[Determination and clinical significance of colloid osmotic pressure in pediatric patients].
The clinical significance of colloid osmotic pressure (COP) in transcapillary fluid exchange and water homeostasis in health and disease is described. Under pathophysiological circumstances measurement of COP should be preferred to COP value calculation. After extensive COP experiences in critically ill adults and numerous refinements in COP monitoring technology, COP studies in neonates and paediatric intensive care patients have been published recently. In these patients hypovolaemia and need of volume replacement therapy are often associated with an increase in capillary permeability. Therefore prevention of general and interstitial colloid and fluid overload is a permanent challenge in the care of the young critically ill patient; e.g. in a case report. Consequently regular COP measurements should be considered in paediatric intensive care, especially in case of oncotic volume replacement therapy.


Urogenital Abnormalities in Adenosine Deaminase Deficiency.
Improved survival in ADA-SCID patients is revealing new aspects of the systemic disorder. Although increasing numbers of reports describe the systemic manifestations of adenosine deaminase deficiency, currently there are no studies in the literature evaluating genital development and pubertal progress in these patients. We collected retrospective data on urogenital system and pubertal development of 86 ADA-SCID patients followed in the period 2000-2017 at the Great Ormond Street Hospital (UK) and 5 centers in Italy. In particular, we recorded clinical history and visits, and routine blood tests and ultrasound scans were performed as part of patients' follow-up. We found a higher frequency of congenital and acquired undescended testes compared with healthy children (congenital, 22% in our sample, 0.5-4% described in healthy children; acquired, 16% in our sample, 1-3% in healthy children), mostly requiring orchidopexy. No urogenital abnormalities were noted in females. Spontaneous pubertal development occurred in the majority of female and male patients with a few cases of precocious or delayed puberty; no patient presented high FSH values. Neither ADA-SCID nor treatment performed (PEG-ADA, BMT, or GT) affected pubertal development or gonadic function. In summary, this report describes a high prevalence of cryptorchidism in a cohort of male ADA-SCID patients which could represent an additional systemic manifestation of ADA-SCID. Considering the impact urogenital and pubertal abnormalities can have on patients' quality of life, we feel it is essential to include urogenital evaluation in ADA-SCID patients to detect any abnormalities, initiate early treatment, and prevent long-term complications.


Cross-language tests of hemispheric strategies in reading nonwords.
Four experiments explored the effects of specific language characteristics on hemispheric functioning in reading nonwords using a lateralized trigram identification task. Previous research using nonsense consonant-vowel-consonant (CVC) trigrams has shown that total error scores reveal a right visual field (RVF) advantage in Hebrew, Japanese, and English. Qualitative error patterns have shown that the right hemisphere uses a sequential strategy, whereas the left hemisphere uses a more parallel strategy in English but shows the opposite pattern in Hebrew. Experiment 1 tested whether this is due to the test language or to the native language of the participants. Results showed that native language had a stronger effect on hemispheric strategies than test language. Experiment 2 showed that latency to target letters in the CVCs revealed the same asymmetry as qualitative errors for Hebrew speakers but not for English speakers and that exposure duration of the stimuli affected misses differentially according to letter position. Experiment 3 used number trigrams to equate reading conventions in the 2 languages. Qualitative error scores still revealed opposing asymmetry patterns. Experiments 1-3 used vertical presentations. Experiment 4 used horizontal presentation, which eliminated sequential processing in both hemispheres in Hebrew speakers, whereas English speakers still showed sequential processing in both hemispheres. Comparison of the 2 presentations suggests that stimulus arrangement affected qualitative errors in the left visual field but not the RVF for English speakers and in both visual fields for Hebrew speakers. It is suggested that these differences result from orthographic and morphological differences between the languages: Reading Hebrew requires attention to be deployed to all the constituents of the stimulus in parallel, whereas reading English allows sequential processing of the letters in both hemispheres. Implications of cross-language studies for models of hemispheric function are discussed.


One-pot Synthesis of Functional Poly(amino ester sulfide)s and Utility in Delivering pDNA and siRNA.
The development of efficacious carriers is an important long-standing challenge in gene therapy. In the past few decades, tremendous progress has been made toward non-viral vectors for gene delivery including cationic lipids and polymers. However, there continues to be a need for clinically translatable polymer-based delivery carriers because they offer tunable degradation profiles and functional groups, diverse structures/morphologies, and scalability in preparation. Herein, we developed a library of 144 degradable polymers with varying amine and hydrophobic content via a facile method that involves thiobutyrolactone aminolysis and consequent thiol-(meth)acrylate or acrylamide addition in one-pot. The polymer platform was evaluated for pDNA and siRNA delivery to HeLa cells in vitro. Hydrophobically modified 5S, 2E1, 6CY1, 5CY2, and 2M1 grafted HEMATL polymers are capable of delivering pDNA depending on the chemical composition and the size of the polyplexes. Hydrophobically modified 5S and 2B grafted HEMATL and 5S grafted ATL polymers exhibit capability for siRNA delivery that approaches the efficacy of commercially available transfection reagents. Due to tunable functionality and scalable preparation, this synthetic approach may have broad applicability in the design of delivery materials for gene therapy.


Deep Learning Model for the Automatic Classification of White Blood Cells.
Blood cell count is highly useful in identifying the occurrence of a particular disease or ailment. To successfully measure the blood cell count, sophisticated equipment that makes use of invasive methods to acquire the blood cell slides or images is utilized. These blood cell images are subjected to various data analyzing techniques that count and classify the different types of blood cells. Nowadays, deep learning-based methods are in practice to analyze the data. These methods are less time-consuming and require less sophisticated equipment. This paper implements a deep learning (D.L) model that uses the DenseNet121 model to classify the different types of white blood cells (WBC). The DenseNet121 model is optimized with the preprocessing techniques of normalization and data augmentation. This model yielded an accuracy of 98.84%, a precision of 99.33%, a sensitivity of 98.85%, and a specificity of 99.61%. The proposed model is simulated with four batch sizes (BS) along with the Adam optimizer and 10 epochs. It is concluded from the results that the DenseNet121 model has outperformed with batch size 8 as compared to other batch sizes. The dataset has been taken from the Kaggle having 12,444 images with the images of 3120 eosinophils, 3103 lymphocytes, 3098 monocytes, and 3123 neutrophils. With such results, these models could be utilized for developing clinically useful solutions that are able to detect WBC in blood cell images.


Photo-activatable Reagents for Bioorthogonal Ligation Reactions.
Light-induced bioorthogonal reactions offer spatiotemporal control over selective biomolecular labeling. This review covers the recent advances in the design of photo-activatable reagents for bioorthogonal conjugation reactions in living systems. These reagents are stable in the absence of light, but transformed into reactive species upon light illumination, which then undergo rapid ligation reactions. The light wavelength has been tuned from ultraviolet to near infrared to enable efficient photo-activation in reactions in deep tissues. The most prominent photo-activatable reagents are presented, including tetrazoles, tetrazines, 9,10-phenanthrenequinone, diarylsydnones, and others. A particular focus is on the strategies for improving reaction kinetics and biocompatibility accomplished through careful molecular engineering. The utilities of these photo-activatable reagents are illustrated through a broad range of biological applications, including in vivo protein labeling, positron emission tomography (PET) imaging, responsive hydrogels, and fluorescence microscopy. The further development and optimization of these biocompatible photo-activatable reagents should lead to new chemical biology strategies for studying biomolecular structure and function in living systems.


The Transcriptional Landscape of Polyploid Wheats and Their Diploid Ancestors during Embryogenesis and Grain Development.
Modern wheat production comes from two polyploid species, Triticum aestivum and Triticum turgidum (var durum), which putatively arose from diploid ancestors Triticum urartu, Aegilops speltoides, and Aegilops tauschii How gene expression during embryogenesis and grain development in wheats has been shaped by the differing contributions of diploid genomes through hybridization, polyploidization, and breeding selection is not well understood. This study describes the global landscape of gene activities during wheat embryogenesis and grain development. Using comprehensive transcriptomic analyses of two wheat cultivars and three diploid grasses, we investigated gene expression at seven stages of embryo development, two endosperm stages, and one pericarp stage. We identified transcriptional signatures and developmental similarities and differences among the five species, revealing the evolutionary divergence of gene expression programs and the contributions of A, B, and D subgenomes to grain development in polyploid wheats. The characterization of embryonic transcriptional programming in hexaploid wheat, tetraploid wheat, and diploid grass species provides insight into the landscape of gene expression in modern wheat and its ancestral species. This study presents a framework for understanding the evolution of domesticated wheat and the selective pressures placed on grain production, with important implications for future performance and yield improvements.plantcell;31/12/2888/FX1F1fx1.


Costs of breast cancer recurrence after initial treatment for HR+, HER2-, high-risk early breast cancer: estimates from SEER-Medicare linked data.
To assess the costs of treated recurrence and survival in elderly patients with early breast cancer (EBC) at high risk of recurrence using Surveillance Epidemiology and End Results (SEER) registry-Medicare linked claims data. This retrospective study included patients aged ≥65 years with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive EBC at high risk of recurrence. Treated recurrences were defined based on treatment events/procedure codes from claims. Primary outcomes were monthly total extra costs and cumulative extra costs of treated recurrence relative to patients with non/untreated recurrence. Costs were calculated using Kaplan-Meier sampling average estimator method and inflated to 2021 US$. Secondary outcomes included analysis by recurrence type and overall survival (OS) after recurrence. Subgroup analysis evaluated costs in patients with Medicare Part D coverage. Among 3081 eligible patients [mean (SD) age at diagnosis was 74.5 (7.1) years], the majority were females (97.4%) and white (87.8%). Treated recurrence was observed in 964 patients (31.3%). The monthly extra cost of treated recurrence was highest at the beginning of the first treated recurrence episode with 6-year cumulative cost of $117,926. Six-year cumulative extra costs were higher for patients with distant recurrences ($168,656) than for patients with locoregional recurrences ($96,465). Median OS was 4.34 years for all treated recurrences, 1.92 years for distant recurrence, and 6.78 years for locoregional recurrence. Similar cumulative extra cost trends were observed in the subgroup with Part D coverage as in the overall population. This study utilizes claims data to identify treated recurrence. Due to age constraints of the dataset, results may not extrapolate to a younger population where EBC is commonly diagnosed. EBC recurrence in this elderly population has substantial costs, particularly in patients with distant recurrences. Therapies that delay or prevent recurrence may reduce long-term costs significantly.


Extraneuraxial hemangioblastoma: A clinicopathologic study of 10 cases with molecular analysis of the VHL gene.
Less than 250 extraneuraxial hemangioblastomas occurring in paraneuraxial or peripheral sites have been reported to date, sporadically or in the setting of von Hippel-Lindau disease. Seventeen such cases underwent molecular genetic analysis, using either the patient's peripheral blood in 9 cases or paraffin embedded tumor tissue in the rest. VHL gene mutations were documented in 3/9 cases in which DNA from peripheral blood lymphocytes was used, all with clinically manifest von Hippel-Lindau disease; instead, no VHL gene alterations were found in all of the 8 cases with sporadic extraneuraxial hemangioblastoma in which DNA from tumor tissue was analyzed. Our aim is to investigate the molecular genetic profile of the VHL gene in extraneuraxial hemangioblastoma using paraffin embedded tumor tissues. The clinical features, histopathology, and molecular investigations of 10 extraneuraxial hemangioblastomas (7 females, 3 males; median age: 47 years) are presented herein. The histopathologic diagnosis was supported by immunohistochemistry (10/10) and electron microscopy (4/10). Molecular genetic analysis was conducted (10/10) for VHL gene mutations, LOH, and gene promoter methylation. Two of the present cases were already published with only limited or no molecular investigations. Four tumors of the present series were paraneuraxial, and 6 peripheral (2 involved soft tissues, and 4 the kidney). One tumor was von Hippel-Lindau disease-associated, 1 was classified as "hemangioblastoma-only VHLD", 7 were sporadic, and one was unknown. All were histopathologically analogous to their counterpart located inside the central nervous system. Immunophenotypically, all tumors expressed vimentin, S-100, NSE, and alpha-inhibin (10/10). Ultrastructurally, unbound lipid droplets filled the cytoplasms of the stromal cells. Molecular analysis revealed 3 inactivating mutations (1 germline, two somatic) in the coding sequence of the VHL gene in 2 different extraneuraxial hemangioblastomas, and LOH in 4 (two as a double hit), all non-renal extraneuraxial hemangioblastomas. Methylation analysis failed to disclose promoter methylation in any case. In conclusion, we report eight new cases from the wide category of extraneuraxial hemangioblastomas (4 paraneuraxial, and 4 renal), one of which was von Hippel-Lindau disease-associated and 7 sporadic. VHL gene alterations were found not only in the von Hippel-Lindau disease-associated tumor, but - for the first time - also in 3 sporadic ones, two of which with novel mutations.


California dragonfly and damselfly (Odonata) database: temporal and spatial distribution of species records collected over the past century.
The recently completed Odonata database for California consists of specimen records from the major entomology collections of the state, large Odonata collections outside of the state, previous literature, historical and recent field surveys, and from enthusiast group observations. The database includes 32,025 total records and 19,000 unique records for 106 species of dragonflies and damselflies, with records spanning 1879-2013. Records have been geographically referenced using the point-radius method to assign coordinates and an uncertainty radius to specimen locations. In addition to describing techniques used in data acquisition, georeferencing, and quality control, we present assessments of the temporal, spatial, and taxonomic distribution of records. We use this information to identify biases in the data, and to determine changes in species prevalence, latitudinal ranges, and elevation ranges when comparing records before 1976 and after 1979. The average latitude of where records occurred increased by 78 km over these time periods. While average elevation did not change significantly, the average minimum elevation across species declined by 108 m. Odonata distribution may be generally shifting northwards as temperature warms and to lower minimum elevations in response to increased summer water availability in low-elevation agricultural regions. The unexpected decline in elevation may also be partially the result of bias in recent collections towards centers of human population, which tend to occur at lower elevations. This study emphasizes the need to address temporal, spatial, and taxonomic biases in museum and observational records in order to produce reliable conclusions from such data.


[Role of the homologous translocation, located on the Y-chromosome, in mutagenesis of the double super-unstable system in Drosophila melanogaster males].
Main features of mutagenesis induced in the double super-unstable system in Drosophila melanogaster males and females was studied earlier. Very different y- and sc-alleles arose under the mutagenesis. These are differed one from another by the expression of yellow and scute loci. However, it was shown that the female's mutagenesis very differed from the male's one. The structure of a homologous chromosome has played an important role in the mutagenesis in Drosophila females. We found here that the homologous translocation in Y chromosome led to double decrease of the frequency of the mutagenesis in males. It is proposed that interconnections between two homologous insertions are essential in the recombinational processes by which alleles change. The nature and mechanism of the sub-lethal allele's formation in the presence of translocation in Y chromosome is discussed.


Recent Developments in the Treatment of Ankle and Subtalar Instability.
It was nearly a centenary ago that severe ankle sprain was recognized as an injury of the ankle ligament(s). With the recent technological advances and tools in imaging and surgical procedures, the management of ankle sprains - including subtalar injuries - has drastically improved. The repair or reconstruction of ankle ligaments is getting more anatomical and less invasive than previously. More specifically, ligamentous reconstruction with tendon graft has been the gold standard in the management of severely damaged ligament, however, it does not reproduce the original ultrastructure of the ankle ligaments. The anatomical ligament structure of a ligament comprises a ligament with enthesis at both ends and the structure should also exhibit proprioceptive function. To date, it remains impossible to reconstruct a functionally intact and anatomical ligament. Cooperation of the regenerative medicine and surgical technology in expected to improve reconstructions of the ankle ligament, however, we need more time to develop a technology in reproducing the ideal ligament complex.


Alu-directed transcriptional regulation of some novel miRNAs.
Despite many studies on the biogenesis, molecular structure and biological functions of microRNAs, little is known about the transcriptional regulatory mechanisms controlling the spatiotemporal expression pattern of human miRNA gene loci. Several lines of experimental results have indicated that both polymerase II (Pol-II) and polymerase III (Pol-III) may be involved in transcribing miRNAs. Here, we assessed the genomic evidence for Alu-directed transcriptional regulation of some novel miRNA genes in humans. Our data demonstrate that the expression of these Alu-related miRNAs may be modulated by Pol-III. We present a comprehensive exploration of the Alu-directed transcriptional regulation of some new miRNAs. Using a new computational approach, a variety of Alu-related sequences from multiple sources were pooled and filtered to obtain a subset containing Alu elements and characterized miRNA genes for which there is clear evidence of full-length transcription (embedded in EST). We systematically demonstrated that 73 miRNAs including five known ones may be transcribed by Pol-III through Alu or MIR. Among the new miRNAs, 33 were determined by high-throughput Solexa sequencing. Real-time TaqMan PCR and Northern blotting verified that three newly identified miRNAs could be induced to co-express with their upstream Alu transcripts by heat shock or cycloheximide. Through genomic analysis, Solexa sequencing and experimental validation, we have identified candidate sequences for Alu-related miRNAs, and have found that the transcription of these miRNAs could be governed by Pol-III. Thus, this study may elucidate the mechanisms by which the expression of a class of small RNAs may be regulated by their upstream repeat elements.


Variable water input controls evolution of the Lesser Antilles volcanic arc.
Oceanic lithosphere carries volatiles, notably water, into the mantle through subduction at convergent plate boundaries. This subducted water exercises control on the production of magma, earthquakes, formation of continental crust and mineral resources. Identifying different potential fluid sources (sediments, crust and mantle lithosphere) and tracing fluids from their release to the surface has proved challenging1. Atlantic subduction zones are a valuable endmember when studying this deep water cycle because hydration in Atlantic lithosphere, produced by slow spreading, is expected to be highly non-uniform2. Here, as part of a multi-disciplinary project in the Lesser Antilles volcanic arc3, we studied boron trace element and isotopic fingerprints of melt inclusions. These reveal that serpentine-that is, hydrated mantle rather than crust or sediments-is a dominant supplier of subducted water to the central arc. This serpentine is most likely to reside in a set of major fracture zones subducted beneath the central arc over approximately the past ten million years. The current dehydration of these fracture zones coincides with the current locations of the highest rates of earthquakes and prominent low shear velocities, whereas the preceding history of dehydration is consistent with the locations of higher volcanic productivity and thicker arc crust. These combined geochemical and geophysical data indicate that the structure and hydration of the subducted plate are directly connected to the evolution of the arc and its associated seismic and volcanic hazards.


Mammographic parenchymal patterns and self-reported soy intake in Singapore Chinese women.
The study aimed to investigate whether self-reported dietary variables were associated with mammographic parenchymal patterns, which have been shown to predict risk of breast cancer. Among the 3,421 women, ages 45-74 years, common to two independent population-based cohorts, mammographic parenchymal patterns and current dietary habits were assessed for 406 randomly chosen participants. Logistic regression methods were used to compare dietary and other lifestyle profiles between subjects classified as displaying high (cases) and low risk (controls) parenchymal patterns. After adjustment for energy intake and other potential confounders, dietary soy protein intake was inversely related to risk of high-risk parenchymal pattern (odds ratio, 0.41; 95% confidence interval, 0.18-0.94, highest versus lowest quartile of intake). Similarly, the highest versus lowest quartile of dietary soy isoflavone intake was significantly related to low-risk parenchymal patterns (odds ratio, 0.44; 95% confidence interval, 0.20-0.98). The association between high soy intake and a reduced risk of mammographic parenchymal patterns that are associated with high breast cancer risk may have important implications in breast cancer prevention.


Endoscopic closure of colon perforation compared to surgery in a porcine model: a randomized controlled trial (with videos).
Endoscopic closure of inadvertent or intentional colon perforations might be valuable if comparable to surgical closure. The aim of this study was to compare endoscopic closure of a 4-cm colon perforation in a porcine model with surgical closure in a multicenter study. University hospitals in the United States and Europe. After creating a 4-cm linear colon perforation, the animals were randomized to either endoscopic or surgical closure. The total procedure time from the beginning of perforation to the completion of procedure was measured. The animals were euthanized after 2 weeks to evaluate healing, unless there was a complication. Fifty-four animals were randomized to either surgical or endoscopic closure of colon perforation. Eight animals developed complications, and 7 of these were euthanized before 2 weeks. Twenty-three animals in each group survived for 2 weeks. Surgical closure of the perforation was successful in all animals in that group, and endoscopic closure was successful in 25 of the 27 animals. The median procedure time was shorter in the surgery group compared to the endoscopy group (35 vs 44 minutes, P = .016). Peritonitis, local adhesions, and leak test results were comparable in both groups. Distant adhesions were less frequent in the endoscopic closure group (26.1% vs 56.5%, P = .03). Five of the 186 T-tags (2.7%) were noted in the adjacent viscera. This porcine study does not mimic clean colon perforation in humans; it mimics dirty colon perforation in humans. Endoscopic closure of a 4-cm colon perforation was comparable to surgery, and this technique can be potentially used for closure of intentional or inadvertent colon perforations.


Knowledge, Attitudes, Practices and Information Needs During the COVID-19 Pandemic in Indonesia.
In the absence of vaccines and specific drugs, prevention effort has been attributed as the primary control mechanism of COVID-19. Knowledge, attitude, and practice are used to determine the current situation and formulate appropriate control interventions as well as risk communication. This study, therefore, aims to assess knowledge, attitude, practice and information needs about COVID-19 in Indonesian society. A cross-sectional study was conducted through an online survey in the third week of August 2020. Purposive and random sampling was used to select the respondents. People with a minimum age of 18 years and residing in Indonesia were allowed to participate in this study. The survey was conducted with an online questionnaire that spread on several platforms such as WhatsApp, Instagram and Facebook by distributing the link and continuous chain messages on that platform. Data were analysed using descriptive, chi-square and logistic regression test. A total of 816 respondents were included in this study. In general, public knowledge about COVID-19 was sufficient, but some topic areas were still low. Most people had a positive attitude about the COVID-19, but they provided a negative response to government policies. Most of the community has taken preventive measures for COVID-19. However, some behaviours received a low percentage. Information about how to prevent COVID-19 was the most wanted information during this pandemic. Social media was a favourite source of information, with the most popular type of visualisation was a table containing numbers. Age and education were significantly associated with knowledge. Some attitudes were affected by age and occupation scope. Gender and health insurance ownership significantly associated with preventive measures. This research highlights the importance of providing valid, effective, efficient, and continuous information to the public through appropriate channels to increase understanding about COVID-19 precautions.


Variation in Care for Patients with Irritable Bowel Syndrome in the United States.
Irritable bowel syndrome (IBS) affects nearly one in seven Americans. Significant national variations in care may exist, due to a current lack of standardized diagnosis and treatment algorithms; this can translate into a substantial additional economic burden. The study examines healthcare resource utilization in patients with IBS and in the subset of IBS patients with constipation (IBS-C) and analyzes the variation of IBS care for these patients across the United States (US). Healthcare resource use (HRU), including gastrointestinal (GI) procedures and tests, all-cause and intestinal-related medical visits, GI specialist visits, and constipation or diarrhea pharmacy prescriptions for IBS patients enrolled in a large US administrative claims database (2001-2012) were analyzed for the 24-month period surrounding first diagnosis. Multivariate regression models, adjusting for age, gender, year of first diagnosis, insurance type, and Charlson comorbidity index, compared HRU across states (each state vs. the average of all other states). Of 201,322 IBS patients included, 77.2% were female. Mean age was 49.4 years. One in three patients had ≥3 distinct GI medical procedures or diagnostic tests; 50.1% visited a GI specialist. Significant HRU differences were observed in individual states compared to the national average. IBS-C patients had more medical visits, procedures, and pharmacy prescriptions for constipation/diarrhea than IBS patients without constipation. This study is the first to identify considerable regional variations in IBS healthcare across the US and to note a markedly higher HRU by IBS-C patients than by IBS patients without constipation. Identifying the reasons for these variations may improve quality of care and reduce the economic burden of IBS.


Topographical specificity of regulation of respiratory and renal sympathetic activity by the midbrain dorsolateral periaqueductal gray.
The midbrain periaqueductal gray (PAG) mediates the physiological responses to a wide range of stressors. It consists of four longitudinal columns that have different anatomical connections and functional properties. Previous anatomical and behavioral studies have led to the hypothesis that the dorsolateral PAG, but not the adjacent lateral and dorsomedial subregions, is a key center that integrates the behavioral response to acute psychological threatening stimuli. In this study, we tested whether, consistent with this hypothesis, activation of neurons in the dorsolateral PAG evokes a pattern of cardiovascular and respiratory responses that is distinct from that evoked from surrounding regions. Arterial pressure, heart rate, renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) were recorded simultaneously in urethane-anesthetized rats. Microinjections of very small amounts of d,l-homocysteic acid (750 pmol in 15 nl) were made in sites throughout the dorsomedial, dorsolateral, and lateral PAG subregions. Increases in RSNA of similar magnitude accompanied by small to moderate increases in arterial pressure and heart rate were evoked from all three PAG subregions. In contrast, large increases in both PNA burst rate (respiratory rate) and overall respiratory activity were evoked only from a highly circumscribed region that corresponded closely to the dorsolateral PAG subregion at an intermediate to caudal level. Within this region, the evoked increases in RSNA and respiratory activity were highly correlated (r = 0.914, P < 0.001), suggesting the possibility that a common population of "command neurons" within the dorsolateral PAG may generate both sympathetic and respiratory responses from this region.


Towards intellectual freedom in an AI Ethics Global Community.
The recent incidents involving Dr. Timnit Gebru, Dr. Margaret Mitchell, and Google have triggered an important discussion emblematic of issues arising from the practice of AI Ethics research. We offer this paper and its bibliography as a resource to the global community of AI Ethics Researchers who argue for the protection and freedom of this research community. Corporate, as well as academic research settings, involve responsibility, duties, dissent, and conflicts of interest. This article is meant to provide a reference point at the beginning of this decade regarding matters of consensus and disagreement on how to enact AI Ethics for the good of our institutions, society, and individuals. We have herein identified issues that arise at the intersection of information technology, socially encoded behaviors, and biases, and individual researchers' work and responsibilities. We revisit some of the most pressing problems with AI decision-making and examine the difficult relationships between corporate interests and the early years of AI Ethics research. We propose several possible actions we can take collectively to support researchers throughout the field of AI Ethics, especially those from marginalized groups who may experience even more barriers in speaking out and having their research amplified. We promote the global community of AI Ethics researchers and the evolution of standards accepted in our profession guiding a technological future that makes life better for all.


Diagnostic accuracy of magnetic resonance imaging in endometrial cancer.
The objectives of this study were to investigate the accuracy of magnetic resonance imaging (MRI) in predicting the depth of myometrial invasion in the preoperative assessment of women with endometrial cancer and to quantify the impact of MRI as an adjunct to predicting patients requiring full surgical staging. This was a diagnostic accuracy study of prospective cases in conjunction with STARD guidelines using collected data from a tumor board within a cancer network. Consecutive series of all endometrial cancers in Northern Ireland over a 21-month period was discussed at the Gynaecological Oncology Multidisciplinary Team/tumor board meeting. This study concerns 183 women who met all the inclusion criteria. Main outcome measure was the correlation between the depth of myometrial invasion suggested by preoperative MRI study and the subsequent histopathological findings following examination of the hysterectomy specimen. Secondary end point was how MRI changed management of women who required surgery to be performed at a central cancer center. For the detection of outer-half myometrial invasion, overall sensitivity of MRI was 0.73 (95% confidence interval [CI], 0.59-0.83), and specificity was 0.83 (95% CI, 0.76-0.89). The positive predictive value was 0.63 (95% CI, 0.50-0.74), and negative predictive value was 0.89 (95% CI, 0.82-0.93). Positive likelihood ratio was 4.35 (95% CI, 2.87-6.61), and negative likelihood ratio was 0.33 (95% CI, 0.21-0.52). Magnetic resonance imaging improved the sensitivity and negative predictive value of endometrial biopsy alone in predicting women with endometrial cancer who require full surgical staging (0.73 vs 0.65 and 0.80 vs 0.78, respectively). Preoperative pelvic MRI is a moderately sensitive and specific method of identifying invasion to the outer half of myometrium in endometrial cancer. Addition of MRI to preoperative assessment leads to improved preoperative assessment, triage, and treatment.


Simultaneous nonrigid registration of multiple point sets and atlas construction.
Groupwise registration of a set of shapes represented by unlabeled point sets is a challenging problem since, usually, this involves solving for point correspondence in a nonrigid motion setting. In this paper, we propose a novel and robust algorithm that is capable of simultaneously computing the mean shape, represented by a probability density function, from multiple unlabeled point sets(represented by finite-mixture models), and registering them nonrigidly to this emerging mean shape. This algorithm avoids the correspondence problem by minimizing the Jensen-Shannon (JS) divergence between the point sets represented as finite mixtures of Gaussian densities. We motivate the use of the JS divergence by pointing out its close relationship to hypothesis testing. Essentially,minimizing the JS divergence is asymptotically equivalent to maximizing the likelihood ratio formed from a probability density of the pooled point sets and the product of the probability densities of the individual point sets. We derive the analytic gradient of the cost function, namely, the JS-divergence, in order to efficiently achieve the optimal solution. The cost function is fully symmetric, with no bias toward any of the given shapes to be registered and whose mean is being sought. A by-product of the registration process is a probabilistic atlas, which is defined as the convex combination of the probability densities of the input point sets being aligned. Our algorithm can be especially useful for creating atlases of various shapes present in images and for simultaneously (rigidly or nonrigidly)registering 3D range data sets (in vision and graphics applications), without having to establish any correspondence. We present experimental results on nonrigidly registering 2D and 3D real and synthetic data (point sets).


Accuracy of daily fluid intake measurements using a "smart" water bottle.
High fluid intake is an effective preventative strategy against recurrent kidney stones but is known to be challenging to achieve. Recently, a smart water bottle (Hidrate Spark™, Minneapolis, MN) was developed as a non-invasive fluid intake monitoring system. This device could help patients who form stones from low urine volume achieve sustainable improvements in hydration, but has yet to be validated in a clinical setting. Hidrate Spark™ uses capacitive touch sensing via an internal sensor. It calculates volume measurements by detecting changes in water level and sends data wirelessly to users' smartphones through an application. A pilot study was conducted to assess accuracy of measured fluid intake over 24 h periods when used in a real life setting. Subjects were provided smart bottles and given short tutorials on their use. Accuracy was determined by comparing 24-h fluid intake measurements calculated through the smart bottle via sensor to standard volume measurements calculated by the patient from hand over the same 24 h period. Eight subjects performed sixty-two 24-h measurements (range 4-14). Mean hand measurement was 57.2 oz/1692 mL (21-96 oz/621-2839 mL). Corresponding mean smart bottle measurement underestimated true fluid intake by 0.5 ozs. (95% CI -1.9, 0.9). Percent difference between hand and smart bottle measurements was 0.0% (95% CI - 3%, 3%). Intraclass correlation coefficient (ICC), calculated to assess consistency between hand measures and bottle measures, was 0.97 (0.95, 0.98) indicating an extremely high consistency between measures. 24-h fluid intake measurements from a novel fluid monitoring system (Hidrate Spark™) are accurate to within 3%. Such technology may be useful as a behavioral aide and/or research tool particularly among recurrent stone formers with low urinary volume.


Observational evidence for a possible new diffusion path.
Transmission electron microscopy of experimentally deformed amphibolite suggests that submicroscopic intracrystalline tubes formed around linear defects may be a previously unrecognized kind of diffusion pathway. Deformed and compositionally altered plagioclase and amphibole crystals include moderate densities of linear defects that morphologically resemble unit dislocations but display unusual contrast. During prolonged electron irradiation, the core regions of the defects expand to well-defined tubes that are approximately 20 nanometers in diameter. Both observations suggest that the regions about the defect cores are glassy and were filled with silicate-water fluid during the experiments. Intracrystalline transport along these tubes would likely be several orders of magnitude faster than traditionally conceived processes of solid-state volume diffusion, grain-boundary solvent transfer, and ordinary pipe diffusion along dislocation cores.


Two new pimelic diphenylamide HDAC inhibitors induce sustained frataxin upregulation in cells from Friedreich's ataxia patients and in a mouse model.
Friedreich's ataxia (FRDA), the most common recessive ataxia in Caucasians, is due to severely reduced levels of frataxin, a highly conserved protein, that result from a large GAA triplet repeat expansion within the first intron of the frataxin gene (FXN). Typical marks of heterochromatin are found near the expanded GAA repeat in FRDA patient cells and mouse models. Histone deacetylase inhibitors (HDACIs) with a pimelic diphenylamide structure and HDAC3 specificity can decondense the chromatin structure at the FXN gene and restore frataxin levels in cells from FRDA patients and in a GAA repeat based FRDA mouse model, KIKI, providing an appealing approach for FRDA therapeutics. In an effort to further improve the pharmacological profile of pimelic diphenylamide HDACIs as potential therapeutics for FRDA, we synthesized additional compounds with this basic structure and screened them for HDAC3 specificity. We characterized two of these compounds, 136 and 109, in FRDA patients' peripheral blood lymphocytes and in the KIKI mouse model. We tested their ability to upregulate frataxin at a range of concentrations in order to determine a minimal effective dose. We then determined in both systems the duration of effect of these drugs on frataxin mRNA and protein, and on total and local histone acetylation. The effects of these compounds exceeded the time of direct exposure in both systems. Our results support the pre-clinical development of a therapeutic approach based on pimelic diphenylamide HDACIs for FRDA and provide information for the design of future human trials of these drugs, suggesting an intermittent administration of the drug.


Hepatocellular carcinoma and survival in patients with primary biliary cirrhosis.
The incidence of hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) is not well known. The aims of this study are to determine HCC incidence and survival, and to identify risk factors associated with these outcomes in patients with PBC. We collected information on 396 patients with PBC at enrollment and followed-up from 6 to 271 months. They were all negative for hepatitis B and C virus markers. HCC was detected by scanning with ultrasonography, computed tomography, or both every 4 to 6 months. Life expectancy (LE) was approximated with the declining exponential approximation of LE. A total of 14 patients developed HCC. The cumulative appearance rate of HCC in patients with advanced-stage PBC (Scheuer's stage III or IV) was significantly higher than that for patients with early-stage (stage I or II) (12.3% and 7.7% by the tenth year, respectively. P =.021). Proportional hazards analysis showed 3 factors are independently associated with the development of HCC: age at the time of diagnosis, male gender, and history of blood transfusion. Age, male gender, and advanced-stage PBC were associated with survival, but HCC development was not. The disease-specific annual mortality rate was estimated to be 0.008 for women and 0.028 for men with advanced-stage PBC. In conclusion, HCC develops in old patients with advanced-stage PBC, but HCC does not affect the patients' survival.


Dentin permeability: changes produced by iontophoresis.
Iontophoretic currents (0--1.0 mA) were applied to dentin disks prepared from human third molars. A negative electrode increased 125I-permeation 10X, while a positive electrode increased 14C-lidocaine 8X. Iontophoresis appears promising as a method to increase the permeation of dentin by ionized substances of therapeutic interest.


Examination for heat-labile, heat-stable, and Shiga-like toxins and for the eaeA gene in Escherichia coli isolates obtained from dogs dying with diarrhea: 122 cases (1992-1996).
To examine Escherichia coli isolates obtained from dogs dying with diarrhea for heat-labile, heat-stable, and Shiga-like toxins and for the eaeA gene, which is associated with attaching and effacing lesions. Retrospective study. 122 dogs. E coli isolates were tested by means of dot-blot hybridization of DNA extracts of cultured bacteria. Medical records of dogs from which E coli isolates with virulence genes had been isolated were examined, and histologic findings and evidence of intercurrent bacterial and viral infections were recorded. None of the E coli isolates obtained from these dogs produced heat-labile, heat-stable, or Shiga-like toxins; however, E coli isolates from 44 of 122 dogs were found to have the eaeA gene. Histologically, multifocal bacterial adherence to the epithelium and epithelial necrosis and detachment were seen in colonic specimens from 20 of 44 (45%) dogs. Escherichia coli was the sole pathogen identified in 15 of 44 (34%) dogs. Intercurrent pathogens, including canine parvovirus (n = 19), Clostridium perfringens (8), rotavirus (5), hookworms (3), coccidia (3), and Salmonella agona (1), were identified in the remaining 29 (66%) dogs. Attaching and effacing E coli can be a primary or secondary pathogen in dogs with diarrhea. Antibiotic treatment is indicated in dogs with diarrhea because of the possibility that it is primarily bacterial in origin and because, even if it is primarily viral in origin, there may be secondary bacterial infection.


Glutathione conjugation of perchloroethylene in rats and mice in vitro: sex-, species-, and tissue-dependent differences.
Perchloroethylene (Per)-induced nephrotoxicity and nephrocarcinogenicity have been associated with metabolism by the glutathione (GSH) conjugation pathway to form S-(1,2,2-trichlorovinyl)glutathione (TCVG). Formation of TCVG was determined in incubations of Per and GSH with isolated renal cortical cells and hepatocytes from male and female Fischer 344 rats and with renal and hepatic cytosol and microsomes from male and female Fischer 344 rats and B6C3F1 mice. The goal was to assess the role of metabolism in the sex and species dependence of susceptibility to Per-induced toxicity. A key finding was that GSH conjugation of Per occurs in kidney as well as in liver. Although amounts of TCVG formation in isolated kidney cells and hepatocytes from male and female rats were generally similar, TCVG formation in subcellular fractions showed marked sex, species, and tissue dependence. This may be due to the presence of multiple pathways for metabolism in intact cells, whereas only the GSH conjugation pathway is active in the subcellular fractions under the present assay conditions. TCVG formation in kidney and liver subcellular fractions from both male rats and mice were invariably higher than corresponding values in female rats and mice. Amounts of TCVG formation in rat liver subcellular fractions were approximately 10-fold higher than in corresponding fractions from rat kidney. Although rats are more susceptible to Per-induced renal tumors than mice, amounts of TCVG formation were 7- to 10-fold higher in mouse kidney subcellular fractions and 2- to 5-fold higher in mouse liver subcellular fractions of both sexes compared to corresponding fractions from the rat. Hence, although the higher amounts of TCVG formation in liver and kidney from male rats correspond to their higher susceptibility to Per-induced renal tumors compared with female rats, the markedly higher amounts of TCVG formation in mice compared with rats suggest that other enzymatic or transport steps in the handling of Per in mice contribute to their relatively low susceptibility to Per-induced renal tumors


The interaction of norepinephrine excretion with blood pressure and race in children.
The purpose of this study was to examine the relationship between urinary norepinephrine excretion and blood pressure, and to determine the influence of race on this relationship. Urinary norepinephrine was used to estimate renal and systemic sympathetic nervous system (SNS) activity. Fifty black and forty-nine white normotensive children aged 9-14 years had their blood pressure measured, and provided an overnight urine sample. Urinary norepinephrine was measured by radioenzymatic assay. Excretion rates of norepinephrine were expressed per milligram urinary creatinine. Black children had age-adjusted mean diastolic and systolic blood pressure which was higher than in white children. For both blacks and whites, nocturnal urinary norepinephrine excretion rates were positively related to age-adjusted mean diastolic blood pressure, but not to systolic blood pressure. Norepinephrine excretion was significantly lower in black children compared with white children. These findings suggest that the higher blood pressures in black children were not causally related to greater SNS activity. The SNS may have been suppressed in black children, possibly by a greater expansion of plasma volume, alternatively, black children may have been more sensitive to the influences of the SNS than white children.


CircUbe3a from M2 macrophage-derived small extracellular vesicles mediates myocardial fibrosis after acute myocardial infarction.
Objective: This study aimed to explore the role of circular RNAs (circRNAs) in M2 macrophage (M2M)-derived small extracellular vesicles (SEVs) in myocardial fibrosis development. Methods: The regulatory role of M2M-derived extracellular vesicles (EVs) was evaluated in a mouse model of acute myocardial infarction. Immunofluorescence, quantitative real-time PCR (RT-qPCR), nanoparticle tracking analysis, Western blot analysis and electron microscopy were used to identify macrophages, large extracellular vesicles (LEVs) and SEVs. The circRNA expression profiles of M0 macrophages (M0Ms) and M2Ms were determined by microarray analysis. Bioinformatic analysis, cell coculture and cell proliferation assays were performed to investigate the expression, function, and regulatory mechanisms of circUbe3a in vitro. qPCR, RNA immunoprecipitation (RIP), dual-luciferase reporter assays, RNA fluorescence in situ hybridization (RNA-FISH), Western blot analysis and a series of rescue experiments were used to verify the correlation among circUbe3a, miR-138-5p and RhoC. Results: CircUbe3a from M2M-derived SEVs triggered functional changes in cardiac fibroblasts (CFs). CircUbe3a was synthesized and loaded into SEVs during increased M2M infiltration after myocardial infarction. The fusion of the released SEVs with the plasma membrane likely caused the release of circUbe3a into the cytosol of CFs. Silencing or overexpressing circUbe3a altered CF proliferation, migration, and phenotypic transformation in vitro. We confirmed that circUbe3a plays a crucial role in enhancing functional changes in CFs by sponging miR-138-5p and then translationally repressing RhoC in vitro. In vivo, the addition of M2M-derived SEVs or overexpression of circUbe3a significantly exacerbated myocardial fibrosis after acute myocardial infarction, and these effects were partially abolished by circUbe3a-specific shRNA. Conclusions: Our findings suggest that M2M-derived circUbe3a-containing SEVs promote the proliferation, migration, and phenotypic transformation of CFs by directly targeting the miR-138-5p/RhoC axis, which may also exacerbate myocardial fibrosis after acute myocardial infarction.


Actuarial status of the OASI (old age survivors insurance) and DI (disability insurance) Trust Funds.
This article summarizes the current financial condition and actuarial status of the Old-Age, Survivors, and Disability Insurance (OASDI) program, as shown in the 1987 Annual Report of the Board of Trustees. The Trustees note that the assets of the OASI and DI Trust Funds, on a combined basis, will be sufficient to permit the timely payment of OASDI benefits for many years into the future, on the basis of all four sets of assumptions shown in the report. For the next 75 years, the estimates show that the OASDI program, overall, is in close actuarial balance, based on the two intermediate sets of assumptions. The DI program by itself, however, is not in close actuarial balance for the next 75 years. The actuarial deficit for the DI program could be remedied by a small reallocation of the contribution rate from OASI to DI, in such a way that the OASI program would remain in close actuarial balance and OASDI benefits would not be affected. Although the Trustees are not recommending such a reallocation, they note that the financial condition of the DI program will need to be carefully monitored.


Cucurbitacins as inducers of cell death and a rich source of potential anticancer compounds.
Triterpenes have been reported to induce cell death. One relevant group of this family of compounds is cucurbitacins, which have been studied as inducers of apoptosis in various cancer cell lines. The most significant mechanisms with regard to the apoptotic effects of cucurbitacins are their ability to modify transcriptional activities via nuclear factors or genes and their capability to activate or inhibit pro- or anti-apoptotic proteins. Still, while the majority of studies on these compounds have dealt with their apoptotic effects on cancer cell lines, several research groups have also explored their anti-inflammatory activities. In general, cucurbitacins are considered to be selective inhibitors of the JAK/STAT pathways; however, other mechanisms may be implicated in their apoptotic effects, including the MAPK pathway (known to be important for cancer cell proliferation and survival), PARP cleavage, expression of active caspase-3, decreased pSTAT3 and JAK3 levels, as well as decreases in various downstream STAT3 targets such as Mcl-1, Bcl-2, Bcl-xL, and cyclin D3, all of which are implicated in apoptosis and the cell cycle. Taking all these effects into account, cucurbitacins may prove useful in the treatment of different kinds of cancers, especially when used with other cytostatic agents.


Isolation of two Ochrobactrum sp. strains capable of degrading the nootropic drug-Piracetam.
Piracetam (2-oxo-1-pyrrolidine acetamide) is a popular cognitive enhancer, which has recently been detected in waste and drinking water. Nootropic drugs are designed to affect human metabolism and act on the nervous system, but their environmental effects have yet to be the subject of detailed studies. In this report, we present the efficient biodegradation of the cognitive enhancer, piracetam. Two bacterial strains capable of using this compound as the sole carbon source were isolated and later identified as Ochrobactrum anthropi strain MW6 and Ochrobactrum intermedium strain MW7. The compound's mineralization and the cleavage of the heterocyclic ring were shown in the experiments with 14C-labeled piracetam. This is also the first report of a pharmaceutical's degradation by the Ochrobactrum genus. This study presents model microorganisms that can be used in further investigation of piracetam's degradation pathways as well as enzymes and genes involved in the process.


Kinetic studies on hepatic handling of glucagon using the model of non-recirculating perfused rat livers.
Using the model of the in vitro non-recirculating perfused rat liver we studied kinetic aspects of the hepatic handling of glucagon. Under conditions of a 20 min glucagon infusion (glucagon mass flows of 0.05, 0.46 and 4.75 ng/g liver/min, respectively) according to a rectangular profile both total and individual glucagon extractions were dependent on mass flow and time. The time course of glucagon extraction started with an acute phase within the first minute of infusion with a maximum value of 70%, which decreased within the following 30 sec by more than 40%. Depending on concentration, there was a progressive decrease in the hepatic extraction of glucagon up to the end of perfusion. Hepatic glucagon degradation was found to take place only at a little extent. Immediately after terminating the hormone infusion, the liver changed over into a glucagon-releasing organ. Kinetics of glucagon infusion and glucagon-induced hepatic glycogenolysis did not distinguish by parallelism but rather by phase shifting.


Aqua walking as an alternative exercise modality during cardiac rehabilitation for coronary artery disease in older patients with lower extremity osteoarthritis.
The purpose of this study was to examine the effects of aqua walking (AW) on coronary artery disease (CAD) and cardiorespiratory fitness in older adults with osteoarthritis in the lower extremity and compare it with that of traditional over-ground walking. Sixty consecutive eligible patients who had undergone percutaneous coronary intervention for CAD with limited ambulation due to lower extremity osteoarthritis were recruited. They were randomly assigned to the AW program group, treadmill/track walking (TW) program group, or non-exercise control group (CON). Assessments were performed before and after 24 weeks of medically supervised exercise training. Significant differences were observed in the change in %body fat (TW: -2.7%, AW: -2.8%, CON: -0.4%), total cholesterol level (TW: -23.6 mg/dL, AW: -27.2 mg/dL, CON: 15.8 mg/dL), resting heart rate (TW: -6.3 bpm, AW: -6.9 bpm, CON: 1.3 bpm), and cardiorespiratory fitness expressed as VO2 peak (TW: 2.3 mL/kg·min-1, AW: 2.0 mL/kg·min-1, CON: -2.5 mL/kg·min-1) over 24 weeks among the groups. However, no significant differences in the change in these measures were found between the TW and AW groups. AW appears to be a feasible alternative exercise modality to over-ground walking for cardiac rehabilitation and can be recommended for older adults with CAD and osteoarthritis.


Distribution of collagenous colitis: utility of flexible sigmoidoscopy.
We investigated the distribution of the collagen band in 33 patients with collagenous colitis to estimate the likelihood of the disease being diagnosed in biopsy specimens from the left side of the colon, such as those obtained using flexible sigmoidoscopy. To be included in this study patients had a subepithelial collagen band greater than or equal to 10 microns, an increase in chronic inflammatory cells in the same specimen, and diarrhoea for which there was no other apparent cause. In 17 patients undergoing full colonoscopy with a thickened collagen band, collagenous colitis was frequently patchy, even though overall the thickened collagen band was almost equally distributed throughout the colon. Rectal biopsy specimens showed a normal collagen band in 73% of patients, while a thickened collagen band was found in 82% of patients in at least one specimen from the left side of the colon. Three patients had a thickened collagen band only in the caecum. In three of eight rectal biopsy specimens with a normal collagen band there was no mucosal inflammation to raise the possibility of proximal disease, although all but one specimen with a normal collagen band from the sigmoid and descending colon were inflamed. Rectal biopsy alone is therefore a relatively poor method of making the diagnosis. Flexible sigmoidoscopy with multiple biopsy specimens from several sites is a reasonable initial investigation but not sufficient to exclude collagenous colitis when based on the presence of a thickened collagen band alone. Should left sided biopsy specimens show a normal collagen band but an inflamed mucosa, total colonoscopy with multiple specimens including the caecum may be required to establish the diagnosis.


Translational toxicology: a developmental focus for integrated research strategies.
Given that toxicology studies the potential adverse effects of environmental exposures on various forms of life and that clinical toxicology typically focuses on human health effects, what can and should the relatively new term of "translational toxicology" be taken to mean? Our assertion is that the core concept of translational toxicology must incorporate existing principles of toxicology and epidemiology, but be driven by the aim of developing safe and effective interventions beyond simple reduction or avoidance of exposure to prevent, mitigate or reverse adverse human health effects of exposures.The field of toxicology has now reached a point where advances in multiple areas of biomedical research and information technologies empower us to make fundamental transitions in directly impacting human health. Translational toxicology must encompass four action elements as follows: 1) Assessing human exposures in critical windows across the lifespan; 2) Defining modes of action and relevance of data from animal models; 3) Use of mathematical models to develop plausible predictions as the basis for: 4) Protective and restorative human health interventions. The discussion focuses on the critical window of in-utero development. Exposure assessment, basic toxicology and development of certain categories of mathematical models are not new areas of research; however overtly integrating these in order to conceive, assess and validate effective interventions to mitigate or reverse adverse effects of environmental exposures is our novel opportunity. This is what we should do in translational toxicology so that we have a portfolio of interventional options to improve human health that include both minimizing exposures and specific preventative/restorative/mitigative therapeutics.


fMRI-based Neuronal Response to New Odorants in the Newborn Brain.
The sense of smell is one of the oldest and the most primitive senses mammals possess, it helps to evaluate the surrounding environment. From birth, smell is an important sensory modality, highly relevant for neonatal behavioral adaptation. Even though human newborns seem to be able to perceive and react to olfactory stimuli, there is still a lack of knowledge about the ontogeny of smell and the underlying central processing involved in odor perception in newborns. Brain networks involved in chemosensory perception of odorants are well described in adults, however in newborns there is no evidence that central olfaction is functional given the largely unmyelinated neonatal central nervous system. To examine this question, we used functional magnetic resonance imaging (fMRI) in the newborn to characterize cortical response to olfactory and trigeminal odorants. Here we show that brain response to odors can be measured and localized using functional MRI in newborns. Furthermore, we found that the developing brain, only few days after birth, processes new artificial odorants in similar cortical areas than adults, including piriform cortex, orbitofrontal cortex and insula. Our work provides evidence that human olfaction at birth relies on brain functions that involve all levels of the cortical olfactory system.


Novel Pyrazole-Containing Compounds Active against Mycobacterium tuberculosis.
In this study, a series of 49 five-membered heterocyclic compounds containing either a pyridine- or a pyrrole-type nitrogen were synthesized and tested against Mycobacterium tuberculosis. Among them, only the 1,3,5-trisubstituted pyrazoles 5-49 exhibited minimum inhibitory concentration values in the low micromolar range, and some also exhibited an improved physicochemical profile without cytotoxic effects. Three pyrazoles were subjected to an animal tuberculosis efficacy model, and compound 6 induced a statistically significant difference in lung bacterial counts compared with untreated mice. Moreover, to determine the target of this series, resistors were generated, and whole genome sequencing revealed mutations in the mmpL3 gene.


Dual requirement for STAT signaling in dendritic cell immunobiology.
Dendritic cells (DC) represent an attractive target for therapeutic manipulation of the immune system and enhancement of insufficient immune response in cancer. STAT family members play key roles in the differentiation and activation of DC, a feature that is currently being exploited in DC-based therapies. We previously reported that the small-molecule Stattic, originally developed as a STAT3-specific inhibitor, also inhibits STAT1 and STAT2 phosphorylation in DC exposed to cytokines or LPS. Aim of this study was to investigate the functional consequences of in vitro treatment with Stattic on DC immunobiology. Interestingly, we observed an opposite effect of Stattic on DC immunophenotype depending on the activation state. While the expression of costimulatory, coinhibitory, MHC class II and CD83 molecules was enhanced in immature DC exposed to Stattic, the LPS induced up-modulation of these molecules was strongly repressed. An effective blockade of LPS-induced secretion of proinflammatory cytokines and capacity to stimulate a Th1 polarization was also observed in the presence of Stattic. Our results indicate that the immunological consequences of STAT inhibition in DC vary depending on the cell activation state. This knowledge is of relevance for anticipating potential effects of STAT-targeted therapeutics, and pursuing selective DC manipulation in clinical applications.


Development of infants of drug dependent mothers.
Infants of mothers who used methadone, heroin, cocaine and other drugs during pregnancy were compared with a group of control infants over the first 30 mths of life. Results of repeated examinations with the Bayley Scales of Infant Development showed a difference between the groups in mental development. No differences were found in a non-verbal version of the mental scale, but infants of drug dependent mothers seem to have specific difficulties in early language development. In psychomotor development, in behaviour during testing and on a questionnaire on activity, infants of drug dependent mothers did not differ from the comparison children.


Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods.
Currently used methodology for determining unbound drug exposure in brain combines measurement of the total drug concentration in the whole brain in vivo with estimation of brain tissue binding from one of two available in vitro methods: equilibrium dialysis of brain homogenate and the brain slice uptake method. This study of 56 compounds compares the fraction of unbound drug in brain (f(u,brain)), determined using the brain homogenate method, with the unbound volume of distribution in brain (V(u,brain)), determined using the brain slice method. Discrepancies were frequent and were primarily related to drug pH partitioning, attributable to the preservation of cellular structures in the slice that are absent in the homogenate. A mathematical model for pH partitioning into acidic intracellular compartments was derived to predict the slice V(u,brain) from measurements of f(u,brain) and drug pK(a). This model allowed prediction of V(u,brain) from f(u,brain) within a 2.2-fold error range for 95% of the drugs compared with a 4.5-fold error range using the brain homogenate f(u,brain) method alone. The greatest discrepancies between the methods occurred with compounds that are actively transported into brain cells, including gabapentin, metformin, and prototypic organic cation transporter substrates. It was concluded that intrabrain drug distribution is governed by several diverse mechanisms in addition to nonspecific binding and that the slice method is therefore more reliable than the homogenate method. As an alternative, predictions of V(u,brain) can be made from homogenate f(u,brain) using the pH partition model presented, although this model does not take into consideration possible active brain cell uptake.


Phylogenetic system and zoogeography of the Plecoptera.
Information about the phylogenetic relationships of Plecoptera is summarized. The few characters supporting monophyly of the order are outlined. Several characters of possible significance for the search for the closest relatives of the stoneflies are discussed, but the sister-group of the order remains unknown. Numerous characters supporting the presently recognized phylogenetic system of Plecoptera are presented, alternative classifications are discussed, and suggestions for future studies are made. Notes on zoogeography are appended. The order as such is old (Permian fossils), but phylogenetic relationships and global distribution patterns suggest that evolution of the extant suborders started with the breakup of Pangaea. There is evidence of extensive recent speciation in all parts of the world.


Detection of hepatitis E virus in milk: Current evidence for viral excretion in a wide range of mammalian hosts.
Infection with hepatitis E virus (HEV) is common in both developing and industrialized nations. Genotypes 3 and 4 are increasingly being reported, particularly in high-income countries where the precise extent of HEV transmission via food is currently unclear. Recently, HEV has been found to be excreted in milk; however, data on the potential milk-borne transmission is still lacking or conflicting and warrants further research on the topic. As such, the aim of the present study was to review the current scientific knowledge and to summarize the existing studies in which HEV has been detected in milk. Exhaustive searches were carried out in Mendeley, PubMed, Scopus and Web of Science. A total of 157 papers were retrieved from the four electronic databases. After removing duplicate articles from the databases (n = 30), exclusion criteria identified unrelated research (n = 115). This allowed the identification of 12 eligible papers. To date, studies on HEV detection in milk were mostly from China (n = 5), followed by Egypt (n = 2), Germany (n = 1), Belgium and Holland (n = 1), Turkey (n = 1), Czech Republic (n = 1) and Spain (n = 1) and were focused on a variety of animals (cow, goat, donkey, buffalo, sheep and camel) and humans. Four out of the 12 eligible studies did not find any evidence of HEV in milk. Moreover, 3 out of the 12 studies detected low rates of HEV (0.2-1.8%) and two were based on a low sample size (n = 1 and n = 4). Interestingly, one study showed very high detection rates and also detected HEV genotype 1 in an animal milk sample, an unusual finding since it only occurs in humans, deserving further studies for confirmation and characterization. Two studies detected high prevalence of HEV genotype 4 in bovine samples from China, with one showing indication of the presence of infectious HEV in milk. To date, there is still a small amount of available data on the HEV presence in milk, posing important questions regarding both animal and human health. Thus, further efforts on this potentially underestimated zoonotic route for HEV should be given, warranting further studies on the topic.


Lineage-Specific Differentiation Is Influenced by State of Human Pluripotency.
Human pluripotent stem cells (hPSCs) have been reported in naive and primed states. However, the ability to generate mature cell types remains the imperative property for utility of hPSCs. Here, we reveal that the naive state enhances self-renewal while restricting lineage differentiation in vitro to neural default fate. Molecular analyses indicate expression of multiple lineage-associated transcripts in naive hPSCs that failed to predict biased functional differentiation capacity. Naive hPSCs can be converted to primed state over long-term serial passage that permits recovery of multi-germ layer differentiation. Suppression of OCT4 but not NANOG allows immediate recovery directly from naive state. To this end, we identified chemical inhibitors of OCT4 that restore naive hPSC differentiation. Our study reveals unique cell-fate restrictions in human pluripotent states and provides an approach to overcome these barriers that harness both efficient naive hPSC growth while maintaining in vitro differentiation essential for hPSC applications.


Mercury levels and fish consumption practices in women of child-bearing age in the Florida Panhandle.
The southeastern United States, and in particular the coastal areas along the Gulf of Mexico (Gulf Coast) in Florida, experience some of the highest levels of mercury deposition in the country. Although the State of Florida's coastal border is among the longest in the United States, and the State has issued fish consumption advisories due to mercury on multiple fish species, few data have been systematically collected to assess mercury levels in the human population of the state or to assess the efficacy of the consumption advisories. Because of the generally high rate of seafood consumption among coastal populations, the human population in the Florida Panhandle, near Pensacola, FL is potentially exposed to elevated levels of mercury. In the present study, we analyzed hair mercury levels in women of child-bearing age (16-49 years) who had resided near Pensacola, FL for at least 1 year. We also surveyed the fish consumption practices of the cohort and evaluated awareness of the Florida Fish Consumption Advisory. Hair mercury levels were significantly higher in women who consumed fish within the 30 days prior to sampling (p<0.05) and in those women who were unaware of the consumption advisory (p<0.05). Only 31% of the women reported knowledge of the consumption advisory and pregnant women exhibited lower awareness of the advisory than non-pregnant women. The data suggest that public health interventions such as education and fish advisories have not reached the majority of women in the counties surrounding Pensacola who are most at risk from consumption of fish with high levels of mercury.


Assessing Rapidity of Recovery After Cancer Surgeries in a Single Overnight Short-Stay Setting.
In the short-stay surgery setting, where patients remain in hospital for a single overnight at most, it is unclear as to whether postoperative length of stay is a good surrogate for assessing rapidity of recovery. We hypothesized that length of stay would be a function of time of surgery and would be a poorer marker of recovery than time of discharge. A cohort of 891 mastectomy and 538 prostatectomy patients had a planned single overnight stay after surgery at an ambulatory surgical hospital during 2016. The relationship between surgical start time and postoperative length of stay or discharge time was assessed. For both mastectomy and prostatectomy patients, 75% of patients were discharged between 10 AM and 12 noon and the median postoperative length of stay was 20 hours. There was a strong association between time of surgery and calculated length of stay. For mastectomies, having a surgery which begins at 6 PM vs 8 AM results in an estimated decrease of 8.8 hours (95% CI, 8.3-9.3) in postoperative length of stay but only 1.2 hours (95% CI, 0.77-1.6) later time of discharge. For prostatectomies, the estimated difference is a decrease of 6.9 hours (95% CI, 6.4-7.4) for postoperative length of stay and 2.5 hours (95% CI, 2.0-3.0) later discharge time. Postoperative length of stay is a poor outcome measure in a short-stay setting. When assessing rapidity of recovery for single overnight stay patients, we advocate the use of discharge time with adjustment for surgery start time. The effect of surgery start time on both postoperative length of stay and discharge time should be investigated to ascertain which is best to assess rapidity of recovery in other ambulatory care settings where recovery involves a single overnight stay.


Negative Nonlinear CD-ee Dependence in Polycrystalline BINOL Thin Films.
Generally, the relationship between the observed circular dichroism and the enantiomeric excess in chiral systems (CD-ee dependence) is linear. While positive nonlinear behavior has often been reported in the past, examples of negative nonlinear (NN) behavior in CD-ee dependence are rare and not well understood. Here, we present a strong NN CD-ee dependence within polycrystalline thin films of BINOL by using second-harmonic-generation circular dichroism (SHG-CD) and commercial CD spectroscopy studies. Theoretical calculations, microscopy, and FTIR studies are employed to further clarify the underlying cause of this observation. This behavior is attributed to the changing supramolecular chirality of the system. Systems exhibiting NN CD-ee dependence hold promise for highly accurate enantiomeric excess characterization, which is essential for the refinement of enantio-separating and -purifying processes in pharmaceuticals, asymmetric catalysis, and chiral sensing. Our findings suggest that a whole class of single-species systems, i.e., racemate crystals, might possess NN CD-ee dependence and thus provide us a vast playground to better understand and exploit this phenomenon.


[Problems in recognizing recurrences of craniocervical malignancies in CT].
A retrospective study was carried out involving 39 patients with malignant tumours of the head and neck in order to differentiate by CT changes due to local tumour or lymph node recurrences and various post-operative or post-irradiation changes. In these patients, two or more CT examinations of the neck were available, derived from a fourth generation scanner. The suspected lesions were classified according to their type and the appearances correlated with the treatment and clinical findings. There was frequent overlap between the appearances of benign and malignant changes, so that in individual cases a definite decision often proved impossible.


Readiness for smoke-free policy and overall strength of tobacco control in rural tobacco-growing communities.
Rural, tobacco-growing areas are disproportionately affected by tobacco use, secondhand smoke, and weak policies. The study determined whether overall strength of Resources, Capacity, and Efforts in tobacco control predicts readiness for smoke-free policy in rural communities, controlling for county population size and pounds of tobacco produced. This was a correlational, cross-sectional analysis of data from key informants (n = 148) and elected officials (n = 83) from 30 rural counties who participated in telephone interviews examining smoke-free policy. Six dimensions of community readiness (knowledge, leadership, resources, community climate, existing smoke-free policies, and political climate) were identified and summed to assess overall readiness for smoke-free policy. General strength of overall Resources, Capacity and Efforts in tobacco control at the county level was measured. Readiness for smoke-free policy was lower in communities with higher smoking rates, higher tobacco production, and smaller population. Efforts related to general tobacco control (i.e., media advocacy, training, and technical assistance) predicted readiness for local smoke-free policy development (standardized β = .35, p = .05), controlling for county population size and pounds of tobacco produced. Given that small, rural tobacco-growing communities are least ready for smoke-free policy change, tailoring and testing culturally sensitive approaches that account for this tobacco-growing heritage are warranted.


Hemipelvic and proximal femoral limb salvage endoprosthesis with tendon ongrowth in a dog.
To report the clinical application of a hemipelvic and proximal femoral endoprosthesis for limb salvage. Retrospective case report. One 5-year-old, neutered female, flat coated retriever with a malignant neoplasia of the left coxofemoral joint. An invasive soft tissue mass (histiocytic sarcoma) with bone lysis of the femoral head and acetabulum was noted on radiographs, computed tomography (CT), and MRI. Custom-designed hemipelvic and proximal femoral endoprostheses were produced from CT images and manufactured with hydroxyapatite coated surfaces to allow tissue integration. The proximal femoral implant allowed tendon ongrowth and muscle attachment. The pelvic implant was anchored to the ilium and ischium with screws, and the femoral implant was cemented. Chemotherapy consisted of lomustine (CCNU). No evidence of implant loosening or local/thoracic metastases was noted on radiographs or CT at 6 weeks and at 3, 6, 9, and 12 months after surgery. A neurapraxia resolved 14 weeks postoperatively. Intensive rehabilitation was performed. At 12 months, activity was unrestricted with minimal residual lameness. The dog was euthanized at 14 months for metastatic disease. Limb salvage with a hemipelvic and proximal femoral endoprosthesis resulted in limb function and survival for 14 months. Neoplasia involving the bones of the coxofemoral joint traditionally requires hemipelvic resection and pelvic limb amputation. This report provides evidence that limb salvage can result in satisfactory levels of activity.


Post-transcriptional regulation of chemokine receptor CXCR4 by estrogen in HER2 overexpressing, estrogen receptor-positive breast cancer cells.
Expression of the chemokine receptor CXCR4, a G protein-coupled receptor, and HER2, a receptor tyrosine kinase, strongly correlates with the aggressive and metastatic potential of breast cancer cells. We studied estrogen regulation of CXCR4 in estrogen receptor (ER)-positive MCF-7 breast cancer cells overexpressing HER2 (MCF7-HER2). Although estrogen evoked no change in CXCR4 mRNA levels, CXCR4 protein was significantly up-regulated after estrogen treatment of these cells, whereas estrogen had no effect on CXCR4 protein level in parental MCF7 cells that are low in HER2. Use of the CXCR4 specific inhibitor, AMD 3100, indicated that this increase in CXCR4 protein was partially responsible for the increase in estrogen-induced migration of these cells. The estrogen-induced increase in CXCR4 protein in MCF-7-HER2 cells was abrogated by the antiestrogen ICI 182780 and by gefitinib (Iressa; a phospho-tyrosine kinase inhibitor), indicating an ER-mediated effect and confirming involvement of receptor tyrosine kinases, respectively. Using specific pathway inhibitors, we show that the estrogen-induced increase in CXCR4 involves PI3K/AKT, MAPK and mTOR pathways. PI3K/AKT and MAPK pathways are known to result in the phosphorylation and functional inactivation of tuberin (TSC2) of tuberous sclerosis complex thereby negating its inhibitory effects on mTOR, which in turn stimulates the translational machinery. Small interfering RNA (siRNA) mediated knockdown of tuberin elevated the level of CXCR4 protein in MCF7-HER2 cells and also nullified further estrogen up-regulation of CXCR4. This study suggests a pivotal role of PI3 K, MAPK and mTOR pathways, via tuberin, in post-transcriptional control of CXCR4, initiated through estrogen-stimulated crosstalk between ER and HER2. Thus, post-transcriptional regulation of CXCR4 by estrogens acting through ER via kinase pathways may play a critical role in determining the metastatic potential of breast cancer cells.


Antihyperglycemic potentials of a threatened plant, Helonias dioica: antioxidative stress responses and the signaling cascade.
Helonias dioica (HD) is a threatened species of herb growing in North America. It is used as a traditional medicine for treating various ailments particularly related to reproductive issues. The root is reported to contain approximately 10% of a saponin (chamaelirin; C(36)H(62)O(18)) apart from certain other fatty acids. As saponins are known to have hypoglycemic effects, we suspected its possible antihyperglycemic potentials. We injected intraperitoneally alloxan (ALX) at the dose of 200 mg/kg body weight (bw) to induce hyperglycemia in mice and tested possible hypoglycemic effects of HD in vivo by deploying two doses (100 and 200 mg/kg bw, respectively). We also tested its effects on the isolated pancreatic islets cells in vitro. We used various standard protocols like reactive oxygen species (ROS) generation and DNA damage, activities of biomarkers like catalase (CAT), superoxide dismutase (SOD), lipid peroxidase (LPO), reduced glutathione (GSH) of the pancreas tissue and glucokinase and glycogen content of the liver of hyperglycemic mice. With a mechanistic approach, we also tracked down the possible signaling pathway involved. We found an elevated level of ROS generation, LPO and overexpression of inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), p38 Map kinase (p38 MAPK), nuclear factor (NF)-κβ, interferon gamma (IFN-γ), cytochrome c, caspase 3, poly [ADP ribose] polymerase (PARP) and cyclo oxygenase 2 (COX2) in ALX-induced diabetic mouse. Treatment of hyperglycemic mice with both the doses of HD showed a significant decrease with respect to all these parameters of study. Thus, our results suggest that HD prevents ALX-induced islet cell damage and possesses antihyperglycemic and antioxidative potentials.


American Academy of Pediatrics. Fluoride supplementation. Committee on Nutrition.
This statement reviews the rationale for the use of fluoride supplements for infants and children. The concept of fluoridation of water supplies as an effective and cost-beneficial method of reducing caries prevalence in the general population is strongly supported. In the absence of an adequately fluoridated water supply, fluoride supplements should be given to all children. This should begin at about 2 weeks of age; the dosage will depend on the concentration of fluoride in the local water supply. Fluoride-containing dentifrices are an important source of topical fluoride, but it is essential that parents be aware of the danger of excessive fluoride intake and that they teach their children to avoid swallowing toothpaste.


Purification effects of amended bioretention columns on phosphorus in urban rainfall runoff.
In order to develop bioretention fillers with better phosphorus removal capacity, we built 12 bioretention columns with six kinds of modified fillers, and analyzed the operation effects of the columns under different conditions through field tests. Results show that adding water treatment residual has optimal removal rates for total phosphorus (TP) (median = 96.80%) and soluble reactive phosphorus (SRP) (median = 97.13%). The water reduction rates of the columns with improved fillers are 1.23-2.04 times that of the bioretention soil media column. The coconut chaff column has the best water storage capacity (median = 40.54%). Among the external factors affecting column operation, influent concentration of pollutants in urban surface runoff is the biggest influence factor on the removal efficiency of TP. However, there are no significant correlations between the removal efficiency of SRP and rainfall, influent concentration, and discharge ratio. The columns modified with medical stone, vermiculite, peat soil, medical stone + peat soil, green zeolite + peat soil all have good removal for phosphorus pollutant. After entering the columns, the contents of TP and SRP in most columns increased. The recommended fillers and the accumulation performance of phosphorus can help to improve purification effects in bioretention systems.


Dental Risks and Precautions during COVID-19 Pandemic: A Systematic Review.
To provide dentists and dental team with insights concerning risk and precautions during COVID-19 outbreak crisis as it would help in decision making among dental community. A comprehensive review of all English and non-English articles was carried out using the available CORD-19 dataset with MEDLINE via PubMed, Cochrane library, Google Scholar and ScienceDirect databases. The study included all articles that matched the search terms. A total of 353 were retrieved, of which 13 articles were reviewed comprehensively. Studies included in this systematic review emphasized on reinforcing strict infection control measures and minimizing human-to-human contact during COVID-19 outbreak. All surfaces in operatory room including waiting area need adequate ventilation and disinfection. Dental patients need to be screened using COVID-19 targeted questions as well as measuring their body temperature. Restricting dental treatments to only emergency cases and rescheduling all routine visits is advised with careful attention to minimize aerosol generation and following highest level of personal protection when treating COVID-19 confirmed cases. Dental offices need to establish a standard protocol of case reporting and referral to other well-prepared facilities. Lastly, online platforms are beneficial tools in providing psychological support to distressed dentists, dental team and dental patients and educating public during COVID-19 crisis. Dental team need to follow strict infection control measures and minimize aerosol generation during COVID-19 outbreak. It is the responsibility of dental care workers to keep themselves informed and ensure safety and control transmission within dental facilities. Further research is required.


Solution-grown millimeter-scale Mn-doped CsPbBr3/Cs4PbBr6 crystals with enhanced photoluminescence and stability for light-emitting applications.
Metal halide perovskites are particularly emerging for optoelectronic applications in light-emitting diodes, photodetectors, and solar cells due to their flourishing photophysical properties. However, the poor stability of three-dimensional (3D) lead halide perovskite nanocrystals (NCs) significantly hampers their optoelectronics and photovoltaics applications. Embedding 3D perovskites into zero-dimensional (0D) perovskite crystals and doping ions of appropriate elements into host lattices provide effective approaches to improve the stability and optical-electronic performance. In this study, millimeter-scale Mn-doped and undoped CsPbBr3/Cs4PbBr6 perovskite crystals were successfully fabricated by a one-step slow cooling method. We systematically investigated the effects of Mn2+ ion doping on the PL performance and stability of CsPbBr3/Cs4PbBr6 crystals. Compared with undoped crystals, the existence of Mn2+ ions not only blue-shifted the PL peak but also improved the luminescence performance and stability of the prepared millimeter-sized crystals. Moreover, doping Mn2+ ions can increase the proportion of radiative recombination at low temperature, which may be because Mn2+ ions can effectively accelerate the decay of a dark exciton by the magnetic mixing of bright and dark excitons. In addition, green LED devices with high efficiency packaged as-grown crystals are explored, which promises further application in display backlights.


Longitudinal observational study of sporadic inclusion body myositis: implications for clinical trials.
Sporadic inclusion body myositis (IBM) is the most common acquired myopathy occurring in adults aged over 50 years. The aim of the study was to assess prospectively the clinical features and functional impact of sporadic inclusion body myositis (IBM). Clinical data, manual muscle testing (MMT), quantitative muscle testing (QMT) of quadriceps muscle and IBM functional rating scale (IBM-FRS) were collected according to a standardised protocol at baseline (n=51) and one-year follow-up (n=23). MMT, quadriceps QMT and IBM-FRS significantly declined after one year (by 5.2%, 27.9%, and 13.8%, respectively). QMT of the quadriceps muscle and IBM-FRS were the most sensitive measures of disease progression. After a median time of seven years of disease duration, 63% of patients had lost independent walking. Disease onset after 55 years of age, but not sex or treatment, is predictive of a shorter time to requirement of a walking stick. We detected no differences in disease presentation and progression between clinically and pathologically defined IBM patients. The study provides evidence that quadriceps QMT and IBM-FRS could prove helpful as outcome measures in future therapeutic trials in IBM.


Hippocampal atrophy is the critical brain change in patients with hypoxic amnesia.
Anoxia is considered a good model for studying amnesia. However, not all individuals who experience anoxic events develop memory problems. Moreover, the question still remains about whether, after anoxia, damage is limited to the hippocampus in patients with amnesia and without other significant cognitive deficits. Here we investigated brain damage in a selected sample of adults affected exclusively by an amnesic syndrome after an anoxic episode. The cerebral MR images of these patients were submitted to visual inspection, volumetric measurements of the mesial temporal structures following manual segmentation, and to Voxel-Based Morphometry of the whole brain. We studied five anoxic patients and thirty-three well-matched healthy subjects. Our aim was to: (a) quantify regional atrophic changes associated with chronic anoxic damage compared to control subjects (Group Comparison Analysis); (b) identify regions of common abnormality across all patients (Conjunction Analysis in the VBM); (c) investigate whether measures of regional volume reduction correlated with neuropsychological memory scores; (d) compare the results obtained with visual inspection and ROI analyses with those obtained with VBM. We found that anoxic patients presented a significant reduction of gray matter volume in the hippocampus bilaterally compared to healthy subjects. The only common atrophic region across all patients was the hippocampus bilaterally. Correlation analysis showed only a trend between the Prose immediate free recall test and the left hippocampus. Our findings confirm that the hippocampus is very sensitive to damage stemming from anoxia. Patients with hypoxic amnesia may present damage in other brain regions, but only hippocampal atrophy is common in all of them.


Treatment of pathological gambling: a critical review of the literature.
The legalization and availability of new forms of gambling are increasing in most Western countries. This trend has contributed to the fact that more individuals are developing gambling problems. As a result, there is a need for effective treatments. Although gambling treatment dates several decades, few empirically supported treatments for pathological gambling have been developed. This critical review includes only controlled treatment studies. The primary inclusion criterion was randomization of participants to an experimental group and to at least 1 control group. Eleven studies were identified and evaluated. Key findings showed that cognitive-behavioral studies received the best empirical support. Recommendations to improve gambling treatment research include better validated psychometric measures, inclusion of process measures, better definition of outcomes, and more precise definition of treatments.


Authorship and study characteristic trends in spine publications from years 2004 to 2017.
The goal of this study was to analyze the trends in authorship and study characteristics in Spine using two overlapping ten-year time periods: 2004-2014 and 2007-2017. To our knowledge, no other literature reports study characteristics and authorship in the same time period for spine that would allow for the assessment of confounding factors of trends. Authorship and study characteristic data was collected from all scientific manuscripts published in Spine during the years of 2004, 2007, 2014, and 2017. Basic statistics and Kruskal-Wallis test were used to analyze the data. We found a significant increase in total number of authors (P<0.0001) without discrepancy of unequivocal increases in author degree type: MD/Equivalent (P≤0.0001), PhD/Doctorate (P=0.0017), Masters (P=0.0015), and Bachelors (P≤0.0001). We observed an increase in industry authorship (P≤0.0001), but without a significant increase in industry funding during the same time span. Increases in administration database studies (P≤0.0001) and economic/value studies (P≤0.0001) were also noted. A significant change in percentage of articles with trauma pathology (decrease, P<0.0001) and deformity (increase, P=0.0002) occurred. The number of multi-institutional studies increased (P≤0.0001), while no change in the number of multi-disciplinary studies. Increases in author number for spine articles over time are a result of a general increase in authors in all degree types, not just non-doctorate degrees. This may be potentially influenced by the increase in multi-institutional studies. From 2004-2017, higher percentages of articles focus on economics. An increase in industry authorship without a corresponding increase in funding suggests industry's more 'hands-on' approach to publication results from their funded studies.


Extraction from Medical Records.
Despite using electronic medical records, free narrative text is still widely used for medical records. Such text cannot be analyzed by statistical tools and be proceed by decision support systems. To make data from texts available for such tasks a supervised machine learning algorithms might be successfully applied. In this work, we develop and compare a prototype of a medical data extraction system based on different artificial neuron networks architectures to process free medical texts in Russian language. The best F-score (0.9763) achieved on a combination of CNN prediction model and large pre-trained word2vec model. The very close result (0.9741) has shown by the MLP model with the same embedding.


Impairment of the chondrogenic phase of endochondral ossification in vivo by inhibition of cyclooxygenase-2.
Many studies have reported on the effects of cyclooxygenase-2 (COX-2) inhibition on osteogenesis. However, far less is known about the effects of COX-2 inhibition on chondrogenic differentiation. Previous studies conducted by our group show that COX-2 inhibition influences in vitro chondrogenic differentiation. Importantly, this might have consequences on endochondral ossification processes occurring in vivo, such as bone fracture healing, growth plate development and ectopic generation of cartilage. The goal of our study was to investigate, in vivo, the effect of COX-2 inhibition by celecoxib on the cartilaginous phase of three different endochondral ossification scenarios. 10 mg/kg/day celecoxib or placebo were orally administered for 25 d to skeletally-immature New Zealand White rabbits (n = 6 per group). Endochondral ossification during fracture healing of a non-critical size defect in the ulna, femoral growth plate and ectopically-induced cartilaginous tissue were examined by radiography, micro-computed tomography (µ-CT), histology and gene expression analysis. Celecoxib treatment resulted in delayed bone fracture healing, alterations in growth plate development and progression of mineralisation. In addition, chondrogenic differentiation of ectopically-induced cartilaginous tissue was severely impaired by celecoxib. In conclusion, we found that celecoxib impaired the chondrogenic phase of endochondral ossification.