Difference in persistent tuberculosis bacteria between in vitro and sputum from patients: implications for translational predictions.
This study aimed to investigate the number of persistent bacteria in sputum from tuberculosis patients compared to in vitro and to suggest a model-based approach for accounting for the potential difference. Sputum smear positive patients (n = 25) provided sputum samples prior to onset of chemotherapy. The number of cells detected by conventional agar colony forming unit (CFU) and most probable number (MPN) with Rpf supplementation were quantified. Persistent bacteria was assumed to be the difference between MPNrpf and CFU. The difference in persistent bacteria between in vitro and human sputum prior to chemotherapy was quantified using different model-based approaches. The persistent bacteria in sputum was 17% of the in vitro levels, suggesting a difference in phenotypic resistance, whereas no difference was found for multiplying bacterial subpopulations. Clinical trial simulations showed that the predicted time to 2 log fall in MPNrpf in a Phase 2a setting using in vitro pre-clinical efficacy information, would be almost 3 days longer if drug response was predicted ignoring the difference in phenotypic resistance. The discovered phenotypic differences between in vitro and humans prior to chemotherapy could have implications on translational efforts but can be accounted for using a model-based approach for translating in vitro to human drug response.


Nonequilibrium thermohydrodynamic effects on the Rayleigh-Taylor instability in compressible flows.
The effects of compressibility on Rayleigh-Taylor instability (RTI) are investigated by inspecting the interplay between thermodynamic and hydrodynamic nonequilibrium phenomena (TNE, HNE, respectively) via a discrete Boltzmann model. Two effective approaches are presented, one tracking the evolution of the local TNE effects and the other focusing on the evolution of the mean temperature of the fluid, to track the complex interfaces separating the bubble and the spike regions of the flow. It is found that both the compressibility effects and the global TNE intensity show opposite trends in the initial and the later stages of the RTI. Compressibility delays the initial stage of RTI and accelerates the later stage. Meanwhile, the TNE characteristics are generally enhanced by the compressibility, especially in the later stage. The global or mean thermodynamic nonequilibrium indicators provide physical criteria to discriminate between the two stages of the RTI.


Overcoming erlotinib resistance in EGFR mutation-positive non-small cell lung cancer cells by targeting survivin.
Loss of PTEN was recently shown to contribute to resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in EGFR mutation-positive non-small cell lung cancer (NSCLC) through activation of the protein kinase AKT. We previously showed that downregulation of the expression of the antiapoptotic protein survivin by EGFR-TKIs contributes to EGFR-TKI-induced apoptosis in EGFR mutation-positive NSCLC cells. We have now investigated the role of survivin expression in EGFR-TKI resistance induced by PTEN loss. The EGFR-TKI erlotinib did not affect survivin expression or induce apoptosis in EGFR mutation-positive NSCLC cells with PTEN loss. Downregulation of survivin either by transfection with a specific short interfering RNA or by exposure to the small-molecule survivin suppressor YM155 reversed erlotinib resistance in such cells in vitro. Furthermore, combination therapy with YM155 and erlotinib inhibited the growth of tumors formed by EGFR mutation-positive, PTEN-deficient NSCLC cells in nude mice to a greater extent than did treatment with either drug alone. These results thus indicate that persistent activation of signaling by the AKT-survivin pathway induced by PTEN loss underlies a mechanism of resistance to erlotinib-induced apoptosis in EGFR mutation-positive NSCLC. They further suggest that the targeting of survivin has the potential to overcome EGFR-TKI resistance in EGFR mutation-positive NSCLC.


Measurement of a Novel Biomarker, Secretory Phospholipase A2 Group IIA as a Marker of Sepsis: A Pilot Study.
Early identification of sepsis is critical as early treatment improves outcomes. We sought to identify threshold values of secretory phospholipase A2 (sPLA2)-IIA that predict sepsis and bacterial infection compared to nonseptic controls in an emergency department (ED) population. This is a prospective cohort of consenting adult patients who met two or more systemic inflammatory response syndrome (SIRS) criteria with clinical diagnosis of infectious source likely (septic patients). Controls were nonseptic consenting adults undergoing blood draw for other ED indications. Both groups had blood drawn, blind-coded, and sent to an outside laboratory for quantitative analysis of sPLA2-IIA levels. The study investigators reviewed patients' inpatient medical record for laboratory, imaging, and microbiology results, as well as clinical course. sPLA2-IIA levels were significantly lower in control patients as compared to septic patients (median = 0 ng/ml [interquartile range (IQR): 0-6.5] versus median = 123 ng/ml [IQR 44-507.75]; P < 0.0001). SPLA2-IIA levels were higher in patients with confirmed source (n = 28 patients, median = 186 ng/ml, 95% confidence interval = 115.1-516.8) as compared to those with no source identified or a viral source (n = 17, median = 68 ng/ml, 95% confidence interval = 38.1-122.7; P = 0.04). Using a cutoff value of 25 ng/ml, sPLA2-IIA had a sensitivity of 86.7% (confidence interval 72.5-94.5) and a specificity of 91.1% (confidence interval 77.9-97.1) in detecting sepsis. sPLA2-IIA shows potential as a biomarker distinguishing sepsis from other disease entities. Further study is warranted to identify predictive value of trends in sPLA-IIA during disease course in septic patients.


Effect of non-steroidal anti-inflammatory drugs on amyloid-beta formation and macrophage activation after platelet phagocytosis.
Recently, we showed that platelet phagocytosis occurs in human atherosclerotic plaques and leads to foam cell formation. Platelet phagocytosis, resulting in macrophage activation and iNOS induction, was associated with the formation of amyloid-beta peptide (Abeta) via proteolytic cleavage of platelet-derived amyloid precursor protein (APP), possibly by secretases. To test the involvement of gamma-secretase in this process, we used indomethacin, ibuprofen, and sulindac sulfide, non-steroidal anti-inflammatory drugs (NSAIDs) known to alter the gamma-secretase cleaving site of APP, on their ability to inhibit macrophage activation evoked by platelet phagocytosis. J774 macrophages were incubated with human platelets or lipopolysaccharide (LPS) with or without NSAIDs. Nitrite was quantified as a measure for inducible nitric oxide synthase (iNOS) activity. Indomethacin, ibuprofen, sulindac sulfide, and meloxicam concentration-dependently reduced nitrite production by macrophages incubated with platelets, but did not alter LPS-induced iNOS activity or platelet uptake. However, acetylsalicylic acid and naproxen, two NSAIDs without effect on the gamma-secretase cleaving site of APP, did not affect nitrite production in either platelet- or LPS-stimulated macrophages. Surface-enhanced laser desorption/ionization time-of-flight mass-spectrometry demonstrated time-dependent formation of Abeta-containing peptides after platelet phagocytosis, which could be inhibited by indomethacin. In conclusion, these results point to the involvement of gamma-secretase in macrophage activation following platelet phagocytosis.


Asymmetric Influence of Vocalic Context on Mandarin Sibilants: Evidence From ERP Studies.
In the present study, we examine the interactive effect of vowels on Mandarin fricative sibilants using a passive oddball paradigm to determine whether the HEIGHT features of vowels can spread on the surface and influence preceding consonants with unspecified features. The stimuli are two pairs of Mandarin words ([sa] ∼ [ʂa] and [su] ∼ [ʂu]) contrasting in vowel HEIGHT ([LOW] vs. [HIGH]). Each word in the same pair was presented both as standard and deviant, resulting in four conditions (/standard/[deviant]: /sa/[ʂa] ∼ /ʂa/[sa] and /su/[ʂu] ∼ /ʂu/[su]). In line with the Featurally Underspecified Lexicon (FUL) model, asymmetric patterns of processing were found in the [su] ∼ [ʂu] word pair where both the MMN (mismatch negativity) and LDN (late discriminative negativity) components were more negative in /su/[ʂu] (mismatch) than in /ʂu/[su] (no mismatch), suggesting the spreading of the feature [HIGH] from the vowel [u] to [ʂ] on the surface. In the [sa] ∼ [ʂa] pair, however, symmetric negativities (for both MMN and LDN) were observed as there is no conflict between the surface feature [LOW] from [a] to [ʂ] and the underlying specified feature [LOW] of [s]. These results confirm that not all features are fully specified in the mental lexicon: features of vowels can spread on the surface and influence surrounding unspecified segments.


Cardiopulmonary Exercise Test Parameters in Athletic Population: A Review.
Although still underutilized, cardiopulmonary exercise testing (CPET) allows the most accurate and reproducible measurement of cardiorespiratory fitness and performance in athletes. It provides functional physiologic indices which are key variables in the assessment of athletes in different disciplines. CPET is valuable in clinical and physiological investigation of individuals with loss of performance or minor symptoms that might indicate subclinical cardiovascular, pulmonary or musculoskeletal disorders. Highly trained athletes have improved CPET values, so having just normal values may hide a medical disorder. In the present review, applications of CPET in athletes with special attention on physiological parameters such as VO2max, ventilatory thresholds, oxygen pulse, and ventilatory equivalent for oxygen and exercise economy in the assessment of athletic performance are discussed. The role of CPET in the evaluation of possible latent diseases and overtraining syndrome, as well as CPET-based exercise prescription, are outlined.


[Aggression in the dental office].
In this study on aggression in the dental practice, 8 dentists and 1 dental nurse who had experienced aggression in their dental practice, were interviewed and filled out a questionnaire. They had responded to a call in 2 Dutch dental journals or were contacted through personal communication. The interviews show that aggression in particular can be expected in patients having not paid their expense account, non compliant patients, or in patients who often come too late or even do not show up at their appointments. Aggression also can appear when patients with toothache are told they cannot be helped immediately. Aggression seems predominantly connected to people under influence of alcohol or drugs, psychiatric patients and people having contacts in criminal circuits. Although the incidence seems relatively low, the occurrence of aggression always has a great impact on the dental team. Therefore it seems useful to study how dentists and their auxiliaries could act to prevent aggression.


Predictors in starting and stopping Internet use between 2002 and 2012 by Dutch adults 65 years and older.
Research has indicated the need to consider the ageing process with technology adoption by older adults. This study examined psychological, health, social and demographic predictors with starting and stopping Internet use by older adults (2002-2012). Data were used from the Longitudinal Aging Study Amsterdam, and Cox regression analyses were done to test predictors over time with starting or stopping Internet use. The results indicated that older adults starting to use the Internet (11.6%) outnumbered those who stopped (3.1%). Psychological, health, social and demographic predictors separately predicted starting and stopping Internet use. Starting use was predicted by lower age, higher education, normal cognition and living alone. The predictors in stopping use were being younger, having a high sense of mastery and being higher educated. The results need to be interpreted as indicative due to the small number of stoppers. Suggestions are made on how to improve usability.


Differential expression of sodium channel activities during the development of chick skeletal muscle cells in culture.
The expression of Na+ channels during differentiation of cultured embryonic chick skeletal muscle cells was investigated using saxitoxin (STX) and batrachotoxin (BTX), which previously have been shown to interact with distinct, separate receptor sites of the voltage-sensitive Na+ channel of excitable cells. In the present study, parallel measurements of binding of [3H]-STX (STX) and of BTX-activated 22Na+ uptake (Na influx) were made in order to establish the temporal relationship of the appearance of these two Na+ channel activities during myogenesis. Na influx was clearly measurable in 2-d cells; from day 3 to day 7 the maximum Na influx approximately doubled when measured with saturating BTX concentrations potentiated by Leiurus scorpion toxin, while the apparent affinity of BTX, measured without scorpion toxin, also increased. Saturable STX binding did not appear consistently until day 3; from then until day 7 the STX binding capacity increased about threefold, whereas the equilibrium dissociation constant (KD) decreased about fourfold. Although Na influx in cells of all ages was totally inhibited by STX or tetrodotoxin (TTX) at 10 microM, lower concentrations (2-50 nM) blocked the influx in 7-d cells much more effectively than that in 3-d cells, where half the flux was resistant to STX at 20-50 nM. Similar but smaller differences characterized the block by TTX. In addition, when protein synthesis is inhibited by cycloheximide, both Na influx and STX binding activities disappear more rapidly in 3-d than in 7-d cells, which shows that these functions are less stable metabolically in the younger cells.


Continuum of care in hard-to-heal wounds by copper dressings: a case series.
The quest for an ideal wound dressing has been a longstanding challenge due to the complex nature of wound healing, including stages of haemostasis, inflammation, maturation and remodelling, with overlapping timelines. This makes it difficult to find a single dressing that optimally supports all phases of wound healing. In addition, the ideal wound dressing should possess antibacterial properties and be capable of effectively debriding and lysing necrotic tissue. Copper is an essential trace element that participates in many of the key physiological wound healing processes. Copper stimulates secretion of various cytokines and growth factors, thus promoting angiogenesis, granulation tissue formation, extracellular matrix proteins secretion and re-epithelialisation. Harnessing this knowledge, we have used copper oxide-impregnated wound dressings in numerous cases and observed their benefits throughout the entire wound healing process. This led us to postulate the 'continuum of care' hypothesis of copper dressings. In this study we describe four cases of hard-to-heal wounds of various aetiologies, in which we applied copper dressings consistently across all stages of wound healing, with rapid uneventful healing. We believe we have successfully implemented the continuum of care principle.


Can the Copenhagen Adduction Exercise Prevent Groin Injuries in Soccer Players? A Critically Appraised Topic.
Injuries that affect the groin region are among the most common in football players. To prevent this condition, studies have focused on strengthening the adductors, hip flexors, or abdominal muscles. Recent investigations have used an eccentric-biased exercise (Copenhagen Adduction Exercise [CAE]) that promotes functional and architectural adaptations in the muscle tissue, though its effect on injury risk reduction is unknown. Can the Copenhagen Adduction Exercise prevent groin injuries in soccer players? The literature was searched for studies investigating the potential groin injury risk reduction effect of the CAE. (1) Three studies met the inclusion criteria and were used for this appraisal; (2) one study observed a significantly lower injury rate ratio favoring the group that used the CAE program; and (3) 2 studies found similar or higher injury rates in the intervention groups, not supporting the inclusion of the CAE as a preventative tool. There is conflicting evidence that usage of the CAE is superior to not performing adductor strengthening exercises in mitigating the risk of sustaining groin injuries. Given the evidence supporting these findings, it is advisable to exercise caution when contemplating the incorporation of the CAE into training regimens aimed at preventing groin injuries. There is Grade B evidence to suggest that inclusion of the CAE may not be associated with reduced injury rates.


Extracellular cytochrome nanowires appear to be ubiquitous in prokaryotes.
Electrically conductive appendages from the anaerobic bacterium Geobacter sulfurreducens, recently identified as extracellular cytochrome nanowires (ECNs), have received wide attention due to numerous potential applications. However, whether other organisms employ similar ECNs for electron transfer remains unknown. Here, using cryoelectron microscopy, we describe the atomic structures of two ECNs from two major orders of hyperthermophilic archaea present in deep-sea hydrothermal vents and terrestrial hot springs. Homologs of Archaeoglobus veneficus ECN are widespread among mesophilic methane-oxidizing Methanoperedenaceae, alkane-degrading Syntrophoarchaeales archaea, and in the recently described megaplasmids called Borgs. The ECN protein subunits lack similarities in their folds; however, they share a common heme arrangement, suggesting an evolutionarily optimized heme packing for efficient electron transfer. The detection of ECNs in archaea suggests that filaments containing closely stacked hemes may be a common and widespread mechanism for long-range electron transfer in both prokaryotic domains of life.


Diallyl trisulfide ameliorates arsenic-induced hepatotoxicity by abrogation of oxidative stress, inflammation, and apoptosis in rats.
The present study investigates the possible ameliorative effects of diallyl trisulfide (DATS) against arsenic (As)-induced hepatotoxicity and oxidative stress in rats. The four experimental groups evaluated include: (1) vehicle control; (2) As (5 mg/kg/day); (3) DATS (80 mg/kg/day) + As; and (4) DATS. Induction of As in rats caused severe hepatotoxicity as evidenced by an elevation of serum aspartate aminotransferase and alanine aminotransferase activities and increased total bilirubin concentration, indicating hepatic function abnormalities. Histopathological examination revealed various structural changes in the liver, characterized by hepatocyte degeneration/necrosis, congestion, sinusoidal dilatation, vacuolation, and inflammatory cell infiltration. The significant decrease in reduced glutathione content, catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities and the significant increase in lipid peroxidation (thiobarbituric acid reactive substance) and protein oxidation (protein carbonyl) contents indicated that As-induced hepatotoxicity was mediated through oxidative stress. As intoxication also elevated the levels of Cas-3 and nitric oxide and increased the expression of nuclear factor-κB p65 in the liver. In contrast, DATS pretreatment significantly improved As-induced serum biochemical, immunohistochemical, and histopathological alterations reflecting hepatic dysfunction. These results may contribute to a better understanding of the hepatoprotective role of DATS, emphasizing the influence of this garlic trisulfide in the diet for human health, possibly preventing the hepatic injury associated with As intoxication, presumably due to its ability to inhibit lipid peroxidation, protein oxidation, and restoration of antioxidant status.


Reduced susceptibility to chlorhexidine in staphylococci: is it increasing and does it matter?
Antiseptic agents are increasingly used for hand hygiene and skin decolonization as key tools for the prevention of healthcare-associated infections. Chlorhexidine, a divalent, cationic biguanide, has a broad spectrum of activity and is one of the most frequently used topical antiseptic agents. Notably, there are an increasing number of prevalence studies that report reduced levels of susceptibility to chlorhexidine. In contrast to bacterial resistance to antibiotics, using parameters such as the MIC to define resistance to antiseptics, including chlorhexidine, is not straightforward. A range of methods have been used for the detection of reduced susceptibility to chlorhexidine, but, importantly, there is no standardized method and no consensus on the definition of chlorhexidine 'resistance'. In this review we have assessed the methods available for the detection of reduced susceptibility to chlorhexidine and the prevalence of coresistance to other antimicrobial agents. We have focused on the development of reduced susceptibility to chlorhexidine and the presence of efflux-mediated resistance genes in staphylococci, and have reviewed the clinical significance of this phenomenon. Lastly, we have identified unanswered questions to further our understanding of this emergent threat. We anticipate that clinical use of chlorhexidine will continue to increase, and it will be important to be alert to the possibility that this may lead to the emergence of new clones with reduced susceptibility. Indiscriminate chlorhexidine use in the absence of efficacy data should be discouraged.


The syngeneic mixed leukocyte reaction: an autoreactive self-renewing cellular network for mature T lymphocytes.
The functional properties of responding T lymphocytes and the nature of the antigenic stimulus in the guinea pig Syngeneic Mixed Leukocyte Reaction (SMLR) are reviewed. The evidence presented here indicates that the SMLR is a polyclonal T cell proliferative response of several distinct antigen-specific clones by virtue of their reactivity with self Ia (I-region-encoded antigens) molecules expressed by accessory cells. Clonal analysis of SMLR-responding cells indicates that individual T cell colonies proliferate in response to syngeneic, unmodified macrophages, but not in response to I-region-disparate macrophages. This autoreactive response of T cell colonies cannot be ascribed to exposure to any extrinsic antigen, and is completely blocked by monoclonal anti-Ia antibodies. Each individual SMLR-T cell colony recognizes a particular Ia epitope on the autologous stimulating cell. Clonal analysis of extrinsic antigen-specific responses revealed three types of proliferating T cell colonies: antigen-specific, Ia-restricted; autoreactive, Ia-restricted; and antigen-specific/autoreactive, Ia-restricted. The finding of T cell colonies with antigen specificity but that could also be stimulated by Ia alone lends support to the hypothesis that the SMLR is a polyclonal T cell response to self Ia molecules. The possible in vivo attributes of the SMLR, and its main effector and regulatory mechanisms are discussed in terms of these findings.


Phytochemical, in-vitro biological and chemo-preventive profiling of Arisaema jacquemontii Blume tuber extracts.
Arisaema jacquemontii is traditionally used in treatment of different diseases. In this study, phytochemical, in vitro biological and chemo-preventive screening of A. jacquemontii was carried out to explore its pharmacological potential. The dried tuber of A. jacquemontii was extracted in 11 organic solvent mixture of different polarity. The extracts were screened for phytochemical assays (phenolics and flavonoids), antioxidants potential (free radical scavenging activity, total antioxidant activity, reducing power), biological activities (antibacterial, antifungal, cytotoxic, antileishmanial, protein kinase inhibition), and chemopreventive activities using different cell lines through standard protocols. Significant amount phenolic contents were determined in EtOH and MeOH extracts (210.3 ± 3.05 and 193.2 ± 3.15 μg GAE/mg, respectively). Maximum flavonoid content was determined in MeOH extract (22.4 ± 4.04 μg QE/mg). Noteworthy, DPPH scavenging activity was also recorded for MeOH extract (87.66%) followed by MeOH+EtOAc extract (85.11%). Considerable antioxidant capacity (7.8 ± 0.12 μg AAE/mg) and reducing power (3.1 ± 0.15 μg AAE/mg) was observed in extract of MeOH. The LC50 against brine shrimp and leishmanial parasite was found 9.01 and 12.87 μg/mL for n-Hex and CHCl3 extracts, respectively. The highest zone of inhibition against Streptomyces hyphae formation (12.5 ± 1.77 mm) by n-Hex extract. Growth zone of inhibition 13.8 ± 1.08 mm was recorded for EtOAc and MeOH extracts, respectively against Micrococcus luteus while 10.0 ± 0.11 mm for MeOH extract against Aspergillus flavus. In-vitro cytotoxic assay showed that n-Hex extract had higher cytotoxicity against DU-145 prostate cancer and HL-60 cancer cell lines. NF-kB and MTP potential showed 34.01 and 44.87 μg/mL for n-Hex and CHCl3 extracts, respectively in chemo-preventive potential. The study concludes that Arisaema jacquemontii bears significant phytochemical activity and pharmacological activities, this plant can be further explored for isolation of active component against a number of aliments.


Multifunctional, polymorphic, ionic fullerene supramolecular materials: self-assembly and thermotropic properties.
An N-methylfulleropyrrolidine (2) bearing three eicosyloxy chains on the laterally substituted phenyl group can be further functionalized to give the ionic fullerene derivative, i.e., N,N-dimethylfulleropyrrolidinium iodide (1). The spectroscopic, electrochemical, self-assembly, and liquid crystalline properties of 1 have been investigated and compared to its neutral precursor 2. Changes in electronic structure upon ionization are observed in the UV spectra. Additionally, a positive potential shift of electrochemical reductions for 1 compared to those of 2 is noted in both homogeneous solution and film state. Driven by the π-π, van der Waals, and electrostatic interactions, the ionic compound 1 is able to form a variety of functional and polymorphic self-assembled structures both from solution and on substrates, including hierarchically organized flakelike microparticles with high water repellency, doughnut-shaped objects with rough surfaces, and long one-dimensional C(60) nanowires (>1 μm). The thermotropic behavior of 1 has also been investigated, and a smectic liquid crystalline phase was observed at elevated temperatures. Further investigations of the thermotropic behavior of 1 revealed that a deionization back-reaction from 1 to the neutral precursor 2 gradually occurred. The mechanism of this deionization reaction is presented and discussed. These investigations provide insight into the effects of added ionicity to alkylated fullerene derivatives, in particular on their self-assembly features and functionality.


Gastric adenocarcinoma of fundic gland type (chief cell predominant type): proposal for a new entity of gastric adenocarcinoma.
Only a few cases of gastric adenocarcinoma of fundic gland type have been reported. Gastric adenocarcinoma with chief cell differentiation (GA-CCD) has been recently reported as a new variant of gastric adenocarcinoma. However, its clinicopathologic features are uncertain. To elucidate them, GA-CCDs exhibiting pepsinogen-I expression (10 lesions: Group A) and randomly selected gastric adenocarcinomas of differentiated type (111 lesions: Group B) were evaluated in this study. Cell differentiation by MUC2, MUC5AC, MUC6, CD10, pepsinogen-I, H+/K+-ATPase and chromogranin A, cell proliferation by Ki-67, and overexpression of p53 protein were evaluated immunohistochemically. In Group A, all GA-CCDs were located in the upper third of the stomach. Tumors were small, with the average maximum diameter ranging from 4 to 20 (average, 8.6) mm. Histologically, GA-CCDs were well-differentiated adenocarcinomas composed of pale gray-blue, basophilic columnar cells with mild nuclear atypia, resembling chief cells. Immunohistochemically, scattered positivity for H+/K+-ATPase was observed in addition to expression of pepsinogen-I and MUC6, indicating focal differentiation toward parietal cells. In Group B, pepsinogen-I was very focally expressed in 2 cases. As these 2 cases exhibited different clinicopathological and histologic features, they cannot be categorized as GA-CCD. Mild atypism, no lymphovascular invasion, low proliferative activity, no overexpression of p53, and no recurrence indicated less aggressiveness of GA-CCD. GA-CCD is rare, but it has distinct clinicopathological characteristics, especially in terms of tumor location, histologic features, phenotypic expression, and low-grade malignancy. We propose gastric adenocarcinoma of fundic gland type (chief cell predominant type) as a new entity of gastric adenocarcinoma.


Precision of cell density estimates and endothelial cell loss with age.
The precision of estimating endothelial cell density of the cornea, using a noncontact method of specular microscopy, was assessed by asking eight individuals with known densities in one operated-on and one unoperated-on eye to have photography on two occasions in the same day. Three photographs of each eye were assessed by two individuals using masking procedures. Interobserver differences were negligible and estimates were similar except for one eye with low density values. The method was applied to a natural history study in which 103 eyes had cell-density estimates at zero and two years, and mean cell loss was found to be 2%. A collateral study using only good photographs that were available at both zero and two years showed a similar loss of 1.86% and reduced the number of counts showing unexpectedly high gains and losses.


Integrated transcriptomic and epigenomic analysis of primary human lung epithelial cell differentiation.
Elucidation of the epigenetic basis for cell-type specific gene regulation is key to gaining a full understanding of how the distinct phenotypes of differentiated cells are achieved and maintained. Here we examined how epigenetic changes are integrated with transcriptional activation to determine cell phenotype during differentiation. We performed epigenomic profiling in conjunction with transcriptomic profiling using in vitro differentiation of human primary alveolar epithelial cells (AEC). This model recapitulates an in vivo process in which AEC transition from one differentiated cell type to another during regeneration following lung injury. Interrogation of histone marks over time revealed enrichment of specific transcription factor binding motifs within regions of changing chromatin structure. Cross-referencing of these motifs with pathways showing transcriptional changes revealed known regulatory pathways of distal alveolar differentiation, such as the WNT and transforming growth factor beta (TGFB) pathways, and putative novel regulators of adult AEC differentiation including hepatocyte nuclear factor 4 alpha (HNF4A), and the retinoid X receptor (RXR) signaling pathways. Inhibition of the RXR pathway confirmed its functional relevance for alveolar differentiation. Our incorporation of epigenetic data allowed specific identification of transcription factors that are potential direct upstream regulators of the differentiation process, demonstrating the power of this approach. Integration of epigenomic data with transcriptomic profiling has broad application for the identification of regulatory pathways in other models of differentiation.


Fully quantum mechanical energy optimization for protein-ligand structure.
We present a quantum mechanical approach to study protein-ligand binding structure with application to a Adipocyte lipid-binding protein complexed with Propanoic Acid. The present approach employs a recently develop molecular fractionation with a conjugate caps (MFCC) method to compute protein-ligand interaction energy and performs energy optimization using the quasi-Newton method. The MFCC method enables us to compute fully quantum mechanical ab initio protein-ligand interaction energy and its gradients that are used in energy minimization. This quantum optimization approach is applied to study the Adipocyte lipid-binding protein complexed with Propanoic Acid system, a complex system consisting of a 2057-atom protein and a 10-atom ligand. The MFCC calculation is carried out at the Hartree-Fock level with a 3-21G basis set. The quantum optimized structure of this complex is in good agreement with the experimental crystal structure. The quantum energy calculation is implemented in a parallel program that dramatically speeds up the MFCC calculation for the protein-ligand system. Similarly good agreement between MFCC optimized structure and the experimental structure is also obtained for the streptavidin-biotin complex. Due to heavy computational cost, the quantum energy minimization is carried out in a six-dimensional space that corresponds to the rigid-body protein-ligand interaction.


Age-dependent sexually asymmetric selection: the use of intrinsic values.
To study the evolutionary role played by differential male and female fertility (sexual asymmetry) both between individuals and over the life span within single individuals, the terms "intrinsic male fertility" and "intrinsic female fertility" are introduced. With the help of these terms, the concept of sexual asymmetry can be made precise and its effect on the establishment and maintenance of genetic polymorphisms can be analyzed. The main conclusions are: (1) any mutant causing a modification of the male fertility parameters which result in an increased intrinsic male fertility becomes established; (2) a corollary of this is that age-specific sexual asymmetry, as results from alternating degrees of female and male flowering in successive reproduction cycles, for example, has only secondary effects on the initial growth rate; (3) under the biologically reasonable premise that modifications of life histories result from reallocation of fixed net reproduction resources (defined as constant total female and male net reproduction output), a shift of net reproduction (whether female, male, or both in arbitrary proportions) to earlier ages is evolutionarily successful in growing but not in declining populations; shifts of net reproduction to later ages have opposite consequences.


Pediatric central nervous system germ cell tumors: a review.
Central nervous system (CNS) germ cell tumors (GCTs) represent approximately 3% of primary pediatric brain tumors and encompass a wide pathologic spectrum. CNS GCTs are most commonly located in the pineal and suprasellar regions of the brain and can be divided into major groups including germinomas and nongerminomatous GCTs (NGGCTs), with teratomas often considered a separate category. The clinical presentation varies by location and size, and it frequently includes endocrine abnormalities, visual changes, and signs of increased intracranial pressure. Neuroimaging studies cannot differentiate GCTs from other tumors, and therefore, the diagnosis usually requires histologic confirmation. The rare exceptions are the cases where characteristic elevations of tumor markers, including alpha-fetoprotein and/or beta-human chorionic gonadotropin are documented in the serum and/or cerebrospinal fluid. In these cases, the imaging findings along with the tumor marker elevation may be diagnostic in themselves without the need for tissue confirmation. Treatment and prognosis differ greatly between groups. Germinomas have a superior prognosis than NGGCTs. Five-year overall survival rates >90% were reported initially with the use of craniospinal irradiation. More recently, the use of chemotherapy in addition to radiation therapy has afforded the ability to decrease the dose and volume of radiation therapy without affecting survival rates. NGGCTs are less radiosensitive than germinomas, but the use of adjuvant chemotherapy has improved survival rates in this group as well. The standard management for CNS GCTs remains controversial. Treatment regimens aimed to improve progression-free and overall survival times are ongoing.


Intelligent data analysis to interpret major risk factors for diabetic patients with and without ischemic stroke in a small population.
This study proposes an intelligent data analysis approach to investigate and interpret the distinctive factors of diabetes mellitus patients with and without ischemic (non-embolic type) stroke in a small population. The database consists of a total of 16 features collected from 44 diabetic patients. Features include age, gender, duration of diabetes, cholesterol, high density lipoprotein, triglyceride levels, neuropathy, nephropathy, retinopathy, peripheral vascular disease, myocardial infarction rate, glucose level, medication and blood pressure. Metric and non-metric features are distinguished. First, the mean and covariance of the data are estimated and the correlated components are observed. Second, major components are extracted by principal component analysis. Finally, as common examples of local and global classification approach, a k-nearest neighbor and a high-degree polynomial classifier such as multilayer perceptron are employed for classification with all the components and major components case. Macrovascular changes emerged as the principal distinctive factors of ischemic-stroke in diabetes mellitus. Microvascular changes were generally ineffective discriminators. Recommendations were made according to the rules of evidence-based medicine. Briefly, this case study, based on a small population, supports theories of stroke in diabetes mellitus patients and also concludes that the use of intelligent data analysis improves personalized preventive intervention.


Effect of a 6-Week Active Play Intervention on Fundamental Movement Skill Competence of Preschool Children.
This study examined the effectiveness of an active play intervention on fundamental movement skills of 3- to 5-year-old children from deprived communities. In a cluster randomized controlled trial design, six preschools received a resource pack and a 6-week local authority program involving staff training with help implementing 60-minute weekly sessions and postprogram support. Six comparison preschools received a resource pack only. Twelve skills were assessed at baseline, postintervention, and at a 6-month follow-up using the Children's Activity and Movement in Preschool Study Motor Skills Protocol. One hundred and sixty-two children (Mean age = 4.64 ± 0.58 years; 53.1% boys) were included in the final analyses. There were no significant differences between groups for total fundamental movement skill, object-control skill or locomotor skill scores, indicating a need for program modification to facilitate greater skill improvements.


Patient Characteristics Associated with Sexual Interest and Activity Among Adults with Spina Bifida.
We sought to identify factors associated with sexual interest and activity among adults with spina bifida and to describe the sexual profile of those who were sexually active. Sexual health of adults with spina bifida is often neglected and current knowledge on the topic is limited. An anonymous web-based survey was advertised and administered between March 2018 and September 2018 and participants 16 years and older with spina bifida were included in this study. Respondents were asked about sexual interest, activity, and function using the validated Patient-Reported Outcomes Measurement Information System Sexual Function Profile. Bivariate and multivariable models with ordinal logistic regression were fitted to evaluate predictors of sexual interest and sexual function. Of the 261 respondents with a self-reported diagnosis of spina bifida (mean age of 38.5 years), 73.2% noted at least a little bit of interest in sexual activity. In multivariate analysis, women were less likely to report higher sexual interest than men (OR=0.53, 95% CI 0.31-0.92, p=0.03) whereas those with higher physical functioning were more likely to have higher sexual interest (OR=1.04, CI 1.01-1.07, p=0.03). Just less than half of respondents (46.4%) were sexually active in the past 30 days, and those with a VP shunt were less likely to engage in sexual activity compared to those without (OR=0.36, 95% CI 0.19-0.68; p<0.01). The mismatch between sexual interest and sexual activity highlights the importance of exploring issues related to sexual health when counseling adult patients with spina bifida.


Performance by spring and fall-calving cows grazing with full, limited, or no access to toxic Neotyphodium coenophialum-infected tall fescue.
Replacing toxic, wild-type Neotyphodium coenophialum-infected tall fescue (E+) with nontoxic, N. coenophialum-infected tall fescue (NE+) has improved cow performance, but producer acceptance of NE+ has been slow. The objective was to compare performance by spring- and fall-calving cows grazing either E+ or NE+ at different percentages of the total pasture area. Gelbvieh×Angus crossbred cows (n=178) were stratified by BW and age within calving season and allocated randomly to 1 of 14 groups representing 5 treatments for a 3-yr study: i) Fall-calving on 100% E+ (F100); ii) Spring-calving on 100% E+ (S100); iii) Fall-calving on 75% E+ and 25% NE+ (F75); iv) Spring-calving on 75% E+ and 25% NE+ (S75); and v) Spring-calving on 100% NE+ (SNE100). Groups allocated to F75 and S75 grazed E+ until approximately 28 d before breeding and weaning, then were then moved to their respective NE+ pasture area for 4 to 6 wk; those allocated to F100, S100, and SNE100 grazed their pastures throughout the entire year. Samples of tall fescue were gathered from specific cells within each pasture at the time cows were moved into that particular cell (∼1 sample/mo). Blood samples were collected from the cows at the start and end of the breeding season. Stocking rate for each treatment was 1 cow/ha. Forage IVDMD, CP, and total ergot alkaloid concentrations were affected (P<0.05) by the treatment×sampling date interaction. Hay offered, cow BW, and BCS at breeding, end of breeding, and at weaning were greater (P<0.05) from fall-calving vs. spring-calving. Cow BW at weaning was greater (P<0.05) from F75 and S75 vs. F100 and S100. The calving season×NE+ % interaction affected (P<0.05) calving rates. Preweaning calf BW gain, actual and adjusted weaning BW, ADG, sale price, and calf value at weaning were greater (P<0.05) from fall-calving vs. spring-calving and from SNE100 vs. S75 except for sale price which was greater (P<0.05) from S75 vs. SNE100. Cow concentrations of serum prolactin at breeding and serum NEFA at the end of breeding were affected (P<0.05) by the calving season×NE+ % interaction. Serum Zn and Cu concentrations from cows were affected (P<0.05) by calving season. A fall-calving season may be more desirable for cows grazing E+, resulting in greater calving rates, cow performance, and calf BW at weaning, whereas limited access to NE+ may increase calving rates, serum prolactin, and NEFA concentrations during certain times in the production cycle, particularly in spring-calving cows.


[Communications by health professionals to patients undergoing diagnostic tests with new technologies].
Descriptive exploratory study with quanti-qualitative approach accomplished at public and private net units in Goiânia--GO from August to September, 1997 aiming at observing clients understanding of communication of the professionals who perform high technology exams and identifying whether any orientation provided to clients about the exams that are to be performed and their impressions during their performance. The population is of clients of both sexes who have undergone high technology diagnosis examinations. The data have been collected by the authors and research aids through semistructured interviews among the study subject clients. By the results, we have concluded that the majority of the clienta does not receive any orientation, lacked information about the exam that is to be performed for several reasons, including fear of the unknown. Communication was restrict. Fear of pain, of the result, discomfort have also been reported.


From feldschers to physician assistants in Bulgaria.
The physician assistant (PA) profession was established in Bulgaria in 2014 in response to a growing shortage of medical staff and was modeled on the United States experience. Feldschers provided a similar role in Bulgaria from 1878 to 1999 but feldscher training was discontinued in 1999 because of a physician surplus. However, healthcare in Bulgaria changed after the country joined the European Union, and some physicians left for better opportunities elsewhere. The loss of physicians and an aging population meant that PAs were seen as a strategy to offset Bulgaria's growing healthcare demand.


Stable isotope analyses on archived fish scales reveal the long-term effect of nitrogen loads on carbon cycling in rivers.
Stable isotope analysis of organic matter in sediment records has long been used to track historical changes in productivity and carbon cycling in marine and lacustrine ecosystems. While flow dynamics preclude stratigraphic measurements of riverine sediments, such retrospective analysis is important for understanding biogeochemical cycling in running waters. Unique collections of riverine fish scales were used to analyse δ(15) N and δ(13) C variations in the food web of two European rivers that experience different degrees of anthropogenic pressure. Over the past four decades, dissolved inorganic N loading remained low and constant in the Teno River (70°N, Finland); in contrast, N loading increased fourfold in the Scorff River (47°N, France) over the same period. Archived scales of Atlantic salmon parr, a riverine life-stage that feeds on aquatic invertebrates, revealed high δ(15) N values in the Scorff River reflecting anthropogenic N inputs to that riverine environment. A strong correlation between dissolved inorganic N loads and δ(13) C values in fish scales was observed in the Scorff River, whereas no trend was found in the Teno River. This result suggests that anthropogenic N-nutrients enhanced atmospheric C uptake by primary producers and its transfer to fish. Our results illustrate for the first time that, as for lakes and marine ecosystems, historical changes in anthropogenic N loading can affect C cycling in riverine food webs, and confirm the long-term interactions between N and C biogeochemical cycles in running waters.


The requirement for fibroblasts in angiogenesis: fibroblast-derived matrix proteins are essential for endothelial cell lumen formation.
A role for fibroblasts in physiological and pathological angiogenesis is now well recognized; however, the precise mechanisms underlying their action have not been determined. Using an in vitro angiogenesis model in combination with a candidate gene approach, column chromatography, and mass spectrometry, we identify two classes of fibroblast-derived factors--one that supports vessel sprouting but not lumen formation, and one that promotes lumen formation. In the absence of fibroblasts a combination of angiopoietin-1, angiogenin, hepatocyte growth factor, transforming growth factor-α, and tumor necrosis factor drives robust endothelial cell (EC) sprouting; however, lumens fail to form. Subsequent addition of fibroblast-conditioned medium restores lumenogenesis. Using small interfering RNA-mediated knockdown, we show that five genes expressed in fibroblasts--collagen I, procollagen C endopeptidase enhancer 1, secreted protein acidic and rich in cysteine, transforming growth factor-β-induced protein ig-h3, and insulin growth factor-binding protein 7--are necessary for lumen formation. Moreover, lumen formation can be rescued by addition of purified protein to knockdown cultures. Finally, using rheology, we demonstrate that the presence of these matricellular proteins results in significantly stiffer gels, which correlates with enhanced lumen formation. These findings highlight the critical role that fibroblast-derived extracellular matrix components play in EC lumen formation and provide potential insight into the role of fibroblasts in the tumor microenvironment.


Segmental foot mobility in individuals with and without diabetes and neuropathy.
Impairment in intrinsic foot mobility has been identified as an important potential contributor to altered foot function in individuals with diabetes mellitus and neuropathy, however the role of limited foot mobility in gait remains poorly understood. The purpose of our study was to examine segmental foot mobility during gait in subjects with and without diabetes and neuropathy. Segmental foot mobility during gait was examined using a multi-segment kinematic foot model in subjects with diabetes (n=15) and non-diabetic control subjects (n=15). Subjects with diabetes showed reduced frontal as well as sagittal plane excursion of the calcaneus relative to the tibia. Decreased excursion of the first metatarsal relative to the calcaneus in the frontal as well as transverse plane was noted in subjects with diabetes. Our findings agree with traditional understanding of foot mechanics and shed new light on patterns and magnitude of motion during gait. Calcaneal pronation, noted in early stance in both groups, was reduced in subjects with diabetes and may have important consequences on joints proximal as well as distal to it. Subjects with diabetes showed reduced foot 'splay' in early stance, indicated by first metatarsal and forefoot eversion. At terminal stance, decreases in calcaneal plantarflexion, first metatarsal and forefoot supination were noted in subjects with diabetes, suggesting that less supination is required in subjects with diabetes to create a rigid lever. In subjects with diabetes, a greater proportion of midfoot stability may be derived from modified/stiffer soft tissue such as the plantar fascia.


Changes in Reimbursement to Emergency Physicians After Medicaid Expansion Under the Patient Protection and Affordable Care Act.
We examine the effect of Medicaid expansion on reimbursement for emergency physicians' professional services. We conducted a retrospective study using data from a national emergency medicine group in a sample of 50 emergency departments (EDs) from July 1, 2012, to June 30, 2015. We categorized facilities in 14 states into full-expansion (23), partial-expansion (17), and nonexpansion (10) categories based on pre-expansion Medicaid eligibility criteria for all adults. We used a difference-in-differences design to assess the effect of Medicaid expansion on provider reimbursement per visit. Secondary outcomes included reimbursement per relative value unit and relative value units per visit, both overall and by payer type, controlling for age, sex, billing codes, and health system relationship. We studied greater than 6.7 million ED visits during July 2012 to December 2015, 3.0 million pre-expansion and 3.7 million postexpansion. After adjusting for covariates, reimbursement per visit increased 6.3% (95% confidence interval 1.4% to 11.1%) in full-expansion relative to nonexpansion states and did not change significantly in partial-expansion versus nonexpansion states. Reimbursement per visit for commercial insurance increased 17.1% (95% confidence interval 9.9% to 24.2%) in full-expansion versus nonexpansion states. Reimbursement for self-pay visits increased 9.7% (95% confidence interval 3.7% to 15.7%) in full-expansion versus nonexpansion states. Changes in payments were driven by higher reimbursement per relative value unit; relative value units per visit declined slightly in full-expansion compared with nonexpansion states. In this sample, full Medicaid expansion increased payments for emergency physicians' professional services compared with reimbursement in nonexpansion states. Higher reimbursement was driven primarily by lower proportions of uninsured patients and increased reimbursement per visit for both commercially insured and self-pay patients in states with full Medicaid expansion.


Rehabilitation unit staff attitudes toward substance abuse: changes and similarities between 1985 and 2001.
(1) To assess the attitudes of the members of an inpatient rehabilitation unit team toward their unit's substance abuse and tobacco use policies, and (2) to compare the findings with those of a survey 16 years earlier. An anonymous repeated assessment of staff attitudes and behaviors. A 47-bed inpatient rehabilitation unit. Rehabilitation unit nurses, occupational and physical therapists, psychologists, physicians, social workers, and speech pathologists. Not applicable. Change in response with time. Seventy percent (89/128) of the staff members completed the survey. Seventy-two percent believed that they were "familiar or very familiar" with the unit's substance abuse policy and 51% were "concerned" or "very concerned" about their patients' alcohol and drug use. Nineteen percent reported complaints about the policy from their patients and 8% reported complaints from family members. Support for a uniform substance abuse policy remained high: 96% supported a uniform policy in both 1985 and 2001. However, only 15% believed that staff drug abuse education was adequate and only 45% believed that the current policy was "adequate" or "very adequate." (Corresponding responses in 1985 were 20% and 50%, respectively.) All but 1 respondent considered tobacco use an addiction, but only 48% believed that their patients were routinely assessed for its use. Support for a uniform substance abuse policy remains strong. Although most team members support the policy, they believe that their education about substance abuse is inadequate. Staff members almost unanimously accept tobacco use as an addiction, but they believe that assessment and intervention efforts are poor.


The optimization of protein secondary structure determination with infrared and circular dichroism spectra.
We have used the circular dichroism and infrared spectra of a specially designed 50 protein database [Oberg, K.A., Ruysschaert, J.M. & Goormaghtigh, E. (2003) Protein Sci. 12, 2015-2031] in order to optimize the accuracy of spectroscopic protein secondary structure determination using multivariate statistical analysis methods. The results demonstrate that when the proteins are carefully selected for the diversity in their structure, no smaller subset of the database contains the necessary information to describe the entire set. One conclusion of the paper is therefore that large protein databases, observing stringent selection criteria, are necessary for the prediction of unknown proteins. A second important conclusion is that only the comparison of analyses run on circular dichroism and infrared spectra independently is able to identify failed solutions in the absence of known structure. Interestingly, it was also found in the course of this study that the amide II band has high information content and could be used alone for secondary structure prediction in place of amide I.


Conducting national burden of disease studies in small countries in Europe- a feasible challenge?
Burden of Disease (BoD) studies use disability-adjusted life years (DALYs) as a population health metric to quantify the years of life lost due to morbidity and premature mortality for diseases, injuries and risk factors occurring in a region or a country. Small countries usually face a number of challenges to conduct epidemiological studies, such as national BoD studies, due to the lack of specific expertise and resources or absence of adequate data. Considering Europe's small countries of Cyprus, Iceland, Luxembourg, Malta and Montenegro, the aim was to assess whether the various national data sources identified are appropriate to perform national BoD studies. The five small countries have a well-established mortality registers following the ICD10 classification, which makes calculation of years of life lost (YLL) feasible. A number of health information data sources were identified in each country, which can provide prevalence data for the calculation of years lived with disability (YLD) for various conditions. These sources include disease-specific registers, hospital discharge data, primary health care data and epidemiological studies, provided by different organisations such as health directorates, institutes of public health, statistical offices and other bodies. Hence, DALYs can be estimated at a national level through the combination of the YLL and YLD information. On the other hand, small countries face unique challenges such as difficulty to ensure sample representativeness, variations in prevalence estimates especially for rarer diseases, existence of a substantial proportion of non-residents affiliated to healthcare systems and potential exclusion from some European or international initiatives. Recently established BoD networks may provide a platform for small countries to share experiences, expertise, and engage with countries and institutions that have long-standing experience with BoD assessment. Apart from mortality registries, adequate health data sources, notably for cancer, are potentially available at the small states to perform national BoD studies. Investing in sharing expert knowledge through engagement of researchers in BoD networks can enable the conduct of country specific BoD studies and the establishment of more accurate DALYs estimates. Such estimates can enable local policymakers to reflect on the relative burden of the different conditions that are contributing to morbidity and mortality at a country level.


[In-vitro and in-vivo activity of itraconazole].
Itraconazole is a lipophilic triazole with potent in vitro activity. It is also highly efficacious after topical, oral and parenteral administration. The antifungal activity of itraconazole has been evaluated against more than 6500 different strains, belonging to more than 260 fungal species using the serial decimal dilution test in fluid media (BHI broth). Candida, Torulopsis, Cryptococcus, Pityrosporum (Dixon broth), various other yeasts, dermatophytes, Aspergillus, Penicillium, Sporothrix, dimorphic fungi (MP and YP), Phaeohyphomycetes, Entomophthorales and various Hyalohyphomycetes are sensitive. Most strains of Fusarium and Zygomycetes are poorly sensitive. Itraconazole was administered orally and parenterally in normal and in immunocompromised guinea-pigs, infected with C. albicans, Cr. neoformans, H. duboisii, Sp. schenckii, P. marneffei and A. fumigatus. It was efficacious both in survival of the animals and in eliminating the fungi from the various tissues. Itraconazole was superior to fluconazole in candidosis, cryptococcosis, sporotrichosis and aspergillosis, to amphotericin B and to flucytosine in candidosis, cryptococcosis and aspergillosis. No comparative studies were done up to now for the other deep mycoses. The results of combination therapy of itraconazole with fluconazole in cryptococcosis were indifferent, with 5-flucytosine or amphotericin B, additive or synergistic in systemic candidosis, cryptococcosis and aspergillosis. No drug-related side-effects were observed after oral or parenteral administration of itraconazole.


Evaluating competence using a portfolio: a literature review and web-based application to the ACGME competencies.
The Accreditation Council for Graduate Medical Education is shifting its focus from a structure and process system of graduate medical education to one that is outcomes based, requiring all residents in training to achieve competence in six broad domains and presenting educators with the challenge of evaluation. We searched the literature and reviewed all articles relating to portfolio assessment in medicine. In addition, we reviewed articles that addressed standard tools currently in use for resident performance assessment. The use of a portfolio allows one to incorporate a variety of assessment tools needed to evaluate the diverse domains of competence and also fosters reflective learning, which is key to professional development. From lessons learned through this review, we developed a Web-based evaluation portfolio for residency training that we describe here in the hope of facilitating this process for others. Web-based portfolio assessment provides an ideal venue for the evaluation of competence and has the ability to provide educators with a research infrastructure to practice evidence-based education.


Reconstructing the population genetic history of the Caribbean.
The Caribbean basin is home to some of the most complex interactions in recent history among previously diverged human populations. Here, we investigate the population genetic history of this region by characterizing patterns of genome-wide variation among 330 individuals from three of the Greater Antilles (Cuba, Puerto Rico, Hispaniola), two mainland (Honduras, Colombia), and three Native South American (Yukpa, Bari, and Warao) populations. We combine these data with a unique database of genomic variation in over 3,000 individuals from diverse European, African, and Native American populations. We use local ancestry inference and tract length distributions to test different demographic scenarios for the pre- and post-colonial history of the region. We develop a novel ancestry-specific PCA (ASPCA) method to reconstruct the sub-continental origin of Native American, European, and African haplotypes from admixed genomes. We find that the most likely source of the indigenous ancestry in Caribbean islanders is a Native South American component shared among inland Amazonian tribes, Central America, and the Yucatan peninsula, suggesting extensive gene flow across the Caribbean in pre-Columbian times. We find evidence of two pulses of African migration. The first pulse--which today is reflected by shorter, older ancestry tracts--consists of a genetic component more similar to coastal West African regions involved in early stages of the trans-Atlantic slave trade. The second pulse--reflected by longer, younger tracts--is more similar to present-day West-Central African populations, supporting historical records of later transatlantic deportation. Surprisingly, we also identify a Latino-specific European component that has significantly diverged from its parental Iberian source populations, presumably as a result of small European founder population size. We demonstrate that the ancestral components in admixed genomes can be traced back to distinct sub-continental source populations with far greater resolution than previously thought, even when limited pre-Columbian Caribbean haplotypes have survived.


A probe-based qRT-PCR method to profile immunological gene expression in blood of captive beluga whales (Delphinapterus leucas).
Cytokines are fundamental for a functioning immune system, and thus potentially serve as important indicators of animal health. Quantitation of mRNA using quantitative reverse transcription polymerase chain reaction (qRT-PCR) is an established immunological technique. It is particularly suitable for detecting the expression of proteins against which monoclonal antibodies are not available. In this study, we developed a probe-based quantitative gene expression assay for immunological assessment of captive beluga whales (Delphinapterus leucas) that is one of the most common cetacean species on display in aquariums worldwide. Six immunologically relevant genes (IL-2Rα, -4, -10, -12, TNFα, and IFNγ) were selected for analysis, and two validated housekeeping genes (PGK1 and RPL4) with stable expression were used as reference genes. Sixteen blood samples were obtained from four animals with different health conditions and stored in RNAlater™ solution. These samples were used for RNA extraction followed by qRT-PCR analysis. Analysis of gene transcripts was performed by relative quantitation using the comparative Cq method with the integration of amplification efficiency and two reference genes. The expression levels of each gene in the samples from clinically healthy animals were normally distributed. Transcript outliers for IL-2Rα, IL-4, IL-12, TNFα, and IFNγ were noticed in four samples collected from two clinically unhealthy animals. This assay has the potential to identify immune system deviation from normal state, which is caused by health problems. Furthermore, knowing the immune status of captive cetaceans could help both trainers and veterinarians in implementing preventive approaches prior to disease onset.


Modeling Search Behaviors during the Acquisition of Expertise in a Sequential Decision-Making Task.
Our daily interaction with the world is plagued of situations in which we develop expertise through self-motivated repetition of the same task. In many of these interactions, and especially when dealing with computer and machine interfaces, we must deal with sequences of decisions and actions. For instance, when drawing cash from an ATM machine, choices are presented in a step-by-step fashion and a specific sequence of choices must be performed in order to produce the expected outcome. But, as we become experts in the use of such interfaces, is it possible to identify specific search and learning strategies? And if so, can we use this information to predict future actions? In addition to better understanding the cognitive processes underlying sequential decision making, this could allow building adaptive interfaces that can facilitate interaction at different moments of the learning curve. Here we tackle the question of modeling sequential decision-making behavior in a simple human-computer interface that instantiates a 4-level binary decision tree (BDT) task. We record behavioral data from voluntary participants while they attempt to solve the task. Using a Hidden Markov Model-based approach that capitalizes on the hierarchical structure of behavior, we then model their performance during the interaction. Our results show that partitioning the problem space into a small set of hierarchically related stereotyped strategies can potentially capture a host of individual decision making policies. This allows us to follow how participants learn and develop expertise in the use of the interface. Moreover, using a Mixture of Experts based on these stereotyped strategies, the model is able to predict the behavior of participants that master the task.


Postoperative Evaluation of Bilateral Reading Performance With Two Intraocular Lenses: Twelve-Month Results.
The aim of this study was to compare the bilateral reading performances within the first 12 months after the implantation of two intraocular lens (IOL) models. The patients involved in this research had bilateral phacoemulsification and implantation of the Acriva Reviol MFM 613 IOL (group 1) or AcrySof ReSTOR SN6AD1 apodized multifocal IOL (group 2). The bilateral reading performance was evaluated preoperatively and postoperatively using the MNREAD acuity charts. The reading speed, critical print size, and reading acuity were measured binocularly at 40 and 60 cm. In addition, the binocular uncorrected visual acuities (far, UDVA; intermediate, UIVA; and near, UNVA) were also measured. Each IOL model was implanted in 30 eyes (15 patients), and 30 patients were included in this study. Overall, there were no statistically significant postoperative differences in the mean UDVA, UIVA and mean (P>0.05). There were statistically significant postoperative differences in the mean reading acuity (group 1, 0.07±0.10 logMAR; group 2, 0.02±0.08 logMAR; P=0.019) at 40 cm. When tested at 60 cm, the reading acuity (0.13±0.10 logMAR and 0.21±0.11 logMAR, respectively; P=0.021) and critical print size (0.25±0.13 logMAR and 0.39±0.16 logMAR, respectively; P=0.005) were significantly better in group 1 than in group 2. Both of the IOLs achieved good visual performances. However, the Acriva Reviol MFM 613 IOL performed better than the AcrySof ReSTOR SN6AD1 at an intermediate distance, whereas the AcrySof ReSTOR SN6AD1 provided better near distance results.


Biochemical and Chemical Biology Study of Rice OsTAR1 Revealed that Tryptophan Aminotransferase is Involved in Auxin Biosynthesis: Identification of a Potent OsTAR1 Inhibitor, Pyruvamine2031.
IAA, a major form of auxin, is biosynthesized from l-tryptophan via the indole-3-pyruvic acid (IPyA) pathway in Arabidopsis. Tryptophan aminotransferases (TAA1/TARs) catalyze the first step from l-tryptophan to IPyA. In rice, the importance of TAA/TARs or YUC homologs in auxin biosynthesis has been suggested, but the enzymatic activities and involvement of the intermediate IPyA in auxin biosynthesis remain elusive. In this study, we obtained biochemical evidence that the rice tryptophan aminotransferase OsTAR1 converts l-tryptophan to IPyA, and has a Km of 82.02 µM and a Vmax of 10.92 µM min-1 m-1, comparable with those in Arabidopsis. Next, we screened for an effective inhibitor of OsTAR1 from our previously reported inhibitor library for TAA1/TARs, designated pyruvamine (PVM). Differing from previous observations in Arabidopsis, hydroxy-type PVMs, e.g. PVM2031 (previous name KOK2031), had stronger inhibitory effects in rice than the methoxy-type. PVM2031 inhibited recombinant OsTAR1 in vitro. The Ki of PVM2031 was 276 nM. PVM2031 treatment of rice seedlings resulted in morphological changes in vivo, such as reduced lateral root density. Exogenous IAA rescued this growth inhibition, suggesting that the inhibitory effect is auxin specific. Furthermore, rice roots showed reduced IAA levels concomitant with reduced levels of IPyA in the presence of the inhibitors, suggesting that the IPyA pathway is an auxin biosynthesis pathway in rice. Since PVM2031 showed stronger inhibitory effects on rice auxin biosynthesis than known tryptophan aminotransferase inhibitors, we propose that the hydroxy-type PVM2031 is an effective tool for biochemical analysis of the function of auxin biosynthesis in rice roots.


[An approach to the right hepatic duct in treating high damage and cicatricial stricture of the bile ducts].
There was proposed an operative access to the duct via the lateral end of transverse hepatic fissura, basing on the results of studying of the right hepatic duct anatomy. The method performed includes the right hepatic lobe mobilization, its fibrous capsule transsection along the transverse fissura in the direction toward right posterior sectorial duct, longitudinal transsection of the duct lateral wall along 1-2 cm with subsequent formation of laterolateral hepaticojejunoanastomosis. Method was tested in 9 patients with high damage and cicatricial stricture of biliary ducts, the result was positive.


Co-composting of distillery wastes with animal manures: carbon and nitrogen transformations in the evaluation of compost stability.
The aim of this work was to study the viability of recycling the solid wastes generated by the winery and distillery industry by means of co-composting with animal manures, as well as to evaluate the quality of the composts obtained. Two piles, using exhausted grape marc and cattle manure or poultry manure, respectively (at ratios, on a fresh weight basis, of 70:30), were composted by the Rutgers static pile composting system. Throughout the composting process, a number of parameters were monitored, such as pH, electrical conductivity, organic matter, water-soluble carbon, water-soluble polyphenols, different forms of nitrogen (organic nitrogen, ammonium and nitrate) and humification indices (humification ratio, humification index, percentage of humic acid-like C, polymerisation ratio and cation exchange capacity), as well as the germination index. Organic matter losses followed first-order kinetics equation in both piles, the highest organic matter mineralisation rate being observed with exhausted grape marc and cow manure. On the other hand, the mixture with the lowest C/N ratio, using exhausted grape marc and poultry manure, showed the highest initial ammonium contents, probably due to the higher and more labile N content of poultry manure. The increase in the cation exchange capacity revealed the organic matter humification during composting. In contrast, other humification parameters, such as the humification ratio and the humification index, did not show the expected evolution and, thus, could not be used to assess compost maturity. Composting produced a degradation of the phytotoxic compounds, such as polyphenols, to give composts without a phytotoxic character. Therefore, composting can be considered as an efficient treatment to recycle this type of wastes, due to composts presented a stable and humified organic matter and without phytotoxic effects, which makes them suitable for their agronomic use.


Exposure of Paris taxi drivers to automobile air pollutants within their vehicles.
To study the exposure of Parisian taxi drivers to automobile air pollutants during their professional activity. A cross sectional study was carried out from 27 January to 27 March 1997, with measurements performed in the vehicles of 29 randomly selected drivers. Carbon monoxide (CO) content was measured over an 8 hour period by a CO portable monitor. The fine suspended particles were measured according to the black smoke index (BS), with a flow controlled portable pump provided with a cellulose filter. The nitrogen oxides, NO and NO(2) were measured with a passive sampler. These drivers are exposed during their professional activity to relatively high concentrations of pollutants (mean, median (SD) 3.8, 2 (1.7) ppm for CO, 168, 164 (53) micrograms/m(3) for BS, 625, 598 (224) micrograms/m(3) for NO, and 139, 131 (43) micrograms/m(3) for NO(2).) For CO the concentrations were clearly lower than the threshold values recommended by the World Health Organisation. The situation is less satisfactory for the other pollutants, especially for the BS index. All concentrations of pollutants recorded were noticeably higher than concentrations in air recorded by the ambient Parisian air monitoring network and were close to, or slightly exceeded, the concentrations measured at the fixed stations close to automobile traffic. Pollutant concentrations were also influenced greatly by weather conditions. This first French study conducted in taxi drivers shows that they are highly exposed to automobile pollutants. The results would justify a medical follow up of this occupational group.


[Reasearch on mechanism of neurotrophins in discogenic low back pain].
Discogenic low back pain is the common type of chronic low back pain. However,its mechanism has not been completely clarified. Considerable evidence shows that neurotrophins play an important role in discogenic low back pain. The paper summarizes the mechanism of neurotrophins on discogenic low back pain according to the pain transfer pathway of neurotrophins in intervertebral disc, dorsal horn ganglia and spinal trigeminal nucleus. Changing the pain transmission by regulating neurotrophins and its receptor will provide a new way for the treatment of discogenic low back pain.


Safe and Inclusive Research Practices for Qualitative Research Involving People with Dementia: A Review of Key Issues and Strategies.
Developing strategies to ensure the safe participation of people with dementia in research is critical to support their wider inclusion in research and to advance knowledge in the areas of dementia policy and practice. This literature review synthesizes and critically appraises different approaches to promote the safe participation of people with dementia in qualitative research. Two databases were searched for articles that discuss the methodological or ethical aspects of qualitative research involving people with dementia. We did not focus on informed consent or ethical review processes as these have been reviewed elsewhere. Key issues that impact participant safety include: language, gatekeepers, the research relationship, communication, dealing with distress, knowledge dissemination, and researcher skills. By synthesizing different approaches to safety and highlighting areas of debate, we hope to advance discussion and to contribute to the development of inclusive research methods.


Zika virus: no cases in the Eastern Mediterranean Region but concerns remain.
Following the WHO declaration on 1 February 2016 of a Public Health Emergency of International Concern (PHEIC) with regard to clusters of microcephaly and neurological disorders potentially associated with Zika virus, the WHO Regional Office for the Eastern Mediterranean conducted three rounds of emergency meetings to address enhancing preparedness actions in the Region. The meetings provided up-to-date information on the current situation and agreed on a set of actions for the countries to undertake to enhance their preparedness and response capacities to Zika virus infection and its complications. The most urgent action is to enhance both epidemiological and entomological surveillance between now and the coming rainy seasons in countries with known presence of Aedes mosquitoes. Zika virus like other vector-borne diseases poses a particular challenge to the countries because of their complex nature which requires multidisciplinary competencies and strong rapid interaction among committed sectors. WHO is working closely with partners and countries to ensure the optimum support is provided to the countries to reduce the risk of this newly emerged health threat.


The effect of Fe content in electrodeposited CoFe/Cu multilayers on structural, magnetic and magnetoresistance characterizations.
A series of CoFe/Cu multilayers were electrodeposited on Ti substrates from the electrolytes containing their metal ion under potentiostatic control, but the Fe concentration in the electrolytes was changed from 0.0125 M to 0.2 M. The deposition was carried out in a three-electrode cell at room temperature. The deposition of Cu layers was made at a cathode potential of -0.3 V with respect to saturated calomel electrode (SCE), while the ferromagnetic CoFe layers were deposited at -1.5 V versus SCE. The structural studies by X-ray diffraction revealed that the multilayers have face-centered-cubic structure. The magnetic characteristics of the films were investigated using a vibrating sample magnetometer and their easy-axis was found to be in film plane. Magnetoresistance measurements were carried out using the Van der Pauw method at room temperature with magnetic fields up to +/- 12 kOe. All multilayers exhibited giant magnetoresistance (GMR) and the GMR values up to 8% were obtained.


Photocatalytic Radical Coupling of Organoborates with α-Halogenated Electron-Poor Olefins.
Herein, we report the visible-light-mediated addition of organoborates to α-halogenated electron-poor olefins enabled by an environmentally benign metal-free catalyst. The method accommodates a variety of boronic acid derivatives as well as alkenes and delivers the corresponding saturated α-halo-derivatives in up to 90% yields. The obtained products are high-value building blocks in organic synthesis, allowing for a variety of follow-up transformations.


A Framework for Determining the Return on Investment of Simulation-Based Training in Health Care.
This article describes a framework that has been developed to monetize the real value of simulation-based training in health care. A significant consideration has been given to the incorporation of the intangible and qualitative benefits, not only the tangible and quantitative benefits of simulation-based training in health care. The framework builds from three works: the value measurement methodology (VMM) used by several departments of the US Government, a methodology documented in several books by Dr Jack Phillips to monetize various training approaches, and a traditional return on investment methodology put forth by Frost and Sullivan, and Immersion Medical. All 3 source materials were adapted to create an integrated methodology that can be readily implemented. This article presents details on each of these methods and how they can be integrated and presents a framework that integrates the previous methods. In addition to that, it describes the concept and the application of the developed framework. As a test of the applicability of the framework, a real case study has been used to demonstrate the application of the framework. This case study provides real data related to the correlation between the pediatric patient cardiopulmonary arrest (CPA) survival rates and a simulation-based mock codes at the University of Michigan tertiary care academic medical center. It is important to point out that the proposed framework offers the capability to consider a wide range of benefits and values, but on the other hand, there are several limitations that has been discussed and need to be taken in consideration.


Precision treatment in colorectal cancer: Now and the future.
Until recently, a one-drug-fits-all model was applied to every patient diagnosed with the same condition. But not every condition is the same, and this has led to many cases of ineffective treatment. Pharmacogenetics is increasingly used to stratify patients for precision medicine treatments, for instance, the UGT1A1*28 polymorphism as a dosage indicator for the use of irinotecan as well as epidermal growth factor receptor (EGFR) immunohistochemistry and KRAS Proto-Oncogene (KRAS) exon 2 mutation tests for determining the likelihood of treatment response to cetuximab or panitumumab treatment in metastatic colorectal cancer (CRC). The other molecular subtypes, such as KRAS exon 3/4, B-Raf Proto-Oncogene, NRAF, PIK3CA, and PETN, were also reported as potential new pharmacogenetic targets for the current and the newly discovered anticancer drugs. In addition to next-generation sequencing (NGS), primary tumor cells for in vivo and in vitro drug screening, imaging biomarker 3'-Deoxy-3'-18F-fluorothymidine positron emission tomography, and circulating tumor DNA (ctDNA) detection methods are being developed and may represent the future direction of precision medicine. This review will discuss the current environment of precision medicine, including clinically approved targeted therapies, the latest potential therapeutic agents, and the ongoing pharmacogenetic trials for CRC patients.


Effects of tetraethylammonium on potassium currents in a molluscan neurons.
The effects of tetraethylammonium (TEA) on the delayed K+ current and on the Ca2+-activated K+ current of the Aplysia pacemaker neurons R-15 and L-6 were studied. The delayed outward K+ current was measured in Ca2+-free ASW containing tetrodotoxin (TTX), using brief depolarizing clamp pulses. External TEA blocks the delayed K+ current reversibly in a dose-dependent manner. The experimental results are well fitted with a Michaelis-Menten expression, assuming a one-to-one reaction between TEA and a receptor site, with an apparent dissociation constant of 6.0 mM. The block depends on membrane voltage and is reduced at positive membrane potentials. The Ca2+-activated K+ current was measured in Ca2+-free artificial seawater (ASW) containing TTX, using internal Ca2+ ion injection to directly activate the K+ conductance. External TEA and a number of other quaternary ammonium ions block the Ca2+-activated K+ current reversibly in a dose-dependent manner. TEA is the most effective blocker, with an apparent dissociation constant, for a one-to-one reaction with a receptor site, of 0.4 mM. The block decreases with depolarization. The Ca2+-activated K+ current was also measured after intracellular iontophoretic TEA injection. Internal TEA blocks the Ca2+-activated K+ current (but the block is only apparent at positive membrane potentials), is increased by depolarization, and is irreversible. The effects of external and internal TEA can be seen in measurements of the total outward K+ current at different membrane potentials in normal ASW.


Formulation of enzyme blends to maximize the hydrolysis of alkaline peroxide pretreated alfalfa hay and barley straw by rumen enzymes and commercial cellulases.
Efficient conversion of lignocellulosic biomass to fermentable sugars requires the synergistic action of multiple enzymes; consequently enzyme mixtures must be properly formulated for effective hydrolysis. The nature of an optimal enzyme blends depends on the type of pretreatment employed as well the characteristics of the substrate. In this study, statistical experimental design was used to develop mixtures of recombinant glycosyl hydrolases from thermophilic and anaerobic fungi that enhanced the digestion of alkaline peroxide treated alfalfa hay and barley straw by mixed rumen enzymes as well as commercial cellulases (Accelerase 1500, A1500; Accelerase XC, AXC). Combinations of feruloyl and acetyl xylan esterases (FAE1a; AXE16A_ASPNG), endoglucanase GH7 (EGL7A_THITE) and polygalacturonase (PGA28A_ASPNG) with rumen enzymes improved straw digestion. Inclusion of pectinase (PGA28A_ASPNG), endoxylanase (XYN11A_THITE), feruloyl esterase (FAE1a) and β-glucosidase (E-BGLUC) with A1500 or endoglucanase GH7 (EGL7A_THITE) and β-xylosidase (E-BXSRB) with AXC increased glucose release from alfalfa hay. Glucose yield from straw was improved when FAE1a and endoglucanase GH7 (EGL7A_THITE) were added to A1500, while FAE1a and AXE16A_ASPNG enhanced the activity of AXC on straw. Xylose release from alfalfa hay was augmented by supplementing A1500 with E-BGLUC, or AXC with EGL7A_THITE and XYN11A_THITE. Adding arabinofuranosidase (ABF54B_ASPNG) and esterases (AXE16A_ASPNG; AXE16B_ASPNG) to A1500, or FAE1a and AXE16A_ASPNG to AXC enhanced xylose release from barley straw, a response confirmed in a scaled up assay. The efficacy of commercial enzyme mixtures as well as mixed enzymes from the rumen was improved through formulation with synergetic recombinant enzymes. This approach reliably identified supplemental enzymes that enhanced sugar release from alkaline pretreated alfalfa hay and barley straw.


Antagonism between retinoic acid receptors.
In the developing mouse, retinoic acid receptors (RARs) beta and gamma 1 are expressed in characteristic spatiotemporal patterns which are correlated with different developmental fates of the respective tissues. Understanding the cues that regulate the expression of the various RARs may therefore provide insights into the process of tissue diversification. Transcription of RAR beta is rapidly upregulated through a retinoic acid-responsive element (here referred to as the beta RARE) in its promoter. Like RAR alpha and RAR beta, RAR gamma 1 has been implicated in the activation of the beta RARE. Therefore, it is puzzling that RAR beta and RAR gamma 1 appear to be expressed in reciprocal patterns. In the present report, we show that RAR gamma 1, one of the two predominant RAR gamma isoforms, can inhibit the activity of RAR gamma 2, RAR beta, and endogenous RAR on the beta RARE. In contrast, the three RAR gamma isoforms tested and RAR beta activated a palindromic thyroid hormone response element with similar levels of efficiency. The differential activity of RAR gamma 1 compared with that of RAR beta appears to reside in both the N-terminal and the C-terminal halves of RAR gamma 1. RAR gamma 1-mediated inhibition of other RARs may involve competition for the response element as well as direct interaction with other receptors and might be part of a regulatory system contributing to the characteristic tissue distribution of the various RARs.


Genotyping of Pneumocystis jirovecii isolates from human immunodeficiency virus-negative patients in China.
Pneumocystis jirovecii is a fungus that causes Pneumocystis pneumonia in immuno-compromised patients. To analyze the genetic diversity of P. jirovecii in HIV-negative patients in China, respiratory specimens were obtained from 105 patients who tested PCR-positive for the presence of the P. jirovecii mitochondrial large subunit ribosomal RNA (mtLSU rRNA) between 2011 and 2013. P. jirovecii isolates were genotyped based on the upstream conserved sequence (UCS) of the major surface glycoprotein (MSG) gene and the internal transcribed spacer (ITS) of nuclear rRNA operon. Eighty-one of the 105 isolates showed a positive PCR for the UCS region. We identified six different patterns comprising two, three, four, or five UCS repeats, including 1, 2, 3 (69.14%), 1, 2, 3, 3 (22.22%), 1, 2 (3.7%), 1, 1, (2.47%), 2, 2, 3, 3 (1.23%), and 1, 1, 2, 3, 3 (1.23%). In regard to the ITS region, 58 of the 105 isolates were cloned and sequenced successfully. Six known ITS1 alleles (A, B, DEL1, E, N, and SYD1), two new alleles (designated as BTM3 and BTM4), six known ITS2 alleles (a, b, i, g, h and O) and one new allele (designated as btm6) were observed. A total of 19 P. jirovecii ITS haplotypes were identified. The most frequent type was Bi (25.9%), followed by Ai (13.8%), Eb (10.3%), and SYD1g (6.9%). Among the 58 specimens examined, 49 (84.5%) were found to contain a single type of P. jirovecii, while 9 (15.5%) contained multiple genotypes. A total of 34 allelic profiles were observed in 58 isolates when the two loci were combined with each other. A Fisher's exact test revealed that there was no statistically significant (P=0.330) association between the most frequent UCS and ITS genotypes. An analysis of the phylogenetic relationship between different patient groups identified two major groups based on the sequence variations of concatenated UCS and ITS sequences in 49 isolates. Our results demonstrated the high genetic variability of P. jirovecii in HIV-negative patients in China.


Gender Diversity at Spine Surgery Academic Conferences: A 15-Year Investigation.
Enhancing gender diversity at academic conferences is critical for advancing women's representation and career trajectories in spine surgery. To discover trends in women's representation at major spine conferences over a 15-year period. Conference records from the 2007-2021 annual meetings of the Congress of Neurological Surgeons (CNS), North American Spine Society (NASS), and Scoliosis Research Society (SRS). Authors of spine-related presentations. Authorship by gender. Retrospective bibliometric analysis with univariate and multivariate modeling to identify trends and predictors of gender diversity. Among 8948 presentations, 750 (8.4%) had female first authors and 618 (6.9%) had female senior authors. There was no change in rates of female first authorship (P=0.41) or senior authorship (P=0.88) over time. The strongest predictors of female first authorship were having a female senior author (OR 7.32, P<0.001), and delivering presentations at SRS (OR 1.95, P=0.001). Factors negatively associated with female first authorship included poster format (OR 0.82, P=0.039) and conference location in the United States/Canada (OR 0.76, P=0.045). Similar trends were encountered for senior authorship. Productivity per senior author was similar between genders (P=0.160); whereas a gender gap in productivity per first author during 2007-2011 (P=0.020) equalized by 2017-2021 (P=0.300). Among the ten most productive authors of each gender, male authors delivered more presentations, but all authors shared similar format, content, and location. Women's representation in spine-related presentations did not increase at three major conferences over a 15-year period. Our findings regarding the positive effects of female mentorship, and international or virtual venues merit further investigation to address the gender gap. The upstream pipeline of recruiting women into academic spine surgery also needs to be addressed.


Pattern of corneal disorders in Ekiti: A tertiary eye center experience.
The cornea is the most significant refractive medium in the eye. Pathologies affecting the cornea usually have a great impact on vision. The etiology of corneal disorder varies from one geographical location to another. The objective of this study was to determine the pattern of corneal disorders at Ekiti State University Teaching Hospital, Ado-Ekiti. A retrospective study of case records of patients with cornea disorders over a 5-year period was carried out. Demographic characteristics, presenting visual acuity, and risk factor for cornea disorders were retrieved. Data were entered into the Statistical Package for the Social Sciences version 20, and statistical significance was inferred at P < 0.05. Corneal disorders accounted for 3.3% of the eye disorders seen during the period of study. The median age was 37 years. Males outnumbered females giving a ratio of 1.9:1 and the age range from 0.25 to 92 years. There were more females than males in the 11-20 years' age group. Students (84, 25.4%) and artisans (62, 18.8%) were the two leading occupational groups. Infectious cases constituted 27.2% of the cases. Visual acuity at presentation was <3/60 in 131 (39.7%) cases. Foreign body entry was the leading etiologic agent in 101 (30.6%) cases. Half of the patients were blind at presentation, and many of them presented after more than 1 week of the onset of symptoms. Corneal foreign body, trauma, and vernal keratoconjunctivitis were the leading known predisposing factors. There will be need to emphasize more on the role of protective eye devices among our people, especially those who engage in outdoor activities.


Identification of the iron-responsive element for the translational regulation of human ferritin mRNA.
Regulated translation of messenger RNA offers an important mechanism for the control of gene expression. The biosynthesis of the intracellular iron storage protein ferritin is translationally regulated by iron. A cis-acting element that is both necessary and sufficient for this translational regulation is present within the 5' nontranslated leader region of the human ferritin H-chain messenger RNA. In this report the iron-responsive element (IRE) was identified by deletional analysis. Moreover, a synthetic oligodeoxynucleotide was shown to be able to transfer iron regulation to a construct that would otherwise not be able to respond to iron. The IRE has been highly conserved and predates the evolutionary segregation between amphibians, birds, and man. The IRE may prove to be useful for the design of translationally regulated expression systems.


Incidence and Morphological Predictors of Intrastent Coronary Thrombus After Drug-Eluting Stent Implantation (from a Multicenter Registry).
The mechanisms responsible for late and very late stent thrombosis remain incompletely understood. This study aimed to evaluate the incidence and morphologic predictors of intrastent thrombus in patients after drug-eluting stent (DES) implantation using optical coherence tomography (OCT). A total of 208 patients with 262 DES who underwent follow-up OCT examination >6 months after DES implantation were included. The detailed vascular morphology including characteristics of neointima was analyzed. Thrombus was identified in 24 patients (11.5%) 11 months after DES implantation. Minimal lumen cross-sectional area was significantly smaller in the thrombus group than in the nonthrombus group (2.9 ± 1.7 vs 4.6 ± 2.0 mm(2); p <0.001). No difference was found in the frequency of uncovered or malapposed struts between the 2 groups. Thin-cap fibroatheroma (20.6% vs 0.1%; p <0.001) and heterogeneous neointima (22.2% vs 9.0%; p = 0.001) were more frequently detected in the thrombus group compared to the nonthrombus group. Second-generation DES showed lower incidence of thrombus, uncovered struts, and extrastent lumen compared with first-generation DES. In conclusion, the present OCT study revealed that smaller lumen cross-sectional area and neointimal morphology are important factors associated with intrastent thrombus. Second-generation DES demonstrated improved arterial healing and a lower incidence of intrastent thrombus compared with first-generation DES.


Molecular Diagnosis of Tubercular Lymphadenopathy from Fine-Needle Aspirates in Pediatric Patients.
The diagnosis of peripheral tubercular lymphadenopathy (TBLN) in pediatric patients is often a challenge because features evident on fine-needle aspiration cytology (FNAC) or tissue biopsy can be deceptive for the reason that they result from an immunological response. This study aimed to evaluate polymerase chain reaction (PCR) for Mycobacterium tuberculosis complex (MTBC) in pediatric patients under clinical suspicion for TBLN and to assess its role in the evaluation of cases cytodiagnosed as reactive lymphoid hyperplasia. This was a cross-sectional study conducted on 45 pediatric patients clinically suspected and unsuspected for TBLN. FNAC, culture on Löwenstein-Jensen medium, and real-time PCR were performed. Comparative values with reference to the culture were calculated. Cytology had a sensitivity and specificity of 38.5 and 87.5%, respectively. Real-time PCR had a sensitivity and specificity of 84.6 and 81.3%, respectively. Of the 32 cases with a cytodiagnosis of reactive lymphoid hyperplasia, 53% were positive both on PCR and culture for M. tuberculosis; the φ value of 0.93 demonstrated a strong association between these 2 methods. Real-time PCR is useful in detecting MTBC in pediatric patients, and it also helps in the diagnosis of cases missed on FNAC.