores determined using the visual analogue scale (VAS) were recorded 6, 12, 24, and 48 hours postoperatively, and all use of analgesics were recorded separately for 72 hours after surgery. Duration of hospitalization, general complications, and local complications due to SINB were also compared among the groups. Results Significant differences were observed between the two groups: I) VAS at 6 hours and at 12 hours after the operation, II) total amounts of analgesics used. VAS at 24 hours and at 48 hours were not significantly different between the two groups. General complications and duration of hospitalization were also not significantly different between the groups. Conclusion US-guided lower limb nerve blocks provide excellent immediate postoperative pain relief and can be used as a safe, and effective method of pain control after BHA.

Nowadays there is strong demand to produce embryos from premium quality cattle, and we can produce embryos using oocytes collected from living premium animals by ovum-pick up (OPU) followed by in vitro fertilization (IVF). However, the developmental competence of IVF oocytes to form blastocysts is variable. The developmental competence of oocytes depends on the size and stages of follicles, and follicle-stimulating hormone priming (FSH-priming) prior to OPU can promote follicular growth and improve the developmental competence of oocytes. Furthermore, following the induction of ovulation using an injection of luteinizing hormone or gonadotropin-releasing hormone after FSH-priming, we can collect in vivo matured oocytes from ovulatory follicles, which show higher developmental competence than oocytes matured in vitro. However, the conventional protocols for FSH-priming consist of multiple FSH injection for 3-4 days, which is stressful for the animal and labor-intensive for the veterinarian. In addition, these techniques cannot be applied to IVF of oocytes collected from bovine ovaries derived from slaughterhouses, which are important sources of oocytes. Here, we review previous research focused on FSH-priming, especially for collecting in vivo matured oocytes and a simplified method for super-stimulation using a single injection of FSH. We also introduce the previous achievements using in vitro pre-maturation culture, which can improve the developmental competence of oocytes derived from non-stimulated animals. (C) 2020 Elsevier Inc. All rights reserved.

The aim was to study the protective effect of ethanolic extract of Achillea millefolium on acute vascular injuries induced by cisplatin in liver, heart and renal tissues 24 hour after administration and using histopathological surveys in wistar rats. 24 adult male wistar rats were randomly divided into four groups. Group I (control group) received physiological saline for 10 days. Animals of group II had single dose of injection of CP (cisplatin) (6 mg/kg, IP) on the ninth day. Group III received Achillea millefolium extract (250 mg/kg, gavage) for 10 consecutive days. Group IV had both Achillea millefolium extract (250 mg/kg, gavage) for 10 consecutive days and a single dose of injection of CP (6 mg/kg, IP) on the ninth day. Kidney, liver and heart organs were collected on 10th day from sacrificed rats and subjected to histopathological analysis. Then the possible histopathological vascular effects of cisplatin on liver, heart, kidney tissues and the protective effect of Achillea millefolium extract was analysed. Obtained data showed the vascular injuries in CP group as congestion of cardiac capillaries (p=0.00) and interstitial edema (p=0.03). In the kidney, shrinkage of glomeruli (p=0.04), widening of Bowman's space (p=0.04), dilatation of cortical capillaries (p=0.01) were significantly altered. The findings of liver organ were increased sinusoidal space (p=0.00) and infiltration of neutrophils in portal space (p=0.01). Pretreatment with ethanolic extract of Achillea millefolium could attenuate these vascular injuries. Briefly, 24 hour after single injection of cisplatin the inflammatory process was seen in vital organs and administration of Achillea millefolium could mitigate these side effects.

Aim. The potential distribution of the cardioelectric field on the body surface during the initial atrial activity and the sequence of depolarization of the atrial subepicardium in rats with experimentally induced pulmonary hypertension were compared. This work is devoted to non-invasive detection of arrhythmogenic foci of atria by using the cardioelectric field on the body surface during experimental pulmonary hypertension.Materials and methods. The method of cardioelectrochronotopography has been used to study the electric field of the heart on the body surface and the sequence of propagation of the excitation wave along the atrial epicardium in rats with experimentally induced pulmonary hypertension caused by a single injection of monocrotaline (60 mg / kg, four weeks after drug administration).Results. Pulmonary hypertension causes the appearance of an additional focus of initial excitation in the area of the pulmonary vein lacunae, which leads to an increase in the heterogeneity of the propagation of the excitation wave along the atrial epicardium. The appearance of the additional excitation focus in the mouths of the pulmonary veins in the left atrium changes the picture of the sequence of depolarization of the atrial epicardium. The heterogeneity of the propagation of the excitation wave along the atrial epicardium is reflected in a different arrangement of zones of positive and negative cardioelectric potentials on the body surface before and during the P-wave in comparison with the initial state.Conclusion. Induced pulmonary hypertension contributes to the appearance of an additional focus of initial excitation in the area of the sleeves of the pulmonary veins of the left atrium in rats. This leads to an increase in the heterogeneity of the propagation of the excitation wave along the atrial epicardium. This is also reflected in the change in the arrangement of the zones of positive and negative cardioelectric potentials on the body surface before and during the P-wave in comparison with the initial state.

Hemophilia A (HemA) patients are currently treated with costly and inconvenient replacement therapy of short-lived factor VIII (FVIII) protein. Development of lipid nanoparticle (LNP)-encapsulated mRNA encoding FVIII can change this paradigm. LNP technology constitutes a biocompatible and scalable system to efficiently package and deliver mRNA to the target site. Mice intravenously infused with the luciferase mRNA LNPs showed luminescence signals predominantly in the liver 4 h after injection. Repeated injections of LNPs did not induce elevation of liver transaminases. We next injected LNPs carrying mRNAs encoding different variants of human FVIII (F8 LNPs) into HemA mice. A single injection of B domain-deleted F8 LNPs using different dosing regimens achieved a wide range of therapeutic activities rapidly, which can be beneficial for various usages in hemophilia treatment. The expression slowly declined yet remained above therapeutic levels up to 5–7 days post-injection. Furthermore, routine repeated injections of F8 LNPs in immunodeficient mice produced consistent expression of FVIII over time. In conclusion, F8 LNP treatment produced rapid and prolonged duration of FVIII expression that could be applied to prophylactic treatment and potentially various other treatment options. Our study showed potential for a safe and effective platform of new mRNA therapies for HemA., Graphical Abstract, Messenger RNA (mRNA) encapsulated in lipid nanoparticles (LNPs) can be efficiently delivered into the liver. LNPs carrying FVIII mRNA (F8 LNPs) produced rapid and prolonged duration of FVIII expression in hemophilia A mice. This safe and effective platform of new mRNA therapies could be used for prophylactic treatment and potentially various other treatment options for hemophilia A patients.

Oil recovery in oil rim reservoirs is usually affected by reservoir and operational parameters. An experiment was designed to develop various types of oil rims with a broader range of uncertainties. Mensuration analysis was used to create the basic grid designs, while the Eclipse software was used to incorporate pressure, volume and temperature and reservoir fluid properties to create a black oil model for oil rims. The reservoir models were conditioned to a simultaneous production scheme through which a response surface model was generated to represent oil recovery for all the models. The models were later classified into drive mechanisms based on the results from the Pareto analysis. Various secondary injection schemes were carried out based on reservoir geometry to investigate their response on oil recovery. Results show that for single injection schemes, oil recovery from water down-dip (6.5%) and water up-dip (4.37%) was higher than gas scheme injection for reservoir model 10. Oil recovered from up-dip and down-dip water injection (7.1%) was higher than gas up-dip and down-dip injection (0.03%) for reservoir model 10, and for the same model, an oil recovery of 7.7% and 5.63% was recorded for gas up-dip and water down-dip injection and gas down-dip and water up-dip injection, respectively. The final analysis shows that there is an appreciable increase in oil recovery when injection rates are increased as seen in water down-dip and up-dip injection with 15.43% recovery for reservoir model 10.

Background and Aims: Total pain free outcome following total knee arthroplasty has led to the evolution of regional blocks. In this series, the authors have revisited and modified Roy et al. 's technique of Ultrasound guided 4 in 1 block for knee and below knee surgeries, to provide a complete comprehensive yet simple single injection technique for postoperative analgesia for Total Knee Arthroplasty (TKA). Material and Methods: After Instituional ethics approval, we performed the modified 4 in 1 block on 10 consenting patients scheduled to undergo total knee arthroplasty. A linear USG-probe was used to identify medial femoral condyle, then vastus and sartorius intersection was identified. The probe was slid till the descending genicular artery branching from superficial femoral artery was visualized proximal to hiatus. At this point the needle with PNS attached, was guided into the Vastus medialis muscle till the stimulation of the nerve to Vastus medialis (0.4-0.5 mA). At this point 5–7 mL of 0.2% Ropivacaine was injected. The needle was guided in plane to perivascular region and after negative aspiration 0.2%ropivacaine 20–25 ml was injected, visualised to push the femoral artery. Results: All ten patients considered in this study had an optimum pain score of

Background: A recently registered device containing 80 mg of adalimumab (ADA) allows an alternative dose escalation regimen with ADA 80 mg every other week (EOW) given as a single subcutaneous injection instead of 40 mg every week. The ADASCAL study evaluated the preferences and satisfaction of inflammatory bowel disease (IBD) patients after switching their ADA regimen from 40 mg weekly to 80 mg EOW given with a single-dose pen. Methods: In this multicentre cross-sectional study, patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW completed the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), a four-item questionnaire [a Likert-type 5-point scale for preferences, two closed questions for convenience and a 100-point visual analogue scale (VAS) to assess which escalated ADA regimen patients would prefer to continue] and two Health-Related Quality of Life (HRQoL) questionnaires: the generic European Quality of Life–5 Dimensions (EQ-5D) and disease-specific Spanish version of the Inflammatory Bowel Disease Questionnaire (SIBDQ-9). Results: In total, 77 patients (64 Crohn’s disease and 13 ulcerative colitis) were included. The TSQM score showed a notably high global satisfaction [83.4, standard deviation (SD) = 14.1] of patients with ADA 80 mg EOW given with a single-dose pen, with high TSQM scores for individual components: effectiveness (77.6, SD = 16.9), convenience (83.7, SD = 14.5) and side effects (86.1, SD = 23.4). Most of the patients (74%) preferred the ADA EOW regimen (59.7% had strong preference, 14.3% slight preference). ADA EOW interferes less with daily activity (59.7%) and with travel plans (81.8%). Most patients (77%) would prefer to continue with ADA EOW (mean VAS score of 84.7, SD = 24.1, where 100 indicates a preference for ADA EOW). Patients reported high HRQoL scores on both the EQ-5D (72.3, SD = 20.1) and SIBDQ-9 (75.1, SD = 14.7). Conclusion: IBD patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW reported a higher preference for the EOW regimen and therefore most decided to continue with a single self-injection EOW.

Hormones used for various purposes in animal breeding are not only important for animal health but also human health and thus meat and meat products need to be checked frequently for hormone residues. As the methods of detecting hormone residues in food samples are difficult and time-consuming, the present study was conducted with the aim of fast and practical determination of prohibited anabolic agents in red meat using LC MS-MS system. For this purpose, the QuEChERS method, which is widely used in pesticide and veterinary drug residue analysis was performed as below. Accordingly, (i) more polar solvent (Acetonitrile) was used in the sample preparation step and (ii) dispersive solid-phase solution was used instead of the solid phase extraction solution in the solution cleaning step. Furthermore, (iii) different groups were injected together in a single injection to analyze different types of anabolic substances with LC-MS/MS in the multi-component analysis phase. After the validation and determination of measurement uncertainty, 20 commercially available red meat tissues were analyzed, and the findings were compared to the literature. It was concluded that the applied method was found to be fast and reliable in the detection of prohibited anabolic agents in red meat tissue.

Although various platelet-rich plasma (PRP) kits are commercially available, the efficacy of these kits for knee osteoarthritis (KOA) has not been fully investigated. This study aimed to investigate the short-term results of leukocyte-poor PRP (LP-PRP) and the factors that contribute to its efficacy. We retrospectively reviewed 124 patients with KOA who were treated with LP-PRP. White blood cell (WBC) and platelet counts in the whole blood and the LP-PRP were measured. KOA severity was assessed using radiography. Clinical evaluation was performed both prior to injection and after an average of 3.3 weeks after the injection using the Japanese Knee Osteoarthritis Measure (JKOM). Responders were defined based on the JKOM. The contributing factors for responders were examined using a multivariate logistic analysis. The responder rate was 58.1% and the contributing factors for responders were a higher visual analog scale score before injection, WBC count in whole blood, and platelet concentration ratio of LP-PRP. The LP-PRP improved the clinical scores in the short term. Certain patient characteristics before injection and the concentration ratio of LP-PRP may be predictors of its efficacy, these may provide clues for elucidating which components of LP-PRP act on KOA pathologies.

Background Strabismus is one of the common health problems among the children. The incidence of the oculocardiac reflex decreases with age and tends to be more pronounced in young, healthy patients, which is clinically significant for pediatric as it is observed with greatest incidence in young healthy neonates and infants undergoing strabismus surgery. Objective to prevent and attenuate the oculocardiac reflex in children age group from (2yrs to 14 yrs) undergoing surgical correction for strabismus. Patients and Methods Three groups were allocated Group C received general anaesthesia combined with pre emptive atropine, Group L received general anaesthesia combined with Peribulbar block with Lidocaine 2 % and Group LB which received general anaesthesia combined with peribulbar block with Levobupivacaine 0.5%. Results In Our study we found that group L which received peribulbar lidocaine 2 % was the most successful group regarding blocking the occurrence of the OCR and with acceptable post operative pain control results. Conclusion In Our study the use of peribulbar block with lidocaine 2 % in combinations with General anaesthesia is very effective against the incidence of OCR in children undergoing strabismus surgery and superior to the Iv pre emptive Atropine with higher surgeon satisfaction while the use of peribulbar levobupivacaine 0.5% combined with general anaesthesia has a great role in post operative pain control with superior patient satisfaction, on the other hand the atropine is a very important emergency drug but our study found that it has a very minor role in both preventing the OCR and post operative pain control in addition to subjecting the patients to the tachycardia and other complications like dryness of the mouth and blushing so its not recommended by our study.

Rapid emergence of SARS-CoV-2 variants is a constant threat and a major hurdle to reach heard immunity. We produced VBI-2905a, an enveloped virus-like particle (eVLP)-based vaccine candidate expressing prefusion spike protein from the Beta variant that contains several escape mutations. VBI-2905a protected hamsters against infection with a Beta variant virus and induced high levels of neutralizing antibodies against Beta RBD. In a heterologous vaccination regimen, a single injection of VBI-2905a in animals previously immunized with VBI-2902, a vaccine candidate expressing S from ancestral SARS-CoV-2, hamsters were equally protected against Beta variant infection. As an alternate strategy to broaden immunity, we produced a trivalent vaccine expressing the prefusion spike protein from SARS-CoV-2 together with unmodifed S from SARS-CoV-1 and MERS-CoV. Relative to immunity induced against the ancestral strain, the trivalent vaccine VBI-2901a induced higher and more consistent antibody binding and neutralizing responses against a panel of variants including Beta, Delta, Kappa, and Lambda, with evidence for broadening of immunity rather than just boosting cross-reactive antibodies.

Background and Objective. The aim of this study was to compare the effect of autologous bone marrow-derived chondrocytes (ABMDCs) with pharmacological management of osteoarthritis of knee (OAK) and assess the benefit of the two in the improvement of pain relief, functional betterment, and quality of life (QOL). Patients and Methods. A prospective, randomized study was undertaken in patients with OAK grades II and III of Kellgren–Lawrence grading (KLG) in two groups. Group I had 5 million of intra-articular ABMDC in the affected joint, and Group II continued the nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy as needed. Before the treatment, patients were meticulously examined and data were entered for age, sex, Body Mass Index (BMI), Visual Analogue Scale (VAS), Modified Knee Society Score-Short Form (MKSSSF), and QOL. Patients were followed up for 3, 12, and 24 months to assess efficacy, safety, and tolerability. To assess the cartilage regeneration of the damaged cartilage, magnetic resonance imaging (MRI) was used. Results. There were a total of 60 patients who were followed up. Three patients in Group II were removed from the analysis as they underwent total knee arthroplasty (TKA). A notably significant improvement was noticed in the ABMDC group on all scores of VAS and MKSSSF with P < 0.0001 . The control group continued to be dissatisfied with the treatment they were taking. Conclusions. This study reveals that a single injection of 5 million of ABMDC was efficient in reducing the symptoms, improving the functional score and betterment of QOL.

Simple Summary In humans, the aim of the transversus thoracis plane block is to desensitise the intercostal nerves running through this plane, providing analgesia to the anterior chest wall. Our objective was twofold: describing an ultrasound-guided transverse approach to the transversus thoracis plane and evaluating the spread of two injectable volumes in canine cadavers. Gross anatomy of the ventral thoracic area and sonoanatomy between the fifth and sixth costal cartilages were described in two dog cadavers. Eight cadavers were used to describe this approach and were subsequently dissected to evaluate the injectate spread and the intercostal nerves staining after low volume (0.5 mL kg−1) and high volume (1 mL kg−1) dye-lidocaine injection. After all injections, the injectable solution was distributed along the transversus thoracis plane, staining a median number (range) of 3 (2–4) and 4 (3–5) nerves with low and high volume, respectively (p = 0.014). The transverse approach to the transversus thoracis plane is a feasible, single injection point technique that provides the staining of several intercostal nerves. The injection of high versus low volume increases the number of stained nerves. Abstract Transversus thoracis plane (TTP) block has demonstrated to produce analgesia in humans undergoing median sternotomy. The objectives of the study were to describe an ultrasound-guided transverse approach to the transversus thoracis plane (t-TTP) and to evaluate the spread of two injectable volumes in canine cadavers. Two cadavers were used to describe relevant gross anatomy of the ventral thoracic area and sonoanatomy between the fifth and sixth costal cartilages. Then, eight cadavers were used to describe the ultrasound-guided injection into the TTP and were dissected to evaluate the injectate spread and the intercostal nerves staining with two different dye-lidocaine volumes: low volume (LV) 0.5 mL kg−1 and high volume (HV) 1 mL kg−1. To compare the spread between both volumes the Fisher’s exact test and Wilcoxon signed-rank test were used. The solution spread along the TTP after all injections, staining a median number (range) of 3 (2–4) and 4 (3–5) nerves with LV and HV, respectively (p = 0.014). The injection of HV versus LV increases the number of stained nerves. Ultrasound-guided t-TTP is a feasible technique that provides staining of several intercostal nerves with a single injection site, so it could be useful to provide analgesia to the ventral chest wall.

In 1991, the U.S. Food & Drug Administration (FDA) approved rmetHuG-CSF for human use. This recombinant methionyl human granulocyte colony-stimulating factor, or filgrastim, saw use in over 1 million patients in its first 5 years on the market. In 2002, the FDA approved a version of filgrastim with covalent linkage to a monomethoxypolyethylene glycol, increasing the molecular size and half-life to replace multiple days of dosing with a single injection. These medications remained standard of care for neutropenia until the Biologics Price Competition and Innovation Act of 2009 created an abbreviated pathway to licensure for biologic products. Practitioners now have their pick of numerous and expanding options for pegfilgrastim biosimilars.

Alzheimer’s disease (AD) is the most common form of dementia. AD has a physical, emotional, and economic impact on the patients and their families and society at large. More than a decade since its discovery, there is still no available treatment. Δ9-tetrahydrocannabinol (THC) is emerging as a promising therapeutic agent. Using THC in conventional-high doses may have deleterious effects. Therefore, we propose to use an ultra-low dose of THC (ULD-THC). We previously published that a single injection of ULD-THC elevated Sirtuin-1 (Sirt-1) levels in the brain and ameliorated cognitive functioning in several models of brain injuries as well as in naturally aging mice. Our working hypothesis suggests that ULD-THC can prevent and even reverse AD pathology. In this preliminary study, we saw that a single injection of ULD-THC alleviated cognitive impairments of a mice model for AD, 5xFAD mice. Our work may establish the foundations for the development of a pharmaceutical preparation for the treatment of AD patients, thus, bringing the ULD-THC treatment closer to clinical application.

As microbiologists and public health officials scramble for weapons to combat antibiotic resistance, they may end up including an unlikely ally in their arsenal: other bacteria. The prime candidate right now is a predatory bacterium known as Bdellovibrio bacteriovorus . Researchers have started to evaluate predatory bacteria such as Bdellovibrio —shown here in a false-color transmission electron microscopy image at 50,000× magnification—as a means of treating intractable, antibiotic-resistant infections. Image credit: Science Source/ALFRED PASIEKA. Found in soils and water globally, B. bacteriovorus are free-living, harmless bacteria—harmless to humans, at least. In the microbial world, they’re voracious predators of gram-negative bacteria, a group that includes Salmonella , Escherichia coli , and several other pathogens. Bdellovibrio punch a hole in the membranes of their prey, enter and consume their contents, then burst out again to find their next meal. “They’re a very efficient killing machine,” says Daniel Kadouri, an associate professor at the Rutgers School of Dental Medicine in Newark, NJ. “They act kind of like the creature in the movie Alien .” Researchers are now beginning to evaluate Bdellovibrio and other similar predatory bacteria as a route to treating intractable, antibiotic-resistant infections. They’re starting to learn how these predators work in different organs and against different pathogens. As they examine various infection scenarios, they are also discovering how these microbes work in concert with the native microbiome and immune cells. Pills full of predatory bacteria won’t replace antibiotics at pharmacies anytime soon. But studying these microbes could help prepare for a future when many antibiotics fail to treat multi-drug-resistant infections. “Right now, the idea that a single injection of live bacteria could be used as therapy seems quite extreme to people,” says microbiologist Elizabeth Sockett of the University of Nottingham in the United Kingdom. “But as we run out of other …

Background and purpose — Targeted delivery of drugs is important to achieve efficient local concentrations and reduce systemic side effects. We hypothesized that locally implanted synthetic hydroxyapatite (HA) particles can act as a recruiting moiety for systemically administered drugs, leading to targeted drug accretion. Methods — Synthetic HA particles were implanted ectopically in a muscle pouch in rats, and the binding of systemically circulating drugs such as zoledronic acid (ZA), tetracycline and 18F-fluoride (18F) was studied. The local biological effect was verified in an implant integration model in rats, wherein a hollow implant was filled with synthetic HA particles and the animals were given systemic ZA, 2-weeks post-implantation. The effect of HA particle size on drug binding and the possibility of reloading HA particles were also evaluated in the muscle pouch. Results — The systemically administered biomolecules (ZA, tetracycline and 18F) all sought the HA moiety placed in the muscle pouch. Statistically significant higher peri-implant bone volume and peak force were observed in the implant containing HA particles compared with the empty implant. After a single injection of ZA at 2 weeks, micro HA particles showed a tendency to accumulate more 14C-zoledronic acid (14C-ZA) than nano-HA particles in the muscle pouch. HA particles could be reloaded when ZA was given again at 4 weeks, showing increased 14C-ZA accretion by 73% in microparticles and 77% in nanoparticles. Interpretation — We describe a novel method of systemic drug loading resulting in targeted accretion in locally implanted particulate HA, thereby biologically activating the material.

Purpose: To evaluate effect of PRGF intra articular injection in patients with internal derangement of TMJ using CT guided versus conventional puncture technique. Materials and methods: Twenty patients with internal derangement without improvement by conservative treatment were divided into two groups: Group I: ten patients underwent arthrocentesis followed by PRGF injection using conventional puncture by anatomical landmarks. Group II: ten patients underwent arthrocentesis followed by PRGF injection using landmark and confirmed by CT. All patients were assessed preoperatively and postoperatively at 1week, 3 and 6 months for pain level, maximum interincisal opening, lateral, protrusive movements, joint tenderness and disk position with MRI after 6 months. Results: In both groups, all clinical variables showed statistical significant discrepancy postoperatively, the discrepancy between both groups was not statistically significant and MRI showed no statistical significant change in disc position. Conclusion: CT confirmed accurate position and depth within TMJ upper compartment in different views, allowed correction with less puncture trials and decreased learning curve of TMJ puncture but it is expensive, time consuming and not available in clinics. Anatomical landmarks is easy and representable method for TMJ puncture but blind technique and needs skill. Single injection of PRGF found efficient in the treatment of internal derangement of TMJ.