Enhancing neutrophil cytotoxicity of a panel of clinical EGFR antibodies by Fc engineering to IgA3.0.

The epidermal growth factor receptor (EGFR) plays an essential role in cellular signaling pathways that regulate cell growth, proliferation and survival, and is often found dysregulated in cancer. Several monoclonal IgG antibodies have been clinically tested over the years which exert their function via blocking the ligand binding domain (thereby inhibiting downstream signaling) and induction of Fc-related effector functions, such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). However, these IgG antibodies do not optimally recruit neutrophils, by far the most abundant white blood cell population in humans. Therefore, we reformatted six therapeutic EGFR antibodies (cetuximab, panitumumab, nimotuzumab, necitumumab, zalutumumab, and matuzumab) into the IgA3.0 format, which is an IgA2 isotype that has been adapted for clinical application. Reformatting these antibodies preserved Fab-mediated functions such as EGFR binding, growth inhibition and ligand blockade. Additionally, whole leukocyte ADCC was significantly increased when using this panel of IgA3.0 antibodies compared to their respective IgG counterparts, with no major differences between IgA3.0 antibodies. In vivo, IgA3.0 matuzumab outperformed the other antibodies, resulting in the strongest suppression of tumor outgrowth in a long intraperitoneal model. We show that neutrophils are important for the suppression of tumor outgrowth. IgA3.0 matuzumab exhibited reduced receptor internalization compared to the other antibodies, possibly accounting for its superior in vivo Fc-mediated tumor cell killing efficacy. In conclusion, reformatting EGFR antibodies into an IgA3.0 format increased Fc-mediated killing while retaining Fab-mediated functions and could therefore be a good alternative for the currently available antibody therapies.

Any resurgence of leprosy cases in the Togo's post-elimination period? Trend analysis of reported leprosy cases from 2010 to 2022.

BACKGROUND: Leprosy, or Hansen's disease, is a chronic infectious disease caused by Mycobacterium leprae. Togo achieved the target of eliminating leprosy as a public health problem in 2000 (less than 1 case/10 000 population). However, new cases of leprosy are still being reported. The aim of this study was to describe and map trends of leprosy cases notified in Togo from 2010 to 2022. METHODS: This was a descriptive cross-sectional study covering a thirteen-year period from January 1, 2010, to December 31, 2022. The data of the study were leprosy surveillance system's data collected monthly between 2010 and 2022. The estimated number of leprosy cases and the incidence rate of leprosy cases were reported for the whole population by region, by district, by calendar year (2010-2022) and by target sub-population (children under 15, women and people with disabilities). Observed case incidence rates were mapped by health district and by year. RESULTS: From January 1, 2010, to December 31, 2022, 1031 new cases of leprosy were diagnosed in Togo. The median age of subjects was 46 years (interquartile range: 33-60), with extremes from 4 to 96 years. Half the subjects were women (50.7%). Variations in the leprosy incidence rate by year show an increase between 2010 and 2022, from 0.7 cases /100,000 population to 1.1 /100,000 population respectively. From 2010 to 2022, the proportion of cases in children remained low, between 0 and 9%. The proportion of women fluctuated between 39.7% and 67.2% between 2010 and 2017, then stabilized at an average of 50% between 2018 and 2022. The proportion of multi-bacillary leprosy cases increased quasi-linearly between 2010 and 2022, from 70 to 96.6%. Mapping of leprosy cases showed that leprosy was notified in all Togo health districts during the study period, apart from the Lacs district, which reported no leprosy cases. CONCLUSION: Togo has achieved the elimination of leprosy as a public health problem. However, the increase in the number of new leprosy cases and the proportion of leprosy cases in children indicate that transmission of the disease is continuing and that supplementary measures are needed.

Scalable production of tissue-like vascularized liver organoids from human PSCs.

The lack of physiological parity between 2D cell culture and in vivo culture has led to the development of more organotypic models, such as organoids. Organoid models have been developed for a number of tissues, including the liver. Current organoid protocols are characterized by a reliance on extracellular matrices (ECMs), patterning in 2D culture, costly growth factors and a lack of cellular diversity, structure, and organization. Current hepatic organoid models are generally simplistic and composed of hepatocytes or cholangiocytes, rendering them less physiologically relevant compared to native tissue. We have developed an approach that does not require 2D patterning, is ECM independent, and employs small molecules to mimic embryonic liver development that produces large quantities of liver-like organoids. Using single-cell RNA sequencing and immunofluorescence, we demonstrate a liver-like cellular repertoire, a higher order cellular complexity, presenting with vascular luminal structures, and a population of resident macrophages: Kupffer cells. The organoids exhibit key liver functions, including drug metabolism, serum protein production, urea synthesis and coagulation factor production, with preserved post-translational modifications such as N-glycosylation and functionality. The organoids can be transplanted and maintained long term in mice producing human albumin. The organoids exhibit a complex cellular repertoire reflective of the organ and have de novo vascularization and liver-like function. These characteristics are a prerequisite for many applications from cellular therapy, tissue engineering, drug toxicity assessment, and disease modeling to basic developmental biology.

The elimination of trachoma as a public health problem in Togo: Successes and challenges.

BACKGROUND: As of May 2022, 15 countries have declared that they have reached their trachoma elimination targets, but only 13 of them, including Togo, have been validated by the World Health Organization as having eliminated the disease as a public health problem. The aim of this study was to describe the broad interventions that have supported the elimination of trachoma as a public health problem in Togo from its inception in 2006 to the validation of its elimination in 2022. METHOD: A review and compilation of data and information contained in the country's submission to World Health Organization for validation of trachoma elimination as a public health problem was conducted. Data from national and local surveillance systems and reports on actions taken after achieving the elimination target were also included. RESULTS: Togo has achieved the elimination of trachoma as a public health problem by 2022. The prevalence of follicular trachoma among children aged 1-9 years is <5% in all nationally defined administrative units suspected of having trachoma after stopping mass treatment for at least 2 years. The prevalence of trichiasis among persons aged 15 years and older is less than 0.2% in all administrative units previously endemic for trachoma and evidence of the ability to manage incident cases of emerging trichiasis in the community has been demonstrated. The key of the success in the elimination process was primarily the political commitment of the health authorities with financial and technical support from various international organizations. CONCLUSION: The elimination of trachoma as a public health problem in Togo is a real success story that can serve as an example for the elimination of other neglected tropical diseases in Africa. But regular monitoring and surveillance is essential to avoid the re-emergence of such disease in the country.

A collagen-based layered chronic wound biofilm model for testing antimicrobial wound products.

A new in vitro chronic wound biofilm model was recently published, which provided a layered scaffold simulating mammalian tissue composition on which topical wound care products could be tested. In this paper, we updated the model even further to mimic the dynamic influx of nutrients from below as is the case in a chronic wound. The modified in vitro model was created using collagen instead of agar as the main matrix component and contained both Staphylococcus aureus and Pseudomonas aeruginosa. The model was cast in transwell inserts and then placed in wound simulating media, which allowed for an exchange of nutrients and waste products across a filter. Three potential wound care products and chlorhexidine digluconate 2% solution as a positive control were used to evaluate the model. The tested products were composed of hydrogels made from completely biodegradable starch microspheres carrying different active compounds. The compounds were applied topically and left for 2-4 days. Profiles of oxygen concentration and pH were measured to assess the effect of treatments on bacterial activity. Confocal microscope images were obtained of the models to visualise the existence of microcolonies. Results showed that the modified in vitro model maintained a stable number of the two bacterial species over 6 days. In untreated models, steep oxygen gradients developed and pH increased to >8.0. Hydrogels containing active compounds alleviated the high oxygen consumption and decreased pH drastically. Moreover, all three hydrogels reduced the colony forming units significantly and to a larger extent than the chlorhexidine control treatment. Overall, the modified model expressed several characteristics similar to in vivo chronic wounds.

Dihydropyridines Potentiate ATP-Induced Currents Mediated by the Full-Length Human P2X5 Receptor.

The P2X5 receptor, an ATP-gated cation channel, is believed to be involved in tumor development, inflammatory bone loss and inflammasome activation after bacterial infection. Therefore, it is a worthwhile pharmacological target to treat the corresponding diseases, especially in minority populations that have a gene variant coding for functional homotrimeric P2X5 channels. Here, we investigated the effects of dihydropyridines on the human full-length P2X5 receptor (hP2X5FL) heterologously expressed in Xenopus oocytes using the two-microelectrode voltage clamp method. Agonist dependency, kinetics and permeation behavior, including Cl- permeability, were similar to hP2X5FL expressed in HEK293 or 1321N1 cells. Additionally, 1,4-dihydropyridines have been shown to interact with various other purinergic receptors, and we have examined them as potential hP2X5 modulators. Of seven commercially available and four newly synthesized dihydropyridines tested at hP2X5FL, only amlodipine exerted an inhibitory effect, but only at a high concentration of 300 µM. Isradipine and-even more-nimodipine stimulated ATP-induced currents in the low micromolar range. We conclude that common dihydropyridines or four new derivatives of amlodipine are not suitable as hP2X5 antagonists, but amlodipine might serve as a lead for future synthesis to increase its affinity. Furthermore, a side effect of nimodipine therapy could be a stimulatory effect on inflammatory processes.

Effects of Early Life Adversity on Tooth Enamel Formation.

In a systemic effort to survive environmental stress, organ systems fluctuate and adapt to overcome external pressures. The evolutionary drive back toward homeostasis makes it difficult to determine if an organism experienced a toxic exposure to stress, especially in early prenatal and neonatal periods of development. Previous studies indicate that primary human teeth may provide historical records of experiences related to stressors during that early time window. To assess the molecular effects of early life adversity on enamel formation, we used a limited bedding and nesting (LBN) mouse model of early life adversity (ELA) to assess changes in the enamel organ gene expression and enamel matrix mineralization. On average, postnatal day 12 (P12) ELA mice weighed significantly less than the controls. When adjusted for animal weight, ELA molar enamel volume was reduced as compared with the controls, and the relative mineral density of molar enamel was significantly increased. There were no obvious changes in enamel matrix crystal morphology or structure in ELA as compared with the control mouse enamel. RNAseq showed extracellular matrix organization to be the most significantly affected GO and reactome pathways, whereas butanote metabolism was the most significantly altered KEGG pathway. Transcripts expressing the enamel matrix proteins amelogenin (Amelx) and enamelin (Enam) were among the top 4 most differentially expressed genes. When evaluating molecular mechanisms for the changes in gene expression in ELA enamel organs, we found significantly increased expression of Dlx3, while transcripts for clock genes Per1 and Nrd1 were downregulated. These findings support the possibility that the developing enamel organ is sensitive to the pressures of early life adversity and produces molecular and structural biomarkers reflecting these challenges.

Keel bone fractures in Danish laying hens: Prevalence and risk factors.

Keel bone fractures (KBF) in commercial poultry production systems are a major welfare problem with possible economic consequences for the poultry industry. Recent investigations suggest that the overall situation may be worsening. Depending on the housing system, fracture prevalences exceeding 80% have been reported from different countries. No specific causes have yet been identified and this has consequently hampered risk factor identification. The objective of the current study was to investigate the prevalence of KBF in Danish layer hens and to identify risk factors in relation to KBF in all major productions systems, including parent stock production. For risk factor identification, production data from the included flocks was used. In total, 4794 birds from 40 flocks were investigated at end-of-lay. All birds were euthanized on farm and underwent inspection and palpation followed by necropsy. All observations were recorded and subsequently analysed using the SAS statistical software package. In flocks from non-caged systems, fracture prevalence in the range 53%-100%, was observed whereas the prevalence in flocks from enriched cages ranged between 50-98%. Furthermore, often multiple fractures (≥4) were observed in individual birds (range 5-81% of the birds with fractures) depending on the flock. The localization of the fractures at the distal end of the keel bone is highly consistent in all flocks (>96%). Macroscopically the fractures varied morphologically from an appearance with an almost total absence of callus, most frequently observed in caged birds, to large callus formations in and around the fracture lines, which was a typical finding in non-caged birds. Despite being housed under cage-free conditions, parent birds had significantly fewer fractures (all flocks were 60 weeks old) per bird, than other birds from cage-free systems. The body weight at end-of-lay had an effect on the risk of having fractures, heavy hens have significantly fewer fractures at end-of-lay. The older the hens were at onset of lay, the lower was the flock prevalence at end-of-lay. Additionally, the daily egg size at onset of lay was of importance for the risk of developing fractures, the production of heavier eggs initially, resulted in higher fracture prevalence at depopulation. The odds ratio of body weight, (+100 g) was 0.97, age at onset of lay (+1 week) was 0.87 and daily egg weight at onset (+1 gram) was 1.03. In conclusion, the study demonstrated a very high prevalence of KBF in hens from all production systems and identified hen size, age at onset of lay and daily egg weight at onset of lay to be major risk factors for development of KBF in the modern laying hen. Further research regarding this is warranted to strengthen the longevity and enhance the welfare of laying hens.

Measuring enzymatic degradation of degradable starch microspheres using confocal laser scanning microscopy.

Degradable starch microspheres (DSM) have long been used for topical haemostasis, temporary vascular occlusion and as drug delivery systems. When used for the latter, exact degradation rates of DSM have high importance, as this ensures a controlled and timed drug delivery. Current methods of analysing degradation rates are based on whole batch measurements, which does not yield information regarding individual times of degradation nor does it provide direct correlation measurements between sphere diameter and specific degradation time. In this paper we present an alternative method for measuring degradation rates of biodegradable starch microspheres using confocal laser scanning microscopy (CLSM). We succeeded in visualizing the degradation by staining the DSM and then following the spheres over time in a confocal microscope, after the addition of α-amylase. Individual degradation rates of single spheres could be followed, allowing a precise correlation measure between sphere size and degradation time. Furthermore, physical abnormalities such as internal cavities were detected within some spheres. These physical differences also had a measurable effect on the rate of degradation. Finally, complete degradation rates could be determined very accurately. To our knowledge, this is the first paper in which DSM degradation is visualized and measured using CLSM. STATEMENT OF SIGNIFICANCE: Using degradable starch microspheres as a drug delivery system, is a continuously evolving field which shows promise in several different areas of illnesses. This paper presents a new method which visualizes enzymatic degradation of starch microspheres in real-time using confocal microscopy. The method is simple, yet the versatility of it suggests that it could be broadly applied within the field of biodegradation. Here, it illuminates a previously uninvestigated parameter: the effect of physical sphere deformities on the rate of degradation. It also provides precise correlation measures between initial sphere size and time of complete degradation.

Mosaicism for copy number variations in the placenta is even more difficult to interpret than mosaicism for whole chromosome aneuploidy.

OBJECTIVE: To compare mosaicisms in prenatal chorionic villus samples (CVSs) with corresponding postpartum placental samples. METHOD: We collected placentas from 15 consecutive cases of mosaicism detected in CVSs and obtained five standardized samples on each placenta after delivery. All pre- and postnatal placental samples were uncultured and analyzed by high-resolution chromosomal microarray. RESULTS: Ten cases of mosaicism for whole chromosome aneuploidy (mWC) and five cases with mosaicism for (sub)chromosomal copy number variations (mCNVs) were included. In 5/10 mWC cases and in 4/5 mCNV cases the prenatally detected aberration was confirmed in the postpartum placenta. Three postpartum placentas revealed various complex aberrations differing from the prenatal results: (1) mosaicisms for different deletions/duplications on 9p and 9q in all samples (prenatal: mosaic 5.3 Mb duplication on 9p24), (2) different regions with deletions/duplications/loss of heterozygosity on 1p in all samples (prenatal: mosaic 2.3 Mb 1p36 duplication), and (3) mosaicism for a duplication on 5q and a deletion on 6p in one out of five samples (prenatal: mosaic trisomy 7). CONCLUSION: CNVs constitute a complex subgroup in placental mosaicism. Counseling of these couples after chorionic villus sampling should not focus on the specific CNV involved, but on the nature of mosaicism and the option of amniocentesis and ultrasound.

Current In Vitro Biofilm-Infected Chronic Wound Models for Developing New Treatment Possibilities.

Significance: The prevalence of chronic wounds is increasing worldwide. The most recent estimates suggest that up to 2% of the population in the industrialized countries is affected. Recent Advances: During the past few decades, bacterial biofilms have been elucidated as one of the primary reasons why chronic wounds fail to heal. Critical Issues: There is a lack of direct causation and evidence of the role that biofilms play in persistent wounds, which complicates research on new treatment options, since it is still unknown which factors dominate. For this reason, several different in vitro wound models that mimic the biofilm infections observed in chronic wounds and other chronic infections have been created. These different models are, among other purposes, used to test a variety of wound care products. However, chronic wounds are highly complex, and several different factors must be taken into consideration along with the infection, including physiochemical and human-supplemented factors. Furthermore, the limitations of using in vitro models, such as the lack of a responsive immune system should always be given due consideration. Future Directions: Present understandings of all the elements and interactions that take place within chronic wounds are incomplete. As our insight of in vivo chronic wounds continues to expand, so too must the in vitro models used to mimic these infections evolve and adapt to new knowledge.

Into the sea: Antimicrobial resistance determinants in the microbiota of little penguins (Eudyptula minor).

Terrestrial and aquatic birds have been proposed as sentinels for the spread of antimicrobial resistant bacteria, but few species have been investigated specifically in the context of AMR in the marine ecosystem. This study contrasts the occurrence of class 1 integrons and associated antimicrobial resistance genes in wild and captive little penguins (Eudyptula minor), an Australian seabird with local population declines. PCR screening of faecal samples (n = 448) revealed a significant difference in the prevalence of class 1 integrons in wild and captive groups, 3.2% and 44.7% respectively, with genes that confer resistance to streptomycin, spectinomycin, trimethoprim and multidrug efflux pumps detected. Class 1 integrons were not detected in two clinically relevant bacterial species, Klebsiella pneumoniae or Escherichia coli, isolated from penguin faeces. The presence of class 1 integrons in the little penguin supports the use of marine birds as sentinels of AMR in marine environments.

National data on the early clinical use of non-invasive prenatal testing in public and private healthcare in Denmark 2013-2017.

INTRODUCTION: In Denmark, non-invasive prenatal testing (NIPT) has been used since 2013. We aimed to evaluate the early clinical use of NIPT in Danish public and private healthcare settings before NIPT became an integrated part of the national guidelines on prenatal screening and diagnosis in 2017. MATERIAL AND METHODS: NIPT data were collected between March 2013 and June 2017 from national public registries and private providers. Results from follow-up samples (chorionic villi, amniotic fluid, postnatal blood or fetal tissue) were included from The Danish Cytogenetics Central Registry and indications and outcome from The Danish Fetal Medicine Database. RESULTS: A total of 3936 NIPT results were included in the study from public hospitals (n = 3463, 88.0%) and private clinics (n = 473, 12.0%). The total number of prenatal tests was 19 713 during the study period: 20% were NIPT analyses (n = 3936) and 80% invasive procedures (n = 15 777). Twenty-five percent of NIPTs in the private clinics were performed before gestational week 11+0 , whereas NIPT in public settings was used only after combined first trimester screening (P < .001). Regardless of indication, the national public sensitivity was 96.9% (95% CI 82.0%-99.8%) for trisomy 21, 100% (95% CI 46.3%-100%) for trisomy 18, 100% (95% CI 5.5%-100%) for trisomy 13, and 87.0% (95% CI 74.5%-92.4%) for any fetal chromosomal aberration. Forty-seven true-positive NIPT results included cases of common aneuplodies (trisomy 21, n = 31; trisomy 18, n = 5; and trisomy 13, n = 1), sex chromosomal aberrations (n = 7) and atypical chromosomal aberrations (n = 3). One false-negative NIPT result occurred (trisomy 21). Of 47 cases, 21 (45%) cases with a true-positive NIPT result resulted in live births by choice; 11 of these children had Down and 4 had Edwards syndrome. CONCLUSIONS: The total number of NIPT analyses was low compared with the number of invasive procedures in the implementation period. In contrast to the generally high termination rate after a positive result following invasive testing in Denmark, a high proportion of true-positive NIPT results from the public setting resulted in live births. NIPT may be an important risk-free alternative to invasive testing for a minority of women in the public setting who wish to use prenatal genetic testing for information only and not for reproductive decision-making.

A longitudinal study of height gaps among Mexican children: Disparities and social inequity.

RATIONALE: Health outcomes such as height are important determinants of social inequities. OBJECTIVE: We assess height gaps in Mexico among boys and girls from distinct subpopulation groups over time. METHOD: We use longitudinal data from the first three waves of the Mexican Family Life Survey (MxFLS) to analyze children's height differentials by gender and by indigenous and poverty status over 7-10 years. We control for children's characteristics, household factors, and mother's height and use the Blinder-Oaxaca Decomposition method to explain disparities in children's height across the three waves of the MxFLS. RESULTS: The main findings suggest that height inequalities among indigenous and extremely poor boys and girls, compared with their non-indigenous and less socioeconomically disadvantaged counterparts, are persistent. The results also reveal that height disparities among girls are consistently greater than those among boys in similar population groups and that height gaps increase over time for girls. CONCLUSIONS: These findings indicate the relevance of social and economic determinants on children's growth potential and the need to examine the association of social determinants on health outcomes. They also underscore the necessity to design and implement public policies that consider a gender perspective.

[Acceptability of the use of mobile phones for HIV management in Togo] / Acceptabilité de l'utilisation de la téléphonie mobile dans la prise en charge du VIH au Togo.

OBJECTIVE: To describe the acceptability and factors associated with the use of mobile telephones in the care of people living with HIV (PLHIV) in Lomé, Togo. METHOD: A cross-sectional study was conducted from January 5th to March 31st, 2018 in Lomé. PLHIV were recruited from the Department of Infectious and Tropical Diseases of the teaching hospital “CHU Sylvanus Olympio” and the NGO “Espoir Vie Togo”. Socio-demographic and clinical data, mobile phone possession and acceptability of communication with health professionals using a mobile phone were collected with a standardized questionnaire during a face-to-face interview. RESULTS: A total of 259 PLHIV (79.6% women) were recruited. The mean age (± standard deviation) of PLHIV was 43.7 ± 9.8 years and the majority (95.4%) had a mobile phone. Almost all (98.1%) of respondents declared that mobile phone could be a means to maintain contact with a health professional. Phone calls (43.0%), text messages (SMS) (35.1%), and voice messages (20.0%) were the preferred means of communication with health professionals. Factors associated with the acceptability of receiving SMS from a health professional were age < 44 years and having at least a secondary level of education. CONCLUSION: PLHIV are receptive to the integration of mobile technology into the management of their condition. M-health could be an opportunity to improve the management of HIV infection in Togo.

[Acceptability of the use of mobile phones for HIV management in Togo]. / Acceptabilité de l'utilisation de la téléphonie mobile dans la prise en charge du VIH au Togo.

OBJECTIVE: To describe the acceptability and factors associated with the use of mobile telephones in the care of people living with HIV (PLHIV) in Lomé, Togo. METHOD: A cross-sectional study was conducted from January 5th to March 31st, 2018 in Lomé. PLHIV were recruited from the Department of Infectious and Tropical Diseases of the teaching hospital “CHU Sylvanus Olympio” and the NGO “Espoir Vie Togo”. Socio-demographic and clinical data, mobile phone possession and acceptability of communication with health professionals using a mobile phone were collected with a standardized questionnaire during a face-to-face interview. RESULTS: A total of 259 PLHIV (79.6% women) were recruited. The mean age (± standard deviation) of PLHIV was 43.7 ± 9.8 years and the majority (95.4%) had a mobile phone. Almost all (98.1%) of respondents declared that mobile phone could be a means to maintain contact with a health professional. Phone calls (43.0%), text messages (SMS) (35.1%), and voice messages (20.0%) were the preferred means of communication with health professionals. Factors associated with the acceptability of receiving SMS from a health professional were age < 44 years and having at least a secondary level of education. CONCLUSION: PLHIV are receptive to the integration of mobile technology into the management of their condition. M-health could be an opportunity to improve the management of HIV infection in Togo.

Baseline immunoreactivity before pregnancy and poly(I:C) dose combine to dictate susceptibility and resilience of offspring to maternal immune activation.

Despite the potential of rodent models of maternal immune activation (MIA) to identify new biomarkers and therapeutic interventions for a range of psychiatric disorders, current approaches using these models ignore two of the most important aspects of this risk factor for human disease: (i) most pregnancies are resilient to maternal viral infection and (ii) susceptible pregnancies can lead to different combinations of phenotypes in offspring. Here, we report two new sources of variability-the baseline immunoreactivity (BIR) of isogenic females prior to pregnancy and differences in immune responses in C57BL/6 dams across vendors-that contribute to resilience and susceptibility to distinct combinations of behavioral and biological outcomes in offspring. Similar to the variable effects of human maternal infection, MIA in mice does not cause disease-related phenotypes in all pregnancies and a combination of poly(I:C) dose and BIR predicts susceptibility and resilience of pregnancies to aberrant repetitive behaviors and alterations in striatal protein levels in offspring. Even more surprising is that the intermediate levels of BIR and poly(I:C) dose are most detrimental to offspring, with higher BIR and poly(I:C) doses conferring resilience to measured phenotypes in offspring. Importantly, we identify the BIR of female mice as a biomarker before pregnancy that predicts which dams will be most at risk as well as biomarkers in the brains of newborn offspring that correlate with changes in repetitive behaviors. Together, our results highlight considerations for optimizing MIA protocols to enhance rigor and reproducibility and reveal new factors that drive susceptibility of some pregnancies and resilience of others to MIA-induced abnormalities in offspring.

Acceptabilité de l'utilisation de la téléphonie mobile dans la prise en charge du VIH au Togo.

OBJECTIVE: To describe the acceptability and factors associated with the use of mobile telephones in the care of people living with HIV (PLHIV) in Lomé, Togo. METHOD: A cross-sectional study was conducted from January 5th to March 31st, 2018 in Lomé. PLHIV were recruited from the Department of Infectious and Tropical Diseases of the teaching hospital "CHU Sylvanus Olympio" and the NGO "Espoir Vie Togo". Socio-demographic and clinical data, mobile phone possession and acceptability of communication with health professionals using a mobile phone were collected with a standardized questionnaire during a face-to-face interview. RESULTS: A total of 259 PLHIV (79.6% women) were recruited. The mean age (± standard deviation) of PLHIV was 43.7 ± 9.8 years and the majority (95.4%) had a mobile phone. Almost all (98.1%) of respondents declared that mobile phone could be a means to maintain contact with a health professional. Phone calls (43.0%), text messages (SMS) (35.1%), and voice messages (20.0%) were the preferred means of communication with health professionals. Factors associated with the acceptability of receiving SMS from a health professional were age < 44 years and having at least a secondary level of education. CONCLUSION: PLHIV are receptive to the integration of mobile technology into the management of their condition. M-health could be an opportunity to improve the management of HIV infection in Togo.

An Algorithm for Automated Separation of Trabecular Bone From Variably Thick Cortices in High-Resolution Computed Tomography Data.

OBJECTIVE: Structural measurements after separation of cortical from trabecular bone are of interest to a wide variety of communities but are difficult to obtain because of the lack of accurate automated techniques. METHODS: We present a structure-based algorithm for separating cortical from trabecular bone in binarized images. Using the thickness of the cortex as a seed value, bone connected to the cortex within a spatially local threshold value is identified and separated from the remaining bone. The algorithm was tested on seven biological data sets from four species imaged using micro-computed tomography (µ-CT) and high-resolution peripheral quantitative computed tomography (HR-pQCT). Area and local thickness measurements were compared to images segmented manually. RESULTS: The algorithm was approximately 11 times faster than manual measurements and the median error in cortical area was -4.47 ± 4.15%. The median error in cortical thickness was approximately 0.5 voxels for µ-CT data and less than 0.05 voxels for HR-pQCT images resulting in an overall difference of -28.1 ± 71.1 µm. CONCLUSION: A simple and readily implementable methodology has been developed that is repeatable, efficient, and requires few user inputs, providing an unbiased means of separating cortical from trabecular bone. SIGNIFICANCE: Automating the segmentation of variably thick cortices will allow for the evaluation of large data sets in a time-efficient manner and allow for full-field analyses that have been previously limited to small regions of interest. The MATLAB code can be downloaded from https://github.com/TBL-UIUC/downloads.git.