Effects of external influences on synthetic cannabinoid trends in New Zealand, 2014 to 2020.

Over the past decade, synthetic cannabinoids have inundated the global market and now form the largest category of new psychoactive substances. Once these chemicals are available on the global market, they can be applied to plant material in a clandestine environment to create an end-product that is smoked by the user. The synthetic cannabinoids AMB-FUBINACA and 5F-ADB were most frequently detected between 2017 and the beginning of 2019. More recently, these two appear to have been replaced by different synthetic cannabinoids. This investigation summarises the recent trends in synthetic cannabinoids detected in New Zealand between 2017 and 2020 and outlines the potential factors influencing these trends.

The phenomenon of para-Fluorophenylpiperazine (pFPP) in combination with the synthetic cannabinoid AMB-FUBINACA in seized plant material in New Zealand.

New psychoactive substances have emerged as a vast and diverse group of illicit drugs over the past decade, with synthetic cannabinoids comprising the largest of the categories. Commonly, a single synthetic cannabinoid is applied to plant material, creating a product that is designed to be smoked by the user. The clandestine preparation process can result in an unevenly distributed product, with varying concentration within and between plant materials. This investigation describes the novel co-detection of the synthetic cannabinoid AMB-FUBINACA, with the piperazine para-fluorophenylpiperazine (pFPP), in a number of plant material samples analysed in New Zealand in 2017. Of 157 samples of plant material containing AMB-FUBINACA, pFPP was detected in 55 of them. A range of pFPP concentrations was observed between the plant material samples, as well as intra-batch variation. The presence of both drugs may be designed to enhance, prolong or balance the psychoactive effects caused from smoking the plant material. However the intended purpose has not been verified. This is the first reported combination of a synthetic cannabinoid and a piperazine in plant material.

The identification and quantification of synthetic cannabinoids seized in New Zealand in 2017.

There has been an explosion of new psychoactive substances (NPS) over the past decade, with synthetic cannabinoids comprising one of the more extensive and chemically diverse groups. Synthetic cannabinoids, like other NPS, are continually evolving with slight alterations in chemical structure, which can lead to unintended and harmful effects for the user. Furthermore, the clandestine preparation of plant material containing one or more synthetic cannabinoid can result in an unevenly distributed product, which poses an additional risk to the user of increased doses. This investigation aimed at providing a snapshot of synthetic cannabinoids in New Zealand in 2017, including the concentrations of synthetic cannabinoids in plant material. Overall, ten different synthetic cannabinoids were detected, with AMB-FUBINACA and 5F-ADB comprising the majority of samples analysed. The synthetic cannabinoid AMB-FUBINACA displayed the greatest range of concentration in plant material, from 5 to over 400 g of synthetic cannabinoid per kilogram of plant material. There was also geographical variation in the synthetic cannabinoids depending on where in New Zealand they were seized from.

Childhood central adiposity at ages 5 and 9 shows consistent relationship with that of the maternal grandmother but not other grandparents.

BACKGROUND: The importance of a life course approach to childhood obesity has been emphasized; however, few studies can prospectively investigate relationships in three-generation families. OBJECTIVE: To prospectively investigate the relationship between grandparental and grandchild waist circumference (WC) at ages 5 and 9 down maternal and paternal lines. METHODS: At baseline in the Lifeways Cross-Generation Cohort, 1094 children were born to 1082 mothers; 585 were examined at age 5 and 298 at age 9. Of the total 589 children with measured WC, data were also available from 745 grandparents. Child WC was standardized for age and sex, and theory-based hierarchical linear regression was used. RESULTS: Maternal grandmother (MGM) WC was predictive of grandchild WC at both time points. At age 5, grandchild's standardized birth weight (B = 0.266, p = 0.001), mother's means tested eligibility for free medical care (B = 1.029, p = 0.001) and grandchild seeing maternal grandparents daily (B = 0.312, p = 0.048) were significant alongside MGM WC (B = 0.015, p = 0.019). At age 9, only MGM WC (B = 0.022, p = 0.033) and mother's WC (B = 0.032, p = 0.005) were significant. Mediation analysis with mother's WC showed significant direct relationship of MGM and grandchild WC. CONCLUSIONS: This prospective cross-generational cohort shows consistent patterns of association between MGM and grandchild WC, not seen in other grandparental lineages.

Caregiver burden of parents of young children with cystic fibrosis.

BACKGROUND: There is a paucity of research examining the impact of informal caregiving on parents of young children with cystic fibrosis (CF). The aim of this study was to examine caregiver burden and identify risk factors associated with high caregiver burden in mothers and fathers of young children with CF. METHODS: This was a cross-sectional study of parents of young children with CF. A total of 213 families were invited to complete the CarerQoL questionnaire, a validated tool composed of two parts: (i) the CarerQol-7D which describes the care situation in terms of the negative and positive effects of caregiving and (ii) the visual analogue scale (VAS) which measures happiness on a scale from 0 to 10 (0=completely unhappy and 10=completely happy). The utility score (US) is a weighted average of the subjective burden derived from the CarerQol-7D (0-100); higher US indicates reduced burden. Differences in mother-father dyad median utility scores were examined using Wilcoxon signed rank test. Generalised linear mixed models were used to identify factors associated with high caregiver burden. RESULTS: At least one parent from 195 families completed the questionnaire (130 mother-father dyads, 189 mothers and 137 fathers). Fathers had a significantly higher median utility score than mothers [(89.2 (IQR 79.6-96.5) vs. 84.7 (74.5-88.0) p<0.001]. Factors found to be significantly associated with higher caregiver burden were increasing child age (OR 1.02; CI: 1.00-1.04), having a child ever positive for Pseudomonas aeruginosa (Pa) (OR 2.48; CI: 1.30-4.73) and being a mother (OR 1.65; CI: 1.02-2.65). CONCLUSIONS: This study contributes new findings to the sparse literature on caregiver burden of parents of young children with CF. Increasing child age and infection with Pa, associated with higher morbidity, were linked to greater parental burden.

Predictors of adults' body mass index and the association with index child's infant birth weight, in the Lifeways Cross-Generation Cohort Study of a thousand families in the Republic of Ireland.

The Lifeways study is novel in having information on three generations of the same families. It is well established that infant birth weight (IBW) predicts individuals' risk of adult chronic disease and more recently studies report cross-generation transmission of risk patterns. The aims of this analysis were to examine whether adults' birth weights were associated with measures of own health status or social position and to relate adults' birth weights to that of the index child's IBW. Finally, we assessed whether birth weight of either adults or children was associated with adult body mass index (BMI) of parents and grandparents. We included 1075 children whose IBW was recorded at recruitment from hospital records and 2546 adult cohort members followed from 2001 until 2014. At baseline, a sub-group of 920 adults had reported own birth weight (RBW). Results showed male adults' RBW were significantly higher than females' (P=0.001). Mothers' RBW was significantly correlated with IBW (r=0.178, P<0.001). In mixed effects linear models with BMI as the outcome variable, of all adults, and in sub-groups of adults with RBW and of mothers only, the IBW was associated with adult BMI adjusting for other predictors. Adults' BMI was positively associated with age (P=0.013), index child's IBW (P=0.001), gender (P<0.001) but not own RBW, adjusting for family identification number. When mothers were removed from the adult models however, IBW ceased to be associated with BMI, a final model showed RBW being associated with adult BMI (P=0.04). There are cross-generational associations in the Lifeways cohort, the maternal association being stronger.

Total HDL cholesterol efflux capacity in healthy children - Associations with adiposity and dietary intakes of mother and child.

BACKGROUND AND AIMS: High-density lipoprotein (HDL) cholesterol efflux capacity in adults may be a measure of the atheroprotective property of HDL. Little however, is known about HDL cholesterol efflux capacity in childhood. We aimed to investigate the relationship between HDL cholesterol efflux capacity and childhood anthropometrics in a longitudinal study. METHODS AND RESULTS: Seventy-five children (mean age = 9.4 ± 0.4 years) were followed from birth until the age of 9 years. HDL cholesterol efflux capacity was determined at age 9 by incubating serum-derived HDL-supernatants with 3H-cholesterol labeled J774 macrophages and percentage efflux determined. Mothers provided dietary information by completing food frequency questionnaires in early pregnancy and then 5 years later on behalf of themselves and their children. Pearson's correlations and multiple regression analyses were conducted to confirm independent associations with HDL efflux. There was a negative correlation between HDL cholesterol efflux capacity and waist circumference at age 5 (r = -0.3, p = 0.01) and age 9 (r = -0.24, p = 0.04) and BMI at age 5 (r = -0.45, p = 0.01) and age 9 (r = -0.19, p = 0.1). Multiple regression analysis showed that BMI at age 5 remained significantly associated with reduced HDL cholesterol efflux capacity (r = -0.45, p < 0.001). HDL-C was negatively correlated with energy-adjusted fat intake (r = -0.24, p = 0.04) and positively correlated with energy-adjusted protein (r = 0.24, p = 0.04) and starch (r = 0.29, p = 0.01) intakes during pregnancy. HDL-C was not significantly correlated with children dietary intake at age 5. There were no significant correlations between maternal or children dietary intake and HDL cholesterol efflux capacity. CONCLUSIONS: This novel analysis shows that efflux capacity is negatively associated with adiposity in early childhood independent of HDL-C.

A Prospective Analysis of the Relationship between Chronic Diseases and Adiposity in older adults: Findings from the Lifeways Cross-Generation Cohort Study of a Thousand Families 2001-2014.

This study assesses the relationship between body mass index (BMI) and adult chronic diseases (diabetes mellitus type 2 [DM2], cardiovascular diseases [CVD] and cancers), in grandparents in the Lifeways Cross-Generation Cohort Study. BMI was either measured or reported, at baseline or 10-year follow-up, in 1,244 grandparents. Cumulative morbidity data were recorded at baseline, 3 and 10-year follow-up through questionnaires, General Practice note search, or both. Just over 42% of grandparents were overweight and 32.1% obese. In the multivariate analysis BMI showed a strong linear association with both DM2 (ptrend <0.001) and CVD (ptrend <0.001). There were no significant associations with cancers, but case numbers were small. Results were similar for waist circumference. This prospective study presents novel Irish data and confirms other recent Irish cross-sectional reports on adiposity and adult chronic disease, highlighting the need for effective health promotion interventions in older adults.

Poor mental health in severely obese patients is not explained by the presence of comorbidities.

The prevalence of obesity, especially severe obesity where body mass index (BMI) exceeds 40 kg m(-2) and where the physical risks are greatest, is increasing. However, little is known about the impact of severe obesity on psychological well-being and self-rated health (SRH). We aimed to investigate this relationship in patients attending an Irish weight management clinic. SRH was measured with a single-item inventory (excellent = 1, poor = 5). Well-being was measured with the validated World Health Organization-Five Well-being Index (WHO-5), in which scores <13 indicate poor well-being. Previous studies of the Irish population have reported mean SRH = 2.56 (males) and 2.53 (females) and mean well-being = 16.96. One hundred eighty-two (46.8%) completed questionnaires were returned. The sample was representative of the clinic population with a mean age of 47.1, mean baseline BMI of 51.9 kg m(-2) and 64.3% females. Mean SRH was 3.73 in males and 3.30 in females; mean well-being was 10.27 in males and 10.52 in females. In the final multivariable models, number of medications, depression and obstructive sleep apnoea, WHO-5 and current BMI were significant predictors of SRH, and secondary level education, social support and mindfulness scores were significant predictors of psychological well-being. Number of medications was not significant. The results suggest that the poor psychological well-being seen is not explained by the presence of comorbidities and that social support and mindfulness may be important targets for improving psychological well-being. Improving psychological well-being in addition to weight loss and effective management of comorbidities may be important for improving SRH.

Non-pulmonary chronic diseases in adults with cystic fibrosis: analysis of data from the Cystic Fibrosis Registry.

The international literature shows that the demography of cystic fibrosis (CF) is changing, with patients increasingly surviving into adulthood. As they age, patients with CF become more susceptible to specific non-pulmonary chronic diseases. In this study, adult data from the CF Registry of Ireland (CFRI) was used to determine the prevalence and associated features of these diseases. 104 (25.7%) adults had diabetes versus 13 (2.9%) children (p < 0.001). Liver disease was present in 47 (11.6%) adults and 26 (5.7%) children (p = 0.002). 173 (42.7%) adults had bone disease versus 25 (5.5%) children (p < 0.001). Adults with one non-pulmonary chronic disease, for example liver disease, were more likely to have another (p = 0.002), those with diabetes and bone disease had a higher number of hospital admissions in the last 12 months (p < 0.001 for both) and higher rates of depression (p = 0.046 and p = 0.049, respectively). These results highlight a number of challenges for the Irish healthcare system.

Limited efficacy of steam sterilization to inactivate vCJD infectivity.

BACKGROUND: The transmission of bovine spongiform encephalopathy (BSE) to humans as variant Creutzfeldt-Jakob Disease (vCJD) raised concerns about potential secondary transmissions due to the resistance of the agents causing transmissible spongiform encephalopathies (TSEs), sometimes known as prions, to commonly used methods of sterilization, notably steam sterilization (or autoclaving). It has been suggested that surgical instruments and other medical devices might retain sufficient infected tissue debris after cleaning and steam sterilization to infect patients on whom they are subsequently used. AIM: To determine whether concerns about the lack of efficacy of steam sterilization of vCJD were justified. METHODS: The reduction in infectivity of brain macerates of vCJD brain after steam sterilization using the standard temperatures and time recommended for autoclaving in UK hospitals (134-137°C for 3 min) was measured. FINDINGS: Reductions in titre of 10(2.3) to >10(3.6) ID(50) were found. In three of four samples, infectivity was recovered after steam sterilization. CONCLUSION: As noted previously, TSE strains derived from BSE sources appear to be more resistant to steam sterilization and other forms of heat inactivation than other TSE sources.

Application of two low-cost adsorption media for removal of toxic metals from contaminated water.

Since the operational costs of commonly used materials for adsorption of toxic metals can be substantial, natural material may be of great interest for treatment applications. Two types of natural material that have shown particular promise are seaweed and seafood waste. In this study, adsorption capacity of Brown seaweed and shrimp shells were compared with a strong acid cation exchange resin (CER). A case study site was used as a reference point and column experiments were designed in a similar manner although at different scale. Each media reduced concentrations of the target metals to levels below defined reference values. If the alternative adsorption media perform as well in the field as the laboratory, the results suggest that the media tested would completely remove the toxic metals in groundwater and runoff water. Seaweed and shrimp shells had stronger affinities for Pb and Cu than CER. However, CER was superior in affinity for Zn, the most weakly bound metal. Moreover, the results showed that Ca in the solution reduced the adsorption capacity of the other metals. This illustrates the limitations of applying the behaviour of the batch studies with single metal solutions to a multi-component system with competitive adsorption.

Prion protein: detection in 'spiked' anaerobic sludge and degradation experiments under anaerobic conditions.

The behavior of the transmissible spongiform encephalopathies (TSE) causing agent denominated "prion protein" in anaerobic sludge (biogas reactor) was assessed with incubation tests. A widely applied screening method for BSE in cattle on the basis of the Western blotting protocol was adapted to detect the Proteinase K resistant, scrapie-form prion protein (PrPSC). As PrPsc source homogenized TSE infected brain tissue of animals late in the clinical phase of disease was taken (301V/VM mouse-BSE; bovine BSE and 22A/SV mouse-scrapie). The incubation under mesophilic conditions did not show any significant reduction of the PrPsc titer. Under thermophilic conditions contradictory results were obtained. The reduction time of PrPsc in water was equal to or longer than the PrPsc reduction time in anaerobic sludge. In comparison, with sterilized (121 degrees C, steam pressure) or poisoned (sodium azide, 1% w/v) sludge used as incubation matrix a much shorter time resulted until no prion protein could be detected.

Inactivation of transmissible spongiform encephalopathy agents during the manufacture of dicalcium phosphate from bone.

Dicalcium phosphate was prepared from industrial crushed bone artificially contaminated with transmissible spongiform encephalopathy agents in two experiments carried out in an accurately scaled-down laboratory model of the industrial manufacturing process. In one experiment, 10 g of mouse brain infected with the 301V strain of mouse-passaged bovine spongiform encephalopathy agent was added to the crushed bone; in the other experiment, 10 g of hamster brain infected with the 263K strain of hamster-passaged scrapie agent was added. Samples of the infectious brain and dried dicalcium phosphate were assayed for the amount of 301V or 263K infectivity present. The titre of infectivity of the 301V-infected brain was 10(7.7) intracerebral ID50/g; that of the 263K-infected brain was 10(8.0) intracerebral ID50/g. The titres of the dried samples of dicalcium phosphate were 10(2.5) ID50/g in the experiment spiked with 301V and 10(2.7) ID50/g in the experiment spiked with 263K. The calculated clearance factors were 10(3.9) for the experiment with 301V and 10(3.8) for the experiment with 263K.

Inactivation of the BSE agent by the heat and pressure process for manufacturing gelatine.

Dietary exposure to the bovine spongiform encephalopathy (BSE) agent is the probable cause of variant Creutzfeldt-Jakob disease in people. The industrial manufacturing process for the production of gelatine and colloidal protein by the heat and pressure process was downscaled accurately and its capacity to remove or inactivate bse infectivity was investigated. Gelatine was made from bones experimentally contaminated with mouse brain infected with the 301V strain of mouse-passaged bse agent in which the infective titre was 10(8.7) ID50/g. No infectivity was detected in the extracted protein (> or =10(0.45) ID50/g), and the calculated clearance factor was 10(6.5) ID50 or more.

Distribution of a bovine spongiform encephalopathy-derived agent over ion-exchange chromatography used in the preparation of concentrates of fibrinogen and factor VIII.

BACKGROUND AND OBJECTIVES: The risk of haemophiliacs contracting variant Creutzfeldt-Jakob disease (vCJD) via treatment with factor VIII concentrates is not known. Therefore, in order to determine the extent to which the vCJD agent might be removed during the preparation of factor VIII concentrate, the partitioning of a bovine spongiform encephalopathy (BSE)-derived agent was measured over the main purification step used to prepare the Scottish National Blood Transfusion Service high-purity factor VIII concentrate (Liberate). MATERIALS AND METHODS: Murine-passaged BSE (strain 301V), in the form of a microsomal fraction prepared from infected brain, was used to 'spike' a solution of factor VIII of intermediate purity. The 'spiked' starting material was subjected to solvent-detergent treatment and then to anion-exchange chromatography with Toyopearl DEAE-650M. All fractions were tested for 301V infectivity using a murine bioassay, including the procedures used to clean the ion-exchange media after use. RESULTS: BSE 301V infectivity was reduced by 2.9 log(10) in the fibrinogen fraction and by 2.7 log(10) in the factor VIII fraction. Over 99% of the added 301V infectivity remained bound to the ion-exchange column after elution of factor VIII. A large quantity of infectivity was subsequently removed by washing the ion-exchange media with 2 m NaCl. No further BSE 301V infectivity was detected in column eluates after treatment with 0.1 m NaOH or a second wash with 2 m NaCl. CONCLUSIONS: Results using a BSE-derived agent suggest that vCJD infectivity would be substantially removed by the ion-exchange process used in the preparation of fibrinogen and factor VIII concentrate. Although 301V infectivity remained bound to the ion-exchange matrix following elution of factor VIII, this appeared to be eliminated by the procedure used for cleaning the ion-exchange media after each use.

Bovine spongiform encephalopathy in sheep?

Bovine spongiform encephalopathy (BSE) in sheep has not been identified under natural conditions at the time of writing and remains a hypothetical issue. However, rumours about the possible finding of a BSE-like isolate in sheep have led to great unrest within the sheep industry, among the general public and within governmental and regulatory bodies. The difficulties of implementing a proper risk assessment and pre-emptive measures, in the absence of a confirmed case, are described. The authors attempt to list what is known about experimental BSE in sheep, the distribution of infectivity in the host, some aspects of risk assessment and management and the most promising methods for differentiating BSE from scrapie in the same host. As for the latter, new and promising methods are being developed and appear suitable for initial screening of isolates of transmissible spongiform encephalopathies, but in the absence of proper validation, use of the 'classical' strain-typing in a mouse panel is still indicated.

Studies on the removal of a bovine spongiform encephalopathy-derived agent by processes used in the manufacture of human immunoglobulin.

BACKGROUND AND OBJECTIVES: There is still uncertainty over how the agent of variant Creutzfeld-Jakob disease (vCJD) would partition during the manufacture of plasma derivatives. In this study, a BSE-derived agent was used as a vCJD model to determine the extent to which infectivity could be removed by selected steps used in the manufacture of intravenous immunoglobulin (IVIG). MATERIALS AND METHODS: Murine-passaged BSE (strain 301V), in the form of a microsomal fraction prepared from infected brain, was used to "spike" the starting material in three experiments. The partitioning of BSE infectivity was measured over Fraction I+III precipitation, borosilicate microfibre depth filtration and Seitz depth filtration, with these steps being examined individually and in series. RESULTS: Most 301V infectivity partitioned into Fraction I+III (log reduction 2.1). Infectivity remaining in Supernatant I+III was reduced by AP20 glass-fibre depth filtration (log reduction 0.6) and subsequently removed to below the limit of detection by Seitz KS80 depth filtration, giving an overall log reduction of > or = 2.9 for the three steps in series. By contrast, glass-fibre depth filtration gave a log reduction of 2.4 when challenged directly with "spiked" feedstock. Seitz KS80 depth filtration gave a log reduction of > or = 3.1 when challenged directly with 'spiked' feedstock and also removed residual infectivity to below the limit of detection when applied as the final step in series. CONCLUSIONS: Results using a BSE-derived agent suggest that vCJD infectivity should be substantially removed from immunoglobulin G (IgG) solutions by Fraction I+III precipitation and Seitz KS80 depth filtration. The three different process steps examined acted in a complementary manner to one another when operated in series. However, the data demonstrated that it would be inappropriate to add together the reduction factors that had been derived for each step in isolation.