Functional host-specific adaptation of the intestinal microbiome in hominids.

Fine-scale knowledge of the changes in composition and function of the human gut microbiome compared that of our closest relatives is critical for understanding the evolutionary processes underlying its developmental trajectory. To infer taxonomic and functional changes in the gut microbiome across hominids at different timescales, we perform high-resolution metagenomic-based analyzes of the fecal microbiome from over two hundred samples including diverse human populations, as well as wild-living chimpanzees, bonobos, and gorillas. We find human-associated taxa depleted within non-human apes and patterns of host-specific gut microbiota, suggesting the widespread acquisition of novel microbial clades along the evolutionary divergence of hosts. In contrast, we reveal multiple lines of evidence for a pervasive loss of diversity in human populations in correlation with a high Human Development Index, including evolutionarily conserved clades. Similarly, patterns of co-phylogeny between microbes and hosts are found to be disrupted in humans. Together with identifying individual microbial taxa and functional adaptations that correlate to host phylogeny, these findings offer insights into specific candidates playing a role in the diverging trajectories of the gut microbiome of hominids. We find that repeated horizontal gene transfer and gene loss, as well as the adaptation to transient microaerobic conditions appear to have played a role in the evolution of the human gut microbiome.

Optimising aerial military medical evacuation dispatching decisions via operations research techniques.

Senior military leaders and medical practitioners continuously seek new ways to improve the performance and organisation of deployed medical evacuation (MEDEVAC) systems to minimise mortality rates of combat casualties. The objective of this paper is to highlight how recent research in the fields of operations research and machine learning can be leveraged to better inform the implementation and modification of current and future MEDEVAC tactics, techniques and procedures for combat operations in a deployed environment. More specifically, this paper discusses state-of-the-art techniques that optimise the management of MEDEVAC assets prior to and during combat operations. These recent research efforts emphasise that military healthcare administrators should contribute to and extend the evolving portfolio of research that seeks to design and develop decision support systems leveraging artificial intelligence and operations research to improve MEDEVAC system performance.

Open hip reduction using a novel transarticular suture stabilisation technique in 24 dogs: a retrospective study of technique, outcome and complications.

CASE HISTORY: Medical records of a single private practice (Illinois, USA) were retrospectively reviewed to identify dogs (n = 24) that had an open hip reduction with a transarticular suture stabilisation technique after presenting with a traumatic coxofemoral luxation between April 2003 and December 2018. CLINICAL FINDINGS: Dogs that met the inclusion criteria were of various breeds with a median body weight of 18.1 (min 4.2, max 54.5) kg and mean age at presentation of 6.5 (min 1, max 11) years. The surgical technique, short-term outcome and complications were extracted from the medical records. Long-term (>2 years) follow-up data was obtained by a telephone interview with each owner. TREATMENT AND OUTCOME: All dogs underwent open hip reduction using a novel transarticular suture stabilisation technique. The outcome was reported by owners to be excellent in 18/24 (75%) dogs with full return of limb function. Sixty-six percent (16/24) of owners reported that no lameness was observed 2 months after surgery. No minor complications were noted in this study. The hips of 6/24 (25%) dogs reluxated after surgery (defined as a major complication), which required femoral head and neck excision surgery. CLINICAL RELEVANCE: Open coxofemoral joint reduction using a novel transarticular suture technique is a viable surgical option to consider in dogs that present with a traumatic coxofemoral luxation.

MR Myelography for the Detection of CSF-Venous Fistulas.

CSF-venous fistula is an important treatable cause of spontaneous intracranial hypotension that is often difficult to detect using traditional imaging techniques. Herein, we describe the technical aspects and diagnostic performance of MR myelography when used for identifying CSF-venous fistulas. We report 3 cases in which the CSF-venous fistula was occult on CT myelography but readily detected using MR myelography.

Looking for the "connection": A clinical vignette on pediatric chest wall masses.

Chest wall masses in the pediatric population are relatively rare, and the differential diagnosis predominantly includes neoplastic soft tissue or osseous tumours, either benign or malignant in etiology, although local infectious processes represent additional diagnostic possibilities. Among recent immigrants, a more diverse array of less commonly observed pathogens warrant consideration. Here, we present a case of a chest wall mass in an immunocompetent child who had recently immigrated from the Philippines.

Les masses de la paroi thoracique sont relativement rares dans la population pédiatrique, et le diagnostic différentiel touche surtout les tumeurs néoplasiques des tissus mous ou des os, d'étiologie bénigne ou maligne, même si les processus infectieux locaux s'ajoutent aux possibilités diagnostiques. Chez des immigrants récents, de nombreux agents pathogènes moins fréquents méritent d'être envisagés. Les chercheurs présentent un cas de masse de la paroi thoracique chez un enfant immunocompétent récemment immigré des Philippines.

Early extubation attempts reduce length of stay in extremely preterm infants even if re-intubation is necessary.

OBJECTIVE: Prolonged mechanical ventilation in the extremely premature infant is associated with the development of bronchopulmonary dysplasia (BPD). Clinically, the decision to extubate the extremely low birth weight (ELBW) infant can be difficult. There is continued debate regarding whether it is better for an ELBW infant to remain on the ventilator or to extubate to nasal constant positive airway pressure (nCPAP). It has also been argued that repeated intubations may be detrimental to ELBW infants. We tested the hypothesis that earlier extubation attempts would decrease length of hospital stay and BPD. STUDY DESIGN: A database maintained on infants born at <27 completed weeks gestation admitted to our all referral NICU for a 36 month period was queried (n = 224). RESULTS: Day of life (DOL) of the first extubation attempt was inversely correlated with birth weight (p <  0.001) and gestational age (p <  0.01). The DOL of the 1st extubation attempt correlated with the need for re-intubation (p <  0.001), but not with mortality (p = 0.27). In survivors, earlier DOL of 1st extubation attempt was associated with shorter LOS (p <  0.001). Earlier DOL of the 1st extubation attempt was associated with less need for supplemental oxygen (p <  0.001) at 36 weeks CGA, while re-intubation was not (p = 0.50). CONCLUSION: In our cohort of extremely premature infants, the earlier the first extubation attempt the sooner the patient was discharged home and the less likely to develop BPD. Our study suggests that extubation should not be delayed in extremely premature infants due to fears of need for re-intubation.

Cardiovascular health and arterial stiffness: the Maine-Syracuse Longitudinal Study.

Ideal cardiovascular health is a recently defined construct by the American Heart Association (AHA) to promote cardiovascular disease reduction. Arterial stiffness is a major risk factor for cardiovascular disease. The extent to which the presence of multiple prevalent cardiovascular risk factors and health behaviors is associated with arterial stiffness is unknown. The aim of this study was to examine the association between the AHA construct of cardiovascular health and arterial stiffness, as indexed by pulse wave velocity (PWV) and pulse pressure. The AHA health metrics, comprising of four health behaviors (smoking, body mass index, physical activity and diet) and three health factors (total cholesterol, blood pressure and fasting plasma glucose), were evaluated among 505 participants in the Maine-Syracuse Longitudinal Study. Outcome measures were carotid-femoral PWV and pulse pressure measured at 4- to 5-year follow-up. Better cardiovascular health, comprising both health factors and behaviors, was associated with lower arterial stiffness, as indexed by PWV and pulse pressure. Those with at least five health metrics at ideal levels had significantly lower PWV (9.8 m s(-1)) than those with two or less ideal health metrics (11.7 m s(-1)) (P < 0.001). This finding remained with the addition of demographic and PWV-related variables (P = 0.004).

Solidification fronts in supercooled liquids: how rapid fronts can lead to disordered glassy solids.

We determine the speed of a crystallization (or, more generally, a solidification) front as it advances into the uniform liquid phase after the system has been quenched into the crystalline region of the phase diagram. We calculate the front speed by assuming a dynamical density functional theory (DDFT) model for the system and applying a marginal stability criterion. Our results also apply to phase field crystal (PFC) models of solidification. As the solidification front advances into the unstable liquid phase, the density profile behind the advancing front develops density modulations and the wavelength of these modulations is a dynamically chosen quantity. For shallow quenches, the selected wavelength is precisely that of the crystalline phase and so well-ordered crystalline states are formed. However, when the system is deeply quenched, we find that this wavelength can be quite different from that of the crystal, so the solidification front naturally generates disorder in the system. Significant rearrangement and aging must subsequently occur for the system to form the regular well-ordered crystal that corresponds to the free energy minimum. Additional disorder is introduced whenever a front develops from random initial conditions. We illustrate these findings with simulation results obtained using the PFC model.

Modeling the structure of liquids and crystals using one- and two-component modified phase-field crystal models.

A modified phase-field crystal model in which the free energy may be minimized by an order parameter profile having isolated bumps is investigated. The phase diagram is calculated in one and two dimensions and we locate the regions where modulated and uniform phases are formed and also regions where localized states are formed. We investigate the effectiveness of the phase-field crystal model for describing fluids and crystals with defects. We further consider a two-component model and elucidate how the structure transforms from hexagonal crystalline ordering to square ordering as the concentration changes. Our conclusion contains a discussion of possible interpretations of the order parameter field.

Directed blood donor program decreases donor exposure for children with sickle cell disease requiring chronic transfusion.

In children with sickle cell disease (SCD), primary and secondary prevention of strokes require indefinite regular blood transfusion therapy. The risks associated with repeated transfusions include alloimmunization and increased donor exposure. The Charles Drew Program is a directed blood donor program designed to lower donor exposure, decreasing the associated complications of transfusion; however, no evidence exists demonstrating the magnitude of the benefit to the recipient. Further, the use of extended red blood cell (RBC) antigen matching for C, E, and K has been well documented in a clinical trial setting but not extensively evaluated in a standard care setting. The goal of this study is to assess the effectiveness in reducing alloimmunization when matching for C, E, and K and the magnitude of the decrease in donor exposure in a directed blood donor program. The rate of alloimmunization and reduction of donor exposure were determined during the course of 1 year in a cohort of children with SCD who received regular directed donor blood transfusions. A total of 24 recipients were in the program, 16 females and 8 males, 4 to 20 years of age. During 2008, alloimmunization was 0 percent and donor exposure was reduced by 20 percent, compared with usual care. Extended RBC antigen matching has the same benefit as in a clinical trial setting for patients with SCD receiving blood transfusion therapy. Despite significant effort, we only achieved a modest decrease in donor exposure and cannot determine the immediate benefit of a directed blood donor program.

Micro-duplications of 1q32.1 associated with neurodevelopmental delay.

Distal partial trisomies involving the region 1q32 have been associated with dysmorphic features and developmental delay [1-11]. To further define the critical region for developmental delay and to investigate the genotype-phenotype association of 1q trisomy syndrome, we report two patients with much smaller (3 Mb and 3.5 Mb in size) trisomic regions on 1q32.1. The two micro-duplications largely overlap and both patients exhibited cognitive and motor delays. Case 1 is a 5-year-old boy with global developmental delay, behavioral problems, pervasive developmental disorder not otherwise specified (PDD-NOS), staring spells, headaches, and paresthesias. Case 2 is a 14-year-old girl with seizures, cognitive and motor difficulties, and minor dysmorphic features. These two cases suggest that 1q32.1 region on distal arm of 1q and genes involved are critical to cognitive and motor development in a gene dosage sensitive manner and that other neurological features are variable within this syndrome.

Relation between dairy food intake and cognitive function: The Maine-Syracuse Longitudinal Study.

Diet modification to alter the course of age-related cognitive decline is becoming increasingly important. Few observational findings suggest that dairy food intake may be positively related to cognitive function, but research in this novel area is limited. The aim of this study was to investigate whether dairy food intake is associated with cognitive function, before and after adjustment for cardiovascular, lifestyle and dietary factors. To do this, a cross-sectional analyses of a subset of the community-based Maine-Syracuse Longitudinal Study (MSLS) sample (N = 972) was undertaken. It was determined that participants who consumed dairy products at least once per day had significantly higher scores on multiple domains of cognitive function compared with those who never or rarely consumed dairy foods, adjusting for cardiovascular risk factors, lifestyle and dietary factors. Frequent dairy food intake is associated with better cognitive performance but underlying causal mechanisms are still to be determined.

Modelling the evaporation of thin films of colloidal suspensions using dynamical density functional theory.

Recent experiments have shown that various structures may be formed during the evaporative dewetting of thin films of colloidal suspensions. Nanoparticle deposits of strongly branched 'flower-like', labyrinthine and network structures are observed. They are caused by the different transport processes and the rich phase behaviour of the system. We develop a model for the system, based on a dynamical density functional theory, which reproduces these structures. The model is employed to determine the influences of the solvent evaporation and of the diffusion of the colloidal particles and of the liquid over the surface. Finally, we investigate the conditions needed for 'liquid-particle' phase separation to occur and discuss its effect on the self-organized nanostructures.

Coronary artery disease in a large renal transplant population: implications for management.

Coronary artery disease (CAD) accounts for approximately one-half of the sizable mortality in patients with end-stage renal disease who have undergone transplantation. The study was a retrospective review of 1460 patients who underwent renal transplantation at the Mount Sinai Medical Center from January 1, 2000 to October 31, 2009. Noninvasive stress testing was performed in 848 patients (88.1%) with 278 patients (32.8%) having abnormal results. Cardiac catheterization was performed in 357 patients (37.1%) and of these, 212 patients had obstructive disease (59.4%). At 5 years posttransplant, there was no statistically significant difference between those with nonobstructive CAD and those who required percutaneous or surgical interventions (adjusted hazard ratio [aHR], 1.243; CI 95%, 0.513-3.010; p = 0.630). Those with medically managed obstructive CAD had significantly higher rates of death at the 5-year period when compared to those who received percutaneous intervention (aHR, 3.792; CI 95%, 1.320-10.895; p = 0.013) or those who received coronary artery bypass grafting (aHR, 6.691; CI 95%, 1.200-37.323). Because noninvasive imaging is poorly predictive of coronary disease in this high-risk population, an anatomic diagnosis is recommended. Revascularization may result in improved long-term outcomes.

Population structure and genetic differentiation associated with breeding history and selection in tomato (Solanum lycopersicum L.).

Tomato (Solanum lycopersicum L.) has undergone intensive selection during and following domestication. We investigated population structure and genetic differentiation within a collection of 70 tomato lines representing contemporary (processing and fresh-market) varieties, vintage varieties and landraces. The model-based Bayesian clustering software, STRUCTURE, was used to detect subpopulations. Six independent analyses were conducted using all marker data (173 markers) and five subsets of markers based on marker type (single-nucleotide polymorphisms, simple sequence repeats and insertion/deletions) and location (exon and intron sequences) within genes. All of these analyses consistently separated four groups predefined by market niche and age into distinct subpopulations. Furthermore, we detected at least two subpopulations within the processing varieties. These subpopulations correspond to historical patterns of breeding conducted for specific production environments. We found no subpopulation within fresh-market varieties, vintage varieties and landraces when using all marker data. High levels of admixture were shown in several varieties representing a transition in the demarcation between processing and fresh-market breeding. The genetic clustering detected by using the STRUCTURE software was confirmed by two statistics, pairwise F(st) (θ) and Nei's standard genetic distance. We also identified a total of 19 loci under positive selection between processing, fresh-market and vintage germplasm by using an F(st)-outlier method based on the deviation from the expected distribution of F(st) and heterozygosity. The markers and genome locations we identified are consistent with known patterns of selection and linkage to traits that differentiate the market classes. These results demonstrate how human selection through breeding has shaped genetic variation within cultivated tomato.

Renin-angiotensin system blockers and modulation of radiation-induced brain injury.

Radiation-induced brain injury remains a major cause of morbidity in cancer patients with primary or metastatic brain tumors. Approximately 200,000 individuals/year are treated with fractionated partial or whole-brain irradiation, and > half will survive long enough (≤6 months) to develop radiation-induced brain injury, including cognitive impairment. Although short-term treatments have shown efficacy, no long-term treatments or preventive approaches are presently available for modulating radiation-induced brain injury. Based on previous preclinical studies clearly demonstrating that renin-angiotensin system (RAS) blockers can modulate radiation-induced late effects in the kidney and lung, we and others hypothesized that RAS blockade would similarly modulate radiation-induced brain injury. Indeed, studies in the last 5 years have shown that both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor antagonists (AT(1)RAs) can prevent/ameliorate radiation-induced brain injury, including cognitive impairment, in the rat. The mechanistic basis for this RAS blocker-mediated effect remains the subject of ongoing investigations. Putative mechanisms include, i] blockade of Ang II/NADPH oxidase-mediated oxidative stress and neuroinflammation, and ii] a change in the balance of angiotensin (Ang) peptides from the pro-inflammatory and pro-oxidative Ang II to the anti-inflammatory and anti-oxidative Ang-1-7). However, given that both ACEIs and AT(1)RAs are 1] well-tolerated drugs routinely prescribed for hypertension, 2] exhibit some antitumor properties, and 3] can prevent/ameliorate radiation-induced brain injury, they appear to be ideal drugs for future clinical trials, offering the promise of improving the quality of life of brain tumor patients receiving brain irradiation.

Microbial fingerprinting using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) applications and challenges.

Recent threats posed by pathogenic microorganisms in food, recreational waters, and as agents of bioterror have underscored the need for the development of more rapid, accurate, and cost-effective methods of microbial characterization and identification. This chapter focuses on the use of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to rapidly characterize and identify microorganisms through generation of characteristic fingerprints of intact cells. While most efforts have focused on bacteria, this technology has also been applied to fungi and viruses. Results of most studies suggest that MALDI-TOF MS can be used to rapidly and accurately characterize microorganisms. A variety of quantitative approaches have been employed in the analysis of MALDI-TOF MS fingerprints of microorganisms. The reproducibility of fingerprints of intact cells remains a primary concern and limitation associated with this approach. Protocols and instrumentation used have varied considerably and likely account for much of the variability in reproducibility reported. Key first steps to overcoming this limitation will be the development of standard approaches to quantifying reproducibility and the development of standard protocols for sample preparation and analysis.

Clinical and prognostic subforms of new daily-persistent headache.

BACKGROUND: According to the International Classification of Headache Disorders (ICHD)-2, primary daily headaches unremitting from onset are classified as new daily-persistent headache (NDPH) only if migraine features are absent. When migraine features are present, classification is problematic. METHODS: We developed a revised NDPH definition not excluding migraine features (NDPH-R), and applied it to consecutive patients seen at the Montefiore Headache Center. We divided this group into patients meeting ICHD-2 criteria (NDPH-ICHD) and those with too many migraine features for ICHD-2 (NDPH-mf). We compared clinical and demographic features in these groups, identifying 3 prognostic subgroups: persisting, remitting, and relapsing-remitting. Remitting and relapsing-remitting patients were combined into a nonpersisting group. RESULTS: Of 71 NDPH-R patients, 31 (43.7%) also met NDPH-ICHD-2 criteria. The NDPH-mf and the NDPH-ICHD-2 groups were similar in most clinical features though the NDPH-mf group was younger, included more women, and had a higher frequency of depression. The groups were similar in the prevalence of allodynia, triptan responsiveness, and prognosis. NDPH-R prognostic subforms were also very similar, although the persisting subform was more likely to be of white race, to have anxiety or depression, and to have a younger onset age. CONCLUSIONS: Current International Classification of Headache Disorders (ICHD)-2 criteria exclude the majority of patients with primary headache unremitting from onset. The proposed criteria for revised new daily-persistent headache definition not excluding migraine features (NDPH-R) classify these patients into a relatively homogeneous group based on demographics, clinical features, and prognosis. Both new daily-persistent headache with too many migraine features for ICHD-2 and new daily-persistent headache meeting ICHD-2 criteria include patients in equal proportions that fall into the persisting, remitting, and relapsing-remitting subgroups. Our criteria for NDPH-R should be considered for inclusion in ICHD-3.