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Skeletal muscles undergo robust regeneration upon injury, and infiltrating immune cells play a major role in not only clearing damaged tissues but also regulating the myogenic process through secreted cytokines. Chemokine C-C motif ligand 8 (Ccl8), along with Ccl2 and Ccl7, has been reported to mediate inflammatory responses to suppress muscle regeneration. Ccl8 is also expressed by muscle cells, but a role of the muscle cell-derived Ccl8 in myogenesis has not been reported. In this study, we found that knockdown of Ccl8, but not Ccl2 or Ccl7, led to increased differentiation of C2C12 myoblasts. Analysis of existing single-cell transcriptomic datasets revealed that both immune cells and muscle stem cells (MuSCs) in regenerating muscles express Ccl8, with the expression by MuSCs at a much lower level, and that the temporal patterns of Ccl8 expression were different in MuSCs and macrophages. To probe a function of muscle cell-derived Ccl8 in vivo, we utilized a mouse system in which Cas9 was expressed in Pax7+ myogenic progenitor cells (MPCs) and Ccl8 gene editing was induced by AAV9-delivered sgRNA. Depletion of Ccl8 in Pax7+ MPCs resulted in accelerated muscle regeneration after barium chloride-induced injury in both young and middle-aged mice, and intramuscular administration of a recombinant Ccl8 reversed the phenotype. Accelerated regeneration was also observed when Ccl8 was depleted in Myf5+ or MyoD+ MPCs by similar approaches. Our results suggest that muscle cell-derived Ccl8 plays a unique role in regulating the initiation of myogenic differentiation during injury-induced muscle regeneration.
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Diferenciación Celular , Quimiocina CCL8 , Desarrollo de Músculos , Músculo Esquelético , Mioblastos , Regeneración , Animales , Ratones , Regeneración/fisiología , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Músculo Esquelético/lesiones , Desarrollo de Músculos/fisiología , Quimiocina CCL8/metabolismo , Quimiocina CCL8/genética , Mioblastos/metabolismo , Mioblastos/fisiología , Ratones Endogámicos C57BL , Línea Celular , Masculino , Quimiocina CCL7/metabolismo , Quimiocina CCL7/genética , Macrófagos/metabolismoRESUMEN
Amorphous solid dispersions (ASDs) can be used to enhance the solubility and bioavailability of poorly soluble drugs. An ASD is often a ternary system containing a drug, a surfactant, and a polymer. Recent work on binary ASDs has observed significant differences between surface and bulk compositions, with impacts on wettability and stability. Here we investigate a ternary ASD composed of the antifungal posaconazole, the surfactant Span 80, and a dispersion polymer (PVP or PVP/VA). The surfactant loading was fixed at the typical level of 5 wt %, and the drug/polymer ratio was varied. We observed strong surface enrichment of the surfactant and simultaneous depletion of the drug. This effect is already pronounced in the binary drug-surfactant system and is enhanced by the addition of the polymers. Between the two polymers, the more hydrophilic PVP causes a stronger enhancement of the surface enrichment effect. These results demonstrate the impact of component interactions on the surface composition of ASDs and the performance.
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Interacciones Hidrofóbicas e Hidrofílicas , Polímeros , Solubilidad , Tensoactivos , Tensoactivos/química , Polímeros/química , Humectabilidad , Triazoles/química , Antifúngicos/química , Povidona/química , HexosasRESUMEN
Chronic spinal cord injury (SCI) lesions retain increased densities of microglia and macrophages. In acute SCI, macrophages induce growth cone collapse, facilitate axon retraction away from lesion boundaries, as well as play a key role in orchestrating the growth-inhibitory glial scar. Little is known about the role of sustained inflammation in chronic SCI, or whether chronic inflammation affects repair and regeneration. We performed transcriptional analysis using the Nanostring Neuropathology panel to characterize the resolution of inflammation into chronic SCI, to characterize the chronic SCI microenvironment, as well as to identify spinal cord responses to macrophage depletion and repopulation using the CSF1R inhibitor, PLX-5622. We determined the ability for macrophage depletion and repopulation to augment axon growth into chronic lesions both with and without regenerative stimulation using neuronal-specific PTEN knockout (PTEN-KO). PTEN-KO was delivered with spinal injections of retrogradely transported adeno associated viruses (AAVrg's). Both transcriptional analyses and immunohistochemistry revealed the ability for PLX-5622 to significantly deplete inflammation around and within chronic SCI lesions, with a return to pre-depleted inflammatory densities after treatment removal. Neuronal-specific transcripts were significantly elevated in mice after inflammatory repopulation, but no significant effects were observed with macrophage depletion alone. Axon densities significantly increased within the lesion after PLX-5622 treatment with a more consistent effect observed in mice with inflammatory repopulation. PTEN-KO did not further increase axon densities within the lesion beyond effects induced by PLX-5622. We identified that PLX-5622 increased axon densities within the lesion that are histologically identified as 5-HT+and CGRP+, both of which are not robustly transduced by AAVrg's. Our work identified that increased macrophage/microglia densities in the chronic SCI environment may be actively retained by homeostatic mechanisms likely affiliated with a sustained elevated expression of CSF1 and other chemokines. Finally, we identify a novel role of sustained inflammation as a prospective barrier to axon regeneration in chronic SCI.
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Fluid intelligence (Gf) involves rational thinking skills and requires the integration of information from different cortical regions to resolve novel complex problems. The effects of non-invasive brain stimulation on Gf have been studied in attempts to improve Gf, but such studies are rare and the few existing have reached conflicting conclusions. The parieto-frontal integration theory of intelligence (P-FIT) postulates that the parietal and frontal lobes play a critical role in Gf. To investigate the suggested role of parietal cortices, we applied high-definition transcranial direct current stimulation (HD-tDCS) to the left and right parietal cortices of 39 healthy adults (age 19-33 years) for 20 min in three separate sessions (left active, right active and sham). After completing the stimulation session, the participants completed a logical reasoning task based on Raven's Progressive Matrices during magnetoencephalography. Significant neural responses at the sensor level across all stimulation conditions were imaged using a beamformer. Whole-brain, spectrally constrained functional connectivity was then computed to examine the network-level activity. Behaviourally, we found that participants were significantly more accurate following left compared to right parietal stimulation. Regarding neural findings, we found significant HD-tDCS montage-related effects in brain networks thought to be critical for P-FIT, including parieto-occipital, fronto-occipital, fronto-parietal and occipito-cerebellar connectivity during task performance. In conclusion, our findings showed that left parietal stimulation improved abstract reasoning abilities relative to right parietal stimulation and support both P-FIT and the neural efficiency hypothesis. KEY POINTS: Abstract reasoning is a critical component of fluid intelligence and is known to be served by multispectral oscillatory activity in the fronto-parietal cortices. Recent studies have aimed to improve abstract reasoning abilities and fluid intelligence overall through behavioural training, but the results have been mixed. High-definition transcranial direct-current stimulation (HD-tDCS) applied to the parietal cortices modulated task performance and neural oscillations during abstract reasoning. Left parietal stimulation resulted in increased accuracy and decreased functional connectivity between occipital regions and frontal, parietal, and cerebellar regions. Future studies should investigate whether HD-tDCS alters abstract reasoning abilities in those who exhibit declines in performance, such as healthy ageing populations.
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Inteligencia , Lóbulo Parietal , Estimulación Transcraneal de Corriente Directa , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Adulto , Lóbulo Parietal/fisiología , Masculino , Femenino , Inteligencia/fisiología , Adulto Joven , Red Nerviosa/fisiología , Magnetoencefalografía/métodosRESUMEN
Microplastics (MPs) accumulate in sediments, yet guidelines for evaluating MP risks in dredged sediments are lacking. The objective of this study was to review existing literature on MPs in sediments to improve fundamental knowledge of MP exposures and develop a publicly available database of MPs in sediments. Twelve percent of the reviewed papers (nine studies) included sediment core samples with MP concentrations generally decreasing with depth, peaking in the top 15 cm. The remaining papers evaluated surficial grab samples (0 to 15 cm depth) from various water bodies with MPs detected in almost every sample. Median MP concentrations (items/kg dry sediment) increased in this order: lakes and reservoirs (184), estuarine (263), Great Lakes nearshore areas and tributaries (290), riverine (410), nearshore marine areas (487), dredge activities (817), and harbors (948). Dredging of recurrent shoaling sediments could be expected to contain MPs at various depths with concentrations influenced by the time elapsed since the last dredging event. These results offer key insights into the presence and variability of MPs in dredged sediments, informing environmental monitoring and risk assessment strategies.
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Monitoreo del Ambiente , Sedimentos Geológicos , Microplásticos , Contaminantes Químicos del Agua , Sedimentos Geológicos/química , Contaminantes Químicos del Agua/análisis , Microplásticos/análisis , Medición de RiesgoRESUMEN
Patchy particles occupy an increasingly important space in soft matter research due to their ability to assemble into intricate phases and states. Being able to fine-tune the interactions among these particles is essential to understanding the principles governing the self-assembly processes. However, current fabrication techniques often yield patches that deviate chemically and physically from the native particles, impeding the identification of the driving forces behind self-assembly. To overcome this challenge, we propose a new approach to synthesizing spherical colloids with a well-defined rough patch on their surface. By treating polystyrene microspheres with vapors of a good solvent, here an acetone-water mixture, we achieve selective polymer corrugation on the particle surface resulting in a chemically similar yet rough surface patch. The key step is the selective condensation of the acetone-water vapors on the apex of the polystyrene microparticles immobilized on a substrate, which leads to rough patch formation. We leverage the ability to tune the vapor-liquid equilibrium of the volatile acetone-water mixture to precisely control the polymer corrugation on the particle surface. We demonstrate the dependence of patch formation on particle and substrate wettability, with the condensation occurring on the particle apex only when it is more wettable than the substrate, which is consistent with Volmer's classical nucleation theory. By combining experiments and molecular dynamics simulations, we identify the role of the rough patch in the depletion interaction-driven self-assembly of the microspheres, which is crucial for designing programmable supracolloidal structures.
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Loss of facial recognition or prosopagnosia has been well-recognized for over a century. It has been categorized as developmental or acquired depending on whether the onset is in early childhood or beyond, and acquired cases can have degenerative or non-degenerative aetiologies. Prosopagnosia has been linked to involvement of the fusiform gyri, mainly in the right hemisphere. The literature on prosopagnosia comprises case reports and small case series. We aim to assess demographic, clinical and imaging characteristics and neurological and neuropathological disorders associated with a diagnosis of prosopagnosia in a large cohort. Patients were categorized as developmental versus acquired; those with acquired prosopagnosia were further subdivided into degenerative versus non-degenerative, based on neurological aetiology. We assessed regional involvement on [18F] fluorodeoxyglucose-PET and MRI of the right and left frontal, temporal, parietal and occipital lobes. The Intake and Referral Center at the Mayo Clinic identified 487 patients with possible prosopagnosia, of which 336 met study criteria for probable or definite prosopagnosia. Ten patients, 80.0% male, had developmental prosopagnosia including one with Niemann-Pick type C and another with a forkhead box G1 gene mutation. Of the 326 with acquired prosopagnosia, 235 (72.1%) were categorized as degenerative, 91 (27.9%) as non-degenerative. The most common degenerative diagnoses were posterior cortical atrophy, primary prosopagnosia syndrome, Alzheimer's disease dementia and semantic dementia, with each diagnosis accounting for >10% of this group. The most common non-degenerative diagnoses were infarcts (ischaemic and haemorrhagic), epilepsy-related and primary brain tumours, each accounting for >10%. We identified a group of patients with non-degenerative transient prosopagnosia in which facial recognition loss improved or resolved over time. These patients had migraine-related prosopagnosia, posterior reversible encephalopathy syndrome, delirium, hypoxic encephalopathy and ischaemic infarcts. On [18F] fluorodeoxyglucose-PET, the temporal lobes proved to be the most frequently affected regions in 117 patients with degenerative prosopagnosia, while in 82 patients with non-degenerative prosopagnosia, MRI revealed the right temporal and right occipital lobes as most affected by a focal lesion. The most common pathological findings in those with degenerative prosopagnosia were frontotemporal lobar degeneration with hippocampal sclerosis and mixed Alzheimer's and Lewy body disease pathology. In this large case series of patients diagnosed with prosopagnosia, we observed that facial recognition loss occurs across a wide range of acquired degenerative and non-degenerative neurological disorders, most commonly in males with developmental prosopagnosia. The right temporal and occipital lobes, and connecting fusiform gyrus, are key areas. Multiple different pathologies cause degenerative prosopagnosia.
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Aspergillus fumigatus causes life-threatening mold pneumonia in immune compromised patients, particularly in those with quantitative or qualitative defects in neutrophils. While innate immune cell crosstalk licenses neutrophil antifungal activity in the lung, the role of epithelial cells in this process is unknown. Here, we find that that surfactant protein C (SPC)-expressing lung epithelial cells integrate infection-induced IL-1 and type III interferon signaling to produce granulocyte-macrophage colony-stimulating factor (GM-CSF) preferentially at local sites of fungal infection and neutrophil influx. Using in vivo models that distinguish the role of GM-CSF during acute infection from its homeostatic function in alveolar macrophage survival and surfactant catabolism, we demonstrate that epithelial-derived GM-CSF increases the accumulation and fungicidal activity of GM-CSF-responsive neutrophils, with the latter being essential for host survival. Our findings establish SPC + epithelial cells as a central player in regulating the quality and strength of neutrophil-dependent immunity against inhaled mold pathogens. HIGHLIGHTS: GM-CSF is essential for host defense against A. fumigatus in the lung IL-1 and IFN-λ promote GM-CSF production by lung epithelial cells in parallelEpithelial cell-derived GM-CSF increases neutrophil accumulation and fungal killing capacityEpithelial cells preferentially upregulate GM-CSF in local sites of inflammation.
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Few publications exist concerning polymorphic control during melt crystallization, particularly when employing heteronucleants. Here, the influence of a polymeric thin film (polyethylene terephthalate, PET) on the crystallization from melt of the polymorphic compound acetaminophen (ACM) in polyethylene glycol (PEG) was investigated. Molten ACM-PEG at different compositions was monitored using in situ Raman spectroscopy for nucleation induction time measurements and phase identification. Furthermore, X-ray diffraction (XRD) served to analyze the preferred orientation (PO) of the pastilles (solidified melt droplets) on PET-coated and uncoated substrates. The results indicate that PET-coated substrates qualitatively accelerate the nucleation of ACM form II (ACM II) in PEG compared to uncoated glass substrates. Additionally, the occurrence of ACM II in PEG was increased by an average of 10% when crystallized on PET-coated substrates compared to uncoated substrates. Overall, these results suggest that ACM can interact through hydrogen bonding with the PET-coated substrate, leading to faster nucleation. This investigation illustrates the effect of PET-coated substrates in the selective crystallization of ACM II in PEG as crystalline solid dispersions (CSDs). Ultimately, the results suggest the implementation of polymeric heteronucleants in melt crystallization processes, specifically, in advanced polymer-based formulation processes for the enhanced polymorphic form control of pharmaceutical compounds in CSDs.
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Restoring function in chronic stages of spinal cord injury (SCI) has often been met with failure or reduced efficacy when regenerative strategies are delayed past the acute or sub-acute stages of injury. Restoring function in the chronically injured spinal cord remains a critical challenge. We found that a single injection of retrogradely transported adeno-associated viruses (AAVrg) to knockout the phosphatase and tensin homolog protein (PTEN) in chronic SCI can effectively target both damaged and spared axons and transiently restore locomotor functions in near-complete injury models. AAVrg's were injected to deliver cre recombinase and/or a red fluorescent protein (RFP) under the human Synapsin 1 promoter (hSyn1) into the spinal cords of C57BL/6 PTENFloxΔ/Δ mice to knockout PTEN (PTEN-KO) in a severe thoracic SCI crush model at both acute and chronic time points. PTEN-KO improved locomotor abilities in both acute and chronic SCI conditions over a 9-week period. Regardless of whether treatment was initiated at the time of injury (acute), or three months after SCI (chronic), mice with limited hindlimb joint movement gained hindlimb weight support after treatment. Interestingly, functional improvements were not sustained beyond 9 weeks coincident with a loss of RFP reporter-gene expression and a near-complete loss of treatment-associated functional recovery by 6 months post-treatment. Treatment effects were also specific to severely injured mice; animals with weight support at the time of treatment lost function over a 6-month period. Retrograde tracing with Fluorogold revealed viable neurons throughout the motor cortex despite a loss of RFP expression at 9 weeks post-PTEN-KO. However, few Fluorogold labeled neurons were detected within the motor cortex at 6 months post-treatment. BDA labeling from the motor cortex revealed a dense corticospinal tract (CST) bundle in all groups except chronically treated PTEN-KO mice, indicating a potential long-term toxic effect of PTEN-KO to neurons in the motor cortex which was corroborated by a loss of ß-tubulin III labeling above the lesion within spinal cords after PTEN-KO. PTEN-KO mice had significantly more ß-tubulin III labeled axons within the lesion when treatment was delivered acutely, but not chronically post-SCI. In conclusion, we have found that using AAVrg's to knockout PTEN is an effective manipulation capable of restoring motor functions in chronic SCI and can enhance axon growth of currently unidentified axon populations when delivered acutely after injury. However, the long-term consequences of PTEN-KO on neuronal health and viability should be further explored.
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Traumatismos de la Médula Espinal , Tubulina (Proteína) , Animales , Humanos , Ratones , Axones/patología , Ratones Endogámicos C57BL , Regeneración Nerviosa/fisiología , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Tractos Piramidales/patología , Recuperación de la Función , Médula Espinal/patología , Traumatismos de la Médula Espinal/patología , Tubulina (Proteína)/metabolismoRESUMEN
Speech rate can be judged clinically using diadochokinetic (DDK) tasks, such as alternating motion rates (AMR) and sequential motion rates (SMR). We evaluated whether acoustic AMR/SMR speech rates would differentiate primary progressive apraxia of speech (PPAOS) from healthy controls, and determined how DDK rates relate to phonetic and prosodic speech characteristics and brain metabolism on FDG-PET. Rate was calculated for each of three AMRs (repetitions of 'puh', 'tuh', and 'kuh') and for SMRs (repetitions of 'puhtuhkuh') for 27 PPAOS patients and 52 controls who underwent FDG-PET. PPAOS patients were slower than controls on all DDK tasks. All DDK rates correlated with apraxia of speech severity, with strongest associations with prosodic speech features. Slower DDK rates were associated with hypometabolism in the right cerebellar dentate and left supplementary motor area. Performance on AMR rate, not just SMR rate, may be impaired in mild PPAOS, but sensitivity and specificity require further study.
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Afasia Progresiva Primaria , Apraxias , Humanos , Habla , Encéfalo/diagnóstico por imagen , Fluorodesoxiglucosa F18/metabolismo , Apraxias/diagnóstico por imagen , Neuroimagen , AcústicaRESUMEN
Historically, low representation of women participants in exercise science and physiology studies has led to a lack of understanding in the response of women to exercise and therapeutic interventions. We hypothesized that 1) the number of women authors, participants, and editorial board members increased over 30 years (1991-2021) and 2) larger representation of women as editors and authors is associated with more women participants. Gender (man/woman) of editorial board members (n = 394), authors (n = 5,735), and participants (n = 2,984,883) of 972 original research articles with human participants published in 1991 and 2021 was analyzed from three journals: Journal of Applied Physiology, Medicine and Science in Sports and Exercise, and British Journal of Sports Medicine. Between 1991 to 2021, the average percent women per article as participants (21.9 ± 31.7% vs. 36.3 ± 30.3%, respectively, P < 0.001), authors (16.4 ± 22.4% vs. 30.9 ± 24.0%, P < 0.001), and editorial board members (13.3 ± 5.4% vs. 41.5 ± 7.3%, P = 0.006) increased. In 2021, the gender proportion of participants in large datasets was similar (50.2 ± 20.2% women). However, studies with smaller datasets (i.e., <â¼3,000 participants) included less women (35.6 ± 30.6%). Women participants (%) were less when the last author was a man rather than a woman in 1991 (19.9 ± 29.5% vs. 34.3 ± 42.2%) and 2021 (31.6 ± 27.7% vs. 51.7 ± 33.4%). In 2021, there was a positive correlation between author and participant gender (% women) (r = 0.42, P < 0.001). Our data suggest that the low representation of women in exercise science and physiology research could be resolved with equitable numbers of women authors and editors and by encouraging men authors to study both women and men participants.NEW & NOTEWORTHY Analysis of human applied physiology studies revealed that the representation of women authors, participants, and editorial board members increased over 30 years but remained lower than men in 2021. Larger representation of women editors and authors was associated with more women participants. Women authors assessed similar numbers of women and men participants, whereas men authors included less women. Equitable representation of women participants may be achieved by closing the gender gap in authorship and editorial board membership.
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Autoria , Equidad de Género , Femenino , Humanos , Masculino , Fisiología , Medicina DeportivaRESUMEN
Poor access to diagnostic testing in resource limited settings restricts surveillance for emerging infections, such as dengue virus (DENV), to clinician suspicion, based on history and exam observations alone. We investigated the ability of machine learning to detect DENV based solely on data available at the clinic visit. We extracted symptom and physical exam data from 6,208 pediatric febrile illness visits to Kenyan public health clinics from 2014-2019 and created a dataset with 113 clinical features. Malaria testing was available at the clinic site. DENV testing was performed afterwards. We randomly sampled 70% of the dataset to develop DENV and malaria prediction models using boosted logistic regression, decision trees and random forests, support vector machines, naïve Bayes, and neural networks with 10-fold cross validation, tuned to maximize accuracy. 30% of the dataset was reserved to validate the models. 485 subjects (7.8%) had DENV, and 3,145 subjects (50.7%) had malaria. 220 (3.5%) subjects had co-infection with both DENV and malaria. In the validation dataset, clinician accuracy for diagnosis of malaria was high (82% accuracy, 85% sensitivity, 80% specificity). Accuracy of the models for predicting malaria diagnosis ranged from 53-69% (35-94% sensitivity, 11-80% specificity). In contrast, clinicians detected only 21 of 145 cases of DENV (80% accuracy, 14% sensitivity, 85% specificity). Of the six models, only logistic regression identified any DENV case (8 cases, 91% accuracy, 5.5% sensitivity, 98% specificity). Without diagnostic testing, interpretation of clinical findings by humans or machines cannot detect DENV at 8% prevalence. Access to point-of-care diagnostic tests must be prioritized to address global inequities in emerging infections surveillance.
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We report the case of a 19-year-old Native American woman who presented with bilateral lower extremity weakness due to spinal cord compression from late-stage Hodgkin's lymphoma. Hodgkin's lymphoma rarely has an initial presentation of spinal cord compression, except in cases of late-stage disease. The patient partially attributed her delayed pursuit of care to the difficulty of scheduling an appointment during the coronavirus (COVID-19) pandemic. The COVID-19 pandemic has impacted access to care and the potential for early detection of disease, as seen in this patient. Additionally, Native Americans on South Dakota Reservations face unique challenges that affect access to healthcare and health outcomes.
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Background. The Do-Live-Well (DLW) framework was first published in 2015 and aimed to fill a theoretical gap in the health promotion literature related to the links between occupational patterns and health. However, the extent of uptake and use of the framework since publication is unknown. Purpose. To explore and reflect on the adoption and application of DLW in the literature. Method. Citation content analysis of two seminal DLW publications was conducted from 2015 to November 2022 across six databases. Findings. Seventeen citations directly applied DLW to inform research (n = 10), practice (n = 5) and knowledge translation (n = 2). Implications. The findings highlight uptake of the framework in a range of settings, and how it can inform an occupation-based understanding of health and well-being. Ongoing knowledge dissemination, development of practice tools, and research to update evidence and examine relevance are needed to further advance the utility and application of the framework.
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Terapia Ocupacional , Humanos , Terapia Ocupacional/métodos , Promoción de la Salud/métodos , OcupacionesRESUMEN
BACKGROUND: Community participation is essential for the successful implementation of primary health care programmes across the globe, including sub-Saharan Africa. The Community-based Health Planning and Services (CHPS) programme is one of the primary health care interventions in Ghana which by design and implementation heavily relies on community participation. However, there is little evidence to establish the factors enabling or inhibiting community participation in the Ghanaian CHPS programme. This study, therefore, explored the enabling and inhibiting factors influencing community participation in the design and implementation of the CHPS programme in the Builsa North Municipality in the Upper East Region of Ghana. METHODS: A qualitative approach, using a cross-sectional design, was employed to allow for a detailed in-depth exploration of the enabling and inhibiting factors influencing community participation in the design and implementation of the CHPS programme. The data were collected in January 2020, through key informant interviews with a stratified purposive sample of 106 respondents, selected from the 15 functional CHPS facilities in the Municipality. The data were audio-recorded, transcribed and manually analysed using thematic analysis. RESULTS: The results showed that, public education on the CHPS concept, capacity of the community to contribute material resources towards the construction of CHPS facilities, strong and effective community leadership provided by community chiefs and assembly persons, the spirit of volunteerism and trust in the benefits of the CHPS programme were the enablers of community participation in the programme. However, volunteer attrition, competing economic activities, lack of sense of ownership by distant beneficiaries, external contracting of the construction of CHPS facilities and illiteracy constituted the inhibiting factors of community participation in the programme. CONCLUSION: Extensive public education, volunteer incentivization and motivation, and the empowerment of communities to construct their own CHPS compounds are issues that require immediate policy attention to enhance effective community participation in the programme.
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Servicios de Salud Comunitaria , Planificación en Salud , Estados Unidos , Humanos , Ghana , Estudios Transversales , Participación de la ComunidadRESUMEN
Molecules at a liquid/vapor interface have different organizations and mobilities from those in the bulk. These differences potentially influence the rate of crystal nucleation, but the effect remains imperfectly understood. We have measured the crystal nucleation rates at the surface and in the bulk of amorphous poscaconazole, a rod-like molecule known to have a preferred interfacial orientation. We find that surface nucleation is vastly enhanced over bulk nucleation, by â¼9 orders of magnitude, and selects a different polymorph (II) from bulk nucleation (I). This phenomenon mirrors the recently reported case of D-arabitol and stems from the similarity of anisotropic surface molecular packing to the structure of the surface-nucleating polymorph. In contrast to these two systems, the surface enhancement of nucleation is weaker (though still significant) in acetaminophen and in water and does not select a different polymorph. Together, the systems investigated to date all feature surface enhancement, not suppression, of crystal nucleation, and those showing a polymorphic change feature (1) structural reconstruction at the surface relative to the bulk and (2) existence of a different polymorph that can take advantage of the surface environment to nucleate. These results help predict the effect of a liquid/vapor interface on crystal nucleation and polymorph selection, especially in systems with a large surface/volume ratio, such as atmospheric water and amorphous particles.