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To develop an ultrasound-guided approach to intercostal nerve injection and to compare the success rate of intercostal nerve injections using blind or ultrasound-guided technique in canine cadavers. Prospective, randomized, descriptive, experimental anatomic study. A total of 14 mid-sized adult canine cadavers. Ultrasound landmarks were identified by dissection of four cadavers and used to develop an ultrasound-guided technique. The remaining 10 cadavers were randomly assigned to blind (five cadavers) or ultrasound-guided (five cadavers) injections of the third to the ninth intercostal nerves bilaterally with 0.03 mL kg–1 of colorant per injection. The target for intercostal injections was the caudal border of the respective rib, between the internal intercostal membrane and the parietal pleura. Additionally, displacement of the parietal pleura without visible intramuscular distribution was considered the end point for ultrasound-guided injections. For each cadaver, a practitioner in training performed the blocks on one hemithorax, while an experienced practitioner performed the blocks on the opposite hemithorax. Injections were considered successful if ≥1 cm of the target nerve was stained with colorant upon dissection. Success rates and length of nerve staining were analyzed with Fisher's exact and t tests, respectively. Data were considered statistically different with p < 0.05. Success rates of blind and ultrasound-guided technique were 57.1% and 91.4%, respectively (p < 0.0001). The length of intercostal nerve staining was 3.1 ± 1.2 cm and 3.6 ± 1.0 cm using blind and ultrasound-guided techniques, respectively (p = 0.02). No differences were observed between the two practitioners for blind (p = 0.33) and ultrasound-guided techniques (p = 0.67). Ultrasound guidance improves the accuracy of intercostal nerve injections when compared with blind technique, independently of the level of expertise in regional anesthesia. [ABSTRACT FROM AUTHOR]

To investigate the distribution and nerve staining of two volumes of lidocaine–dye solution after ultrasound-guided erector spinae plane (ESP) injections in canine cadavers. Experimental cadaveric study. A total of nine canine cadavers. ESP injections were performed between the longissimus thoracis muscle and the dorsolateral edge of the ninth thoracic transverse process. Two cadavers were transversally cryosectioned after unilateral ESP injections [0.6 mL kg–1; high volume (HV)]. In seven cadavers, bilateral ESP injections with HV or low volume (0.3 mL kg–1; LV) were performed. Gadodiamide was added to the injectate for two cadavers and magnetic resonance imaging (MRI) was performed pre- and post-injection. Injectate distribution and nerve staining of the branches of the spinal nerves were recorded after gross anatomical dissection. The thoracic paravertebral and epidural spaces were examined for dye solution. Cryosections, MRI and gross dissections showed that the injectate spread dorsally to the transverse processes, over the ventromedial aspect of the longissimus thoracis muscle where the medial and lateral branches of the dorsal branches of the spinal nerves are located. LV and HV stained a median (range) of 4 (2–7) and 4 (3–8) medial branches, respectively (p = 0.52). LV and HV stained 4 (2–5) and 5 (4–7) lateral branches (p = 0.26), respectively. Ventral branches were not stained, and dye was not identified in the epidural or paravertebral spaces. and clinical relevance Medial and lateral branches were consistently stained over several spinal segments. The number of nerves stained was not different with HV or LV, and the ventral branches of the spinal nerves were not stained in any cadaver. ESP block may find a clinical application to desensitize structures innervated by the medial and lateral branches of the dorsal branches of the thoracic spinal nerves. [ABSTRACT FROM AUTHOR]

To describe the gross and ultrasound anatomy of the parasacral region and an ultrasound-guided greater ischiatic notch (GIN) plane approach aimed at staining the lumbosacral trunk (LST) in canine cadavers. To evaluate if the ultrasound-guided GIN plane approach is non-inferior to the previously described ultrasound-guided parasacral approach at staining the LST. Prospective, randomized, non-inferiority experimental anatomic study. A total of 17 (23.9 ± 5.2 kg) mesocephalic canine cadavers. Anatomic and echographic landmarks, and the feasibility of performing a GIN plane technique were evaluated using two canine cadavers. The remaining 15 cadavers had each hemipelvis randomly assigned to be administered either parasacral or GIN plane injection of 0.15 mL kg–1 dye solution. The parasacral region was dissected after injections to assess the staining of LST, cranial gluteal nerve, pararectal fossa and pelvic cavity. The stained LST were removed and processed for histological evaluation of intraneural injections. A one-sided z-test for non-inferiority (non-inferiority margin –14%) was used to statistically evaluate the success of the GIN plane versus the parasacral approach. Data were considered statistically significant when p < 0.05. The GIN plane and parasacral approach stained the LST in 100% and 93.3% of the injections, respectively. The success rate difference between treatments was 6.7% [95% confidence interval, –0.6 to 19.0%; p < 0.001 for non-inferiority]. The GIN plane and parasacral injections stained the LST for 32.7 ± 16.8 mm and 43.1 ± 24.3 mm, respectively (p = 0.18). No evidence of intraneural injection was found. The ultrasound-guided GIN plane technique resulted in nerve staining that was non-inferior to the parasacral technique and may be considered an alternative to the parasacral approach to block the LST in dogs. [ABSTRACT FROM AUTHOR]

To evaluate the impact of a 30% end-inspiratory pause (EIP) on alveolar tidal volume (V Talv), airway (V Daw) and physiological (V Dphys) dead spaces in mechanically ventilated horses using volumetric capnography, and to evaluate the effect of EIP on carbon dioxide (CO 2) elimination per breath (Vco 2 br–1), PaCO 2, and the ratio of PaO 2 -to-fractional inspired oxygen (PaO 2 :F i O 2). Prospective research study. A group of eight healthy research horses undergoing laparotomy. Anesthetized horses were mechanically ventilated as follows: 6 breaths minute–1, tidal volume (V T) 13 mL kg–1, inspiratory-to-expiratory time ratio 1:2, positive end-expiratory pressure 5 cmH 2 O and EIP 0%. Vco 2 br–1 and expired tidal volume (V TE) of 10 consecutive breaths were recorded 30 minutes after induction, after adding 30% EIP and upon EIP removal to construct volumetric capnograms. A stabilization period of 15 minutes was allowed between phases. Data were analyzed using a mixed-effect linear model. Significance was set at p < 0.05. The EIP decreased V Daw from 6.6 (6.1–6.7) to 5.5 (5.3–6.1) mL kg–1 (p < 0.001) and increased V Talv from 7.7 ± 0.7 to 8.6 ± 0.6 mL kg–1 (p = 0.002) without changing the V TE. The V Dphys to V TE ratio decreased from 51.0% to 45.5% (p < 0.001) with EIP. The EIP also increased PaO 2 :F i O 2 from 393.3 ± 160.7 to 450.5 ± 182.5 mmHg (52.5 ± 21.4 to 60.0 ± 24.3 kPa; p < 0.001) and Vco 2 br–1 from 0.49 (0.45–0.50) to 0.59 (0.45–0.61) mL kg–1 (p = 0.008) without reducing PaCO 2. The EIP improved oxygenation and reduced V Daw and V Dphys , without reductions in PaCO 2. Future studies should evaluate the impact of different EIP in healthy and pathological equine populations under anesthesia. [ABSTRACT FROM AUTHOR]

Objective To determine if neuromuscular monitoring at the pelvic limb accurately reflects neuromuscular function in the larynx after administration of rocuronium in anesthetized dogs. Study design Prospective experimental study. Animals Six healthy Beagle dogs. Methods Anesthesia was maintained in dogs with isoflurane and a continuous infusion of dexmedetomidine. Rocuronium (0.6 mg kg-1) was administered intravenously to induce neuromuscular block. Train-of-four (TOF) impulses were applied to the left recurrent laryngeal nerve (RLn) and the peroneal nerve (Pn). The evoked TOF ratio (TOFR; T4:T1) was measured with electromyography (EMG) simultaneously at the larynx and at the pelvic limb. Spontaneous recoveries of T1 to 25% (T125%) and 75% (T175%) of twitch height, and to TOFR of 0.70 and 0.90 (TOFR0.90) at each EMG site were compared. Results Data from five dogs were analyzed. Times to T125% were similar at the pelvic limb and larynx when measured by EMG; time to T175% was slower at the larynx by 6 ± 4 minutes (p = 0.012). The larynx had a slower recovery to TOFR0.70 (41 ± 13 minutes) and TOFR0.90 (45 ± 13 minutes) than did the pelvic limb [29 ± 8 minutes (p = 0.011) and 33 ± 9 minutes (p = 0.003), respectively]. When the pelvic limb EMG returned to TOFR0.70 and TOFR0.90, the larynx EMG TOFR0.70 and TOFR0.90 values were 0.32 ± 0.12 (p = 0.001) and 0.38 ± 0.13 (p = 0.001), respectively. Conclusions and clinical relevance After administration of rocuronium, neuromuscular function assessed by EMG recovered approximately 36% slower at the larynx than at the pelvic limb. The results in these dogs suggest that quantitative neuromuscular monitoring instrumented at a pelvic limb may be unable to exclude residual block at the larynx in anesthetized dogs. [ABSTRACT FROM AUTHOR]

Background: The morbidity and mortality of extraparenchymal neurocysticercosis (EP-NC) remain high and effectiveness of current medical treatment is suboptimal. Various factors have been implicated in the severity of EP-NC and in the poor response to treatment, but the possible role of host immune and endocrine systems has not yet been examined thoroughly. Methodology/Principal findings: 42 participants with EP-NC before receiving standard treatment and 25 healthy controls were included in the study. Treatment response was assessed by comparing pre/post treatment parasite volumes from 3D MRI. Prior to treatment among participants with EP-NC, specific stimulation induced an increased specific proliferative response accompanied by a significant increase in IL-4, NK, NKT, Bregs and Tregs cells, whereas in healthy controls, specific stimulation induced a significant increase in IL-1β, IL-5, CCL5, IL-6, TNF-α, NK and Bregs cells. Significant differences between participants with EP-NC and healthy controls in the specific inflammatory response were observed. Participants with EP-NC prior to treatment had significantly weaker responses of proinflammatory cytokines (IL-6, TNF-α) and NK cells, and stronger IL-4 response. Anthelmintic treatment did not promote significant peripheral immunological changes at any time, although inflammation was sustained in the cerebrospinal fluid. Serum estradiol concentration significantly decreased after anthelmintic treatment among males, and cortisol correlated negatively with IL-6 and positively with IFN-γ levels. No pre-treatment immunologic or endocrinologic parameters were significantly associated with response to treatment. Conclusion/Significance: Prior to anthelmintic treatment, EP-NC was characterized by low lymphocyte reactivity accompanied by a regulatory response, which may be involved in the lack of peripheral immunological changes during and after treatment, although a central inflammatory response was present. This weak specific peripheral response could favor the chronicity of the infection and the poor response to treatment. Our findings highlight the need for new anti-inflammatory treatment focused on the central nervous system with less systemic immunosuppressive effects. Author summary: Neurocysticercosis is a central nervous system infection with the helminth Taenia solium in its larval stage. It is a marker of poverty and remains endemic in countries of Latin America, Africa, and Asia. The severity of neurocysticercosis and the prognosis of patients depend on the location of the parasites. Extraparenchymal infection involving the subarachnoid and/or ventricular space is associated with high morbidity and mortality and a suboptimal response to current anthelminthic treatment regimens. We examined peripheral immunological parameters and hormones of 42 participants with extraparenchymal neurocysticercosis before and after treatment, and their associations with subsequent treatment response. Prior to treatment, compared with healthy controls, there was low lymphocyte reactivity with a regulatory response, which may explain the lack of peripheral immunological changes during and after treatment. This weak specific peripheral response could favor the chronicity of the infection and the poor response to treatment and should be considered in research to improve patient outcomes. [ABSTRACT FROM AUTHOR]

To describe an ultrasound-guided lateral pre-iliac (LPI) and parasacral (PS) approach in feline cadavers (phase I) and compare the perioperative analgesic use and complications in cats administered LPI and PS blocks (group PNB) or epidural anesthesia (group EPI) for pelvic limb surgery (phase II). Experimental uncontrolled, anatomic and retrospective cohort study. A group of eight feline cadavers and 52 medical records. Bilateral LPI and PS approaches with 0.1 mL kg–1 of dye to stain the femoral and obturator nerves and the lumbosacral trunk, respectively, were performed on each cadaver. Nerve staining effect was evaluated upon dissections (phase I). Perioperative analgesics use, and complication rates were retrospectively compared between groups PNB and EPI (phase II). Continuous data were compared using the Mann–Whitney U test and the prevalence of events with Fisher's exact test. Differences were considered significant when p < 0.05. Dissections revealed that the LPI approach stained 94% and 75% of the femoral and obturator nerves, respectively. The PS approach stained 100% of the lumbosacral trunks. Cats enrolled in group PNB (n = 23) were administered lower doses of intraoperative opioids than those in group EPI (n = 25) (p = 0.006). Intraoperative rescue analgesia was required in 60% and 17.4% of cats enrolled in groups EPI and PNB, respectively (p = 0.003). Group PNB required more intraoperative anticholinergics than group EPI (p = 0.02). There were no differences in postoperative pain scores, analgesic use and complication rates. The ultrasound-guided LPI and PS approach stained the femoral/obturator nerves and the lumbosacral trunk, respectively, in feline cadavers. Furthermore, PNB was associated with lower intraoperative opioid use and similar postoperative pain and analgesic use compared with epidural anesthesia in a cohort of cats undergoing surgery of the pelvic limb. [ABSTRACT FROM AUTHOR]

To develop and assess the efficacy of an ultrasound (US)-guided pericapsular hip desensitization (PHD) technique in dogs. Prospective, randomized, anatomical study and a case series. A total of 30 healthy dogs, eight canine cadavers and seven dogs with hip osteoarthritis. After studying the US anatomy of the medial aspect of the coxofemoral joint and determining an acoustic window to perform an US-guided PHD in healthy dogs, the US-guided PHD was performed bilaterally in canine cadavers. A low [(LV) 0.1 mL kg–1] and high [(HV) 0.2 mL kg–1] volume of dye was injected per hip on each cadaver. The staining of the pericapsular nerves was assessed by anatomical dissection, and comparison between LV and HV was assessed using Fisher's exact test. Then, the US-guided PHD was performed using a triamcinolone–bupivacaine solution in dogs with hip osteoarthritis. Dynamic pain response was assessed before and after injection. The canine brief pain inventory (CBPI) questionnaire was used to assess treatment efficacy and duration. The US-guided PHD could be performed by inserting the needle between the iliopsoas muscle and the periosteum of the ilium. The articular branches of the femoral and obturator nerves were stained in all cadavers using both volumes. The main femoral nerve was never stained, but the main obturator nerve was stained in 37.5% and 100% of injections using LV and HV, respectively (p = 0.026). Treated animals showed decreased dynamic pain response after the injection. Compared with baseline, CBPI scores were reduced by ≥ 50% for ≥ 12 weeks in all but one dog. The US-guided PHD with both 0.1 and 0.2 mL kg–1 volumes stained the articular branches of the femoral and obturator nerves in canine cadavers and was associated with clinical improvement in dogs with hip osteoarthritis. [ABSTRACT FROM AUTHOR]

To investigate the injectate spread and nerve staining of ultrasound-guided erector spinae plane (ESP) injections at the thoracolumbar spine in canine cadavers. Prospective, randomized, descriptive, anatomic study. A total of 15 canine cadavers. The location of the medial and lateral branches of the dorsal branches of the spinal nerves (DBSN) from the tenth thoracic (T10) to the third lumbar vertebra (L3) were identified by dissection of three cadavers. ESP injections of dye (0.5 mL kg–1) were performed in seven cadavers using as landmarks the T12 transverse process (ESP Tp) on one side and the lateral aspect of the T12 mammillary process (ESP Mp) on the opposite side. Additionally, five cadavers were injected with dye (0.5 mL kg–1) bilaterally on the lateral aspect of the L2 mammillary process (ESP Mp_L2). Nerve staining effect was analyzed after gross anatomic dissections. The number of stained nerves was analyzed using the Mann–Whitney U test. Gross anatomic dissections showed that the medial and lateral branches of the DBSN change their path in relation to the epaxial muscles caudal to T11. Approaches ESP Tp and ESP Mp at T12 stained 2 (0–2) and 3 (2–4) medial (p = 0.01) and 3 (3–4) and 2 (0–2) lateral (p = 0.03) branches, respectively. Injection ESP Mp_L2 stained 3 (2–4) medial and 2 (0–3) lateral branches. Injections ESP Mp and ESP Mp_L2 produced a preferential cranial spread from the injection site. No ventral branches of the spinal nerves were stained with either technique. These results suggest that the mammillary process should be used as anatomic landmark to perform ultrasound-guided ESP blocks in the thoracolumbar spine caudal to T11 when targeting the medial branches of the DBSN. Injections should be performed one spinal segment caudal to the level intended to desensitize. [ABSTRACT FROM AUTHOR]

• Treatment with camostat did not affect the cycle threshold change in the early phase of COVID-19 disease. • Clinical improvement was similar in patients with COVID-19 treated with camostat or a placebo. • Treatment with camostat did not affect the SARS-CoV-2 neutralizing antibody response. • This randomized controlled trial showed the safe use of 300 mg camostat three times daily in patients with COVID-19. • Camostat mesylate is not effective as an antiviral drug for ambulatory patients with COVID-19. This study aimed to assess the efficacy and safety of 300 mg camostat mesylate three times daily in a fasted state to treat early phase COVID-19 in an ambulatory setting. We conducted a phase II randomized controlled trial in symptomatic (maximum 5 days) and asymptomatic patients with confirmed COVID-19 infection. Patients were randomly assigned in a 2:1 ratio to receive either camostat mesylate or a placebo. Outcomes included change in nasopharyngeal viral load, time to clinical improvement, the presence of neutralizing antibodies, and safety. Of 96 participants randomized between November 2020 and June 2021, analyses were performed on the data of 90 participants who completed treatment (N = 61 camostat mesylate, N = 29 placebo). The estimated mean change in cycle threshold between day 1 and day 5 between the camostat and placebo group was 1.183 (P = 0.511). The unadjusted hazard ratio for clinical improvement in the camostat group was 0.965 (95% confidence interval, 0.480-1.942, P = 0.921 by Cox regression). The percentage distribution of the 50% neutralizing antibody titer at day 28 visit and frequency of adverse events were similar between the two groups. Under this protocol, camostat mesylate was not found to be effective as an antiviral drug against SARS-CoV-2. Trial registration: ClinicalTrials.gov NCT04625114 ; November 12, 2020. [ABSTRACT FROM AUTHOR]

Liver X receptors (LXRs) are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. However, exactly how LXRs modulate inflammation during infection remains unknown. To explore this, we used a mouse model of Mycobacterium tuberculosis infection. Upon intratracheal infection with M. tuberculosis, LXRs and LXR target genes were induced in CD11c+ lung and alveolar cells. Furthermore, mice deficient in both LXR isoforms, LXRalpha and LXRbeta (Lxra-/-Lxrb-/- mice), were more susceptible to infection, developing higher bacterial burdens and an increase in the size and number of granulomatous lesions. Interestingly, mice solely deficient in LXRalpha, but not those lacking only LXRbeta, mirrored the susceptibility of the Lxra-/-Lxrb-/- animals. Lxra-/-Lxrb-/- mice failed to mount an effective early neutrophilic airway response to infection and showed dysregulation of both pro- and antiinflammatory factors in CD11c+ lung cells. T cell responses were strongly affected in Lxra-/-Lxrb-/- mice, showing near-complete abrogation of the infection-induced Th1 function - and even more so Th17 function - in the lungs. Treatment of WT mice with the LXR agonists TO901317 and GW3965 resulted in a 10-fold decrease of the pulmonary bacterial burden and a comparable increase of Th1/Th17 function in the lungs. The dependence of LXR signaling on the neutrophil IL-17 axis represents what we believe to be a novel function for these nuclear receptors in resistance to M. tuberculosis infection and may provide a new target for therapeutics. [ABSTRACT FROM AUTHOR]

We report a lentiviral vector harboring the human β2-microglobulin promoter, with predominant expression in immune cells and minimal proximal enhancers to improve vector safety. This lentiviral vector efficiently transduces major dendritic cell subsets in vivo. With a mycobacterial immunogen, we observed distinct functional signatures and memory phenotype in lentiviral vector- or Adenovirus type 5 (Ad5)-immunized mice, despite comparable antigen-specific CD8+ T cell magnitudes. Compared to Ad5, lentiviral vector immunization resulted in higher multifunctional and IL-2-producing CD8+ T cells. Furthermore, lentiviral vector immunization primed CD8+ T cells towards central memory phenotype, while Ad5 immunization favored effector memory phenotype. Studies using HIV antigens in outbred rats demonstrated additional clear-cut evidence for an immunogenic advantage of lentiviral vector over Ad5. Additionally, lentiviral vector provided enhance therapeutic anti-tumor protection than Ad5. In conclusion, coupling lentiviral vector with β2-microglobulin promoter represents a promising approach to produce long-lasting, high-quality cellular immunity for vaccinal purposes. Ku et al. report a lentiviral (LV) vector system in which expression of vaccine antigens is driven by β2-microglobulin (β2m) promoter. Conducting comparative studies in mice and rats, they find that LV-based vaccine outperforms the 'gold-standard' Ad5 by inducing a polyfunctional and long-lived immune response. [ABSTRACT FROM AUTHOR]

The synthesis of mycobacterial mycolic acid related wax esters and of their trehalose di- and mono-esters is described. The trehalose dimycolates (TDMs) synthesised activated bone marrow derived dendritic cells (BMDCs) in vitro more strongly than trehalose dibehenate or the trehalose monomycolates (TMMs). The inflammatory effects were similar to those of TDM from either a synthetic keto- or methoxy-mycolic acid, but somewhat stronger than those of a TDM from an α-mycolic acid. In vivo, the effects of one wax ester TDM were similar to those of the methoxy-MA and α-mycolic acid TDMs and trehalose dibehenate. [ABSTRACT FROM AUTHOR]

Objective To determine the needle-to-nerve distances during electrical nerve location in dogs at different currents and pulse duration using a peripheral nerve stimulator ( PNS) under ultrasound control ( US), and the minimal electrical thresholds ( MET) necessary to obtain a motor response ( MR) after achieving needle-to-nerve contact. Study design Prospective in vivo experimental trial in a clinical setting Animals Thirty dogs, scheduled for locoregional anaesthesia of the sciatic nerve. Methods Needle-to-nerve distance was measured ultrasonographically after obtaining the MR of sciatic nerve with 2, 1 and 0.5 mA and pulse duration 0.1 ms (NS0.1). Thereafter the needle was placed in contact with the nerve and MET was determined. The procedure was repeated with 0.3 ms (NS0.3). Finally the needle was reintroduced to contact the sciatic nerve guided only by US, thus MET- US was determined. Data were analysed using Kruskal- Wallis or Mann- Whitney tests. Results Needle-to-nerve distances were greater when MR was obtained with 2 mA than with 1 and 0.5 mA at 0.1 and 0.3 ms. No significant differences were observed between the needle-to-nerve distances using 0.1 or 0.3 ms. The MET [median (range)] was 0.4 (0.18-1.3) mA in NS0.1, 0.32 (0.12-0.8) mA in NS0.3; while MET- US was 0.7 (0.32-1.5) mA. When the needle contacted the nerve, the MR achieved with currents below 0.3 mA was obtained in 17.2, 40 and 0% of cases using NS0.1, NS0.3 and US respectively. Conclusions and clinical relevance The electrical current necessary to obtain a MR decreased as the needle moved towards the nerve. However when the needle tip contacted the nerve, an MR with low current intensity could not be obtained. Thus the absence of motor response at currents below 0.3 mA cannot rule out needle-epineurium contact. When ultrasound is combined with PNS, it is more important to assess the correct needle position than searching for an MR at low currents. [ABSTRACT FROM AUTHOR]

Objective To describe a new approach to block the femoral nerve and to evaluate the distribution of a dye injected into the psoas compartment using a new femoral nerve block approach; to assess its clinical application, when combined with a sciatic nerve block, for surgical anaesthesia/analgesia of the pelvic limb in dogs. Study design Prospective anatomical, research and clinical study. Animals Two dog cadavers; two dogs that had to be euthanized for reasons unrelated to this study, and 15 dogs undergoing pelvic limb orthopaedic surgery. Methods Phase 1: anatomical dissections were performed to determine a simple method to approach the femoral nerve within the psoas compartment. Phase 2: 0.1 mL kg−1 of a lidocaine-new methylene blue solution was injected bilaterally after successful electrolocation of the femoral nerve in two anaesthetized dogs. Colorant spread was evaluated through femoral nerve dissections after euthanasia. Phase 3: in 15 dogs undergoing pelvic limb orthopaedic surgery under light general anaesthesia with isoflurane, intra-operative analgesic effect (cardiovascular responses) and early post-operative pain score, of the novel femoral nerve block combined with a sciatic nerve block as the sole analgesic protocol, were evaluated. Results Phase 1: a needle inserted from the lateral aspect of the lumbar muscles, cranially to the iliac crest and with a 30-45° caudo-medial direction, reaches the femoral nerve in the caudal portion of the psoas compartment. Phase 2: Four femoral nerves were stained >2 cm. Phase 3: this novel lateral pre-iliac approach, combined with the sciatic nerve block, blunted the intra-operative cardiovascular response to surgical stimulation in 13 out of 15 anaesthetized dogs. In addition, rescue analgesia was not required in the early post-operative 2-hour period. Conclusion and clinical relevance The lateral pre-iliac femoral nerve block technique may provide adequate intra- and early post-operative pain relief in dogs undergoing pelvic limb surgery. [ABSTRACT FROM AUTHOR]

Objective To evaluate the endotracheal tube cuff pressure achieved by four different inflation methods. Study design Prospective clinical study. Animals Eighty client owned dogs. Methods After anaesthesia induction, endotracheal intubation was performed using plastic or silicone tubes. A clinician unaware of tube type inflated the cuff by simple digital palpation (method A), thereafter the cuff was deflated and inflated again by a second clinician who tried to reproduce a previously learned cuff pressure of between 19 and 24 mmHg (method B). During method C the cuff was inflated to the minimum occlusive volume at an airway pressure of 20 cm H2O, and in method D the cuff was incrementally deflated until an audible air leak could be heard from the oral cavity at an airway pressure of 25 cm H2O. For all the methods, an operator recorded the actual cuff pressure obtained using a manometer. Heart rate, respiratory rate and mean arterial pressure were monitored throughout the procedure. Results The mean inflation pressure for plastic tubes was 56 ± 28 mmHg for method A, 20 ± 9 mmHg for method B, 35 ± 32 mmHg for method C and 46 ± 39 mmHg for method D. Pressures using silicone tubes were significantly higher than for plastic tubes, the mean registered pressures being 79 ± 39, 33 ± 16, 77 ± 50 and 92 ± 56 mmHg for methods A, B, C and D. Conclusions and Clinical Relevance None of the methods evaluated in this study can be considered effective for inflating the endotracheal tube cuff to within the optimal range when using silicone tubes. Direct measurement of the cuff pressure with a manometer is therefore recommended. [ABSTRACT FROM AUTHOR]

Objective To describe the landmarks and methodology to approach the thoracic paravertebral space in dogs; to evaluate if intercostal muscular response could be evoked by a nerve-stimulator; to radiographically assess the distribution pattern of a radio-opaque contrast medium after thoracic paravertebral injections. Study design Randomized, controlled, experimental trial. Animals Two mongrel dog cadavers (anatomical study) and 24 mongrel dogs (experimental study). Methods For the anatomic study 0.2 mL kg−1 of new methylene blue (NMB) was injected at the 5th thoracic paravertebral space; for the experimental study dogs were divided into three groups and received 1 (T5), 2 (T4 and T6) or 4 (T4, T5, T6 and T7) paravertebral injections of iohexol. The paravertebral approach was performed with insulated needles using landmarks and a blind technique. When the needle tip reached the respective thoracic paravertebral space, the nerve-stimulator was switched-on and the presence/absence of intercostal muscular twitch was registered, thus a total volume of 0.2 mL kg−1 of iohexol, divided into equal parts for each injection point, was administered. Radiological studies were performed with two orthogonal projections at different times. Positive injection was confirmed when the paravertebral space was occupied by iohexol in both projections. Results NMB was distributed in the T5 paraverterbal space. In the experimental study, when the needle tip reached the respective paravertebral space, intercostal twitching was obtained in 80% of the total injections with a stimulating current of 0.5 mA. The incidence of positive cases when the intercostal twitch was obtained with 0.5 mA was 83.3%. The main distribution pattern observed was cloud like without longitudinal diffusion. Conclusion and clinical relevance Intercostal muscular responses obtained with a stimulating current of 0.5 mA could be useful to locate thoracic spinal nerves in dogs and in our study the injected solution was confined to one thoracic paravertebral space. [ABSTRACT FROM AUTHOR]

Abstract: Neurocysticercosis (NC) is a parasitic disease caused by the infiltration of the larval stage of Taenia solium in the central nervous system. Clinical presentations are heterogeneous and particularly depend, on the age and gender of the host. We designed a clinical study to evaluate the hormonal changes associated with neurocysticercosis and the relationships between disease heterogeneity, endocrine and immunological status. A total of 50 patients and 22 healthy subjects were included. A precise clinical and radiological description of disease for each patient was recorded. A broad hormonal profile was assessed for each participant and, in a sub-group of patients, immunological features were also evaluated. Compared with controls, all patients had lower dehydroepiandrosterone (DHEA) concentration; male patients also had lower concentrations of 17β-estradiol and higher concentrations of luteinising hormone (LH). In the clinically severe patients, lower concentrations of progesterone and androstenedione were found in women. Higher concentrations of follicle stimulating hormone (FSH) and lower concentrations of testosterone were found in men when compared with the less clinically severe patients. Significant correlations were found between estradiol and IL-10 in male patients, and between dehydroepiandrosterone (DHEA) and IL-1β, and androstenedione and IL-17 in female patients. To our knowledge the present study constitutes the first demonstration that the presence of T. solium larvae in the central nervous system can modify the host environment by the induction of endocrine and immunological changes. These results provide a stimulating background to analyse the repercussions of these changes on the course of the disease and on patient reproductive health. [Copyright &y& Elsevier]

Abstract: Mycobacterium avium subsp. paratuberculosis (Map), the etiological agent of chronic enteritis of the small intestine in domestic and wild ruminants, causes substantial losses to livestock industry. Control of this disease is seriously hampered by the lack of adequate diagnostic tools and vaccines. Here we report on the immunogenicity of eight Map specific antigens, i.e. MAP1693c, Ag3, MAP2677c (identified by post-genomic and immunoproteomic analysis of Map secretome) and Ag5, Ag6, MAP1637c, MAP0388 and MAP3743 (identified by bioinformatic in silico screening of the Map genome). Strong, antigen-specific IFN-γ responses were induced in mice vaccinated with plasmid DNA encoding MAP1693c, MAP1637c, MAP0388 and MAP3743. In contrast, T cell responses in Map infected mice were directed preferentially against Ag5 and to a lesser extent against MAP3743. None of the tested DNA vaccines conferred protection against subsequent challenge with Map. [Copyright &y& Elsevier]

Abstract: The effect of zoo visitors on the behaviour and physiological responses of the Mexican wolf has not been documented but is worthy of investigation since it is a critically endangered native species and most of the population live in zoos. The effect of the number of visitors was assessed in 12 wolves (five males and seven females) in three zoos of central Mexico. Each wolf was observed for a total of 72h on Saturdays, Sundays, Mondays and Tuesdays (6h/day) during a three-week period. Scan sampling was used to obtain individual time budgets. A faecal sample was collected on the following morning of each observation day from 10 wolves to determine cortisol level (RIA). A repeated measures analysis of variance revealed that there was an effect of day on the proportion of time lying (P <0.01), eating (P <0.01) and in locomotion (P <0.01). Wolves spent less time lying on Saturdays and Sundays (0.2980±0.012 and 0.3266±0.012, respectively) than on Mondays and Tuesdays (0.3821±0.012 and 0.4075±0.012, respectively), as well as less time eating on weekend days (Saturdays 0.1214±0.015, Sundays 0.0556±0.015) than in the other 2days (Mondays 0.816±0.015 and Tuesdays 0.0915±0.015). Mean faecal cortisol was 203.7ng/g of DM and ranged from 113.10 to 314.48ng/g. There was an effect of day on the faecal cortisol response (P <0.01) with wolves having higher cortisol response on Sundays (242.50ng/g±8.48) compared to the other 3days (Saturdays 192.71±8.48, Mondays 170.73ng/g±7.80, Tuesdays 183.82ng/g±8.48). This is the first study that measures faecal cortisol of Mexican wolves. These results indicate that the amount of visitors in zoos influence the behaviour and adrenal activity of these animals which could be undesirable for ex situ conservation efforts of this endangered species. [Copyright &y& Elsevier]

Abstract: Mycobacterium avium subsp. paratuberculosis (MAP), the etiological agent of chronic enteritis of the small intestine in domestic and wild ruminants, causes substantial losses to livestock industry. Control of this disease is seriously hampered by the lack of adequate diagnostic tools, vaccines and therapies. In this study, we have evaluated the vaccine potential of two MAP proteins, i.e. MAP0586c and MAP4308c, previously identified by postgenomic and immunoproteomic analysis of MAP secretome as novel serodiagnostic antigens. Immunizations of BALB/c and C57BL/6 mice with plasmid DNA encoding MAP0586c and MAP4308c induced strong Th1 type immune responses to both antigens, whereas antibody responses were only induced upon immunization with DNA encoding MAP4308c. Homologous boosting of DNA vaccinated mice with recombinant protein resulted in strong antibody responses against both proteins. Using synthetic overlapping peptides, immunodominant H-2d and H-2b restricted Th1 T cell epitopes were identified. Finally, MAP infected mice generated strong MAP0586c-specific T cell responses and MAP0586c DNA vaccination could protect BALB/c but not C57BL/6 mice against MAP challenge mice to the same extent as the Mycobacterium bovis BCG vaccine, indicating that this putative transglycosylase is an interesting vaccine candidate that warrants further investigation. [Copyright &y& Elsevier]

• The glioblastoma multiforme cells synthesize DHT, androsterone and dihydroandrosterone. • Finasteride and dutasteride inhibit the synthesis of androgens and estrogens. • These 5α-reductase inhibitors block several progesterone derivatives. • Glioblastoma cells synthesize corticosteroids. Glioblastoma (GBM) is the most aggressive local brain tumor and effective treatments are lacking. Many studies have proposed an important participation of steroid hormones in the development of gliomas. Evidence was provided by statistics analysis where the incidence in adult population is 50% higher in men than in women. Female patients have a better prognosis for survival compared to male patients with GBM. Also, the expression of receptors to estrogen, progesterone and androgens in glioma cell lines and tumor biopsies, and glucocorticoid receptors in GBM cell lines had been reported. Here we have investigated the effect of the pharmacological inhibition of 5-α reductases on the capacity of GBM derived cell lines C6 (rat) and U87 (human) to synthesize neurosteroids. As the knowledge of the pathways used to synthesize neurosteroids by GBM derived cells was incomplete, we have investigated the synthesis of these steroids by C6 and U87 cells using tritiated precursors and thin layer chromatography (TLC). Increasing concentrations of finasteride and dutasteride were added to U87 culture media that was collected after 24 and 48 h. The results of the study showed that C6 cells incubated with 3H-cholesterol yielded dihydroandrosterone, hydroxytestosterone, androstenediol, androstenedione and estriol, while U87 cells also synthesized progesterone, and androstanedione. Incubation with 3H-androstenedione or 3H-testosterone mainly yielded dihydrotestosterone, androsterone, dihydroandrosterone, hydroxytestosterone, and estradiol in both lines. To note, we showed here for the first time that U87 cells synthesize corticosteroids. Addition of finasteride or dutasteride to U87 cells reduced androgen and estrogen synthesis. Dutasteride also decreased the synthesis of dihydrocorticosterone and allotetrahydrodesoxycorticosterone while deoxycorticosterone was accumulated. In summary, both GBM cell lines synthesize numerous neurosteroids, including 5-α reductase products and 3α-HSD pathways that were inhibited by finasteride and dutasteride. These inhibitors may be considered as tools to control neurosteroid synthesis of potential relevance for GBM survival. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the feasibility of an ultrasound-guided technique targeting the medial branches of the dorsal ramus of the spinal nerves (DRSN) by injecting a dye solution at the caudal aspect of the base of lumbar mammillary processes [i.e. the retromammillary (RM) space]., Study Design: Feasibility, descriptive, anatomical study., Animals: Eleven canine cadavers., Methods: Using anatomical dissections, the relationship between the mammillary processes and the branches of the DRSN of the thoracolumbar and lumbar spine was studied in two cadavers. Subsequently, ultrasound-guided RM injections were administered in nine cadavers, randomly assigned to low volume (LV; 0.01 mL kg -1 ) of a dye solution at multiple points from L3 to L6 on one side, and high volume (HV; 0.4 mL kg -1 ) at a single L4 point on the contralateral side. Gross anatomical dissections were immediately performed after the injections. The RM injections were feasible if ultrasonographic landmarks were identifiable in at least 80% of cases, and 80% of LV injections showed medial branch staining. A one-sample binomial test was used for testing feasibility., Results: The medial branches emerged shortly after the DRSN exited the intervertebral foramen and traveled towards the caudal aspect of the base of the mammillary process, which served as the target injection point. With LV, 36 out of 36 (100%) injected medial branches were stained, meeting the criteria of feasibility (p < 0.001). The median (range) number of stained medial branches per cadaver were 4 (4-4) and 2 (1-3), with LV and HV, respectively. Although no lateral branches were stained with LV, 1 (0-2) was stained with HV. Neither ventral branch staining nor epidural spread was noted in any cadaver., Conclusions and Clinical Relevance: Ultrasound-guided RM injections are feasible and allow for selective staining of the medial branch of the DRSN in canine cadavers at the lumbar spine., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare perioperative opioid consumption in dogs undergoing pelvic limb surgeries and receiving a lumbosacral plexus block by combining a lumbar [lateral pre-iliac (LPI)] block with a lumbosacral trunk [i.e. parasacral (PS group) or greater ischiatic notch plane (GIN group)] block. Study design Retrospective, descriptive, exploratory, noninferiority cohort study., Methods: Medical records of 37 client-owned dogs were analyzed. Intraoperative (primary outcome) and postoperative (24 hours) opioid use, 24 hour cumulative pain scores and prevalence of complications were compared between the two groups. Opioid use was quantified in morphine equivalents (ME, mg kg -1 ). The noninferiority limit for intraoperative opioid consumption was set at 0.05 ME kg -1 hour -1 . Demographic data, procedure duration, surgery type and perioperative dexmedetomidine and ketamine use were also collected. A t-test or Wilcoxon rank-sum test, a Fisher's exact test and multivariable linear regression were used. Significance was set at p < 0.05., Results: The GIN and PS groups comprised 17 and 20 dogs, respectively. Total intraoperative ME consumption was 0.17 (0.11-0.21) and 0.22 (0.16-0.30) mg kg -1 hour -1 for the GIN and PS groups, respectively (p = 0.077). The noninferiority analysis adjusted by surgery type and body mass revealed that the mean difference between the groups (GIN - PS) was -0.039 (95% CI -0.11-0.03, p = 0.247) ME mg kg -1 hour -1 , indicating that the GIN group was not inferior to the PS group regarding intraoperative ME consumption. Dexmedetomidine and ketamine use, postoperative ME consumption and pain scores were similar between groups., Conclusions and Clinical Relevance: This retrospective study and preliminary observations support the clinical use of the GIN plane block, demonstrating its noninferiority to the PS block when combined with the LPI block for multimodal perioperative analgesia in dogs undergoing pelvic limb surgeries., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Background: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability., Aims: To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19., Methods: A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded., Results: Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died., Conclusions: IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration., Competing Interests: Conflict of Interest The authors have no other relevant affiliations or financial involvement with any organization or entity that has a financial interest in, or financial conflict with, the subject matter or materials discussed in the manuscript, except as stated., (Copyright © 2024. Published by Elsevier Inc.)

No data in the literature have evaluated sex hormone dose escalation for treating abnormal sleep of ovariectomized rats-nor studies on the role of sex hormones in GABA synthesis of rats' sleep-related areas. The main aim of this study was to determine the maximum tolerated dose (MTD) of estradiol (ET), progesterone (PT), and the mixture of both (EPT) to restore normal sleep in a model of menopause in rats. The second purpose was to describe the in vitro activity of glutamate decarboxylase (GAD) in sleep-related brain areas in the presence or absence of sex hormones. A weekly dose-escalation design of ET, PT, or EPT was implemented in ovariectomized rats (six per group). Dose escalation continued until the dose at which 100% of the rats exhibited a state of "complete somnolence." Doses that were not toxic or did not show side effects were considered. For in vitro experiments, sleep-related brain areas were separated and incubated with radiolabeled glutamate. Estradiol (17β-E 2 ), progesterone (P), and pyridoxal phosphate (PLP) were added to this assay, and GAD activity was determined. Under the same conditions, a second test was carried out, but the P antagonist RU486 was added to assess the role of P in GAD activity. Ovariectomy increased periodic awakenings compared to those determined for the SHAM group. The EPT for ovariectomized rats was very effective by the fifth week in decreasing arousal and achieving a similar sleep behavior to the SHAM-control group. Rats tolerated the ET, PT, and EPT well to the maximum planned dose (0.66 mg/kg and 4.4 mg/kg, respectively). No lethal events occurred; the MTD was reached. The in vitro studies indicated that the presence of 17β-E 2 plus P in the assay triggered the activity of isotype 65 GAD in all the studied brain areas. RU486 in the incubation medium blocked such activity; however, the action of isotype 67 GAD was not blocked by RU486. A dose-escalation model was determined; the MTD coincided with the maximum dose of ET and PT used. However, the EPT combination restored normal sleep in the menopause model compared to the SHAMs without toxic effects. The in vitro model demonstrated that 17β-E 2 plus P presence in the assay increased the activity of GAD 65 in the studied brain tissues., Competing Interests: The authors declare no conflict of interest

Objective: To define the morbidity and mortality rates in goats undergoing general anesthesia at a large animal teaching hospital., Study Design: Retrospective, single-cohort, observational study., Animals: Records of 193 client-owned goats., Methods: Data were collected from 218 medical records on 193 goats undergoing general anesthesia between January 2017 and December 2021. Demographic data, anesthetic management, recovery period and perianesthetic complications were recorded. Perianesthetic death was defined as anesthesia-related or anesthesia-contributory death occurring within 72 hours after recovery. Records of goats that were euthanized were reviewed to ascertain the cause of euthanasia. Each explanatory variable was individually investigated by univariable penalized maximum likelihood logistic regression, followed by multivariable analysis. Statistical significance was set at p < 0.05., Results: Perianesthetic mortality was 7.3%, but was 3.4% when considering only goats undergoing elective procedures. Multivariable analysis showed that gastrointestinal surgeries [odds ratio (OR) 19.17, standard error (SE) 12.99, 95% confidence interval (CI) 5.08-72.33; p < 0.01] and requirement for perianesthetic norepinephrine infusion (OR 10.85, SE 8.82, 95% CI 2.21-53.33; p < 0.01) were associated with increased mortality. Maintaining other variables equal, the use of perianesthetic ketamine infusion was associated with decreased mortality (OR 0.09, SE 0.09, 95% CI 0.01-0.73; p = 0.02). Anesthesia-related or anesthesia-contributory complications included hypothermia (52.4%), bradycardia (38.1%), hypotension (35.3%), hypoxemia (14.8%), regurgitation/aspiration (7.3%), azotemia/acute renal failure (4.6%), myopathies/neuropathies (4.1%) and fever of unknown origin (2.7%)., Conclusions and Clinical Relevance: In this population, gastrointestinal surgeries and the requirement for perianesthetic norepinephrine infusion were associated with increased mortality in goats undergoing general anesthesia, while ketamine infusion may have a protective effect., (Copyright © 2023 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Mexico City is one of the most polluted cities in the world, and one in which air contamination is considered a public health threat. Numerous studies have related high concentrations of particulate matter and ozone to several respiratory and cardiovascular diseases and a higher human mortality risk. However, almost all of those studies have focused on human health outcomes, and the effects of anthropogenic air pollution on wildlife species is still poorly understood. In this study, we investigated the impacts of air pollution in the Mexico City Metropolitan Area (MCMA) on house sparrows (Passer domesticus). We assessed two physiological responses commonly used as biomarkers: stress response (the corticosterone concentration in feathers), and constitutive innate immune response (the concentration of both natural antibodies and lytic complement proteins), which are non-invasive techniques. We found a negative relationship between the ozone concentration and the natural antibodies response (p = 0.003). However, no relationship was found between the ozone concentration and the stress response or the complement system activity (p > 0.05). These results suggest that ozone concentrations in air pollution within MCMA may constrain the natural antibody response in the immune system of house sparrows. Our study shows, for the first time, the potential impact of ozone pollution on a wild species in the MCMA presenting the Nabs activity and the house sparrow as suitable indicators to assess the effect of air contamination on the songbirds., (© 2023. The Author(s).)

Introduction: Tuberculosis (TB) caused by Mycobacterium tuberculosis mainly affects the lungs, but can spread to other organs. TB chronically activates the immune and endocrine systems producing remarkable functional changes.So far, it is unknown whether pulmonary non-disseminated TB cause changes in the female reproductive system and lung endocrinology., Objective: To investigate whether pulmonary TB produces immunoendocrine alterations of the female mice reproductive organs, and lung estradiol synthesis., Methods: BALB/c mice were infected intratracheally with Mycobacterium tuberculosis (Mtb) strain H37Rv. Groups of six non-infected and infected animals were euthanized on different days. Bacillary loads were determined in the lungs, ovaries and uterus. Immunohistochemistry and morphometry studies were performed in histological sections. Serum estradiol wasassayed, and supernatantfrom cultured lung cells was analyzed by Thin Layer Chromatography (TLC)., Results: Mtb only grew in lung tissue. Histopathology revealed abnormal folliculogenesis and decreased corpora lutea. Altered ovarian expression of IL-6, IL-1β was found. The infection increased serum estradiol. Estradiol synthesis by infected lung cells triplicate after 30 pi days.Aromatase immunostaining was found in the alveolar and bronchial epithelium, being stronger in the infected lungs, mainly in macrophages., Conclusion: Pulmonary TB affects the histophysiology of the female reproductive system in absence of its local infection, and disturbslung endocrinology., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions. Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: By end December of 2021, COVID-19 has infected around 276 million individuals and caused over 5 million deaths worldwide. Infection results in dysregulated systemic inflammation, multi-organ dysfunction, and critical illness. Cells of the central nervous system are also affected, triggering an uncontrolled neuroinflammatory response. Low doses of glucocorticoids, administered orally or intravenously, reduce mortality among moderate and severe COVID-19 patients. However, low doses administered by these routes do not reach therapeutic levels in the CNS. In contrast, intranasally administered dexamethasone can result in therapeutic doses in the CNS even at low doses., Methods: This is an approved open-label, multicenter, randomized controlled trial to compare the effectiveness of intranasal versus intravenous dexamethasone administered in low doses to moderate and severe COVID-19 adult patients. The protocol is conducted in five health institutions in Mexico City. A total of 120 patients will be randomized into two groups (intravenous vs. intranasal) at a 1:1 ratio. Both groups will be treated with the corresponding dexamethasone scheme for 10 days. The primary outcome of the study will be clinical improvement, defined as a statistically significant reduction in the NEWS-2 score of patients with intranasal versus intravenous dexamethasone administration. The secondary outcome will be the reduction in mortality during hospitalization., Conclusions: This protocol is currently in progress to improve the efficacy of the standard therapeutic dexamethasone regimen for moderate and severe COVID-19 patients., Trial Registration: ClinicalTrials.gov NCT04513184 . Registered November 12, 2020. Approved by La Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) with identification number DI/20/407/04/36. People are currently being recruited., (© 2022. The Author(s).)