Pyramidal Projection Research Articles

Sexual differences in neuronal and synaptic properties across subregions of the mouse insular cortex

BackgroundThe insular cortex (IC) plays a pivotal role in processing interoceptive and emotional information, offering insights into sex differences in behavior and cognition. The IC comprises two distinct subregions: the anterior insular cortex (aIC), that processes emotional and social signals, and the posterior insular cortex (pIC), specialized in interoception and perception of pain. Pyramidal projection neurons within the IC integrate multimodal sensory inputs, influencing behavior and cognition. Despite previous research focusing on neuronal connectivity and transcriptomics, there has been a gap in understanding pyramidal neurons characteristics across subregions and between sexes.MethodsAdult male and female C57Bl/6J mice were sacrificed and tissue containing the IC was collected for ex vivo slice electrophysiology recordings that examined baseline sex differences in synaptic plasticity and transmission within aIC and pIC subregions.ResultsClear differences emerged between aIC and pIC neurons in both males and females: aIC neurons exhibited distinctive features such as larger size, increased hyperpolarization, and a higher rheobase compared to their pIC counterparts. Furthermore, we observed variations in neuronal excitability linked to sex, with male pIC neurons displaying a greater level of excitability than their female counterparts. We also identified region-specific differences in excitatory and inhibitory synaptic activity and the balance between excitation and inhibition in both male and female mice. Adult females demonstrated greater synaptic strength and maximum response in the aIC compared to the pIC. Lastly, synaptic long-term potentiation occurred in both subregions in males but was specific to the aIC in females.ConclusionsWe conclude that there are sex differences in synaptic plasticity and excitatory transmission in IC subregions, and that distinct properties of IC pyramidal neurons between sexes could contribute to differences in behavior and cognition between males and females.

2 Rethinking the Neuropsychology of g: Structural and Functional Lesion Network Mapping of General Cognitive Ability

Objective:General cognitive ability (g) is central to our understanding of human cognition, as it accounts for nearly half of individual differences in performances on diverse cognitive tests. There is growing interest in the brain networks necessary for g because such knowledge could elucidate neural mechanisms of g. Prior work highlighted the association between g and frontoparietal functional networks. However, the specificity of this relationship has been questioned. Moreover, no studies have compared the relative importance of structural and functional networks for g, and most studies have relied on data from neurologically healthy individuals, which limits causal brain-behavior inference. Lesion network mapping (LNM) can overcome such limitations. LNM integrates lesion location and structural and functional brain network data, and allows for inference upon networks necessary for cognitive functions. Here, we used data from three cohorts of patients with focal brain lesions to perform a large-scale LNM study of g. We also compared the relative value of lesion-behavior mapping, and structural and functional LNM, for predicting g across cohorts.Participants and Methods:Using data from 402 individuals with chronic, focal brain lesions from the Iowa Neurological Patient Registry, we created a bifactor model to estimate g from the shared variance across neuropsychological tests. To create “cognitive comparisons,” we also estimated the unique aspects of domain-specific abilities (visuospatial processing, memory, and processing speed) by removing domain-general variance from each. Next, we used multivariate lesion-behavior mapping to create statistically weighted maps linking deficits in g and domain-specific abilities to regions of focal brain damage. To perform LNM, the local maxima of the lesion-behavior maps were used as seeds for structural and functional connectivity analyses based on normative diffusion-weighted imaging and resting-state functional connectivity data, respectively. The resulting maps were collapsed using principal components analysis (PCA). We quantified the overlap between each map and the lesion volumes of patients from two validation cohorts (n = 101, n = 100). We used these scores to predict observed g in the validation cohorts while controlling for lesion volume. We also compared the relative predictive value of the lesion-behavior maps, and the structural and functional LNMs.Results:Lesion-behavior mapping indicated that lesions of left frontal white matter, bilateral frontal operculum/insula, and a region of white matter in the posterior left hemisphere were associated with impairments in g. Across all lesion-behavior mapping and LNM results, only two of the structural LNM maps linked to g were statistically significantly predictive of g in both validation cohorts: a map corresponding to the anterior thalamic radiation, and another corresponding to left frontal pyramidal projections. Both added value beyond lesion-behavior mapping and functional LNM.Conclusions:The results are notable in several respects: they highlight the importance of structural networks for g, de-emphasize the relevance of functional networks for g, and suggest novel brain circuitry involved in g. Our findings are consistent with animal studies implicating anterior thalamic nuclei in working memory, a cognitive function central to g. Clinically, our study highlights the importance of considering domain-general deficits and the effects of focal lesions on distributed cognitive networks.

Evolutionary scaling and cognitive correlates of primate frontal cortex microstructure.

Investigating evolutionary changes in frontal cortex microstructure is crucial to understanding how modifications of neuron and axon distributions contribute to phylogenetic variation in cognition. In the present study, we characterized microstructural components of dorsolateral prefrontal cortex, orbitofrontal cortex, and primary motor cortex from 14 primate species using measurements of neuropil fraction and immunohistochemical markers for fast-spiking inhibitory interneurons, large pyramidal projection neuron subtypes, serotonergic innervation, and dopaminergic innervation. Results revealed that the rate of evolutionary change was similar across these microstructural variables, except for neuropil fraction, which evolves more slowly and displays the strongest correlation with brain size. We also found that neuropil fraction in orbitofrontal cortex layers V-VI was associated with cross-species variation in performance on experimental tasks that measure self-control. These findings provide insight into the evolutionary reorganization of the primate frontal cortex in relation to brain size scaling and its association with cognitive processes.

Cataracta octopoda: Complex anterior pyramidal and sutural cataract simulating an octopus configuration

A middle aged man presented with glare in right eye. On slit lamp examination, he had lenticular opacity in both eyes emanating from central suture with pyramidal projection above the anterior capsular surface with radiating spokes simulating an octopus like configuration which was confirmed on anterior segment tomography. Hence we describe a special entity cataracta octopoda which is a combination of anterior pyramidal and sutural cataract. Posterior segment evaluation was unremarkable. His low vision was attributable to amblyopia developed due to lenticular opacity. However cataract surgery was offered to him in both eyes primarily to treat glare as well as an added benefit of improving some vision due to the aberrated lens with central opacity. He had gained few lines of vision with resolution of glare symptoms.

Synergistic Effect of Dual Surface Modified Ecoflex Polymer for Dynamic Triboelectric Nanogenerator Towards Sustainable Battery‐Free Tally Counter

AbstractTriboelectric nanogenerators (TENGs) scavenge electricity from low‐frequency mechanical motions. This study proposes a simple and cost‐effective method to synthesize a dual‐surface modified Ecoflex polymer (SME Sponge) with a porous inner structure and micro pyramidal projections on its surface. An Ecoflex‐Aluminum‐based contact separation triboelectric nanogenerator (EA‐CS TENG) is fabricated to investigate the impact of pores and micro pyramidal projections on triboelectric performance. The performances are evaluated with and without an air gap between the materials. Despite the gapless responses being lower than those with the air gap, the gapless system demonstrates the capability to charge a 0.1 µF capacitor up to 0.8 V with mechanical forces of 9 N, validating the potential of surface‐modified porous triboelectric materials for gapless TENGs. Additionally, the device with an air gap achieves a charge of 0.1 µF up to 3.3 V with mechanical forces of 9 N. Finally, a completely self‐powered tally counter is employed to verify the powering and sensing applications of EA‐CS TENG with an air gap. This study confirms the feasibility of utilizing low‐cost EA‐CS TENG as a renewable energy source for generating electricity from mechanical motions and driving devices without the need for batteries.

Single-neuron analysis of dendrites and axons reveals the network organization in mouse prefrontal cortex.

The structures of dendrites and axons form the basis for the connectivity of neural network, but their precise relationship at single-neuron level remains unclear. Here we report the complete dendrite and axon morphology of nearly 2,000 neurons in mouse prefrontal cortex (PFC). We identified morphological variations of somata, dendrites and axons across laminar layers and PFC subregions and the general rules of somatodendritic scaling with cytoarchitecture. We uncovered 24 morphologically distinguishable dendrite subtypes in 1,515 pyramidal projection neurons and 405 atypical pyramidal projection neurons and spiny stellate neurons with unique axon projection patterns. Furthermore, correspondence analysis among dendrites, local axons and long-range axons revealed coherent morphological changes associated with electrophysiological phenotypes. Finally, integrative dendrite-axon analysis uncovered the organization of potential intra-column, inter-hemispheric and inter-column connectivity among projection neuron types in PFC. Together, our study provides a comprehensive structural repertoire for the reconstruction and analysis of PFC neural network.

Acute-stress induces the structural plasticity in hippocampal neurons of 15 and 30-day-old chick, Gallus gallus domesticus

To study the stress effect on neuronal architecture in the avian hippocampus (a vital component of the neural circuitry mediating stress responses), chick constitutes an interesting animal model. The hippocampus due to its susceptible and vulnerable nature towards acute-stress effect shows pronounced structural and morphological plasticity. Therefore, to perform a detailed investigation of the acute-stress effect on neuronal architecture in the hippocampus, the present study targets to examine the role of a single acute-stress session of 24-hours food and water deprivation in inducing structural plasticity in 15 and 30-day-old chick by using Golgi-Cox staining technique.The findings of the present study have displayed that the chick hippocampus contains highly spinous multipolar, pyramidal, and stellate neuronal cells, along with four variably shaped spines namely filopodia, thin, stubby, and mushroom, over their dendritic branches. In the hippocampus of a 15-day-old chick, the multipolar projection and the stellate neurons show a significant decrease in their spine density under acute-stress, while the pyramidal projection neurons show a significant increase. All the hippocampus neuronal cells of 30-day-old chicks have shown a significant decrease in their dendritic spine density under stressful environment. Therefore, the present research study establishes structural plasticity in hippocampus neurons due to changes in environmental conditions that may affect the animal’s behavior.

SELF: A Novel Algorithm for Deciding the Position of Lateral Osteotomies in Rhinoplasty Patients with Minimal External Deviation.

Although the different techniques and instruments described for lateral osteotomies date back decades, the literature on deciding the position of lateral osteotomies between the sides is limited. In general, the position of lateral osteotomies is decided by frontal view and palpation, but this is not always easy, especially in minimally deviated noses. The SELF algorithm, which includes 4 developmentally related parameters, was used to decide the position and number of lateral osteotomies. Parameters of the SELF algorithm are septal position in nasal floor, external alar length, lateral pyramidal length and frontal pyramidal deviation's starting side. After considering and evaluating these parameters, either double lateral or high lateral osteotomy was performed on the side where the bony wall was considered to be longer. Out of 521 patients whose lateral osteotomy level was decided by applying the SELF algorithm, 493 were female, and 28 were male. The ages of the patients ranged from 18 to 59 years. Based on the SELF algorithm, 401 double lateral and 85 high lateral osteotomies were performed on the side with the longest anterior-posterior distance of the bony pyramid. No serious complications, either functionally or aesthetically, were encountered related to lateral osteotomies performed based on the SELF algorithm. There is a relationship between the position of the septum at the nasal floor, external alar length, lateral pyramidal projection and frontal deviation, as the tissues in the nose are shaped in relation to each other during development. The SELF algorithm based on these parameters can provide assistance to the surgeon in terms of selecting the position and number of lateral osteotomies, especially in minimally deviated noses. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

STUDY OF OCCURRENCE OF THE ANTERIOR TUBERCLE IN THE MARGIN OF THE OCCIPITAL FORAMEN IN BIHAR STATE REGION

Background: The presence of structures that pass along the anterior margin of the occipital foramen interposed between the basilar part of the occipital and the atlas may reduce the circumference of the foramen causing compression of the spinal cord and leading to signs and symptoms of neurological decits due to its asymmetry. The aim of this study was to determine the incidence of anterior tubercle at the occipital foramen margin. Out of 50 skulls, 2 (4%) skulls shows occurrence of the anterior tubercle in the margin the occipital foramen/foramen magnum with different antero-posterior and transverse measurement . Tubercle was found in the anterior margin of the occipital foramen in 2 (two) skull, The incidence of occipital tubercle, probably formed by the apical ligament exostosis of the dens, was 04 %. In 1st case the tubercle had a triangular shape, was situated at the midpoint of the anterior margin of the foramen, with its apex facing back toward the occipital foramen and measuring about 4mm in the antero-posterior direction and 3 mm in the transverse. In 2nd case a pyramidal projection was found at the anterior margin of foramen magnum, with the apex directed backwards towards the posterior margin of foramen magnum. The tubercle measured 3.5 mm antero-posteriorly and 2mm transversely. The knowledge of the presence of the occipital tubercle is of great clinical importance, as it may lead in many cases to compression of the neurovascular structures.

Neuronal localization of m1 muscarinic receptor immunoreactivity in the monkey basolateral amygdala.

The basolateral nuclear complex (BNC) of the amygdala plays an important role in the generation of emotional/motivational behavior and the consolidation of emotional memories. Activation of M1 cholinergic receptors (M1Rs) in the BNC is critical for memory consolidation. Previous receptor binding studies in the monkey amygdala demonstrated that the BNC has a high density of M1Rs, but did not have sufficient resolution to identify which neurons in the BNC expressed them. This was accomplished in the present immunohistochemical investigation using an antibody for the m1 receptor (m1R). Analysis of m1Rs in the monkey BNC using immunoperoxidase techniques revealed that their expression was very dense in the BNC, and suggested that virtually all of the pyramidal projection neurons (PNs) in all of the BNC nuclei were m1R-immunoreactive (m1R+). This was confirmed with dual-labeling immunofluorescence using staining for calcium/calmodulin-dependent protein kinase II (CaMK) as a marker for BNC PNs. However, additional dual-labeling studies indicated that one-third of inhibitory interneurons (INs) expressing glutamic acid decarboxylase (GAD) were also m1R+. Moreover, the finding that 60% of parvalbumin (PV) immunoreactive neurons were m1R+ indicated that this IN subpopulation was the main GAD+ subpopulation exhibiting m1R expression. The cholinergic innervation of the amygdala is greatly reduced in Alzheimer's disease and there is currently considerable interest in developing selective M1R positive allosteric modulators (PAMs) to treat the symptoms. The results of the present study indicate that M1Rs in both PNs and INs in the primate BNC would be targeted by M1R PAMs.

N-Type Calcium Channels Control GABAergic Transmission in Brain Areas related to Fear and Anxiety

N-type (CaV2.2) calcium channels are key for action potential-evoked transmitter release in the peripheral and central nervous system. Previous studies have highlighted the functional relevance of N-type calcium channels at both the peripheral and central level. In the periphery, N-type calcium channels regulate nociceptive and sympathetic responses. At the central level, N-type calcium channels have been linked to aggression, hyperlocomotion, and anxiety. Among the areas of the brain that are involved in anxiety are the basolateral amygdala, medial prefrontal cortex, and ventral hippocampus. These three areas share similar characteristics in their neuronal circuitry, where pyramidal projection neurons are under the inhibitory control of a wide array of interneurons including those that express the peptide cholecystokinin. This type of interneuron is well-known to rely on N-type calcium channels to release GABA in the hippocampus, however, whether these channels control GABA release from cholecystokinin-expressing interneurons in the basolateral amygdala and medial prefrontal cortex is not known. Here, using mouse models to genetically label cholecystokinin-expressing interneurons and electrophysiology, we found that in the basolateral amygdala, N-type calcium channels control ~50% of GABA release from these neurons onto pyramidal cells. By contrast, in the medial prefrontal cortex N-type calcium channels are functionally absent in synapses of cholecystokinin-expressing interneurons, but control ~40% of GABA release from other types of interneurons. Our findings provide insights into the precise localization of N-type calcium channels in interneurons of brain areas related to anxiety.

Distinct populations of cortical pyramidal neurons mediate drug reward and aversion

Processing within the anterior cingulate cortex (ACC) is crucial for the patterning of appropriate behavior, and ACC dysfunction following chronic drug use is thought to play a major role in drug addiction. However, cortical pyramidal projection neurons can be subdivided into two major types (intratelencephalic (IT) and pyramidal tract (PT)), with distinct inputs and projection targets, molecular and receptor profiles, morphologies and electrophysiological properties. Yet, how each of these cell populations modulate behavior related to addiction is unknown. We demonstrate that PT neurons regulate the positive features of a drug experience whereas IT neurons regulate the negative features. These findings support a revised theory of cortical function in addiction, with distinct cells and circuits mediating reward and aversion.

Expression of the type 1 cannabinoid receptor (CB1R) in CCK-immunoreactive axon terminals in the basolateral amygdala of the rhesus monkey (Macaca mulatta)

Studies in rodents have shown that interactions between cholecystokinin (CCK) and the endogenous cannabinoid system in the basolateral nuclear complex of the amygdala (BNC) modulate anxiety-like behavior and fear learning/expression. One of the main cell types implicated is a CCK-immunoreactive (CCK+) basket cell that innervates the somata of pyramidal projection neurons (PNs) and expresses the type 1 cannabinoid receptor (CB1R) in its axon terminals. Although numerous studies have elucidated the anatomy and physiology of these CCK+/CB1R + interneurons in rodents, it has not been determined if they exist in primates. The present investigation used immunohistochemical techniques in the monkey to answer this question. It was found that the monkey BNC, as in rodents, has a very high density of CB1R + axons, including CB1R + axon terminals that form basket-like plexuses contacting somata of PNs. These axons, as well as axons in the neuropil, exhibit extensive colocalization of CCK and CB1R. These findings suggest that the same synaptic mechanisms involved in CCK-CB1R interactions in rodents may also apply to primates, and that therapies that target the cannabinoid system in the BNC may be useful for treating fear and anxiety in human patients.

The ambiguity of mutuality: discourse and power in corporate value regimes

Corporate values offer a means for consecrating alternative regimes of worth within businesses, explicitly orienting firms around more than the pursuit of profits. This paper examines how corporate values come to be constructed and diffused as a framework for interpretation and action through analysis of Food Co.’s flagship principle: ‘mutuality’. Tracing the deployment of mutuality through Food Co.’s internal processes (within the embodied practice and narratives of employees) and external relationships (within Food Co.’s bottom of the pyramid project in Kenya), the paper illustrates how the ambiguity of mutuality forms a strategic resource for the company by (i) sheltering multiple meanings and interpretations, thus enabling resonance among different situations and subject positions; (ii) allowing for syncretism between seemingly opposing and categorically different forms; and (iii) generating a space for negotiation and dealing with uncertainty. Employing these three themes of ambiguity as an organizing frame for our discussion, we highlight how the ambiguity of corporate values absorbs the contradictions emblematic of the ‘heterarchical firm’ (Stark 2000), while obscuring the obligations and expectations the concept entails as it moves beyond Food Co. to outsourced ‘entrepreneurs’ in Kenya. Language generates the appearance of equivalence and benevolence while seeking new spaces for accumulation and legitimizing the incorporation of labor on precarious terms.

The Giza pyramid: learning from this megaproject

Purpose The purpose of this paper is to demonstrate the contemporary relevance of the management of the Great Pyramid of Giza project. Design/methodology/approach The paper uses evidence from the literature from many disciplines concerning both the objectives and construction of the pyramid. It relates this to recent discussion concerned with the issues faced in megaproject management, which are core to the discussion of success and failure. Findings The analysis shows the significance of the “break-fix model” of megaproject management and how having a sequence of megaprojects builds management through a learning process. It demonstrates the significance of innovation arising from the experience of previous projects in solving major technical challenges and illustrates the importance of the organisation and ethical management of a substantial workforce. Research limitations/implications There is very limited reliable documentary evidence from the time of the construction of Giza (c.2560 BCE). Many sources concerning ancient Egypt are still widely contested. However, the use of research from a combination of disciplines demonstrates the relevance of the project and the importance of learning from history to contemporary project management. Originality/value The authors believe that this is the first paper to analyse the Giza pyramid project from a project management perspective. This was arguably the most significant construction project of ancient history and the paper explains the lessons, which can be learned, which are very significant to today’s megaprojects.

Road segmentation with image-LiDAR data fusion in deep neural network

Robust road segmentation is a key challenge in self-driving research. Though many image based methods have been studied and high performances in dataset evaluations have been reported, developing robust and reliable road segmentation is still a major challenge. Data fusion across different sensors to improve the performance of road segmentation is widely considered an important and irreplaceable solution. In this paper, we propose a novel structure to fuse image and LiDAR point cloud in an end-to-end semantic segmentation network, in which the fusion is performed at decoder stage instead of at, more commonly, encoder stage. During fusion, we improve the multi-scale LiDAR map generation to increase the precision of multi-scale LiDAR map by introducing pyramid projection method. Additionally, we adapted the multi-path refinement network with our fusion strategy and improve the road prediction compared with transpose convolution with skip layers. Our approach has been tested on KITTI ROAD dataset and have a competitive performance.

DeepBouton: Automated Identification of Single-Neuron Axonal Boutons at the Brain-Wide Scale.

Fine morphological reconstruction of individual neurons across the entire brain is essential for mapping brain circuits. Inference of presynaptic axonal boutons, as a key part of single-neuron fine reconstruction, is critical for interpreting the patterns of neural circuit wiring schemes. However, automated bouton identification remains challenging for current neuron reconstruction tools, as they focus mainly on neurite skeleton drawing and have difficulties accurately quantifying bouton morphology. Here, we developed an automated method for recognizing single-neuron axonal boutons in whole-brain fluorescence microscopy datasets. The method is based on deep convolutional neural networks and density-peak clustering. High-dimensional feature representations of bouton morphology can be learned adaptively through convolutional networks and used for bouton recognition and subtype classification. We demonstrate that the approach is effective for detecting single-neuron boutons at the brain-wide scale for both long-range pyramidal projection neurons and local interneurons.

Laminar Organization and Projections of the Motor Cortex of the Sheep

The organization of the motor cortex of the sheep is a gateway to understand quadrupedal locomotion, and a possible point of reference for comparison with other terrestrial Cetartiodactyla and hoofed mammals in general. The cortical structure, its laminar subdivision and projections, received scarce attention in the past.Since recent data using modern technics are lacking, we analyzed the lamination of the motor cortical columns using conventional histology, digital imaging and alternative statistical inference. We also traced the motor cortex projections using MR and Diffusion Tensor Imaging (DTI). Sampling topography was based on the available literature and physiological evidence.Our data suggest that the thickness of motor cortex of the sheep is comparable to that of other terrestrial Cetartiodactyla, but thicker than that of marine members of the same Order of equivalent body size. Analyses of the cortical columns showed a five‐layered agranular cortex only partially similar to that of rodents and primates. Layer I contained more round and sparse cells, while layer V had the most heterogeneous cell population profile, including gigantocellular pyramidal neurons.MR results and DTI revealed that the a) a robust bundle of fibers reaches the central pattern generators in the brainstem (Figure 1), thus indirectly emphasizing the existence of several extrapyramidal tracts; and b) the corticospinal tracts, presumed to be minor and limited in Cetartiodactyls given their limited dexterity in respect to primates and carnivores, forms a pathway comparable in size (if not superior) to the extrapyramidal tracts.Our data contrast the generally accepted idea that the extrapyramidal tracts are overwhelmingly dominant in ruminants, and that pyramidal projections to the spinal cord are minimal.Support or Funding InformationThis study was supported by Grant # 2015Y5W9YP from the Italian Ministry of Education, University and Research to Bruno Cozzi, including also all the other Authors.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Innovating to increase access to diabetes care in Kenya: an evaluation of Novo Nordisk’s base of the pyramid project

ABSTRACTBackground: The Base of the Pyramid (BoP) project is a public–private partnership initiated by Novo Nordisk that aims to facilitate access to diabetes care for people at the base of the economic pyramid in low- and middle-income countries (LMICs). In Kenya, the BoP, through a partnership model, aims to strengthen five pillars of diabetes care: increased awareness of diabetes; early diagnosis of diabetes; access to quality care by trained professionals; stable and affordable insulin supply; and improved self-management through patient education.Objectives: This study evaluates the extent to which BoP Kenya is scalable and sustainable, whether stakeholders share in its value, and whether BoP Kenya has improved access to diabetes care.Method: The Rapid Assessment Protocol for Insulin Access (RAPIA), an approach developed to provide a broad situational analysis of diabetes care, was used to examine health infrastructure and diabetes care pathways in Kenya. At the national level, the RAPIA was applied in a SWOT analysis of the BoP through in-depth interviews with key stakeholders. At individual and county health system levels, RAPIA was adapted to explore the impact of the BoP on access to diabetes care through a comparison of an intervention and control county.Results: The BoP was implemented in 28 of 47 counties in Kenya. Meru, a county where BoP was implemented, had 35 of 62 facilities (56%) participating in the BoP. Of the five pillars of the BoP, most notable progress was made in achieving the fourth (stable and affordable insulin supply). A price ceiling of 500KSh (US$5) per vial of insulin was established in the intervention county, with greater fluctuation and stock-outs in the non-intervention county. Despite reduced insulin costs, many patients with diabetes could not afford the additive expenses of monitoring, medicines, and travel. Less progress was made over the other pillars, which also faced challenges to sustainability and scalability.Conclusion: In the context of the rising prevalence of non-communicable diseases in LMICs, cross-sector approaches to improving access to care are increasingly needed. Public–private partnerships such as the BoP are necessary but not sufficient to ensure access to health care for people with diabetes at the base of the economic pyramid in Kenya.

Sex Differences in Context-Driven Reinstatement of Methamphetamine Seeking is Associated with Distinct Neuroadaptations in the Dentate Gyrus.

The present study examined differences in operant responses in adult male and female rats during distinct phases of addiction. Males and females demonstrated escalation in methamphetamine (0.05 mg/kg, i.v.) intake with females showing enhanced latency to escalate, and bingeing. Following protracted abstinence, females show reduced responses during extinction, and have greater latency to extinguish compared with males, indicating reduced craving. Females demonstrated lower context-driven reinstatement compared to males, indicating that females have less motivational significance to the context associated with methamphetamine. Whole-cell patch-clamp recordings on dentate gyrus (DG) granule cell neurons (GCNs) were performed in acute brain slices from controls and methamphetamine experienced male and female rats, and neuronal excitability was evaluated from GCNs. Reinstatement of methamphetamine seeking reduced spiking in males, and increased spiking in females compared to controls, demonstrating distinct neuroadaptations in intrinsic excitability of GCNs in males and females. Reduced excitability of GCNs in males was associated with enhanced levels of neural progenitor cells, expression of plasticity-related proteins including CaMKII, and choline acetyltransferase in the DG. Enhanced excitability in females was associated with an increased GluN2A/2B ratio, indicating changes in postsynaptic GluN subunit composition in the DG. Altered intrinsic excitability of GCNs was associated with reduced mossy fiber terminals in the hilus and pyramidal projections, demonstrating compromised neuroplasticity in the DG in both sexes. The alterations in excitability, plasticity-related proteins, and mossy fiber density were correlated with enhanced activation of microglial cells in the hilus, indicating neuroimmune responses in both sexes. Together, the present results indicate sexually dimorphic adaptive biochemical changes in excitatory neurotransmitter systems in the DG and highlight the importance of including sex as a biological variable in exploring neuroplasticity and neuroimmune changes that predict enhanced relapse to methamphetamine-seeking behaviors.