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Caregiver-infant interactions shape infants' early visual experience; however, there is limited work from low-and middle-income countries (LMIC) in characterizing the visual cognitive dynamics of these interactions. Here, we present an innovative dyadic visual cognition pipeline using machine learning methods which captures, processes, and analyses the visual dynamics of caregiver-infant interactions across cultures. We undertake two studies to examine its application in both low (rural India) and high (urban UK) resource settings. Study 1 develops and validates the pipeline to process caregiver-infant interaction data captured using head-mounted cameras and eye-trackers. We use face detection and object recognition networks and validate these tools using 12 caregiver-infant dyads (4 dyads from a 6-month-old UK cohort, 4 dyads from a 6-month-old India cohort, and 4 dyads from a 9-month-old India cohort). Results show robust and accurate face and toy detection, as well as a high percent agreement between processed and manually coded dyadic interactions. Study 2 applied the pipeline to a larger data set (25 6-month-olds from the UK, 31 6-month-olds from India, and 37 9-month-olds from India) with the aim of comparing the visual dynamics of caregiver-infant interaction across the two cultural settings. Results show remarkable correspondence between key measures of visual exploration across cultures, including longer mean look durations during infant-led joint attention episodes. In addition, we found several differences across cultures. Most notably, infants in the UK had a higher proportion of infant-led joint attention episodes consistent with a child-centered view of parenting common in western middle-class families. In summary, the pipeline we report provides an objective assessment tool to quantify the visual dynamics of caregiver-infant interaction across high- and low-resource settings.

Abstract Over the last several years, the study of working memory (WM) for simple visual features (e.g., colors, orientations) has been dominated by perspectives that assume items in WM are stored independently of one another. Evidence has revealed, however, systematic biases in WM recall which suggest that items in WM interact during active maintenance. In the present study, we report two experiments that replicate a repulsion bias between metrically similar colors during active storage in WM. We also observed that metrically similar colors were stored with lower resolution than a unique color held actively in mind at the same time. To account for these effects, we report quantitative simulations of two novel neurodynamical models of WM. In both models, the unique behavioral signatures reported here emerge directly from laterally-inhibitory neural interactions that serve to maintain multiple, distinct neural representations throughout the WM delay period. Simulation results show that the full pattern of empirical findings was only obtained with a model that included an elaborated spatial pathway with sequential encoding of memory display items. We discuss implications of our findings for theories of visual working memory more generally.

Universal accessibility implies that everybody has an equal chance to access anything, which should also apply to the tourism industry. The United Nations World Tourism Organisation has pleaded that tourism be open to all, despite any impairments. Universal accessibility is not always available to visually, intellectually, mobility, psychiatrically and learning impoverished persons. People with Disabilities are often denied tourist activity pleasures enjoyed by healthy persons. The obvious challenges include restriction of mobility, but few facilities are visually impaired-friendly, besides addressing the other impairments. The study question was to investigate whether hospitality staff are educated or trained to assist people with disabilities to enjoy fully the facilities offered to paying guests at places of accommodation. The study adopted a mixed methodology, following a cluster and convenient sampling framework, focussing on the Cape Winelands area of Cape Town, South Africa. The results indicate that hospitality staff are interested in receiving disability awareness training, but that essential appropriate training would benefit disabled travel as a market segment in South Africa. This study is of material importance to tourism organisations, such as Cape Town Tourism and Wesgro, in promoting tourism in one of the major destinations in world tourism.

Visual working memory (VWM) is a central cognitive system used to compare views of the world and detect changes in the local environment. This system undergoes dramatic development in the first two years; however, we know relatively little about the functional organization of VWM at the level of the brain. Here, we used image-based functional near-infrared spectroscopy (fNIRS) to test four hypotheses about the spatial organization of the VWM network in early development. Four-month-olds, 1-year-olds, and 2-year-olds completed a VWM task while we recorded neural activity from 19 cortical regions-of-interest identified from a meta-analysis of the adult fMRI literature on VWM. Results showed significant task-specific functional activation near 6 of 19 ROIs, revealing spatial consistency in the brain regions activated in our study and brain regions identified to be part of the VWM network in adult fMRI studies. Working memory related activation was centered on bilateral anterior intraparietal sulcus (aIPS), left temporoparietal junction (TPJ), and left ventral occipital complex (VOC), while visual exploratory measures were associated with activation in right dorsolateral prefrontal cortex, left TPJ, and bilateral IPS. Results show that a distributed brain network underlies functional changes in VWM in infancy, revealing new insights into the neural mechanisms that support infants’ improved ability to remember visual information and to detect changes in an on-going visual stream.

Previous neuroimaging studies have reported a posterior to anterior shift of activation in ageing (PASA). Here, we explore the nature of this shift by modulating load (1,2 or 3 items) and perceptual complexity in two variants of a visual working memory task (VWM): a ‘simple’ color and a ‘complex’ shape change detection task. Functional near-infrared spectroscopy (fNIRS) was used to record changes in activation in younger (N=24) and older adults (N=24). Older adults exhibited PASA by showing lesser activation in the posterior cortex and greater activation in the anterior cortex when compared to younger adults. Further, they showed reduced accuracy at loads 2 and 3 for the simple task and across all loads for the complex task. Activation in the posterior and anterior cortices was modulated differently for younger and older adults. In older adults, increasing load in the simple task was accompanied by decreasing activation in the posterior cortex and lack of modulation in the anterior cortex, suggesting the inability to encode and/or maintain representations without much aid from higher-order centres. In the complex task, older adults recruited verbal working memory areas in the posterior cortex, suggesting that they used adaptive strategies such as labelling the shape stimuli. This was accompanied by reduced activation in the anterior cortex reflecting the inability to exert top-down modulation to typical VWM areas in the posterior cortex to improve behavioral performance.

Nine-banded armadillos (Dasypus novemcinctus) are naturally infected with Mycobacterium leprae and are implicated in the zoonotic transmission of leprosy in the United States. In Mexico, the existence of such a reservoir remains to be characterized. We describe a wild armadillo infected by M. leprae in the state of Nuevo León, Mexico.

The number of new cases of leprosy reported worldwide has remained essentially unchanged for the last decade despite continued global use of free multidrug therapy (MDT) provided to any diagnosed leprosy patient. In order to more effectively interrupt the chain of transmission, new strategies will be required to detect those with latent disease who contribute to furthering transmission. To improve the ability to diagnose leprosy earlier in asymptomatic infected individuals, we examined the combined use of two well-known biomarkers of M. leprae infection, namely the presence of M. leprae DNA by PCR from earlobe slit skin smears (SSS) and positive antibody titers to the M. leprae-specific antigen, Phenolic Glycolipid I (anti-PGL-I) from leprosy patients and household contacts living in seven hyperendemic cities in the northern state of Pará, Brazilian Amazon. Combining both tests increased sensitivity, specificity and accuracy over either test alone. A total of 466 individuals were evaluated, including 87 newly diagnosed leprosy patients, 52 post-treated patients, 296 household contacts and 31 healthy endemic controls. The highest frequency of double positives (PGL-I+/RLEP+) were detected in the new case group (40/87, 46%) with lower numbers for treated (12/52, 23.1%), household contacts (46/296, 15.5%) and healthy endemic controls (0/31, 0%). The frequencies in these groups were reversed for double negatives (PGL-I-/RLEP-) for new cases (6/87, 6.9%), treated leprosy cases (15/52, 28.8%) and the highest in household contacts (108/296, 36.5%) and healthy endemic controls (24/31, 77.4%). The data strongly suggest that household contacts that are double positive have latent disease, are likely contributing to shedding and transmission of disease to their close contacts and are at the highest risk of progressing to clinical disease. Proposed strategies to reduce leprosy transmission in highly endemic areas may include chemoprophylactic treatment of this group of individuals to stop the spread of bacilli to eventually lower new case detection rates in these areas.

Human settlement of Madagascar traces back to the beginning of the first millennium with the arrival of Austronesians from Southeast Asia, followed by migrations from Africa and the Middle East. Remains of these different cultural, genetic, and linguistic legacies are still present in Madagascar and other islands of the Indian Ocean. The close relationship between human migration and the introduction and spread of infectious diseases, a well-documented phenomenon, is particularly evident for the causative agent of leprosy, Mycobacterium leprae. In this study, we used whole-genome sequencing (WGS) and molecular dating to characterize the genetic background and retrace the origin of the M. leprae strains circulating in Madagascar (n = 30) and the Comoros (n = 3), two islands where leprosy is still considered a public health problem and monitored as part of a drug resistance surveillance program. Most M. leprae strains (97%) from Madagascar and Comoros belonged to a new genotype as part of branch 1, closely related to single nucleotide polymorphism (SNP) type 1D, named 1D-Malagasy. Other strains belonged to the genotype 1A (3%). We sequenced 39 strains from nine other countries, which, together with previously published genomes, amounted to 242 genomes that were used for molecular dating. Specific SNP markers for the new 1D-Malagasy genotype were used to screen samples from 11 countries and revealed this genotype to be restricted to Madagascar, with the sole exception being a strain from Malawi. The overall analysis thus ruled out a possible introduction of leprosy by the Austronesian settlers and suggests a later origin from East Africa, the Middle East, or South Asia.

Abstract Bacterial colonization of the urogenital tract is limited by innate defenses, including the production of antimicrobial peptides (AMPs). Uropathogenic Escherichia coli (UPEC) resist AMP‐killing to cause a range of urinary tract infections (UTIs) including asymptomatic bacteriuria, cystitis, pyelonephritis, and sepsis. UPEC strains have high genomic diversity and encode numerous virulence factors that differentiate them from non‐UTI‐causing strains, including ompT. As OmpT homologs cleave and inactivate AMPs, we hypothesized that UPEC strains from patients with symptomatic UTIs have high OmpT protease activity. Therefore, we measured OmpT activity in 58 clinical E. coli isolates. While heterogeneous OmpT activities were observed, OmpT activity was significantly greater in UPEC strains isolated from patients with symptomatic infections. Unexpectedly, UPEC strains exhibiting the greatest protease activities harbored an additional ompT‐like gene called arlC (ompTp). The presence of two OmpT‐like proteases in some UPEC isolates led us to compare the substrate specificities of OmpT‐like proteases found in E. coli. While all three cleaved AMPs, cleavage efficiency varied on the basis of AMP size and secondary structure. Our findings suggest the presence of ArlC and OmpT in the same UPEC isolate may confer a fitness advantage by expanding the range of target substrates.

Leprosy is caused by the yet-uncultured pathogen Mycobacterium leprae. Here, Benjak et al. obtain M. leprae genome sequences from DNA extracted from patients' skin biopsies and, by analysing 154 genomes from 25 countries, provide insight into the pathogen’s evolution and antimicrobial resistance.

Abstract Early detection of leprosy is key to reduce the ongoing transmission. Antibodies directed against M. leprae PGL-I represent a useful biomarker for detecting multibacillary (MB) patients. Since efficient leprosy diagnosis requires field-friendly test conditions, we evaluated two rapid lateral flow assays (LFA) for detection of Mycobacterium leprae-specific antibodies: the visual immunogold OnSite Leprosy Ab Rapid test [Gold-LFA] and the quantitative, luminescent up-converting phosphor anti-PGL-I test [UCP-LFA]. Test performance was assessed in independent cohorts originating from three endemic areas. In the Philippine cohort comprising patients with high bacillary indices (BI; average:4,9), 94%(n = 161) of MB patients were identified by UCP-LFA and 78%(n = 133) by Gold-LFA. In the Bangladeshi cohort, including mainly MB patients with low BI (average:1), 41%(n = 14) and 44%(n = 15) were detected by UCP-LFA and Gold-LFA, respectively. In the third cohort of schoolchildren from a leprosy hyperendemic region in Brazil, both tests detected 28%(n = 17) seropositivity. Both rapid tests corresponded well with BI(p

BACKGROUND:Erythema nodosum leprosum (ENL) is a systemic inflammatory complication occurring mainly in patients with lepromatous leprosy (LL) and borderline lepromatous leprosy (BL). Prednisolone is widely used for treatment of ENL reactions. However, it has been reported that prolonged treatment with prednisolone increases the risk for prednisolone-induced complications such as osteoporosis, diabetes, cataract and arteriosclerosis. It has been speculated that perhaps these complications result from lipid profile alterations by prednisolone. The effects of extended prednisolone treatment on lipid profiles in ENL patients have not been studied in leprosy patients with ENL reactions. Therefore, in this study we conducted a case-control study to investigate the changes in lipid profiles and serological responses in Ethiopian patients with ENL reaction after prednisolone treatment. METHODS:A prospective matched case-control study was employed to recruit 30 patients with ENL and 30 non-reactional LL patient controls at ALERT Hospital, Ethiopia. Blood samples were obtained from each patient with ENL reaction before and after prednisolone treatment as well as from LL controls. The serological host responses to PGL-1, LAM and Ag85 M. leprae antigens were measured by ELISA. Total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were measured by spectrophotometric method. RESULTS:The host antibody response to M. leprae PGL-1, LAM and Ag85 antigens were significantly reduced in patients with ENL reactions compared to LL controls after treatment. Comparison between patients with acute and chronic ENL showed that host-response to PGL-1 was significantly reduced in chronic ENL after prednisolone treatment. Untreated patients with ENL reactions had low lipid concentration compared to LL controls. However, after treatment, both groups had comparable lipid profiles except for LDL, which was significantly higher in patients with ENL reaction. Comparison within the ENL group before and after treatment showed that prednisolone significantly increased LDL and HDL levels in ENL patients and this was more prominent in chronic ENL than in acute patients with ENL. CONCLUSION:The significantly increased prednisolone-induced LDL and TG levels, particularly in patients with chronic ENL reactions, is a concern in the use of prednisolone for extended periods in ENL patients. The findings highlight the importance of monitoring lipid profiles during treatment of patients to minimize the long-term risk of prednisolone-induced complications.

We examined associations between dietary patterns at 12 months, characterised using multiple methodologies, and risk of obesity and early childhood caries (ECC) at 24−36 months. Participants were Australian toddlers (n = 1170) from the Study of Mothers’ and Infants’ Life Events affecting oral health (SMILE) birth cohort. Principal Components Analysis (PCA) and the Dietary Guideline Index for Children and Adolescents (DGI-CA) were applied to dietary intake data (1, 2 or 3-days) at 12 months, and regression analysis used to examine associations of dietary patterns with body mass index Z-score and presence of ECC at 24−36 months. Two dietary patterns were extracted using PCA: family diet and cow’s milk and discretionary combination. The mean DGI-CA score was 56 ± 13 (out of a possible 100). No statistically significant or clinically meaningful associations were found between dietary pattern or DGI-CA scores, and BMI Z-scores or ECC (n = 680). Higher cow’s milk and discretionary combination pattern scores were associated with higher energy and free sugars intakes, and higher family diet pattern scores and DGI-CA scores with lower free sugars intakes. The association between dietary patterns and intermediate outcomes of free sugars and energy intakes suggests that obesity and/or ECC may not yet have manifested, and thus longitudinal investigation beyond two years of age is warranted.

Leprosy remains as a public health problem and its physiopathology is still not fully understood. MicroRNAs (miRNA) are small RNA non-coding that can interfere with mRNA to regulate gene expression. A few studies using DNA chip microarrays have explored the expression of miRNA in leprosy patients using a predetermined set of genes as targets, providing interesting findings regarding the regulation of immune genes. However, using a predetermined set of genes restricted the possibility of finding new miRNAs that might be involved in different mechanisms of disease. Thus, we examined the miRNome of tuberculoid (TT) and lepromatous (LL) patients using both blood and lesional biopsies from classical leprosy patients (LP) who visited the Dr. Marcello Candia Reference Unit in Sanitary Dermatology in the State of Pará and compared them with healthy subjects. Using a set of tools to correlate significantly differentially expressed miRNAs with their gene targets, we identified possible interactions and networks of miRNAs that might be involved in leprosy immunophysiopathology. Using this approach, we showed that the leprosy miRNA profile in blood is distinct from that in lesional skin as well as that four main groups of genes are the targets of leprosy miRNA: (1) recognition and phagocytosis, with activation of immune effector cells, where the immunosuppressant profile of LL and immunoresponsive profile of TT are clearly affected by miRNA expression; (2) apoptosis, with supportive data for an antiapoptotic leprosy profile based on BCL2, MCL1, and CASP8 expression; (3) Schwann cells (SCs), demyelination and epithelial–mesenchymal transition (EMT), supporting a role for different developmental or differentiation gene families, such as Sox, Zeb, and Hox; and (4) loss of sensation and neuropathic pain, revealing that RHOA, ROCK1, SIGMAR1, and aquaporin-1 (AQP1) may be involved in the loss of sensation or leprosy pain, indicating possible new therapeutic targets. Additionally, AQP1 may also be involved in skin dryness and loss of elasticity, which are well known signs of leprosy but with unrecognized physiopathology. In sum, miRNA expression reveals new aspects of leprosy immunophysiopathology, especially on the regulation of the immune system, apoptosis, SC demyelination, EMT, and neuropathic pain.

BACKGROUND:Leprosy diagnosis is mainly based on clinical evaluation, although this approach is difficult, especially for untrained physicians. We conducted a temporary campaign to detect previously unknown leprosy cases in midwestern Brazil and to compare the performance of different serological tests. METHODS:A mobile clinic was stationed at the main bus terminal in Brasília, Brazil. Volunteers were quizzed and given a clinical exam to allow categorization as either patients, known contacts of patients or non-contacts, and blood was collected to determine anti-PGL-I and anti-LID-1 antibody titers by ELISA and by the NDO-LID rapid test. New cases of leprosy and the impact of performing this broad random surveillance strategy were evaluated. Accuracy values and concordance between the test results were evaluated among all groups. RESULTS:Four hundred thirty-four individuals were evaluated, and 44 (10.1%) were diagnosed with leprosy. Borderline forms were the most frequent presentation. Both tests presented higher positivity in those individuals with multibacillary disease. Serological tests demonstrated specificities arround 70% for anti-PGL-1 and anti-LID ELISA; and arround 40% for NDO-LID. Sensitivities ranged from 48 to 62%. A substantial agreement between NDO-LID and ELISA with concomitant positive results was found within leprosy patients (Kappa index = 0.79 CI95% 0.36-1.22). CONCLUSIONS:The unexpectedly high leprosy prevalence in this population indicates ongoing community-based exposure to Mycobacterium leprae antigens and high rates of subclinical infection. All tests showed low specificity and sensitivity values and therefore cannot be considered for use as stand-alone diagnostics. Rather, considering their positivity among MB patients and non-patients, these tests can be considered effective tools for screening and identifying individuals at high risk who might benefit from regular monitoring.

Although leprosy is curable with drug treatment, the identification of biomarkers of infection, disease progression and treatment efficacy would greatly help to reduce the overall prevalence of the disease. Reliable biomarkers would also reduce the incidence of grade-2 disability by ensuring that those who are most at risk are diagnosed and treated early or offered repeated treatments in the case of relapse. In this study, we examined the reactivity of sera from lepromatous and tuberculoid leprosy patients (LPs) against a panel of 12 recombinant Mycobacterium leprae proteins and found that six proteins were strongly recognised by multibacillary (MB) patients, while only three were consistently recognised by paucibacillary patients. To better understand the dynamics of patient antibody responses during and after drug therapy, we measured antibody titres to four recombinant proteins, phenolic glycolipid-I and lipoarabinomannan at baseline and up to two years after diagnosis to investigate the temporal changes in the antibody titres. Reactivity patterns to individual antigens and decreases in antibody titres were patient-specific. Antibody titres to proteins declined more rapidly vs. those to carbohydrate and glycolipid antigens. Compared to baseline values, increases in antibody titres were observed during reactional episodes in one individual. Additionally, antibody responses against a subset of antigens that provided a good prognostic indicator of disease progression were analysed in 51 household contacts of MB index cases for up to two years. Although the majority of these contacts showed no change or exhibited decreases in antibody titres, seven individuals developed higher titres towards one or more of these antigens and one individual with progressively higher titres was diagnosed with borderline lepromatous leprosy 19 months after enrolment. The results of this study indicate that antibody titres to specific M. leprae antigens can be used to monitor treatment efficacy in LPs and assess disease progression in those most at risk for developing this disease.