Phylogenetic diversity and susceptibility of Candida species from women using contraceptive devices in northcentral Nigeria

Background: The use of contraceptive devices predisposes women to vulvovaginal candidiasis (VVC) globally. Despite the high incidence of VVC and antifungal resistance to azoles, the genetic diversity and resistance pattern among contraceptive users in Nigeria is poorly investigated. This study therefore sought to characterize and determine the phylogenetic breadth of Candida species as well as their resistance to antifungal agents. Methodology: This study recruited 1,600 women using contraceptive devices who visited selected gynaecology and obstetrics clinics in northcentral Nigeria. Candida species were isolated and characterized using conventional methods and sequencing of the internal transcribed spacer (ITS) region of the ribosomal DNA (rDNA). Bayesian phylogenetic analysis was used to characterize the diversity of Candida species and primer-specific PCR was used to detect the presence of resistant genes. Agar well diffusion technique was used for the determination of antifungal susceptibility profiles. Data analysis was done by Kruskal-Wallis Chi-square test on R Console software version 3.2.2, followed by post-hoc Wilcoxon rank sum test with Bonferroni correction for multiple pairwise comparisons of means where there was a significant difference between the antifungal agents. The level of significance was set at p < 0.05. Results: A total of 710 (44.3%) out of the 1,600 women using contraceptive devices had VVC with five species of Candida identified in them. Although Candida albicans was the predominant (43.2%, n=307) species, other non-albicans Candida species include Candida (Nakaseomyces) glabrata (19.0%, n=135), Candida tropicalis (15.8%, n=112), Candida parapsilosis (8.9%, n=63), and Candida akabanensis (13.1%, n=93) which were phenotypically identified as Candida (Nakaseomyces) glabrata. All the Candida species showed varying degrees of susceptibilities to voriconazole, fluconazole and nystatin. However, resistance of C. albicans to fluconazole was 29.0%, C. tropicalis to nystatin (46.0%) and to voriconazole (14.0%), while C. akabanensis was 100.0% resistant to voriconazole and fluconazole. Kruskal-Wallis Chi-square test showed nystatin as the most effective antifungal agent against the Candida species (χ2=786.03, df=2, p<0.001). Also, resistant gene Erg11 was identified in all the Candida species that were phenotypically resistant to the antifungal agents tested. Conclusion: Women using contraceptive devices in northcentral Nigeria harbor phylogenetically diverse Candida species including C. akabanensis, an uncommon cause of VVC. Of these Candida species, C. albicans, C. tropicalis and C. akabanensis were notable for multidrug drug resistance as well as harboring Erg11 resistance gene.

Epigenetic balance ensures mechanistic control of MLL amplification and rearrangement.

MLL/KMT2A amplifications and translocations are prevalent in infant, adult, and therapy-induced leukemia. However, the molecular contributor(s) to these alterations are unclear. Here, we demonstrate that histone H3 lysine 9 mono- and di-methylation (H3K9me1/2) balance at the MLL/KMT2A locus regulates these amplifications and rearrangements. This balance is controlled by the crosstalk between lysine demethylase KDM3B and methyltransferase G9a/EHMT2. KDM3B depletion increases H3K9me1/2 levels and reduces CTCF occupancy at the MLL/KMT2A locus, in turn promoting amplification and rearrangements. Depleting CTCF is also sufficient to generate these focal alterations. Furthermore, the chemotherapy doxorubicin (Dox), which associates with therapy-induced leukemia and promotes MLL/KMT2A amplifications and rearrangements, suppresses KDM3B and CTCF protein levels. KDM3B and CTCF overexpression rescues Dox-induced MLL/KMT2A alterations. G9a inhibition in human cells or mice also suppresses MLL/KMT2A events accompanying Dox treatment. Therefore, MLL/KMT2A amplifications and rearrangements are controlled by epigenetic regulators that are tractable drug targets, which has clinical implications.

Parasitological, serological, and molecular survey of trypanosomosis (Surra) in camels slaughtered in northwestern Nigeria.

Surra is a parasitic disease caused by Trypanosoma evansi and transmitted non-cyclically by biting flies. The disease significantly affects the health, productivity, and market value of camels thereby constituting a major constraint to food safety, security, and economy. This is the first study on the prevalence of surra in northwestern Nigeria, using a range of diagnostic tests along the parasitological-serological-molecular continuum hence, emphasizing it as a major enzootic risk for camels in Nigeria. In this cross-sectional study, 600 blood samples were collected from camels at major abattoirs in northwestern Nigeria and evaluated for the prevalence of T. evansi using parasitological (Giemsa staining), serological (CATT/T. evansi), and molecular (VSG-PCR and sequencing) methods. The overall prevalence of surra recorded in this study was 5.3%, 11.5%, and 22.5% using Giemsa-stained blood smears, CATT/T. evansi, and VSG-PCR respectively. However, higher prevalence rates at 6.0%, 13.7%, and 26.7% by Giemsa-stained blood smears, CATT/T. evansi, and VSG-PCR were recorded in Katsina State compared with results from Kano State. A significantly (p < 0.05) higher prevalence by VSG-PCR was observed when compared with both parasitological and serological methods used. Although age and body condition scores were associated (p < 0.05) with surra prevalence in sampled camels, no seasonal association (p > 0.05) was recorded. Sequencing of the VSG region of Trypanosoma spp. Further confirmed the presence of T. evansi as the aetiological agent of surra from the sampled camels. Findings from this study call for the implementation of adequate control measures aimed at reducing the impact of T. evansi infections on camel production in Nigeria.

Castration delays epigenetic aging and feminizes DNA methylation at androgen-regulated loci.

In mammals, females generally live longer than males. Nevertheless, the mechanisms underpinning sex-dependent longevity are currently unclear. Epigenetic clocks are powerful biological biomarkers capable of precisely estimating chronological age and identifying novel factors influencing the aging rate using only DNA methylation data. In this study, we developed the first epigenetic clock for domesticated sheep (Ovis aries), which can predict chronological age with a median absolute error of 5.1 months. We have discovered that castrated male sheep have a decelerated aging rate compared to intact males, mediated at least in part by the removal of androgens. Furthermore, we identified several androgen-sensitive CpG dinucleotides that become progressively hypomethylated with age in intact males, but remain stable in castrated males and females. Comparable sex-specific methylation differences in MKLN1 also exist in bat skin and a range of mouse tissues that have high androgen receptor expression, indicating that it may drive androgen-dependent hypomethylation in divergent mammalian species. In characterizing these sites, we identify biologically plausible mechanisms explaining how androgens drive male-accelerated aging.

Menopause and cognitive complaints: are ovarian hormones linked with subjective cognitive decline?

Subjective cognitive decline (SCD) and the loss of ovarian hormones after menopause have been independently linked to later-life Alzheimer's disease (AD). The objective of this review was to determine whether menopause and the loss of ovarian hormones contribute to cognitive complaints and SCD in women. This would suggest that SCD at the menopausal transition might be an important marker of eventual cognitive decline and AD. We conducted a literature search using PubMed, PsycINFO and Web of Science in July 2020. All English-language studies assessing SCD and cognitive complaints with respect to menopause and ovarian hormones were included. A total of 19 studies were included. Studies found that cognitive complaints increased across the menopause transition and were associated with reductions in attention, verbal and working memory, and medial temporal lobe volume. Women taking estrogen-decreasing treatments also had increased cognitive complaints and reduced working memory and executive function. The current literature provides impetus for further research on whether menopause and the loss of ovarian hormones are associated with cognitive complaints and SCD. Clinicians may take particular note of cognitive complaints after menopause or ovarian hormone loss, as they might presage future cognitive decline.

Co-epidemics: have measures against COVID-19 helped to reduce Lassa fever cases in Nigeria?

While the coronavirus disease 2019 (COVID-19) pandemic has multiple devastating public health and socio-economic effects across the world, Nigeria along with other West African countries is simultaneously faced with a recurrent Lassa fever epidemic. The complicating scenario is the similarity in the clinical manifestation of COVID-19 and Lassa fever, making the misdiagnosis of the initial presentation of both diseases a significant risk with an increased likelihood of co-infection. However, the strict implementation of COVID-19 infection prevention and control measures across Nigeria after the initial outbreaks concurrently resulted in the reduction of Lassa fever cases. The abrupt change in the behaviour of Lassa fever epidemiological data, which are attributable to the implementation of COVID-19 infection prevention and control measures at the national, sub-national and community levels, requires detailed investigation during and after the COVID-19 epidemic to elucidate the interactions and evolutionary dynamics of Lassa fever cases in Nigeria.

Characterization and evaluation of lactic acid bacteria from indigenous raw milk for potential probiotic properties.

Raw milk contains wide microbial diversity, composed mainly of lactic acid bacteria (LAB), which are used as probiotics in both human and animal husbandry. We isolated, characterized, and evaluated LAB from indigenous Bangladeshi raw milk to assess probiotic potential, including antagonistic activity (against Escherichia coli O157: H7, Enterococcus faecalis, Salmonella Typhimurium, Salmonella Enteritidis, and Listeria monocytogenes), survivability in simulated gastric juice, tolerance to phenol and bile salts, adhesion to ileum epithelial cells, auto- and co-aggregation, hydrophobicity, α-glucosidase inhibitory activity, and antibiotic susceptibility tests. The 4 most promising LAB strains showed probiotic potential and were identified as Lactobacillus casei, Lactobacillus plantarum (which produced plantaricin EF), Lactobacillus fermentum, and Lactobacillus paracasei. These strains inhibited all pathogens tested at various degrees, and competitively excluded pathogens with viable counts of 3.0 to 6.0 log cfu/mL. Bacteriocin, organic acids, and low-molecular-weight substances were mainly responsible for antimicrobial activity by the LAB strains. All 4 LAB strains were resistant to oxacillin and 3 were resistant to vancomycin and streptomycin, with multiple antibiotic resistance indices >0.2. After further in vivo evaluation, these LAB strains could be considered probiotic candidates with application in the food industry.

Association between testosterone, semen parameters, and live birth in men with unexplained infertility in an intrauterine insemination population.

OBJECTIVE: To determine whether men with unexplained infertility and low total T (TT) have abnormal spermatogenesis and lower fecundity. DESIGN: Secondary analysis of the prospective, randomized, multicenter clinical trial, Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS). SETTING: Infertility clinics. PATIENT(S): Nine hundred couples with unexplained infertility enrolled in AMIGOS. Semen analysis with an ejaculate of at least 5 million total motile sperm was required for enrollment. For inclusion in this secondary analysis, a fasting TT was required. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Logistic regression, adjusted for age and body mass index, assessed the association between low TT (defined as <264 ng/dL), semen parameters, and pregnancy outcome. RESULT(S): Seven hundred eighty-one men (mean age, 34.2 ± 5.7 years) with a median (interquartile range) TT of 411 (318-520) ng/dL were included. Men with TT <264 ng/dL were less likely to have normal (≥4% strict Kruger) morphology (unadjusted odds ratio [OR], 0.56; 95% confidence interval [CI], 0.34, 0.92; adjusted OR, 0.59; 95% CI, 0.35, 0.99). There was no association between low TT and semen volume < 1.5 mL, sperm concentration < 15 × 106/mL, or motility < 40%. Among couples whose male partner had low TT, 21 (18.8%) had a live birth, compared with 184 (27.5%) live births in couples with a male partner having TT > 264 ng/dL. The odds of live birth decreased by 40% in couples whose male partner had low TT (unadjusted OR, 0.60; 95% CI, 0.36, 1.00; adjusted OR, 0.65; 95% CI, 0.38, 1.12). CONCLUSION(S): In couples with unexplained infertility, low TT in the male partner was associated with abnormal sperm morphology and lower live birth rates. CLINICAL TRIAL REGISTRATION NUMBER: NCT01044862.

A Comparison of different scoring terminations rules for visual acuity testing: from a computer simulation to a clinical study.

Purpose: To compare four visual acuity (VA) scoring termination rules. Methods: A computer simulation generated 30,000 virtual patients who underwent 10 repetitions for each of four termination rules, on both the Snellen and ETDRS charts (2.4 million tests performed in total). Three termination rules focused on the smallest character row: all characters were correctly identified (100%), one character was incorrectly identified (one miss) and 50% or more of the characters were correctly identified (50%). The forth termination rule used a calculation in which each character, when correctly recognized, contributed a proportional increment (per-letter). Accuracy, test-retest variability (TRV) and test duration were measured. Next, a clinical study was conducted in which 254 subjects underwent three repetitions of the ETDRS VA test from 4 m, and VA scores for each of the four scoring termination rules were calculated. Results: In the Snellen simulation, the mean accuracy of the 100%, one miss, 50% and per-letter termination rules in decimal was 0.23 (-0.16 logMAR), 0.11 (-0.09 logMAR), 0.10 (-0.08 logMAR), and -0.08 (0.08 logMAR) respectively; while with the ETDRS simulation, the mean accuracy in decimal was 0.34 (-0.22 logMAR), 0.14 (-0.11 logMAR), 0.07 (-0.06 logMAR), and 0.07 (-0.05 logMAR), respectively. For the ETDRS simulation, the per-letter had the lowest TRV values and the longest test duration. In the clinical study (n = 254), the reproducibility of the 100%, one miss, 50% and per-letter was 0.50, 0.53, 0.17, 0.14, respectively. Conclusions: Clinical study and simulation data both suggest that the 100% and one-miss termination rules have higher TRVs, while the 50% and per-letter demonstrated much tighter, and rather close, TRV values.

Automatic localization of the subthalamic nucleus on patient-specific clinical MRI by incorporating 7 T MRI and machine learning: Application in deep brain stimulation.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has shown clinical potential for relieving the motor symptoms of advanced Parkinson's disease. While accurate localization of the STN is critical for consistent across-patients effective DBS, clear visualization of the STN under standard clinical MR protocols is still challenging. Therefore, intraoperative microelectrode recordings (MER) are incorporated to accurately localize the STN. However, MER require significant neurosurgical expertise and lengthen the surgery time. Recent advances in 7 T MR technology facilitate the ability to clearly visualize the STN. The vast majority of centers, however, still do not have 7 T MRI systems, and fewer have the ability to collect and analyze the data. This work introduces an automatic STN localization framework based on standard clinical MRIs without additional cost in the current DBS planning protocol. Our approach benefits from a large database of 7 T MRI and its clinical MRI pairs. We first model in the 7 T database, using efficient machine learning algorithms, the spatial and geometric dependency between the STN and its adjacent structures (predictors). Given a standard clinical MRI, our method automatically computes the predictors and uses the learned information to predict the patient-specific STN. We validate our proposed method on clinical T2 W MRI of 80 subjects, comparing with experts-segmented STNs from the corresponding 7 T MRI pairs. The experimental results show that our framework provides more accurate and robust patient-specific STN localization than using state-of-the-art atlases. We also demonstrate the clinical feasibility of the proposed technique assessing the post-operative electrode active contact locations.

Microelectrode Recordings Validate the Clinical Visualization of Subthalamic-Nucleus Based on 7T Magnetic Resonance Imaging and Machine Learning for Deep Brain Stimulation Surgery.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a proven and effective therapy for the management of the motor symptoms of Parkinson's disease (PD). While accurate positioning of the stimulating electrode is critical for success of this therapy, precise identification of the STN based on imaging can be challenging. We developed a method to accurately visualize the STN on a standard clinical magnetic resonance imaging (MRI). The method incorporates a database of 7-Tesla (T) MRIs of PD patients together with machine-learning methods (hereafter 7 T-ML). OBJECTIVE: To validate the clinical application accuracy of the 7 T-ML method by comparing it with identification of the STN based on intraoperative microelectrode recordings. METHODS: Sixteen PD patients who underwent microelectrode-recordings guided STN DBS were included in this study (30 implanted leads and electrode trajectories). The length of the STN along the electrode trajectory and the position of its contacts to dorsal, inside, or ventral to the STN were compared using microelectrode-recordings and the 7 T-ML method computed based on the patient's clinical 3T MRI. RESULTS: All 30 electrode trajectories that intersected the STN based on microelectrode-recordings, also intersected it when visualized with the 7 T-ML method. STN trajectory average length was 6.2 ± 0.7 mm based on microelectrode recordings and 5.8 ± 0.9 mm for the 7 T-ML method. We observed a 93% agreement regarding contact location between the microelectrode-recordings and the 7 T-ML method. CONCLUSION: The 7 T-ML method is highly consistent with microelectrode-recordings data. This method provides a reliable and accurate patient-specific prediction for targeting the STN.

Anti-Salmonella activity of metabolites from African soldier termites, Macrotermes bellicosus

Background: The global emergence and rapid dissemination of multidrug resistant Salmonella strains necessitate research to find new antimicrobials that will effectively be used against these pathogens. In the present study, anti-Salmonella activity of metabolites from African Soldier Termites, Macrotermes bellicosus was demonstrated and subsequently compared with a potent antibiotic, ciprofloxacin. Materials and Methods: N-hexane, ethylacetate, methanol and aqueous extracts of metabolites from the M. bellicosus were assayed for anti-Salmonella activity using the agar dilution method in the determination of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The inhibitory activities of the extracts were compared to ciprofloxacin (256µg/ml). Also, the bioactive components of the extracts were determined using standard techniques. Results: At 4000 µg/ml, N-hexane extract inhibited the growth of Salmonella Typhi, S. Paratyphi A, B and C while ethylacetate extract was able to inhibit S. Paratyphi A and C. Methanolic and aqueous extracts at the same concentration were unable to inhibit these strains of Salmonella. Furthermore, our findings revealed that the MIC of ethylacetate extract was 2000µg/ml for S. Paratyphi A and B, 250µg/ml for S. Typhi, and 125µg/ml for S. Paratyphi C. Also, the MIC of hexane extract was 4000µg/ml for S. Paratyphi B, 2000 µg/ml for S. Paratyphi C, 500µg/ml for S. Typhi and 250µg/ml for S. Paratyphi A respectively. The screening of bioactive components revealed the presence of cardiac glycosides and alkaloids. Conclusion: Our results provide evidence of anti-Salmonella action of metabolites from African Soldier Termites, M. bellicosus. N-hexane and ethylacetate extracts of M. bellicosus may be explored as novel antimicrobials for the treatment of typhoid and paratyphoid fevers thereby reducing the pressure exerted on available antibiotics

Evolution of skeletal and muscular morphology within the functionally integrated lower jaw adduction system of sculpins and relatives (Cottoidei).

Vertebrate lever mechanics are defined by the morphology of skeletal elements and the properties of their muscular actuators; these metrics characterize functional diversity. The components of lever systems work in coordination ("functional integration") and may show strong covariation across evolutionary history ("evolutionary integration"), both of which have been hypothesized to constrain phenotypic diversity. We quantified evolutionary integration in a functionally integrated system - the lower jaw of sculpins and relatives (Actinopterygii: Cottoidei). Sculpins primarily rely on suction feeding for prey capture, but there is considerable variation in evasiveness of their prey, resulting in variation in anatomy of the lower jaw-closing mechanism. We used functionally-relevant linear measurements to characterize skeletal and muscular components of this system among 25 cottoid species and two outgroup Hexagrammoidei (greenling) species. We quantified evolutionary covariation and correlation of jaw-closing mechanical advantage (i.e., skeletal leverage) and muscle architecture (i.e., gearing) by correlating phylogenetically independent contrasts and fitting phylogenetically corrected generalized least squares models. We found no evidence of evolutionary covariation in muscle architecture and skeletal leverage. While we found a positive evolutionary correlation between out-lever length and adductor muscle fiber length, there was no significant evolutionary correlation between in-lever length and adductor muscle fiber length. We also found a positive evolutionary correlation between in- and out-lever lengths. These results suggest that skeletal morphology and muscle morphology contribute independently to biomechanical diversity among closely related species, indicating the importance of considering both skeletal and muscular variation in studies of ecomorphological diversification.

Patient-specific anatomical model for deep brain stimulation based on 7 Tesla MRI.

OBJECTIVE: Deep brain stimulation (DBS) requires accurate localization of the anatomical target structure, and the precise placement of the DBS electrode within it. Ultra-high field 7 Tesla (T) MR images can be utilized to create patient-specific anatomical 3D models of the subthalamic nuclei (STN) to enhance pre-surgical DBS targeting as well as post-surgical visualization of the DBS lead position and orientation. We validated the accuracy of the 7T imaging-based patient-specific model of the STN and measured the variability of the location and dimensions across movement disorder patients. METHODS: 72 patients who underwent DBS surgery were scanned preoperatively on 7T MRI. Segmentations and 3D volume rendering of the STN were generated for all patients. For 21 STN-DBS cases, microelectrode recording (MER) was used to validate the segmentation. For 12 cases, we computed the correlation between the overlap of the STN and volume of tissue activated (VTA) and the monopolar review for a further validation of the model's accuracy and its clinical relevancy. RESULTS: We successfully reconstructed and visualized the STN in all patients. Significant variability was found across individuals regarding the location of the STN center of mass as well as its volume, length, depth and width. Significant correlations were found between MER and the 7T imaging-based model of the STN (r = 0.86) and VTA-STN overlap and the monopolar review outcome (r = 0.61). CONCLUSION: The results suggest that an accurate visualization and localization of a patient-specific 3D model of the STN can be generated based on 7T MRI. The imaging-based 7T MRI STN model was validated using MER and patient's clinical outcomes. The significant variability observed in the STN location and shape based on a large number of patients emphasizes the importance of an accurate direct visualization of the STN for DBS targeting. An accurate STN localization can facilitate postoperative stimulation parameters for optimized patient outcome.

Period doubling in period-one steady states.

Nonlinear classical dissipative systems present a rich phenomenology in their "route to chaos," including period doubling, i.e., the system evolves with a period which is twice that of the driving. However, typically the attractor of a periodically driven quantum open system evolves with a period which exactly matches that of the driving. Here, we analyze a periodically driven many-body open quantum system whose classical correspondent presents period doubling. We show that by studying the dynamical correlations, it is possible to show the occurrence of period doubling in the quantum (period-one) steady state. We also discuss that such systems are natural candidates for clean and intrinsically robust Floquet time crystals.

BRCA1 through Its E3 Ligase Activity Regulates the Transcription Factor Oct1 and Carbohydrate Metabolism.

The tumor suppressor BRCA1 regulates the DNA damage response (DDR) and other processes that remain incompletely defined. Among these, BRCA1 heterodimerizes with BARD1 to ubiquitylate targets via its N-terminal E3 ligase activity. Here, it is demonstrated that BRCA1 promotes oxidative metabolism by degrading Oct1 (POU2F1), a transcription factor with proglycolytic and tumorigenic effects. BRCA1 E3 ubiquitin ligase mutation skews cells toward a glycolytic metabolic profile while elevating Oct1 protein. CRISPR-mediated Oct1 deletion reverts the glycolytic phenotype. RNA sequencing (RNAseq) confirms deregulation of metabolic genes downstream of Oct1. BRCA1 mediates Oct1 ubiquitylation and degradation, and mutation of two ubiquitylated Oct1 lysines insulates the protein against BRCA1-mediated destabilization. Oct1 deletion in MCF-7 breast cancer cells does not perturb growth in standard culture, but inhibits growth in soft agar and xenograft assays. In primary breast cancer clinical specimens, Oct1 protein levels correlate positively with tumor aggressiveness and inversely with BRCA1. These results identify BRCA1 as an Oct1 ubiquitin ligase that catalyzes Oct1 degradation to promote oxidative metabolism and restrict tumorigenicity. Mol Cancer Res; 16(3); 439-52. ©2018 AACR.

Influences on teleconsultation project utilization rates: the role of dominant logic.

BACKGROUND: This research analyzes teleconsultation from both a mechanistic and complex adaptive system (CAS) dominant logic in order to further understand the influence of dominant logic on utilization rates of teleconsultation projects. In both dominant logics, the objective of teleconsultation projects is to increase access to and quality of healthcare delivery in a cost efficient manner. A mechanistic dominant logic perceives teleconsultation as closely resembling the traditional service delivery model, while a CAS dominant logic focuses on the system's emergent behavior of learning resulting from the relationships and interactions of participating healthcare providers. METHODS: Qualitative case studies of 17 teleconsultation projects that were part of four health sciences center (HSC) based telemedicine networks was utilized. Data were collected at two points in time approximately 10 years apart. Semi-structured interviews of 85 key informants (clinicians, administrators, and IT professionals) involved in teleconsultation projects were the primary data collection method. RESULTS: The findings indicated that the emergent behavior of effective and sustainable teleconsultation projects differed significantly from what was anticipated in a mechanistic dominant logic. Teleconsultation projects whose emergent behavior focused on continuous learning enabled remote site generalists to manage and treat more complex cases and healthcare problems on their own without having to refer to HSC specialists for assistance. In teleconsultation projects that continued to be effectively utilized, participant roles evolved and were expanded. Further, technology requirements for teleconsultation projects whose emergent behavior was learning did not need to be terribly sophisticated. CONCLUSIONS: When a teleconsultation project is designed with a mechanistic dominant logic, it is less likely to be sustained, whereas a teleconsultation project designed with a CAS dominant logic is more likely to be sustained. Consistent with a CAS dominant logic, teleconsultation projects that continued to be utilized involved participants taking on new roles and continuously learning. This continuous learning enabled remote site generalists to better handle the constantly changing nature of the problems faced. A CAS dominant logic provides a theoretical framework which explains why the teleconsultation literature about the role of technology, which is based on a mechanistic dominate logic, does not have adequate explanatory power.