Effect of Passive Administration of Monoclonal Antibodies Recognizing Simian Immunodeficiency Virus (SIV) V2 in CH59-Like Coil/Helical or ß-Sheet Conformations on Time of SIVmac251 Acquisition.

The monoclonal antibodies (MAbs) NCI05 and NCI09, isolated from a vaccinated macaque that was protected from multiple simian immunodeficiency virus (SIV) challenges, both target an overlapping, conformationally dynamic epitope in SIV envelope variable region 2 (V2). Here, we show that NCI05 recognizes a CH59-like coil/helical epitope, whereas NCI09 recognizes a ß-hairpin linear epitope. In vitro, NCI05 and, to a lesser extent, NCI09 mediate the killing of SIV-infected cells in a CD4-dependent manner. Compared to NCI05, NCI09 mediates higher titers of antibody-dependent cellular cytotoxicity (ADCC) to gp120-coated cells, as well as higher levels of trogocytosis, a monocyte function that contributes to immune evasion. We also found that passive administration of NCI05 or NCI09 to macaques did not affect the risk of SIVmac251 acquisition compared to controls, demonstrating that these anti-V2 antibodies alone are not protective. However, NCI05 but not NCI09 mucosal levels strongly correlated with delayed SIVmac251 acquisition, and functional and structural data suggest that NCI05 targets a transient state of the viral spike apex that is partially opened, compared to its prefusion-closed conformation. IMPORTANCE Studies suggest that the protection against SIV/simian-human immunodeficiency virus (SHIV) acquisition afforded by the SIV/HIV V1 deletion-containing envelope immunogens, delivered by the DNA/ALVAC vaccine platform, requires multiple innate and adaptive host responses. Anti-inflammatory macrophages and tolerogenic dendritic cells (DC-10), together with CD14+ efferocytes, are consistently found to correlate with a vaccine-induced decrease in the risk of SIV/SHIV acquisition. Similarly, V2-specific antibody responses mediating ADCC, Th1 and Th2 cells expressing no or low levels of CCR5, and envelope-specific NKp44+ cells producing interleukin 17 (IL-17) also are reproducible correlates of decreased risk of virus acquisition. We focused on the function and the antiviral potential of two monoclonal antibodies (NCI05 and NCI09) isolated from vaccinated animals that differ in antiviral function in vitro and recognize V2 in a linear (NCI09) or coil/helical (NCI05) conformation. We demonstrate that NCI05, but not NCI09, delays SIVmac251 acquisition, highlighting the complexity of antibody responses to V2.

Synthesis of (-)-Cannabidiol (CBD), (-)-Δ9- and (-)-Δ8-Tetrahydrocannabinols, Encapsulation of CBD with Nanoparticles for Controlled Delivery and Biological Evaluation.

Cannabidiol (CBD) is garnering increasing interest due to its significant biological activity. This natural compound is one of the major cannabinoids in Cannabis sativa L. In this work, we describe the encapsulation of CBD in solid and hollow pH-sensitive poly(4-vinylpyridine) (solid@p4VP and hollow@p4VP) nanoparticles, and temperature-sensitive poly(N-isopropylacrylamide) (solid@pNIPAM and hollow@pNIPAM) nanoparticles for transport and release CBD in a controlled manner. The CBD loading into these smart polymeric systems was effective and their release profiles, solubility and resistance to stomach and intestinal conditions were evaluated, showing satisfactory properties and improved bioavailability with respect to free CBD. Finally, the A549 human lung cancer cell line was used as lung adenocarcinoma epithelial cellular model to carry out preliminary assays of the in vitro activity of the vehiculized CBD. For all these studies, synthetic CBD was employed, for which a new efficient and scalable synthesis of cannabinoids has been developed.

Attitudes and experiences related to the deaths of COVID-19 patients among nursing staff: A qualitative evidence synthesis.

AIM: To identify and synthesize the experiences and attitudes of nursing staff regarding the deaths of COVID-19 patients. REVIEW METHODS: A qualitative evidence synthesis was carried out, using Noblit and Hare's meta-ethnographic approach. The review protocol was listed in PROSPERO (CRD42022330928). Studies published from January 2020 to January 2022 that met the criteria were searched in PubMed, Web of Science, Scopus, CINAHL, CUIDEN and PsycInfo. A total of 12 articles were included. RESULTS: Thirty-three metaphors emerged, which were grouped into three main themes: Determining factors of care, Feelings about death and Strategies for coping with death. Nurses reported the high emotional toll, the absence of family and the lack of staff, protocol and training as determining factors. Furthermore, staff had doubts about the quality of care that COVID-19 patients received. As coping strategies, nurses developed avoidance behaviours towards COVID-19 patients, selective memories, resilience, and/or leaving the profession. CONCLUSIONS: The difficulty in providing adequate nursing care and the high number of deaths has increased anxiety and stress among nurses. These factors, alongside their lived experiences of seeing patients suffering, many dying alone without family members, have had psychological repercussions on nursing staff. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The results demonstrate a high emotional toll and doubts surrounding their caregiving role caused by the lack of professional training needed to face a pandemic. This research shows what has been learned for future pandemics and highlights basic components that could provide a foundation for coping interventions for healthcare professionals. IMPACT: WHAT PROBLEM DID THE STUDY ADDRESS?: The challenges posed by COVID-19 patient deaths for nursing staff around the world and also by the pandemic circumstances in which those deaths occurred. WHAT WERE THE MAIN FINDINGS?: The high number of deceased patients who were isolated from family members, communication with family members and doubts surrounding care given during the pandemic have created feelings of fear, stress and anxiety, as well as obsessive thoughts that have changed nursing staff's perception of death due to COVID-19. WHERE AND ON WHOM WILL THE RESEARCH HAVE AN IMPACT?: Results will be useful for preparing for future pandemics, and for policymakers and health staff in supporting healthcare professionals by creating programmes to help them cope with the emotional toll they have felt after dealing with death in such unprecedented circumstances. REPORTING METHOD: The authors have adhered to the PRISMA guidelines and the eMERGe Reporting Guidance. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Effect of continuous positive airway pressure helmet on respiratory function following surgical procedures in brachycephalic dogs: A randomized controlled trial.

OBJECTIVE: To evaluate the effect of continuous positive airway pressure (CPAP) on respiratory function in the early postoperative period of brachycephalic dogs. STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: A total of 32 dogs. METHODS: Dogs were assigned to recover with or without CPAP (control) and assessed at specific time points over 1 h. Treatment was discontinued for dogs with a CPAP tolerance score of 3 or more (from a range of 0-4). The primary outcome was pulse oximetry (SpO2). Secondary outcomes were arterial O2 pressure (PaO2)/FiO2 ratio (PaO2/FiO2), arterial CO2 pressure (PaCO2), and rectal temperature. For dogs that reached a CPAP tolerance score of 3 or more, only the data collected up to the time point before discontinuation were included in the analysis. The treatment effect (ß) was analyzed using random effects models and the results were reported with 95% confidence intervals. RESULTS: Dogs were assigned randomly to each protocol. Baseline characteristics in both groups were comparable. Arterial blood gases were obtained in seven control group dogs and nine CPAP group dogs. Treatment did not affect SpO2 (ß = -0.1, -2.1 to 2.0) but affected the PaO2/FiO2 ratio (ß = 58.1, 2.6 to 113.6), with no effects on PaCO2 (ß = -4.3, -10.5 to 1.9) or temperature (ß = 0.4, -0.8 to 1.6). CONCLUSION: In postoperative brachycephalic dogs, CPAP had no effect on SpO2 but improved the PaO2/FiO2 ratio in brachycephalic dogs postoperatively. CLINICAL SIGNIFICANCE: Continuous positive airway pressure offers a valuable solution to improve gas exchange efficiency, a prevalent concern in postoperative brachycephalic dogs, with the potential to enhance overall outcomes.

Sugammadex for reversal of moderate-to-deep rocuronium block in a clinical setting: A retrospective report of 10 dogs.

OBJECTIVE: To compare recovery times of sugammadex with spontaneous recovery from rocuronium-induced neuromuscular block (NMB) in dogs. STUDY DESIGN: Retrospective, unmatchedcase-control study. ANIMALS: A total of 10 dogs administered sugammadex and 10 dogs recovering spontaneously from rocuronium-induced NMB. METHODS: Files of dogs administered rocuronium between March and August 2023 were inspected. The train-of-four (TOF) count at the time of sugammadex administration and the time between administration and TOF ratio >90% (recovery time) were recorded. The recovery time for those not administered reversal agents was considered from the first TOF value >0 until TOF ratio >90%. The dose of sugammadex and the cumulative dose of rocuronium were recorded. Rocuronium doses and recovery times were compared using Mann-Whitney tests. The coefficient of determination (R2) between the cumulative rocuronium dose and sugammadex dose and the recovery time were calculated. RESULTS: Dogs in the sugammadex and spontaneous recovery groups were administered intravenously (IV) 0.76 (0.4-2.6) and 0.61 (0.3-2.9) mg kg-1 of rocuronium, respectively (p = 0.325). Recovery time after 3.9 (2.9-5.5) mg kg-1 of sugammadex IV was 1 (1-3) minutes and was 20 (10-35) min for spontaneous recovery (p < 0.0001). The R2 for rocuronium and sugammadex doses and recovery times were 0.19 (p = 0.2) and 0.012 (p = 0.758). CONCLUSIONS AND CLINICAL RELEVANCE: Sugammadex 2.9-5.5 mg kg-1 reversed moderate (TOF count 1-3) or deep (TOF count 0) rocuronium-induced NMB within 3 minutes, substantially faster than spontaneous recovery.

Evaluation of a rapid sequence induction technique in dogs with or without rocuronium.

OBJECTIVE: To determine, using a rapid sequence induction (RSI) technique, whether rocuronium improves the quality and speed of endotracheal intubation in healthy dogs. STUDY DESIGN: Randomized, crossover, experimental study. ANIMALS: Six adult intact male Beagles (12.3 ± 0.4 kg). METHODS: Dogs were premedicated with intravenous acepromazine (0.03 mg kg-1) and hydromorphone (0.1 mg kg-1). Ten minutes later, anesthesia was induced with intravenous propofol (2 mg kg-1 over 5 seconds), followed by saline (0.06 mL kg-1, CT group) or rocuronium (0.6 mg kg-1, RT group), with orotracheal intubation attempted after 45 seconds. Intubation time (IT) and conditions (IC) were assessed. PaO2, PaCO2, arterial blood pH and serum cortisol were obtained before and after RSI. After endotracheal intubation, saline (0.04 mL kg-1) or sugammadex (4 mg kg-1) were administered intravenously in CT or RT groups, respectively. Spontaneous ventilation restoration was noted. RESULTS: The IT was 54.3 ± 6.9 (mean ± SD) and 57.8 ± 5.2 seconds for CT and RT, respectively (p = 0.385). All laryngoscopies indicated good IC in both treatment groups. Heart rate was lower in CT group than in RT group (66 ± 16 versus 103 ± 39 beats minute-1, p = 0.016). PaCO2, pH, PaO2 and cortisol did not differ between treatments. Compared with baseline, PaCO2 increased from 47.7 ± 6.2 to 58.8 ± 5.8 (p < 0.001) and pH decreased from 7.35 ± 0.04 to 7.28 ± 0.04 (p = 0.003), independent of treatment. Dogs in both treatment groups returned to spontaneous ventilation within 30 seconds of RSI. CONCLUSIONS AND CLINICAL RELEVANCE: RSI resulted in respiratory acidosis without hypoxemia or increased cortisol. Rocuronium did not improve IT or IC. Spontaneous ventilation was observed immediately after administering saline or sugammadex. The co-administration of rocuronium showed no clinical benefits over propofol alone in RSI in healthy dogs.

Onset and duration of action of escalating doses of atracurium in anesthetized healthy goats.

OBJECTIVE: The aim of this study was to describe the onset and duration of action of escalating doses of atracurium in healthy, anesthetized goats. STUDY DESIGN: Randomized, blinded, triple crossover study. Animals A total of eight (five males and three females) healthy goats weighing 42.7-123.5 kg and aged from 11 months to 8 years. METHODS: Goats were anesthetized three times with propofol and anesthesia was maintained with isoflurane. One of three doses of atracurium was administered intravenously 30 minutes after induction: 0.25 mg kg-1 (AT25), 0.5 mg kg-1 (AT50) or 0.75 mg kg-1 (AT75). Acceleromyographic train-of-four ratio (TOFR) followed by train-of-four counts (TOFC) were recorded at 30 second intervals after atracurium administration to determine blockade onset (TOFC = 0). The TOFR followed by TOFC were recorded at 5 minute intervals until return to pre-atracurium baseline (TOFR = 1.0). Normally distributed data were analyzed with repeated measures anova and a Tukey multiple comparison test. Data not normally distributed were analyzed with a Friedman test and a Dunn's multiple comparison test. RESULTS: For AT50 and AT75, 100% of goats achieved TOFC = 0 after atracurium administration. For AT25, however, 87.5% of goats achieved TOFC = 0 after atracurium administration. The onset time was shorter for AT75 [1.5 (0.5-1.5) minutes; median (range)] than for AT25 [2 (1-4) minutes] (p = 0.048). The duration of action [from onset time to complete reversal (TOFR = 1.0)] was significantly shorter for AT25 (52 ± 12 minutes, mean ± SD) than for AT50 (77 ± 18 minutes) (p < 0.001) and AT75 (85 ± 16 minutes) (p < 0.001). There was no significant difference in duration between AT50 and AT75 (p = 0.238). CONCLUSIONS AND CLINICAL RELEVANCE: Doses of 0.5 and 0.75 mg kg-1 atracurium may produce complete neuromuscular blockade in healthy, anesthetized goats.

Haemodynamic effects of labetalol in isoflurane-anaesthetized dogs that received dexmedetomidine: A randomized clinical trial.

OBJECTIVE: To test whether labetalol improved cardiovascular function in anaesthetized dogs injected with dexmedetomidine. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A group of 20 healthy client-owned dogs undergoing ovariohysterectomy. METHODS: Each dog received dexmedetomidine (5 µg kg-1) and methadone (0.2 mg kg-1) intramuscularly. General anaesthesia was induced with propofol and maintained with isoflurane in oxygen. All dogs were mechanically ventilated, and epidural anaesthesia with lidocaine was performed. Standard anaesthetic monitoring, invasive blood pressure, oesophageal Doppler and near-infrared tissue perfusion/oxygenation were applied. Peak velocity (PV), mean acceleration and stroke distance (SD) from the oesophageal Doppler were recorded. Arterial elastance (Ea) was calculated. Tissue oxygenation (rStO2) was also recorded. Prior to surgery, animals received either 0.1 mg kg-1 of labetalol intravenously (IV) over 60 seconds or the equivalent volume of saline. Data were recorded for 20 minutes. Age, weight and propofol dose were compared with a Wilcoxon rank-sum test. The effects of time, treatment and their interaction with haemodynamic and perfusion variables were analysed with mixed-effect models and Tukey's post hoc tests. RESULTS: Significant effects of the interaction between treatment and time were observed whereby heart rate (HR) was higher in dogs given labetalol (p = 0.01), whereas arterial blood pressure and Ea were lower (p < 0.01). Similarly, PV, SD and rStO2 were higher in the labetalol group, and significant effects were detected for the interaction between treatment and time (p < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Labetalol at a dose of 0.1 mg kg-1 IV in dogs under general anaesthesia and administered a pre-anaesthetic medication of dexmedetomidine produced mild vasodilation (reduction of Ea), resulting in an increase in HR and left ventricular outflow. Although labetalol could be an effective option to achieve haemodynamic optimization after dexmedetomidine-induced vasoconstriction, future studies are needed to assess long-term effects.

Three-dimensional electrical impedance tomography to study regional ventilation/perfusion ratios in anesthetized pigs.

This study aimed to develop a three-dimensional (3-D) method for assessing ventilation/perfusion (V/Q̇) ratios in a pig model of hemodynamic perturbations using electrical impedance tomography (EIT). To evaluate the physiological coherence of changes in EIT-derived V/Q̇ ratios, global EIT-derived V/Q̇ mismatches were compared with global gold standards. The study found regional heterogeneity in the distribution of V/Q̇ ratios in both the ventrodorsal and craniocaudal directions. Although global EIT-derived indices of V/Q̇ mismatch consistently underestimated both low and high V/Q̇ mismatch compared with global gold standards, the direction of the change was similar. We made the software available at no cost for other researchers to use. Future studies should compare regional V/Q̇ ratios determined by our method against other regional, high-resolution methods.NEW & NOTEWORTHY In this study, we introduce a novel 3-D method for assessing ventilation-perfusion (V/Q̇) ratios using electrical impedance tomography (EIT). Heterogeneity in V/Q̇ distribution showcases the significant potential for enhanced understanding of pulmonary conditions. This work signifies a substantial step forward in the application of EIT for monitoring and managing lung diseases.

The Influence of Early-Life Health Conditions on Life Course Health.

We expand on previous studies investigating the links between early health and later health by examining four distinct dimensions of early-life health and multiple life course outcomes, including the age of onset of serious cardiovascular diseases (CVDs) and several job-related health outcomes. The four dimensions of childhood health are mental, physical, self-reported general health, and severe headaches or migraines. The data set we use includes men and women in 21 countries from the Survey of Health, Ageing and Retirement in Europe. We find that the different dimensions of childhood health have unique ties to later outcomes. For men, early mental health problems play a stronger role for life course job-related health outcomes, but early poor/fair general health is more strongly linked to the spike in onset of CVDs in their late 40s. For women, these links between childhood health dimensions and life course outcomes are similar but are less clear-cut than for men. The spike in onset of CVDs in women's late 40s is driven by those with severe headaches or migraines, while those with early poor/fair general health or mental health problems do worse as captured by job-related outcomes. We also delve into and control for possible mediating factors. Exploring the links between several dimensions of childhood health and multiple health-related life course outcomes will enable a better understanding of how health inequalities originate and are shaped over the course of people's lives.