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IntroductionThere has been a resurgence in nicotine inhalation in adolescents due to the popularity and availability of Electronic Nicotine Delivery Systems (ENDS). Almost five times as many US high-school seniors inhale nicotine vapor daily compared with those who smoke tobacco. This study was conducted to determine the impact of repeated adolescent vapor inhalation of nicotine on behavior in adulthood.MethodsMale and female Sprague-Dawley rats were exposed to 30-minute sessions of ENDS vapor inhalation, twice daily, from post-natal day (PND) 31-40. Conditions included vapor from the propylene glycol (PG) vehicle or nicotine (30 mg/mL in the PG). Animals were assessed for effects of nicotine on open field (PND 74-105) and wheel activity (PND 126-180) and for volitional exposure to nicotine vapor (PND 285-395). Plasma nicotine and cotinine were assessed in separate groups of male and female Wistar and Sprague-Dawley rats after a single nicotine inhalation session.ResultsGroup mean plasma nicotine ranged from 39 to 59 ng/mL post-session with minimal strain differences detected. Adolescent nicotine exposure enhanced sensitivity to the locomotor stimulating effects of nicotine (0.1-0.8 mg/kg, s.c.) in an open field in female rats, but didn't change the effects of nicotine on wheel activity. Female rats exposed to nicotine (30 mg/mL) vapor as adolescents responded more vigorously than PG-exposed females to nicotine vapor in a fixed ratio 5 challenge.ConclusionsRepeated adolescent nicotine vapor inhalation leads to enhanced liability for volitional exposure to nicotine vapor in adulthood in female rats, but minimal change in spontaneous locomotor behavior.ImplicationsThese results show that adolescent vaping of nicotine can lead to lasting sensitization to the effects of nicotine in adulthood, including volitional responding for nicotine vapor. Demonstration of this in a controlled animal model establishes causality in a manner not possible from longitudinal evidence in human populations. These findings further highlight the importance of decreasing adolescent nicotine exposure to e-cigarettes to reduce consumption in adulthood.

Abstract: Introduction: There has been a recent resurgence in nicotine inhalation in adolescents due to the popularity and availability of Electronic Nicotine Delivery Systems (ENDS). Almost five times as many US high-school seniors inhale nicotine vapor daily compared with those who smoke tobacco. This study was conducted to determine the impact of repeated adolescent vapor inhalation of nicotine on behavior in adulthood. Methods: Male and female Sprague-Dawley rats were exposed to 30-minute sessions of ENDS vapor inhalation, twice daily, from Post-Natal Day (PND) 31 to PND 40. Conditions included vapor from the propylene glycol (PG) vehicle or nicotine (30 mg/mL in the PG). Animals were assessed for effects of nicotine on open field (PND 74-105) and wheel activity (PND 126-180) and for the self-administration of nicotine vapor (PND 285-395). Plasma levels of nicotine and cotinine were assessed in separate groups of male and female Wistar and Sprague-Dawley rats after a single nicotine inhalation session. Results: Group mean plasma nicotine ranged from 39 to 59 ng/mL post-session with minimal strain differences detected. Adolescent nicotine exposure modestly enhanced sensitivity to the locomotor stimulating effects of nicotine (0.1-0.8 mg/kg, s.c.) in an open field in female rats, but didn’t change effects of nicotine on wheel activity. Female rats exposed to nicotine (30 mg/mL) vapor as adolescents responded more vigorously than PG exposed females for nicotine vapor in a FR5 challenge. Conclusions: Repeated adolescent nicotine vapor inhalation leads to enhanced liability for nicotine self-administration in adulthood in female rats, but minimal change in spontaneous locomotor behavior.

Introduction The fragility and sensitivity of the skin in people with albinism (PWA) have necessitated extensive research across molecular genetics, dermatology, and cosmetology. These efforts aim to address the increased susceptibility of albino skin to sun damage and dermatological conditions. Purpose This study investigates the dermatological efficacy of two galenic formulations, one based on Mathesia and the other on Curcuma longa L. (Zingiberaceae) oil, assessing their antimicrobial, anti-inflammatory, and photoprotective properties for the skin of PWA. Methods Using freeze-drying techniques for Mathesia and slight modifications of Sahouli et al.'s method for extracting Curcuma longa L. oil, we developed two creams. Their macroscopic properties, pH levels, and tyrosine concentrations were analyzed. UV-visible spectrophotometry determined their sun protection factor (SPF). An antibiogram test assessed their antimicrobial activity, and a clinical test evaluated their efficacy on PWA with and without skin conditions. Results The study revealed that both creams had good texture and appropriate pH levels. However, neither cream provided sufficient photoprotection for the sensitive skin of PWA. The Mathesia-based cream demonstrated a higher antimicrobial efficacy compared to the turmeric oil-based and neutral creams. Clinical tests showed 75% of participants had very satisfactory results, with the turmeric oil-based cream showing the most significant overall efficacy. Conclusion The creams exhibited beneficial antimicrobial and anti-inflammatory properties but were inadequate for UV protection of albino skin. Future research should focus on increasing active ingredient concentrations or exploring alternative plants to enhance tyrosine content and SPF values, potentially offering better protection and therapeutic effects for PWA.

Preventing, reducing, and improving infection control have been struggles that have preoccupied the World Health Organization for many years. The present study aims to evaluate the efficacy of Bactigel hydro-alcoholic gel on the cutaneous flora of hands. The study was conducted by interviewing people on their knowledge and use of hydro-alcoholic products and culture of palm flora samples before and after hand disinfection. Results showed that 90% of respondents knew about hydro-alcoholic products, 96.3% of whom had already used them, and 92.3% were still used. In addition, 90% do not have alcohol-sensitive skin, and 80% use soap and water with soap for hygiene in their homes. Bactigel significantly reduced the microbial load on palms by 90.04%. Based on these results, Bactigel hydro-alcoholic gel is effective against skin germs. It is concluded that Bactigel can only be effective in the community when compliance is good hand hygiene.

RationaleOpioids are effective medications, but they have several key limitations including the development of tolerance, establishment of dependence, diversion for non-medical use, and the development of addiction. Therefore, any drugs which act in an additive or synergistic fashion with opioids to address medical applications have the potential to reduce opioid-related harms.ObjectivesTo determine if heroin and Δ9-tetrahydrocannabinol (THC) interact in an additive or independent manner to alter nociception, body temperature, and spontaneous locomotor activity when inhaled or injected.MethodsGroups of female and male rats, implanted with radiotelemetry transmitters, were exposed to vapor generated from heroin (50 mg/mL in propylene glycol vehicle; PG), THC (50 mg/mL), or the combination for assessment of effects on temperature and activity. Thermal nociception was assessed with a warm water tail-withdrawal assay.ResultsHeroin inhalation increased temperature and activity whereas THC inhalation decreased temperature and activity in both female and male Sprague-Dawley rats. Effects of combined inhalation were in opposition, and additional experiments found the same outcome for the injection of heroin (0.5 mg/kg, s.c.) and THC (10 mg/kg, i.p.) alone and in combination. In contrast, the co-administration of heroin and THC by either inhalation or injection produced additive effects on thermal nociception in both male and female Sprague-Dawley and Wistar rats.ConclusionsThis study shows that additive effects of THC with an opioid on a medical endpoint such as analgesia may not generalize to other behavioral or physiological effects, which may be a positive outcome for unwanted side effects.

Introduction Oxidative stress and antibiotic resistance are currently a major public health problem; hence, the search for new sources of anti-infective agents is essential. Purpose The aim of the present study was to determine the micrographic profile of Solanum lycopersicum leaves and Curcuma longa rhizomes; and to evaluate the bio-optimisation of the antioxidant and antibacterial activity of Solanum lycopersicum by association with Curcuma longa extract. Methods The powder was observed using the Steimetz reagent, while antibacterial activity was assessed using the microdilution method in a liquid medium, and antioxidant activity was assessed using the free radical scavenging test with DPPHº and ABTS. Results The study showed that the powders of these two species have characteristic elements such as starch grains, fragments of spiral vessels, etc. The antioxidant power of the combination of extracts was greater than that recorded with Solanum lycopersicum alone, at the same concentrations, by the two tests used. The antibacterial activity revealed that the synergy of extracts from these two plants was effective against most of the strains tested, even at very low doses in some cases. Conclusion These results provide a basis for validating combinations of different plant extracts in the pharmacopoeia of the Democratic Republic of the Congo.

Summary: Background: Robustly examining associations between long-term conditions may be important in identifying opportunities for intervention in multimorbidity but is challenging when evidence is limited. We have developed a Bayesian inference framework that is robust to sparse data and used it to quantify morbidity associations in the oldest old, a population with limited available data. Methods: We conducted a retrospective cross-sectional study of a representative dataset of primary care patients in Scotland as of March 2007. We included 40 long-term conditions and studied their associations in 12,009 individuals aged 90 and older, stratified by sex (3039 men, 8970 women). We analysed associations obtained with Relative Risk (RR), a standard measure in the literature, and compared them with our proposed measure, Associations Beyond Chance (ABC). To enable a broad exploration of interactions between long-term conditions, we built networks of association and assessed differences in their analysis when associations are estimated by RR or ABC. Findings: Our Bayesian framework was appropriately more cautious in attributing association when evidence is lacking, particularly in uncommon conditions. This caution in reporting association was also present in reporting differences in associations between sex and affected the aggregated measures of multimorbidity and network representations. Interpretation: Incorporating uncertainty into multimorbidity research is crucial to avoid misleading findings when evidence is limited, a problem that particularly affects small but important subgroups. Our proposed framework improves the reliability of estimations of associations and, more in general, of research into disease mechanisms and multimorbidity. Funding: National Institute for Health and Care Research.

Abstract Background After decades of success in reducing malaria through the scale-up of pyrethroid long-lasting insecticidal nets (LLINs), the decline in the malaria burden has stalled, coinciding with the rapid spread of pyrethroid resistance. In a previously reported study, nets treated with a pyrethroid and a synergist, piperonyl butoxide (PBO), demonstrated superior efficacy compared to standard pyrethroid LLINs (std-LLINs) against malaria. Evidence was used to support the public health recommendation of PBO-Pyrethroid-LLIN by the World Health Organization in 2018. This study looks at the third year of rollout of these nets in Muleba district, Tanzania to inform whether policy guidelines need to be updated. Methods A four-group cluster randomized trial (CRT) using a two-by-two factorial design was carried out between January 2014 and December 2017. A total of 48 clusters, were randomized in a 1:1:1:1 ratio to the following treatment groups, each intervention being provided once in 2015: 1/std-LLIN; 2/PBO-pyrethroid LLIN; 3/std-LLIN + Indoor Residual Spraying (IRS) and 4/PBO-Pyrethroid-LLIN + IRS. During the third year follow-up, malaria infection prevalence in 80 children per cluster, aged 6 months to 14 years, was measured at 28- and 33-months post-intervention and analysed as intention-to-treat (ITT) and per protocol (PP). Mosquito collections were performed monthly in all clusters, using CDC light traps in 7 randomly selected houses per cluster. Results At 28 and 33 months, study net usage among household participants was only 47% and 31%, respectively. In ITT analysis, after 28 months malaria infection prevalence among 7471 children was 80.9% in the two std-LLIN groups compared to 69.3% in the two PBO-Pyrethroid-LLIN (Odds Ratio: 0.45, 95% Confidence Interval: 0.21–0.95, p-value: 0.0364). After 33 months the effect was weaker in the ITT analysis (prevalence 59.6% versus 49.9%, OR: 0.60, 95%CI:0.32–1.13, p-value: 0.1131) but still evident in the PP analysis (57.2% versus 44.2%, OR: 0.34, 95%CI: 0.16–0.71, p-value: 0.0051). Mean number of Anopheles per night collected per house was similar between PBO-Pyrethroid-LLIN groups (5.48) and std-LLIN groups (5.24) during the third year. Conclusions Despite low usage of PBO- Pyrethroid LLIN, a small impact of those nets on malaria infection prevalence was still observed in the 3rd year with the most protection offered to children still using them. To maximize impact, it is essential that net re-distribution cycles are aligned with this LLIN lifespan to maintain maximum coverage. Trial registration: The trial was registered with ClinicalTrials.gov (registration number NCT02288637).

Changes in pollutant concentrations in environmental media occur both from pollutant transport in water or air and from local processes, such as adsorption, degradation, precipitation, straining, and so on. The terms "fate and transport" and "transport and fate" reflect the coupling of moving with the carrier media and biogeochemical processes describing local transformations or interactions. The Journal of Environmental Quality (JEQ) was one of the first to publish papers on fate and transport (F&T). This paper is a minireview written to commemorate the 50th anniversary of JEQ and show how the research interests, methodology, and public attention have been reflected in fate and transport publications in JEQ during the last 40 years. We report the statistics showing how the representation of different pollutant groups in papers changed with time. Major focus areas have included the effect of solution composition on F&T and concurrent F&T, the role of organic matter, and the relative role of different F&T pathways. The role of temporal and spatial heterogeneity has been studied at different scales. The value of long-term F&T studies and developments in modeling as the F&T research approach was amply demonstrated. Fate and transport studies have been an essential part of conservation measure evaluation and comparison and ecological risk assessment. For 50 years, JEQ has delivered new insights, methods, and applications related to F&T science. The importance of its service to society is recognized, and we look forward to new generations of F&T researchers presenting their contributions in JEQ.

The α-pyrrolidino-phenone cathinone stimulants first came to widespread attention because of bizarre behavior consequent to the use of α-pyrrolidinopentiophenone (α-PVP, "flakka") reported in popular press. As with other designer drugs, diversification of cathinones has been driven by desirable subjective effects, but also by attempts to stay ahead of legal controls of specific molecules. The α-pyrrolidinohexiophenone (α-PHP) and α-pyrrolidinopropiophenone (α-PPP) compounds have been relatively under-investigated relative to α-PVP and provide a key opportunity to also investigate structure-activity relationships, i.e., how the extension of the alpha carbon chain may affect potency or efficacy. Female rats were used to contrast the effects of α-PHP and α-PPP with those of α-PVP in altering wheel activity and effects on spontaneous locomotion, temperature and intracranial self-stimulation reward. The α-PPP, α-PHP and α-PVP compounds (5, 10 mg/kg, i.p.) suppressed wheel activity. Inhalation of α-PHP or α-PVP also suppressed wheel activity, but for an abbreviated duration compared with the injection route. Spontaneous activity was increased, and brain reward thresholds decreased, in a dose-dependent manner by all three compounds; only small decrements in body temperature were observed. These data show that all three of the α-pyrrolidino-phenone cathinones exhibit significant stimulant-like activity in female rats. Differences were minor and abuse liability is therefore likely to be equivalent for all three α-pyrrolidino-phenones.

Background and purposeThe extra medical use of, and addiction to, prescription opioid analgesics is a growing health problem. To characterize how prescription opioid abuse develops, this study investigated the affective consequences of escalating prescription opioid use using intracranial self-stimulation (ICSS) reward and oxycodone intravenous self-administration (IVSA) models.Experimental approachMale Wistar rats were given access to oxycodone IVSA (0.15 mg·kg-1 per infusion, i.v.) in short-access (ShA; 1 h) or long-access (LgA; 12 h) sessions for five sessions per week followed by intermittent 60-h discontinuations from drug access, a novel explicit test of the negative reinforcement hypothesis. Separate groups were first trained in the ICSS procedure and then in oxycodone IVSA in 11-h LgA sessions.Key resultsRats given LgA to oxycodone escalated their responding more than ShA rats, with further significant increases observed following each 60-h discontinuation. Presession brain reward thresholds increased with sequential daily LgA IVSA sessions, consistent with a growing negative affective state consequent to successive daily intoxication/abstinence cycles. A 1-h oxycodone IVSA interval was sufficient to normalize these elevated reward thresholds, as was, paradoxically, a 60-h weekend abstinence. The increase in ICSS thresholds was attenuated in a group treated with the long-acting κ-opioid antagonist norbinaltorphimine prior to IVSA training.Conclusion and implicationsChanges in brain reward function during escalation of oxycodone self-administration are driven by an interplay between κ-opioid receptor-mediated negative affective state associated with escalated oxycodone intake and dynamic restoration of brain reward status during longer periods of abstinence.

RationaleDespite a long history of use in synaptic physiology, the lobster has been a neglected model for behavioral pharmacology. A restaurateur proposed that exposing lobster to cannabis smoke reduces anxiety and pain during the cooking process. It is unknown if lobster gill respiration in air would result in significant Δ9-tetrahydrocannabinol (THC) uptake and whether this would have any detectable behavioral effects.ObjectiveThe primary goal was to determine tissue THC levels in the lobster after exposure to THC vapor. Secondary goals were to determine if THC vapor altered locomotor behavior or nociception.MethodsTissue samples were collected (including muscle, brain and hemolymph) from Homarus americanus (N = 3 per group) following 30 or 60 min of exposure to vapor generated by an e-cigarette device using THC (100 mg/mL in a propylene glycol vehicle). Separate experiments assessed locomotor behavior and hot water nociceptive responses following THC vapor exposure.ResultsTHC vapor produced duration-related THC levels in all tissues examined. Locomotor activity was decreased (distance, speed, time-mobile) by 30 min inhalation of THC. Lobsters exhibit a temperature-dependent withdrawal response to immersion of tail, antennae or claws in warm water; this is novel evidence of thermal nociception for this species. THC exposure for 60 min had only marginal effect on nociception under the conditions assessed.ConclusionsVapor exposure of lobsters, using an e-cigarette based model, produces dose-dependent THC levels in all tissues and reduces locomotor activity. Hot water nociception was temperature dependent, but only minimal anti-nociceptive effect of THC exposure was confirmed.

Abstract Background The efficacy of immunization against an airborne pathogen depends in part on its ability to induce antibodies at the major entry site of the virus, the mucosa. Recent studies have revealed that mucosal immunity is poorly activated after vaccination with messenger RNA vaccines, thus failing in blocking virus acquisition upon its site of initial exposure. Little information is available about the induction of mucosal immunity by inactivated and recombinant coronavirus disease 2019 (COVID‐19) vaccines. This study aims to investigate this topic. Methods Saliva and plasma samples from 440 healthy Congolese were collected including (1) fully vaccinated 2 month postvaccination with either an inactivated or a recombinant COVID‐19 vaccine and (2) nonvaccinated control group. Total anti‐severe acute respiratory syndrome coronavirus 2 receptor‐binding domain IgG and IgA antibodies were assessed using in‐house enzyme‐linked immunosorbent assays for both specimens. Findings Altogether, the positivity of IgG was significantly higher in plasma than in saliva samples both in vaccinated and nonvaccinated control groups. Inversely, IgA positivity was slightly higher in saliva than in plasma of vaccinated group. The overall IgG and IgA levels were respectively over 103 and 14 times lower in saliva than in plasma samples. We found a strong positive correlation between IgG in saliva and plasma also between IgA in both specimens (r = .70 for IgG and r = .52 for IgA). Interestingly, contrary to IgG, the level of salivary IgA was not different between seropositive control group and seropositive vaccinated group. No significant difference was observed between recombinant and inactivated COVID‐19 vaccines in total IgG and IgA antibody concentration release 2 months postvaccination both in plasma and saliva. Conclusion Inactivated and recombinant COVID‐19 vaccines in use in the Republic of Congo poorly activated mucosal IgA‐mediated antibody response 2 months postvaccination.

RationaleOpioids are effective medications, but they have several key limitations including the development of tolerance, establishment of dependence, diversion for non-medical use, and the development of addiction. Therefore, any drugs which act in an additive or synergistic fashion with opioids to address medical applications have the potential to reduce opioid-related harms.ObjectivesTo determine if heroin and Δ9-tetrahydrocannabinol (THC) interact in an additive or independent manner to alter nociception, body temperature, and spontaneous locomotor activity when inhaled or injected.MethodsGroups of female and male rats, implanted with radiotelemetry transmitters, were exposed to vapor generated from heroin (50 mg/mL in propylene glycol vehicle; PG), THC (50 mg/mL), or the combination for assessment of effects on temperature and activity. Thermal nociception was assessed with a warm water tail-withdrawal assay.ResultsHeroin inhalation increased temperature and activity whereas THC inhalation decreased temperature and activity in both female and male Sprague-Dawley rats. Effects of combined inhalation were in opposition, and additional experiments found the same outcome for the injection of heroin (0.5 mg/kg, s.c.) and THC (10 mg/kg, i.p.) alone and in combination. In contrast, the co-administration of heroin and THC by either inhalation or injection produced additive effects on thermal nociception in both male and female Sprague-Dawley and Wistar rats.ConclusionsThis study shows that additive effects of THC with an opioid on a medical endpoint such as analgesia may not generalize to other behavioral or physiological effects, which may be a positive outcome for unwanted side effects.

Male rats escalate intravenous self-administration of entactogen psychostimulants, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxymethamphetamine (MDMA) under extended access conditions, as with typical psychostimulants. Here, we investigated whether female rats escalate self-administration of methylone, 3,4-methylenedioxypentedrone (pentylone), and MDMA and then studied consequences of MDMA and pentylone self-administration on GABAA receptor and kappa opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA), a brain area critically dysregulated by extended access self-administration of alcohol or cocaine. Adult female Wistar rats were trained to self-administer methylone, pentylone, MDMA (0.5 mg/kg/infusion), or saline-vehicle using a fixed-ratio 1 response contingency in 6-h sessions (long-access: LgA) followed by progressive ratio (PR) dose-response testing. The effects of pentylone-LgA, MDMA-LgA and saline on basal GABAergic transmission (miniature post-synaptic inhibitory currents, mIPSCs) and the modulatory role of KOR at CeA GABAergic synapses were determined in acute brain slices using whole-cell patch-clamp. Methylone-LgA and pentylone-LgA rats similarly escalated their drug intake (both obtained more infusions compared to MDMA-LgA rats), however, pentylone-LgA rats reached higher breakpoints in PR tests. At the cellular level, baseline CeA GABA transmission was markedly elevated in pentylone-LgA and MDMA-LgA rats compared to saline-vehicle. Specifically, pentylone-LgA was associated with increased CeA mIPSC frequency (GABA release) and amplitude (post-synaptic GABAA receptor function), while mIPSC amplitudes (but not frequency) was larger in MDMA-LgA rats compared to saline rats. In addition, pentylone-LgA and MDMA-LgA profoundly disrupted CeA KOR signaling such as both KOR agonism (1 mM U50488) and KOR antagonism (200 nM nor-binaltorphimine) decreased mIPSC frequency suggesting recruitment of non-canonical KOR signaling pathways. This study confirms escalated self-administration of entactogen psychostimulants under LgA conditions in female rats which is accompanied by increased CeA GABAergic inhibition and altered KOR signaling. Collectively, our study suggests that CeA GABA and KOR mechanisms play a critical role in entactogen self-administration like those observed with escalation of alcohol or cocaine self-administration.

Over the last two decades the United States has experienced a significant increase in the medical and non-medical use of opioid drugs, resulting in record numbers of opioid-related overdoses and deaths. There was an initial increase in non-medical use of prescription opioids around 2002, followed later by increased heroin use and then most recently fentanyl. Inhalation is a common route of administration for opioids, with a documented history spanning back to Mediterranean antiquity and up through modern use with e-cigarette devices. Unfortunately, preclinical studies using inhalation as the route of administration remain relatively few. This study was conducted to determine the efficacy of e-cigarette vapor inhalation of heroin in rats. Non-contingent exposure to heroin or methadone vapor produced anti-nociceptive efficacy in male and female rats. Female rats were trained to self-administer heroin vapor; the most-preferring half of the distribution obtained more vapor reinforcers when the concentration of heroin was reduced in the vapor vehicle and when pre-treated with the opioid receptor antagonist naloxone. The anti-nociceptive effect of heroin self-administered by vapor was identical in magnitude to that produced by intravenous self-administration. Finally, anxiety-like behavior increased 24-48 h after last heroin vapor access, consistent with withdrawal signs observed after intravenous self-administration. In sum, these studies show that rewarding and anti-nociceptive effects of heroin are produced in rats by vapor inhalation using e-cigarette technology. Importantly, self-administration models by this route can be deployed to determine health effects of inhaled heroin or other opioids.

The use of Δ9-tetrahydrocannabinol (THC) by inhalation using e-cigarette technology grows increasingly popular for medical and recreational purposes. This has led to development of e-cigarette based techniques to study the delivery of THC by inhalation in laboratory rodents. Inhaled THC reliably produces hypothermic and antinociceptive effects in rats, similar to effects of parenteral injection of THC. This study was conducted to determine the extent to which the hypothermic response depends on interactions with the CB1 receptor, using pharmacological antagonist (SR141716, AM-251) approaches. Groups of rats were implanted with radiotelemetry devices capable of reporting activity and body temperature, which were assessed after THC inhalation or injection. SR141716 (4 mg/kg, i.p.) blocked or attenuated antinociceptive effects of acute THC inhalation in male and female rats. SR141716 was unable to block the initial hypothermia caused by THC inhalation, but temperature was restored to normal more quickly. Alterations in antagonist pre-treatment time, dose and the use of a rat strain with less sensitivity to THC-induced hypothermia did not change this pattern. Pre-treatment with SR141716 (4 mg/kg, i.p.) blocked hypothermia induced by i.v. THC and reversed hypothermia when administered 45 or 90 min after THC (i.p.). SR141716 and AM-251 (4 mg/kg, i.p.) sped recovery from, but did not block, hypothermia caused by vapor THC in female rats made tolerant by prior repeated THC vapor inhalation. The CB2 antagonist AM-630, had no effect. These results suggest that hypothermia consequent to THC inhalation is induced by other mechanisms in addition to CB1 receptor activation.

Background and purposeAdolescents are regularly exposed to ∆9 -tetrahydrocannabinol (THC) via smoking and, more recently, vaping cannabis extracts. Growing legalization of cannabis for medical and recreational purposes, combined with decreasing perceptions of harm, makes it increasingly important to determine the consequences of frequent adolescent exposure for motivated behaviour and lasting tolerance in response to THC.Experimental approachesMale and female rats inhaled THC vapour, or that from the propylene glycol (PG) vehicle, twice daily for 30 min from postnatal day (PND) 35-39 and PND 42-46 using an e-cigarette system. Thermoregulatory responses to vapour inhalation were assessed by radio-telemetry during adolescence and from PND 86-94. Chow intake was assessed in adulthood. Blood samples were obtained from additional adolescent groups following initial THC inhalation and after 4 days of twice daily exposure. Additional groups exposed repeatedly to THC or PG during adolescence were evaluated for intravenous self-administration of oxycodone as adults.Key resultsFemale, not male, adolescents developed tolerance to the hypothermic effects of THC inhalation in the first week of repeated exposure despite similar plasma THC levels. Each sex exhibited tolerance to THC hypothermia in adulthood after repeated adolescent THC. However, enhanced potency was found in females. Repeated THC male rats consumed more food than their PG-treated control group, without significant bodyweight differences. Adolescent THC did not alter oxycodone self-administration in either sex but increased fentanyl self-administration in females.Conclusions and implicationsRepeated THC vapour inhalation in adolescent rats has lasting consequences observable in adulthood.

Emergence of the Omicron BA.1/2 SARS-CoV-2 subvariants led to a wave of infection South Africa. Here, the authors use serological data from a prospective household study to characterise infection rates in the context of diverse immune histories following vaccination and exposure to different variants.

South Africa has experienced 4 waves of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, the fourth dominated by the Omicron variant of concern (1). Data on the proportion of [...]

Background Survival and gonotrophic cycle duration are important determinants of the vectorial capacity of malaria vectors but there are a limited number of approaches to estimate these quantities from field data. Time-series of observations of mosquitoes at different stages in the life-cycle are under-used. Methods Anopheles funestus mosquitoes were caught using various methods over a 7.6-year period in Furvela, Mozambique. Survival and oviposition cycle duration were estimated using (i) an existing time-series approach for analysing dissections of mosquitoes caught in light-traps, extended to allow for variability in the duration of the cycle; (ii) an established approach for estimating cycle duration from resting collection data; (iii) a novel time-series approach fitted to numbers and categories of mosquitoes caught in exit-traps. Results Data were available from 7,396, 6,041 and 1,527 trap-nights for exit-traps, light-traps and resting collections respectively. Estimates of cycle duration varied considerably between the different methods. The estimated proportion of female mosquitoes surviving each day of 0.740 (95% credible interval [0.650–0.815]) derived from light-trap data was much lower than the estimated daily survival of male mosquitoes from the model fitted to exit-trap data (0.881, 95% credible interval [0.747–0.987]). There was no tendency for the oviposition cycle to become shorter at higher temperature while the odds of survival of females through the cycle was estimated to be multiplied by 1.021 for every degree of mean weekly temperature increase (95% credible interval [0.991–1.051]). There was negligible temperature dependence and little inter-annual variation in male survival. Discussion The time-series approach fitted to the exit-traps suggests that male An. funestus have higher survival than do females, and that male survival was temperature independent and unaffected by the introduction of long-lasting insecticidal nets (LLINs). The patterns of temperature dependence in females are at variance with results of laboratory studies. Time series approaches have the advantage for estimating survival that they do not depend on representative sampling of mosquitoes over the whole year. However, the estimates of oviposition cycle duration were associated with considerable uncertainty, which appears to be due to variability between insects in the duration of the resting period, and the estimates based on exit-trap data are sensitive to assumptions about relative trapping efficiencies.