Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: facilitating research through infrastructure, workforce, resources and funding.

BACKGROUND: The National Hemophilia Foundation (NHF) conducted extensive, inclusive community consultations to guide prioritization of research in coming decades in alignment with its mission to find cures and address and prevent complications enabling people and families with blood disorders to thrive. RESEARCH DESIGN AND METHODS: With the American Thrombosis and Hemostasis Network, NHF recruited multidisciplinary expert working groups (WG) to distill the community-identified priorities into concrete research questions and score their feasibility, impact, and risk. WG6 was charged with identifying the infrastructure, workforce development, and funding and resources to facilitate the prioritized research. Community input on conclusions was gathered at the NHF State of the Science Research Summit. RESULTS: WG6 detailed a minimal research capacity infrastructure threshold, and opportunities to enable its attainment, for bleeding disorders centers to participate in prospective, multicenter national registries. They identified challenges and opportunities to recruit, retain, and train the diverse multidisciplinary care and research workforce required into the future. Innovative collaborative approaches to trial design, resource networking, and funding to surmount obstacles facing research in rare disorders were elucidated. CONCLUSIONS: The innovations in infrastructure, workforce development, and resources and funding proposed herein may contribute to facilitating a National Research Blueprint for Inherited Bleeding Disorders.

Research is critical to advancing the diagnosis and care of people with inherited bleeding disorders (PWIBD). This research requires significant infrastructure, including people and resources. Hemophilia treatment centers (HTC) need many different skilled care professionals including doctors, nurses, and other providers; also statisticians, data managers, and other experts to process patients' clinical information into research. Attracting diverse qualified professionals to the clinical and research work requires long-term planning, recruiting individuals in training programs and retaining them as they become experts. Research infrastructure includes physical servers running database software, networks that link them, and the environment in which these components function. US Centers for Disease Control and Prevention (CDC) and American Thrombosis and Hemostasis Network (ATHN) coordinate and fund data collection at HTCs on the health and well-being of thousands of PWIBD into a registry used in research studies.National Hemophilia Foundation (NHF) and ATHN asked our group of health care professionals, technology experts, and lived experience experts (LEE) to identify the infrastructure, workforce, and resources needed to do the research most important to PWIBD. We identified the types of CDC/ATHN studies all HTCs should be able to perform, and the physical and human infrastructure this requires. We prioritized finding the best clinical trial designs to study inherited bleeding disorders, identifying ways to share personnel and tools between HTCs, and innovating how research is governed and funded. Involving LEEs in designing, managing, and carrying out research will be key in conducting research to improve the lives of PWIBD.

Differential DNA methylation of steatosis and non-alcoholic fatty liver disease in adolescence.

BACKGROUND AND AIMS: Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks. APPROACH AND RESULTS: We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially methylated CpG sites (dmCpGs) for which ≥ 2 probes per gene remained significant across four statistical models with a nominal p value < 0.007. EWAS identified dmCpGs related to three genes (ANK1, MIR10a, PTPRN2) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced (ANK1 n = 6, MIR10a n = 7, PTPRN2 n = 3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p < 2.3 × 10-3). CONCLUSIONS: We identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.

Improved Biogas Production from Human Excreta Using Chicken Feather Powder: A Sustainable Option to Eradicating Poverty.

It has been proposed that providing energy for cooking and lighting would solve over 65% of energy needs in rural communities. The use of biomass resources has been found not sustainable as other bioproducts such as biodiesel and bioethanol depend on it. More so that there is a depletion of bioresources in some parts of the world. The shift into animal waste such as poultry droppings and cattle dung has huge prospects, but it is not sustainable in the long term as rural farmers depend on it. The use of human excreta is the most available and sustainable due to the human population. This research aims to provide a workable blueprint of biogas production to meet energy needs. The research considers a laboratory-scale experiment whose result is used to project the medium-scale biodigester. Microbial culturing from human waste is used to initiate the codigestion of human excreta and powdered chicken feathers. It is observed that this procedure drastically reduces the high nitrogen content in the biogas and improves its methane and carbon dioxide content. It is observed that the scaled-up biodigester in a worst case scenario can function at 67%. Design parameters are documented for the onward adoption of the technique.

The GOAL-Hem journey: Shared decision making and patient-centred outcomes.

INTRODUCTION: GOAL-Hem is a novel, haemophilia-specific, patient-centred outcome measure (PCOM) based on goal attainment scaling, allowing people with haemophilia (PwH) to set and monitor the attainment of individualized goals for treatment. AIM: To provide a thorough overview of the creation, validation, and development of GOAL-Hem. METHODS: Clinician workshops were held to develop a haemophilia-specific goal menu. Qualitative data from semistructured interviews with PwH and their caregivers guided further revisions to the goal menu (i.e., goal domains and descriptors). A feasibility study was performed including a 12-week, prospective, noninterventional evaluation involving clinicians and PwH at four US haemophilia treatment centres. Finally, the Patient Voice Study gathered feedback from PwH and their caregivers via an online survey, interviews, and a focus group. RESULTS: The feasibility study validated GOAL-Hem with successful outcomes in construct/content validity and responsiveness, including a large effect in patient- and clinician-rated goal attainments. The Patient Voice Study led to significant refinement of GOAL-Hem goals and descriptors, resulting in a more straightforward and relatable menu for PwH and their caregivers. Overall, GOAL-Hem captured qualitative data in areas important to PwH and employed quantitative methods to evaluate meaningful changes in those areas. The individualized tool was well equipped to handle the complex and chronic nature of haemophilia and was endorsed by PwH, their caregivers, and clinicians. CONCLUSION: The GOAL-Hem development journey may serve as a roadmap for other PCOMs in a variety of settings, including clinical studies, haemophilia treatment centres for care planning, and as a tool to gather real-world evidence.

Collaborative Mining of Whole Genome Sequences for Intelligent HIV-1 Sub-Strain(s) Discovery.

BACKGROUND: Effective global antiretroviral vaccines and therapeutic strategies depend on the diversity, evolution, and epidemiology of their various strains as well as their transmission and pathogenesis. Most viral disease-causing particles are clustered into a taxonomy of subtypes to suggest pointers toward nucleotide-specific vaccines or therapeutic applications of clinical significance sufficient for sequence-specific diagnosis and homologous viral studies. These are very useful to formulate predictors to induce cross-resistance to some retroviral control drugs being used across study areas. OBJECTIVE: This research proposed a collaborative framework of hybridized (Machine Learning and Natural Language Processing) techniques to discover hidden genome patterns and feature predictors for HIV-1 genome sequences mining. METHODS: 630 human HIV-1 genome sequences above 8500 bps were excavated from the National Center for Biotechnology Information (NCBI) database (https://www.ncbi.nlm.nih.gov) for 21 countries across different continents, except for Antarctica. These sequences were transformed and learned using a self-organizing map (SOM). To discriminate emerging/new sub-strain(s), the HIV-1 reference genome was included as part of the input isolates/samples during the training. After training the SOM, component planes defining pattern clusters of the input datasets were generated for cognitive knowledge mining and subsequent labeling of the datasets. Additional genome features, including dinucleotide transmission recurrences, codon recurrences, and mutation recurrences, were finally extracted from the raw genomes to construct output classification targets for supervised learning. RESULTS: SOM training explains the inherent pattern diversity of HIV-1 genomes as well as interand intra-country transmissions in which mobility might play an active role, as corroborated by the literature. Nine sub-strains were discovered after disassembling the SOM correlation hunting matrix space attributed to disparate clusters. Cognitive knowledge mining separated similar pattern clusters bounded by a certain degree of correlation range, as discovered by the SOM. Kruskal-Wallis ranksum test and Wilcoxon rank-sum test showed statistically significant variations in dinucleotide, codon, and mutation patterns. CONCLUSION: Results of the discovered sub-strains and response clusters visualizations corroborate the existing literature, with significant haplotype variations. The proposed framework would assist in the development of decision support systems for easy contact tracing, infectious disease surveillance, and studying the progressive evolution of the reference HIV-1 genome.

Physicochemical Parameters of Raw Pet Food and Dehydrated Pet Treats Developed from Beef Processing Co-Products.

Pet humanization and premiumization of pet foods have led to significant changes in the co-product market, as pet food companies are looking for more profitable protein sources for their products. Co-products such as beef liver (BL) and beef heart (BH) can be combined to generate restructured pet foods rich in vitamins and nutrients. Sodium alginate and encapsulated calcium lactate (ALGIN) can improve the acceptability of meat pieces by transforming them into a singular shape. The objective of this experiment was to assess the physiochemical parameters of co-products for utilization in raw pet foods and restructured pet treats generated from BL and BH by using ALGIN as a structure-forming agent. Results demonstrated increased cooking loss as ALGIN inclusion decreased, but cooking loss decreased as BL proportions increased (p = 0.0056). Expressible moisture of raw pet food decreased as ALGIN inclusion increased, but more moisture was released from treats when BL proportions increased (p < 0.0001). Increasing ALGIN and BH led to increased water activity of cooked treats (p < 0.0001). Thus, we suggest that BL and BH combinations with ALGIN inclusion produces a viable platform for higher inclusions of co-products in pet treats. Additionally, these ingredients improved the finished product quality characteristics of raw pet foods.

Shelf-Life Evaluation of Ingredient Combinations and Technologies for Use in Pet Food Formulations.

Poultry co-product chicken frames (CF) and wooden breast (WB) along with ingredient technology use may bring enhanced value to the pet food industry. Therefore, the current study focused on evaluating CF and WB combinations along with sodium alginate and encapsulated calcium lactate pentahydrate (ALGIN) inclusion within a fresh pet food formulation under simulated shelf-life conditions. Fresh chicken frames (CF) and boneless-skinless wooden breast (WB) were ground and allocated randomly to one of ten treatment combinations with either 0.5 or 1.0% added ALGIN. Ground treatments were placed into a form and fill vacuum package and stored using a reach-in refrigerated case for 21 days. Packages were evaluated for instrumental surface color, lipid oxidation, water activity, and pH on days 1, 3, 7, 14 and 21 of the display. Packages of pet food were lighter, less red, and more yellow (p < 0.05) with increasing percentages of CF regardless of ALGIN inclusion, whereas pH was greater (p < 0.05) and lipid oxidation was less (p < 0.05) with increasing percentage of WB. Water activity increased (p < 0.05) when WB and ALGIN inclusion increased. The current results suggest that the use of ALGIN in a poultry co-product pet food formulation can improve shelf-life characteristics such as surface color and lipid oxidation in fresh pet food.

Processed HIV prognostic dataset for control experiments.

This paper provides a control dataset of processed prognostic indicators for analysing drug resistance in patients on antiretroviral therapy (ART). The dataset was locally sourced from health facilities in Akwa Ibom State of Nigeria, West Africa and contains 14 attributes with 1506 unique records filtered from 3168 individual treatment change episodes (TCEs). These attributes include sex, before and follow-up CD4 counts (BCD4, FCD4), before and follow-up viral load (BRNA, FRNA), drug type/combination (DTYPE), before and follow-up body weight (Bwt, Fwt), patient response to ART (PR), and classification targets (C1-C5). Five (5) output membership grades of a fuzzy inference system ranging from very high interaction to no interaction were constructed to model the influence of adverse drug reaction (ADR) and subsequently derive the PR attribute (a non-fuzzy variable). The PR attribute membership clusters derived from a universe of discourse table were then used to label the classification targets as follows: C1=no interaction, C2=very low interaction, C3=low interaction, C4=high interaction, and C5=very high interaction. The classification targets are useful for building classification models and for detecting patients with ADR. This data can be exploited for the development of expert systems, for useful decision support to treatment failure classification [1] and effectual drug regimen prescription.

Dataset on effect of sand grain size and water salinity on oil recovery.

This research investigates the combined effect of grain size and water salinity on oil recovery. Water flooding experiment was carried out using unconsolidated formation from Niger Delta. Five groups consisting of five samples, were tested for the effective interaction of two factors (grain size and salinity) and how they affect oil recovery. Each group was assigned a particular grain size while the prepared brine concentration was varied within a specified range. The selected grain sizes were obtained from laboratory sieve analyses. For each sand sample, the same concentration of brine used in saturating it was poured into the accumulator and connected to the flooding tube to displace a column of crude oil. The control valve was opened to cause oil displacement. The amount of brine used to displace the crude oil was ten times the pore volume and all the oil in each sample was recovered by the saturated brine solution. Laboratory investigations show that oil recovery was highest for brine concentration of 15,000 ppm; this was also the case in relation to oil recovery and sand grain sizes.

Dengue in parts of the Guinea Savannah region of Nigeria and the risk of increased transmission.

BACKGROUND: Dengue virus (DENV) is spreading to parts of the world where it had not been previously reported. Increased international travel has led to intercontinental importation of dengue by visitors returning from countries in sub-Saharan Africa. Although dengue is well documented in the rain forest region of Nigeria, there is a dearth of information in the Guinea Savannah region, which is a major transit point for local and international visitors in the most populous nation in Africa. We provide preliminary evidence of dengue activity in the Guinea Savannah and highlight the risk factors. METHODS: Blood was collected from a cross-section of 200 patients attending four hospitals in Anyigba, Kogi State. Anti-dengue antibody was identified using DENV immunoglobulin G (IgG) immunoassays. Questionnaires were used to obtain sociodemographic variables and risk factors. Data were analysed with SPSS version 16.0 for Windows. RESULTS: Forty-two (20.5%) participants had anti-DENV IgG antibodies. Persons within the 45-59 y age group were more seropositive, with a rate of 35%. Males were more seropositive compared with females. Marriage, formal education, involvement in business activities and the presence of grasses around homes were associated with higher IgG seropositivity. The presence of open water containers around human dwellings and a lack of mosquito net use are predisposing factors. CONCLUSIONS: This study identified past exposure to DENV among people in Anyigba, located in the Guinea Savannah region. Proper diagnosis of febrile episodes is required to improve case management and curtail off-target treatment. The high rate of previous exposure of patients to dengue indicates the need to strengthen vector control and dengue surveillance programs.

Dataset on corrosion degradation behaviour of mild steel in developed nano-cutting coolant from agro waste.

Investigation of the corrosion degradation behaviour of mild steel in an admixture of coconut shell and egg shell (CS-ES) based nano-fluid was presented in this study. Mild steel coupons were immersed in different concentrations (nine concentrations and the control as a reference) of the developed nano-fluid for a period of 24, 48, 72, 96, 120, 144 and 168 h. Corrosion rate was calculated based on ASTM Standard G1-03 standard practice for preparing, cleaning and evaluation of corrosion test specimens. Open circuit potential measurements (OCP) were also carried out. The potential of the steel samples in the nano-fluid with respect to time was investigated. This dataset could be used in evaluating the performance of mild steel in CS-ES based nano-fluid.

Urinary catheterisation of female dogs: a comparison between three techniques for catheter placement.

The objective of this study was to describe a new technique for urinary catheterisation of female dogs using a novel catheterisation device (NCD) and to compare the time taken to place a catheter using this technique with traditional techniques. A secondary objective was to survey participants on which of the techniques they preferred. Female canine cadavers of varying sizes were utilised and veterinary students who had not previously placed a urinary catheter were enrolled. Each participant performed three catheterisation techniques, Visual with speculum (SPEC), Blind Palpation (BP) and catheterisation with NCD on three sizes of dog. Time required using each technique was compared using Kaplan-Meier plots and mixed models Cox Proportional Hazards regression. Median times to catheterisation were 300 s (IQR 261-417 s) with the SPEC method, 420 s (IQR 253-545 s) with the NCD method and 725 s (574-1032s) with the BP method. Both SPEC and NCD methods were significantly faster compared to the BP method, with Hazard Ratios of 3.66 (95% CI 1.94-6.91, P < 0.001) and 3.57 (95% CI 1.87-6.81, P < 0.001), respectively. Six of nine participants found the NCD the easiest technique, 5/9 of the participants found the palpation technique most difficult and 4/9 found the speculum technique most difficult. BP appears to be the technique of least preference and increased time requirement. The novel urinary catheterisation device may provide a simpler method of visualisation of the urethral papilla and may provide a more sterile way of placing the catheter, although further investigation is needed to confirm this.

Radiological and toxicity risk exposures of oil based mud: health implication on drilling crew in Niger Delta.

Naturally occurring radioactive materials (NORMs) and the presence of toxic metals in drilling fluids/their additives have raised research interests in recent times owing to the risks associated with the exposure times for drillers of petroleum wells. In this study, two drilling fluids A and B were formulated, while two other Mud Samples C and D were obtained from drilled shale and shale-sand formation zones. All four fluids were collected and analyzed for the presence of radioactive and heavy metals. Lead (Pb), mercury (Hg), cadmium Cd), zinc (Zn), chromium (Cr), aluminum (Al), arsenic (As), nickel (Ni), and copper (Cu) were detected in the mud samples. The heavy metal contents of the mud samples are in the following decreasing order of magnitude Hg > Pb > Cd > Cr. In Samples A-D, Hg, Pb, Cr, and Cd were found to have significant concentrations, and the concentrations of these metals increased in the mud samples after they were used for drilling. The concentration of Hg was above the permissible limit. Also, the concentrations of Pb, Cu, As, and Al found in Mud Samples A and B can cause skin irritations over long-term exposures, while Cd, Hg, Zn, and Ni present in the samples were within levels that can cause lung infections or immune breakdown when ingested over long periods. The quantities of Cd, Hg, and Cu detected in Mud Samples C and D can cause skin irritations over long-term exposures, while those of As, Zn, Ni, and Al were seen to have the potential to cause dermal infections/diseases. Based on the results obtained, the cancer risk for the drilling crew lies within 1.1 × 10-3 - 7.7 × 10-3 HQ. The highest dose rate, radium release, and external hazard index were obtained for Mud Sample C whose radium equivalent was judged to be far below the critical safe limit for the drillers. The radium equivalent activity for the two field mud samples (C and D) were estimated to be 27.467 and 22.978 Bq kg-1, respectively, which is the maximum activity obtained for the analyzed samples. The maximum radium equivalent activity for Mud Sample C was estimated as 27.48 Bq kg-1 with a corresponding external hazard index of 0.7. Based on the analysis, there is a significant correlation between the concentration of heavy metals and the radionuclides found in the mud samples.

Fuzzy-multidimensional deep learning for efficient prediction of patient response to antiretroviral therapy.

Drug component interactions are most likely to trigger unexpected pharmacological effects with unknown causal mechanisms, hence, demanding the discovery of patterns to establish suitable and effective regimens. This paper proposes a novel framework that embeds machine learning (ML) and multidimensional scaling (MDS) techniques, for efficient prediction of patient response to antiretroviral therapy (ART). To achieve this, experiment databases were created from two independent sources: a publicly available HIV domain datasets of patients with failed treatment - hosted by the Stanford University, hereinafter referred to as the Stanford HIV database, and locally sourced datasets gathered from 13 prominent healthcare facilities treating HIV patients in Akwa Ibom State of Nigeria, hereinafter referred to as the Akwa-Ibom HIV database: with 5,780 and 3,168 individual treatment change episodes (TCEs) of HIV treatment indicators (baseline CD4 count (BCD4), followup CD4 count (FCD4), baseline viral load (BRNA), followup viral load (FRNA), and drug type combination (DType)), observed from 1,521 and 1,301 unique patient records, respectively. A hybridised (two-stage) classification system consuming the Interval Type-2 Fuzzy Logic (IT2FL) and Deep Neural Network (DNN) was employed to model and optimise patients' response to ART with appreciable error pruning achieved through MDS. Visualisation of the experiment databases showed remarkable immunological changes in the Akwa-Ibom HIV database, as the FCD4 of TCEs clustered far above the BCD4, compared to the Stanford HIV database, where over 40% of FCD4 clustered below the BCD4. Similar changes were noticed for the RNA, as more FRNA copies clustered below the BRNA for the Akwa-Ibom datasets, compared to the Stamford datasets. DNN classification results for both databases showed best performance metrics for the Levenberg-Marquardt algorithm when compared with the resilient backpropagation algorithm, with improved drug pattern predictions for experiment with MDS. This paper is most likely to evolve an avenue that triggers interesting combination(s) for optimum patient response, while ensuring minimal side effects, as further findings revealed the superiority of the proposed approach over existing approaches.

Abnormalities of the external genitalia and groins among primary school boys in Bida, Nigeria.

BACKGROUND: Abnormalities of the male external genitalia and groin, a set of lesions which may be congenital or acquired, are rather obscured to many kids and their parents and Nigerian health care system has no formal program to detect them. OBJECTIVES: To identify and determine the prevalence of abnormalities of external genitalia and groin among primary school boys in Bida, Nigeria. METHODS: This was a cross-sectional study of primary school male pupils in Bida. A detailed clinical examination of the external genitalia and groin was performed on them. RESULTS: Abnormalities were detected in 240 (36.20%) of the 663 boys, with 35 (5.28%) having more than one abnormality. The three most prevalent abnormalities were penile chordee (37, 5.58%), excessive removal of penile skin (37, 5.58%) and retractile testis (34, 5.13%). The prevalence of complications of circumcision was 15.40% and included excessive residual foreskin, excessive removal of skin, skin bridges and meatal stenosis. Undescended testes were seen in 6 (0.90%) boys, with median age of 9 years and 2 were bilateral. Also, micropenis was detected in 27 (4.07%) of the pupils. CONCLUSION: Inguino-penoscrotal abnormalities are common in our community (36.20%). Screening of pre-school and school children to detect them should be introduced into the school health programs in Nigeria.

Hierarchy measurement for modeling network dynamics under directed attacks.

A fundamental issue in the dynamics of complex systems is the resilience of the network in response to targeted attacks. This paper explores the local dynamics of the network attack process by investigating the order of removal of the nodes that have maximal degree, and shows that this dynamic network response can be predicted from the graph's initial connectivity. We demonstrate numerically that the maximal degree M(τ) of the network at time step τ decays exponentially with τ via a topology-dependent exponent. Moreover, the order in which sites are removed can be approximated by considering the network's "hierarchy" function h, which measures for each node V_{i} how many of its initial nearest neighbors have lower degree versus those that have a higher one. Finally, we show that the exponents we identified for the attack dynamics are related to the exponential behavior of spreading activation dynamics. The results suggest that the function h, which has both local and global properties, is a novel nodal measurement for network dynamics and structure.

The association of host and genetic melanoma risk factors with Breslow thickness in the Western Australian Melanoma Health Study.

BACKGROUND: Breslow thickness is the most important predictor of survival in localized malignant melanoma. A number of melanoma risk factors have been shown to be associated with Breslow thickness; however, the role of genetic loci has been little investigated to date. OBJECTIVES: To investigate the association of known melanoma susceptibility genetic loci with Breslow thickness. METHODS: Participants were 800 individuals from the Western Australian Melanoma Health Study who completed a questionnaire and provided a DNA sample. Genetic association analyses between single-nucleotide polymorphisms (SNPs) from 15 candidate melanoma susceptibility genes and Breslow thickness were performed, controlling for relevant covariates. RESULTS: Older age at diagnosis and absence of naevi were associated with increased Breslow thickness. Following adjustment for multiple testing, no SNPs were significantly associated with Breslow thickness. CONCLUSIONS: Associations observed between Breslow thickness and age and naevi reinforce current knowledge. Some evidence of shared genetic determinants between melanoma risk and Breslow thickness was found. Further studies are required to confirm this finding.

Increased decidual mRNA expression levels of candidate maternal pre-eclampsia susceptibility genes are associated with clinical severity.

INTRODUCTION: Pre-eclampsia (PE) has a familial association, with daughters of women who had PE during pregnancy having more than twice the risk of developing PE themselves. Through genome-wide linkage and genetic association studies in PE-affected families and large population samples, we previously identified the following as positional candidate maternal susceptibility genes for PE; ACVR1, INHA, INHBB, ERAP1, ERAP2, LNPEP, COL4A1 and COL4A2. The aims of this study were to determine mRNA expression levels of previously identified candidate maternal pre-eclampsia susceptibility genes from normotensive and severe PE (SPE) pregnancies and correlate mRNA expression levels with the clinical severity of SPE. METHODS: Third trimester decidual tissues were collected from both normotensive (n = 21) and SPE pregnancies (n = 24) and mRNA expression levels were determined by real-time PCR. Gene expression was then correlated with several parameters of clinical severity in SPE. Statistical significance was determined by Mann-Whitney U test and Spearman's Correlation. RESULTS: The data demonstrate significantly increased decidual mRNA expression levels of ACVR1, INHBB, ERAP1, ERAP2, LNPEP, COL4A1 and COL4A2 in SPE (p < 0.05). Increased mRNA expression levels of several genes - INHA, INHBB, COL4A1 and COL4A2 were correlated with earlier onset of PE and earlier delivery of the fetus (p < 0.05). CONCLUSION: These results suggest altered expression of maternal susceptibility genes may play roles in PE development and the course of disease severity.

Stem cell-based therapy for neonatal lung disease: it is in the juice.

Bronchopulmonary dysplasia, the chronic lung disease of prematurity, is the most common complication in extremely premature infants (born before 28 wk gestation). Despite advances in perinatal care, modern clinical management remains devoid of therapies specifically promoting lung repair and lung growth. Recent progress in stem cell biology has uncovered the promise of stem/progenitor cells to repair damaged organs. Contrary to the original theory that stem cells engraft and repopulate the damaged organ, evidence suggests that stem cells act via a paracrine mechanism. This review highlights the preclinical evidence for the therapeutic potential of cell-based therapies in animal models of neonatal chronic lung injury and the multiple therapeutic avenues offered by soluble stem cell-derived factors.