Home visits in rural general practice: what does the future hold?

INTRODUCTION: Declining house-call rates have been documented worldwide; however, up-to-date data on current rates are lacking, particularly in rural settings. Systematic reviews in this area are inconsistent; however, other work, principally qualitative research, demonstrates benefits for both doctors and patients. The aim of this study was to establish the current rate of, and reasons for, home visits in a rural general practice setting. METHODS: This was a descriptive observational study in the north-west of Ireland. Fourteen general practice training practices with approximately 30 000 patients were recruited. Data on house calls done in each practice were collected during May and June 2019. Anonymised data were analysed using Microsoft Excel and GraphPad. RESULTS: Data were received on 547 house calls. The rate of house calls done within normal working hours (443) was calculated at 87 house calls/1000 patients/year (raw proportion 1.44%). Using the N-1 χ2 test, this rate was compared to that calculated in a similar 2009 study (143/1000/year; raw proportion 2.43%), giving a difference of 0.991% (95% confidence interval 0.759-1.22%; p<0.001). This is a statistically significant reduction of 40% over 10 years. Most (86.2%) house calls were to patients aged over 65 years. House calls were commonly done for respiratory infection (17%), other infections (12%), palliative care (11%) and pain (11%). Most patients were managed solely within the community (88.3%), with 45.8% of those requiring a prescription, and only 11.7% of house calls being referred to hospital. CONCLUSION: There are documented benefits to home visits and yet the rate of house calls has been declining worldwide. With no recent literature on the rate or reasons for home visits in rural general practice, this research has demonstrated that the house call rate in the north-west of Ireland is falling, mirroring the decline seen in other parts of Europe, Australia and the USA. These house calls are mainly for elderly patients to address infection or palliative care, and the majority can be managed successfully by general practitioners in the community. With an ageing population with increasing multi-morbidity, planning for care delivery to these patients is important for clinicians going forward. We now need to decide if house calls are a service worth saving.

Odorant-receptor-mediated regulation of chemosensory gene expression in the malaria mosquito Anopheles gambiae.

Mosquitoes locate and approach humans based on the activity of odorant receptors (ORs) expressed on olfactory receptor neurons (ORNs). Olfactogenetic experiments in Anopheles gambiae mosquitoes revealed that the ectopic expression of an AgOR (AgOR2) in ORNs dampened the activity of the expressing neuron. This contrasts with studies in Drosophila melanogaster in which the ectopic expression of non-native ORs in ORNs confers ectopic neuronal responses without interfering with native olfactory physiology. RNA-seq analyses comparing wild-type antennae to those ectopically expressing AgOR2 in ORNs indicated that nearly all AgOR transcripts were significantly downregulated (except for AgOR2). Additional experiments suggest that AgOR2 protein rather than mRNA mediates this downregulation. Using in situ hybridization, we find that AgOR gene choice is active into adulthood and that AgOR2 expression inhibits AgORs from turning on at this late stage. Our study shows that the ORNs of Anopheles mosquitoes (in contrast to Drosophila) are sensitive to a currently unexplored mechanism of AgOR regulation.

Diet Drugs Trick Mosquitoes into Feeling Full.

After a bloodmeal, Aedesaegypti mosquitoes lose interest in bloodfeeding. Duvall et al. (Cell 2019;176:687-701) determined that the neuropeptide Y (NPY)-like receptor 7 (NPYLR7) controls mosquito satiety and also identified six NPYLR7 drug targets that suppress biting. This work highlights an innovative approach in vector control linking insect behavior to drug discovery.

Olfactory Neurons and Brain Centers Directing Oviposition Decisions in Drosophila.

The sense of smell influences many behaviors, yet how odors are represented in the brain remains unclear. A major challenge to studying olfaction is the lack of methods allowing activation of specific types of olfactory neurons in an ethologically relevant setting. To address this, we developed a genetic method in Drosophila called olfactogenetics in which a narrowly tuned odorant receptor, Or56a, is ectopically expressed in different olfactory neuron types. Stimulation with geosmin (the only known Or56a ligand) in an Or56a mutant background leads to specific activation of only target olfactory neuron types. We used this approach to identify olfactory sensory neurons (OSNs) that directly guide oviposition decisions. We identify 5 OSN-types (Or71a, Or47b, Or49a, Or67b, and Or7a) that, when activated alone, suppress oviposition. Projection neurons partnering with these OSNs share a region of innervation in the lateral horn, suggesting that oviposition site selection might be encoded in this brain region.

Independent Effects of γ-Aminobutyric Acid Transaminase (GABAT) on Metabolic and Sleep Homeostasis.

Breakdown of the major sleep-promoting neurotransmitter, γ-aminobutyric acid (GABA), in the GABA shunt generates catabolites that may enter the tricarboxylic acid cycle, but it is unknown whether catabolic by-products of the GABA shunt actually support metabolic homeostasis. In Drosophila, the loss of the specific enzyme that degrades GABA, GABA transaminase (GABAT), increases sleep, and we show here that it also affects metabolism such that flies lacking GABAT fail to survive on carbohydrate media. Expression of GABAT in neurons or glia rescues this phenotype, indicating a general metabolic function for this enzyme in the brain. As GABA degradation produces two catabolic products, glutamate and succinic semialdehyde, we sought to determine which was responsible for the metabolic phenotype. Through genetic and pharmacological experiments, we determined that glutamate, rather than succinic semialdehyde, accounts for the metabolic phenotype of gabat mutants. This is supported by biochemical measurements of catabolites in wild-type and mutant animals. Using in vitro labeling assays, we found that inhibition of GABAT affects energetic pathways. Interestingly, we also observed that gaba mutants display a general disruption in bioenergetics as measured by altered levels of tricarboxylic acid cycle intermediates, NAD(+)/NADH, and ATP levels. Finally, we report that the effects of GABAT on sleep do not depend upon glutamate, indicating that GABAT regulates metabolic and sleep homeostasis through independent mechanisms. These data indicate a role of the GABA shunt in the development of metabolic risk and suggest that neurological disorders caused by altered glutamate or GABA may be associated with metabolic disruption.

Heating and cooling the Drosophila melanogaster clock.

Most biological phenomena are under control of a circuit known as the 'molecular circadian clock.' Over the past forty years of research in Drosophila melanogaster, studies have made significant advances in our understanding of the molecular timing mechanism of this circuit, which is determined by a core inhibitory feedback loop. While the timing mechanism of the molecular circadian clock is endogenous, it is well established that exogenous cues such as light and temperature modulate its timing. In the following article, we summarize our current understanding of how temperature interacts with the molecular circadian clock in adult Drosophila.

Natural Populations of Drosophila melanogaster Reveal Features of an Uncharacterized Circadian Property: The Lower Temperature Limit of Rhythmicity.

Most cyclic biological processes are under control of a circadian molecular timing system that synchronizes these phenomena to the 24-h day. One generic property of circadian-controlled processes is that they operate within a specific temperature range, below which the manifestation of rhythm ceases. Little is known about the evolutionary relevance of the lower temperature limit of rhythmicity or about the mechanism underlying the loss of overt circadian behavior below this lower limit, especially in one model organism of chronobiology, Drosophila melanogaster. Natural populations of Drosophila are evolving under divergent selection pressures and so provide a source of diversity necessary to address these issues. Using lines derived from African populations, we find that there is natural variation in the expression of rhythmic behavior under low-temperature conditions. We found evidence that this variability is evolutionarily relevant at extremely low temperature (12 °C) because high-altitude populations exhibit selection for locally adapted genomes that contribute to rhythmic behavior. Lines resistant to 15 °C show an additional layer of diversity in their response to temperature extremes because some lines are resistant to low temperature (15 °C) only, whereas others are cross-resistant to high and low temperature (15 °C and 30 °C). Genetic analysis of one cold-resistant circadian line at 15 °C reveals that the phenotype maps to the X-chromosome but not to the core clock genes, per and sgg. Analysis of the central clock cells of this line reveals that maintenance of rhythm is associated with robust clock function, which is compromised in a standard laboratory strain. These data indicate that the cold-resistant circadian phenotype is clock based. This study highlights the importance of using natural populations to inform us of the basic features of circadian traits, especially those that might be under temperature-based selection.

Social brains in context: lesions targeted to the song control system in female cowbirds affect their social network.

Social experiences can organize physiological, neural, and reproductive function, but there are few experimental preparations that allow one to study the effect individuals have in structuring their social environment. We examined the connections between mechanisms underlying individual behavior and social dynamics in flocks of brown-headed cowbirds (Molothrus ater). We conducted targeted inactivations of the neural song control system in female subjects. Playback tests revealed that the lesions affected females' song preferences: lesioned females were no longer selective for high quality conspecific song. Instead, they reacted to all cowbird songs vigorously. When lesioned females were introduced into mixed-sex captive flocks, they were less likely to form strong pair-bonds, and they no longer showed preferences for dominant males. This in turn created a cascade of effects through the groups. Social network analyses showed that the introduction of the lesioned females created instabilities in the social structure: males in the groups changed their dominance status and their courtship patterns, and even the competitive behavior of other female group-mates was affected. These results reveal that inactivation of the song control system in female cowbirds not only affects individual behavior, but also exerts widespread effects on the stability of the entire social system.