COVID-19 Pandemic and Microplastic Pollution.
The world is suffering from aggravating, waste-generated consequences, and the contribution of microplastics to this problem is only increasing. A contributing factor to increased microplastic usage is the change in the use of personal protective equipment (PPE) from specific use in limited locations (e.g., hospitals) to general use in widespread locations to protect against the current COVID-19 pandemic. This has resulted in an overflow of microfiber waste from homes, schools, streets, and elsewhere, in every country. While various institutes have issued warnings regarding increasing PPE waste, there is no positive indication of an end to the pandemic in the near future. In this review, we examine the impact of the pandemic on microplastic production, consumption, and disposal, and suggest strategies for lessening environmental pollution. In preparation for the worst-case scenario in which PPE becomes a new normal (in the COVID-19 era), it is recommended that governments and other responsible organisations set up a structured monitoring system for the distribution and disposal of PPE to ensure the most effective waste management possible for continuous sustainable development.


The enzymatic function of the honorary enzyme: S-nitrosylation of hemoglobin in physiology and medicine.
The allosteric transition within tetrameric hemoglobin (Hb) that allows both full binding to four oxygen molecules in the lung and full release of four oxygens in hypoxic tissues would earn Hb the moniker of 'honorary enzyme'. However, the allosteric model for oxygen binding in hemoglobin overlooked the essential role of blood flow in tissue oxygenation that is essential for life (aka autoregulation of blood flow). That is, blood flow, not oxygen content of blood, is the principal determinant of oxygen delivery under most conditions. With the discovery that hemoglobin carries a third biologic gas, nitric oxide (NO) in the form of S-nitrosothiol (SNO) at β-globin Cys93 (βCys93), and that formation and export of SNO to dilate blood vessels are linked to hemoglobin allostery through enzymatic activity, this title is honorary no more. This chapter reviews evidence that hemoglobin formation and release of SNO is a critical mediator of hypoxic autoregulation of blood flow in tissues leading to oxygen delivery, considers the physiological implications of a 3-gas respiratory cycle (O2/NO/CO2) and the pathophysiological consequences of its dysfunction. Opportunities for therapeutic intervention to optimize oxygen delivery at the level of tissue blood flow are highlighted.


Frequency-Specific Analysis of Hearing Outcomes Associated with Ossiculoplasty Versus Stapedotomy.
Surgery on the ossicular chain may impact its underlying mechanical properties. This study aims to investigate comparative differences in frequency-specific hearing outcomes for ossiculoplasty versus stapedotomy. A retrospective chart review was conducted on subjects who underwent ossiculoplasty with partial ossicular replacement prosthesis (PORP) or laser stapedotomy with self-crimping nitinol/fluoroplastic piston, and achieved closure of postoperative pure tone average air-bone gap (PTA-ABG) ≤ 15 dB. 45 PORP and 38 stapedotomy cases were included, with mean length of follow-up of 7.6 months. The mean change in PTA-ABG was similar for the 2 procedures (-17.9 dB vs -18.1 dB, P = .98). Postoperative ABG closure for stapedotomy was superior at 1000 Hz (8.9 dB vs 13.9 dB, P = .0003) and 4000 Hz (11.8 dB vs 18.0 dB, P = .0073). Both procedures also had improved postoperative bone conduction (BC) thresholds at nearly all frequencies, but there was no statistical difference in the change in BC at any particular frequency between the 2 procedures. Both procedures achieved a similar mean change in PTA-ABG. Stapedotomy was superior to PORP at ABG closure at 1000 Hz and at 4000 Hz, with 1000 Hz the most discrepant. The exact mechanism responsible for these changes is unclear, but the specific frequencies affected suggest that differences in each procedure's respective impact on the native resonant frequency and mass load of the system could be implicated.


Remnant of Unrelated Amniote Sex Chromosomal Linkage Sharing on the Same Chromosome in House Gecko Lizards, Providing a Better Understanding of the Ancestral Super-Sex Chromosome.
Comparative chromosome maps investigating sex chromosomal linkage groups in amniotes and microsatellite repeat motifs of a male house gecko lizard (Hemidactylus frenatus, HFR) and a flat-tailed house gecko lizard (H. platyurus, HPL) of unknown sex were examined using 75 bacterial artificial chromosomes (BACs) from chicken and zebra finch genomes. No massive accumulations of microsatellite repeat motifs were found in either of the gecko lizards, but 10 out of 13 BACs mapped on HPL chromosomes were associated with other amniote sex chromosomes. Hybridization of the same BACs onto multiple different chromosome pairs suggested transitions to sex chromosomes across amniotes. No BAC hybridization signals were found on HFR chromosomes. However, HFR diverged from HPL about 30 million years ago, possibly due to intrachromosomal rearrangements occurring in the HFR lineage. By contrast, heterochromatin likely reshuffled patterns between HPL and HFR, as observed from C-positive heterochromatin distribution. Six out of ten BACs showed partial homology with squamate reptile chromosome 2 (SR2) and snake Z and/or W sex chromosomes. The gecko lizard showed shared unrelated sex chromosomal linkages-the remnants of a super-sex chromosome. A large ancestral super-sex chromosome showed a correlation between SR2 and snake W sex chromosomes.


[The whole treatment of cleft lip and/or palate by the team of Dr. Chancholle in Toulouse].
Our choice in the treatment of the C.L.P. child is that the child is accepted by his parents and by Society as well as possible. In this way, the most important points are: to inform parents and Society of the ability of the child to a normal and satisfactory life. This information must be based upon the exact knowledge of what is really the cleft disease, its causes, and not only the genetic ones, the whole troubles induced by the cleft, local and general, and their treatment: by neonatal operation and, however was the choice of operative technic, by educative and reeducative means based on an exact knowledge of the modified physiology of the child: above all, sensory-motricity coordination and early speech-therapy before speech. The follow-up of the child at the difficult time of school admission, and cooperation between all the members of the team and the teachers.


Effects of Thermal Cross-Linking on the Structure and Property of Asymmetric Membrane Prepared from the Polyacrylonitrile.
Improving the thermal and chemical stabilities of classical polymer membranes will be beneficial to extend their applications in the high temperature or aggressive environment. In this work, the asymmetric ultrafiltration membranes prepared from the polyacrylonitrile (PAN) were used to fabricate the cross-linking asymmetric (CLA) PAN membranes via thermal cross-linking in air to improve their thermal and chemical stabilities. The effects of thermal cross-linking parameters such as temperature and holding time on the structure, gas separation performance, thermal and chemical stabilities of PAN membranes were investigated by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), positron annihilation lifetime spectroscopy (PALS), scanning electron microscopy (SEM), thermogravimetic analysis (TGA) and gas permeation test. The thermal cross-linking significantly influences the chemical structure, microstructure and pore structure of PAN membrane. During the thermal cross-linking, the shrinkage of membrane and coalescence or collapse of pore and microstructure make large pores diminish, small pores disappear and pore volumes reduce. The gas permeances of CLA-PAN membranes increase as the increasing of cross-linking temperature and holding time due to the volatilization of small molecules. The CLA-PAN membranes demonstrate excellent thermal and chemical stabilities and present good prospects for application in ultrafiltration for water treatment and for use as a substrate for nanofiltration or gas separation with an aggressive and demanding environment.


Analysis of plasma protein biomarkers in childhood onset multiple sclerosis.
Multiple sclerosis (MS) manifesting before age 18 years is defined as pediatric MS (pMS). We analysed plasma proteins in pMS by an untargeted proteomic approach. Patients with pMS (Group pMS, n = 33), patients with demyelinating disease not meeting pMS diagnostic criteria (unclassified demyelinating disease, Group U, n = 4) and age-matched healthy subjects (Group C, n = 40) were included. Plasma proteomic analysis was performed using Q-TOF LC/MS. Proteins having fold change >1.2 and found to be statistically different (p < 0.05) between the groups were identified and discussed with a clinical perspective. Group pMS had higher alpha 1B glycoprotein (A1BG), complement factor B (CFB), plasminogen (PLG), alpha-2-antiplasmin (α2-AP, SERPINF2), inter alpha trypsin inhibitor heavy chain H2 (ITIH2), and lower centrosomal protein of 290 (CEP290) and F-box/LRR-repeat protein 17 (FBXL17) concentrations than Group C. Measurements from Group U, whose definite diagnoses were established as pMS (n = 3) and myelin oligodendrocyte glycoprotein antibody-associated disease (n = 1) on follow-up after the study, were statistically close to the results of Group pMS. Plasma protein changes observed in our study were related to the inflammation, coagulation and oxidative stress pathways. If confirmed and validated in larger groups, these results may indicate potential biomarker(s) for demyelinating diseases at proteome level and could encourage studies for the development of novel diagnostic kits.


Knowledge, attitude and practices regarding dengue and its vector among medical practitioners in Malakand region, Pakistan.
Dengue fever (DF) is increasingly recognized as one of the world's major mosquito borne diseases and causes significant morbidity and mortality in tropical and subtropical countries. Dengue fever is endemic in most part of Pakistan and continues to be a public health concern. Knowledge, attitude and practices can play an important role in management of the disease. Current study was aimed to determine the level of knowledge, attitude and practices regarding dengue fever among health practitioners, to study the level of knowledge and attitude with preventive practices for dengue fever. A cross sectional study was carried out in medical practitioners of the four districts of Malakand region during October to November 2019. A pre-structured questionnaire was used to collect data from medical practitioners. Data was analyzed using Graph Pad version 5. Significant value was considered when less than 0.05 (at 95% confidence of interval). The results revealed that most of participants have seen dengue vector (62%), the media being the most quoted source of information. Nearly 81.2% participants were aware from transmission of dengue fever is by mosquito bite. Practices based upon preventive measures were found to be predominantly focused towards prevention of mosquito bites rather than elimination of breeding places. Although the knowledge regarding DF and mosquito control measure was quite high among the medical practitioners but this knowledge was not put into practice. Further studies are required to aware the people about dengue and its vector in order to get prevention and control.


IMRT and HDR-ICBT for Locally Advanced Clear Cell Adenocarcinoma of the Cervix in Uterus Didelphys Associated With Unilateral Renal Agenesis.
Clear cell adenocarcinoma of the cervix (CCAC) with genitourinary malformations is rare. Here, we report a case of CCAC in uterus didelphys (UD) associated with unilateral renal agenesis (URA) that was treated with intensity-modulated radiotherapy (IMRT) and high-dose rate intracavitary brachytherapy (HDR-ICBT). We also retrospectively reviewed the medical records of CCAC cases with genitourinary malformations treated at the National Cancer Center/Cancer Hospital (Beijing, China) between December 2006 and June 2017. Eight cases of this rare condition were identified by pathologic diagnosis. Seven patients received surgical treatment including radical hysterectomy (n = 4), modified radical hysterectomy (n = 1), and total hysterectomy (n = 2). Five patients received adjuvant radiotherapy and chemotherapy after surgery. One patient with CCAC in UD associated with URA was treated with radical IMRT and adjuvant chemotherapy. The eight patients were followed up for an average of 7.9 years; in seven cases, there was no evidence of disease recurrence, while one patient relapsed and died after 1.5 years of treatment. On the basis of these findings, locally advanced CCAC in UD associated with URA can be effectively treated with radical IMRT.


Nasopharyngeal angiofibroma: (a nine-year experience).
In a nine-year period 50 nasopharyngeal angiofibromas, of whom 13 had recurrent tumour, were treated surgically at the All India Institute of Medical Sciences, New Delhi. A new staging system according to the regions involved was used; 31 patients in whom the tumour was limited to the nasopharynx (Stage I) and those with superior spread into the ethmoid or sphenoid sinuses (Stage IIA) had their tumours removed by a transpalatal route, alone or in combination with other approaches. Tumours with lateral extensions into the pterygopalatine or infratemporal fossae or the cheek (Stage IIB), and those with simultaneous superior and lateral spread (Stage III) underwent a transmaxillary excision (19 cases). In two of the three cases with intracranial extension (Stage IV), the tumour was removed successfully from below. There was no mortality. The usefulness of the transmaxillary approach, especially in recurrent cases, is emphasized. No adjuvant modalities were employed in this series and blood loss was acceptable.


CoReCG: a comprehensive database of genes associated with colon-rectal cancer.
Cancer of large intestine is commonly referred as colorectal cancer, which is also the third most frequently prevailing neoplasm across the globe. Though, much of work is being carried out to understand the mechanism of carcinogenesis and advancement of this disease but, fewer studies has been performed to collate the scattered information of alterations in tumorigenic cells like genes, mutations, expression changes, epigenetic alteration or post translation modification, genetic heterogeneity. Earlier findings were mostly focused on understanding etiology of colorectal carcinogenesis but less emphasis were given for the comprehensive review of the existing findings of individual studies which can provide better diagnostics based on the suggested markers in discrete studies.Colon Rectal Cancer Gene Database (CoReCG), contains 2056 colon-rectal cancer genes information involved in distinct colorectal cancer stages sourced from published literature with an effective knowledge based information retrieval system. Additionally, interactive web interface enriched with various browsing sections, augmented with advance search facility for querying the database is provided for user friendly browsing, online tools for sequence similarity searches and knowledge based schema ensures a researcher friendly information retrieval mechanism.Colorectal cancer gene database (CoReCG) is expected to be a single point source for identification of colorectal cancer-related genes, thereby helping with the improvement of classification, diagnosis and treatment of human cancers. lms.snu.edu.in/corecg.


On the impact of spike segmentation on motor unit identification in dynamic surface electromyograms.
We discuss the adaptation of preexisting Convolution Kernel Compensation (CKC) surface electromyogram (EMG) decomposition technique to dynamic muscle contractions. In particular, three different algorithms for segmentation of motor unit (MU) spike trains into MU firings are discussed and mutually compared on synthetic dynamic surface EMG. The first segmentation algorithm employs a priori knowledge of the regularity of MU firings. The second one builds on K-means classification of MU spikes, whereas the third one combines both the regularity of MU firings and the previously introduced Pulse-to-Noise Ratio (PNR). On average, 5.5 ± 0.6 MUs were identified with sensitivity of 88.4 % ± 17.0 %, 83.8 % ± 16.7 % and 90.7 % ± 15.1 % for the first, the second and the third segmentation algorithm, respectively, demonstrating the feasibility of MU identification in moderate dynamic muscle contractions. In our tests, the third segmentation approach demonstrated superior accuracy in MU identification.


Effector cell sensitivity to sugar moieties. III. Inhibition by monosaccharides of interleukin-2 enhanced natural killing against viral and nonviral tumor target cells.
Human NK cells recognize multiple target antigens. The ligands (antigens) involved in this interaction have not been clearly identified. Previously, we have shown that some monosaccharides inhibit NK mediated cytolysis in a concentration-dependent fashion and that NK cell activity involves recognition of carbohydrate structures on target cells via receptors on the effector cell surface. Using human IL-2 or recombinant IL-2, we have found that monosaccharides inhibit IL-2 enhanced functional activity in a concentration-dependent fashion; that increased expression of endogenous monosaccharide binding receptors on effector cells occurs after treatment with IL-2; and that greater quantities of monosaccharide were required to obtain equivalent inhibition of IL-2 enhanced NK activity. Our data reinforces the growing belief that effector cells express receptors with different sugar specificities and that quantitative differences in sugar specificities is a likely reason for NK cells having heterogeneous polyclonal activity.


Modulating microRNAs in cancer: Next-generation therapies.
MicroRNAs (miRNAs) are a class of endogenously expressed non-coding regulators of the genome with an ability to mediate a variety of biological and pathological processes. There is growing evidence demonstrating frequent dysregulation of microRNAs in cancer cells, which is associated with tumor initiation, development, migration, invasion, resisting cell death, and drug resistance. Studies have shown that modulation of these small RNAs is a novel and promising therapeutic tool in the treatment of a variety of diseases, especially cancer, due to their broad influence on multiple cellular processes. However, suboptimal delivery of the appropriate miRNA to the cancer sites, quick degradation by nucleases in the blood circulation, and off target effects have limited their research and clinical applications. Therefore, there is a pressing need to improve the therapeutic efficacy of miRNA modulators, while at the same time reducing their toxicities. Several delivery vehicles for miRNA modulators have been shown to be effective in vitro and in vivo. In this review, we will discuss the role and importance of miRNAs in cancer and provide perspectives on currently available carriers for miRNA modulation. We will also summarize the challenges and prospects for the clinical translation of miRNA-based therapeutic strategies.


Neurophysiological and Subjective Analysis of VR Emotion Induction Paradigm.
The ecological validity of emotion-inducing scenarios is essential for emotion research. In contrast to the classical passive induction paradigm, immersive VR fully engages the psychological and physiological components of the subject, which is considered an ecologically valid paradigm for studying emotion. Several studies investigate the emotional responses to different VR tasks or games using subjective scales. However, little research regards VR as an eliciting material, especially when systematically analyzing emotional processes in VR from a neurophysiological perspective. To fill this gap and scientifically evaluate VR's ability to be used as an active method for emotion elicitation, we investigate the dynamic relationship between explicit information (subjective evaluations) and implicit information (objective neurophysiological data). A total of 28 participants are enlisted to watch eight VR videos while their SAM/IPQ scores and EEG data are recorded simultaneously. In ecologically valid scenarios, the subjective results demonstrate that VR has significant advantages for evoking emotion in arousal-valence. This conclusion is backed by our examination of objective neurophysiological evidence that VR videos effectively induce high-arousal emotions. In addition, we obtain features of critical channels and frequency oscillations associated with emotional valence, thereby validating previous research in more lifelike circumstances. In particular, we discover hemispheric asymmetry in the occipital region under high and low emotional arousal, which adds to our understanding of neural features and the dynamics of emotional arousal. As a result, we successfully integrate EEG and VR to demonstrate that VR is more pragmatic for evoking natural feelings and is beneficial for emotional research. Our research has set a precedent for new methodologies of using VR induction paradigms to acquire a more reliable explanation of affective computing.


Online coupling of enantioselective capillary gas chromatography with proton nuclear magnetic resonance spectroscopy.
The hyphenation of enantioselective capillary gas chromatography and mass spectrometry is not always sufficient to distinguish between structural isomers, thus requiring peak identification by NMR spectroscopy. Here the first online coupling of enantioselective capillary gas chromatography with proton nuclear resonance spectroscopy is described for the unfunctionalized chiral alkane 2,4-dimethylhexane resolved on octakis(6-O-methyl-2,3-di-O-pentyl)-gamma-cyclodextrin at 60 degrees C. NMR allows constitutional and configurational isomers (diastereomers and enantiomers) to be distinguished. Enantiomers display identical spectra at different retention times, which enable an indirect identification of these unfunctionalized alkanes. The presented method is still at an early development stage, and will require instrumental optimization in the future.


Autonomic reactions to mutilation pictures: positive affect facilitates safety signal processing.
For survival, humans are continuously vigilant for signs of danger. Equally important, but less studied, is our ability to detect and respond to safety cues. The trait of positive affect may be a key component determining human variability in safety detection. Here we investigate autonomic and self-report reactivity to pictures of mutilated bodies, after reading a text about the art of mimicking injuries in the movies. Participants that scored high in positive affect trait showed attenuated autonomic reactions to the mutilation pictures. Thus, high positive affect facilitated engagement in safety cues and modulated reflexive reactions of the brain's defense system.


Lipophilic flavonoids from Orthosiphon spicatus prevent oxidative inactivation of 15-lipoxygenase.
15-Lipoxygenase from soybeans is inactivated by bubbling air through enzyme solutions. This inactivation is prevented by flavonoids from the East Asian medicinal plant Orthosiphon spicatus, previously found to be inhibitors of the enzyme. 5,7,4'-Trimethylapigenin, eupatorin and 5,7,3',4'-tetramethylluteolin show the strongest enzyme-stabilizing effects, decreasing loss of activity by 50% at concentrations of 2.0 +/- 0.04, 2.4 +/- 0.3 and 4.3 +/- 1.1 microM, respectively. There is no significant correlation between enzyme-inhibiting and enzyme-stabilizing effect. The Orthosiphon flavonoids show radical-scavenging activity towards the diphenylpicrylhydrazyl radical. This is correlated to their enzyme-stabilizing effect, but not to their inhibitory activity towards 15-lipoxygenase. When the enzyme is inactivated by air bubbling, a loss of sulfhydryl groups is observed. Sinensetin, a poor stabilizer of the enzyme, shows less efficiency in protecting sulfhydryl groups than tetramethylscutellarein, which stabilizes the enzyme more efficiently. Thus, oxidation of sulfhydryl groups may contribute to the observed air-induced inactivation of 15-lipoxygenase.


Congenital Syphilis: A U.S. Perspective.
Congenital syphilis still represents a worldwide public health problem. If left untreated, it can lead to fetal demise and high neonatal morbidity and mortality. Unfortunately, in the last decade, there has been a resurgence of cases in the U.S. This review discusses the ongoing problem of this preventable congenital infection, vertical transmission and clinical manifestations while providing a guidance for the evaluation and management of infants born to mothers with reactive serologic tests for syphilis.


[Treatment of congenital heart diseases with pulmonary artery cerclage. Immediate and medium term results in 51 patients].
The aim of this study was to assess the results of pulmonary artery banding in a retrospective study of 51 consecutive children treated from January 1980 to December 1993. The study population was 24 girls and 27 boys with an average age of 6.2 months, of average weight of 4.01 kg. The cardiac conditions treated were ventricular septal defects in 24 cases (isolated and associated with one or more cardiovascular malformations or multiple), complete atrioventricular canal in 12 cases (isolated or associated with several cardiovascular malformations), single ventricle in 7 cases, double outlet right ventricle in 3 cases, transposition of the great arteries with ventricular septal defect in 2 cases, tricuspid atresia in 2 cases, and a complex lesion with double discordance in one case. The average duration of banding was 2.35 years (n = 49). Hospital morality of banding was 1.9% (1/51). Late mortality was 14.8% (7/47). Twenty-one patients (42.8%) had complications of banding. The survival rates of children who underwent banding was 86.8% at 1 year and 80.6% at 11 years. The low hospital mortality leaves a role for pulmonary artery banding as a palliative procedure in congenital heart disease in which early correction is impossible or carries and unacceptable risk. Complications of banding justify attempts to improve the technique, by making adjustable bands.


Graves' Thyrotoxicosis Following SARS-CoV-2 Infection.
Graves' disease is an autoimmune thyroid disease that is thought to develop following environmental exposure in patients with genetic predisposition. Our objective is to present the first report of Graves' disease onset immediately following recovery from mild coronavirus disease 2019 (COVID-19), a close temporal occurrence that should be studied further. We describe the clinical course and laboratory features, including thyroid function studies, antibody testing, and polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2. A 21-year-old woman with prediabetes, obesity, asthma, and gastroesophageal reflux disease presented to the emergency department reporting 3 days of tachycardia, palpitations, anxiety, and shortness of breath. Laboratory investigation revealed a thyroid-stimulating hormone level of 0.01 (0.30-5.00) mcIU/mL with a free thyroxine level of 3.8 (0.6-1.6) ng/dL, prompting endocrinology consultation. On physical examination, she had mild diffuse thyromegaly without tenderness and a history, which included hypothyroidism in her mother. Antibody testing results demonstrated thyroid-stimulating immunoglobulin and thyrotropin receptor antibody levels of 2.6 (<1.3) thyroid-stimulating immunoglobulin index and 17 (0.00-1.75) IU/L, respectively. Sixteen days before presenting to the ED, she was diagnosed with COVID-19 by polymerase chain reaction test after reporting typical symptoms, including fever. Infectious symptoms resolved within 10 days. She achieved clinical and laboratory improvements with a combination of methimazole and beta blocker therapy. This case documents the occurrence of Graves' thyrotoxicosis following mild symptomatic COVID-19. Whether the preceding infection is coincidental or contributed to GD development requires definitive studies. This presentation may align with the theory of a viral link in the development of autoimmune thyroid disease in those with genetic predisposition.


[Polyglandular autoimmune syndromes : An overview].
Polyglandular autoimmune syndromes (PGAS), also known as autoimmune polyendocrinopathy syndromes (APS), are a heterogeneous group of rare, genetically caused diseases of the immune system which lead to inflammatory damage of various endocrine glands resulting in malfunctions. In addition, autoimmune diseases of non-endocrine organs may also be found. Early diagnosis of PGAS is often overlooked because of heterogeneous symptoms and the progressive occurrence of the individual diseases. The two most important forms of PGAS are the juvenile and adult types. The juvenile type (PGAS type 1) is caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21, exhibits geographic variations in incidence and is defined by the combination of mucocutaneous candidiasis, Addison's disease and hypoparathyroidism. In addition, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome and other autoimmune diseases can also occur. The adult form of PGAS (PGAS type 2) is a multigenetic disorder associated with some HLA haplotypes, is more common than the juvenile type, shows female predominance and exhibits the combination of type 1 diabetes, autoimmune thyroid disease, Addison's disease and other autoimmune disorders. The histological alterations in affected organs of PGAS patients are similar to findings in sporadically occurring autoimmune diseases of these organs but there are no pathognomic fine tissue findings. If patients exhibit autoimmune changes in two different endocrine glands or if there are indications of several autoimmune disorders from the patient history, it is important to consider PGAS and inform the clinicians of this suspicion.


Time Series Gene Expression Profiles Analysis Identified Several Potential Biomarkers for Sepsis.
Sepsis is a life-threatening disorder and leads to organ dysfunction and death. Therefore, searching for more alternative biomarkers is of great significance for sepsis assessment and surveillance. In our study, the gene expression profiles of 163 samples from healthy controls and septic patients were analyzed and 8 gene co-expression modules were identified by constructing weighted gene co-expression network. The blue and yellow modules showed close correlations with the phenotypic trait "days postsepsis." Besides, differentially expressed genes (DEGs) over time in septic patients were screened using Short Time-series Expression Miner (STEM) program. The intersection of genes in the blue and yellow modules and DEGs, which were significantly enriched in "HTLV-1 infection" pathway, was analyzed with protein-protein interaction network. The logistic regression model based on these eight mRNAs was constructed to determine the type of the sample reliably. Eight vital genes CECR1, ANXA2, ELANE, CTSG, AZU1, PRTN3, LYZ, and DEFA4 presented high scores and may be associated with sepsis, which provided candidate biomarkers for sepsis.


Scope and limitations of an efficient four-component reaction for dihydropyridin-2-ones.
A broad range of isonitrile-functionalized 3,4-dihydropyridin-2-ones could be prepared using a four-component reaction between phosphonates, nitriles, aldehydes, and isocyanoacetates. The reaction involves initial formation of a 1-azadiene intermediate which is trapped in situ by an isocyanoacetate to give the desired heterocyclic scaffold through cyclocondensation. The full scope and limitations of this four-component reaction are described. Variation of the nitrile and aldehyde inputs proved to be extensively possible, but variation of the phosphonate input remains limited. Regarding the isocyanoacetate, alpha-aryl isocyanoacetates give moderate to high yields and result in a complete diastereoselectivity for the 3,4-cis isomer. Alpha-alkyl isocyanoacetates gave the corresponding dihydropyridin-2-ones in moderate yields, most of them as mixtures of diastereomers. Elevated temperatures during cyclocondensation generally increased the yield and resulted in a change of the diastereomeric ratio in favor of the cis-diastereomer. In addition to isocyanoacetates, a limited number of other alpha-acidic esters resulted in the formation of dihydropyridin-2-ones, albeit in much lower yield. Computational studies show that the observed difference in yield cannot be simply correlated to specific physical properties (including acidity) of the different alpha-acidic esters.


[Usefulness of a grid using fiber interspace material].
We had the opportunity to employ an anti-scatter grid, which uses fiber as the interspace material. The X-ray transmission rate of fiber is higher than aluminum, so we predicted that the use of a fiber grid would reduce radiation exposure. The purpose of this study was to evaluate the usefulness of the fiber grid. The physical characteristics and influence of focus-grid decentering were compared between the fiber grid and three kinds of antiscatter grids that use aluminum as the interspace material (Al grid). The contrast improvement factor and selectivity of the fiber grid was higher than the Al grid, and the Bucky factor of the fiber grid was lower. The interspace material and grid ratio also influenced focus-grid decentering. The results of this study suggest the potential for reduction of radiation exposure by the use of a fiber grid.


Complete response following treatment of plasma cell leukemia with venetoclax and dexamethasone: A case report.
Plasma cell leukemia (PCL) is a rare but aggressive variant of multiple myeloma (MM) with a poor prognosis. Due to the limited number of prospective clinical trials studying PCL, treatment options are often extrapolated from data available for the treatment of MM. Venetoclax has recently demonstrated antimyeloma activity in patients with relapsed/refractory MM carrying the t(11;14) translocation. However, few cases have reported the analogous efficacy of venetoclax in PCL. A 64-year-old Caucasian male developed relapsed PCL despite treatment with hyperCD (hyperfractionated cyclophosphamide and dexamethasone) and Dara-KRd (daratumumab, carfilzomib, lenalidomide, dexamethasone). Due to the refractory nature of his disease and the presence of a t(11:14) translocation, the patient was subsequently initiated on venetoclax 400 mg daily and dexamethasone 4 mg once weekly. The patient achieved a complete response by International Myeloma Working Group criteria three months after initiating venetoclax-dexamethasone, including a repeat bone marrow biopsy that showed no abnormal plasma cells. He successfully underwent consolidation with melphalan-based autologous stem cell transplantation. He remains disease-free 9 months after venetoclax initiation. Combination all-oral therapy with venetoclax and dexamethasone can induce deep hematologic responses in patients with relapsed/refractory PCL carrying the t(11;14) translocation.


Effect of urea treatment on recovery of staphylococcal enterotoxin A from heat-processed foods.
The effects of urea treatment on the potential reactivation of heat-damaged antigenic components of staphylococcal enterotoxin A (SEA) were examined with cooked foods, including mushrooms, ham, bologna, salami, and turkey. The thermal stability of purified SEA spiked into foods and native SEA produced by Staphylococcus aureus in foods was also examined. Food samples containing either spiked or native SEA were thermally processed by autoclaving or retorting. This was followed sequentially by toxin extraction, urea treatment, dialysis, reconstitution, and SE assays with the reversed passive latex agglutination and/or enzyme immunoassay kit. The results indicate that (i) urea treatment did not result in any reactivation of heat-inactivated antigenic components of SEA in any of the foods tested, (ii) the serological components of purified SEA were destroyed (> or = 96%) by autoclaving at 121.1 degrees C for 5 to 15 min or by retorting at an F0 of 4 to 18, and (iii) the immunological property of the native SEA was approximately threefold-more heat resistant than that of the purified SEA. The study suggested that the current urea method is not suitable for the detection of heat-denatured SEA in the thermally processed foods.


Identification of IgE.
Progress in protein chemistry in the 1950s revealed that the biologic activities of proteins, such as hemoglobin and enzymes, are based on partial structures in the protein molecules. This principle suggested to us the possibility that the human antibodies responsible for induction of reaginic hypersensitivity reactions might have unique structures that are lacking in the antibody molecules involved in immunity and that the differences in the structures of human antibody molecules can be recognized by the immune systems of experimental animals. Our studies were based on the hypothesis that reaginic antibody activity is associated with a unique immunoglobulin isotype, which is now called IgE. As expected, identification of IgE facilitated the analysis of immunologic mechanisms of reaginic hypersensitivity. Subsequent studies revealed that IgE specifically bound to basophilic granulocytes and mast cells through the Fc portion of the molecules and that cross-linking of the cell-bound IgE antibody molecules by allergen induced the release of bioactive mediators, such as histamine and leukotrienes, which initiate allergic reactions.


DNA hypomethylation-mediated overexpression of carbonic anhydrase 9 induces an aggressive phenotype in ovarian cancer cells.
Both genetic and epigenetic alterations can lead to abnormal expression of metastasis-regulating genes in tumor cells. Recent studies suggest that aberrant epigenetic alterations, followed by differential gene expression, leads to an aggressive cancer cell phenotype. We examined epigenetically regulated genes that are involved in ovarian cancer metastasis. We developed SK-OV-3 human ovarian carcinoma cell xenografts in mice. We compared the mRNA expression and DNA methylation profiles of metastatic tissues to those of the original SK-OV-3 cell line. Metastatic implants showed increased mRNA expression of the carbonic anhydrase 9 (CA9) gene and hypomethylation at CpG sites in the CA9 promoter. Treatment of wild-type SK-OV-3 cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine reduced methylation of the CA9 promoter and increased CA9 mRNA expression. Eight CpGs, which were located at positions -197, -74, -19, -6, +4, +13, +40, and +86, relative to the transcription start site, were hypomethylated in metastatic tumor implants, compared to that of wild-type SK-OV-3. Overexpression of CA9 induced an aggressive phenotype, including increased invasiveness and migration, in SK-OV-3 cells. Alterations in the DNA methylation profile of the CA9 promoter were correlated with a more aggressive phenotype in ovarian cancer cells.


[Mushroom poisoning with a long period of development].
A group of 87 patients with the signs of poisoning with mushrooms with along period of incubation (t = 12.4 +/- 6.2 h) has been reported. Nausea, vomiting and diarrhea dominate in the clinical picture in the first phase and hepatic and/or renal insufficiency in the second phase. Forty-one patients (47.1%) had "only" clinical symptoms without severe parenchymatous impairments. Forty-six (54.9%) had evidence of a hepatic lesion and 8 patients (10.8%) had renal function impaired, 6 of which needed hemodialysis. There was a significant correlation between elevation of serum transaminases and prolongation of prothrombin complex, resulting from the decreased synthetic liver function (SGPT1/PV1r = -0.424, p = 0.00; SGOT1/PV1r = -0.448, p = 0.000) during the first days after poisoning. Hepatic and renal damage was not identical in all the cases, and there was no correlation between the elevation of serum transaminases and retention of nitrogen substances. When analysing the effect of therapy on elevation of serum transaminases and prolongation of prothrombin complex, a significant difference between elevation of serum transaminases and prolongation of prothrombin time was found in patients on competitive inhibition with penicillin or silibinin, as compared to the patients only on plasmapheresis (p = 0.004 for SGOT, p = 0.000 for SGPT). These data unquestionably suggest the efficacy of competitive inhibition in the treatment of poisoning with mushrooms of a long period of incubation. In favour of this therapy also speaks the group of seriously ill patients who were simultaneously on plasmapheresis and competitive inhibition and who had better improvement than those "only" on plasmapheresis (p = 0.004 for SGOT).(ABSTRACT TRUNCATED AT 250 WORDS)


[Mid-term multi-center outcomes of bilateral radial artery as conduits in coronary artery bypass grafting].
Objective: To evaluate the mid-term outcomes of bilateral radial artery (BRA) grafts in coronary artery bypass grafting (CABG). Methods: All perioperative medical records and follow-up results of CABG with BRA grafts in multi-centers of China were analyzed retrospectively. Results: A total of 211 patients (170 males and 41 females) underwent CABG grafting with BRA conduits between August 2013 and September 2018, with a mean age of (56.5±9.7) years old (rang 41 to 73 years). There were 161 cases of triple-vessel disease and 50 cases of two-vessel disease. Ninety patients had diabetes mellitus (DM), 35 patients with peripheral vascular disease, 4 patients with chronic obstructive pulmonary disease and 11 with heart valve disease. Two patients underwent off-pump CABG and 209 patients accepted on-pump CABG with commitment valve surgery. There were 210 cases of total arterial revascularization and 161 cases using left thoracic artery conduits, with a graft number of 2-4 (2.7±0.9). No operation-related death occurred, atrial fibrillation happened in 12 patients, hemothorax in 7 cases, and forearm hematoma in one case, hypoxemia in 13 cases and pneumonia in one case. The duration of mechanical ventilation was (8.3±4.7) hours and the mean hospital length of stay was (7.1±2.9) days. Follow-up was completed in 191 patients (90.52%) with a duration of 3-59 (35.5±9.3) months. The mean left ventricular ejection fraction at 3 months after operation was significantly improved, compared to that of the pre-operation (61.0%±7.2% vs 47.1%±5.3%, P=0.017). All patients survived, except that one died from brain injury. No major cardiac events occurred, with a cumulative survival rate of 100% at 1 year and 99.53% at 3 year after operation, respectively. It was showed in coronary CT angiography (CTA) examination that all grafts in 132 patients were patent at the mean follow-up duration of (21.5±6.4) months. Conclusions: BRA grafts as arterial conduit in CABG are proved to be safe, easy for total arterial revascularization and have good mid-term clinical results.


CaSm: an Sm-like protein that contributes to the transformed state in cancer cells.
A novel gene encoding a protein containing Sm motif-like domains was found to have elevated expression in pancreatic cancer and in several cancer-derived cell lines. CaSm (for Cancer-associated Sm-like) mRNA is up-regulated in 87.5% (seven of eight) of pancreatic tumor/normal pairs. Similarly, cell lines from cancers originating in liver, ovary, lung, and kidney show increased CaSm expression compared to their normal tissue cognates. CaSm encodes a 133-amino acid open reading frame that contains the two Sm motifs found in the common snRNP proteins, with the greatest homology to the Sm G protein (60% similarity). Two hypothetical proteins from Caenorhabditis elegans and Saccharomyces cerevisiae share even greater similarity (72.8 and 67.7%, respectively), suggesting a broad family of proteins containing Sm motifs. Antisense CaSm RNA is able to alter the transformed phenotype of pancreatic cancer cells by reducing their ability to form large colonies in soft agar when compared to untransfected cells. Therefore, CaSm expression appears to be necessary for maintenance of the transformed state.


Biomedical science journals in the Arab world.
Medieval Arab scientists established the basis of medical practice and gave important attention to the publication of scientific results. At present, modern scientific publishing in the Arab world is in its developmental stage. Arab biomedical journals are less than 300, most of which are published in Egypt, Lebanon, and the Kingdom of Saudi Arabia. Yet, many of these journals do not have on-line access or are indexed in major bibliographic databases. The majority of indexed journals, however, do not have a stable presence in the popular PubMed database and their indexes are discontinued since 2001. The exposure of Arab biomedical journals in international indices undoubtedly plays an important role in improving the scientific quality of these journals. The successful examples discussed in this review encourage us to call for the formation of a consortium of Arab biomedical journal publishers to assist in redressing the balance of the region from biomedical data consumption to data production.


Utilization of epinephrine-soaked gauzes to address bleeding from osteotomy sites in non-tourniquet total knee arthroplasty: a retrospective cohort study.
Reducing tourniquet inflation time is important because of the complications of tourniquet extensively used for the control of hemorrhage in total knee arthroplasty (TKA). Bleeding management is critical to acquire a relative bloodless arthrotomy interface for maximize cement fixation in non-tourniquet TKA. The purpose of this study was to investigate hemostatic and hemodynamic effects of epinephrine-soaked gauzes in cemented TKAs. A retrospective cohort study of 101 patients in two groups was performed. The first group (n = 51) underwent unilateral TKA with our procedures of epinephrine use, the second group (n = 50) had the same protocol with tourniquet and no epinephrine utilization. Surgical field visualization was assessed by grading scale for difficulty of intraoperative visualization due to blood and number of surgical field clearances. Perioperative blood loss was recorded. Hemodynamic parameters were observed in the epinephrine group. There was statistically significant difference (p < 0.01) on surgeon-rated difficulty in visualization in the epinephrine group between before and after use of epinephrine, and no statistically significant difference (p = 0.96) between two groups before cementing. No statistically significant result on numbers of surgical field clearances between two groups (p = 0.25) was found. Epinephrine group showed significant difference in hidden blood loss compared with no epinephrine group (576.6 ± 229.3 vs 693.2 ± 302.9, respectively, p = 0.04). The hemodynamic effects of epinephrine may be under control. The procedure of epinephrine soaked gauzes, as a prudent adjunct, may be effective to reduce blood loss and obtain bloodless bone sections in non-tourniquet TKAs, regardless of hemodynamics.


Recent Advances in Enhancement Techniques for Blood Fingerprints.
The blood fingerprint enhancement is not so eye-catching as latent fingerprint development in forensic community, but it is indeed an important piece of evidence for personal identification, forensic analysis and even reconstruction of crime scenes. In over past ten years, novel reagents, advanced materials and emerging techniques have growingly participated in blood fingerprint enhancement, which not only leads to a higher level of developing sensitivity, selectivity and contrast, but also endows blood impressions with more forensic significance. This review summarizes recent advances in conventional chemical reagents targeting at heme, protein and amino acid as well as emerging enhancement techniques based on advanced materials, new equipment or methods. Some critical issues in forensic science are also discussed, including partial blood fingerprint enhancement, false positive of developing reagents, the compatibility of blood enhancement technique and DNA, fingerprint age determination, and so on. Finally, we have proposed several urgent problems to be solved and the prospects of some promising techniques were proposed in the field of blood fingerprint enhancement in future work.


Real-Time MRI Navigated Ultrasound for Preoperative Tumor Evaluation in Breast Cancer Patients: Technique and Clinical Implementation.
Real-time magnetic resonance imaging (MRI) navigated ultrasound is an image fusion technique to display the results of both MRI and ultrasonography on the same monitor. This system is a promising technique to improve lesion detection and analysis, to maximize advantages of each imaging modality, and to compensate the disadvantages of both MRI and ultrasound. In evaluating breast cancer stage preoperatively, MRI and ultrasound are the most representative imaging modalities. However, sometimes difficulties arise in interpreting and correlating the radiological features between these two different modalities. This pictorial essay demonstrates the technical principles of the real-time MRI navigated ultrasound, and clinical implementation of the system in preoperative evaluation of tumor extent, multiplicity, and nodal status in breast cancer patients.


Infrared spectra of CH(2)=Zr(H)NC, CH(3)-ZrNC, and eta(2)-Zr(NC)-CH(3) produced by reactions of laser-ablated Zr atoms with acetonitrile.
The zirconium methylidene isocyanide, methyl isocyanide, and eta(2)-nitrile-pi-complexes are observed in the matrix IR spectra from reactions of laser-ablated Zr atoms and acetonitrile isotopomers. The methylidene CH(2)=Zr(H)NC has a C(1) agostic structure in line with simple early transition-metal methylidenes recently produced from reactions with small alkanes and methyl halides, and the extent of agostic distortion is also comparable. Formation of the isocyanide complexes from acetonitrile is interesting but not surprising according to previous studies of metal reactions with nitrile-containing compounds, and their stabilities over the cyanide species are reproduced by DFT calculations. Observation of the relatively rare nitrile pi-complex and its photodissociation suggests that the reaction proceeds in the order of Zr<--NCCH(3), eta(2)-Zr(NC)-CH(3), CH(3)-ZrNC, and CH(2)=Zr(H)NC. The intermediate transition-state structures are also examined.


Rab escort protein 1 (REP1) in intracellular traffic: a functional and pathophysiological overview.
The intracellular distribution of proteins, compartments, substrates, and products is an active process called intracellular traffic. Control of intracellular traffic is established by small GTP-binding proteins (Rab proteins). Rab proteins are modified by geranyl-geranyl moieties necessary for membrane association and target-protein recognition. Geranyl-geranyl groups are transferred to Rab proteins by geranyl-geranyl transferase 2 (GGTase2). GGTase2 requires Rab escort protein 1 (REP1) to bind Rab proteins. REP1 null mutations underlie an X-linked retinal degeneration called choroideremia (CHM). This review summarizes the current biochemical and clinical knowledge on REP1 and CHM.


Reliability and Minimal Detectable Change for Sit-to-Stand Tests and the Functional Gait Assessment for Individuals With Parkinson Disease.
This study examined test-retest relative (intraclass correlation coefficient [ICC]) and absolute (minimum detectable change [MDC]) reliabilities for the 5 times sit-to-stand (5×STS), 30-second sit-to-stand (30sSTS), and the functional gait assessment (FGA) tests in people with Parkinson disease (PD). In addition, correlation of these functional tests with a history of falls was examined over a 6-month period, and the internal consistency of the FGA was established. Twenty-two patients with PD (Hoehn and Yahr stages 1-3) completed 3 functional tests over 2 test-retest periods of 6 to 8 days. Falls were self-reported for the prior 6 months. Moderate-to-excellent test-retest ICC(2,2) and MDC95 values were found for the 30sSTS (0.94, 3 times) and ICC(2,1) and MDC95 values were found for the FGA (0.86, 4 points). The 5×STS demonstrated a lower ICC(2,2) and a high MDC95 value (0.74, 10 seconds). A significant correlation was only found between past falls and the FGA test (r =-0.48, P < .05) during session 1. Cronbach α values for the 10-item FGA during session 1 and session 2 were 0.75 and 0.85, respectively. To assess for change over time, we found the 30sSTS and the FGA tests can be used reliably in patients with PD. A lower FGA score was associated with a higher chance of falls, and good internal consistency of the FGA was found.


Seeking and processing influenza vaccine information: a study of health care workers at a large urban hospital.
In response to low influenza vaccination rates among health care workers, health officials have explored determinants of uptake and developed communication interventions. Key to these efforts is how workers seek and attend to vaccine information. We applied a model of risk information seeking and processing to survey 226 physicians and nurses at a large, urban hospital (response rate = 5.7%; cooperation rate = 91.5%). Our goals were to (1) apply the model to a new setting, audience, and issue and (2) explore novel concepts (e.g., source credibility and information usefulness) and moderating relationships among variables. Consistent with previous research, information subjective norms-perceived social pressure to remain informed about vaccination-were a strong predictor of information seeking and systematic processing. Neither source credibility nor information usefulness independently increased explained variance, although they moderated the relationship between norms and communication behavior. We discuss theoretical and practical implications of these findings.


Renoprotective properties of pirfenidone in subtotally nephrectomized rats.
Renal fibrosis is the final common pathway of chronic kidney disease, and its progression predicts the degree of renal dysfunction. We investigated the renoprotective properties of pirfenidone in a remnant kidney model of chronic renal failure to determine its pharmacological potency compared to enalapril. Five-sixths nephrectomized rats were fed diet containing pirfenidone (approximately 700mg/kg/day) for 8weeks. Pirfenidone steadily inhibited the progression of proteinuria, but not to a significant degree. Pirfenidone prevented the elevation of plasma creatinine and blood urea nitrogen. At the end of the experiment, pirfenidone had reduced systolic blood pressure by means of its renoprotective effect. In a histological study, pirfenidone improved interstitial fibrosis in the renal cortex. These effects were supported by the suppression of the expression of TGF-beta and fibronectin in the mRNA of the kidney. In contrast, pirfenidone had little effect on the expression of alpha-smooth muscle actin, which is one of the proteins responsible for epithelial-mesenchymal transition. This property was confirmed by the TGF-beta-induced transdifferentiation observed in cultured normal rat kidney tubular epithelial NRK52E cells. These results suggest that pirfenidone improves the progression of chronic renal failure via its antifibrotic action, although pirfenidone has less effective TGF-beta-induced epithelial to mesenchymal transdifferentiation.


Fracture Diodes: Directional Asymmetry of Fracture Toughness.
Toughness describes the ability of a material to resist fracture or crack propagation. It is demonstrated here that fracture toughness of a material can be asymmetric, i.e., the resistance of a medium to a crack propagating from right to left can be significantly different from that to a crack propagating from left to right. Such asymmetry is unknown in natural materials, but we show that it can be built into artificial materials through the proper control of microstructure. This paves the way for control of crack paths and direction, where fracture-when unavoidable-can be guided through predesigned paths to minimize loss of critical components.


The Efficiency of Different Arthroscopic Discopexy Techniques Based on Clinical and Radiographic Findings: A Systematic Review.
The aim of this systematic review was to evaluate the effectiveness of different temporomandibular joint arthroscopic discopexy techniques. The systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and an electronic search was performed using MEDLINE (PubMed), The Cochrane Library, ScienceDirect databases using a combination of the terms ''discopexy,'' ''disc recapture,'' ''disc fixation,'' and ''temporomandibular joint'' to identify clinical trials published from 2010. In total, 493 records were screened, of which only 9 fulfilled the inclusion criteria and were included in qualitative data synthesis. The results of clinical findings evaluation showed that arthroscopic discopexy statistically significantly improved levels of pain (VAS) and maximum interincisal opening whereas magnetic resonance imaging evaluation showed disc position improvement of up to 90% to 100%. In conclusion, this review provides the evidence of the potential benefits of arthroscopic disc fixation in the treatment of patients with internal derangements : reduced pain, increased maximum interincisal opening, and improved disc position evaluated by magnetic resonance imaging, whereas disc fixation using suturing techniques seems to be the most appropriate method.


Carbendazim: disposition, cellular permeability, metabolite identification, and pharmacokinetic comparison with its nanoparticle.
The purpose of this study was to systematically evaluate the pharmacokinetic profiles of carbendazim, a novel anticancer drug. Carbendazim reached the highest concentrations in stomach and small intestine by 1 h after oral administration (500 mg/kg) to tumor-bearing nude mice. Four hours later, carbendazim in the large intestine reached maximum concentrations, probably because of pH-induced precipitation of the drug in the large intestine. The highest concentrations of carbendazim in well-perfused tissues, solid tumor, and blood ranged from 63 to 164 microg/g by 4 h. The percentage of carbendazim distributed to solid tumor by 4 h was higher than most well-perfused tissues. Carbendazim concentrations in blood were similar to, or somewhat lower than, those in tumor and other tissues. By 24 h post-dosing, carbendazim concentrations in tissues and blood declined to almost basal levels. The total percentage of administered carbendazim eliminated in urine was 25.7%, and in feces 16.6% within 24 h. Carbendazim exhibited fast permeation across Caco-2 and HT-29 carcinoma cell lines with corresponding permeability coefficients 7.74-8.06 x 10(-5) and 6.8-8.42 x 10(-5) (cm/s). The overall plasma protein binding of carbendazim (0.2-125 microg/mL) assessed by ultrafiltration ranged from 60 to 74%. Comparative pharmacokinetics was conducted in rats by high-pressure liquid chromatography to evaluate the relative bioavailability of carbendazim versus its nanoparticle formulation. Carbendazim and its nanoparticle reached T(max) at 2.01 and 1.57 h, respectively. The relative bioavailability of nanoparticle carbendazim versus regular carbendazim was 166%. High-pressure liquid chromatography analysis of the rat serum obtained at 20 h after oral dosing revealed a carbendazim metabolite, which was identified by mass spectroscopy analysis as 2-aminobenzimidazole, a hydrolyzed product of carbendazim. Incubation of carbendazim with human and rat liver microsomes produced a metabolite identified by mass spectrometry as 5(6)- or 4(7)-hydroxyl carbendazim. The comprehensive pharmacokinetic information is important to the current clinical investigation of carbendazim.


Successful cord blood transplantation in an adult acute lymphoblastic leukemia patient with congenital heart disease.
Recent advances in surgical corrections and supportive care for congenital heart disease have resulted in increasing numbers of adult survivors who may develop hematological malignancies. Treatments including chemotherapy for such patients may cause serious hemodynamic or cardiac complications, especially in those receiving stem cell transplantation. We present a 29-year-old woman with acute lymphoblastic leukemia and congenital heart disease. She had been diagnosed with pulmonary atresia with an intact ventricular septum at birth, and the anomaly was surgically corrected according to the Fontan technique at age 9 years. Her induction chemotherapy required modifications due to poor cardiac status with Fontan circulation. However, after surgical procedures including total cavopulmonary connection and aortic valve replacement at first complete remission, her cardiac status was significantly improved. Subsequently, she underwent cord blood stem cell transplantation at the third complete remission. She required intensive supportive care for circulatory failure as a pre-engraftment immune reaction and stage III acute graft versus host disease of the gut, but recovered from these complications. She was discharged on day 239, and remained in complete remission at 1-year post-transplantation.


Synthesis and in vitro evaluation of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles: high-affinity ligands for the N,N'-di-o-tolylguanidine-labeled sigma binding site.
A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclo[b]indoles substituted at the 5 and/or 11 positions was synthesized from tropinone. Affinity for sigma binding sites was determined using [3H]-N,N'-di-o-tolylguanidine ([3H]DTG) and [3H]-(+)-3-(3-hydroxyphenyl)-N-1-propylpiperidine ([3H]-(+)-3-PPP) and for the dopamine D2 receptor labeled with [3H]sulpiride. Nearly all compounds studied in this series possessed a higher affinity for [3H]DTG than [3H]-(+)-PPP-labeled sigma sites, suggesting that [3H]DTG and [3H]-(+)-3-PPP radioligands label pharmacologically distinct sigma binding sites, as reported previously. Substitution at the 11 position with side chains containing a four-carbon tether resulted in compounds having the highest affinity for the [3H]DTG-labeled sigma site. The most potent and selective member of this series was 11-[4-(2-furanyl)butyl]-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept [b] indole (40). Enantioselectivity was investigated by preparing the (+)- and (-)-isomers of 40. These studies revealed that (+)-40 was more potent at the [3H]-DTG-labeled sigma site whereas (-)-40 had a higher affinity at sigma sites labeled with [3H]-(+)-PPP. Racemic 40 was observed to possess a higher affinity than either of its respective enantiomers at both the [3H]DTG- and [3H]-(+)-3-PPP-labeled sites, suggesting an allosteric interaction.


The Emerging Role of RNA as a Therapeutic Target for Small Molecules.
Recent advances in understanding different RNAs and unique features of their biology have revealed a wealth of information. However, approaches to identify small molecules that target these newly discovered regulatory elements have been lacking. The application of new biochemical screening and design-based technologies, coupled with a resurgence of interest in phenotypic screening, has resulted in several compelling successes in targeting RNA. A number of recent advances suggest that achieving the long-standing goal of developing drug-like, biologically active small molecules that target RNA is possible. This review highlights advances and successes in approaches to targeting RNA with diverse small molecules, and the potential for these technologies to pave the way to new types of RNA-targeted therapeutics.


History of disease and the longue durée.
This paper summarizes Grmek's theoretical contribution to history of disease and explores to what extent the longue durée could still be a useful concept in order to better understand past perceptions of, and reactions to, diseases. The case of the medical responses to epidemic disease in pre-industrial Europe is synthetically expounded in order to illustrate this issue.


Evidence-based practice and research utilization activities among rural nurses.
To identify the extent to which rural nurses utilize evidence-based practice guidelines from scientific research in their practice; to describe both previous and current research utilization activities in which they have participated, and to identify the specific barriers they face in their practice settings. Data for this descriptive study were collected through questionnaires with open-ended questions focused on (a) current utilization of nursing research findings, (b) previous involvement in nursing research activities, and (c) participation in medical research activities. The participants were 106 nurses from various practice areas in six rural counties of a southwestern state in the United States. Results revealed that only 20.8% of the participants stated they were currently involved in research utilization, and they were mostly nurses with bachelor's degrees. The two most common areas of current research utilization were pain management and pressure ulcer prevention and management. Barriers to research utilization, such as rural isolation and lack of nursing research consultants, were identified. The types of research utilization activities identified by these nurses indicate how much the facilities in which these nurses work in the rural areas are striving with the utilization of available scientific evidence. Rural nurses face unique barriers related to situational and geographic factors, with implications for nursing administrators, researchers, and educators.


EMG-Based Estimation of Limb Movement Using Deep Learning With Recurrent Convolutional Neural Networks.
A novel model based on deep learning is proposed to estimate kinematic information for myoelectric control from multi-channel electromyogram (EMG) signals. The neural information of limb movement is embedded in EMG signals that are influenced by all kinds of factors. In order to overcome the negative effects of variability in signals, the proposed model employs the deep architecture combining convolutional neural networks (CNNs) and recurrent neural networks (RNNs). The EMG signals are transformed to time-frequency frames as the input to the model. The limb movement is estimated by the model that is trained with the gradient descent and backpropagation procedure. We tested the model for simultaneous and proportional estimation of limb movement in eight healthy subjects and compared it with support vector regression (SVR) and CNNs on the same data set. The experimental studies show that the proposed model has higher estimation accuracy and better robustness with respect to time. The combination of CNNs and RNNs can improve the model performance compared with using CNNs alone. The model of deep architecture is promising in EMG decoding and optimization of network structures can increase the accuracy and robustness.


Insomnia Caused by Serotonin Depletion is Due to Hypothermia.
Serotonin (5-hydroxytryptamine, 5-HT) neurons are now thought to promote wakefulness. Early experiments using the tryptophan hydroxylase inhibitor para-chlorophenylalanine (PCPA) had led to the opposite conclusion, that 5-HT causes sleep, but those studies were subsequently contradicted by electrophysiological and behavioral data. Here we tested the hypothesis that the difference in conclusions was due to failure of early PCPA experiments to control for the recently recognized role of 5-HT in thermoregulation. Adult male C57BL/6N mice were treated with PCPA (800 mg/kg intraperitoneally for 5 d; n = 15) or saline (n = 15), and housed at 20 °C (normal room temperature) or at 33 °C (thermoneutral for mice) for 24 h. In a separate set of experiments, mice were exposed to 4 °C for 4 h to characterize their ability to thermoregulate. PCPA treatment reduced brain 5-HT to less than 12% of that of controls. PCPA-treated mice housed at 20 °C spent significantly more time awake than controls. However, core body temperature decreased from 36.5 °C to 35.1 °C. When housed at 33 °C, body temperature remained normal, and total sleep duration, sleep architecture, and time in each vigilance state were the same as controls. When challenged with 4 °C, PCPA-treated mice experienced a precipitous drop in body temperature, whereas control mice maintained a normal body temperature. These results indicate that early experiments using para-chlorophenylalanine that led to the conclusion that 5-hydroxytryptamine (5-HT) causes sleep were likely confounded by hypothermia. Temperature controls should be considered in experiments using 5-HT depletion.


Neuromolecular Underpinnings of Negative Cognitive Bias in Depression.
This selective review aims to summarize the recent advances in understanding the neuromolecular underpinnings of biased cognition in depressive disorder. We begin by considering the cognitive correlates of depressed mood and the key brain systems implicated in its development. We then review the core findings across two domains of biased cognitive function in depression: pessimistic judgment bias and abnormal response to negative feedback. In considering their underlying substrates, we focus on the neurochemical mechanisms identified by genetic, molecular and pharmacological challenge studies. We conclude by discussing experimental approaches to the treatment of depression, which are derived largely from an improved understanding of its cognitive substrates.


Gas Transport in Interacting Planar Brushes.
Recent experiments on melts of spherical nanoparticles (NPs) densely grafted with polymer chains show enhanced gas transport relative to the neat polymer (without NPs). As a means of understanding this unexpected behavior, we consider here the simpler case of two interacting planar brushes, under conditions representing a polymer melt far below its critical point (i.e., where the "free volume" or holes act akin to a poor solvent). Computer simulations illustrate, in agreement with mean-field ideas, that the density profile far away from the walls is flat but with a value that is marginally larger than the corresponding polymer melt under identical state conditions. We find that tracer particles, which represent the gas of interest, segregate preferentially to the grafting surface, with this result being relatively insensitive to the nature of polymer-surface interactions. These brush layers therefore correspond to heterogeneous transport media: the gas molecules near the grafting surface have accelerated dynamics (presumably parallel to the wall) relative to the corresponding polymer melt, but they have slower dynamics in the central region of the brush. We therefore find that gas molecules perform hop-like motions - they spend a significant part of their time in the regions of fast transport, separated by motions where they "hop" from one surface to the other. These phenomena in combination lead to an overall speedup in gas dynamics in these brush layers relative to a polymer melt, in good agreement with the experimental data.


Human Amniotic Mesenchymal Stem Cells Promote Endogenous Bone Regeneration.
Bone regeneration has become a research hotspot and therapeutic target in the field of bone and joint medicine. Stem cell-based therapy aims to promote endogenous regeneration and improves therapeutic effects and side-effects of traditional reconstruction of significant bone defects and disorders. Human amniotic mesenchymal stem cells (hAMSCs) are seed cells with superior paracrine functions on immune-regulation, anti-inflammation, and vascularized tissue regeneration. The present review summarized the source and characteristics of hAMSCs and analyzed their roles in tissue regeneration. Next, the therapeutic effects and mechanisms of hAMSCs in promoting bone regeneration of joint diseases and bone defects. Finally, the clinical application of hAMSCs from current clinical trials was analyzed. Although more studies are needed to confirm that hAMSC-based therapy to treat bone diseases, the clinical application prospect of the approach is worth investigating.


Kinesiophobia Levels in Fibromyalgia Syndrome and the Relationship Between Pain, Disease Activity, Depression.
This study aims to compare kinesiophobia levels between patients with fibromyalgia syndrome (FMS) and healthy volunteers and to investigate the factors associated with kinesiophobia in FMS. This case-control study included 88 female patients with FMS (mean age 41.61 years; range 21 to 61 years) and 67 female healthy volunteers (mean age 41.34 years; range 19 to 59 years). The participants' age, body mass index (BMI), and educational status were recorded. Patients were evaluated using a visual analog scale for pain, the Fibromyalgia Impact Questionnaire (FIQ) for disease activity, the Hamilton Depression Scale (HAM-D) for depression level, and the Tampa Scale for Kinesiophobia (TSK) for kinesiophobia. Additionally, the patients' serum 25-hydroxyvitamin D levels were measured. No significant differences were found between the patient and control groups in terms of age, BMI, and educational status (p>0.05). The mean TSK scores were 42.0±7.6 in the patient group and 37.2±8.8 in the control group. TSK score was significantly higher in the patient group (p<0.001). BMI levels, FIQ scores, and vitamin D concentrations were significantly associated with TSK scores according to the linear regression analysis (p<0.05). However, age, symptom duration, and HAM-D scores were not found to be associated with TSK scores (p>0.05). Kinesiophobia scores were significantly higher in patients with FMS. Physicians should focus on kinesiophobia when evaluating patients with FMS and inform patients about the importance and treatment strategies of kinesiophobia.


Talbot array illuminator with multilevel phase gratings.
Construction of one-dimensional multilevel phase gratings is described that, when illuminated by a coherent plane wave, lead to the formation of amplitude binary gratings with an arbitrary value of the opening ratio. The gratings are proposed as array illuminators that can provide a significantly high compression factor together with a large number of uniformly illuminated points.


Study of Hemolysis During Storage of Blood in the Blood Bank of a Tertiary Health Care Centre.
The aim of RBC storage system in a blood bank is to counteract damage to the metabolic machinery and the membrane, to improve post-transfusion viability. In recent years, the need for strict control over the quality of blood has been emphasised. Such quality indicator includes extend of hemolysis and morphological changes of RBC during storage. This study was design to see extend of hemolysis and level of plasma lactate dehydrogenase (LDH) and plasma potassium, during processing and storage at different intervals under blood bank condition. Forty-six donors were selected and blood units were collected and stored under blood bank conditions. Mean plasma haemoglobin of stored blood was estimated by tetra methyl benzidine method (TMB) and percentage hemolysis was calculated on day 0, 1, 7, 21, 28, 35 and 42 days. Similarly plasma LDH and plasma potassium level was also assessed during storage. It was noted that free haemoglobin level and percentage hemolysis progressively increased with storage along with the level of LDH and potassium. However, extend of hemolysis did not exceed the permissible limit of 0.8% up to 42 days of storage. 15 blood bags which showed visual hemolysis on day 28 did not exceeded the threshold of 0.8% hemolysis, when interpreted by TMB method. It was concluded that TMB method is better than visual method for determination of hemolysis. The reduced hemolysis at this centre may be accounted for the use of additive solution SAGM (Saline, Adenine, Glucose, Mannitol) and DEHP (di-2-ethyl hexyl phthalate) as plasticizer in blood bags for storage.


Agnogenic myeloid metaplasia with pulmonary hematopoiesis.
Agnogenic myeloid metaplasia (AMM) is characterized by bone marrow fibrosis, splenomegaly and leukoerythroblastic anemia and is frequently accompanied by extramedullary hematopoiesis (EMH). Pulmonary interstitial EMH associated with myelofibrosis has rarely been described in the medical literature and is usually fatal. We report the case of a 77-year-old man with agnogenic myeloid metaplasia (AMM) treated with hydroxyurea, who seven years after diagnosis presented with dyspnea and severe hypoxemia. Radionuclide bone marrow scanning demonstrated increased tracer activity on the bases of both lungs, consistent with non-hepatosplenic EMH. Pulmonary EMH is rare in patients with AMM, but should be considered in patients with hypoxemia and respiratory distress.


Nonpeptidic endothelin-converting enzyme inhibitors and their potential therapeutic applications.
Endothelins (ETs) are potent vasoconstrictors, promitogens, and inflammatory mediators. They have been implicated in the pathogenesis of various cardiovascular, renal, pulmonary, and central nervous system diseases. Since the final step of the biosynthesis of ETs is catalyzed by a family of endothelin-converting enzymes (ECEs), inhibitors of these enzymes may represent novel therapeutic agents. Currently, seven isoforms of these metalloproteases have been identified; they all share a significant amino acid sequence identity with neutral endopeptidase 24.11 (NEP), another metalloprotease. Therefore, it is not surprising that the majority of ECE inhibitors also possess potent NEP inhibitory activity. To date, three classes of ECE inhibitors have been synthesized: dual ECE/NEP inhibitors, triple ECE/NEP/ACE inhibitors, and selective ECE inhibitors. Potential clinical applications of these compounds in hypertension, chronic heart failure, restenosis, renal failure, and cerebral vasospasm deduced from studies with relevant animal models are reviewed.


Improved stability of "naked" gold nanoparticles enabled by in situ coating with mono and multivalent thiol PEG ligands.
Unprotected ("naked") gold nanoparticles with high monodispersity ([d], 5.5± 0.5 nm) were obtained in a facile and single-step microwave-assisted hydrolytic decomposition of the molecular precursor [NMe4][Au(CF3)2]. Given their chloride-free surface chemistry, the as-obtained gold nanoparticles were in situ functionalized with mono-, di-, and trivalent thiolated PEG ligands in order to study the influence of multivalent character of the ligands on the stability of the colloidal solutions. For this purpose, a novel tridentate ligand was synthesized and the previously reported syntheses of mono- and divalent thiol ligands were improved. Owing to the pristine character of the Au nanoparticles no ligand exchange was required, and the colloidal and chemical stability of the mono- and multivalent functionalized particles purely depended on the ligating ability of the thiolated groups. In situ-functionalized Au nanoparticles showed a strikingly (2 orders of magnitude higher) improved stability against small nucleophiles such as sodium cyanide compared to gold nanoparticles coated with citrate ligands and functionalized via a ligand-exchange reaction. The monovalent thiol PEG ligand produced most stable colloids against cyanide, which is explained by a strongly increased numerical ligand-density on the surface. Gold colloids stabilized by di- and trivalent ligands exhibited high stability in aqueous solutions with high NaCl concentrations (2 M) in contrast to those functionalized with the monovalent PEG ligand, which were only temporally stable in dilute NaCl solutions. The beneficial effect of the multivalence of the ligands was further demonstrated by the incorporation of an additional chelating ligand (dithiothreitol) to the colloidal dispersions.


Detection of food-borne bacteria in ready to eat betel leaf sold at local markets in Mymensingh.
The present study was undertaken to determine bacterial load as well as characterize bacterial flora of ready to eat (RTE) betel leaf sold at local markets in Mymensingh city. A total of 25 RTE betel leaf samples were collected from five local markets such as Kamal-Ranjit (KR) market, Shesh more, Kewatkhali, Jobber more, and Ganginar par. Total viable count of bacteria in betel leaf (log10 mean colony forming unit±standard deviation/ml) was 7.58±0.04 for KR market, 7.72±0.06 for Shesh more, 7.62±0.04 for Kewatkhali, 7.40±0.03 for Jobber more, and 7.60±0.06 for Ganginar par. A total of 98 bacterial isolates belong to five genera (Escherichia coli, Salmonella spp., Vibrio spp., Bacillus spp., and Staphylococcus spp.) were identified. The prevalence of E. coli was 17.34%, Salmonella spp. was 25.51%, Vibrio spp. was 19.39%, Bacillus spp. was 18.37%, and Staphylococcus spp. was 19.39%. Antibiotic sensitivity test showed that all isolates were sensitive to two antibiotics such as ciprofloxacin and gentamicin. Four isolates (E. coli, Salmonella spp., Vibrio spp., and Staphylococcus spp.) were resistant to two antibiotics (ampicillin and cephalexin). Antibiogram profile of bacterial isolates of betel leaf suggests that they were multidrug resistance. Data of this study indicate that betel leaf sold at local market harbors multidrug resistance food-borne bacteria which might cause public health hazards if these antibiotic resistant transfer to human through food chain.


High-Resolution Vertical Polarization Excited Dark-Field Microscopic Imaging of Anisotropic Gold Nanorods for the Sensitive Detection and Spatial Imaging of Intracellular microRNA-21.
As an important biomarker for early diagnosis of cancers, sensitive detection and high-resolution imaging of microRNA-21 in cancer cells have become important and challengeable. In this work, highly sensitive detection and spatial imaging of intracellular microRNA-21 were realized by the reduced signal background through vertical polarization excitation with a polarizer. The lateral local surface plasmon resonance property of gold nanorods (AuNRs) displayed a pronounced green color with low scattering intensity, which was adjusted to red color with strong scattering intensity when the core-satellite gold nanoparticle (AuNP) assembly was constructed on the side of AuNRs through a catalyzed hairpin assembly (CHA) circuit in the presence of microRNA-21. This unique approach allows for effectively reducing the strong background signal to improve the sensitivity of detection. Additionally, the proposed strategy can not only realize the sensitive detection of microRNA-21 with the limit of detection as low as 2 pM (3σ) but also achieve the high spatial imaging of cancer cells, which provided a specific strategy for the construction and imaging of intracellular imaging probes. It is believed that the simple and sensitive approach on the basis of lateral local surface plasmon resonance property of anisotropic AuNRs with excellent sensitivity combined with high spatial imaging holds promising potentials to visualize intracellular microRNAs with low abundance.


Organellar genome comparisons of Sargassum polycystum and S. plagiophyllum (Fucales, Phaeophyceae) with other Sargassum species.
Sargassum polycystum C. Agardh and Sargassum plagiophyllum C. Agardh are inhabitants of tropical coastal areas, their populations are negatively influenced by global warming and marine environment changes. The mitochondrial and chloroplast genomes of these species have not been sequenced. The mitochondrial genomes of S. polycystum and S. plagiophyllum were 34,825 bp and 34,862 bp, respectively, and their corresponding chloroplast genomes were 124,493 bp and 124,536 bp, respectively. The mitochondrial and chloroplast genomes of these species share conserved synteny, sequence regions and gene number when compared with the organellar genomes of other Sargassum species. Based on sequence analysis of 35 protein-coding genes, we deduced that S. polycystum and S. plagiophyllum were closely related with S. ilicifolium; these species diverged approximately 0.3 million years ago (Ma; 0.1-0.53 Ma) during the Pleistocene period (0.01-2.59 Ma). Rates of synonymous and non-synonymous substitutions in the mitochondrial genome of the Sargassum genus were 3 times higher than those in the chloroplast genome. In the mitochondrial genome, rpl5, rpl31 and rps11 had the highest synonymous substitution rates. In the chloroplast genome, psaE, rpl14 and rpl27 had the highest synonymous substitution rates. Phylogenetic analysis confirms the close relationship between the two sequenced species and S. ilicifolium. Both synonymous and non-synonymous substitution rates show significant divergence between the group of mitochondrial genomes versus the group of chloroplast genomes. The deciphering of complete mitochondrial and chloroplast genomes is significant as it advances our understanding of the evolutionary and phylogenetic relationships between species of brown seaweeds.


Bose-Einstein Condensation of Efimovian Triples in the Unitary Bose Gas.
In an atomic Bose-Einstein condensate quenched to the unitary regime, we predict the sequential formation of a significant fraction of condensed pairs and triples. At short distances, we demonstrate the two-body and Efimovian character of the condensed pairs and triples, respectively. As the system evolves, their size becomes comparable to the interparticle distance, such that many-body effects become significant. The structure of the condensed triples depends on the size of Efimov states compared with density scales. Unexpectedly, we find universal condensed triples in the limit where these scales are well separated. Our findings provide a new framework for understanding dynamics in the unitary regime as the Bose-Einstein condensation of few-body composites.


[Arterial embolization in hemorrhagic renal angiomyolipoma].
Renal angiomyolipoma (AML) is a rare benign tumour (2-3%) comprising variable proportions of an adipose component, which is often the most abundant, a smooth muscle contingent and a vascular contingent. The objective of this study is to demonstrate the value of embolization of bleeding angiomyolipomas. 2 patient, aged 22 and 62 years, presented with perirenal haematoma secondary to bleeding angiomyolipoma and were treated by selective arterial embolization. In one case, partial nephrectomy was subsequently performed because of the size of the angiomyolipoma (10 cm). In the other case, attempted partial nephrectomy at 3 months failed due to the proximity of the renal hilum and nephrectomy was performed. Beyond a diameter of 4 cm, the risk of perirenal haemorrhage is proportional to the size of the tumour. When surgery is required, selective arterial embolization is the first stage of treatment allowing partial nephrectomy in the majority of cases.


Treatment of Surgical Scars With Combination Pulsed Dye and Fractional Nonablative Laser: A Randomized Controlled Trial.
To assess the effectiveness and safety of combined pulsed-dye laser (PDL) and NAFL for treatment of surgical scars. PDL and NAFL have not been compared to healing by time alone. Randomized controlled, single-blinded clinical trial at an urban, university hospital. Healthy adults' status post skin surgery with primary closure were randomized to either 3 sessions of combination PDL and NAFL every 2 to 8 weeks, or control of no treatment. At baseline and 36-week follow-up, Patient and observer Scar Assessment Scale and Scar Cosmesis Assessment and Rating were completed by participants and blinded physicians. The primary outcome was scar improvement, as measured by the score difference over time. Of 76 participants, 52 completed the study (July 2017 to June 2019). No severe adverse events were reported. Patient and observer Scar Assessment Scale assessments demonstrated improvement in total score in the laser group compared to controls, as reported by patients [mean difference (standard deviation), laser: 12.86 (6.91) vs control: 7.25 (6.34); P = 0.004] and blinded physicians [18.32 (8.69) vs 13.08 (9.63); P = 0.044]. Patients observed a greater improvement in scar thickness [3.68 (2.04) vs 1.88 (1.85); P = 0.002] and stiffness [3.57 (2.78) vs 1.50 (2.11); P = 0.004] with lasers, and physicians reported greater improvement in vascularity [3.71 (1.98) vs 1.71 (1.52); P = 0.0002]. The live Scar Cosmesis Assessment and Rating subscore for erythema improved significantly with lasers [1.04 (0.79) vs 0.42 (0.50); P = 0.001]. Combined PDL and NAFL resulted in scar improvement. Scar thickness, stiffness, and erythema were improved. ClinicalTrials.gov (NCT03057964).


Bilateral hydronephrosis secondary to endometriosis managed by endoscopic ureteral stent placement in a captive Guinea baboon (Papio papio).
Spontaneous endometriosis is an estrogen-dependent, progressive and painful disease that affects a variety of nonhuman primates, including several species of baboons (Papio sp.). This case documents multimodal management of severe endometriosis in a captive female baboon within a zoological institution. An 18-yr-old, intact female Guinea baboon (Papio papio) was found to have an enlarged uterus. Fifteen months post ovariohysterctomy, scarring associated with endometrial tissue resulted in ureteral strictures, bilateral hydronephrosis, and azotemia. Cystoscopic placement of bilateral ureteral stents with fluoroscopy was performed and resulted in short-term clinical improvement. The animal's condition declined and euthanasia was elected 4 mo after ureteral stent placement. Severe endometriosis with secondary inflammation resulting in bilateral hydroureter and hydronephrosis, as well as concurrent cystitis, ureteritis, and pyelonephritis were confirmed at necropsy. Despite possible complications, ureteral stents can be considered a useful therapeutic option in patients with ureteral disease.


Microbiome-Derived Metabolites in Allogeneic Hematopoietic Stem Cell Transplantation.
The gut microbiome has emerged as a major character in the context of hematopoietic stem cell transplantation. The biology underpinning this relationship is still to be defined. Recently, mounting evidence has suggested a role for microbiome-derived metabolites in mediating crosstalk between intestinal microbial communities and the host. Some of these metabolites, such as fiber-derived short-chain fatty acids or amino acid-derived compounds, were found to have a role also in the transplant setting. New interesting data have been published on this topic, posing a new intriguing perspective on comprehension and treatment. This review provides an updated comprehensive overview of the available evidence in the field of gut microbiome-derived metabolites and hematopoietic stem cell transplantation.


Lazy approaches for interval timing correlation of sensor data streams.
We propose novel algorithms for the timing correlation of streaming sensor data. The sensor data are assumed to have interval timestamps so that they can represent temporal uncertainties. The proposed algorithms can support efficient timing correlation for various timing predicates such as deadline, delay, and within. In addition to the classical techniques, lazy evaluation and result cache are utilized to improve the algorithm performance. The proposed algorithms are implemented and compared under various workloads.


Insulin inhibits phagocytosis in normal human neutrophils via PKCalpha/beta-dependent priming of F-actin assembly.
This study investigated the effects of insulin on the phagocytosis of C3bi - and IgG-opsonized yeast particles in normal human neutrophils. Neutrophils were incubated in different insulin concentrations for 30 minutes and stimulated by C3bi - or IgG-opsonized yeast particles. Phagocytosis was quantified by both light microscopy and FACscan flow cytometry. Laser confocal microscopy was used for quantification of F-actin levels. Elevated insulin concentrations decreased neutrophil phagocytosis of both types of targets. This defect was shown to be in part due to a delayed phagocytosis in the presence of insulin. Following a 30 minute incubation, insulin was found to increase the accumulation of cortical F-actin, without affecting the total cellular F-actin content. The specific PKCalpha/beta inhibitor, Go6976, abolished the insulin-mediated increase in cortical F-actin content and both Go6976 and the PKCalpha/beta/delta/epsilon-specific inhibitor GF109203X reversed the inhibitory effects of insulin on phagocytosis. Hyperinsulinemia in vitro can inhibit phagocytosis of opsonized targets in normal human neutrophils. This effect of insulin is dependent on activation of PKCalpha and/or PKCbeta, and these insulin signals may interfere with the dynamic assembly/disassembly and/or distribution of F-actin, which is required for the phagocytosis process.


Validation of the functional rating index for the assessment of athletes with neck pain.
To validate the culturally-adapted Persian Functional Rating Index (PFRI) for assessing neck pain (NP) in athletes. In this cross-sectional study, 100 athletes with NP and 50 healthy athletes participated and responded to the PFRI. Fifty athletes with NP completed the PFRI for at least 7 d later to establish test-retest reliability. The athletes with NP responded to all items, indicating excellent clinical utility. No floor and ceiling effects were found, indicating content validity and responsiveness. The PFRI revealed capability to discriminate between the athletes with NP and healthy athletes. The PFRI demonstrated strong correlation with the Numerical Rating Scale (Spearman's rho = 0.94), and the Persian Neck Disability Index (Pearson r = 0.995), supporting criterion and construct validity. Internal consistency reliability was high (Cronbach's α coefficient: 0.97). The test-retest reliability was excellent (ICCagreement = 0.96). The absolute reliability values of standard error of measurement and smallest detectable change were 3.2 and 8.84, respectively. An exploratory factor analysis yielded one factor explaining 78.03% of the total variance. The PFRI is a valid and reliable measure of functional status in athletes with NP.


Conditional testing of multiple variants associated with bone mineral density in the FLNB gene region suggests that they represent a single association signal.
Low bone mineral density (BMD) is a primary risk factor for osteoporosis and is a highly heritable trait, but appears to be influenced by many genes. Genome-wide linkage studies have highlighted the chromosomal region 3p14-p22 as a quantitative trait locus for BMD (LOD 1.1 - 3.5). The FLNB gene, which is thought to have a role in cytoskeletal actin dynamics, is located within this chromosomal region and presents as a strong candidate for BMD regulation. We have previously identified significant associations between four SNPs in the FLNB gene and BMD in women. We have also previously identified associations between five SNPs located 5' of the transcription start site (TSS) and in intron 1 of the FLNB gene and expression of FLNB mRNA in osteoblasts in vitro. The latter five SNPs were genotyped in this study to test for association with BMD parameters in a family-based population of 769 Caucasian women. Using FBAT, significant associations were seen for femoral neck BMD Z-score with the SNPs rs11720285, rs11130605 and rs9809315 (P = 0.004 - 0.043). These three SNPs were also found to be significantly associated with total hip BMD Z-score (P = 0.014 - 0.026). We then combined the genotype data for these three SNPs with the four SNPs we previously identified as associated with BMD and performed a conditional analysis to determine whether they represent multiple independent associations with BMD. The results from this analysis suggested that these variants represent a single association signal. The SNPs identified in our studies as associated with BMD appear to be part of a single association signal between the FLNB gene and BMD in our data. FLNB is one of several genes located in 3p14-p22 that has been identified as significantly associated with BMD in Caucasian women.


DOT1L Is a Novel Cancer Stem Cell Target for Triple-Negative Breast Cancer.
Although chemotherapies kill most cancer cells, stem cell-enriched survivors seed metastasis, particularly in triple-negative breast cancers (TNBC). TNBCs arise from and are enriched for tumor stem cells. Here, we tested if inhibition of DOT1L, an epigenetic regulator of normal tissue stem/progenitor populations, would target TNBC stem cells. Effects of DOT1L inhibition by EPZ-5676 on stem cell properties were tested in three TNBC lines and four patient-derived xenograft (PDX) models and in isolated cancer stem cell (CSC)-enriched ALDH1+ and ALDH1- populations. RNA sequencing compared DOT1L regulated pathways in ALDH1+ and ALDH1- cells. To test if EPZ-5676 decreases CSC in vivo, limiting dilution assays of EPZ-5676/vehicle pretreated ALDH1+ and ALDH1- cells were performed. Tumor latency, growth, and metastasis were evaluated. Antitumor activity was also tested in TNBC PDX and PDX-derived organoids. ALDH1+ TNBC cells exhibit higher DOT1L and H3K79me2 than ALDH1-. DOT1L maintains MYC expression and self-renewal in ALDH1+ cells. Global profiling revealed that DOT1L governs oxidative phosphorylation, cMyc targets, DNA damage response, and WNT activation in ALDH1+ but not in ALDH1- cells. EPZ-5676 reduced tumorspheres and ALDH1+ cells in vitro and decreased tumor-initiating stem cells and metastasis in xenografts generated from ALDH1+ but not ALDH1- populations in vivo. EPZ-5676 significantly reduced growth in vivo of one of two TNBC PDX tested and decreased clonogenic 3D growth of two other PDX-derived organoid cultures. DOT1L emerges as a key CSC regulator in TNBC. Present data support further clinical investigation of DOT1L inhibitors to target stem cell-enriched TNBC.