Helping Others Facilitates Well-Being for Indigenous Peoples Living With HIV/AIDS in Canada.

Research has found that helping others facilitates well-being for Indigenous peoples living with HIV and AIDS, but limited research exists that investigates the mechanism(s) underlying this relationship. Indigenous perspectives posit that helping others facilitates well-being through the development of an individual's spiritual, physical, emotional, and mental aspects (four aspects). Similarly, self-determination theory posits that helping others facilitates well-being by satisfying basic psychological needs. In the present study, we examined if helping others facilitates well-being through the fulfillment of the spiritual, physical, emotional, and mental aspects among Indigenous peoples living with HIV and AIDS. We used a convergent parallel mixed methods design, coupled with a community-engaged approach grounded in the United Nations Greater Involvement of People Living with HIV and AIDS principles and Indigenous and decolonizing research methodologies. Survey (n = 117) and interview data (n = 9) collected by an Indigenous-led HIV/AIDS organization in Canada were employed to examine the relationship between helping, the four aspects, and well-being. Participants were primarily First Nations leaders and mentors who live with HIV/AIDS, with some Métis and Inuit. A parallel multiple mediation model and reflexive thematic analysis were used to analyze the relationship between helping, the four aspects, and well-being. Mixed-methods findings support the idea that helping others promotes well-being by fulfilling the emotional and mental aspects. Qualitative findings demonstrated this relationship for all four aspects. This research may facilitate the development of programs to support Indigenous peoples living with HIV/AIDS well-being and contribute to the literature on integrating Indigenous perspectives and methodologies within psychological research.

The Hunter-8 Scale Prehospital Triage Workflow for Identification of Large Vessel Occlusion and Brain Haemorrhage.

OBJECTIVE: The Hunter-8 prehospital stroke scale predicts large vessel occlusion in hyperacute ischemic stroke patients (LVO) at hospital admission. We wished to test its performance in the hands of paramedics as part of a prehospital triage algorithm. We aimed to determine (a) the proportion of patients identified by the Hunter-8 algorithm, receiving reperfusion therapies, (b) whether a call to stroke team improved this, and (c) performance for LVO detection using an expanded LVO definition. METHODS: A prehospital workflow combining pre-morbid functional status, time from symptom onset, and the Hunter-8 scale was implemented from July 2019. A telephone call to the stroke team was prompted for potential treatment candidates. Classic LVO was defined as a proximal middle cerebral artery (MCA-M1), terminal internal carotid artery, or tandem occlusion. Extended LVO added proximal MCA-M2 and basilar occlusions. RESULTS: From July 2019 to April 2021, there were 363 Hunter-8 activations, 320 analyzed: 181 (56.6%) had confirmed ischemic strokes, 13 (4.1%) transient ischemic attack, 91 (28.5%) stroke mimics, and 35 (10.9%) intracranial hemorrhage. Fifty-two patients (16.3%) received reperfusion therapies, 35 with Hunter-8 ≥ 8. The stroke doctor changed the final destination for 76 patients (23.7%), and five received reperfusion therapies. The AUCs for classic and extended LVO were 0.73 (95% CI 0.66-0.79) and 0.72 (95% CI 0.65-0.77), respectively. CONCLUSION: The Hunter-8 workflow resulted in 28.7% of confirmed ischemic stroke patients receiving reperfusion therapies, with no secondary transfers to the comprehensive stroke center. The role of communication with stroke team needs to be further explored.

Role of neuroimaging before reperfusion therapy. Part 1 - IV thrombolysis - Review.

This review paper summarises the yield of the different imaging modalities in the evaluation of patients for IV thrombolysis. Non-contrast CT and CTA or brain MRI combined with MRA are the recommended sequences for the evaluation of patients within the 4.5 hours time window. Multimodal MRI (DWI/PWI), and more recently, CT perfusion, offer reliable surrogate of salvageable penumbra, the target mismatch, which is now currently used as selection criteria for revascularisation treatment in an extended time window. Those sequences may also help the physician for the management of other limited cases when the diagnosis of acute ischemic stroke is difficult. Another approach the DWI/FLAIR mismatch has been proposed to identify among wake-up stroke patients those who have been experiencing an acute ischemic stroke evolving from less than 4.5hrs. Other biomarkers, such as the clot imaging on MRI and CT, help to predict the recanalisation rate after IVT, while the impact of the presence microbleeds on MRI remains to be determined.

Factors associated with typical enteropathogenic Escherichia coli infection among children <5 years old with moderate-to-severe diarrhoea in rural western Kenya, 2008-2012.

Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37-3.17), and convulsions (aOR 2.83, 95% CI 1.12-7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3-3.6) and wasted (OR 2.5, 95% CI 1.3-4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47-5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.

Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers.

BACKGROUND: Whole-genome sequencing (WGS) is a powerful method for revealing the diversity and complexity of the somatic mutation burden of tumours. Here, we investigated the utility of tumour and matched germline WGS for understanding aetiology and treatment opportunities for high-risk individuals with familial breast cancer. PATIENTS AND METHODS: We carried out WGS on 78 paired germline and tumour DNA samples from individuals carrying pathogenic variants in BRCA1 (n = 26) or BRCA2 (n = 22) or from non-carriers (non-BRCA1/2; n = 30). RESULTS: Matched germline/tumour WGS and somatic mutational signature analysis revealed patients with unreported, dual pathogenic germline variants in cancer risk genes (BRCA1/BRCA2; BRCA1/MUTYH). The strategy identified that 100% of tumours from BRCA1 carriers and 91% of tumours from BRCA2 carriers exhibited biallelic inactivation of the respective gene, together with somatic mutational signatures suggestive of a functional deficiency in homologous recombination. A set of non-BRCA1/2 tumours also had somatic signatures indicative of BRCA-deficiency, including tumours with BRCA1 promoter methylation, and tumours from carriers of a PALB2 pathogenic germline variant and a BRCA2 variant of uncertain significance. A subset of 13 non-BRCA1/2 tumours from early onset cases were BRCA-proficient, yet displayed complex clustered structural rearrangements associated with the amplification of oncogenes and pathogenic germline variants in TP53, ATM and CHEK2. CONCLUSIONS: Our study highlights the role that WGS of matched germline/tumour DNA and the somatic mutational signatures can play in the discovery of pathogenic germline variants and for providing supporting evidence for variant pathogenicity. WGS-derived signatures were more robust than germline status and other genomic predictors of homologous recombination deficiency, thus impacting the selection of platinum-based or PARP inhibitor therapy. In this first examination of non-BRCA1/2 tumours by WGS, we illustrate the considerable heterogeneity of these tumour genomes and highlight that complex genomic rearrangements may drive tumourigenesis in a subset of cases.

Functional advantage of educated KIR2DL1(+) natural killer cells for anti-HIV-1 antibody-dependent activation.

Evidence from the RV144 HIV-1 vaccine trial implicates anti-HIV-1 antibody-dependent cellular cytotoxicity (ADCC) in vaccine-conferred protection from infection. Among effector cells that mediate ADCC are natural killer (NK) cells. The ability of NK cells to be activated in an antibody-dependent manner is reliant upon several factors. In general, NK cell-mediated antibody-dependent activation is most robust in terminally differentiated CD57(+) NK cells, as well as NK cells educated through ontological interactions between inhibitory killer immunoglobulin-like receptors (KIR) and their major histocompatibility complex class I [MHC-I or human leucocyte antigen (HLA-I)] ligands. With regard to anti-HIV-1 antibody-dependent NK cell activation, previous research has demonstrated that the epidemiologically relevant KIR3DL1/HLA-Bw4 receptor/ligand combination confers enhanced activation potential. In the present study we assessed the ability of the KIR2DL1/HLA-C2 receptor/ligand combination to confer enhanced activation upon direct stimulation with HLA-I-devoid target cells or antibody-dependent stimulation with HIV-1 gp140-pulsed CEM.NKr-CCR5 target cells in the presence of an anti-HIV-1 antibody source. Among donors carrying the HLA-C2 ligand for KIR2DL1, higher interferon (IFN)-γ production was observed within KIR2DL1(+) NK cells than in KIR2DL1(-) NK cells upon both direct and antibody-dependent stimulation. No differences in KIR2DL1(+) and KIR2DL1(-) NK cell activation were observed in HLA-C1 homozygous donors. Additionally, higher activation in KIR2DL1(+) than KIR2DL1(-) NK cells from HLA-C2 carrying donors was observed within less differentiated CD57(-) NK cells, demonstrating that the observed differences were due to education and not an overabundance of KIR2DL1(+) NK cells within differentiated CD57(+) NK cells. These observations are relevant for understanding the regulation of anti-HIV-1 antibody-dependent NK cell responses.

Vibriosis, not cholera: toxigenic Vibrio cholerae non-O1, non-O139 infections in the United States, 1984-2014.

Toxigenic strains of Vibrio cholerae serogroups O1 and O139 have caused cholera epidemics, but other serogroups - such as O75 or O141 - can also produce cholera toxin and cause severe watery diarrhoea similar to cholera. We describe 31 years of surveillance for toxigenic non-O1, non-O139 infections in the United States and map these infections to the state where the exposure probably originated. While serogroups O75 and O141 are closely related pathogens, they differ in how and where they infect people. Oysters were the main vehicle for O75 infection. The vehicles for O141 infection include oysters, clams, and freshwater in lakes and rivers. The patients infected with serogroup O75 who had food traceback information available ate raw oysters from Florida. Patients infected with O141 ate oysters from Florida and clams from New Jersey, and those who only reported being exposed to freshwater were exposed in Arizona, Michigan, Missouri, and Texas. Improving the safety of oysters, specifically, should help prevent future illnesses from these toxigenic strains and similar pathogenic Vibrio species. Post-harvest processing of raw oysters, such as individual quick freezing, heat-cool pasteurization, and high hydrostatic pressurization, should be considered.

Social jetlag, obesity and metabolic disorder: investigation in a cohort study.

BACKGROUND: Obesity is one of the leading causes of preventable death worldwide. Circadian rhythms are known to control both sleep timing and energy homeostasis, and disruptions in circadian rhythms have been linked with metabolic dysfunction and obesity-associated disease. In previous research, social jetlag, a measure of chronic circadian disruption caused by the discrepancy between our internal versus social clocks, was associated with elevated self-reported body mass index, possibly indicative of a more generalized association with obesity and metabolic dysfunction. METHODS: We studied participants from the population-representative Dunedin Longitudinal Study (N=1037) to determine whether social jetlag was associated with clinically assessed measurements of metabolic phenotypes and disease indicators for obesity-related disease, specifically, indicators of inflammation and diabetes. RESULTS: Our analysis was restricted to N=815 non-shift workers in our cohort. Among these participants, we found that social jetlag was associated with numerous clinically assessed measures of metabolic dysfunction and obesity. We distinguished between obese individuals who were metabolically healthy versus unhealthy, and found higher social jetlag levels in metabolically unhealthy obese individuals. Among metabolically unhealthy obese individuals, social jetlag was additionally associated with elevated glycated hemoglobin and an indicator of inflammation. CONCLUSIONS: The findings are consistent with the possibility that 'living against our internal clock' may contribute to metabolic dysfunction and its consequences. Further research aimed at understanding that the physiology and social features of social jetlag may inform obesity prevention and have ramifications for policies and practices that contribute to increased social jetlag, such as work schedules and daylight savings time.

Phenotypical and functional profiles of natural killer cells exhibiting matrix metalloproteinase-mediated CD16 cleavage after anti-HIV antibody-dependent activation.

Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) has been linked to protection from HIV infection and slower progression towards AIDS. However, antibody-dependent activation of NK cells results in phenotypical alterations similar to those observed on NK cells from individuals with progressive HIV infection. Activation of NK cells induces matrix metalloproteinase (MMP)-mediated cleavage of cell surface CD16. In the present study we assessed the phenotype and functional profile of NK cells exhibiting post-activation MMP-mediated CD16 cleavage. We found that NK cells achieving the highest levels of activation during stimulation exhibit the most profound decreases in CD16 expression. Further, we observed that educated KIR3DL1(+) NK cells from human leucocyte antigen (HLA)-Bw4-carrying donors exhibit larger decreases in CD16 expression post-activation than the KIR3DL1(-) NK cell subset containing cells educated via other inhibitory receptor/ligand combinations and non-educated NK cells. Lastly, we assessed the ex-vivo expression of CD16 on educated KIR3DL1(+) NK cells and the KIR3DL1(-) NK cell subset from HLA-Bw4-carrying HIV-uninfected and HIV-infected donors. Suggestive of in-vivo activation of KIR3DL1(+) NK cells during HIV infection, CD16 expression was higher on KIR3DL1(+) than KIR3DL1(-) NK cells in uninfected donors but similar on both subsets in HIV-infected donors. These results are discussed in the context of how they may assist with understanding HIV disease progression and the design of immunotherapies that utilize antibody-dependent NK cell responses.

Higher mortality in patients with right hemispheric intracerebral haemorrhage: INTERACT1 and 2.

BACKGROUND AND PURPOSE: Controversy exists over the prognostic significance of the affected hemisphere in stroke. We aimed to determine the relationship between laterality of acute intracerebral haemorrhage (ICH) and poor clinical outcomes. METHODS: A subsidiary analysis of the INTERACT Pilot and INTERACT2 studies--randomised controlled trials of patients with spontaneous acute ICH with elevated systolic blood pressure (BP), randomly assigned to intensive (target systolic BP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Outcomes were the combined and separate end points of death and major disability (modified Rankin scale (mRS) scores of 3-6, 6 and 3-5, respectively) at 90 days. RESULTS: A total of 2708 patients had supratentorial/hemispheric ICH and information on mRS at 90 days. Patients with right hemispheric ICH (1327, 49%) had a higher risk of death at 90 days compared to those with left hemispheric ICH after adjustment for potential confounding variables (OR, 1.77 (95% CI 1.33 to 2.37)). There were no differences between patients with right and left hemispheric ICH regarding the combined end point of death or major disability or major disability in the multivariable-adjusted models (1.07 (0.89 to 1.29) and 0.85 (0.72 to 1.01), respectively). CONCLUSIONS: Right hemispheric lesion was associated with increased risk of death in patients with acute ICH. The laterality of the ICH does not appear to affect the level of disability in survivors. TRIAL REGISTRATION NUMBER: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079.

Cholera in the United States, 2001-2011: a reflection of patterns of global epidemiology and travel.

US cholera surveillance offers insight into global and domestic trends. Between 2001 and 2011, 111 cases were reported to the Centers for Disease Control and Prevention. Cholera was associated with international travel in 90 (81%) patients and was domestically acquired in 20 (18%) patients; for one patient, information was not available. From January 2001 to October 2010, the 42 (47%) travel-associated cases were associated with travel to Asia. In October 2010, a cholera epidemic started in Haiti, soon spreading to the Dominican Republic (Hispaniola). From then to December 2011, 40 (83%) of the 48 travel-associated cases were associated with travel to Hispaniola. Of 20 patients who acquired cholera domestically, 17 (85%) reported seafood consumption; 10 (59%) ate seafood from the US Gulf Coast. In summary, an increase in travel-associated US cholera cases was associated with epidemic cholera in Hispaniola in 2010-2011. Travel to Asia and consumption of Gulf Coast seafood remained important sources of US cholera cases.

Effect of anticholinergics on the overactive bladder and bowel domain of the electronic personal assessment questionnaire (ePAQ).

INTRODUCTION AND HYPOTHESIS: Evidence suggests that OAB (overactive bladder) can occur alongside disorders of the colon, such as irritable bowel syndrome (IBS). Moreover, patients with constipation are more likely to develop OAB symptoms than those without. Anticholinergic medications (AcH) are commonly used for treating OAB, and can result in the unwanted side effects of constipation. We aimed to study the relationship of AcH, and their effects on quality of life using the electronic Personal Assessment Questionnaire (ePAQ) by assessing changes in the bowel and bladder domains, pre- and post-AcH treatment. METHODS: Ninety patients completed the ePAQ pre- and post-AcH treatment from January 2011 to April 2014. Data were collected retrospectively and prospectively, and analysed using a paired t test. Effect size (ES) was calculated for OAB and bowel domains to quantify the effect on QoL. RESULTS: There was a significant improvement in the OAB (p = 0.0005) and bowel domains (p = 0.0005). In the bowel domains, the largest effect size was seen for IBS (0.5) followed by continence (0.4), evacuation (0.375) and a small ES was seen for constipation (0.2). There was a reduction in the "degree of bother" in OAB and bowel domains. CONCLUSIONS: Patients may benefit from the possible effects of AcH on their bowels, and assessment of all aspects of pelvic floor function is important before commencing AcH. This may help to counsel patients, with possibly improved compliance with therapy.

Mutations in EXPH5 result in autosomal recessive inherited skin fragility.

Several different genes have been implicated in the pathophysiology of inherited blistering skin diseases. Recently, autosomal recessive loss-of-function mutations in EXPH5 (encoding exophilin-5, also known as Slac2-b, a protein involved in intracellular vesicle transport) were identified in a new mechanobullous disease resembling a form of epidermolysis bullosa simplex (EBS). Here, we searched for mutations in EXPH5 in a 4-year-old white boy with EBS in whom initial Sanger sequencing of known genes implicated in intraepidermal skin fragility failed to identify pathogenic mutations. Transmission electron microscopy of rubbed nonlesional patient skin revealed disruption of keratinocytes in the lower epidermis with cytolysis and acantholysis, keratin filament clumping and prominent perinuclear cytoplasmic vesicles, and provided the clue to the candidate gene pathology. Sanger sequencing of genomic DNA showed compound heterozygosity for two new mutations in EXPH5, c.1947dupC (p.Pro649fsPro*11) and c.2249C>A (p.Ser750*). Immunofluorescence microscopy of patient skin showed a complete absence of exophilin-5 labelling. This case represents the third pedigree with EXPH5 mutations resulting in inherited skin fragility. The clinical and molecular data expand genotype-phenotype correlation in this new form of EBS and demonstrate the important role of exophilin-5 in keratinocyte cell biology.

Bladder perforation during sling procedures: diagnosis and management of injury.

INTRODUCTION AND HYPOTHESIS: Midurethral slings are an effective and minimally invasive treatment for stress urinary incontinence. One of the most common intraoperative complications is bladder perforation, complicating between 2 and 10% of all operations, and on average 4.7%. It is usually corrected during surgery, with repositioning of the trocars. The purpose of this video is to demonstrate a method of replacing the trocars under direct vision. METHODS: This video exhibits a bladder perforation during insertion of a retropubic midurethral sling (Advantage Fit; Boston Scientific) and gives a step-by step guide to the removal and repositioning of the sling under direct visualisation. CONCLUSION: Repositioning of the trocars under direct vision in cases of bladder perforation may have numerous advantages. It may prevent damage to the urethra, possibly reduce the risk of postoperative infection and may be beneficial for trainees.

Non-song vocalizations of pygmy blue whales in Geographe Bay, Western Australia.

Non-song vocalizations of migrating pygmy blue whales (Balaenoptera musculus brevicauda) in Western Australia are described. Simultaneous land-based visual observations and underwater acoustic recordings detected 27 groups in Geographe Bay, WA over 2011 to 2012. Six different vocalizations were recorded that were not repeated in a pattern or in association with song, and thus were identified as non-song vocalizations. Five of these were not previously described for this population. Their acoustic characteristics and context are presented. Given that 56% of groups vocalized, 86% of which produced non-song vocalizations and 14% song units, the inclusion of non-song vocalizations in passive-acoustic monitoring is proposed.

Defining acute ischemic stroke tissue pathophysiology with whole brain CT perfusion.

BACKGROUND: This study aimed to identify and validate whole brain perfusion computed tomography (CTP) thresholds for ischemic core and salvageable penumbra in acute stroke patients and develop a probability based model to increase the accuracy of tissue pathophysiology measurements. METHODS: One hundred and eighty-three patients underwent multimodal stroke CT using a 320-slice scanner within 6hours of acute stroke onset, followed by 24hour MRI that included diffusion weighted imaging (DWI) and dynamic susceptibility weighted perfusion imaging (PWI). Coregistered acute CTP and 24hour DWI was used to identify the optimum single perfusion parameter thresholds to define penumbra (in patients without reperfusion), and ischemic core (in patients with reperfusion), using a pixel based receiver operator curve analysis. Then, these results were used to develop a sigma curve fitted probability based model incorporating multiple perfusion parameter thresholds. RESULTS: For single perfusion thresholds, a time to peak (TTP) of +5seconds best defined the penumbra (area under the curve, AUC 0.79 CI 0.74-0.83) while a cerebral blood flow (CBF) of < 50% best defined the acute ischemic core (AUC 0.73, CI 0.69-0.77). The probability model was more accurate at detecting the ischemic core (AUC 0.80 SD 0.75-0.83) and penumbra (0.85 SD 0.83-0.87) and was significantly closer in volume to the corresponding reference DWI (P=0.031). CONCLUSIONS: Whole brain CTP can accurately identify penumbra and ischemic core using similar thresholds to previously validated 16 or 64 slice CTP. Additionally, a novel probability based model was closer to defining the ischemic core and penumbra than single thresholds.

Bluetongue disease in sheep in New South Wales - April 2023.

In 2016, bluetongue virus (BTV), serotype 16 (BTV-16), was detected in New South Wales (NSW) in sentinel cattle for the first time. Over the next 6 years, BTV-16 has been detected regularly and over an increasing area of the BTV zone in NSW. In April 2023, disease was reported in sheep on two farms on the Northern Tablelands of NSW. The consistent clinical signs included reduced exercise tolerance, facial swelling, serous nasal discharges with encrustation of the nasal plane, subcutaneous oedema of the neck and brisket and variable congestion of the coronary band. Affected sheep were mainly mature ewes and rams, with an estimated morbidity of 20% over a period of 6-8 weeks. Although there were several unexpected deaths, no veterinary examination was sought. Predominantly BTV-16 RNA was detected in sick sheep, with an incidence of infection of approximately 40% in a cross section of one flock. These events represent the first confirmation of disease due to bluetongue virus in NSW. As these cases occurred in a region with a high density of sheep, if there is ongoing transmission of BTV-16 during subsequent summers, further disease might be expected.

Using FRET to analyse signals controlling cell adhesion and migration.

Cell adhesion and migration are dynamic, complex processes that require tight temporal control of signalling cascades at defined subcellular sites to occur. Decades of research have used biochemical methods to identify numerous signalling pathways that are involved in the coordination of adhesion, membrane protrusion and contractility that all contribute to migration. However, understanding the way in which these signals are controlled within discrete sites in individual cells undergoing migration is essential to enable a clearer understanding of how these pathways are integrated during motility. Recent advances in the generation of fluorescent protein variants have enabled the development of probes to analyse localized changes in protein conformation, activation or interactions in single cells using microscopy. Many of these probes are based on the use of fluorescence resonance energy transfer that permits precise determination of interacting species based on the emission or lifetime properties of the fluorophores involved. Here, we provide an overview of some of the recent studies that have developed such probes and examples of how these biosensors have been used to further our understanding of cell migration signalling.

The effects of cannabidiol on the antigen-induced contraction of airways smooth muscle in the guinea-pig.

(-)-Δ(9)-Tetrahydrocannabinol has been demonstrated to have beneficial effects in the airways, but its psychoactive effects preclude its therapeutic use for the treatment of airways diseases. In the present study we have investigated the effects of (-)-cannabidiol, a non-psychoactive component of cannabis for its actions on bronchial smooth muscle in vitro and in vivo. Guinea-pig bronchial smooth muscle contractions induced by exogenously applied spasmogens were measured isometrically. In addition, contractile responses of bronchial smooth muscle from ovalbumin-sensitized guinea-pigs were investigated in the absence or presence of (-)-cannabidiol. Furthermore, the effect of (-)-cannabidiol against ovalbumin-induced airway obstruction was investigated in vivo in ovalbumin-sensitized guinea-pigs. (-)-Cannabidiol did not influence the bronchial smooth muscle contraction induced by carbachol, histamine or neurokinin A. In contrast, (-)-cannabidiol inhibited anandamide- and virodhamine-induced responses of isolated bronchi. A fatty acid amide hydrolase inhibitor, phenylmethanesulfonyl fluoride reversed the inhibitory effect of (-)-cannabidiol on anandamide-induced contractions. In addition, (-)-cannabidiol inhibited the contractile response of bronchi obtained from allergic guinea-pigs induced by ovalbumin. In vivo, (-)-cannabidiol reduced ovalbumin-induced airway obstruction. In conclusion, our results suggest that cannabidiol can influence antigen-induced airway smooth muscle tone suggesting that this molecule may have beneficial effects in the treatment of obstructive airway disorders.

A liquid metal dropper for experiments on the wettability of liquid metals on plasma facing components.

A liquid metal dropper has been developed as a part of the Ion-Gas-Neutral Interactions with Surfaces 2 (IGNIS-2) facility at The Pennsylvania State University. The dropper has the capability of directly applying drops to candidate plasma facing materials for nuclear fusion reactors to enable measurements of their liquid metal wetting properties. The results presented here are specific to the use of lithium in the dropper. This paper discusses the design choices of the liquid metal dropper and its chamber, including the heating and temperature control and the dropper's motorized operation. Lithium drops of masses ranging from 0.05 g up to 0.13 g, equivalent to drop diameters between 5.6 mm to 1 cm, have been consistently dispensed by the dropper. A new algorithm is developed and used to automate the analysis of the contact angle between the liquid drops and substrate material for efficient analysis of video data recorded to study the wetting properties of candidate plasma-facing components.