Foam drying stabilization of an oral vaccine for SARS-CoV-2 expressed in Salmonella enterica serovar Typhi Ty21a

083 Thermostabilization of measles vaccines using preservation by vaporization

Bendamustine hydrochloride, a thermolabile biopharmaceutical, in lyophilized form is unsteady proving difficult to maintain activity and shelf life. To counterbalance the thermo-fragile nature of this product and eliminate limitations of lyophilization an alternative method with rational selection of stabilizers is developed. The present research work was aimed to screen sugar-phosphate composite mixtures to enhance storage stability of drug using evaporative foam drying. The effect of foaming agents and their strengths, pH and temperature on product features were investigated. The physicochemical stability of products prepared using sugars, polymer and inorganic water soluble phosphates alone and in combination was studied. The products were characterized for residual moisture, reconstitution time and drug content. The amount of drug retained after processing and at storage was analyzed by HPLC. Foam dried products were tested for short term stability as per ICH guidelines for biologicals. Pluronic® F108 at 0.6% exhibited optimum foamability. Foams were stable at 0.4% polyvinyl pyrrolidone K30. The enhancement in drug stability by evaporative foam drying attributed to electrostatic interaction between protonable groups of drug and deprotonable groups of composite stabilizer mixture during dehydration. The processing and storage stability of drug in composite glass was superior at normal storage. Proper selection of stabilizers for this technique is a key to successful stabilization of drug at ambient temperatures without loss of their activity during shipping and storage without refrigeration. Keywords:.

Oral booster vaccine antigen-Expression of full-length native SARS-CoV-2 spike protein in lettuce chloroplasts.

Passive immunization against COVID-19 by anti-SARS-CoV-2 spike IgG in commercially available immunoglobulin preparations in severe antibody deficiency

Introduction In patients with burns > 20% TBSA, hypermetabolism, evaporative water loss, infection risk and discomfort are all amplified by exposure to cold ambient temperatures. Post-operative patient hypothermia is also detrimental. It is essential to not only maintain a warm patient room temperature, but also to be able to rapidly increase room temperature in the burn ICU. The purpose of this study was to measure typical patient room temperatures in a burn ICU at an adult regional ABA-verified burn center, and to evaluate our ability to intervene and raise room temperature. Methods The ambient temperatures of nine patient rooms were recorded from 14 June to 14 August, 2019. Temperature was measured every minute by a wall-mounted smart sensor placed at standardized positions away from windows or electronic equipment. All devices were tested prior to use, with temperature and humidity accurate and standardized to < 0.2oC and 2% respectively at 18-25oC. Data was transmitted to a mobile smartphone. On 15 August 2019 all room temperatures were manually adjusted to ‘maximum’. This was identified as a sound change initiative, and replicated a potential medical order to increase the ambient temperature should a hypothermic patient be imminently returning from the operating room or resuscitation area after admission. Results Over the baseline observation period (Figure 1) the mean ± SD room temperature was 23.3 ± 1oC. Temperatures deviated below a mean of 22oC during 166 hours per room (11.5%, range 3–362). Following the intervention on 15 August (Figure 2), ambient temperature increased minimally in 6/9 rooms and only by 2–3°C in two rooms (mean rise of 1.03oC; range -0.88oC to 3.26oC). Conclusions The burn ICU rooms are relatively cold and our ability to raise ambient temperature quickly is limited. Further QI change ideas include: 1) a facility engineering assessment 2) set alarms on the smart sensors to alert staff when room temperature falls below a designated threshold. Applicability of Research to Practice This project has identified an important future QI initiative to maintain warm ambient patient room temperatures in the burn ICU.

Introduction: Patients with major burn injuries are particularly susceptible to hypothermia. The ability to maintain and rapidly increase ambient temperatures may reduce the impact of hypothermia and the hypermetabolic response. The purpose of this study was to determine ambient patient room temperatures in a burn intensive care unit (ICU) and to evaluate our ability to adjust these temperatures. Methods: The ambient temperatures of 9 burn ICU patient rooms were recorded hourly over a 6-month period in an American Burn Association-verified burn centre. Temperatures were recorded using wall-mounted smart sensors, transmitted to a mobile smartphone application via Bluetooth, and then exported to Excel for analysis. On 2 predetermined dates, thermostats in all rooms were simultaneously set to maximum, and monitored over 3 h. This represented a sound change initiative, and replicated a medical order to increase the ambient temperature during critical stages of patient care. Results: We recorded 4394 individual hourly temperature measurements for each of the 9 rooms. The mean ambient temperature was 23.5 ± 0.3 °C (range 22.8-24). After intervention 1, ambient temperatures increased <2 °C in 7 rooms and by only 2 °C-3 °C in the other 2 rooms. The overall mean increase in temperature over 3 h across all rooms was 1.03 °C ± 1.19 °C (range -0.88 to 3.26). Following intervention 2, temperatures could be increased by ≥2 °C in only 2 rooms with an overall mean increase in temperature of only 0.76 °C ± 0.99 °C (range -0.29 to 2.43) across all rooms. Conclusions: The burn ICU rooms were relatively cool and our ability locally to adjust ambient temperatures quickly was limited. Burn centres should have regular facility assessments to assess whether ambient temperatures can be adjusted expeditiously when required.

The interaction between the SARS-CoV-2 virus Spike protein receptor binding domain (RBD) and the ACE2 cell surface protein is required for viral infection of cells. Mutations in the RBD are present in SARS-CoV-2 variants of concern that have emerged independently worldwide. For example, the B.1.1.7 lineage has a mutation (N501Y) in its Spike RBD that enhances binding to ACE2. There are also ACE2 alleles in humans with mutations in the RBD binding site. Here we perform a detailed affinity and kinetics analysis of the effect of five common RBD mutations (K417N, K417T, N501Y, E484K, and S477N) and two common ACE2 mutations (S19P and K26R) on the RBD/ACE2 interaction. We analysed the effects of individual RBD mutations and combinations found in new SARS-CoV-2 Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P1) variants. Most of these mutations increased the affinity of the RBD/ACE2 interaction. The exceptions were mutations K417N/T, which decreased the affinity. Taken together with other studies, our results suggest that the N501Y and S477N mutations enhance transmission primarily by enhancing binding, the K417N/T mutations facilitate immune escape, and the E484K mutation enhances binding and immune escape.

Decision letter: Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics

Recent research supports the use of cold IV fluid as a method for initiating therapeutic hypothermia in post-cardiac arrest resuscitation. However, prehospital care programs employing this treatment have encountered various difficulties. Barriers to prehospital induced hypothermia protocols include the lack of effective or economically reasonable methods to maintain cold saline in the field. Objective. Determine the time that a standard commercial cooler can maintain two 1-liter normal saline solution (NSS) bags below 4°C in 3 different environments. Methods. Environments simulating an ambulance compartment were created for the experiment. NSS temperatures were continuously recorded inside a standard commercial cooler with or without ice packs (IPs) under one of three scenarios: ambient room temperature (25°C) without (IPs), ambient room temperature with IPs and 50°C ambient temperature with IPs. Four trials under each condition were performed. Time to warm to 4°C was compared using Kaplan-Meier log rank test. Results. In a room temperature environment with IPs, the NSS warmed to 4°C in a mean interval of 29 hrs 53 mins versus in ambient room temperature without IPs (1 hr 21 mins) versus in constant hot environment of 50°C with IPs (10 hrs 50 mins). A significant difference was found between the three environments (log-rank =17.90, dF =2, p =0.0001). Conclusions. Low technology methods in the form of a cooler and IPs can provide cold NSS storage for longer than a full 24 hour shift in a room temperature ambulance. In hot ambient conditions, 4°C NSS can be maintained for nearly 11 hours using this method. This model exhibits an economical, easily deployable cold saline storage unit.

3,4-Methylenedioxymethamphetamine (MDMA) produces acute dopamine and 5-HT release in rat brain and a hyperthermic response, which is dependent on the ambient room temperature in which the animal is housed. We examined the effect of ambient room temperature (20 and 30 degrees C) on MDMA-induced dopamine and 5-HT efflux in the striatum and shell of nucleus accumbens (NAc) of freely moving rats by using microdialysis. Locomotor activity and rectal temperature were also evaluated. In the NAc, MDMA (2.5 or 5 mg/kg, i.p.) produced a substantial increase in extracellular dopamine, which was more marked at 30 degrees C. 5-HT release was also increased by MDMA given at 30 degrees C. In contrast, MDMA-induced extracellular dopamine and 5-HT increases in the striatum were unaffected by ambient temperature. At 20 degrees C room temperature, MDMA did not modify the rectal temperature but at 30 degrees C it produced a rapid and sustained hyperthermia. MDMA at 20 degrees C room temperature produced a two-fold increase in activity compared with saline-treated controls. The MDMA-induced increase in locomotor activity was more marked at 30 degrees C due to a decrease in the activity of the saline-treated controls at this high ambient temperature. These results show that high ambient temperature enhances MDMA-induced locomotor activity and monoamine release in the shell of NAc, a region involved in the incentive motivational properties of drugs of abuse, and suggest that the rewarding effects of MDMA may be more pronounced at high ambient temperature.

Objective. Research over the last decade has supported the use of cold intravenous (IV) fluid as a method for initiating therapeutic hypothermia in post–cardiac arrest resuscitation. However, prehospital care programs employing this treatment have encountered various difficulties. Barriers to prehospital induced hypothermia (IH) protocols include the lack of effective or economically reasonable methods to maintain cold saline in the field. Validation of a simple method could allow agencies to equip numerous rigs with cold saline. The aim of this study was to determine whether a standard commercial cooler can maintain two 1-L normal saline solution (NSS) bags below 4°C in three different environments. Methods. Environments simulating those of an ambulance compartment were created for the experiment. NSS temperatures were continuously recorded inside a standard commercial cooler under one of three scenarios: ambient room temperature (25°C) without ice packs, ambient room temperature with ice packs, and 50°C ambient temperature with ice packs. Four trials under each condition were performed. Results. In a room-temperature environment without ice packs, the NSS warmed to 4°C in a mean interval of 1 hour 21 minutes. Using room temperature with ice packs, the NSS warmed to 4°C in a mean interval of 29 hours 53 minutes. In a constant hot environment of 50°C, the NSS warmed to 4°C in a mean interval of 10 hours 50 minutes. A significant difference was found between the three environments (log-rank = 17.90, df = 2, p = 0.0001). Conclusions. Prehospital refrigeration devices are needed for current and future IH protocols. Low-technology methods in the form of a cooler and ice packs can provide cold saline storage for longer than a full 24-hour shift in a room-temperature ambulance. In extremely hot conditions, 4°C NSS can be maintained for nearly 11 hours using this method. This model exhibits an economical, easily deployable cold saline storage unit.

Room temperature in scientific protocols and experiments should be defined: a reproducibility issue.

1 The effect of morphine (10 or 20 mg/kg s.c.), pethidine (25 or 50 mg/kg s.c.) or methadone (4 or 8 mg/kg s.c.) on the body temperature of nontreated and p-chlorophenylalanine-pretreated rats was studied at room (21+/-0.2 degrees C) or low ambient (12+/-0.2 degrees C) temperature. 2 Neither pethidine nor smaller doses of morphine and methadone altered the mean rectal temperature of rats kept at room temperature but larger doses of morphine and methadone produced significant hypothermia. 3 All narcotic analgesics at doses used in the present investigation produced significant hypothermia in rats maintained in a low ambient temperature. The hypothermia was prevented by naloxone (1 mg/kg s.c.). 4 The administration of p-chlorophenylalanine (PCPA, 320 mg/kg i.p.) 48 h before the narcotic injection prevented the fall in body temperature both at room and low ambient temperature. 5 The administration of narcotic analgesics at doses, which when administered by themselves did not alter the body temperature of rats, produced significant hyperthermia in rats pretreated with PCPA. 6 When rats pretreated with PCPA were given 5-hydroxytryptophan (75 mg/kg s.c.) 30 min before narcotic administration, the usual response to narcotics was restored. 7 It appears that pethidine and methadone as well as morphine have both hyperthermic and hypothermic actions in rats and that 5-hydroxytryptamine may be involved in the narcotic-induced hypothermia not only at room temperature but also at low ambient temperature.

Control of heat flow in both near and far field through thermal radiation is of fundamental interest for applications in thermal management and energy conversion. One challenge is how we can realize high contrast control of heat flow with high temporal frequencies and without moving parts. We try to resolve this problem and propose two schemes in the near field: one based on electrical tuning of silicon and the other based on optical pumping of doped silicon slabs. Both methods rely on the change of free carriers, leading to tuning of the plasma frequency, resulting in modulation of near-field thermal radiation. Calculations based on fluctuational electrodynamics show that the electric method gives 10% tuning range. On the other hand, heat transfer coefficient between two silicon films can be tuned from near zero to 600 Wm-2K-1 with a gap distance of 100 nm at room temperature with the optical pumping method. In the far field, we predict and demonstrate two spectrally selective absorbers based on semiconductors, by utilizing their band gap properties and dedicated photonic structure design. The germanium photonic crystals have around 95% absorption from 500 nm to 1000 µm and over 0.9 over the entire visible and near infrared spectrum. The effective absorptivity is as high as 0.91. The black silicon achieves 100% absorption for light with wavelength under 1 µm. The effective absorptivity is as high as 0.96. Field test shows that black silicon is able to maintain at 130 degrees Celcius under unconcentrated condition. Another interesting topic is to achieve over 100 Wm-2 electricity-free cooling power density with simple fabrication method by passive radiative cooling under direction sunlight. We theoretically predicted three schemes for achieving this goal and experimentally demonstrate that a polymer-coated fused silica mirror, as a near-ideal black-body in the mid-infrared and near-ideal reflector in the solar spectrum, achieves radiative cooling below ambient air temperature under direct sunlight (8.2 °C) and at night (8.4 °C). Its performance exceeds that of a multi-layer thin film stack fabricated using vacuum deposition methods by nearly 3 °C. Furthermore, we estimate the cooler has an average net cooling power of about 127 Wm-2 during daytime at ambient temperature, more than twice that reported previously, even considering the significant influence of external conduction and convection. Our work demonstrates that abundant materials and straight-forward fabrication can be used to achieve daytime radiative cooling, advancing applications such as dry cooling of thermal power plants.

Effects of ambient humidity and temperature on the NO2 sensing characteristics of WS2/graphene aerogel