Pull-Out Strength Comparison Among Conventional Pedicle Screw, Cortical Infero-Superior, and Cortical Supero-Inferior Trajectories in Yorkshire Porcine Lumbar Spines: A Biomechanical Study.
Posterior instrumentation of the spine presents a challenge, especially in conditions with low bone quality. Pedicle screw insertion with cortical bone trajectory is designed to add interface between the screw and the bone through engagement between pedicles and the cortex when compared to conventional screw course. Pedicle screw insertion trajectory from cortical infero-superior and the proposed cortical supero-inferior should obtain better pull-out performance than conventional pedicle trajectory. We aim to evaluate the pull-out strength differences among conventional pedicle screw, cortical infero-superior, and cortical supero-inferior trajectories. Samples from Yorkshire porcine lumbar spine (L1-L5; n = 30) were relieved of soft tissue attachments and dried. Morphometric measurements were conducted, and the samples were randomly assigned to 3 groups. The screws were inserted into the vertebrae by drilling with the 3 trajectories: conventional, cortical infero-superior, and cortical supero-inferior. The trajectories of the screws were examined using x-rays. Pull-out tests were conducted by applying uniaxial traction in line with the screw trajectory with a translational speed of 5 mm/min. The results of the pull-out are measured in Newtons. We obtained a mean value of pull-out force in conventional trajectory of 491.72 ± 187.2 N, cortical infero-superior of 822.16 ± 295.73 N, and cortical supero-inferior of 644.14 ± 201.97 N. Cortical infero-superior and cortical supero-inferior trajectories attained 67% and 30% higher pull-out mean, respectively. Using 1-way analysis of variance and a post hoc Tukey test revealed a significant difference between cortical infero-superior and conventional trajectories (P < .01). Differing pull-out strengths between cortical infero-superior and supero-inferior trajectories showed no statistical significance. Results of our study showed a 30% higher pull-out strength in our proposed trajectory than the conventional one, although not statistically significant. The trajectory of the screws within the lumbar spine seemed to have an impact in pull-out strength. Cortical bone engagement using the novel trajectories may increase pull-out strength of pedicle screws. Level 5.


Clinical profile and treatment outcomes of Boerhaave's syndrome: A 13-year experience from an upper gastrointestinal surgical unit.
IBoerhaave's syndrome (BS) is a rare, but potentially fatal condition, characterized by barogenic esophageal rupture and carries a high mortality. We aimed to study our institutional experience of managing patients with BS. A retrospective review of patients with BS presenting to a tertiary care centre from 2005 to 2018 was carried out in this study. Clinical presentation, diagnostic evaluations, treatments received, and treatment outcomes were studied. Perforations were classified as early (<24 hours) and delayed (>24 hours), based on the time elapsed. Surgical complications were graded using Clavien-Dindo grade. The Pittsburgh perforation severity score was correlated with short-term treatment outcomes. Of the 12 patients [male, 75%; mean (range) age, 53 (28-80) years] included, 10 patients had a delayed (>24 hours) presentation. Chest pain was the dominant symptom (58.3%); six patients presented either in shock (n= 1) or with organ failure (n= 3) or both (n= 2). All the perforations were sited in the lower thoracic esophagus, of which three were contained and nine were uncontained. The seal of the perforation was achieved by surgical repair in four patients (primary repair, 2; repair over a T-tube, 2) and endoscopic techniques in four patients (clipping, 1; stenting, 3). Sepsis drainage [surgical, 7 (open-5, minimally-invasive-2); non-surgical, 5] and feeding jejunostomy were performed in all patients. Five (41.7%) patients received a re-intervention. Median (range) hospital stay was 25.5 (12-101) days, 30-day operative morbidity was 50%, and there was one in-hospital death. The Pittsburgh perforation severity score was as follows: 2-5 in two patients and >5 in 10 patients; there were more delayed presentations, increased surgical interventions, post-procedure morbidity, and in-hospital mortality in the latter group, but the differences were statistically not significant. In 11 patients followed-up [median (range):1507 (17-5929) days], there was no disease recurrence, symptomatic reflux or dysphagia. Favourable treatment outcomes, including reduced mortality and organ preservation can be achieved for Boerhaave's perforations, through a multimodality approach. Minimally invasive, endoluminal or open surgical techniques may be safely utilized in its management. The Pittsburgh severity score can be a useful clinical tool that can be used to select the initial intervention and to predict treatment outcomes.


Protective Effects the Akt Activator SC79 in Hepatic Ischemia-Reperfusion Injury.
BACKGROUND SC79 has been reported to protect against experimental ischemia-elicited neuronal death and brain injury and to protect myocardiocytes from hypoxia/reoxygenation (H/R) injury. Here, we investigated the effects of SC79 in primary hepatocytes in vitro and in rat liver in vivo following hypoxia-reoxygenation (H/R) and hepatic I/R injury. MATERIAL AND METHODS The livers of Sprague-Dawley rats were subjected to 45 min of ischemia followed by 2-24 h of reperfusion. The primary hepatocytes were subjected to hypoxia for 6 h and for 2-24 h. The hepatocytes cells or the hepatic I/R injury model livers were treated with SC79 or/and LY294002 at different times and concentrations. The serum ALT, AST, histologic examination, cellular viability, and cell apoptosis were assessed. The levels of phospho-Akt, Bad, Bim, Bax, Bcl-2, and Bcl-XL were determined by Western blot analysis. RESULTS SC79 improved viability and inhibited apoptosis in hepatocytes following H/R. SC79 decreased serum AST and ALT, markedly improved pathology, and decreased cell apoptosis in livers following I/R. In addition, SC79 promoted the expression of phospho-Akt, Bcl-2, and Bcl-XL, and decreased the expression of Bid, Bax, and Bim. PI3K inhibitor (LY294002) pre-treatment completely abolished the above-mentioned effects of SC79. CONCLUSIONS The protective role of SC79 against H/R of hepatocytes or hepatic I/R injury is related to activation of phosphorylation of Akt, resulting in the decrease of pro-apoptotic protein of Bim, Bax, and Bad, and increase of the anti-apoptotic protein Bcl-2 and Bcl-xL induced by cell H/R and hepatic I/R injury.


Nurses' attitudes toward sexuality in adolescent patients.
This descriptive study surveyed the sexual attitudes and nursing practice of 39 nurses who care for adolescents in a large metropolitan teaching hospital. A questionnaire containing 32 Likert scale items and 29 yes/no questions was used to survey the nurses' attitudes toward the sexuality of their patients and the use of sex education and counseling in their patient care. Frequency of answers generated by the participants was used to ascertain their sexual attitudes and characteristics of their nursing practice. Findings indicate that, although the sample recognized the importance of sexuality for the adolescent patient and were theoretically capable of addressing issues of adolescent sexuality, nurses were uncomfortable incorporating issues of sexuality, counseling, and education into their nursing practice.


Family history of cancer and risk of lung cancer among lifetime nonsmoking women in the United States.
In a multicenter study of lung cancer in lifetime nonsmokers in the United States, 646 female lung cancer patients and 1,252 population controls were interviewed regarding history of cancer in their first-degree relatives. A 30% increased risk (95% confidence interval 0.9-1.8) was found for a history of respiratory tract cancer in parents or siblings after adjustment for exposure to environmental tobacco smoke (ETS) in adult life. Lung cancer, which represented approximately two thirds of the respiratory tract cancers, occurred more frequently in first-degree relatives of lung cancer patients than in comparable relatives of population controls (ETS-adjusted odds ratio = 1.29, 95% confidence interval 0.9-1.9). In particular, a significant threefold increased risk for lung cancer was associated with lung cancer diagnosed in mothers and sisters. The increased risk in relation to family history of lung cancer was observed among parents and siblings who were smokers as well as in those who were nonsmokers. The association with family history of lung cancer was strengthened when the analysis was restricted to adenocarcinoma of the lung (ETS-adjusted odds ratio = 1.50, 95% confidence interval 1.0-2.2). However, there was no association between family history of other cancers and risk of lung cancer in nonsmokers.


A nonsynaptic mechanism underlying interictal discharges in human epileptic neocortex.
Very fast oscillations (VFOs, >80 Hz) are important for physiological brain processes and, in excess, with certain epilepsies. Putative mechanisms for VFO include interneuron spiking and network activity in coupled pyramidal cell axons. It is not known whether either, or both, of these apply in pathophysiological conditions. Spontaneously occurring interictal discharges occur in human tissue in vitro, resected from neocortical epileptic foci. VFO associated with these discharges was manifest in both field potential and, with phase delay, in excitatory synaptic inputs to fast spiking interneurons. Recruitment of somatic pyramidal cell and interneuron spiking was low, with no correlation between VFO power and synaptic inputs to principal cells. Reducing synaptic inhibition failed to affect VFO occurrence, but they were abolished by reduced gap junction conductance. These data suggest a lack of a causal role for interneurons, and favor a nonsynaptic pyramidal cell network origin for VFO in epileptic human neocortex.


Denaturation-resistant bifunctional colloidal superstructures assembled via the proteinaceous barnase-barstar interface.
To date, a number of biomolecule-mediated nanoparticle self-assembly systems have been developed that are amenable to controllable disassembly under relatively gentle conditions. However, for some applications such as design of self-assembled multifunctional theragnostic agents, high stability of the assembled structures can be of primary importance. Here, we report extraordinarily high durability of protein-assisted nanoparticle self-assembly systems yielding bifunctional colloidal superstructures resistant to extreme denaturing conditions intolerable for most proteins (e.g., high concentrations of chaotropic agents, high temperature). Among the tested systems (barnase-barstar (BBS), streptavidin-biotin, antibody-antigen, and protein A-immunoglobulin), the BBS is notable due to the combination of its high resistance to severe chemical perturbation and unique advantages offered by genetic engineering of this entirely protein-based system. Comparison of the self-assembly systems shows that whereas in all cases the preassembled structures proved essentially resistant to extreme conditions, the ability of the complementary biomolecular pairs to mediate assembly of the initial biomolecule-particle conjugates differs substantially in these conditions.


Chemistry and technology of green gram (Vigna radiata [L.] Wilczek).
Green gram or mung bean (Vigna radiata [L.] Wilczek) is an important food legume grown under tropical and subtropical conditions. It is an excellent source of protein and is almost free from flatulence-causing factors. Because of this, green gram seeds are preferred for feeding babies and those convalescing. The seeds contain a higher proportion of lysine than any other legume seeds. The seeds are processed and consumed as cooked whole beans or splits (dhals), sprouts, immature seeds, and flour and are used in various recipes. The proposed work will incorporate available information on nutritional composition, processing, and utilization of green gram. The results reported in the literature on the above aspects of green gram will be analyzed critically, and future research needs will be defined to improve the utilization of green gram as human food.


Does the temperature of beverages affect the surface roughness, hardness, and color stability of a composite resin?
To investigate the effect of beverages' temperature on the surface roughness, hardness, and color stability of a composite resin. Fifty specimens of the Filtek Z250 composite (3M ESPE, Dental Products, St.Paul, MN, USA) were prepared and initial roughness, microhardness, and color were measured. Then the specimens were randomly divided into five groups of 10 specimens each: Coffee at 70°C, coffee at 37°C, cola at 10°C, cola at 37°C, and artificial saliva (control). After the samples were subjected to 15 min × 3 cycles per day of exposure to the solutions for 30 days, the final measurements were recorded. After immersion in beverages, the artificial saliva group showed hardness values higher than those of the other groups (P < 0.001) and the microhardness values were significantly different from the initial values in all groups except for the control group. Both cola groups showed roughness values higher than the baseline values (P < 0.05), while the other groups showed values similar to the baseline measurements. When ΔE measurements were examined, the 70°C coffee group showed the highest color change among all the groups (P < 0.05). High-temperature solutions caused alterations in certain properties of composites, such as increased color change, although they did not affect the hardness or roughness of the composite resin material tested.


MRI screening for breast cancer in women with familial or genetic predisposition: design of the Dutch National Study (MRISC).
Mammography screening of women aged 50-70 years for breast cancer has proven to be effective in reducing breast cancer mortality. There is no consensus about the value of breast cancer screening in women aged 40-49 years. Five to ten per cent of all breast cancers are hereditary. One of the options to reduce the risk of breast cancer mortality for women with a familial or genetic predisposition is intensive surveillance. However, the effectiveness of mammography screening for breast cancer in these women, who are mainly younger than 50 years, is unproven. MRI might increase the effectiveness of screening in women with a familial or genetic predisposition. This paper describes the design of the Dutch national study for Magnetic Resonance Imaging (MRI) screening in women with a familial or genetic predisposition. The aims of this study are to investigate: the value of regular surveillance in women with a familial or genetic predisposition for breast cancer, the efficacy of MRI as compared to mammography, cost-effectiveness of regular screening and quality of life during surveillance. Included are women with a lifetime risk of familial breast cancer of 15% or more or BRCA1/2 mutation carriers, who visit one of the Dutch family cancer clinics. The aim is to include 2,500 women. The study started on 1 November 1999. On 1 January 2002, more than 1,700 women, including 210 proven carriers of a BRCA1 or BRCA2 mutation, were included in the study.


Social and coping reasons for drinking: predicting alcohol misuse in adolescents.
Motivational models of alcohol consumption suggest a positive relationship between reasons for drinking and the amount of alcohol consumed. The present study examined race, gender, and age as moderators of the relationship between social and coping motives and alcohol misuse in black and white adolescents. A representative population sample (N = 699) of male and female (54%) adolescents between the ages of 13 and 16 was recruited using a random-digit-dial telephone procedure. Six face-to-face interviews with subjects and their families were carried out at approximately yearly intervals. Information gathered assessed alcohol use, social and coping motives for drinking, and psychological distress. Multiple analyses, including both cross-sectional and longitudinal logistic regression analyses and survival analysis were used to examine the relationship of drinking motives to adolescent alcohol misuse. Contrary to our predictions, social motive was a somewhat better predictor of alcohol misuse than was coping motive, particularly during mid- to late adolescence. However, there was some limited evidence of a significant relationship between coping motives and alcohol misuse in the mid-adolescent age group. Some support was found for racial differences such that social motives are better predictors of alcohol misuse among whites than among blacks and coping motives are better predictors among blacks. Few gender differences were found in the relationship of drinking motives and alcohol misuse. These findings suggest a stronger tendency for social and coping motives to influence alcohol misuse during mid to late than in early adolescence. Research examining the development of motives and the mechanisms by which they influence drinking behavior is needed.


Characterization of the human N-CAM promoter.
In contrast with the complex series of splicing choices that generate the various membrane-associated isoforms of the neural cell-adhesion molecule alternative splicing of 5' exons does not contribute to additional molecular diversity. A single regulatory unit in genomic DNA, mapping to a 5 kb restriction-endonuclease-HindIII fragment, controls the expression of all major RNA size classes. DNA sequence analysis of a 2 kb fragment spanning the two major identified transcriptional initiation sites (194 and 188 bp from the ATG codon) and translation start codon indicates that the regulatory unit does not possess classical TATA or CCAAT motifs. The region of the putative promoter exhibits a GC-rich content and a high frequency of the dinucleotide CpG, both characteristics of a HTF(HpaII tiny fragments)-island. Introduction of deletion-mutant chimaeric-gene constructs into human and rodent N-CAM-expressing cell lines defines an active promoter region of 467 bp (-144 to -611 bp from the ATG codon). This region of genomic DNA contains consensus sites for the interaction of known transcriptional factors.


Most Women with Previous Gestational Diabetes Mellitus Have Impaired Glucose Metabolism after a Decade.
Of 1324 women diagnosed with gestational diabetes mellitus (GDM) in Sweden, 25% reported >10 years after the delivery that they had developed diabetes mellitus. We assessed the long-term risk of all glucose metabolic abnormalities in a subgroup of these women. Women (n = 51) previously diagnosed with GDM by capillary blood glucose ≥9.0 mmol/L (≈plasma glucose ≥10.0 mmol/L) after a 2 h 75 g oral glucose tolerance test (OGTT) were included. All underwent a clinical and biochemical evaluation, including a second 2 h 75 g OGTT. Individuals with known type 1 diabetes were excluded. At the follow-up, 12/51 (24%) reported previously diagnosed type 2 diabetes. Another four cases were diagnosed after the second OGTT, increasing the prevalence to 16/51 cases (31%). Impaired fasting plasma glucose (IFG) was diagnosed in 13/51 women and impaired glucose tolerance (IGT) in 10/51 women, leaving only 12 women (24%) with normal glucose tolerance. In addition, 2/51 women had high levels of glutamic acid decarboxylase (GAD) antibodies; of these, one woman classified as type 2 diabetes was reclassified as type 1 diabetes, and the second GAD-positive woman was diagnosed with IGT. Of the women diagnosed with GDM by a 2 h 75 g OGTT, a large proportion had impaired glucose metabolism a decade later, including type 1 and type 2 diabetes.


Technological Analysis of the World's Earliest Shamanic Costume: A Multi-Scalar, Experimental Study of a Red Deer Headdress from the Early Holocene Site of Star Carr, North Yorkshire, UK.
Shamanic belief systems represent the first form of religious practice visible within the global archaeological record. Here we report on the earliest known evidence of shamanic costume: modified red deer crania headdresses from the Early Holocene site of Star Carr (c. 11 kya). More than 90% of the examples from prehistoric Europe come from this one site, establishing it as a place of outstanding shamanistic/cosmological significance. Our work, involving a programme of experimental replication, analysis of macroscopic traces, organic residue analysis and 3D image acquisition, metrology and visualisation, represents the first attempt to understand the manufacturing processes used to create these artefacts. The results produced were unexpected--rather than being carefully crafted objects, elements of their production can only be described as expedient.


Array-based expression analysis of mouse liver genes: effect of age and of the longevity mutant Prop1df.
Ames dwarf mice, homozygous for the df allele at the Prop1 locus, live 40% to 70% longer than nonmutant siblings and represent the first single-gene mutant that extends life span in a mammal. To gain insight into the basis for the longevity of the Ames dwarf mouse, we measured liver mRNA levels for 265 genes in a group of 11 df/df mice, (three to four mice per age group), at ages 5, 13, and 22 months, and in 13 age- and sex-matched control mice. The analysis showed seven genes where the effects of age reach p < .01 in normal mice and six others with possible age effects in dwarf mice, but none of these met Bonferroni-adjusted significance thresholds. Thirteen genes showed possible effects of the df/df genotype at p < .01. One of these, insulin-like growth factor 1 (IGF-1), was statistically significant even after adjustment for multiple comparisons; and genes for two IGF-binding proteins, a cyclin, a heat shock protein, p38 mitogen-activated protein kinase, and an inducible cytochrome P450 were among those implicated by the survey. In young control mice, half of the expressed genes showed SDs that were more than 58% of the mean, and a simulation study showed that genes with this degree of interanimal variation would often produce false-positive findings when conclusions were based on ratio calculations alone (i.e., without formal significance testing). Many genes in our data set showed apparent young-to-old or normal-to-dwarf ratios above 2, but the large majority of these proved to be genes where high interanimal variation could create high ratios by chance alone, and only a few of the genes with large ratios achieved p < .05. The proportion of genes showing relatively large changes between 5 and 13 months, or from 13 to 22 months of age, was not diminished by the df/df genotype, providing no support for the idea that the dwarf mutation leads to global delay or deceleration of the pace of age-dependent changes in gene expression. These survey data provide the foundation for replication studies that should provide convincing proof for age- and genotype-specific effects on gene expression and thus reveal key similarities among the growing number of mouse models of decelerated aging.


Development and testing of SPECT/CT lung phantoms made from expanding polyurethane foam.
Currently, single-photon emission computed tomography (SPECT)/computed tomography (CT) lung phantoms are commonly constructed using polystyrene beads and interstitial radioactive water. However, this approach often results in a phantom with a density (typically -640 HU) that is considerably higher than that of healthy lung (-750 to -850 HU) or diseased lung (-900 to -950 HU). Furthermore, the polystyrene and water phantoms are often quite heterogeneous in both density and activity concentration, especially when reused. This work is devoted to examining methods for creating a more realistic lung phantom for quantitative SPECT/CT using 99m Tc-laced expanding polyurethane foam (EPF). Numerous aspects of EPF utilization were studied, including stoichiometric mixing to control final foam density and the effect of water during growth. We also tested several ways of molding the foam lung phantoms. The most successful method utilized a three-part silicone mold that allowed for creation of a two-lobe phantom, with a different density and activity concentration in each lobe. The final phantom design allows for a more anatomically accurate geometry as well as customizable density and activity concentration in the different lobes of the lung. We demonstrated final lung phantom densities between -760 and -690 HU in the "healthy" phantom and -930 to -890 HU in the "unhealthy" phantom tissue. On average, we achieved 15% activity concentration nonuniformity and 12% density nonuniformity within a given lobe. Final EPF lung phantoms closely matched the densities of both health and diseased lung tissue and had sufficient uniformities in both density and activity concentration for most nuclear medicine applications. Management of component moisture content is critical for phantom reproducibility.


Validation and calibration of a novel GEM biosensor for specific detection of Cd2+, Zn2+, and Pb2.
In this study, we designed a novel genetic circuit sensitive to Cd2+, Zn2+ and Pb2+ by mimicking the CadA/CadR operon system mediated heavy metal homeostasis mechanism of Pseudomonas aeruginosa. The regular DNA motifs on natural operon were reconfigured and coupled with the enhanced Green Fluorescent Protein (eGFP) reporter to develop a novel basic NOT type logic gate CadA/CadR-eGFP to respond metal ions mentioned above. A Genetically Engineered Microbial (GEM)-based biosensor (E.coli-BL21:pJET1.2-CadA/CadR-eGFP) was developed by cloning the chemically synthesised CadA/CadR-eGFP gene circuit into pJET1.2-plasmid and transforming into Escherichia coli (E. coli)-BL21 bacterial cells. The GEM-based biosensor cells indicated the reporter gene expression in the presence of Cd2+, Zn2+ and Pb2+ either singly or in combination. Further, the same biosensor cells calibrated for fluorescent intensity against heavy metal concentration generated linear graphs for Cd2+, Zn2+ and Pb2+ with the R2 values of 0.9809, 0.9761 and 0.9758, respectively as compared to non-specific metals, Fe3+ (0.0373), AsO43- (0.3825) and Ni2+ (0.8498) making our biosensor suitable for the detection of low concentration of the former metal ions in the range of 1-6 ppb. Furthermore, the GEM based biosensor cells were growing naturally within the concentration range of heavy metals, at 37 °C and optimum pH = 7.0 in the medium, resembling the characteristics of wildtype E.coli. Finally, the novel GEM based biosensor cells developed in this study can be applied for detection of targeted heavy metals in low concentration ranges (1-6 ppb) at normal bacterial physiological conditions.


Lower Limb Joint Torque Prediction Using Long Short-Term Memory Network and Gaussian Process Regression.
The accurate prediction of joint torque is required in various applications. Some traditional methods, such as the inverse dynamics model and the electromyography (EMG)-driven neuromusculoskeletal (NMS) model, depend on ground reaction force (GRF) measurements and involve complex optimization solution processes, respectively. Recently, machine learning methods have been popularly used to predict joint torque with surface electromyography (sEMG) signals and kinematic information as inputs. This study aims to predict lower limb joint torque in the sagittal plane during walking, using a long short-term memory (LSTM) model and Gaussian process regression (GPR) model, respectively, with seven characteristics extracted from the sEMG signals of five muscles and three joint angles as inputs. The majority of the normalized root mean squared error (NRMSE) values in both models are below 15%, most Pearson correlation coefficient (R) values exceed 0.85, and most decisive factor (R2) values surpass 0.75. These results indicate that the joint prediction of torque is feasible using machine learning methods with sEMG signals and joint angles as inputs.


Cardiac complication after experimental human malaria infection: a case report.
A 20 year-old healthy female volunteer participated in a clinical Phase I and IIa safety and efficacy trial with candidate malaria vaccine PfLSA-3-rec adjuvanted with aluminium hydroxide. Eleven weeks after the third and last immunization she was experimentally infected by bites of Plasmodium falciparum-infected mosquitoes. When the thick blood smear became positive, at day 11, she was treated with artemether/lumefantrine according to protocol. On day 16 post-infection i.e. two days after completion of treatment, she woke up with retrosternal chest pain. She was diagnosed as acute coronary syndrome and treated accordingly. She recovered quickly and her follow-up was uneventful. Whether the event was related to the study procedures such as the preceding vaccinations, malaria infection or antimalarial drugs remains elusive. However, the relation in time with the experimental malaria infection and apparent absence of an underlying condition makes the infection the most probable trigger. This is in striking contrast, however, with the millions of malaria cases each year and the fact that such complication has never been reported in the literature. The rare occurrence of cardiac events with any of the preceding study procedures may even support a coincidental finding. Apart from acute coronary syndrome, myocarditis can be considered as a final diagnosis, but the true nature and patho-physiological explanation of the event remain unclear.


Introducing an adolescent cognitive maturity index.
Children show substantial variation in the rate of physical, cognitive, and social maturation as they traverse adolescence and enter adulthood. Differences in developmental paths are thought to underlie individual differences in later life outcomes, however, there remains a lack of consensus on the normative trajectory of cognitive maturation in adolescence. To address this problem, we derive a Cognitive Maturity Index (CMI), to estimate the difference between chronological and cognitive age predicted with latent factor estimates of inhibitory control, risky decision-making and emotional processing measured with standard neuropsychological instruments. One hundred and forty-one children from the Adolescent Development Study (ADS) were followed longitudinally across three time points from ages 11-14, 13-16, and 14-18. Age prediction with latent factor estimates of cognitive skills approximated age within ±10 months (r = 0.71). Males in advanced puberty displayed lower cognitive maturity relative to peers of the same age; manifesting as weaker inhibitory control, greater risk-taking, desensitization to negative affect, and poor recognition of positive affect.


Steady-state neutrophil homeostasis is dependent on TLR4/TRIF signaling.
Polymorphonuclear neutrophil granulocytes (neutrophils) are tightly controlled by an incompletely understood homeostatic feedback loop adjusting the marrow's supply to peripheral needs. Although it has long been known that marrow cellularity is inversely correlated with G-CSF levels, the mechanism linking peripheral clearance to production remains unknown. Herein, the feedback response to antibody induced neutropenia is characterized to consist of G-CSF–dependent shifts of marrow hematopoietic progenitor populations including expansion of the lin-/Sca-1/c-kit (LSK) and granulocyte macrophage progenitor (GMP) compartments at the expense of thrombopoietic and red cell precursors. Evidence is provided that positive feedback regulation is independent from commensal germs as well as T, B, and NK cells. However, in vivo feedback is impaired in TLR4-/- and TRIF-/-, but not MyD88-/- animals. In conclusion, steady-state neutrophil homeostasis is G-CSF–dependent and regulated through pattern-recognition receptors,thereby directly linking TLR-triggering to granulopoiesis. Steady-state and emergency granulopoiesis are both dependent on TLR signaling.


Parotid heterotopia with pleomorphic adenoma.
We observed an unusual and clinically unsuspected pleomorphic adenoma developing in the anterior midcervical region of a young man. The tumor developed within an ectopic parotid-type salivary gland. Surgical extirpation seems to have been curative. Embryologic concepts explaining the histogenesis of ectopic salivary glands (ESGs) are explored, and the problem of their concurrence with neoplasms is addressed. An additional feature was the presence of well-developed lymph nodes within the glandular complex, a morphologic component of ESGs that has not been previously emphasized.


The role of multiple hydrogen-bonding groups in specific alcohol binding sites in proteins: insights from structural studies of LUSH.
It is now generally accepted that many of the physiological effects of alcohol consumption are a direct result of binding to specific sites in neuronal proteins such as ion channels or other components of neuronal signaling cascades. Binding to these targets generally occurs in water-filled pockets and leads to alterations in protein structure and dynamics. However, the precise interactions required to confer alcohol sensitivity to a particular protein remain undefined. Using information from the previously solved crystal structures of the Drosophila melanogaster protein LUSH in complexes with short-chain alcohols, we have designed and tested the effects of specific amino acid substitutions on alcohol binding. The effects of these substitutions, specifically S52A, T57S, and T57A, were examined using a combination of molecular dynamics, X-ray crystallography, fluorescence spectroscopy, and thermal unfolding. These studies reveal that the binding of ethanol is highly sensitive to small changes in the composition of the alcohol binding site. We find that T57 is the most critical residue for binding alcohols; the T57A substitution completely abolishes binding, while the T57S substitution differentially affects ethanol binding compared to longer-chain alcohols. The additional requirement for a potential hydrogen-bond acceptor at position 52 suggests that both the presence of multiple hydrogen-bonding groups and the identity of the hydrogen-bonding residues are critical for defining an ethanol binding site. These results provide new insights into the detailed chemistry of alcohol's interactions with proteins.


Alcohol, tobacco and coffee consumption and the risk of pancreatic cancer: results from the Canadian Enhanced Surveillance System case-control project. Canadian Cancer Registries Epidemiology Research Group.
The relationship between alcohol, tobacco and coffee consumption and pancreatic cancer was investigated using population-based case-control data obtained from eight Canadian provinces. Our findings are based on analyses performed on 583 histologically confirmed pancreatic cancer cases and 4813 controls. Questionnaire data were obtained directly from 76% of the cases. Male subjects with 35 or more cigarette pack-years had an increased risk of developing pancreatic cancer relative to never smokers (OR= 1.46, 95% CI 1.00-2.14). Similarly, women reporting at least 23 cigarette pack-years of smoking had an odds ratio of 1.84 (95% CI 1.25-2.69). For the most part, consumption of total alcohol, wine, liquor and beer was not associated with pancreatic cancer. Coffee drinking was not related to pancreatic cancer. More work is needed to clarify the role of these and other potentially modifiable risk factors as a means to reduce the incidence of this disease for which treatment results remain disappointing.


Impact of Mandibular Symphyseal Distraction Osteogenesis (MSDO) on the Sagittal Dimension and Long-Term Skeletal stability.
To evaluate the long-term effects of mandibular symphyseal distraction osteogenesis (MSDO) on the correction of class II malocclusion correction and dental crowding. Twenty-two patients received MSDO and presented class II malocclusion with transverse mandibular discrepancy. The authors collected data on 2 different cephalometric analyses. On Tweed analysis, The authors recorded ANB, SNA, SNB, and FMA angles. On Delaire analysis, we recorded the distance from Pti (pterygoid inferior) to ENAt (anterior nasal spine) and the distance from Cos (superior condyle) to Pog (pogonion). Superimpositions studies were performed at pre-treatment phase (T1) and post-treatment phase (T2) to evaluate the new position and changes in the dimensions of the mandible and maxilla. On superimposition of Tweed analysis of T1 and T2, reduction of ANB was seen in 18 patients, no change in ANB in 2 patients, and increase in ANB (by 1 deg) in 2 patients. Superimposition of Delaire analysis showed a mean difference of 0.3 mm (SD, 3.6 mm) between T1 and T2 for the maxilla and a mean difference of 6.0 mm (SD, 7.3 mm) for the mandible. Mandibular symphyseal distraction osteogenesis performed after the pubertal growth peak can effectively correct class II malocclusion and dental crowding with a single light surgical procedure.


Beyond city expansion: multi-scale environmental impacts of urban megaregion formation in China.
Environmental degradation caused by rapid urbanization is a pressing global issue. However, little is known about how urban changes operate and affect environments across multiple scales. Focusing on China, we found urbanization was indeed massive from 2000 to 2015, but it was also very uneven, exhibiting high internal city dynamics. Urban areas in China as a whole became less green, warmer, and had exacerbated PM2.5 pollution. However, environmental impacts differed in newly developed versus older areas of cities. Adverse impacts were prominent in newly urbanized areas, while old urban areas generally showed improved environmental quality. In addition, regional environmental issues are emerging as cities expand, connect and interact to form urban megaregions. To turn urbanization into an opportunity for, rather than an obstacle to, sustainable development, we must move beyond documenting urban expansion to understand the environmental consequences of both internal city dynamics and the formation of urban megaregions.


Outcome after percutaneous endoscopic gastrostomy in children and young adults.
Factors predicting outcome after percutaneous endoscopic gastrostomy (PEG) in large pediatric cohorts are not well defined. We hypothesized that definable preoperative clinical factors predict the need for further intervention to provide enteral access after PEG. Our aim was to identify factors associated with PEG outcome. A retrospective review of 760 (407 boys and 353 girls) patients was performed after PEG at the Johns Hopkins Children's Center from 1994 to 2005. Logistic or multiple linear regression was used to analyze indication; diagnosis; age; prematurity; neurological impairment; weight-for-age z scores; modified barium swallow; postoperative complications; need for fundoplication (FP), gastrojejunal tube, or jejunostomy; and length of hospital stay. The median age was 1 year (range 0-26 years). The most common indications given for PEG were failure to thrive (n = 373) and dysphagia (n = 27). Postoperative FP, gastrojejunal tube, or jejunostomy were performed in 66 (10%), 24 (4%), and 9 (1%) patients, respectively. Preoperative report indicated that dysphagia and direct aspiration on modified barium swallow was strongly associated with patients undergoing FP after PEG, 10.6% of patients (P = 0.008, odds ratio 2.4) and 11.2% of patients (P = 0.013, odds ratio 2.8), respectively. Younger preoperative age was also associated with the need for FP (P = 0.0006; median age of 5.8 vs 14 months). Patients with preoperative dysphagia had a longer median length of hospital stay: 8 versus 3 days (P < 0.00001). Patients with neurological impairment demonstrated greater weight gain than neurologically normal patients after PEG (P = 0.04). Minor postoperative complications (most commonly wound infection) were observed in 4% (27/747) of children before hospital discharge from PEG and in 20% of children (138/682) after discharge. There were only 2 major complications (gastric separation and gastrocolonic fistula.). There were no fatalities. Preoperative diagnosis, indication, prematurity, and neurological impairment did not influence postoperative complications.


Serostatus disclosure among a cohort of HIV-infected pregnant women enrolled in HIV care in Moshi, Tanzania: A mixed-methods study.
HIV-infected pregnant women face complex decisions about whether and how to disclose their serostatus. Previous studies have shown that HIV disclosure is associated with better care engagement, emotional adjustment to the disease, and reduced risk of HIV transmission, but women face both real and perceived barriers to disclosure. We examined patterns and predictors of HIV disclosure in a cohort of 200 women diagnosed or confirmed to have HIV during antenatal care in the Kilimanjaro region of Tanzania and followed participants to three months postpartum. Twenty women also completed qualitative in-depth interviews during pregnancy and three months postpartum. During the pregnancy period (at least 30 days post-diagnosis), 79.5% of women had disclosed to at least one other person, with disclosures generally restricted to the father of the child and/or a small number of close family members. By three months postpartum, 11.9% of women had still not disclosed to anyone. Women who presented to antenatal care with an established HIV diagnoses and married women were more likely to report disclosures. Social support was positively associated with disclosure. In qualitative interviews, women pointed to community gossip and stigma as barriers to disclosure. Those who had not disclosed to the father of the child noted fears of abandonment during the vulnerable pregnancy period. Despite expressed fears, participants reported overall positive experiences of disclosure that led to increased support. Taken together, these results point to the need for comprehensive, flexible, and culturally informed interventions that assist pregnant and postpartum women in deciding when and how to disclose. Such interventions should acknowledge and explore common barriers to disclosure, including fears of public stigma and personal consequences. Given the strong associations between disclosure, social support, and community stigma, interventions for disclosure should be nested in broader efforts of public education and HIV stigma reduction.


Surgical treatment of low-grade chondrosarcoma involving the appendicular skeleton: long-term functional and oncological outcomes.
The traditional treatment for chondrosarcoma is wide local excision (WLE), as these tumors are resistant to chemotherapy and radiation treatment. While achieving negative margins has traditionally been the goal of chondrosarcoma resection, multiple studies have demonstrated good short-term results after intralesional procedures for low-grade chondrosarcomas (LGCS) with curettage and adjuvant treatments (phenol application, cauterization or cryotherapy) followed by either cementation or bone grafting. Due to the rarity of this diagnosis and the recent application of this surgical treatment modality to chondrosarcoma, most of the information regarding treatment outcomes is retrospective, with short or intermediate-term follow-up. The aim of this study was to assess the long-term results of patients with LGCS of bone treated with intralesional curettage (IC) treatment versus WLE. This retrospective analysis aims to characterize the oncologic outcomes (local recurrence, metastases) and functional outcomes in these two treatment groups at a single institution. Using an institutional musculoskeletal oncologic database, we retrospectively reviewed medical records of all patients with LGCS of the appendicular skeleton that underwent surgical treatment between 1985 and 2007. Thirty-two patients (33 tumors) were identified with LGCS; 17 treated with IC and 15 with WLE. Seventeen patients (18 tumors) with a minimum clinical and radiologic follow-up of 10 years were included. Nine patients were treated with IC (four with no adjuvant, three with additional phenol, one with liquid nitrogen and one with H2O2) with either bone graft or cement augmentation, and nine others were treated with WLE and reconstruction with intercalary/osteoarticular allograft or megaprosthesis. The mean age at surgery was 41 years (range 14-66 years) with no difference (p = 0.51) between treatment cohorts. There was a mean follow-up of 13.5 years in the intralesional cohort (range 10-19 years) and 15.9 years in the WLE cohort (range 10-28 years, p = 0.36). Tumor size varied significantly between groups and was larger in patients treated with WLE (8.2 ± 3.1 cm versus 5.4 ± 1.2 cm, at the greatest dimension, p = 0.021). There were two local recurrences (LR), one in the intralesional group and one in the wide local excision group, occurring at 3.5 months and 2.9 years, respectively, and both required revision. No further LR could be detected with long-term follow-up. The MSTS score at final follow-up was significantly higher for patients managed with intralesional procedures (28.7 ± 1.7 versus 25.7 ± 3.4, p = 0.033). There were less complications requiring reoperation in the intralesional group compared with the wide local excision group, although this difference was not found to be statistically significant (one versus four patients, respectively; p = 0.3). This series of low-grade chondrosarcoma, surgically treated with an intralesional procedures, with 10-year follow-up, demonstrates excellent local control (88.9%). Complications were infrequent and minor and MSTS functional scores were excellent. Wide resection of LGCS was associated with lower MSTS score and more complications. In our series, the LR in both groups were detected within the first 3.5 years following the index procedure, and none were detected in the late surveillance period.


A Dynamic Energy Budget (DEB) model for the keystone predator Pisaster ochraceus.
We present a Dynamic Energy Budget (DEB) model for the quintessential keystone predator, the rocky-intertidal sea star Pisaster ochraceus. Based on first principles, DEB theory is used to illuminate underlying physiological processes (maintenance, growth, development, and reproduction), thus providing a framework to predict individual-level responses to environmental change. We parameterized the model for P. ochraceus using both data from the literature and experiments conducted specifically for the DEB framework. We devoted special attention to the model's capacity to (1) describe growth trajectories at different life-stages, including pelagic larval and post-metamorphic phases, (2) simulate shrinkage when prey availability is insufficient to meet maintenance requirements, and (3) deal with the combined effects of changing body temperature and food supply. We further validated the model using an independent growth data set. Using standard statistics to compare model outputs with real data (e.g. Mean Absolute Percent Error, MAPE) we demonstrated that the model is capable of tracking P. ochraceus' growth in length at different life-stages (larvae: MAPE = 12.27%; post-metamorphic, MAPE = 9.22%), as well as quantifying reproductive output index. However, the model's skill dropped when trying to predict changes in body mass (MAPE = 24.59%), potentially because of the challenge of precisely anticipating spawning events. Interestingly, the model revealed that P. ochraceus reserves contribute little to total biomass, suggesting that animals draw energy from structure when food is limited. The latter appears to drive indeterminate growth dynamics in P. ochraceus. Individual-based mechanistic models, which can illuminate underlying physiological responses, offer a viable framework for forecasting population dynamics in the keystone predator Pisaster ochraceus. The DEB model herein represents a critical step in that direction, especially in a period of increased anthropogenic pressure on natural systems and an observed recent decline in populations of this keystone species.


Mobilizing Transit-Amplifying Cell-Derived Ectopic Progenitors Prevents Hair Loss from Chemotherapy or Radiation Therapy.
Genotoxicity-induced hair loss from chemotherapy and radiotherapy is often encountered in cancer treatment, and there is a lack of effective treatment. In growing hair follicles (HF), quiescent stem cells (SC) are maintained in the bulge region, and hair bulbs at the base contain rapidly dividing, yet genotoxicity-sensitive transit-amplifying cells (TAC) that maintain hair growth. How genotoxicity-induced HF injury is repaired remains unclear. We report here that HFs mobilize ectopic progenitors from distinct TAC compartments for regeneration in adaptation to the severity of dystrophy induced by ionizing radiation (IR). Specifically, after low-dose IR, keratin 5+ basal hair bulb progenitors, rather than bulge SCs, were quickly activated to replenish matrix cells and regenerated all concentric layers of HFs, demonstrating their plasticity. After high-dose IR, when both matrix and hair bulb cells were depleted, the surviving outer root sheath cells rapidly acquired an SC-like state and fueled HF regeneration. Their progeny then homed back to SC niche and supported new cycles of HF growth. We also revealed that IR induced HF dystrophy and hair loss and suppressed WNT signaling in a p53- and dose-dependent manner. Augmenting WNT signaling attenuated the suppressive effect of p53 and enhanced ectopic progenitor proliferation after genotoxic injury, thereby preventing both IR- and cyclophosphamide-induced alopecia. Hence, targeted activation of TAC-derived progenitor cells, rather than quiescent bulge SCs, for anagen HF repair can be a potential approach to prevent hair loss from chemotherapy and radiotherapy. Cancer Res; 77(22); 6083-96. ©2017 AACR.


Red clover (Trifolium pratense) isoflavones and serum homocysteine in premenopausal women: a pilot study.
There is limited information on the effect of isoflavones on homocysteine concentrations, a risk factor for a number of chronic diseases. Twenty-three premenopausal women participated in a double-blind, randomized, parallel study for four menstrual cycles. Subjects consumed either placebo or purified red clover (Trifolium pratense) isoflavone (86 mg/day) tablets. Blood samples were collected weekly during cycles 1, 3, and 4 for determination of serum folate and total homocysteine concentrations. Dietary intake was monitored monthly. Concentrations of folate and homocysteine in serum did not change significantly in either group, and there were no significant differences observed between the follicular and luteal phases of the menstrual cycle. The participants' dietary records indicated that nutrient intake was constant, and compliance was confirmed by analysis of urinary isoflavone concentrations and tablet counts in returned containers. These results suggest that in the absence of any dietary modification, supplementation with purified isoflavones that are predominantly methoxylated has no effect on serum homocysteine or folate in premenopausal women.


Early assessment of pressure sore risk.
If they are to prevent at-risk patients developing pressure sores, and ensure optimum healing time for those already existing, it is vital that nurses understand the aetiology of pressure sores and employ a system of risk assessment.


Evaluating Summary Methods for Multilocus Species Tree Estimation in the Presence of Incomplete Lineage Sorting.
Species tree estimation is complicated by processes, such as gene duplication and loss and incomplete lineage sorting (ILS), that cause discordance between gene trees and the species tree. Furthermore, while concatenation, a traditional approach to tree estimation, has excellent performance under many conditions, the expectation is that the best accuracy will be obtained through the use of species tree estimation methods that are specifically designed to address gene tree discordance. In this article, we report on a study to evaluate MP-EST-one of the most popular species tree estimation methods designed to address ILS-as well as concatenation under maximum likelihood, the greedy consensus, and two supertree methods (Matrix Representation with Parsimony and Matrix Representation with Likelihood). Our study shows that several factors impact the absolute and relative accuracy of methods, including the number of gene trees, the accuracy of the estimated gene trees, and the amount of ILS. Concatenation can be more accurate than the best summary methods in some cases (mostly when the gene trees have poor phylogenetic signal or when the level of ILS is low), but summary methods are generally more accurate than concatenation when there are an adequate number of sufficiently accurate gene trees. Our study suggests that coalescent-based species tree methods may be key to estimating highly accurate species trees from multiple loci.


Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride.
This study was carried out to show the effect of particle size reduction and bioadhesion on the dissolution and relative bioavailability of dicumarol. Formulations were produced by a variety of methods including a novel technique to reduce particle size as well as phase inversion with poly(fumaric-co-sebacic)anhydride p(FA:SA) to create nanospheres. Drug was administered to groups of pigs and rats via oral gavage of a suspension, and dicumarol concentration in the blood was measured using a double extraction technique. In vitro results showed improved dissolution in both the micronized formulation and the encapsulated p(FA:SA) nanospheres. In vivo, relative bioavailability of a spray-dried formulation was increased by 17% in the rat and 72% in the pig by further reduction in particle size. The bioadhesive p(FA:SA) formulation also improved relative bioavailability over the spray-dried drug, increasing it by 55% in the rat and 96% in the pig. Additionally, the p(FA:SA) formulation prolonged Tmax and decreased Cmax in both species. This work demonstrates the importance of particle size and bioadhesion to improve oral bioavailability of ducumarol.


A Bayesian method for measuring risk propensity in the Balloon Analogue Risk Task.
The Balloon Analogue Risk Task (BART) is widely-used to measure risk propensity in theoretical, clinical, and applied research. In the task, people choose either to pump a balloon to increase its value at the risk of the balloon bursting and losing all value, or to bank the current value of the balloon. Risk propensity is most commonly measured as the average number of pumps on trials for which the balloon does not burst. Burst trials are excluded because they necessarily underestimate the number of pumps people intended to make. However, their exclusion discards relevant information about people's risk propensity. A better measure of risk propensity uses the statistical method of censoring to incorporate all of the trials. We develop a new Bayesian method, based on censoring, for measuring both risk propensity and behavioral consistency in the BART. Through applications to previous data we demonstrate how the method can be extended to consider the correlation of risk propensity with external measures, and to compare differences in risk propensity between groups. We provide implementations of all of these methods in R, MATLAB, and the GUI-based statistical software JASP.


Influence of skin colour on diagnostic accuracy of the jaundice meter JM 103 in newborns.
To assess the diagnostic accuracy of the JM 103 as a screening tool for neonatal jaundice and explore differential effects based on skin colour. We prospectively compared the transcutaneous bilirubin (TcB) and serum bilirubin (TSB) measurements of newborns over a 3 month-period. Skin colour was assigned via reference colour swatches. Diagnostic measures of the TcB/TSB comparison were made and clinically relevant TcB cut-off values were determined for each skin colour group. 451 infants (51 light, 326 medium and 74 dark skin colour) were recruited. The association between TcB and TSB was high for all skin colours (rs>0.9). The Bland-Altman analysis showed an absolute mean difference between the two measures of 13.3±26.4 µmol/L with broad limits of agreement (-39.4-66.0 µmol/L), with TcB underestimating TSB in light and medium skin colours and overestimating in dark skin colour. Diagnostic measures were also consistently high across skin colours, with no clinically significant differences observed. The JM 103 is a useful screening tool to identify infants in need of serum bilirubin, regardless of skin colour. The effect of skin colour on the accuracy of this device at high levels of serum bilirubin could not be assessed fully due to small numbers in the light and dark groups.


Gender-specific disruptions in emotion processing in younger adults with depression.
One of the principal theories regarding the biological basis of major depressive disorder (MDD) implicates a dysregulation of emotion-processing circuitry. Gender differences in how emotions are processed and relative experience with emotion processing might help to explain some of the disparities in the prevalence of MDD between women and men. This study sought to explore how gender and depression status relate to emotion processing. This study employed a 2 (MDD status) x 2 (gender) factorial design to explore differences in classifications of posed facial emotional expressions (N=151). For errors, there was an interaction between gender and depression status. Women with MDD made more errors than did nondepressed women and men with MDD, particularly for fearful and sad stimuli (Ps <.02), which they were likely to misinterpret as angry (Ps <.04). There was also an interaction of diagnosis and gender for response cost for negative stimuli, with significantly greater interference from negative faces present in women with MDD compared to nondepressed women (P=.01). Men with MDD, conversely, performed similarly to control men (P=.61). These results provide novel and intriguing evidence that depression in younger adults (<35 years) differentially disrupts emotion processing in women as compared to men. This interaction could be driven by neurobiological and social learning mechanisms, or interactions between them, and may underlie differences in the prevalence of depression in women and men.


Hemophagocytic lymphohistiocytosis in the setting of HELLP Syndrome.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper activation of the immune system. Rare cases associated with HELLP syndrome and other similar conditions in pregnancy have been reported. Despite the improved survival rates with etoposide and dexamethasone-based regimens, HLH remains a challenging disease. Experience in pregnant patients is exceedingly rare.


Anticoagulant prophylaxis against venous thromboembolism following severe traumatic brain injury: A prospective observational study and systematic review of the literature.
Venous thromboembolism (VTE) is a serious complication following severe traumatic brain injury (TBI), however, anticoagulant prophylaxis remains controversial due to concerns of intracranial hemorrhage (ICH) progression. We examined anticoagulant prophylaxis practice patterns at a major trauma centre and determined risk estimates for VTE and ICH progression classified by timing of anticoagulant initiation. A 1-year prospective analysis of consecutive patients with severe TBI admitted to a Level-I trauma centre was conducted. In addition, we systematically reviewed the literature to identify studies on VTE and anticoagulant prophylaxis after severe TBI. 64 severe TBI patients were included. 83% of patients received anticoagulant prophylaxis, initiated ≥3d post-TBI in 67%. The in-hospital VTE incidence was 16% and there was no significant difference between patients who received early (<3d) versus late (≥3d) prophylaxis (10% vs. 16%). Rates of ICH progression (0% vs. 7%) were similar between groups. Our systematic review identified 5 studies with VTE rates ranging from 5 to 10% with prophylaxis, to 11-30% without prophylaxis. The effect of timing of anticoagulant prophylaxis initiation on ICH progression was not reported in any study. VTE is a common complication after severe TBI. Anticoagulant prophylaxis is often started late (≥3d) post-injury. Randomized trials are justifiable and necessary to provide practice guidance with regards to optimal timing of anticoagulant prophylaxis.


Control technology for crystalline silica exposures in construction: wet abrasive blasting.
This study was designed to document the effect that wet abrasive blasting has on reducing worker exposure to crystalline silica, which has been associated with silicosis and premature death. In this study, worker exposure to respirable crystalline silica was monitored during wet abrasive blasting on the exterior walls of a parking garage to remove surface concrete and expose the underlying aggregate. In this process a wet sand mix comprised of 80% dry sand and 20% water was used. Sampling and analysis revealed that the geometric mean respirable quartz concentration was 0.2 mg/m(3) for workers conducting abrasive blasting and 0.06 mg/m(3) for helpers. When abrasive blasting was conducted in areas that apparently had reduced natural ventilation, dust exposures appeared to increase. When compared with other published data, this case study suggests that wet abrasive blasting causes less exposure to crystalline silica than dry abrasive blasting.


Maximum likelihood estimation in random effects cure rate models with nonignorable missing covariates.
We introduce a method of parameter estimation for a random effects cure rate model. We also propose a methodology that allows us to account for nonignorable missing covariates in this class of models. The proposed method corrects for possible bias introduced by complete case analysis when missing data are not missing completely at random and is motivated by data from a pair of melanoma studies conducted by the Eastern Cooperative Oncology Group in which clustering by cohort or time of study entry was suspected. In addition, these models allow estimation of cure rates, which is desirable when we do not wish to assume that all subjects remain at risk of death or relapse from disease after sufficient follow-up. We develop an EM algorithm for the model and provide an efficient Gibbs sampling scheme for carrying out the E-step of the algorithm.


MTAP loss: a possible therapeutic approach for glioblastoma.
Glioblastoma is the most lethal form of brain tumor with a recurrence rate of almost 90% and a survival time of only 15 months post-diagnosis. It is a highly heterogeneous, aggressive, and extensively studied tumor. Multiple studies have proposed therapeutic approaches to mitigate or improve the survival for patients with glioblastoma. In this article, we review the loss of the 5'-methylthioadenosine phosphorylase (MTAP) gene as a potential therapeutic approach for treating glioblastoma. MTAP encodes a metabolic enzyme required for the metabolism of polyamines and purines leading to DNA synthesis. Multiple studies have explored the loss of this gene and have shown its relevance as a therapeutic approach to glioblastoma tumor mitigation; however, other studies show that the loss of MTAP does not have a major impact on the course of the disease. This article reviews the contrasting findings of MTAP loss with regard to mitigating the effects of glioblastoma, and also focuses on multiple aspects of MTAP loss in glioblastoma by providing insights into the known findings and some of the unexplored areas of this field where new approaches can be imagined for novel glioblastoma therapeutics.


Links between Household-Level Income-Generating Agricultural Intervention and the Psychological Well-Being of Adolescent Girls in Human Immunodeficiency Virus-Affected Households in Southwestern Kenya: A Qualitative Inquiry.
Adolescent girls may experience poor psychological well-being, such as social isolation, shame, anxiety, hopelessness, and despair linked to food insecurity. This study aimed to investigate the experiences with and perceived effects of a household-level income-generating agricultural intervention on the psychological well-being of adolescent girls in human immunodeficiency virus (HIV)-affected households in southwestern Kenya. We conducted 62 in-depth interviews with HIV-affected adolescent girls and caregiver dyads in Adolescent Shamba Maisha (NCT03741634), a sub-study of adolescent girls and caregivers with a household member participating in Shamba Maisha (NCT01548599), a multisectoral agricultural and finance intervention trial aimed to improve food security and HIV health indicators. Participants were purposively sampled to ensure diversity in terms of age and location. Data were audiotaped, transcribed, translated, and uploaded into Dedoose (Sociocultural Research Consultants, LLC) software for management. Data were analyzed thematically based on reports from Dedoose. We found evidence that a household-level structural intervention aimed at increasing food and financial security among persons living with HIV can contribute to better psychological well-being among adolescent girls residing in these households. The intervention also affected: 1) reduction of social isolation, 2) reduction of shame and stigma, 3) increased attendance and concentration in school, 4) improved caregiver mental health, and 5) reduced parental aggression and improved household communication. These associations were reported more commonly among those in the intervention arm than the control arm. This study extends existing research by demonstrating how multisectoral structural interventions delivered at a household level can improve the psychological well-being of adolescents. We recommend that future research test livelihood interventions designed specifically for adolescent girls that integrate food-security interventions with other elements to address the social and psychological consequences of food insecurity holistically. This trial was registered at clinicaltrials.gov as NCT03741634.


Determinants of COVID-19 Vaccine Acceptance in Saudi Arabia: A Web-Based National Survey.
Vaccine hesitancy is a potential threat to global public health. Since there is an unprecedented global effort to develop a vaccine against the COVID-19 pandemic, much less is known about its acceptance in the community. Understanding key determinants that influence the preferences and demands of a future vaccine by the community may help to develop strategies for improving the global vaccination program. The aim of this study was to assess the prevalence of the acceptance of COVID-19 vaccine and their determinants among people in Saudi Arabia. A web-based, cross-sectional study was conducted using snowball sampling strategy under a highly restricted environment. A bilingual, self-administered anonymous questionnaire was designed and sent to the study participants through social media plat-forms and email. Study participants were recruited across the country, including the four major cities (Riyadh, Dammam, Jeddah, and Abha) in Saudi Arabia. Key determinants that predict vaccine acceptance among respondents were modelled using logistic regression analysis. Of the 1000 survey invitees, 992 responded to the survey. Of the 992 respondents, 642 showed interest to accept the COVID-19 vaccine if it is available. Willingness to accept the future COVID-19 vaccine is relatively high among older age groups, being married participants with education level postgraduate degree or higher (68.8%), non-Saudi (69.1%), employed in government sector (68.9%). In multivariate model, respondents who were above 45 years (aOR: 2.15; 95% CI: 1.08-3.21) and married (aOR: 1.79; 95% CI: 1.28-2.50) were significantly associated with vaccine acceptance (p < 0.05). Addressing sociodemographic determinants relating to the COVID-19 vaccination may help to increase uptake of the global vaccination program to tackle future pandemics. Targeted health education interventions are needed to increase the uptake of the future COVID-19 vaccine.


The Effect of Diagnostic Ureterorenoscopy on Intravesical Recurrence in Patients Undergoing Nephroureterectomy for Primary Upper Tract Urinary Carcinoma.
The objective of this study is to evaluate the effect of diagnostic ureterorenoscopy (URS) prior to radical nephroureterectomy (RNU) on intravesical recurrence (IVR), in patients with primary upper urinary tract urothelial carcinoma (UTUC). Retrospective analysis of 354 patients, who underwent RNU for UTUC from 10 urology centers between 2005 and 2019, was performed. The primary endpoint was the occurrence of IVR after RNU. Patients were divided into URS prior to RNU (Group 1) and no URS prior to RNU (Group 2). Rates of IVR after RNU were compared, and a Cox proportional hazards model was used to evaluate potential predictors of IVR. After exclusion, a total of 194 patients were analyzed: Group 1 n = 95 (49.0%) and Group 2 n = 99 (51.0%). In Group 1, a tumor biopsy and histopathological confirmation during URS were performed in 58 (61.1%). The mean follow-up was 39.17 ± 39.3 (range 12-250) months. In 54 (27.8%) patients, IVR was recorded after RNU, and the median recurrence time within the bladder was 10.0 (3-144) months. IVR rate was 38.9% in Group 1 versus 17.2% in Group 2 (p = 0.001). In Group 1, IVR rate was 43.1% in those undergoing intraoperative biopsy versus 32.4% of patients without biopsy during diagnostic URS (p =0.29). Intravesical recurrence-free survival (IRFS) was longer in Group 2 compared to Group 1 (median IRFS was 111 vs. 60 months in Groups 2 and 1, respectively (p< 0.001)). Univariate analysis revealed that IRFS was significantly associated with URS prior to RNU (HR: 2.9, 95% CI 1.65-5.41; p < 0.001). In multivariate analysis, URS prior to RNU (HR: 3.5, 95% CI 1.74-7.16; p < 0.001) was found to be an independent prognostic factor for IRFS. Diagnostic URS was associated with the poor IRFS following RNU for primary UTUC. The decision for a diagnostic URS with or without tumor biopsy should be reserved for cases where this information might influence further treatment decisions.


Biological interaction networks are conserved at the module level.
Orthologous genes are highly conserved between closely related species and biological systems often utilize the same genes across different organisms. However, while sequence similarity often implies functional similarity, interaction data is not well conserved even for proteins with high sequence similarity. Several recent studies comparing high throughput data including expression, protein-protein, protein-DNA, and genetic interactions between close species show conservation at a much lower rate than expected. In this work we collected comprehensive high-throughput interaction datasets for four model organisms (S. cerevisiae, S. pombe, C. elegans, and D. melanogaster) and carried out systematic analyses in order to explain the apparent lower conservation of interaction data when compared to the conservation of sequence data. We first showed that several previously proposed hypotheses only provide a limited explanation for such lower conservation rates. We combined all interaction evidences into an integrated network for each species and identified functional modules from these integrated networks. We then demonstrate that interactions that are part of functional modules are conserved at much higher rates than previous reports in the literature, while interactions that connect between distinct functional modules are conserved at lower rates. We show that conservation is maintained between species, but mainly at the module level. Our results indicate that interactions within modules are much more likely to be conserved than interactions between proteins in different modules. This provides a network based explanation to the observed conservation rates that can also help explain why so many biological processes are well conserved despite the lower levels of conservation for the interactions of proteins participating in these processes.Accompanying website: http://www.sb.cs.cmu.edu/CrossSP.


The Perfect Match! A Review and Tutorial on Issues Related to Matching Groups in Investigations of Children with Neurodevelopmental Conditions.
Research concerned with children and young people who have neurodevelopmental disabilities (ND) in relation to early language acquisition usually involves comparisons with matched group(s) of typically developing individuals. In these studies, several important and complex issues need to be addressed. Three major issues are related to: (1) the choice of a variables on which to carry out group matching; (2) recruiting children into the study; and (3) the statistical analysis of the data. To assist future research on this topic, we discuss each of these three issues and provide recommendations about what we believe to be the best course of action. To provide a comprehensive review of the methodological issues, we draw on research beyond the topic of early language acquisition. Our overall aim is to contribute to research that considers questions about delay or differences in development patterns of development and about identifying potentially causal variables.


Hearing aid benefit in everyday environments.
Hearing aid benefit was measured for three matched groups of eleven hearing-impaired subjects, each serving in one typical listening environment. Benefit was quantified in terms of improvement in intelligibility score for the Connected Speech Test. Each subject was individually fitted with three hearing aids, differing in nominal frequency response slope by a total of 8 dB/octave. Research questions centered on the amount of benefit typically realized in everyday environments and the interactions of this benefit with frequency response and/or visual cues. Results revealed: (1) mean benefit in a living-room type setting was about 24% and significantly greater than in a reverberant setting (7%) and a noisy setting (-1%); (2) despite the relatively large mean difference in benefit between the reverberant and noisy environments, the difference was not statistically significant (p greater than 0.05); (3) the addition of visual cues did not change hearing aid benefit in any tested environment; (4) there was no significant overall trend for any of the three different frequency-response slopes to give superior benefit in any environment; (5) 76% of the subjects achieved significantly different benefit (p less than 0.05) in at least one hearing aid condition when data were considered on an individual basis; and (6) articulation indices in the aided conditions did not successfully predict the observed within-subject benefit differences. Benefit was significantly related to speech reception threshold in the living-room environment. However, in the less favorable environments, benefit and hearing loss were not related despite the fact that benefit varied considerably across subjects.


Helicobacter pylori Immune Response in Children Versus Adults.
H. pylori is perhaps the most prevalent human pathogen worldwide and infects almost half of the world's population. Despite the decreasing prevalence of infection overall, it is significant in developing countries. Most infections are acquired in childhood and persist for a lifetime unless treated. Children are often asymptomatic and often develop a tolerogenic immune response that includes T regulatory cells and their products, immunosuppressive cytokines, such as interleukin (IL)-10, and transforming growth factor-β (TGF-β). This contrasts to the gastric immune response seen in H. pylori-infected adults, where the response is mainly inflammatory, with predominant Th1 and Th17 cells, as well as, inflammatory cytokines, such as TNF-α, IFN-γ, IL-1, IL-6, IL-8, and IL-17. Therefore, compared to adults, infected children generally have limited gastric inflammation and peptic ulcer disease. H. pylori surreptitiously subverts immune defenses to persist in the human gastric mucosa for decades. The chronic infection might result in clinically significant diseases in adults, such as peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. This review compares the infection in children and adults and highlights the H. pylori virulence mechanisms responsible for the pathogenesis and immune evasion.


Influence of vitamin D3 deficiency and 1,25 dihydroxyvitamin D3 on de novo insulin biosynthesis in the islets of the rat endocrine pancreas.
Because 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) is known to activate the biosynthesis of numerous proteins in various tissues, experiments were undertaken to compare the influence of 1,25(OH)2D3 in vitro on both the secretion and biosynthesis of insulin in islets of Langerhans from both 4-week vitamin D3-deficient rats and normal rats. Islets were either incubated or perifused after a 6-h induction period in the presence of various concentrations of 1, 25(OH)2D3 from 10(-12) M, which was inactive in controls, to 10(-6) M. Experiments were performed in the presence of a non-labelled amino acid mixture, to favour protein synthesis. Tritiated tyrosine was added as tracer during glucose stimulation. The newly synthesised proteins, labelled with [3H]tyrosine, were extracted by an acid-alcohol method and separated by gel chromatography adapted for low-molecular-weight proteins. Even in the presence of the amino acid mixture, the insulin response of the islets to 16.7 mM glucose was decreased by vitamin D3 deficiency and improved by 1,25(OH)2D3. This beneficial effect did not occur in basal conditions, but only during glucose stimulation, and was observed in both phases of insulin release. Moreover, these effects disappeared in the presence of 5x10(-4 )M cycloheximide, a protein biosynthesis inhibitor. Islets from vitamin D3-deficient rats exhibited a general decrease in the amount of de novo biosynthesised proteins and of [3H]tyrosine-labelled insulin and proinsulin fractions. A 6-h period of 1,25(OH)2D3 induction significantly improved the amount of de novo biosynthesised proteins, and particularly of newly synthesised insulin in response to a 2-h glucose stimulation. Calculation of the rate of conversion of newly synthesised proinsulin-like material to insulin as the [3H]insulin/[3H]proinsulin-like material ratio provided evidence for a dose-dependent increase, induced by 1, 25(OH)2D3, that could exceed that of normal islets. These data support the hypothesis that 1,25(OH)2D3 in vitro not only facilitated the biosynthetic capacity of the beta cell - which was highly induced during a 16.7-mM glucose stimulation, via a global activation of islets protein biosynthesis - but also produced an acceleration of the conversion of proinsulin to insulin.


Elevated Oxidative Stress in Patients with Congenital Heart Disease and the Effect of Cyanosis: A Meta-Analysis.
Oxidative stress is an important pathophysiological mechanism in the development of numerous cardiovascular disorders. To improve therapy and preventive strategies, clinicians need a better understanding of the underlying pathophysiological mechanisms of congenital heart diseases (CHD). The objective of this meta-analysis was to determine whether oxidative stress is elevated in patients with CHD compared to healthy controls, and to evaluate whether a difference in oxidative stress parameters can be observed between patients with cyanotic (cCHD) and acyanotic CHD (aCHD). Therefore, 21 studies investigating oxidative stress in peripheral blood of both children and adults with CHD were reviewed. Different methods to assess the oxidant status were compared and divided into three categories: pro-oxidative or anti-oxidative stress markers and the ratio of pro-to-anti oxidative stress markers.This meta-analysis showed elevated oxidative stress levels in patients with CHD, and more specifically in patients with cCHD. Moreover, this indicates that there could be potential in oxidative stress measurements as a new biomarker of disease severity. Further research will be needed to clarify the exact role of oxidative stress and its contributors in CHD in order to get a better and more in-depth understanding of the underlying pathophysiology of CHD, especially the higher susceptibility of the right ventricle (RV) to progress to heart failure (HF). This could facilitate the development of antioxidant treatments and RV-specific HF therapies, which are necessary to improve survival in these patients and could be of particular importance in cCHD.


Growth and biochemical markers of growth in children with snoring and obstructive sleep apnea.
The pathophysiological mechanisms of growth impairment frequently associated with the obstructive sleep apnea syndrome (OSAS) in children are poorly defined. The main objective of this study was to evaluate whether nighttime upper airway obstruction attributable to adenotonsillar hypertrophy and subsequent surgical treatment affect the circulating concentrations of insulin-like growth factor-I (IGF-I) and IGF-binding protein 3 (IGFBP-3) along with other growth parameters in children. We initially studied 70 children (mean age: 5.8 years; range: 2.4-10.5 years) admitted to a university hospital because of clinical symptoms of OSAS. Their sleep was monitored with a 6-channel computerized polygraph. Data on anthropometry and circulating concentrations of IGF-I and IGFBP-3 were generated and compared with corresponding characteristics in control children (N = 35). Thirty children with an obstructive apnea-hypopnea index (OAHI) of 1 or more were categorized as children with OSAS (mean OAHI: 5.4 [95% confidence interval for mean (CI): 3.8-6.9]), whereas 40 children with an OAHI of <1 were considered as primary snorers (PS) (mean OAHI 0.13 [95% CI: 0.05-0.21]). Nineteen children with OAHI >2 underwent adenotonsillectomy attributable to OSAS and were reassessed 6 months later together with 34 nonoperated children with OAHI <2. There were no initial differences in relative height and weight for height between the 3 groups of children. No differences were observed in peripheral IGF-I concentrations, but both OSAS and PS children had reduced peripheral IGFBP-3 levels. The operated children with initial OSAS experienced a highly significant reduction in their OAHI from 7.1 (95% CI: 5.1-9.1) to 0.37 (95% CI: 0.2-0.95). Weight-for-height, body mass index, body fat mass, and fat-free mass increased during the follow-up in the operated children with OSAS, whereas only fat-free mass and relative height increased in the PS children. Both the IGF-I and the IGFBP-3 concentrations increased significantly in the operated children, whereas no significant changes were seen in the PS children. These observations indicate that growth hormone secretion is impaired in children with OSAS and PS. Respiratory improvement after adenotonsillectomy in children with OSAS results in weight gain and restored growth hormone secretion.


Effect of Same-Sex Marriage Referendums on the Suicidal Ideation Rate among Nonheterosexual People in Taiwan.
: Taiwan held voter-initiated referendums to determine same-sex marriage legalization on 24 November 2018. This study aims to compare suicidal ideation rates in heterosexual and nonheterosexual participants of a first-wave survey (Wave 1, 23 months before the same-sex marriage referendums) and a second-wave survey (Wave 2, one week after the same-sex marriage referendums) in Taiwan and to examine the influence of gender, age, and sexual orientation on the change in suicidal ideation rates in nonheterosexual participants. In total, 3286 participants in Wave 1 and 1370 participants in Wave 2 were recruited through a Facebook advertisement. Each participant completed an online questionnaire assessing suicidal ideation. The proportions of heterosexual and nonheterosexual participants with suicidal ideation were compared between the Wave 1 and Wave 2 surveys. Suicidal ideation rates between participants in the Wave 1 and Wave 2 surveys were further compared by stratifying nonheterosexual participants according to gender, age, and sexual orientation. Nonheterosexual participants in the Wave 2 survey had a higher suicidal ideation rate than those in the Wave 1 survey, whereas no difference was observed in suicidal ideation rates between heterosexual participants in Wave 2 and Wave 1. Nonheterosexual participants who were female, younger, gay, lesbian, and bisexual in Wave 2 had a higher suicidal ideation rate than those in Wave 1. The suicidal ideation rate significantly increased in nonheterosexual participants experiencing the same-sex marriage referendums in Taiwan. Whether civil rights of sexual minority individuals can be determined through referendums should be evaluated.


The effects of serotonin depletion and raphe grafts on hippocampal electrophysiology and behavior.
The involvement of the serotonergic system in spatial learning and a possible correlation between serotonergic modulation of hippocampal electrical activity and spatial learning were studied in rats. Control, partial septal-lesioned (SL), 5,7-dihydroxytryptamine (5,7-DHT)-injected (DHT), double-lesioned (5,7-DHT and SL; DL), and DL rats that were transplanted with embryonic raphe grafts into the hippocampus (RG) were tested in a spatial task in a water maze and in an active avoidance shuttle-box task. The responses of the dentate gyrus (DG) to perforant-path (PP) stimulation were examined in the same rats, under the following conditions: (1) priming stimulation of the PP (testing feedback inhibition), (2) priming stimulation of the commissural pathway (testing feedforward inhibition), (3) during repeated stimulation of the PP at 7 Hz (frequency potentiation), and (4) following tetanic stimulation [long-term potentiation (LTP)]. DL, but not DHT or SL, treatment severely impaired the performance of rats in both reference- and working-memory tasks in the water maze. This effect was not seen in the shuttle box. The ability of the DG to exhibit LTP, which was reduced in the DHT and SL rats, was apparently similar to controls in the DL group, DL, but not DHT or SL alone, resulted in a reduction of inhibition in the DG. Both the behavioral deficits and the reduction in hippocampal inhibition were ameliorated by intrahippocampal raphe grafts. These results indicate that the serotonergic innervation of the hippocampus plays a role in spatial learning when the septohippocampal neurotransmission systems are disrupted. Furthermore, these results suggest that restoration of modulation of hippocampal inhibition, by raphe grafts, underlies the behavioral recovery observed in these rats.


Cytogenetic damage after ischemia and reperfusion.
Tourniquets are often used to provide a bloodless operating field. However, they carry the risk of adverse effects caused by DNA damage from the free radicals generated during postischemic reperfusion of the blood. The aim of this study was to evaluate the cytogenetic damage caused by postischemic reperfusion on peripheral lymphocytes of five women and six men undergoing total knee arthroplasty "bloodless" operation using samples received before, during, immediately, and 1 h after the operations. The sister chromatid exchange assay was applied to peripheral blood lymphocyte cultures and the levels of sister chromatid exchanges were analyzed as a quantitative index of genotoxicity, along with the values of mitotic index and proliferation rate index as qualitative indices of cytotoxicity and cytostaticity, respectively. We observed that postischemic reperfusion induced cytogenetic damages specifically through reperfusion. DNA effects were most pronounced after tourniquet release and declined afterward without returning to preischemic baseline values. Our findings suggest the presence of a functional association between postischemic reperfusion and cytogenetic damage that may have important clinical implications.


Coronavirus IBV: structural characterization of the spike protein.
The spike protein (S; surface projection) of avian infectious bronchitis virus (IBV) strain M41 comprises two glycopolypeptides, S1 (mol. wt. 90 X 10(3] and S2 (mol. wt. 84 X 10(3], in equimolar proportions. The apparent mol. wt. of S was calculated as 354 (+/- 17) X 10(3) following co-sedimentation with catalase in sucrose gradients. Incubation of radiolabelled IBV with urea resulted in the removal of most S1, but none of S2, from the virus particle. A similar result was obtained using low concentrations of SDS, although some nucleocapsid, but not matrix, protein was also released. 2% SDS alone was as effective as 2% SDS plus 2% 2-mercaptoethanol for the separation of S1 and S2 prior to SDS-polyacrylamide gel electrophoresis. Dithiothreitol did not remove S from virions but did decrease the buoyant density of the virus from 1.18 g/ml to 1.16 g/ml, and changed the configuration of S. It is concluded that IBV S protein is an oligomer comprising two copies of each of S1 and S2, although the possibility that there are three copies of each glycopolypeptide cannot be discounted. S is attached to the membrane by S2, while S1 has little or no contact with the membrane and may form the major part of the bulbous end of S. Interpeptide disulphide bonds do not occur in S, and the association of S1 and S2 is weak.


Unraveling FATP1, regulated by ER-β, as a targeted breast cancer innovative therapy.
The biochemical demands associated with tumor proliferation prompt neoplastic cells to augment the import of nutrients to sustain their survival and fuel cell growth, with a consequent metabolic remodeling. Fatty acids (FA) are crucial in this process, since they have a dual role as energetic coins and building blocks. Recently, our team has shown that FATP1 has a pivotal role in FA transfer between breast cancer cells (BCCs) and non-cancerous cells in the microenvironment. We aimed to investigate the role of FATP1 in BCCs and also to explore if FATP1 inhibition is a promising therapeutic strategy. In patients' data, we showed a higher expression of FATP1/SLC27A1 in TNBC, which correlated with a significant decreased overall survival (OS). In vitro, we verified that FA and estradiol stimulated FATP1/SLC27A1 expression in BCCs. Additionally, experiments with estradiol and PHTPP (ER-β antagonist) showed that estrogen receptor-β (ER-β) regulates FATP1/SLC27A1 expression, the uptake of FA and cell viability, in four BCC lines. Furthermore, the inhibition of FATP1 with arylpiperazine 5k (DS22420314) interfered with the uptake of FA and cell viability. Our study, unraveled FATP1 as a putative therapeutic target in breast cancer (BC).


Using a data mining approach to discover behavior correlates of chronic disease: a case study of depression.
The purposes of this methodological paper are: 1) to describe data mining methods for building a classification model for a chronic disease using a U.S. behavior risk factor data set, and 2) to illustrate application of the methods using a case study of depressive disorder. Methods described include: 1) six steps of data mining to build a disease model using classification techniques, 2) an innovative approach to analyzing high-dimensionality data, and 3) a visualization strategy to communicate with clinicians who are unfamiliar with advanced statistics. Our application of data mining strategies identified childhood experience living with mentally ill and sexual abuse, and limited usual activity as the strongest correlates of depression among hundreds variables. The methods that we applied may be useful to others wishing to build a classification model from complex, large volume datasets for other health conditions.


Venezuelan equine encephalitis.
Venezuelan equine encephalitis virus (VEEV) remains a naturally emerging disease threat as well as a highly developed biological weapon. Recently, progress has been made in understanding the complex ecological and viral genetic mechanisms that coincide in time and space to generate outbreaks. Enzootic, equine avirulent, serotype ID VEEV strains appear to alter their serotype to IAB or IC, and their vertebrate and mosquito host range, to mediate repeated VEE emergence via mutations in the E2 envelope glycoprotein that represent convergent evolution. Adaptation to equines results in highly efficient amplification, which results in human disease. Although epizootic VEEV strains are opportunistic in their use of mosquito vectors, the most widespread outbreaks appear to involve specific adaptation to Ochlerotatus taeniorhynchus, the most common vector in many coastal areas. In contrast, enzootic VEEV strains are highly specialized and appear to utilize vectors exclusively in the Spissipes section of the Culex (Melanoconion) subgenus.


Microplastics in coastal urban sediments: Discrepancies in concentration and character revealed by different approaches to sample processing.
Intertidal, silty sediment samples have been collected from three coastal locations with different uses and anthropogenic signatures in the vicinity of Plymouth, southwest England, and analysed for microplastics (MPs) by two independent means. Firstly, MPs were counted and characterised directly on unprocessed dried sediment under a stereo microscope, and secondly MPs were isolated from sediment by flotation in ZnCl2 solution and filtration before analysis. Direct counting resulted in average (± one standard deviation) numbers of MPs per g of dry sediment of 0.77 ± 0.16 at a marina-harbour, 0.58 ± 0.30 under a busy road bridge and 0.79 ± 0.43 adjacent to country parkland. After flotation and filtration, concentrations were reduced to 0.24 ± 0.11, 0.18 ± 0.06 and 0.48 ± 0.38 MP g-1, respectively. Observations were attributed to hetero-aggregation of small fibres with settling sediment during flotation, and the presence of MPs (including paints) that were too dense to float or that had aggregated or agglomerated with denser sediment and construction material in situ. The findings have implications for the efficacy of flotation procedures, accurate estimations of MP concentrations in sediment and the representativeness of MPs by type, and inter-site comparisons of MPs that are widely reported in the literature.


Effect of parenteral lipid emulsion on preterm infant PUFAs and their downstream metabolites.
Oxylipins synthesized by oxidation of long-chain polyunsaturated fatty acids (LCPUFAs) are bioactive downstream lipid mediators. The aim of this study was to describe oxylipin levels in preterm infants born 30 to 33 weeks' gestation who were enrolled in a randomized controlled trial in which peripheral parenteral nutrition (P-PN), including lipid emulsion (containing soy, medium chain triglyceride, olive and fish oil), was compared with 10% glucose on growth during the transition to enteral feeds. Of the 92 infants randomized to the P-PN study, the first 72 (P-PN n = 34, control n = 38) had blood taken for fatty acid analyses. P-PN infants received parenteral nutrition including 3% protein, 8% glucose and 17% SMOFlipid® lipid (containing soy, medium chain triglyceride, olive and fish oil), and control infants 10% glucose. Both groups commenced enteral feeds when clinically stable. 32 oxylipins and 5 free fatty acids were screened (using ultra-high-performance liquid chromatography-tandem mass spectrometry), and 5 total LCPUFA were measured (using gas chromatography), on study days 1 (baseline), 2, 4, 7, 14 and 21. Both total and free LA, ALA and EPA were significantly higher in the P-PN group compared with control over the first week of life. Whereas total AA was significantly lower and free DHA significantly higher over the same time period. All LA, ALA, EPA and four DHA derived oxylipins detected were significantly higher in the P-PN group compared with the control group during the first week of life, with three AA derived oxylipins significantly lower and one significantly higher. Parenteral lipid emulsion resulted in a change in total and free fatty acids and related oxylipins with the profiles suggesting increased omega-6 driven inflammation. Further studies to investigate the association between the oxylipin levels and nutrition and to determine whether the oxylipin profiles influence the clinical outcome in preterm infants are warranted.


Retinal Phenotype in the rd9 Mutant Mouse, a Model of X-Linked RP.
Retinal degeneration 9 (rd9) mice carry a mutation in the retina specific "Retinitis Pigmentosa GTPase Regulator (RPGR)" Open Reading Frame (ORF) 15 gene, located on the X chromosome and represent a rare model of X-linked Retinitis Pigmentosa (XLRP), a common and severe form of retinal degeneration (Wright et al., 2010; Tsang and Sharma, 2018). The rd9 RPGR-ORF15 mutation in mice causes lack of the protein in photoreceptors and a slow degeneration of these cells with consequent decrease in Outer Nuclear Layer (ONL) thickness and amplitude of ERG responses, as previously described (Thompson et al., 2012). However, relative rates of rod and cone photoreceptor loss, as well as secondary alterations occurring in neuronal and non-neuronal retinal cell types of rd9 mutants remain to be assessed. Aim of this study is to extend phenotype analysis of the rd9 mouse retina focusing on changes occurring in cells directly interacting with photoreceptors. To this purpose, first we estimated rod and cone survival and its degree of intraretinal variation over time; then, we studied the morphology of horizontal and bipolar cells and of the retinal pigment epithelium (RPE), extending our observations to glial cell reactivity. We found that in rd9 retinas rod (but not cone) death is the main cause of decrease in ONL thickness and that degeneration shows a high degree of intraretinal variation. Rod loss drives remodeling in the outer retina, with sprouting of second-order neurons of the rod-pathway and relative sparing of cone pathway elements. Remarkably, despite cone survival, functional defects can be clearly detected in ERG recordings in both scotopic and photopic conditions. Moderate levels of Muller cells and microglial reactivity are sided by striking attenuation of staining for RPE tight junctions, suggesting altered integrity of the outer Blood Retina Barrier (BRB). Because of many features resembling slowly progressing photoreceptor degeneration paradigms or early stages of more aggressive forms of RP, the rd9 mouse model can be considered a rare and useful tool to investigate retinal changes associated to a process of photoreceptor death sustained throughout life and to reveal disease biomarkers (e.g., BRB alterations) of human XLRP.