UNASSIGNED: To compare the efficacy and safety of intravenous and intramuscular oxytocin in preventing atonic primary postpartum haemorrhage in the third stage of labour.
UNASSIGNED: A double-blind randomised clinical study on consenting women without risk factors for primary postpartum haemorrhage in labour at term. Two hundred and thirty-two women were randomly allotted into intravenous (n = 115) and intramuscular (n = 117) oxytocin groups in the active management of the third stage of labour. All participants received 10 IU of oxytocin, either IV or IM, and 1 ml of water for injection as a placebo via a route alternate to that of administration of oxytocin within 1 min of the baby\'s delivery. The primary outcome measures were mean postpartum blood loss and haematocrit change. Trial Registration No.: PACTR201902721929705.
UNASSIGNED: The baseline socio-demographic and clinical characteristics were similar between the two groups (p > 0.05). There was no statistically significant difference between the two groups with regards to the mean postpartum blood loss (254.17 ± 34.85 ml versus 249.4 ± 39.88 ml; p = 0.210), haematocrit change (2.4 (0.8%) versus 2.1 (0.6%); p = 0.412) or adverse effects (p > 0.05). However, the use of additional uterotonics was significantly higher in the intravenous group (25 (21.73%) versus 17 (14.53%); p = 0.032).
UNASSIGNED: Although oxytocin in both study groups showed similar efficacy in terms of preventing atonic primary postpartum haemorrhage, participants who received intravenous oxytocin were more likely to require additional uterotonics to reduce their likelihood of having an atonic primary postpartum haemorrhage. However, both routes have similar side effect profiles.

BACKGROUND: Epinephrine (adrenaline) is currently the only cardiac agent recommended during neonatal resuscitation. The inability to predict which newborns are at risk of requiring resuscitative efforts at birth has prevented the collection of large, high-quality human data.
CONCLUSIONS: Information on the optimal dosage and route of epinephrine administration is extrapolated from neonatal animal studies and human adult and pediatric studies. Adult resuscitation guidelines have previously recommended vasopressin use; however, neonatal studies needed to create guidelines are lacking. A review of the literature demonstrates conflicting results regarding epinephrine efficacy through various routes of access as well as vasopressin during asystolic cardiac arrest in animal models. Vasopressin appears to improve hemodynamic and post-resuscitation outcomes compared to epinephrine in asystolic cardiac arrest animal models.
CONCLUSIONS: The current neonatal resuscitation guidelines recommend epinephrine be primarily given via the intravenous or intraosseous route, with the endotracheal route as an alternative if these routes are not feasible or unsuccessful. The intravenous or intraosseous dose ranges between 0.01 and 0.03 mg/kg, which should be repeated every 3-5 min during chest compressions. However, the optimal dosing and route of administration of epinephrine remain unknown. There is evidence from adult and pediatric studies that vasopressin might be an alternative to epinephrine; however, the neonatal data are scarce.

Cats are often easily stressed and uncooperative. The use of sedative agents in the feline species is widely used to perform even minor clinical and diagnostic procedures. The aim of this study is to assess the impact on tear film production of the intrarectal route (IR) administration of a mixture of dexmedetomidine, ketamine and midazolam in comparison with the intramuscular (IM) one. A group of twenty cats were involved in a randomized and blinded clinical trial. A clinical and ophthalmological examination was conducted on the cats. The IR group received dexmedetomidine 0.003 mg kg-1, ketamine 4 mg kg-1 and midazolam 0.4 mg kg-1; the IM group received dexmedetomidine 0.003 mg kg-1, ketamine 2 mg kg-1 and midazolam 0.2 mg kg-1. A Shirmer tear test I (STT- I) was conducted 1 h before sedation and 2\', 10\', 20\', 30\', 40\', and 80\' post drug administration. The reaction to STT-I administration was also evaluated. The IM group has a lower mean tear production than the IR group for all time points evaluated. Cats in the IM group showed less reaction to STT-I administration. This study may suggest that the effect of sedative agents administered by the IR route has a lower incidence on tear production than the IM one. The use of eye lubricant is recommended in any case.

Mesenchymal stromal cell (MSC) therapy for diabetic neuropathy (DN) has been extensively researched in vitro and in pre-clinical studies; however, the clinical scenario thus far has been disappointing. Temporary recovery, a common feature of these studies, indicates that either the retention of transplanted cells deteriorates with time or recovery of supportive endogenous cells, such as bone marrow-derived MSCs (BM-MSCs), does not occur, requiring further replenishment. In DN, BM-MSCs are recognized mediators of Schwann cell regeneration, and we have earlier shown that they suffer impairment in the pre-neuropathy stage. In this study, we attempted to further elucidate the mechanisms of functional recovery by focusing on changes occurring at the cellular level in the sciatic nerve, in conjunction with the biodistribution and movement patterns of the transplanted cells, to define the interval between doses.
We found that two doses of 1 × 106 dental pulp stromal cells (DPSCs) transplanted intramuscularly at an interval of 4 weeks effectively improved nerve conduction velocity (NCV) and restored motor coordination through improving sciatic nerve architecture, Schwann cell survival and myelination. Despite very minimal recovery of endogenous BM-MSCs, a temporary restoration of NCV and motor function was achieved with the first dose of DPSC transplantation. However, this did not persist, and a repeat dose was needed to consolidate functional improvement and rehabilitate the sciatic nerve architecture.
Thus, repeat intramuscular transplantation of DPSCs is more effective for maintenance of Schwann cell survival and myelination for functional recovery after onset of DN.

The aim of this clinical trial was to evaluate the impacts of administration via the intrarectal route (IR) in cats on their heart and respiratory rates, blood pressure, body temperature, and sedation quality compared to the intramuscular route (IM). The intramuscular group (IMG) received 0.003 mg kg−1 dexmedetomidine, 2 mg kg−1 ketamine, and 0.2 mg kg−1 midazolam while the intrarectal group (IRG) protocol was 0.003 mg kg−1 dexmedetomidine, 4 mg kg−1 ketamine, and 0.4 mg kg−1 midazolam. Cardiorespiratory values, temperature, and sedation score were measured 2 min after administration and then every 5 min up to the 40th minute. Cats belonging to IRG reacted less strongly to the drug, as opposed to those receiving intramuscular administration (2/10 in IRG vs. 8/10 in IMG). Average time between drug administration and standing position was 44.9 ± 5.79 in IRG and 57 ± 9.88 min in IMG. In IRG, maintenance of SpO₂ values is >95% at each time point. Median and range peak of sedation {7 (5)} in IMG occurs at 20th, 25th, and 30th minutes post drug administration while was lower in IRG. Cardiorespiratory values were slightly lower in IMG than in IRG, but always constant in both treatments. Temperature did not differ between groups. At this dosage, although sedation score was higher in IMG, intrarectal route could be efficacious for performing minimally invasive clinical and diagnostic procedures in cats.

Despite the intramuscular route being the most used vaccination strategy against SARS-CoV-2, the intradermal route has been studied around the globe as a strong candidate for immunization against SARS-CoV-2. Adjuvants have shown to be essential vaccine components that are capable of driving robust immune responses and increasing the vaccination efficacy. In this work, our group aimed to develop a vaccination strategy for SARS-CoV-2 using a trimeric spike protein, by testing the best route with formulations containing the adjuvants AddaS03, CpG, MPL, Alum, or a combination of two of them. Our results showed that formulations that were made with AddaS03 or CpG alone or AddaS03 combined with CpG were able to induce high levels of IgG, IgG1, and IgG2a; high titers of neutralizing antibodies against SARS-CoV-2 original strain; and also induced high hypersensitivity during the challenge with Spike protein and a high level of IFN-γ producing CD4+ T-cells in mice. Altogether, those data indicate that AddaS03, CpG, or both combined may be used as adjuvants in vaccines for COVID-19.

OBJECTIVE: To compare the efficacy of dexamethasone when administered preoperatively through sublingual and intramuscular routes for evaluating the reduction in pain, swelling, and trismus after removal of impacted mandibular third molar.
METHODS: The study was conducted on patients who required surgical removal of impacted mandibular third molars under local anesthesia. A total of 150 patients were considered for the study who were divided into two groups of 75 patients each. Patients in the sublingual group were administered with 2 ml of dexamethasone 8 mg along with 2 ml of normal saline through sublingual route and patients in the intramuscular group were administered with 2 ml of dexamethasone 8 mg through intramuscular route 1 h before the commencement of mandibular third molar surgery. The subjects of all two groups were evaluated for pain, swelling, and trismus on 1st, 3rd, and 7th postoperative days.
RESULTS: Patients in the sublingual group had significantly less pain and increased mouth opening on 1st, 3rd, and 7th postoperative days when compared to patients in the intramuscular group (P < 0.05), while the amount of swelling in the sublingual group was significantly less only on the 3rd and 7th postoperative days when compared to patients in the intramuscular group (P < 0.05). Four patients in the sublingual group consumed one dose of paracetamol 500 mg as a rescue drug on the day of surgery. In the intramuscular group, 9 patients consumed one dose of the same rescue drug on the day of surgery and 11 patients consumed one dose of rescue drug both on the day of surgery and on the 1st postoperative day.
CONCLUSIONS: This study concludes that preoperative administration of dexamethasone 8 mg through sublingual route had better efficacy than intramuscular route in controlling pain, swelling and trismus after mandibular third molar surgery.

Our previous work has demonstrated the benefits of transcutaneous immunization in targeting Langerhans cells and preferentially inducing CD8 T-cell responses.
In this randomized phase Ib clinical trial including 20 HIV uninfected volunteers, we compared the safety and immunogenicity of the MVA recombinant vaccine expressing HIV-B antigen (MVA-B) by transcutaneous and intramuscular routes. We hypothesized that the quality of innate and adaptive immunity differs according to the route of immunization and explored the quality of the vector vaccine-induced immune responses. We also investigated the early blood transcriptome and serum cytokine levels to identify innate events correlated with the strength and quality of adaptive immunity.
We demonstrate that MVA-B vaccine is safe by both routes, but that the quality and intensity of both innate and adaptive immunity differ significantly. Transcutaneous vaccination promoted CD8 responses in the absence of antibodies and slightly affected gene expression, involving mainly genes associated with metabolic pathways. Intramuscular vaccination, on the other hand, drove robust changes in the expression of genes involved in IL-6 and interferon signalling pathways, mainly those associated with humoral responses, and also some levels of CD8 response.
Thus, vaccine delivery route perturbs early innate responses that shape the quality of adaptive immunity.
http://ClinicalTrials.gov, identifier PER-073-13.

BACKGROUND: Hepatitis B infection is one of the most common infections worldwide, with its vaccination being an effective preventive measure. Nonresponse to hepatitis B vaccination increases population susceptibility to virus dissemination along with detrimental complications. Despite twice intramuscular vaccination series, 14.3% in the general population and 50% in hemodialysis patients fail to mount a response against hepatitis B. We aimed to evaluate the effectiveness of intradermal (ID) vaccination in the nonresponders amongst the general and hemodialysis population.
METHODS: A total of 5 doses of 10 μg of hepatitis B vaccine was given intradermally, 2 weeks apart, to both the study groups: patients who were on hemodialysis and the general population group who previously had failed to achieve satisfactory antibody titers with the IM administration of the vaccine. A hepatitis B surface antibody (HBsAb) titer of ≥10 IU/mL and ≥100 IU/mL were considered \"responder\" and \"good responder,\" respectively.
RESULTS: Out of a total of 95 participants, 49 (51.6%) were hemodialysis-dependent. Most of the participants were females 49 (51.6%). The mean age of all the participants was 39.02 ± 13.5 years (range: 18-70 years). Overall, 75.8% of the participants responded to the ID vaccination with a mean HBsAb titer of 263.5 ± 350.1 IU/L. Almost similar vaccination response was observed in both the hemodialysis and general population i.e., 75.5% and 76.1%, respectively (P = 1.00). In the hemodialysis group, the absence of hypertension (P = 0.04) and age ≥36 years (P = 0.016) were associated with an ID vaccination response.
CONCLUSIONS: For those not responding to the conventional IM route of the hepatitis B vaccine, the ID route is an effective way of immunization in this group and this approach would lead to a decrease in infection rates in the vulnerable population such as those on hemodialysis.

BACKGROUND: In recent times, studies have demonstrated that carbon nanotubes are good candidates for use as vehicles for transfection of exogenous material into the cells. However, there are few studies evaluating the behavior of carbon nanotubes as DNA vectors and few of these studies have used multi-walled carbon nanotubes (MWCNTs) or carboxylated MWCNTs. Thus, this study aims to assess the MWCNTs\' (carboxylated or not) efficiency in the increase in expression of the tetravalent vaccine candidate (TVC) plasmid vector for dengue virus in vitro using Vero cells, and in vivo, through the intramuscular route, to evaluate the immunological response profile.
RESULTS: Multi-walled carbon nanotubes internalized by Vero cells, have been found in the cytoplasm and nucleus associated with the plasmid. However, it was not efficient to increase the messenger ribonucleic acid (mRNA) compared to the pure vaccine candidate associated with Lipofectamine(®) 2000. The in vivo experiments showed that the use of intramuscular injection of the TVC in combination with MWCNTs reduced the immune response compared to pure TVC, in a general way, although an increase was observed in the population of the antibody-producing B cells, as compared to pure TVC.
CONCLUSIONS: The results confirm the data found by other authors, which demonstrate the ability of nanotubes to penetrate target cells and reach both the cytoplasm and the cell nucleus. The cytotoxicity values are also in accordance with the literature, which range from 5 to 20 µg/mL. This has been found to be 10 µg/mL in this study. Although the expression levels are higher in cells that receive the pure TVC transfected using Lipofectamine(®) 2000, the nanotubes show an increase in B-cells producing antibodies.