Face-selective responses in combined EEG/MEG recordings with fast periodic visual stimulation (FPVS).

Fast periodic visual stimulation (FPVS) allows the recording of objective brain responses of human face categorization (i.e., generalizable face-selective responses) with high signal-to-noise ratio. This approach has been successfully employed in a number of scalp electroencephalography (EEG) studies but has not been used with magnetoencephalography (MEG) yet, let alone with combined MEG/EEG recordings and distributed source estimation. Here, we presented various natural images of faces periodically (1.2 Hz) among natural images of objects (base frequency 6 Hz) whilst recording simultaneous EEG and MEG in 15 participants. Both measurement modalities showed face-selective responses at 1.2 Hz and harmonics across participants, with high and comparable signal-to-noise ratio (SNR) in about 3 min of stimulation. The correlation of face categorization responses between EEG and two MEG sensor types was lower than between the two MEG sensor types, indicating that the two sensor modalities provide independent information about the sources of face-selective responses. Face-selective EEG responses were right-lateralized as reported previously, and were numerically but non-significantly right-lateralized in MEG data. Distributed source estimation based on combined EEG/MEG signals confirmed a more bilateral face-selective response in visual brain regions located anteriorly to the common response to all stimuli at 6 Hz and harmonics. Conventional sensor and source space analyses of evoked responses in the time domain further corroborated this result. Our results demonstrate that FPVS in combination with simultaneously recorded EEG and MEG may serve as an efficient localizer paradigm for human face categorization.

Type 1 interferonopathy presenting as juvenile idiopathic arthritis with interstitial lung disease: report of a new phenotype.

BACKGROUND: STING-associated vasculopathy with onset in infancy (SAVI) is a type 1 interferonopathy manifesting as a pulmonary and vascular syndrome resulting from gain-of-function mutations in TMEM173, the gene encoding STING. Familial reports in the literature are sparse. CASE PRESENTATION: We report a case series of SAVI in a three generation kindred, with a phenotype of interstitial lung disease (ILD) and rheumatoid factor positive polyarticular juvenile idiopathic arthritis (JIA). Current and historical medical records were reviewed for clinical and laboratory information. Whole blood from cases 1 and 2, plus stored appendicectomy tissue from case 3, underwent DNA sequencing of the TMEM173 gene. Peripheral blood RNA was obtained from cases 1 and 2 for functional assessment of the TMEM173 mutation. DNA sequencing identified the same heterozygous TMEM173 mutation (c.463G > A; p.Val155Met) in all three cases, consistent with a diagnosis of the autosomal dominant condition SAVI. Functional assessment of this mutation identified a prominent interferon signature which was confirmed on repeat testing. CONCLUSIONS: SAVI presented in this family as ILD with early onset juvenile rheumatoid arthritis. This condition should be considered in all rheumatoid arthritis patients with early-onset ILD and in all JIA patients with ILD.

Human Papilloma Virus Vaccination Compliance in a Military Aviation Training Community.

INTRODUCTION: Human Papilloma Virus (HPV) vaccination compliance as reported by the CDC in 2011 falls short of a national goal to have 80% of adolescents vaccine-complete by 2020. The Naval Aviation Schools Command, Pensacola, Florida offers a single point of contact for military aviation trainees offering near-complete capture of an HPV vaccine target population. The purpose of this study is to identify baseline HPV vaccination rates among military aviation trainees and whether or not the provision of educational materials at the start of aviation training would increase future HPV vaccination compliance. MATERIALS AND METHODS: Approval to conduct this study was obtained from the Institutional Review Board of Naval Medical Center Portsmouth, Virginia. Our population of interest consisted of US Navy and Marine Corps student naval aviators, student naval flight officers (officers), and student enlisted air crew (enlisted) reporting for aviation related duty. A convenience sampling of officer and enlisted student classes checking in for training was performed over a period of 6 months. The first 3 months of students were assigned as the intervention group and the remaining 3 months of students were assigned to the control group. This study was conducted in two parts: (1) an anonymous survey captured cross-sectional data of self-reported HPV vaccine use, and (2) prospective analysis of service members' HPV vaccine rates before and after educational intervention as documented within the military's electronic health record system, Armed Forces Health Longitudinal Technology Application (AHLTA). RESULTS: AHLTA immunization status was evaluated for 1,164 personnel; 114 (9.8%) were excluded for missing basic vaccination information. Of the remaining 1,050, another 199 (19%) members were excluded as already vaccine complete (evidenced by three shots documented) prior to entry into the study. Within the 199 service members with documented baseline HPV vaccination completion, 197/199 (99%) were officers and 2/199 (0.1%) were enlisted. A total of 851 personnel were included for prospective analysis. Person-time of 100 person years was used and the vaccination rate translates to 16.62/100 person years (95% CI 11.29, 23.59) within intervention vs. 2.96/100 person years (95% CI 0.80, 7.58) within control groups and are significantly different (P = 0.0001). Comparing intervention and control groups, rate ratios = 5.61 (95% CI 2.14, 18.64) and rate differences = 13.66 (95% CI 7.13, 20.19). Among intervention group survey responders who previously reported nonvaccine use, 50.5% reported a change in opinion about obtaining the vaccination, with a higher proportion of enlisted members reporting a change in opinion (62.8% vs. 39.7%, P = 0.0053). CONCLUSIONS: Electronic health records immunizations review noted a baseline vaccine completion rate of 19%. Our study showed a health inequity between enlisted and officers, with officers having 99% of the documented baseline completion rates per AHLTA data. Our prospective analysis noted statistically significant rate differences of 13.66% and rate ratios of 5.61 between intervention and control groups. This analysis of AHLTA data combined with survey response of 50.5% indicating a change in opinion about HPV vaccine use among those who had not yet started vaccine series suggests targeted education would be a low-cost intervention to improve HPV vaccine use rates.

Gender Differences in Dry-EEG Manifestations During Acute and Insidious Normobaric Hypoxia.

INTRODUCTION: Prior research suggests there may be gender differences with regards to hypoxia resilience. Our study was designed to determine whether there were differences between genders in neuronal electrical activity at simulated altitude and whether those changes correlated with cognitive and aviation performance decrements.METHODS: There were 60 student Naval Aviators or Flight Officers who completed this study (30 women, 30 men). Participants were exposed to increasing levels of normobaric hypoxia and monitored with dry EEG while flying a fixed-base flight simulation. Gender differences in brainwave frequency power were quantified using MATLAB. Changes in flight and cognitive performance were analyzed via simulation tasks and with a cognitive test validated under hypoxia.RESULTS: Significant decreases in theta and gamma frequency power occurred for women compared to men with insidious hypoxic exposures to 20K, with an average frequency power decrease for women of 19.4% compared to 9.3% for men in theta, and a 42.2% decrease in gamma for women compared to 21.7% for men. Beta frequency power correlated highest between genders, with an average correlation coefficient of r = 0.95 across seven channels.DISCUSSION: Results of this study suggest there is identifiable brain wave suppression for both men and women with hypoxic exposure and, moreover, there are significant differences in this suppression between genders. Beta frequency power was most sensitive for both genders and highly correlative compared to other brainwave frequencies. The implications of these findings are important considerations for next-generation aviation helmets, which may employ this technology as an early warning mechanism.Rice GM, Snider D, Drollinger S, Greil C, Bogni F, Phillips J, Raj A, Marco K, Linnville S. Gender differences in dry-EEG manifestations during acute and insidious normobaric hypoxia. Aerosp Med Hum Perform. 2019; 90(4):369-377.

Dry-EEG Manifestations of Acute and Insidious Hypoxia During Simulated Flight.

INTRODUCTION: Recently, portable dry electroencephalographs (dry-EEGs) have indexed cognitive workload, fatigue, and drowsiness in operational environments. Using this technology this project assessed whether significant changes in brainwave frequency power occurred in response to hypoxic exposures as experienced in military aviation.METHODS: There were 60 (30 women, 30 men) student Naval Aviators or Flight Officers who were exposed to an intense (acute) high-altitude (25,000 ft) normobaric hypoxic exposure, and 20 min later, more gradual (insidious) normobaric hypoxic exposure up to 20,000 ft while flying a fixed-wing flight simulation and monitored with a dry-EEG system. Using MATLAB, EEG frequencies and power were quantified and analyzed. Cognitive performance was also assessed with a cognitive task validated under hypoxia. Normobaric hypoxia and O2 saturation (Spo2) were produced and monitored using the Reduced Oxygen Breathing Device (ROBD2).RESULTS: Significant Spo2 decreases were recorded at acute 25K and insidious 20K simulated altitudes. Significant power decreases were recorded in all frequencies (alpha, beta, gamma, and theta) and all channels with acute 25K exposures. Gamma, beta, and theta frequency power were significantly decreased with insidious 20K exposures at most of the channels. The frequency power decreases corresponded to significant decreases in cognitive performance and flight performance. Most importantly, frequency power suppressions occurred despite 42% of the volunteers not perceiving they were hypoxic in the acute phase, nor 20% in the insidious phase.DISCUSSION: Results suggest EEG suppression during acute/insidious hypoxia can index performance decrements. These findings have promising implications in the development of biosensors that mitigate potential in-flight hypoxic physiological episodes.Rice GM, Snider D, Drollinger S, Greil C, Bogni F, Phillips J, Raj A, Marco K, Linnville S. Dry-EEG manifestations of acute and insidious hypoxia during simulated flight. Aerosp Med Hum Perform. 2019; 90(2):92-100.

[Familial chilblain lupus: Four cases spanning three generations]. / Lupus-engelures familial : quatre cas sur trois générations.

BACKGROUND: Familial chilblain lupus is a hereditary form of cutaneous lupus erythematosus seen in young children. It shows autosomal dominant inheritance due to mutations in the TREX-1 gene, or, more rarely, SAMHD1 or TMEM173 (STING). It belongs to the type I interferonopathies, i.e. inflammatory diseases associated with excessive interferon production and characterized by a positive "interferon signature". This is a rare entity with fewer than 10 families described to date. We report a new family followed over several years. PATIENTS AND METHODS: The patients were four subjects from the same family and spanning three generations (a brother and sister aged 17 and 15 years, their 39-year-old mother, and their 60-year-old grandfather). The initial cutaneous lesions on the extremities were described as papular, erythematous, purplish, infiltrated, hyperkeratotic, pruritic and/or painful. They occurred in childhood, improved during summer and stabilized over time. Immunological abnormalities such as positive antinuclear antibodies were noted. The interferon signature was positive in all patients. Molecular analysis of TREX-1, SAMHD1 and STING genes in both children showed no evidence of mutation. DISCUSSION: The cutaneous involvement was classic except for absence of the scarring and mutilating progression, photosensitivity and vasculopathy reported in other families. There was no intrafamily variability other than unconstant immunological abnormalities. At the molecular level, no mutations in the known genes were identified. A complementary molecular analysis is in progress. CONCLUSION: We report a new case of familial LEF, thus adding to knowledge about this very rare form of lupus erythematosus.

Diagnostic accuracy of haptoglobin within ovarian cyst fluid as a potential point-of-care test for epithelial ovarian cancer: an observational study.

OBJECTIVE: To investigate haptoglobin within ovarian cyst fluid (OCF) as a diagnostic biomarker for epithelial ovarian cancer (EOC) and develop an in vitro diagnostic point-of-care device test (IVDPCT) for use in the operating theatre. DESIGN: Retrospective and prospective cohort study. SETTING: South-East Asia. POPULATION: Women with suspicious ovarian cysts. METHODS: Proteomic, immunohistochemical and ELISA methods measured haptoglobin in OCF to differentiate benign and EOCs. Diagnostic performance of haptoglobin was compared with CA125, risk malignancy indices (RMI) and frozen section. Blinded validation of the IVDPCT was performed. MAIN OUTCOME MEASURES: Prediction of malignancy. RESULTS: Haptoglobin concentration measured by ELISA was 0.70 ± 0.09 mg/ml in patients with benign cysts (n = 87), 6.22 ± 0.53 mg/ml in early stage-EOC (n = 17), and 6.57 ± 0.65 mg/ml in late stage-EOC (n = 20). Haptoglobin in EOCs was significantly higher than in benign cysts (P < 0.0001). Haptoglobin using rapid colorimetric assay (RCA) on a training set had a sensitivity of 97.3% and a specificity 92.0%, comparable to ELISA and frozen sections. The haptoglobin AUROC curve was 0.999 (95% CI 0.997-1.000) compared with 0.895 (95% CI 0.814-0.977, P < 0.05) for CA125. Haptoglobin performed significantly better than all the RMIs (P < 0.01). Blinded validation studies showed a minor drop in average diagnostic performance (sensitivity 85.2% and specificity 90.5%) compared with the training set. However, when compared with frozen section, haptoglobin was no worse in diagnostic accuracy for malignancy. CONCLUSION: Haptoglobin was identified as a biomarker for the detection of EOC with potential as a point-of-care diagnostic tool. TWEETABLE ABSTRACT: Haptoglobin within ovarian cyst fluid: a biomarker for epithelial ovarian cancer and point-of-care diagnostics.

Comprehensive molecular screening strategy of OCLN in band-like calcification with simplified gyration and polymicrogyria.

Occludin (OCLN) is an important component of the tight junction complex, providing apical intercellular connections between adjacent cells in endothelial and epithelial tissue. In 2010 O'Driscoll et al reported mutations in OCLN to cause band-like calcification with simplified gyration and polymicrogyria (BLC-PMG). BLC-PMG is a rare autosomal recessive syndrome, characterized by early onset seizures, progressive microcephaly, severe developmental delay and deep cortical gray matter and basal ganglia calcification with symmetrical, predominantly fronto-parietal, polymicrogyria. Here we report 4 additional cases of BLC-PMG with novel OCLN mutations, and provide a summary of the published mutational spectrum. More generally, we describe a comprehensive molecular screening strategy taking into account the technical challenges associated with the genetic architecture of OCLN, which include the presence of a pseudo-gene and copy number variants.

Role of Exosomes in Placental Homeostasis and Pregnancy Disorders.

The human placenta is a unique organ that performs the function of the majority of fetal organs across gestation. How the placenta communicates with maternal tissues to prepare them for pregnancy is not fully understood. Recently, it has been established that placental cells can communicate with maternal tissues to regulate their biological function via extracellular vesicles (EVs). EVs are subclassified into exosomes or microvesicles (MVs) according to their size, cell or tissue of origin, functions, and physical features. Exosomes are a specific type of EVs from an endocytic origin, while MVs are released via budding from the plasma membrane. With regards to pregnancy, the role of EVs has been described in several functions such as immune responses and maternal metabolic adaptation to gestation. Interestingly, EVs of placental origin can be detected in a variety of body fluids including urine and blood, and have been identified in the maternal circulation at as early as 6 weeks of gestation. Moreover, the number of exosomes across gestation is higher in complications of pregnancies such as preeclampsia and gestational diabetes mellitus compared to normal pregnancies. Circulating exosomes contains proteins and RNAs that are representative of the cell of origin, including surface and cytoplasmic protein, messenger RNA, and micro-RNAs. Finally, exosomes are capable of transferring their contents to other cells and regulating the biological function of the target cell. In this review, we will discuss the effect of the maternal microenvironment on secretion and content of placenta-derived EVs, and how this may lead to complications of pregnancies with a special emphasis on exosomes.

Plasma exosome profiles from dairy cows with divergent fertility phenotypes.

Cell-to-cell communication in physiological and pathological conditions may be influenced by neighboring cells, distant tissues, or local environmental factors. Exosomes are specific subsets of extracellular vesicles that internalize and deliver their content to near and distant sites. Exosomes may play a role in the maternal-embryo crosstalk vital for the recognition and maintenance of a pregnancy; however, their role in dairy cow reproduction has not been established. This study aimed to characterize the exosome profile in the plasma of 2 strains of dairy cow with divergent fertility phenotypes. Plasma was obtained and characterized on the basis of genetic ancestry as fertile (FERT; <23% North American genetics, New Zealand Holstein-Friesian strain, n=8) or subfertile (SUBFERT; >92% North American genetics, North American Holstein-Friesian strain, n=8). Exosomes were isolated by differential and buoyant density centrifugation and characterized by size distribution (nanoparticle tracking analysis, NanoSight NS500, NanoSight Ltd., Amesbury, UK), the presence of CD63 (Western blot), and their morphology (electron microscopy). The total number of exosomes was determined by quantifying the immunoreactive CD63 (ExoELISA kit, System Biosciences), and the protein content established by mass spectrometry. Enriched exosome fractions were identified as cup-shape vesicles with diameters around 100 nm and positive for the CD63 marker. The concentration of exosomes was 50% greater in FERT cows. Mass spectrometry identified 104 and 117 proteins in FERT and SUBFERT cows, of which 23 and 36 were unique, respectively. Gene ontology analysis revealed enrichment for proteins involved in immunomodulatory processes and cell-to-cell communication. Although the role of exosomes in dairy cow reproduction remains to be elucidated, their quantification and content in models with divergent fertility phenotypes could provide novel information to support both physiological and genetic approaches to improving dairy cow fertility.

ADA2 deficiency: case report of a new phenotype and novel mutation in two sisters.

The objective of this paper is to: describe the phenotype compound heterozygote for mutations in CECR1 in two children. We describe the clinical and immunological phenotype, including the assessment of ADA2 activity, cytokine expression, interferon-stimulated and neutrophil-stimulated gene signatures, and the results of CECR1 sequencing. The first patient presented with intermittent fever, cutaneous vasculitis, myalgia and muscle inflammation on MRI leading to a provisional diagnosis of periarteritis nodosa. Subsequently, two cerebral lacunar lesions were identified following a brain stroke. Clinical features improved on anti-tumour necrosis factor therapy. The first patient's sister demonstrated early-onset, long-lasting anaemia with mild biological inflammation; at the ages of 3 and 5 years, she had presented 2 acute, transient neurological events with lacunar lesions on MRI. CECR1 sequencing identified both sisters to be compound heterozygous for a p.Tyr453Cys mutation and a previously undescribed deletion of exon 7. ADA2 activity was reduced by 50%. Neutrophil-stimulated genes were not overexpressed, but interferon-stimulated genes were. The expression of a panel of other cytokine transcripts was not significantly altered. In conclusion, searching for CECR1 mutation or assessing ADA2 activity should be considered in patients with an atypical presentation of inflammatory disease.

Differential Regulation of Eicosanoid and Endocannabinoid Production by Inflammatory Mediators in Human Choriodecidua.

An increase in intrauterine prostaglandin production is critical for the onset and progression of labor in women and indeed all mammalian species studied. Endocannabinoids can act as substrates for enzymes of the prostaglandin biosynthetic pathways and can be utilized to generate other related compounds such as prostamides. The end products are indistinguishable by radioimmunoassay. We have separated such compounds by mass spectrometry. We now show that inflammatory stimuli such as LPS and proinflammatory cytokines act differentially on these pathways in human choriodecidua and preferentially create drive through to prostaglandin end products. These findings create doubt about the interpretation of data on prostaglandin biosynthesis in intrauterine tissues from pregnant women especially in the presence of an infection. The possibility is raised that separation of these products might reduce variability in results and lead to potential uses for their measurement in the diagnosis of preterm labor.

Wearable Accelerometers in High Performance Jet Aircraft.

INTRODUCTION: Wearable accelerometers have become ubiquitous in the fields of exercise physiology and ambulatory hospital settings. However, these devices have yet to be validated in extreme operational environments. The objective of this study was to correlate the gravitational forces (G forces) detected by wearable accelerometers with the G forces detected by high performance aircraft. METHODS: We compared the in-flight G forces detected by the two commercially available portable accelerometers to the F/A-18 Carrier Aircraft Inertial Navigation System (CAINS-2) during 20 flights performed by the Navy's Flight Demonstration Squadron (Blue Angels). Postflight questionnaires were also used to assess the perception of distractibility during flight. RESULTS: Of the 20 flights analyzed, 10 complete in-flight comparisons were made, accounting for 25,700 s of correlation between the CAINS-2 and the two tested accelerometers. Both accelerometers had strong correlations with that of the F/A-18 Gz axis, averaging r = 0.92 and r = 0.93, respectively, over 10 flights. Comparison of both portable accelerometer's average vector magnitude to each other yielded an average correlation of r = 0.93. Both accelerometers were found to be minimally distracting. DISCUSSION: These results suggest the use of wearable accelerometers is a valid means of detecting G forces during high performance aircraft flight. Future studies using this surrogate method of detecting accelerative forces combined with physiological information may yield valuable in-flight normative data that heretofore has been technically difficult to obtain and hence holds the promise of opening the door for a new golden age of aeromedical research.

Evidence for -Gz Adaptation Observed with Wearable Biosensors During High Performance Jet Flight.

INTRODUCTION: Few studies have evaluated physiological responses to high acceleration forces during actual flight and to our knowledge no normative data has been acquired by technologies such as wearable biosensors during high performance jet aircraft operations. METHODS: In-flight physiological data from an FDA cleared portable triaxial accelerometer and bio-sensor were observed from five active duty F-18 pilots of the Naval Flight Demonstration Squadron (Blue Angels). Of the five pilots, three were formation pilots who flew lower G profiles and two were solo pilots who flew higher G profiles. Physiological parameters monitored were heart rate, respiratory rate, temperature, caloric expenditure, and duration of exposure to levels of acceleration. RESULTS: Evaluated were 25 practice demonstration flights; 9 flights were excluded secondary to incomplete or inaccurate physiological data. We observed no significant bradycardia during a total of 189 maneuvers which met inclusion criteria for push-pull events (PPE) or isolated -Gz exposures. Further analysis of 73 PPE revealed an overall significant rise in HR following the PPE, where mean heart rate was 106 (95% CI, 100:112) at the beginning of the push and 129 (95% CI, 123:135) following the pull. DISCUSSION: A majority of the flights monitored provided reliable physiological data. Initial data suggests, contrary to currently held aeromedical doctrine, maneuvers such as the "push-pull" do not evoke vasovagal based bradycardic responses in aerobatic pilots. Possible explanations for these findings are sympathetic nervous system activation through adaptation and/or sustained isometric resistance from control inputs, both of which are areas of future research for our team.Rice GM, Snider D, Moore JL, Lavan JT, Folga R, VanBrunt TB. Evidence for -Gz adaptation observed with wearable biosensors during high performance jet flight. Aerosp Med Hum Perform. 2016; 87(12):996-1003.

Unusual cutaneous features associated with a heterozygous gain-of-function mutation in IFIH1: overlap between Aicardi-Goutières and Singleton-Merten syndromes.

Cutaneous lesions described as chilblain lupus occur in the context of familial chilblain lupus or Aicardi-Goutières syndrome. To date, seven genes related to Aicardi-Goutières syndrome have been described. The most recently described encodes the cytosolic double-stranded RNA receptor IFIH1 (also known as MDA5), a key component of the antiviral type I interferon-mediated innate immune response. Enhanced type I interferon signalling secondary to gain-of-function mutations in IFIH1 can result in a range of neuroinflammatory phenotypes including classical Aicardi-Goutières syndrome. It is of note that none of the patients with a neurological phenotype so far described with mutations in this gene was reported to demonstrate cutaneous involvement. We present a family segregating a heterozygous pathogenic mutation in IFIH1 showing dermatological involvement as a prominent feature, variably associated with neurological disturbance and premature tooth loss. All three affected individuals exhibited increased expression of interferon-stimulated genes in whole blood, and the mutant protein resulted in enhanced interferon signalling in vitro, both in the basal state and following ligand stimulation. Our results further extend the phenotypic spectrum associated with mutations in IFIH1, indicating that the disease can be confined predominantly to the skin, while also highlighting phenotypic overlap with both Aicardi-Goutières syndrome and Singleton-Merten syndrome.

New biomarkers for the prediction of spontaneous preterm labour in symptomatic pregnant women: a comparison with fetal fibronectin.

OBJECTIVE: To identify cervicovaginal fluid (CVF) biomarkers predictive of spontaneous preterm birth in women with symptoms of preterm labour. DESIGN: Retrospective cohort study. SETTING: Melbourne, Australia. POPULATION: Women with a singleton pregnancy admitted to the Emergency Department between 22 and 36 weeks of gestation presenting with symptoms of preterm labour. METHODS: Two-dimensional electrophoresis was used to analyse the CVF proteome. Validation of putative biomarkers was performed using enzyme-linked immunosorbent assay (ELISA) in an independent cohort. Optimal concentration thresholds of putative biomarkers were determined and the predictive efficacy for preterm birth was compared with that of fetal fibronectin. MAIN OUTCOME MEASURES: Prediction of spontaneous preterm labour within 7 days. RESULTS: Differentially expressed proteins were identified by proteomic analysis in women presenting with 'threatened' preterm labour without cervical change who subsequently delivered preterm (n = 12 women). ELISA validation using an independent cohort (n = 129 women) found albumin and vitamin D-binding protein (VDBP) to be significantly altered between women who subsequently experienced preterm birth and those who delivered at term. Prediction of preterm delivery within 7 days using a dual biomarker model (albumin/VDBP) provided 66.7% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 96.7% negative predictive value (NPV), compared with fetal fibronectin yielding 66.7, 87.9, 36.4 and 96.2%, respectively (n = 64). Using the maximum number of screened samples, the predictive utility of albumin/VDBP yielded a sensitivity of 77.8%, specificity and PPV of 100% and NPV of 98.0% (n = 109). CONCLUSIONS: The dual biomarker model of albumin/VDBP is more efficacious than fetal fibronectin in predicting spontaneous preterm delivery in symptomatic women within 7 days. A clinical diagnostic trial is required to test this model on a larger population to confirm these findings and to further refine the predictive values.

Myostatin in the placentae of pregnancies complicated with gestational diabetes mellitus.

INTRODUCTION: Gestational diabetes mellitus (GDM) is characterised by maternal glucose intolerance and insulin resistance during pregnancy. Myostatin, initially identified as a negative regulator of muscle development may also function in the regulation of placental development and glucose uptake. Myostatin expression in placentae of GDM complicated pregnancies is unknown. However, higher myostatin levels occur in placentae of pregnancies complicated with preeclampsia. We hypothesise that myostatin will be differentially expressed in GDM complicated pregnancies. METHODS: Myostatin concentrations (ELISA) were evaluated in plasma of presymptomatic women who later developed GDM and compared to plasma of normal glucose tolerant (NGT) women. Furthermore, myostatin protein expression (Western blot) was studied in placentae of pregnant women with GDM (treated with diet or insulin) compared to placentae of NGT women. RESULTS: No significant difference in myostatin concentration was seen in plasma of pre-symptomatic GDM women compared to NGT women. In placenta significant differences in myostatin protein expressions (higher precursor; p < 0.05and lower dimer: p < 0.005) were observed in GDM complicated compared to NGT pregnancies. Furthermore, placentae of GDM women treated with insulin compared to diet have higher dimer (p < 0.005) and lower precursor (p < 0.05). Compared to lean women, placentae of obese NGT women were lower in myostatin dimer expression (p < 0.05). DISCUSSION: Myostatin expression in placental tissue is altered under stress conditions (e.g. obesity and abnormal glucose metabolism) found in pregnancies complicated with GDM. We hypothesise that myostatin is active in these placentae and could affect glucose homoeostasis and/or cytokine production thereby altering the function of the placenta.

IFPA Meeting 2013 Workshop Report II: use of 'omics' in understanding placental development, bioinformatics tools for gene expression analysis, planning and coordination of a placenta research network, placental imaging, evolutionary approaches to understanding pre-eclampsia.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At the IFPA meeting 2013 twelve themed workshops were presented, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of new technologies for placenta research: 1) use of 'omics' in understanding placental development and pathologies; 2) bioinformatics and use of omics technologies; 3) planning and coordination of a placenta research network; 4) clinical imaging and pathological outcomes; 5) placental evolution.

Therapies in Aicardi-Goutières syndrome.

Aicardi-Goutières syndrome (AGS) is a genetically determined disorder, affecting most particularly the brain and the skin, characterized by the inappropriate induction of a type I interferon-mediated immune response. In most, but not all, cases the condition is severe, with a high associated morbidity and mortality. A number of important recent advances have helped to elucidate the biology of the AGS-related proteins, thus providing considerable insight into disease pathology. In this study, we outline the clinical phenotype of AGS, paying particular attention to factors relevant to therapeutic intervention. We then discuss the pathogenesis of AGS from a molecular and cell biology perspective. Finally, we suggest possible treatment strategies in light of these emerging insights.

Urinary tract calculi in military aviators.

BACKGROUND: Urinary tract calculi are a common affliction in the United States and estimates of the adult lifetime risk of developing this condition range from 10 to 15%. Although highly variable, the clinical presentation of someone afflicted with urinary tract calculi typically involves varying degrees of pain, nausea, hematuria, and dysuria. Current disease, as well as a history of urinary tract calculi, is potentially disqualifying for aviation duties in the United States military as well as for commercial aviators. METHODS: Utilizing population based data from the Defense Medical Epidemiology Database (DMED), the current descriptive epidemiology of urinary tract calculi among military aviators was examined. RESULTS: Based on the data collected, the overall annual incidence density of urinary tract calculi for DoD personnel is approximately 4.8 events/1000 PY. The overall annual incidence density of urinary tract calculi is slightly lower in aviators as compared to the nonaviator DoD population (4.4 events/1000 PY vs. 4.8 events/1000 PY). DISCUSSION: Even though in-flight incapacitation from this malady is believed to be exceedingly rare, the incidence of urinary tract stones and their related morbidity should remain an important area of clinical focus.