Educating pharmacy students through a pandemic: Reflecting on our COVID-19 experience.

The impact of the COVID-19 pandemic on pharmacy education worldwide has been immense, affecting students, educators and regulatory agencies. Pharmacy programmes have had to rapidly adapt in their delivery of education, maintaining standards while also ensuring the safety of all stakeholders. In this commentary, we describe the challenges, compromises and solutions adopted by our institution throughout the pandemic, the lessons learnt, adaptive measures taken, and strategies to develop and future-proof our curricula.

Ethologically based behavioural and neurochemical characterisation of mice with isoform-specific loss of dysbindin-1A in the context of schizophrenia.

Dysbindin-1 is implicated in several aspects of schizophrenia, including cognition and both glutamatergic and dopaminergic neurotransmission. Targeted knockout of dysbindin-1A (Dys-1A KO), the most abundant and widely expressed isoform in the brain, is associated with deficits in delay/interference-dependent working memory. Using an ethologically based approach, the following behavioural phenotypes were examined in Dys-1A KO mice: exploratory activity, social interaction, anxiety and problem-solving ability.

Acute stress in adolescence vs early adulthood following selective deletion of dysbindin-1A: Effects on anxiety, cognition and other schizophrenia-related phenotypes.

Background: As exposure to stress has been linked to the onset and maintenance of psychotic illness, its pathogenesis may involve environmental stressors interacting with genetic vulnerability.

Aim: To establish whether acute stress interacts with a targeted mutation of the gene encoding the neurodevelopmental factor dystrobrevin-binding protein 1 (DTNBP1), resulting in a specific loss of the isoform dysbindin-1A, to influence schizophrenia-relevant phenotypes in mice during adolescence and adulthood.

Methods: Male and female mice with a heterozygous or homozygous deletion of DTNBP1 were assessed in the open field test following acute restraint stress in adolescence (Day 35) and young adulthood (Day 60-70).

Dysregulation of Specialized Delay/Interference-Dependent Working Memory Following Loss of Dysbindin-1A in Schizophrenia-Related Phenotypes.

Dysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated a novel mutant mouse, dys-1A, with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment.

Altered cytokine profile, pain sensitivity, and stress responsivity in mice with co-disruption of the developmental genes Neuregulin-1×DISC1.

The complex genetic origins of many human disorders suggest that epistatic (gene×gene) interactions may contribute to a significant proportion of their heritability estimates and phenotypic heterogeneity. Simultaneous disruption of the developmental genes and schizophrenia risk factors Neuregulin-1 (NRG1) and Disrupted-in-schizophrenia 1 (DISC1) in mice has been shown to produce disease-relevant and domain-specific phenotypic profiles different from that observed following disruption of either gene alone. In the current study, anxiety and stress responsivity phenotypes in male and female mutant mice with simultaneous disruption of DISC1 and NRG1 were examined.

Associations between single-nucleotide polymorphisms of ADIPOQ, serum adiponectin and increased type 2 diabetes mellitus risk in Bahraini individuals.

This study aimed to estimate the frequency of the SNPs (+45T>G and +276G>T) genotypes and investigate the association between the two SNPs and adiponectin concentration, metabolic parameters and risk of T2DM in the Bahraini population. We genotyped the two ADIPOQ SNPs in 140 unrelated T2DM patients and 66 nondiabetic controls using the polymerase chain reaction-restriction fragment length polymorphism assay. Lipid profile was measured by enzymatic methods.

Epistatic and Independent Effects on Schizophrenia-Related Phenotypes Following Co-disruption of the Risk Factors Neuregulin-1 × DISC1.

Few studies have addressed likely gene × gene (ie, epistatic) interactions in mediating risk for schizophrenia. Using a preclinical genetic approach, we investigated whether simultaneous disruption of the risk factors Neuregulin-1 (NRG1) and Disrupted-in-schizophrenia 1 (DISC1) would produce a disease-relevant phenotypic profile different from that observed following disruption to either gene alone. NRG1 heterozygotes exhibited hyperactivity and disruption to prepulse inhibition, both reversed by antipsychotic treatment, and accompanied by reduced striatal dopamine D2 receptor protein expression, impaired social cognition, and altered glutamatergic synaptic protein expression in selected brain areas.

Phenotypic effects of maternal immune activation and early postnatal milieu in mice mutant for the schizophrenia risk gene neuregulin-1.

Risk of schizophrenia is likely to involve gene × environment (G × E) interactions. Neuregulin 1 (NRG1) is a schizophrenia risk gene, hence any interaction with environmental adversity, such as maternal infection, may provide further insights into the basis of the disease. This study examined the individual and combined effects of prenatal immune activation with polyriboinosinic-polyribocytidilic acid (Poly I:C) and disruption of the schizophrenia risk gene NRG1 on the expression of behavioral phenotypes related to schizophrenia.

Phenotypic effects of repeated psychosocial stress during adolescence in mice mutant for the schizophrenia risk gene neuregulin-1: a putative model of gene × environment interaction.

There is a paucity of animal models by which the contributions of environmental and genetic factors to the pathobiology of psychosis can be investigated. This study examined the individual and combined effects of chronic social stress during adolescence and deletion of the schizophrenia risk gene neuregulin-1 (NRG1) on adult mouse phenotype. Mice were exposed to repeated social defeat stress during adolescence and assessed for exploratory behaviour, working memory, sucrose preference, social behaviour and prepulse inhibition in adulthood.

Physiological and behavioural responsivity to stress and anxiogenic stimuli in COMT-deficient mice.

Catechol-O-methyltransferase, an enzyme involved in regulating brain catecholamine levels, has been implicated in anxiety, pain and/or stress responsivity. Elements of this putative association remain unclarified, notably whether: (a) COMT variation modulates responses to acute and/or chronic stress equally; (b) acute pharmacological inhibition of COMT produces comparable effects on anxiety to that observed after deletion of the COMT gene; (c) COMT genotype modulates action of anxiolytic drugs. We aimed to further investigate the relationship between reduced COMT function, anxiety and stress responsivity in mice.

Genetic vs. pharmacological inactivation of COMT influences cannabinoid-induced expression of schizophrenia-related phenotypes.

Catechol-O-methyltransferase (COMT) is an important enzyme in the metabolism of dopamine and disturbance in dopamine function is proposed to be central to the pathogenesis of schizophrenia. Clinical epidemiological studies have indicated cannabis use to confer a 2-fold increase in risk for subsequent onset of psychosis, with adolescent-onset use conveying even higher risk. There is evidence that a high activity COMT polymorphism moderates the effects of adolescent exposure to cannabis on risk for adult psychosis.

Chronic adolescent exposure to Δ-9-tetrahydrocannabinol in COMT mutant mice: impact on psychosis-related and other phenotypes.

Cannabis use confers a two-fold increase in the risk for psychosis, with adolescent use conferring even greater risk. A high-low activity catechol-O-methyltransferase (COMT) polymorphism may modulate the effects of adolescent Δ-9-tetrahydrocannabinol (THC) exposure on the risk for adult psychosis. Mice with knockout of the COMT gene were treated chronically with THC (4.

Disruption of thermal nociceptive behaviour in mice mutant for the schizophrenia-associated genes NRG1, COMT and DISC1.

Abnormalities in pain perception, especially altered warmth and heat pain sensitivity, have been reported in schizophrenia. Therefore, genes associated with schizophrenia, including neuregulin-1 (NRG1), catechol-O-methyltranferase (COMT) and disrupted-in-schizophrenia-1 (DISC1), may play a role in modulating the physiological and psychological effects of pain stimuli in such patients. Thermal pain sensitivity was assessed in NRG1, COMT and DISC1 mutant mice, and the anti-nociceptive effects of acute Delta(9)-tetrahydrocannabinol (THC) were compared in NRG1 and COMT mutants.

Confirmation that the renin gene distal enhancer polymorphism REN-5312C/T is associated with increased blood pressure.

Background: Studies of knockout and transgenic mice have demonstrated key roles for genes encoding components of the renin angiotensin system in blood pressure regulation. However, whether polymorphisms in these genes contribute to the cause of essential hypertension in humans is still a matter of debate.

Methods And Results: We performed an experiment with dense tagging single-nucleotide polymorphism coverage of 4 genes encoding proteins that control the overall activity of the cascade, namely renin, angiotensinogen, angiotensin-converting enzyme, and angiotensin-converting enzyme 2, in 2 Irish populations.

Schizophrenia-related endophenotypes in heterozygous neuregulin-1 'knockout' mice.

Neuregulin-1 (NRG1) has been shown to play a role in glutamatergic neurotransmission and is a risk gene for schizophrenia, in which there is evidence for hypoglutamatergic function. Sensitivity to the behavioural effects of the psychotomimetic N-methyl-D-aspartate receptor antagonists MK-801 and phencyclidine (PCP) was examined in mutant mice with heterozygous deletion of NRG1. Social behaviour (sociability, social novelty preference and dyadic interaction), together with exploratory activity, was assessed following acute or subchronic administration of MK-801 (0.

The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations.

Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers.

Phenotype of spontaneous orofacial dyskinesia in neuregulin-1 'knockout' mice.

Studies in antipsychotic-naïve patients with schizophrenia indicate a baseline level of spontaneous involuntary movements, particularly orofacial dyskinesia. Neuregulin-1 is associated with risk for schizophrenia and its functional role can be studied in 'knockout' mice. We have shown previously that neuregulin-1 'knockouts' evidence disruption in social behaviour.

Phenotypic characterization of cognition and social behavior in mice with heterozygous versus homozygous deletion of catechol-O-methyltransferase.

Catechol-O-methyltransferase is an important enzyme in the metabolism of dopamine and an important regulator of aspects of dopamine-dependent working memory in prefrontal cortex that are disturbed in schizophrenia. This study investigated the phenotype of mice with heterozygous deletion vs. homozygous knockout of the catechol-O-methyltransferase gene across paradigms that access processes relevant for psychotic illness.

Exploratory and habituation phenotype of heterozygous and homozygous COMT knockout mice.

Catechol-O-methyltransferase (COMT) inactivates dopamine in prefrontal cortex and is associated clinically with a schizophrenia endophenotype. Using an ethologically based approach, the phenotype of mice with heterozygous COMT deletion was characterised by decreased rearing with increased sifting and chewing. Heterozygous COMT deletion is associated with a distinctive phenotype.

Phenotypic characterization of spatial cognition and social behavior in mice with 'knockout' of the schizophrenia risk gene neuregulin 1.

Neuregulin-1 (NRG1) has been identified as a candidate susceptibility gene for schizophrenia. In the present study the functional role of the NRG1 gene, as it relates to cognitive and social processes known to be disrupted in schizophrenia, was assessed in mice with heterozygous deletion of transmembrane (TM)-domain NRG1 in comparison with wildtypes (WT). Social affiliative behavior was assessed using the sociability and preference for social novelty paradigm, in terms of time spent in: (i) a chamber containing an unfamiliar conspecific vs.

Disruption of orofacial movement topographies in congenic mutants with dopamine D5 but not D4 receptor or DARPP-32 transduction 'knockout'.

The role of D(1)-like [D(1), D(5)] and D(2)-like [D(2), D(3), D(4)] dopamine receptors and dopamine transduction via DARPP-32 in topographies of orofacial movement was assessed in restrained mice with congenic D(4) vs. D(5) receptor vs. DARPP-32 'knockout'.

Sexually dimorphic changes in the exploratory and habituation profiles of heterozygous neuregulin-1 knockout mice.

The neuregulin-1 gene is widely expressed in the central nervous system and is associated with increased risk for schizophrenia. Using an ethologically based approach, the phenotype of neuregulin-1 heterozygous knockout mice was examined by revealing the individual elements of behaviour in the murine repertoire over the prolonged course of interaction with the environment. During initial exploration, neuregulin-1 mutants displayed a phenotype characterized by increases in locomotion and rearing free, with sex-specific alterations in sifting and grooming.

Ethological resolution of behavioral topography and D2-like vs. D1-like agonist responses in congenic D4 dopamine receptor "knockouts": identification of D4:D1-like interactions.

To clarify the involvement of dopamine D4 receptors in behavioral regulation, the phenotypic ethogram of congenic D4 "knockout" mice was studied in terms of (i) course of exploration and habituation, and (ii) topographical responsiveness to the selective D2-like agonist RU 24213 and the selective D1-like agonists A 68930, SK&F 83959 and SK&F 83822. Congenic D4 knockouts were characterized by a small reduction in exploratory sniffing with delayed habituation of sifting. The magnitude and topographical specificity of these effects indicated that any functional role for D4 receptors in exploratory processes is subtle.

Ethological resolution of behavioural topography and D1-like versus D2-like agonist responses in congenic D5 dopamine receptor mutants: identification of D5:D2-like interactions.

The phenotypic ethogram of congenic dopamine D(5) receptor "knockout" mice was evaluated. Each individual topography of behaviour within the natural repertoire was assessed over the extended course of initial exploration of and subsequent habituation to the environment, and following challenge with a series of D(1)-like agonists. Over initial exploration, D(5)-null mice evidenced a modest reduction in locomotion and a modest increase in sifting.

Frequency distribution of the Los Angeles and Duarte galactose-1-phosphate uridyltransferase variant alleles in the Irish population.

Anonymous population screening was carried out to detect the N314D, Los Angeles (D1), and Duarte (D2) alleles of the galactose-1-phosphate uridyltransferase gene in Ireland using 743 blood samples, covering the Traveller (n = 243) and non-Traveller (n = 500) population groups. The frequency of the N314D substitution was found to be 0.099 overall.