Covering the Distance: A Study of Parent and Teen Attitudes on COVID-19 Mitigation Measures During the COVID-19 Pandemic.

Background The Unity® Consortium surveyed teens and parents and guardians of teens across the country at three distinct time points or waves during the COVID-19 pandemic to assess participant attitudes and beliefs regarding COVID-19 mitigation guidelines, such as mask-wearing and physical distancing. Methodology A third-party market research company conducted 15-minute, online surveys from nationally representative panels. Surveys were conducted at three distinct time points or waves (August 2020, February 2021, and June 2021) with 300 teens aged 13-18 years in each wave and 593/531/500 parents and guardians of teens aged 13-18 years in each wave, respectively. Participants responded using a five-point Likert scale (strongly agree to strongly disagree) on their COVID-19 experiences, including the perceived importance of strictly following mask-wearing and/or social distancing guidelines and the perceived effectiveness of mask-wearing and social distancing in preventing the spread of COVID-19. Data were analyzed for differences across waves and demographic variables. Statistical analyses included frequencies, analysis of variance (ANOVA), and t-tests/z-tests. Results While significantly more parents and teens in Waves 2 and 3 knew someone who was hospitalized or died due to COVID-19 compared to Wave 1, significantly fewer in Wave 3 reported experiencing a lot or some stress and worry regarding the pandemic. By Wave 3, 58% of teens and 56% of parents had received at least one dose of a COVID-19 vaccine. Despite changes in experiences over time, a significant majority of parents and teens consistently agreed on the importance and effectiveness of social distancing and masking guidelines against the spread of COVID-19. In Wave 3, the demographic variables significantly associated with agreement on importance included race (Black (92%) > White (80%)), community type (urban (91%) > suburban (79%) and rural (73%)), and positive vaccination status of parents and teens (92%/89%) > not vaccinated (73%/73%), respectively). The demographic variables significantly associated with agreement on effectiveness included race (Black (91%) > White (81%)), community type (urban (89%) > suburban (83%) and rural (71%)), and positive vaccination status of parents and teens (94%/90% > not vaccinated (72%/70%), respectively). Conclusions This study into the perceived importance and perceived effectiveness of mitigation strategies during the COVID-19 pandemic revealed differences in attitudes among sociodemographic groups. Understanding these differences can help shape how adherence to public health guidelines in a pandemic is promoted.

Producer practices and attitudes: Non-replacement male calf management in the Australian dairy industry.

Currently, there is no standardized rearing method or production guidelines for non-replacement male dairy calves that maximizes their economic viability. Producers have highlighted the need to match consumer expectations, but even with broadscale welfare improvement across the dairy industry, challenges remain at providing reliable and valuable pathways for non-replacement male dairy calves for beef production. A key consumer concern has been the use of on-farm euthanasia. Euthanasia has been a catalyst for change in the industry from a human and animal welfare perspective. The practice of euthanasia can lead to a decline in personnel wellbeing. To investigate the relationship between on-farm management practices of non-replacement male dairy calves and producer perceptions of their value proposition, an online questionnaire was provided to Australian dairy producers between June and October 2021. The aim was to identify supply-chain profitability of non-replacement male calves and investigate the attitudes and effects of euthanasia on producer wellbeing as part of managing these calves. A total of 127 useable responses were obtained, and a Bayesian network (BN) was utilized to model the interdependencies between management practices and wellbeing among participants. The results indicated that in general, dairy producers desired high welfare standards in their enterprises with regard to non-replacement male calves as well as expressed a desire to meet industry and consumers' expectations. In line with anecdotal reports of a reduction in practice, euthanasia was not identified as common practice in this group; however, producers were still accessing early-life markets for non-replacement male calves with operational requirements and environmental factors influencing their decisions. Producers expressed dissatisfaction with market access for their calves, as well as the lack of suitability of Australian beef grading standards for dairy-bred carcasses. Australian dairy managers and owners identified that euthanasia influenced employee wellbeing; however, they did not acknowledge euthanasia had an effect on their own wellbeing. Overall, the findings of this study indicate that all non-replacement male calf breeds had the potential to access profitable markets, and avoidance of euthanasia is a strong driver of change among dairy beef production systems in Australia.

Meta-Analysis of qPCR for Bovine Respiratory Disease Based on MIQE Guidelines.

Qualitative and quantitative PCR-based tests are widely used in both diagnostics and research to assess the prevalence of disease-causing pathogens in veterinary medicine. The efficacy of these tests, usually measured in terms of sensitivity and specificity, is critical in confirming or excluding a clinical diagnosis. We undertook a meta-analysis to assess the inherent value of published PCR diagnostic approaches used to confirm and quantify bacteria and viruses associated with bovine respiratory disease (BRD) in cattle. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A thorough search of nine electronic databases (Web of Science, EBSCOhost, Cambridge journals online, ProQuest, PubMed, Sage journals online, ScienceDirect, Wiley online library and MEDLINE) was undertaken to find studies that had reported on the use of PCR and/or qPCR for the detection and/or quantification of BRD associated organisms. All studies meeting the inclusion criteria for reporting quantitative PCR for identification of BRD associated microorganisms were included in the analysis. Studies were then assessed on the applications of the Minimum Information for Publication of Quantitative Real-Time PCR Experiment (MIQE) and PCR primer/probe sequences were extracted and tested for in silico specificity using a high level of stringency. Fourteen full-text articles were included in this study. Of these, 79% of the analysed articles did not report the application of the MIQE guidelines in their study. High stringency in silico testing of 144 previously published PCR primer/probe sequences found many to have questionable specificity. This review identified a high occurrence of primer/probe sequences with a variable in silico specificity such that this may have implications for the accuracy of reporting. Although this analysis was only applied to one specific disease state, identification of animals suspected to be suffering from bovine respiratory disease, there appears to be more broadly a need for veterinary diagnostic studies to adopt international best practice for reporting of quantitative PCR diagnostic data to be both accurate and comparable between studies and methodologies.

Genotypic identification of Panicum spp. in New South Wales, Australia using DNA barcoding.

Australia has over 30 Panicum spp. (panic grass) including several non-native species that cause crop and pasture loss and hepatogenous photosensitisation in livestock. It is critical to correctly identify them at the species level to facilitate the development of appropriate management strategies for efficacious control of Panicum grasses in crops, fallows and pastures. Currently, identification of Panicum spp. relies on morphological examination of the reproductive structures, but this approach is only useful for flowering specimens and requires significant taxonomic expertise. To overcome this limitation, we used multi-locus DNA barcoding for the identification of ten selected Panicum spp. found in Australia. With the exception of P. buncei, other native Australian Panicum were genetically separated at the species level and distinguished from non-native species. One nuclear (ITS) and two chloroplast regions (matK and trnL intron-trnF) were identified with varying facility for DNA barcode separation of the Panicum species. Concatenation of sequences from ITS, matK and trnL intron-trnF regions provided clear separation of eight regionally collected species, with a maximum intraspecific distance of 0.22% and minimum interspecific distance of 0.33%. Two of three non-native Panicum species exhibited a smaller genome size compared to native species evaluated, and we speculate that this may be associated with biological advantages impacting invasion of non-native Panicum species in novel locations. We conclude that multi-locus DNA barcoding, in combination with traditional taxonomic identification, provides an accurate and cost-effective adjunctive tool for further distinguishing Panicum spp. at the species level.

Efficiency Correction Is Required for Accurate Quantitative PCR Analysis and Reporting.

BACKGROUND: Quantitative PCR (qPCR) aims to measure the DNA or RNA concentration in diagnostic and biological samples based on the quantification cycle (Cq) value observed in the amplification curves. Results of qPCR experiments are regularly calculated as if all assays are 100% efficient or reported as just Cq, ΔCq, or ΔΔCq values. CONTENTS: When the reaction shows specific amplification, it should be deemed to be positive, regardless of the observed Cq. Because the Cq is highly dependent on amplification efficiency that can vary among targets and samples, accurate calculation of the target quantity and relative gene expression requires that the actual amplification efficiency be taken into account in the analysis and reports. PCR efficiency is frequently derived from standard curves, but this approach is affected by dilution errors and hampered by properties of the standard and the diluent. These factors affect accurate quantification of clinical and biological samples used in diagnostic applications and collected in challenging conditions. PCR efficiencies determined from individual amplification curves avoid these confounders. To obtain unbiased efficiency-corrected results, we recommend absolute quantification with a single undiluted calibrator with a known target concentration and efficiency values derived from the amplification curves of the calibrator and the unknown samples. SUMMARY: For meaningful diagnostics or biological interpretation, the reported results of qPCR experiments should be efficiency corrected. To avoid ambiguity, the Minimal Information for Publications on Quantitative Real-Time PCR Experiments (MIQE) guidelines checklist should be extended to require the methods that were used (1) to determine the PCR efficiency and (2) to calculate the reported target quantity and relative gene expression value.

Vaccine Hesitancy in the Time of COVID-19: Attitudes and Intentions of Teens and Parents Regarding the COVID-19 Vaccine.

To assess attitudes and intentions related to the COVID-19 vaccine during the pandemic, we surveyed adolescents aged 13-18 years and the parents of 13-18-year-olds using national research panels on three occasions or "waves": before the COVID-19 vaccine was available, after it was available for adults, and after it was available for ages ≥12 years. Data on experiences with COVID-19, the importance of adolescent vaccines, and intentions regarding COVID-19 vaccination were analyzed across time points. We found that parental concerns about vaccine safety significantly increased from Wave 1 to 2. Social media had a negative influence on parents' and adolescents' opinions about vaccine safety. Demographic variables were associated with vaccination rates reported in Wave 3, consistent with known inequities related to vaccine access. Parents (70%) were supportive of concomitant COVID-19 vaccination with other adolescent vaccines for teens. It is important to address variables associated with vaccine hesitancy to increase COVID-19 vaccine coverage rates in the US.

Barriers to Utilizing Non-replacement Male Calves in the Australian Dairy Industry: A Qualitative Study.

Male non-replacement calves in dairy systems represent an underutilized economic resource for dairy producers worldwide. Despite this, increasing the practice of rearing non-replacement male calves has significant barriers both in on-farm adoption and practice. Poor neonatal rearing practices, higher levels of morbidity and mortality, and disaggregated production pathways with multiple points of handling, have all been described as barriers to adoption of surplus calf production. To identify the critical decision-determining challenges associated with broader adoption of raising non-replacement stock, and to investigate the whole-of-value chain issues faced by dairy producers to rear non-replacement male calves, we undertook a series of semi-structured interviews with Australian dairy producers to interrogate their key challenges. To achieve this, a constructivist grounded theory approach was used to inform the process of analysis of in-depth interviews with Australian dairy producers regarding their current practices and perceptions. Five major themes emerged from these conversations that were key barriers to on-farm non-replacement calf rearing in the producer group participants. These were: impacts of drought on cost and availability of feed for these calves and the whole herd; the management requirements of non-replacement male calves as an additional workload to that of their current operation; their attitudes and current practices to and surrounding euthanasia; perceived ease of supply-chain access for these calves, and their perceptions of the economic value of dairy-beef product as a return on investment. Understanding the barriers to adoption of non-replacement calf rearing, and addressing the value proposition for dairy beef, can assist increased uptake of non-replacement calf rearing. These findings will allow development of strategies to address these barriers, and extension of viable management strategies to increase adoption of profitable business practices surrounding non-replacement male calf production.

PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease.

BACKGROUND: Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. RESULTS: Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture. CONCLUSIONS: A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation.

Tremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates.

The neuroactive mycotoxin lolitrem B causes a neurological syndrome in grazing livestock resulting in hyperexcitability, muscle tremors, ataxia and, in severe cases, clonic seizures and death. To define the effects of the major toxin lolitrem B in the brain, a functional metabolomic study was undertaken in which motor coordination and tremor were quantified and metabolomic profiling undertaken to determine relative abundance of both toxin and key neurotransmitters in various brain regions in male mice. Marked differences were observed in the duration of tremor and coordination between lolitrem B pathway members, with some showing protracted effects and others none at all. Lolitrem B was identified in liver, kidney, cerebral cortex and thalamus but not in brainstem or cerebellum which were hypothesised previously to be the primary site of action. Metabolomic profiling showed significant variation in specific neurotransmitter and amino acid profiles over time. This study demonstrates accumulation of lolitrem B in the brain, with non-detectable levels of toxin in the brainstem and cerebellum, inducing alterations in metabolites such as tyrosine, suggesting a dynamic catecholaminergic response over time. Temporal characterisation of key pathways in the pathophysiological response of lolitrem B in the brain were also identified.

The aetiology, prevalence and morbidity of outbreaks of photosensitisation in livestock: A review.

BACKGROUND: Photosensitisation is a clinical condition occurring in both humans and animals that causes significant injury to affected individuals. In livestock, outbreaks of photosensitisation caused by ingestion of toxic plants are relatively common and can be associated with significant economic loss. OBJECTIVES: The agents that are most commonly implicated in outbreaks of photosensitisation have not been formally investigated on a global scale. To address this question, a systematic review of the literature was undertaken to determine the most common causative agents implicated in outbreaks of photosensitisation in livestock in Australia and globally, as well as the prevalence and morbidity of such outbreaks. METHODS: A systematic database search was conducted to identify peer-reviewed case reports of photosensitisation in livestock published worldwide between 1900 and April 2018. Only case reports with a full abstract in English were included. Non peer-reviewed reports from Australia were also investigated. Case reports were then sorted by plant and animal species, type of photosensitisation by diagnosis, location, morbidity and mortality rate and tabulated for further analysis. RESULTS: One hundred and sixty-six reports qualified for inclusion in this study. Outbreaks were reported in 20 countries. Australia (20), Brazil (20) and the United States (11) showed the highest number of peer-reviewed photosensitisation case reports from this analysis. Hepatogenous (Type III) photosensitisation was the most frequently reported diagnosis (68.5%) and resulted in higher morbidity. Panicum spp., Brachiaria spp. and Tribulus terrestris were identified as the most common causes of hepatogenous photosensitisation globally. CONCLUSIONS: Hepatogenous photosensitisation in livestock represents a significant risk to livestock production, particularly in Australia, Brazil, and the United States. Management of toxic pastures and common pasture weeds may reduce the economic impact of photosensitisation both at a national and global level.

Chemometric analysis of Amaranthus retroflexus in relation to livestock toxicity in southern Australia.

Amaranthus retroflexus L., an introduced invasive weed in southern Australia, has been associated with acute renal failure and/or mortality in a number of livestock species. While its leaves, flowers and stems are generally reported to contain high levels of nitrogen, few studies have fully characterised the chemical composition of A. retroflexus foliage with respect to mammalian toxicity. We performed extensive metabolic profiling of stems, leaves, roots and inflorescence tissues of A. retroflexus collected from three spatially and/or temporally distinct toxicity outbreaks, and report on the 1) composition of primary and secondary metabolites in methanolic extracts of A. retroflexus tissues using HPLC and HPLC-MS QToF and 2) chemometric analysis of A. retroflexus extracts in relation to the associated toxin(s). All tissues of A. retroflexus possessed an abundance of N-containing metabolites, particularly quaternary ammonium compounds which were identified as betaines, two of which (valine betaine and isoleucine betaine) are rarely encountered in plants. Cytotoxicity to murine fibroblasts was highest in extracts of leaf tissue and was associated with a single, a small modified peptide with high similarity to N-acetyl-L-α-aspartyl-L-alanyl-L-α-aspartyl-L-α-glutamyl-O-(carboxymethyl)-L-tyrosyl-L-leucinamide, a synthetic phosphotyrosyl mimic involved in cell signaling processes. One possible mode of action leading to acute renal failure in grazing livestock by a modified peptide such as this is proposed.

Can metamorphosis survival during larval development in spiny lobster Sagmariasus verreauxi be improved through quantitative genetic inheritance?

BACKGROUND: One of the major impediments to spiny lobster aquaculture is the high cost of hatchery production due to the long and complex larval cycle and poor survival during the many moult stages, especially at metamorphosis. We examined if the key trait of larval survival can be improved through selection by determining if genetic variance exists for this trait. Specifically, we report, for the first time, genetic parameters (heritability and correlations) for early survival rates recorded at five larval phases; early-phyllosoma stages (instars 1-6; S1), mid-phyllosoma stages (instars; 7-12; S2), late-phyllosoma stages (instars 13-17; S3), metamorphosis (S4) and puerulus stage (S5) in hatchery-reared spiny lobster Sagmariasus verreauxi. RESULTS: The data were collected from a total of 235,060 larvae produced from 18 sires and 30 dams over nine years (2006 to 2014). Parentage of the offspring and full-sib families was verified using ten microsatellite markers. Analysis of variance components showed that the estimates of heritability for all the five phases of larval survival obtained from linear mixed model were generally similar to those obtained from threshold logistic generalised models (0.03-0.47 vs. 0.01-0.50). The heritability estimates for survival traits recorded in the early larval phases (S1 and S2) were higher than those estimated in later phases (S3, S4 and S5). The existence of the additive genetic component in larval survival traits indicate that they could be improved through selection. Both phenotypic and genetic correlations among the five survival measures studied were moderate to high and positive. The genetic associations between successive rearing periods were stronger than those that are further apart. CONCLUSIONS: Our estimates of heritability and genetic correlations reported here in a spiny lobster species indicate that improvement in the early survival especially during metamorphosis can be achieved through genetic selection in this highly economic value species.

STEROIDAL SAPONIN TOXICITY IN EASTERN GREY KANGAROOS ( MACROPUS GIGANTEUS): A NOVEL CLINICOPATHOLOGIC PRESENTATION OF HEPATOGENOUS PHOTOSENSITIZATION.

We describe the clinicopathologic features of a mortality event characterized by blindness and dermatitis affecting eastern grey kangaroos ( Macropus giganteus), secondary to hepatogenous photosensitization. Affected animals exhibited photophobic behavior, blindness, ataxia, recumbency, lethargy, ear shaking, and behavior consistent with distress or depression. The photophobia manifested as abnormal shade-seeking during the day, including finding refuge under or in structures used frequently by people. Severely affected kangaroos were jaundiced and had markedly elevated serum bilirubin and gamma glutamyl-transpeptidase concentrations. Blindness in affected animals was attributed to moderate to severe corneal opacity due to corneal edema and inflammation. Skin lesions were typically subtle on gross examination even in cases which had severe necrotizing dermatitis histologically. Histologic lesions in the liver of affected animals included the presence of acicular clefts typical of steroidal saponins. The outbreak was associated with pasture dominated by the invasive grass, Panicum gilvum, which is a recognized source of saponin-induced photosensitization in livestock.

Acute-onset high-morbidity primary photosensitisation in sheep associated with consumption of the Casbah and Mauro cultivars of the pasture legume Biserrula.

BACKGROUND: Primary photosensitisation (PS) subsequent to ingestion of the pasture legume Biserrula pelecinus L. (biserrula) has recently been confirmed in grazing livestock. Given the potential utility of this pasture species in challenging climates, a grazing trial was undertaken to examine if both varieties 'Casbah' and 'Mauro' were able to cause photosensitisation in livestock, and if this could be mitigated by grazing in winter, or in combination with other common pasture species. RESULTS: A controlled grazing trial was undertaken in winter in Australia with plots containing a dominant pasture of Biserrula pelecinus L. cv. 'Casbah' or 'Mauro', or mixed biserrula/perennial ryegrass populations. A photosensitisation grading system was established. 167 prime meat ewe lambs were introduced to the plots and monitored twice daily. Mild clinical signs were observed at 72 h on pasture. All animals were removed from biserrula dominant stands at this point. Four animals grazing 'Casbah' dominant pasture rapidly proceeded to severe photosensitisation in the following 12 h. Animals remaining on mixed biserrula/ryegrass stands did not exhibit severe PS but showed an 89% incidence of mild to moderate photosensitisation over the following 14 days. Animals on mixed lucerne showed significantly lower PS score than animals grazing biserrula varieties of any composition. The trial was halted at 14 days as only plots with low biserrula proportion still contained unaffected animals. Necropsy revealed severe multifocal erythematous ulcerations and alopecia of the ear pinnae, severe bilateral periorbital and conjunctival oedema and variably severe subcutaneous facial oedema. No evidence of hepatopathy was present. A diagnosis of acute unseasonal primary photosensitisation caused by biserrula ingestion with no other underlying pathology was confirmed. CONCLUSIONS: We report an unseasonal outbreak of acute photosensitisation in sheep grazing Biserrula pelecinus L cvs.'Casbah' and 'Mauro' with exceedingly high morbidity. A grading system is also proposed as a tool for objective and consistent clinical appraisal of future PS outbreaks. This finding expands our definition of seasonal and temporal risk periods for biserrula photosensitisation, and is the first to identify that both commercial cultivars of biserrula can cause primary photosensitisation in sheep.

Minicircle Mediated Gene Delivery to Canine and Equine Mesenchymal Stem Cells.

Gene-directed tissue repair offers the clinician, human or veterinary, the chance to enhance cartilage regeneration and repair at a molecular level. Non-viral plasmid vectors have key biosafety advantages over viral vector systems for regenerative therapies due to their episomal integration however, conventional non-viral vectors can suffer from low transfection efficiency. Our objective was to identify and validate in vitro a novel non-viral gene expression vector that could be utilized for ex vivo and in vivo delivery to stromal-derived mesenchymal stem cells (MSCs). Minicircle plasmid DNA vector containing green fluorescent protein (GFP) was generated and transfected into adipose-derived MSCs from three species: canine, equine and rodent and transfection efficiency was determined. Both canine and rat cells showed transfection efficiencies of approximately 40% using minicircle vectors with equine cells exhibiting lower transfection efficiency. A Sox9-expressing minicircle vector was generated and transfected into canine MSCs. Successful transfection of the minicircle-Sox9 vector was confirmed in canine cells by Sox9 immunostaining. This study demonstrate the application and efficacy of a novel non-viral expression vector in canine and equine MSCs. Minicircle vectors have potential use in gene-directed regenerative therapies in non-rodent animal models for treatment of cartilage injury and repair.

Moderate heritability of hepatopancreatic parvovirus titre suggests a new option for selection against viral diseases in banana shrimp (Fenneropenaeus merguiensis) and other aquaculture species.

BACKGROUND: In shrimp farming, major production losses are caused by viruses. Hepatopancreatic parvovirus (HPV) is one of the viral pathogens that infect banana shrimp (Fenneropenaeus merguiensis). HPV is thought to slow down growth and cause mortality in the juvenile stages of banana shrimp. Genetic improvement through selection of shrimp resistant to viral diseases is one approach to address this issue. This is the first detailed report on an aquaculture species that investigates whether viral titre varies among families and is heritable, and thus whether viral titre per se is a possible candidate trait for selection to produce resistant stock. RESULTS: HPV titre was measured by quantitative polymerase chain reaction of DNA extracted from 1137 offspring (from 48 full-sib families). Estimated heritability of HPV titre, based on the linear animal mixed model, was moderate (h(2) = 0.41). Genetic correlations of HPV with body traits (weight, length and width of body, head and tail) ranged from -0.13 to -0.38. HPV titre was negatively correlated with raw and cooked body colour (-0.33 and -0.43, respectively). CONCLUSIONS: This is the first study based on a large dataset that provides evidence that viral titre may have a genetic component in penaeid shrimp or even in any aquaculture species. The moderate heritability estimated for this trait suggests that resistance to HPV may be achieved by selecting for low HPV titre. With moderate and negative correlations, selection for resistance to HPV should gradually improve body traits and colour of banana shrimp.

Complex Membrane Channel Blockade: A Unifying Hypothesis for the Prodromal and Acute Neuropsychiatric Sequelae Resulting from Exposure to the Antimalarial Drug Mefloquine.

The alkaloid toxin quinine and its derivative compounds have been used for many centuries as effective medications for the prevention and treatment of malaria. More recently, synthetic derivatives, such as the quinoline derivative mefloquine (bis(trifluoromethyl)-(2-piperidyl)-4-quinolinemethanol), have been widely used to combat disease caused by chloroquine-resistant strains of the malaria parasite, Plasmodium falciparum. However, the parent compound quinine, as well as its more recent counterparts, suffers from an incidence of adverse neuropsychiatric side effects ranging from mild mood disturbances and anxiety to hallucinations, seizures, and psychosis. This review considers how the pharmacology, cellular neurobiology, and membrane channel kinetics of mefloquine could lead to the significant and sometimes life-threatening neurotoxicity associated with mefloquine exposure. A key role for mefloquine blockade of ATP-sensitive potassium channels and connexins in the substantia nigra is considered as a unifying hypothesis for the pathogenesis of severe neuropsychiatric events after mefloquine exposure in humans.

Super pharmacological levels of calcitriol (1,25-(OH)2D3) inhibits mineral deposition and decreases cell proliferation in a strain dependent manner in chicken mesenchymal stem cells undergoing osteogenic differentiation in vitro.

The biologically active form of vitamin D3, calcitriol (1,25-(OH)2D3), plays a key role in mineral homeostasis and bone formation and dietary vitamin D3deficiency is a major cause of bone disorders in poultry. Supplementary dietary cholecalciferol (25-hydroxyvitamin D, 25-OH), the precursor of calcitriol, is commonly employed to combat this problem; however, dosage must be carefully determined as excess dietary vitamin D can cause toxicity resulting in a decrease in bone calcification, hypercalcinemia and renal failure. Despite much research on the therapeutic administration of dietary vitamin D in humans, the relative sensitivity of avian species to exogenous vitamin D has not been well defined. In order to determine the effects of exogenous 1,25-(OH)2D3during avian osteogenesis, chicken bone marrow-derived mesenchymal stem cells (BM-MSCs) were exposed to varying doses of 1,25-(OH)2D3during in vitro osteogenic differentiation and examined for markers of early proliferation and osteogenic induction. Similar to humans and other mammals, poultry BM-MSCs were found to be highly sensitive to exogenous 1,25-(OH)2D3with super pharmacological levels exerting significant inhibition of mineralization and loss of cell proliferation in vitro. Strain related differences were apparent, with BM-MCSs derived from layers strains showing a higher level of sensitivity to 1,25-(OH)2D3than those from broilers. These data suggest that understanding species and strain specific sensitivities to 1,25-(OH)2D3is important for optimizing bone health in the poultry industry and that use of avian BM-MSCs are a useful tool for examining underlying effects of genetic variation in poultry.