Alzheimer’s dementia (AD) is a progressive, neurodegenerative disease often accompanied by neuropsychiatric symptoms that profoundly impact both patients and caregivers. Agitation is among the most prevalent and distressing of these symptoms and often requires treatment. Appropriate therapeutic interventions depend on understanding the biological basis of agitation and how it may be affected by treatment. This narrative review discusses a proposed pathophysiology of agitation in Alzheimer’s dementia based on convergent evidence across research approaches. Available data indicate that agitation in Alzheimer’s dementia is associated with an imbalance of activity between key prefrontal and subcortical brain regions. The monoamine neurotransmitter systems serve as key modulators of activity within these brain regions and circuits and are rendered abnormal in AD. Patients with AD who exhibited agitation symptoms during life have alterations in neurotransmitter nuclei and related systems when the brain is examined at autopsy. The authors present a model of agitation in Alzheimer’s dementia in which noradrenergic hyperactivity along with serotonergic deficits and dysregulated striatal dopamine release contribute to agitated and aggressive behaviors.

Osteoarthritis (OA), a disease with a multifactorial aetiology and an enigmatic root cause, affects the quality of life of many elderly patients. Even though there are certain medications utilised to reduce the symptomatic effects, a reliable treatment method to reverse the disease is yet to be discovered. Zinc is a cofactor of over 3000 proteins and is the only metal found in all six classes of enzymes. We explored zinc’s effect on the immune system and the bones as OA affects both. We also discussed zinc-dependent enzymes, highlighting their significant role in the disease’s pathogenesis. It is important to note that both excessive and deficient zinc levels can negatively affect bone health and immune function, thereby exacerbating OA. The purpose of this review is to offer a better understanding of zinc’s impact on OA pathogenesis and to provide clarity regarding its beneficial and detrimental outcomes. We searched thoroughly systematic reviews, meta-analysis, review articles, research articles and randomised controlled trials to ensure a comprehensive review. In brief, using zinc supplementation in the treatment of OA may act as a doubled-edged sword, offering potential benefits but also posing risks.

Guillain-Barre syndrome (GBS) is the commonest cause of acute polyradiculoneuropathy that requires hospitalization. Many of these patients experience systemic and disease-related complications during its course. Notable among them is hyponatremia. Though recognized for decades, the precise incidence, prevalence, and mechanism of hyponatremia in GBS are not well known. Hyponatremia in GBS patients is associated with more severe in-hospital disease course, prolonged hospitalization, higher mortality, increased costs, and a greater number of other complications in the hospital and worse functional status at 6 months and at 1 year. Though there are several reports of low sodium associated with GBS, many have not included the exact temporal relationship of sodium or its serial values during GBS thereby underestimating the exact incidence, prevalence, and magnitude of the problem. Early detection, close monitoring, and better understanding of the pathophysiology of hyponatremia have therapeutic implications. We review the complexities of the relationship between hyponatremia and GBS with regard to its pathophysiology and treatment.

The evolution of the understanding of the intestinal microbiota and its influence on our organism leverages it as a potential protagonist in therapies aimed at diseases that affect not only the intestine but also neural pathways and the central nervous system itself. This study, developed from a thorough systematic review, sought to demonstrate the influence of the intervention on the intestinal microbiota in subjects with Alzheimer’s disease. Clinical trials using different classes of probiotics have depicted noteworthy remission of symptoms, whose measurement was performed based on screenings and scores applied before, during, and after the period of probiotics use, allowing the observation of changes in functionality and symptomatology of patients. On the other hand, faecal microbiota transplantation requires further validation through clinical trials, even though it has already been reported in case studies as promising from the symptomatology point of view. The current compilation of studies made it possible to demonstrate the potential influence of the intestinal microbiota on Alzheimer’s pathology. However, new clinical studies with a larger number of participants are needed to obtain further clarification on pathophysiological correlations.

Important developments in the conceptualisation and classification of negative symptoms have contributed to refining hypotheses on their pathophysiology. The uptake of recent progress is still only partial and the whole field might make a leap forward once relevant studies fully make use of assessment tools based on current conceptualisations.

Cardiac arrhythmias occur at all ages. Cardiac mapping and ablation are established methods for curing arrhythmia substrates; however, complications may occur. We report a patient with transient Wenckebach heart block during radiofrequency ablation in the setting of Wolff Parkinson White syndrome despite the ablation catheter being well away from the atrioventricular node, and we speculate on the potential mechanism.

Female laboratory rats (Rattus norvegicus; Wistar, Alderley Park) were housed as singletons or groups of three in units of two cages. Units were divided by different types of barrier which allowed varying degrees of social contact across the barrier. Singletons were established either with another singleton on the other side of the barrier or with a group of three as neighbours. Single-housing among females had markedly less effect on time budgeting and pathophysiological measures than among males in a similar, earlier study. In particular, singletons showed a less marked increase in self-directed behaviours, particularly tail chasing, and a smaller reduction in undirected movement around the cage. The smaller reduction in mobility may reflect a greater tendency for singly housed females to attempt escape. Females generally showed much higher levels of escape-oriented behaviours than males and up to a threefold increase in such behaviours when housed singly. Differences in time budgeting and in the apparent significance of social separation between the sexes can be interpreted in terms of differences in socio-sexual strategy and potential mating opportunity, with singleton males responding to their cage as a territory, but singleton females seeking to re-establish social contact. Such an interpretation is consistent with the effects of barrier type on behaviour in singleton females, in which time spent in escape-oriented behaviours reflected the extent to which the barrier facilitated, or frustrated, contact with neighbours.

Male laboratory rats (Rattus norvegicus; Wistar, Alderley Park) were housed as singletons or groups of three in units of two joined, but divided cages. Units were divided by different types of barrier that allowed different degrees of social contact across the barrier. Singletons were established either with another singleton as a neighbour on the other side of the barrier, or with a group of three as neighbours. Relative to group-housed animals, singly-housed rats showed reduced activity and a greater incidence of self-directed behaviours and behaviours apparently related to escape or seeking social information. Pathophysiological evidence was consistent with Baenninger's (1967) suggestion that tail manipulation in singletons is a surrogate social response, but was also consistent with an overall increase in self-directed activity, reflecting elasticity in time budgeting. Variation in the degree of increase in self-directed activity among singletons and the negative correlation between self-directed activity and organ pathology may have reflected differences in the ability of individuals to avoid an activity limbo. While reduced corticosterone concentration and organ pathology compared with grouped rats implied that separation may remove social stress, responses to contact with neighbours, and correlations between behaviours and organ pathology suggested that rats may actively seek social interaction. Broad differences in stress responses between single and grouped housing conditions may therefore be an inadequate yardstick to the animals’ welfare. However, exposure to neighbours reduced the aggressiveness of singly-housed males when they were eventually introduced into an unfamiliar group, suggesting that a degree of exposure to neighbours (separation, but not isolation) may have some welfare benefits for laboratory-housed rats, depending on procedures.

Although antipsychotics were discovered over fifty years ago, it took another decade until dopamine antagonism was demonstrated as central to their clinical effectiveness. Since accumulated evidence implicates the dopamine system in the pathophysiology of schizophrenia, all licensed first-line treatments operate primarily via antagonism of the dopamine D2 receptor. However, dopamine D2 receptor blockade does not effectively treat negative, cognitive and affective symptoms and, in a significant proportion of patients, it does not improve positive symptoms either. Therefore, additional neurochemical targets were considered. The “revised dopamine hypothesis” proposes that positive symptoms emerge due to hyperactive dopamine transmission in mesolimbic areas, while hypoactive dopamine transmission via the mesocortical pathway in the prefrontal cortex is linked to negative, cognitive, and partly affective symptoms. In this context, the role of D3 receptors were recognised. However, there is also evidence for the involvement of other neurotransmitter systems, suggesting that dopamine signalling relies on a suite of receptors that are thought to either facilitate or inhibit neurotransmitter activity through several interconnected neural circuits. Furthermore, there seem to be clusters of symptoms that cross the boundaries of disorders. Symptoms having similar pathophysiology at neurotransmitter level can be treated with the same drug or class of drugs. Thus, one particular drug might be effective in more than one indication. This lecture aims to illustrate the process of a new drug development by explaining how the underlying pathophysiology on receptor level impacts clinical studies and vice versa.