Intersections between Young Women's Racial/Ethnic Identities and Sexual Orientation on Rates of Sexual Violence and Substance Use.
Little is known about whether there are differences in rates of sexual violence and its association with substance use based on women's identities, specifically the intersection of their race/ethnicity and sexual orientation. Women (N = 546; 18 to 29 years of age) recruited from a reproductive healthcare clinic reported their race, ethnicity, sexual orientation, sexual violence history and substance use. Five logistic regressions examined (a) rates of sexual violence, and (b) the strength of the associations between sexual violence and four substance use outcomes (heavy alcohol use, marijuana use, cigarette use, number of cigarettes used) based on sexual orientation. Subsequent logistic regressions examined race/ethnicity as a moderator of the associations between sexual orientation and (a) rates of sexual violence and (b) substance use. Most women surveyed were heterosexual (64%), and 35% of all women reported unwanted sex. Sexual minority women (SMW) reported higher rates of sexual violence and substance use than heterosexual women. Sexual violence was more strongly associated with heavy alcohol use, but not with marijuana or cigarette use, for SMW than heterosexual women. Rates of sexual violence varied based on the intersection of sexual orientation and race/ethnicity. Although SMW were more likely to report sexual violence than heterosexual women, this association was weaker for Black/Latinx women than for non-Hispanic White women (aOR = 0.39, 95%CI [0.18, 0.82]). Race/ethnicity did not moderate the strength of associations between sexual violence and substance use. SMW exhibit increased risk for sexual violence and substance use, and victimization was associated with heavy alcohol use. Few racial/ethnic differences emerged as a function of sexual orientation, so SMW are a group with unique needs around sexual violence experiences and substance use, regardless of race/ethnicity. Healthcare providers should be aware of the link between substance use and prior victimization when treating SMW.


Observation and investigation of three endosperm transport tissues in sorghum caryopses.
Endosperm transport tissues in sorghum caryopses include endosperm transfer cells, endosperm conducting cells, and the embryo surrounding region. To elucidate the structural changes of these tissues and their relationship with the caryopsis development, sorghum caryopses were analyzed at different days after pollination using light, fluorescence, and electron microscopy. The following results were obtained: post-phloem maternal tissues included the placentochalaza and the nucellar projection-like nucellus. Well-developed endosperm transfer cells exhibited very evident flange-type wall ingrowths. Very few wall ingrowths were present in the initially developed endosperm transfer cells when the level of sucrose from the initially developed vascular system was low. At the middle stage of caryopsis development, the level of sucrose from the well-developed vascular system was high. Endosperm transfer cells increased in both area and layer amount, and their wall ingrowths increased in both length and density. Later in caryopsis development, the level of sucrose from the degenerated vascular system was low and wall ingrowths distorted in the degenerated endosperm transfer cells. Endosperm conducting cells primarily occupied the most part of endosperm, but decreased gradually because the upper part transformed into the starchy endosperm and the lower part degenerated to give space to the embryo growth. Although the embryo surrounding region initially enveloped the small embryo, it rapidly degenerated and finally disappeared. Our data showed that (1) the caryopsis vascular system influenced the differentiation of endosperm transfer cells by controlling the sugar levels (2) and configuration of endosperm transport tissues were probably altered to favor the growth of filial tissues.


Making inpatient medication reconciliation patient centered, clinically relevant, and implementable: a consensus statement on key principles and necessary first steps.
This white paper identifies potential solutions to help ensure the utility and sustainability of this critical patient safety issue.


LOGGIC Core BioClinical Data Bank: Added clinical value of RNA-Seq in an international molecular diagnostic registry for pediatric low-grade glioma patients.
The international, multicenter registry LOGGIC Core BioClinical Data Bank aims to enhance the understanding of tumor biology in pediatric low-grade glioma (pLGG) and provide clinical and molecular data to support treatment decisions and interventional trial participation. Hence, the question arises whether implementation of RNA sequencing (RNA-Seq) using fresh frozen (FrFr) tumor tissue in addition to gene panel and DNA methylation analysis improves diagnostic accuracy and provides additional clinical benefit. Analysis of patients aged 0 to 21 years, enrolled in Germany between April 2019 and February 2021, and for whom FrFr tissue was available. Central reference histopathology, immunohistochemistry, 850k DNA methylation analysis, gene panel sequencing, and RNA-Seq were performed. FrFr tissue was available in 178/379 enrolled cases. RNA-Seq was performed on 125 of these samples. We confirmed KIAA1549::BRAF-fusion (n = 71), BRAF V600E-mutation (n = 12), and alterations in FGFR1 (n = 14) as the most frequent alterations, among other common molecular drivers (n = 12). N = 16 cases (13%) presented rare gene fusions (eg, TPM3::NTRK1, EWSR1::VGLL1, SH3PXD2A::HTRA1, PDGFB::LRP1, GOPC::ROS1). In n = 27 cases (22%), RNA-Seq detected a driver alteration not otherwise identified (22/27 actionable). The rate of driver alteration detection was hereby increased from 75% to 97%. Furthermore, FGFR1 internal tandem duplications (n = 6) were only detected by RNA-Seq using current bioinformatics pipelines, leading to a change in analysis protocols. The addition of RNA-Seq to current diagnostic methods improves diagnostic accuracy, making precision oncology treatments (MEKi/RAFi/ERKi/NTRKi/FGFRi/ROSi) more accessible. We propose to include RNA-Seq as part of routine diagnostics for all pLGG patients, especially when no common pLGG alteration was identified.


A deep insight into the suppression mechanism of Sedum alfredii root exudates on Pseudomonas aeruginosa based on quorum sensing.
Quorum sensing (QS) plays an important role in the intensive communication between plants and microbes in the rhizosphere during the phytoremediation. This study explored the influence of the root exudates of hyperaccumulator Sedum alfredii on Pseudomonas aeruginosa based on QS. The effects of the components of root exudates, genes expression and transcription regulation of QS system (especially the las system) in Pseudomonas aeruginosa wild-type strain (WT) and rhl system mutant strain (ΔrhlI) were systematically analyzed and discussed. The WT and ΔrhlI exposed to gradient root exudates (0×, 1×, 2×, 5× and 10×) showed a concentration-corrective inhibition on protease production, with the inhibition rates of 51.4-74.5% and 31.2-50.0%, respectively. Among the components of the root exudates of Sedum alfredii, only thymol had an inhibition effects to the root exudates on the activity of protease and elastase. The inhibition rates of 50 μmol/L thymol on protease and elastase in WT were 44.7% and 24.3%, respectively, which was consistent with the variation in ΔrhlI. The gene expression of lasB declined 36.0% under the 1× root exudate treatment and 73.0% under the 50 μmol/L thymol treatment. Meanwhile, there was no significant impact on N-3-oxo-dodecanoyl-L-homoserine lactone signal production and the gene expression of lasI and lasR. Therefore, thymol from Sedum alfredii root exudates could inhibit the formation of protease and elastase in Pseudomonas aeruginosa by suppressing the expression of lasB, without any significant influence on the main las system as a potential natural QS inhibitor.


[Prevalence of fecal incontinence among adult women in Beijing district].
To investigate the prevalence of fecal incontinence (FI) among adult women in Beijing area, and to analysis risk factors associated with FI. A stratified multiple-cluster systemic method was used to recruit women ≥ 20 years old in 6 districts of Beijing. A self-administrated questionnaire was used to collect information about FI and possible risk factors. There were three thousand and 58 women participated in the survey, the average age was (48 ± 16) years (range 20-79 years). The prevalence of FI was 1.28% (39/3058), which was related to age. There were five factors entered the logistic regress model, which were included age ≥ 40 years old (OR = 3.3, 95%CI: 1.7-6.8), urinary incontinence (OR = 3.0, 95%CI: 1.5-6.1), vaginal delivery (OR = 2.4, 95%CI: 1.2-4.9), household per capita income ≤ 2000 RMB per month (OR = 3.3, 95%CI: 1.6-6.5), and feeling fatigue (OR = 3.0, 95%CI: 1.5-5.8). Prevalence of FI is low among adult women in Beijing area, while risk factors associated with FI are complicated and further studies are necessary to be conducted.


Lappaconitine and N-deacetyllappaconitine potentiate footshock-induced analgesia in rats.
The effects of lappaconitine (LA) and N-deacetyllappaconitine (DLA) on footshock-induced analgesia (FSIA) were studied by the rat tail flick test. Rats subjected to 90 s nonescaping footshock had a significant increase in tail flick latency. Naloxone (4 micrograms, i.c.v.) partially antagonized the FSIA. After 5 consecutive exposures to footshock, rats developed a complete tolerance to the FSIA. The rats tolerant to FSIA showed a cross-tolerance to morphine- but not LA- and DLA-induced analgesia. Administrations of subanalgesic doses of LA and DLA potentiated the FSIA in both intact and adrenalectomized rats.


Propofol mediates bone metastasis by regulating PC-derived exosomal miR-142-3p.
In this study we investigated the role of propofol in mediating prostate cancer (PCa) bone metastasis through regulating exosomal factors derived from PCa. We isolated exosomes from PCa cells and co-cultured them with mesenchymal stem cells (MSCs). PCa-derived exosomes increased calcium deposition of MSCs and upregulated ALPL'Alkaline phosphatase, tissue-nonspecific isozyme) and BGLAP (Bone Gamma-Carboxyglutamate Protein) expression. Propofol treatment reduced alkaline phosphatase (ALP) activity, and ALPL and BGLAP expression that was induced by PCa-derived exosomes in MSCs. miRNAs present in cancer cell-derived exosomes increased osteogenesis in these cells. We evaluated miRNA expression in PCa cells after treatment with propofol, and found that miR-142-3p was upregulated in PCa cells. Furthermore, we transfected MSCs with miR-142-3p mimics or inhibitors and revealed that miR-142-3p mimics reduced calcium deposition and downregulated ALP activity, and ALPL and BGLAP levels, while miR-142-3p inhibitors increased calcium deposition and increased ALP activity, and ALPL and BGLAP levels. Finally, we determined that MSCs co-cultured with PCa-derived exosomes and transfected with miR-142-3p mimic exhibited reduced calcium deposition and lower ALP activity, and expression of ALPL and BGLAP. These data demonstrate that propofol inhibits osteogenic differentiation and mineralization of MSCs induced by PCa-derived exosomes by regulation of miR-142-3p levels.


[Postural changes during echocardiography. Is this manoeuver necessary in the differential diagnosis of fixed and free floating thrombus?].
A case of a 62 year-old woman with mitral stenosis and thrombosis of the left atrium diagnosed by two-dimensional echocardiography (2D-Echo) is reported. During the procedure, postural changes were performed and characterized the thrombus as floating one. The postural changes during 2D-echo examination allows differential diagnosis among fixed and free floating atrial thrombus. Such postural manoeuvres are also important in evaluating prognosis and therapeutic management of mitral stenosis.


Modalities of renal replacement therapy and clinical outcomes of patients with acute kidney injury in a resource-limited setting: Results from a SEA-AKI study.
To determine the effects of modalities of renal replacement therapy (RRT) on the 30-d mortality and renal recovery in patients with acute kidney injury (AKI). A multicenter cohort study was conducted in 17 hospitals from Thailand and Indonesia. We recruited patients who were admitted to the Intensive care unit and diagnosed with AKI. Relevant mode of RRT, as intermittent hemodialysis (IHD), continuous renal replacement therapy (CRRT), peritoneal dialysis (PD), or sustained low efficiency dialysis (SLED), was initiated as indicated. From 2844 patients with AKI, 449 cases (8.1%) received RRT. There were no significant differences in the 30-d mortality between those initially treated with CRRT, PD, and SLED compared to those treated with IHD. The renal recovery was similar for each RRT mode. The three independent factors of death were the primary diagnosis of kidney disease, higher APACHE II score, and non-renal SOFA score. Only 48 (10.7%) patients had been switched to another mode of RRT. All four modes of RRT (IHD, CRRT, PD, and SLED) are acceptable treatments for severe AKI and gave a similar survival rate.


Comparative transcriptome analyses reveal genes related to pigmentation in the petals of a flower color variation cultivar of Rhododendron obtusum.
Rhododendron is an important woody ornamental plant, and breeding varieties with different colors is a key research goal. Although there have been a few reports on the molecular mechanisms of flower colors and color patterning in Rhododendron, it is still largely unknown what factors regulate flower pigmentation in Rhododendron. In this study, the flower color variation cultivar 'Yanzhi Mi' and the wild-type (WT) cultivar 'Dayuanyangjin' were used as research objects, and the pigments and transcriptomes of their petals during five flower development stages were analyzed and compared. The results showed that derivatives of cyanidin, peonidin and pelargonidin might be responsible for the pink color of mutant petals and that the S2 stage was the key stage of flower color formation. In total, 412,910 transcripts and 2780 differentially expressed genes (DEGs) were identified in pairwise comparisons of WT and mutant petals. GO and KEGG enrichment analyses of the DEGs showed that 'DNA-binding transcription factor activity', 'Flavonoid biosynthesis' and 'Phenylpropanoid biosynthesis' were more active in mutant petals. Early anthocyanin pathway candidate DEGs (CHS3-CHS6, CHI, F3Hs and F3'H) were significantly correlated and were more highly expressed in mutant petals than in WT petals in the S2 stage. An R2R3-MYB unigene (TRINITY_DN55156_c1_g2) was upregulated approximately 10.5-fold in 'Yanzhi Mi' petals relative to 'Dayuanyangjin' petals in the S2 stage, and an R2R3-MYB unigene (TRINITY_DN59015_c3_g2) that was significantly downregulated in 'Yanzhi Mi' petals in the S2 stage was found to be closely related to Tca MYB112 in cacao. Taken together, the results of the present study could shed light on the molecular basis of anthocyanin biosynthesis in two Rhododendron obtusum cultivars and may provide a genetic resource for breeding varieties with different flower colors.


Integrating a Facially Driven Treatment Planning to the Digital Workflow for Rehabilitation of Edentulous Arches: A Case Report.
This case report presents the integration of a digital facially driven prosthetic plan to the computer-assisted implant planning for rehabilitation of edentulous arches. Diagnosis of edentulous arches is hampered by the lack of intraoral references. However, a digital facial profile analysis facilitates the treatment plan, taking into consideration the harmony among teeth, lips, and face to restore a pleasant smile. The first appointment consisted of digital documentation including intraoral scans, facial scans, and photographs. Based on these data, a smile frame was created to guide the digital wax-up. Cone-beam computed tomography (CBCT) scans were merged to facial and intraoral scans to perform the virtual surgical planning. Integration between facial, intraoral, and bone tissues were used as a reference to define implant position and prosthetic planning. The digital planning was integrated into the surgical procedure using stackable templates, and an immediate loading was performed. The interim prosthesis was manufactured based on the digital wax-up. With digital data, quality control could be performed to evaluate the esthetic outcome of the treatment. An esthetic and functional rehabilitation was possible using the respective digital workflow to define harmony between a smile and facial tissues. A digital treatment implant planning can be conducted considering patient's individual needs to improve the esthetic outcome.


Association of a fetus in fetu and two teratomas: US and MRI.
We report a case of an abdominal mass in a newborn girl containing a fetus in fetu and two teratomas. Obstetrical sonography revealed the abnormality at 28 weeks of gestation. Post-natal US examination suggested the diagnosis of a fetus in fetu upon the finding of a vertebral column and fetal skeletal bones. US also showed two other rounded masses connected to the main lesion by vascular bundles. Preoperative MRI examination supplied further information regarding tissue composition and vascularisation of the mass lesion. The diagnosis was confirmed by pathological examination. Aetiological factors and radiological diagnosis of this rare tumour are reviewed and discussed.


Craniopharyngioma.
Craniopharyngiomas are partly cystic embryogenic malformations of the sellar and parasellar region. With an overall incidence of 0.5-2.0 new cases per million population per year, approximately 30-50% of all cases represent childhood craniopharyngioma. Typical manifestations at diagnosis are some combination of headache, visual impairment, polyuria/polydypsia, growth retardation, and significant weight gain. Therapy of choice in patients with favorable tumor localization is complete resection with specific focus on maintaining functions of the optic nerve and hypothalamic-pituitary axes. In patients whose unfavorable tumor localization makes maintaining hypothalamic functionality surgically challenging, a limited resection followed by local irradiation is recommended. The overall survival rates are high (92%) but occurrences of reduced quality of life are also high. Recurrences after complete resection and progressions of residual tumor after incomplete resection are frequent postsurgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of postsurgical irradiation is currently under investigation in the randomized multinational trial KRANIOPHARYNGEOM 2007 that analyzes quality of life as primary endpoint. Childhood craniopharyngioma should be recognized as a chronic disease requiring constant monitoring of the clinical and quality of life consequences in order to provide optimal care of surviving patients.


All-trans- and 9-cis-retinoic acids activate the human cyclooxynase-2 gene: a role for DR1 as RARE or RXRE.
The human COX-2 promoter contains a direct repeat 1 (DR1) which was shown to confer responsiveness to PPARs. We found that in AN(3)CA and F9 cells, this hCOX-2 DR1 mediates responsiveness to all-trans-retinoic acid (tRA) or 9-cis-retinoic acid (9cRA), but this effect was suppressed by PPARδ. Truncated PPARδ lacking the activation domain AF2 cannot suppress RA-induced activation of the hCOX-2 gene via DR1, suggesting that cofactor recruitment by AF2 is required for the suppression by PPARδ. Gel shift assay showed that PPAR/RXR, RARβ/RXR, and RXR/RXR, bind to hCOX-2 DR1, revealing the promiscuity of this DR1. Particularly, RXR homodimer was able to bind to this DR1 only in the presence of 9cRA. Our results established that tRA and 9cRA are potent inducers of hCOX-2 and that the hCOX-2 DR1 could either serve as RARE or RXRE depending on cellular contexts.


Efficient production of glycosylated Cypridina luciferase using plant cells.
Cypridina noctiluca luciferase has been utilized for biochemical and molecular biological applications, including bioluminescent enzyme immunoassays, far-red luminescence imaging, and high-throughput reporter assays. Some of these applications require a large amount of purified luciferase. However, conventional protein expression systems are not capable of producing sufficient quantities of protein with a high quality and purity without laborious and costly purification processes. To improve the productivity and expand the breadth of possibilities for Cypridina luciferase applications, we employed a variety of secretion expression systems, including yeast, mammalian cells, and silk worms. In this study, we established a simple production procedure using plant cell cultures. The plant cell culture BY-2 efficiently secreted luciferase, which was easily purified using a simple one-step ion-exchange chromatography method. The production yield was 20-30 mg of luciferase per liter of culture medium, and its Km for the luciferin (0.45 μM) was similar to that of the native protein. Additionally, we characterized its glycosylation pattern and confirmed that the two potential N-glycosylation sites were modified with plant-type oligosaccharide chains. Interestingly, the oligosaccharide chains could be trimmed without any detectable decrease in recombinant protein activity. Therefore, the results of our study indicate that this method offers a more cost-effective production method for Cypridina luciferase than conventional methods.


Nickel-Catalyzed Cyclization Strategy for the Synthesis of Pyrroloquinolines, Indoloquinolines, and Indoloisoquinolines.
An inexpensive and benchtop stable Ni-catalyst/Zn system for the synthesis of pyrrolo/indoloquinolines and indolo[2,1-a]isoquinolines is explored. This platform provides a one-pot entry for the preparation of various pyrrolo and indoloquinolines/isoquinolines, which involves successive C-C and C-N bond formation, respectively. In addition, we have also performed the preliminary photophysical studies for the synthesized compounds.


Autism spectrum heterogeneity: fact or artifact?
The current diagnostic practices are linked to a 20-fold increase in the reported prevalence of ASD over the last 30 years. Fragmenting the autism phenotype into dimensional "autistic traits" results in the alleged recognition of autism-like symptoms in any psychiatric or neurodevelopemental condition and in individuals decreasingly distant from the typical population, and prematurely dismisses the relevance of a diagnostic threshold. Non-specific socio-communicative and repetitive DSM 5 criteria, combined with four quantitative specifiers as well as all their possible combinations, render limitless variety of presentations consistent with the categorical diagnosis of ASD. We propose several remedies to this problem: maintain a line of research on prototypical autism; limit the heterogeneity compatible with a categorical diagnosis to situations with a phenotypic overlap and a validated etiological link with prototypical autism; reintroduce the qualitative properties of autism presentations and of current dimensional specifiers, language, intelligence, comorbidity, and severity in the criteria used to diagnose autism in replacement of quantitative "social" and "repetitive" criteria; use these qualitative features combined with the clinical intuition of experts and machine-learning algorithms to differentiate coherent subgroups in today's autism spectrum; study these subgroups separately, and then compare them; and question the autistic nature of "autistic traits".


Validating Fractalkine receptor as a target and identifying candidates for drug discovery against type 2 diabetes.
Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases employing abnormal levels of insulin. Enhancing the insulin production is greatly aided by the regulatory mechanisms of the Fractalkine receptor (CX3CR1) system in islet β-cell function. However, elements including a high-fat diet, obesity, and ageing negatively impact the expression of CX3CR1 in islets. CX3CL1/CX3CR1 receptor-ligand complex is now recognized as a novel therapeutic target. It suggests that T2DM-related β-cell dysfunction may result from lower amount of these proteins. We analyzed the differential expression of CX3CR1 gene samples taken from persons with T2DM using data obtained from the Gene Expression Omnibus database. Homology modeling enabled us to generate the three-dimensional structure of CX3CR1 and a possible binding pocket. The optimized CX3CR1 structure was subjected to rigorous screening against a massive library of 693 million drug-like molecules from the ZINC15 database. This screening process led to the identification of three compounds with strong binding affinity at the identified binding pocket of CX3CR1. To further evaluate the potential of these compounds, molecular dynamics simulations were conducted over a 50 ns time scale to assess the stability of the protein-ligand complexes. These simulations revealed that ZINC000032506419 emerged as the most promising drug-like compound among the three potent molecules. The discovery of ZINC000032506419 holds exciting promise as a potential therapeutic agent for T2D and other related metabolic disorders. These findings pave the way for the development of effective medications to address the complexities of T2DM and its associated metabolic diseases.


The Trials and Tribulations of Assembling Large Medical Imaging Datasets for Machine Learning Applications.
With vast interest in machine learning applications, more investigators are proposing to assemble large datasets for machine learning applications. We aim to delineate multiple possible roadblocks to exam retrieval that may present themselves and lead to significant time delays. This HIPAA-compliant, institutional review board-approved, retrospective clinical study required identification and retrieval of all outpatient and emergency patients undergoing abdominal and pelvic computed tomography (CT) at three affiliated hospitals in the year 2012. If a patient had multiple abdominal CT exams, the first exam was selected for retrieval (n=23,186). Our experience in attempting to retrieve 23,186 abdominal CT exams yielded 22,852 valid CT abdomen/pelvis exams and identified four major categories of challenges when retrieving large datasets: cohort selection and processing, retrieving DICOM exam files from PACS, data storage, and non-recoverable failures. The retrieval took 3 months of project time and at minimum 300 person-hours of time between the primary investigator (a radiologist), a data scientist, and a software engineer. Exam selection and retrieval may take significantly longer than planned. We share our experience so that other investigators can anticipate and plan for these challenges. We also hope to help institutions better understand the demands that may be placed on their infrastructure by large-scale medical imaging machine learning projects.


PPDPF alleviates hepatic steatosis through inhibition of mTOR signaling.
Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in the world, however, no drug treatment has been approved for this disease. Thus, it is urgent to find effective therapeutic targets for clinical intervention. In this study, we find that liver-specific knockout of PPDPF (PPDPF-LKO) leads to spontaneous fatty liver formation in a mouse model at 32 weeks of age on chow diets, which is enhanced by HFD. Mechanistic study reveals that PPDPF negatively regulates mTORC1-S6K-SREBP1 signaling. PPDPF interferes with the interaction between Raptor and CUL4B-DDB1, an E3 ligase complex, which prevents ubiquitination and activation of Raptor. Accordingly, liver-specific PPDPF overexpression effectively inhibits HFD-induced mTOR signaling activation and hepatic steatosis in mice. These results suggest that PPDPF is a regulator of mTORC1 signaling in lipid metabolism, and may be a potential therapeutic candidate for NAFLD.


Three cases of vagal nerve schwannoma and review of literature.
Schwannoma arising from the vagus is an uncommon (2-5%) benign nerve tumour. This tumour most often presents as a slow growing asymptomatic solitary neck mass which rarely undergoes malignant transformation. Definitive pre-operative diagnosis may be difficult and investigations such as FNAC have low specificity. The carotid artery and internal jugular vein may be displaced antero-laterally. Diagnosis is based on clinical suspicion and confirmation is obtained by means of surgical pathology. Surgical excision is the treatment of choice for this tumour, with recurrence being rare. We describe three cases of schwannoma involving the vagus who presented differently to our unit during past 5 years.


Searching for hidden information with Gabor Transform in generalized tonic-clonic seizures.
The analysis of generalized tonic clonic seizures is usually difficult with scalp EEG due to muscle artifact. We applied Gabor Transform to evaluate 20 seizures from 8 consecutive patients admitted for video-EEG monitoring. We studied the relative intensity ratios of alpha, theta and delta bands over time. In 14/20 events we found a significant decremental activity in the delta band at the onset of the seizure indicating that this is dominated by theta and alpha bands. We conclude that GT is a useful auxiliary tool in the analysis of ictal activity that sheds light on the underlying pathophysiological mechanisms.


A dual functional chondro-inductive chitosan thermogel with high shear modulus and sustained drug release for cartilage tissue engineering.
We report a chitosan-based nanocomposite thermogel with superior shear modulus resembling that of cartilage and dual pro-chondrogenic and anti-inflammatory functions. Two therapeutic agents, kartogenin (KGN) and diclofenac sodium (DS), are employed to promote chondrogenesis of stem cells and suppress inflammation, respectively. To extend the release time in a controlled manner, KGN is encapsulated in the uniform-sized starch microspheres and DS is loaded into the halloysite nanotubes. Both drug carriers are doped into the maleimide-modified chitosan hydrogel to produce a shear modulus of 167 ± 5 kPa that is comparable to that of articular cartilage (50-250 kPa). Owing to the hydrogel injectability and relatively suitable gelation time (5 ± 0.5 min) at 37 °C, this system potentially constitutes a manageable platform for clinical practice. Moreover, sustained linear drug release for over a month boosts chondro-differentiation of stem cells to eliminate the necessity for multiple administrations. Considering virtues such as thermogel strength and ability to co-deliver anti-inflammatory and chondro-inductive biomolecules continuously, the materials and strategy have promising potential in functional cartilage tissue engineering.


Influence of Anesthetic Techniques on Perioperative Outcomes after Endovascular Aneurysm Repair.
The purpose of the study was to explore the influence of anesthetic techniques on perioperative outcomes after endovascular aneurysm repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA) in a Chinese population. A retrospective review was performed in patients after elective EVAR for infrarenal AAA at our single center. Patients were classified into general anesthesia (GA), regional anesthesia (RA), and local anesthesia (LA) groups. The primary outcomes (30-day mortality and morbidity) and secondary outcomes [procedure time, mean arterial pressure (MAP), and length of hospital stay (LOS)] were collected and analyzed. From January 2006 to December 2015, 486 consecutive patients underwent elective EVAR at our center. GA was used in 155 patients (31.9%), RA in 56 (11.5%), and LA in 275 (56.6%). The GA patients had fewer respiratory comorbidities, shorter and more angulated proximal necks, and more concomitant iliac aneurysms. LA during EVAR was significantly associated with a shorter procedure time (GA, P < 0.001; RA, P < 0.001) and shorter LOS (GA, P = 0.002; RA, P = 0.001), but a higher MAP (GA, P < 0.001; RA, P < 0.001) compared with GA and RA. LA was associated with a significantly lower risk of cardiac (odds ratio (OR) 4.27, 95% confidence interval (CI) 1.21-15.04), pulmonary (OR 5.37, 95% CI 1.58-18.23), and systemic complications (OR 4.15, 95% CI 1.85-9.33) compared with GA. RA was also associated with a decreased risk of systemic complications (OR 4.74, 95% CI 1.19-18.92) compared with GA. There was no difference in the 30-day mortality, neurologic complications, renal complications, and intraoperative extra procedures among the 3 groups. Anesthetic techniques for EVAR have no influence on the 30-day mortality. LA for EVAR appears to be beneficial concerning the procedure time, LOS, and 30-day systemic complications for patients after elective EVAR for infrarenal AAA in the Chinese population.


Nanosilver reinforced Parmelia sulcata extract efficiently induces apoptosis and inhibits proliferative signalling in MCF-7 cells.
The Lichen, Parmelia sulcata synthesizes various secondary metabolites, in which phenolic based compounds received much attention due to their importance in biomedical application. Especially the phenolic compound was effective against the cancer treatment. An effective administration of such plant natural product can represent a significant conventional management of cancer in terms of chemoprevention. The nanomedicines are group of agents that selectively interfere the cancer cells which leads to reduction of side effect thereby reducing the doses. Silver nanoparticles is a promising antitumor agent, however, the conventional production of silver nanoparticles have many drawbacks which led to increase in need of eco-friendly biological production methods. In this study, we made an attempt to synthesise a nano silver (Ps-AgNPs) from phenolic extract of lichen Parmelia sulcata extract. The Ps-AgNps was applied for anticancer activity using MCF-7 cells and the effect was characterised by western blotting method. The FTIR, XRD, UV and TEM results confirms the presence of silver nanoparticles in phenolic extract of lichen Parmelia sulcata. The cytotoxicity assay shows that the Ps-AgNPs is toxic against cancer cells (MCF-7) but not to normal cells (NIH3T3), which confirm the selective induction of cell death (apoptosis) against cancer cells. The Western blot analysis also clearly indicates the down regulation of inflammatory genes (TNF-alpha and IL-6) and cell cycle genes (PCNA and Cyclin-D1) thus promoting intrinsic apoptotic pathway. The results suggest that Ps-AgNPs can effectively kill cancer cells and can be used as an alternative therapeutic agent for cancer treatment.


Delivery of growth factor-based therapeutics in vascular diseases: Challenges and strategies.
Either cardiovascular or peripheral vascular diseases have become the major cause of morbidity and mortality worldwide. Recently, growth factors therapeutics, whatever administrated in form of exogenous growth factors or their relevant genes have been discovered to be an effective strategy for the prevention and therapy of vascular diseases, because of their promoting angiogenesis. Besides, as an alternative, stem cell-based therapy has been also developed in view of their paracrine-mediated effect or ability of differentiation toward angiogenesis-related cells under assistance of growth factors. Despite of being specific and potent, no matter growth factors or stem cells-based therapy, their full clinical transformation is limited from bench to bedside. In this review, the potential choices of therapeutic modes based on types of different growth factors or stem cells were firstly summarized for vascular diseases. The confronted various challenges such as lack of non-invasive delivery method, the physiochemical challenge, the short half-life time, and poor cell survival, were carefully analyzed for these therapeutic modes. Various strategies to overcome these limitations are put forward from the perspective of drug delivery. The expertised design of a suitable delivery form will undoubtedly provide valuable insight into their clinical application in the regenerative medicine.


Allophonic perception of VOT contrasts in Spanish children with dyslexia.
Previous studies have evidenced a different mode of speech perception in dyslexia, characterized by the use of allophonic rather than phonemic units. People with dyslexia perceive phonemic features (such as voicing) less accurately than typical readers, but they perceive allophonic features (i.e., language-independent differences between speech sounds) more accurately. In this study, we investigated the perception of voicing contrasts in a sample of 204 Spanish children with or without dyslexia. Identification and discrimination data were collected for synthetic sounds varying along three different voice onset time (VOT) continua (ba/pa, de/te, and di/ti). Empirical data will be contrasted with a mathematical model of allophonic perception building up from neural oscillations and auditory temporal processing. Children with dyslexia exhibited a general deficit in categorical precision; that is, they discriminated among phonemically contrastive pairs (around 0-ms VOT) less accurately than did chronological age controls, irrespective of the stimulus continuum. Children with dyslexia also exhibited a higher sensitivity in the discrimination of allophonic features (around ±30-ms VOT), but only for the stimulus continuum that was based on a nonlexical contrast (ba/pa). Fitting the neural network model to the data collected for this continuum suggests that allophonic perception is due to a deficit in "subharmonic coupling" between high-frequency oscillations. Relationships with "temporal sampling framework" theory are discussed.


An orthodontic acrylic resin containing seaweed Ulva lactuca as a photoactive phytocompound in antimicrobial photodynamic therapy: Assessment of anti-biofilm activities and mechanical properties.
Uncontrolled accumulation of microbial plaque and formation of biofilm on the surface orthodontic acrylic removable appliances increases the risk of enamel decalcification and periodontal diseases. The purpose of the present study was to evaluate antimicrobial activities, anti-virulence potencies, and mechanical properties of orthodontic acrylic resin containing different concentrations of Ulva lactuca (a green marine macroalga) following photo-activation against Streptococcus mutans. Minimum inhibitory concentration (MIC) of U. lactuca was determined against S. mutans. Acrylic resin specimens with different concentrations of U. lactuca (0.2 %, 0.5 %, 1%, 2.5 %, 5%, and 10 % weight/weight) were fabricated. Flexural strength values, antimicrobial effects, and anti-biofilm activities of samples were assessed in comparison with original acrylic resin as the control group. Also, the expression of the virulence-associated genes was assessed by quantitative real-time polymerase chain reaction. U. lactuca at concentrations of 1-10% significantly reduced the S. mutans growth rate by 20.3%-63.3% in comparison to the control group (P < 0.05). Therefore, the concentration of 1% of U. lactuca was considered as a MIC. The highest and lowest flexural strength values were observed in the control group (43.5 ± 2.4 MPa) and the group with a 10 % concentration of U. lactuca (19.2 ± 1.8 MPa), respectively. Flexural strength values decreased in samples containing 2.5 %, 5%, and 10 % concentrations of U. lactuca in comparison to the control group significantly (P > 0.05). In the disc agar diffusion test, the growth inhabitation zones around samples containing different concentrations of photo-activated U. lactuca ranged from 13 mm to 25 mm in diameter. Interestingly, the anti-biofilm activity of U. lactuca-mediated aPDT against S. mutans was dose-dependent. Additionally, the sub-MIC dose of U. lactuca (0.5 %) following photo-activation could significantly decrease the expression levels of gtfB, gtfC, and gtfD to 4.1-, 5.3-, and 7.4-fold, respectively. Adding photo-activated U. lactuca to the orthodontic acrylic resin at a concentration of 1% increases its antibacterial and anti-biofilm activities besides not detrimentally affects its flexural strength.


The views of Aotearoa/New Zealand adults over 60 years regarding the End of Life Choice Act 2019.
This study described the views of older New Zealand adults toward assisted dying and specifically the End of Life Choice Act (2019), an Act making assisted dying legal. An anonymous postal and online survey of 636 adults 60 years and older was conducted. The majority of respondents did not support legalization (85.7%), while 8.8% were in favor (5.5% did not specify a view). Weighted binary logistic regression indicated that the odds of support for legalization were lower in those respondents with a religious affiliation (OR = .020, S.E. = 0.60, p = .00), and there were 2.66 times greater odds in those identifying as male (S.E. = 0.34, p = .005). On the other hand, those respondents under 65 years had increased odds of supporting legalization (OR = 1.89, S.E. = .029, p = .045). Results indicate that most participants were concerned about potential abuses and coercive practices if assisted dying became legally available in New Zealand.


A randomized, double-blind, multicenter comparison of the efficacy and tolerability of Restylane versus Zyplast for the correction of nasolabial folds.
Bovine collagen is extensively used for facial soft tissue augmentation but provides only temporary correction and can cause hypersensitivity reactions. Hyaluronic acid derivatives potentially offer improved longevity of correction and a reduced risk of immunogenicity and hypersensitivity. To compare the efficacy and safety of nonanimal stabilized hyaluronic acid gel (Restylane; Q-Med, Uppsala, Sweden) with that of bovine collagen (Zyplast) for treatment of nasolabial folds. One hundred thirty-eight patients with prominent nasolabial folds were randomized to treatment with hyaluronic acid gel and bovine collagen on contralateral sides of the face. Treatments were repeated at 2-week intervals, as required, to achieve "optimal cosmetic result" (baseline). Outcomes were evaluated by a blinded investigator at 2, 4, and 6 months after baseline. Less injection volume was required for "optimal cosmetic result" with hyaluronic acid gel than with bovine collagen, and patients and investigators judged hyaluronic acid gel to be more effective in maintaining cosmetic correction. The investigator-based Wrinkle Severity Rating Scale and Global Aesthetic Improvement Scale assessments at 6 months after baseline indicated that hyaluronic acid gel was superior in 56.9% and 62.0% of patients, respectively, whereas bovine collagen was superior in 9.5% and 8.0% of patients, respectively. The frequency, intensity, and duration of local injection-site reactions were similar for the two products. Nonanimal stabilized hyaluronic acid provides a more durable aesthetic improvement than bovine collagen and is well tolerated.


Principal sequence pattern analysis of episodes of excess mortality due to heat in the Barcelona metropolitan area.
The aim of the study is to classify the synoptic sequences associated with excess mortality during the warm season in the Barcelona metropolitan area. To achieve this purpose, we undertook a principal sequence pattern analysis that incorporates different atmospheric levels, in an attempt at identifying the main features that account for dynamic and thermodynamic atmospheric processes. The sequence length was determined by the short-term displacement between temperature and mortality. To detect this lag, we applied the cross-correlation function to the residuals obtained from the modelling of the daily temperature and mortality series of summer. These residuals were estimated by means of an autoregressive integrated moving average (ARIMA) model. A 7-day sequence emerged as the basic temporal unit for evaluating the synoptic background that triggers the temperature related to excess mortality in the Barcelona metropolitan area. The principal sequence pattern analysis distinguished three main synoptic patterns: two dynamic configurations produced by southern fluxes related to an Atlantic low, which can be associated with heat waves recorded in southern Europe, and a third pattern identified by a stagnation situation associated with the persistence of a blocking anticyclone over Europe, related to heat waves recorded in northern and central western Europe.


Causal relationship extraction from biomedical text using deep neural models: A comprehensive survey.
The identification of causal relationships between events or entities within biomedical texts is of great importance for creating scientific knowledge bases and is also a fundamental natural language processing (NLP) task. A causal (cause-effect) relation is defined as an association between two events in which the first must occur before the second. Although this task is an open problem in artificial intelligence, and despite its important role in information extraction from the biomedical literature, very few works have considered this problem. However, with the advent of new techniques in machine learning, especially deep neural networks, research increasingly addresses this problem. This paper summarizes state-of-the-art research, its applications, existing datasets, and remaining challenges. For this survey we have implemented and evaluated various techniques including a Multiview CNN (MVC), attention-based BiLSTM models and state-of-the-art word embedding models, such as those obtained with bidirectional encoder representations (ELMo) and transformer architectures (BioBERT). In addition, we have evaluated a graph LSTM as well as a baseline rule based system. We have investigated the class imbalance problem as an innate property of annotated data in this type of task. The results show that a considerable improvement of the results of state-of-the-art systems can be achieved when a simple random oversampling technique for data augmentation is used in order to reduce class imbalance.


MicroRNA-199a-5p regulates glioma progression via targeting MARCH8.
MicroRNA-199a-5p (miR-199a-5p) was reported to play crucial roles in cancer progression. However, its role in glioma remains largely unknown. RT-qPCR was employed to analyze miR-199a-5p expression level in glioma cell lines. The effects of miR-199a-5p on cell proliferation and invasion were investigated in vitro. We showed that miR-199a-5p expression level was significantly downregulated in glioma cell lines compared with a normal cell. In addition, miR-199a-5p overexpression suppresses glioma cell proliferation and invasion in vitro. Bioinformatic analysis and Luciferase assay suggested that the membrane-associated ring-CH-type finger 8 (MARCH8) was a target of miR-199a-5p. Furthermore, MARCH8 overexpression could partially reverse the effects of miR-199a-5p on glioma cells. These findings suggested that miR-199a-5p may function as a tumor suppressor in glioma by targeting MARCH8.


Body image and sexuality concerns in women with breast cancer-related lymphedema: a cross-sectional study.
(1) To determine, in women with breast cancer-related lymphedema (BCRL), the frequency, intensity and distress of body image and sexuality concerns. (2) To examine relationships between body image and sexuality concerns, and lymphedema, personal and cancer treatment factors. Women with BCRL (n = 64) completed the Lymphedema Symptom Intensity and Distress Scale - Arm (LSIDS-A), which focuses on the intensity and distress of a range of lymphedema symptoms. They also underwent a lymphedema assessment. Responses to eight questions from the LSIDS-A regarding sexuality, body image and intimate relationships were considered. Frequency of responses was tabulated. Multiple linear regressions were used to determine if specific factors were related to higher intensity and distress scores associated with body image and sexuality issues. Body image and sexuality concerns were common (48%, 23% respectively). Participants reported a range (0-10) of intensity and distress related to body image and sexuality symptoms. Univariate linear regression revealed greater intensity of sexuality concerns was associated with younger age, whilst distress related to sexuality concerns was associated with higher inter-arm bioimpedance ratio and shorter duration of lymphedema. Body image concerns were not related to any considered factors. Body image and sexuality concerns are common, intense and distressing for patients with breast cancer lymphedema. Assessment of both the intensity and distressed caused by these symptoms is necessary to understand the impact of lymphedema.


Significant Variation in Blood Transfusion Practice Persists Following Adolescent Idiopathic Scoliosis Surgery.
Retrospective case control study. To review current transfusion practise following Adolescent Idiopathic Scoliosis (AIS) surgery and assess risks of complication from transfusion in this cohort. No study to date has investigated variation in blood transfusion practices across surgeons and hospitals following AIS surgery. Data were extracted from the Statewide Planning and Research Cooperative System. Using International Classification of Diseases (ICD-9) all patients with (ICD-9) code for AIS (737.30) ("idiopathic scoliosis") and underwent spinal fusion between 2000 and 2015 were included. Bivariate and mixed-effects logistic regression analyses were performed to assess patient, surgeon, and hospital factors associated with perioperative allogeneic red blood cell transfusion. Additional multivariable analyses examined the association between transfusion and infectious complications. Of the 7689 patients who underwent AIS surgery, 21.1% received a perioperative blood transfusion. After controlling for patient factors, wide variation in risk-adjusted transfusion rates was present with a 10-fold difference in transfusion rates observed across surgeons (4.4%-46.1%) and hospitals (5.1%-50%). Patient factors did not explain any of the surgeon or hospital variation. Use of autologous blood transfusion, higher surgeon procedure volume, and greater surgeon years in practice were independently associated with lower odds of allogeneic blood transfusion (P < 0.001), and surgeon and hospital characteristics explained 45% of surgeon variation but only 2.4% of hospital variation. Allogeneic blood transfusion was independently associated with postoperative wound infection (OR = 1.87, 95% CI = 1.20-2.93), pneumonia (OR = 1.68, 95% CI = 1.26-2.44), and sepsis (OR = 2.42, 95% CI = 1.11-5.83). Significant variation exists across both surgeons and hospitals in perioperative blood transfusion utilization following AIS surgery. Use of autologous blood transfusion and implementing institutional transfusion protocols may reduce unwarranted variation and potentially decrease infectious complication rates.Level of Evidence: 3.


Superiority of SpiroZin2 Versus FluoZin-3 for monitoring vesicular Zn2+ allows tracking of lysosomal Zn2+ pools.
Small-molecule fluorescent probes are powerful and ubiquitous tools for measuring the concentration and distribution of analytes in living cells. However, accurate characterization of these analytes requires rigorous evaluation of cell-to-cell heterogeneity in fluorescence intensities and intracellular distribution of probes. In this study, we perform a parallel and systematic comparison of two small-molecule fluorescent vesicular Zn2+ probes, FluoZin-3 AM and SpiroZin2, to evaluate each probe for measurement of vesicular Zn2+ pools. Our results reveal that SpiroZin2 is a specific lysosomal vesicular Zn2+ probe and affords uniform measurement of resting Zn2+ levels at the single cell level with proper calibration. In contrast, FluoZin-3 AM produces highly variable fluorescence intensities and non-specifically localizes in the cytosol and multiple vesicular compartments. We further applied SpiroZin2 to lactating mouse mammary epithelial cells and detected a transient increase of lysosomal free Zn2+ at 24-hour after lactation hormone treatment, which implies that lysosomes play a role in the regulation of Zn2+ homeostasis during lactation. This study demonstrates the need for critical characterization of small-molecule fluorescent probes to define the concentration and localization of analytes in different cell populations, and reveals SpiroZin2 to be capable of reporting diverse perturbations to lysosomal Zn2+.


Asymmetric synthesis of substituted tropinones using the intramolecular mannich cyclization reaction and acyclic N-sulfinyl beta-amino ketone ketals.
Sulfinimine-derived, enantiopure N-sulfinyl beta-amino ketone ketals on hydrolysis give dehydropyrrolidine ketones that on treatment with (Boc)(2)O/DMAP afford substituted tropinones in good yield.


Structural and functional characterization of three polyketide synthase gene clusters in Bacillus amyloliquefaciens FZB 42.
Although bacterial polyketides are of considerable biomedical interest, the molecular biology of polyketide biosynthesis in Bacillus spp., one of the richest bacterial sources of bioactive natural products, remains largely unexplored. Here we assign for the first time complete polyketide synthase (PKS) gene clusters to Bacillus antibiotics. Three giant modular PKS systems of the trans-acyltransferase type were identified in Bacillus amyloliquefaciens FZB 42. One of them, pks1, is an ortholog of the pksX operon with a previously unknown function in the sequenced model strain Bacillus subtilis 168, while the pks2 and pks3 clusters are novel gene clusters. Cassette mutagenesis combined with advanced mass spectrometric techniques such as matrix-assisted laser desorption ionization-time of flight mass spectrometry and liquid chromatography-electrospray ionization mass spectrometry revealed that the pks1 (bae) and pks3 (dif) gene clusters encode the biosynthesis of the polyene antibiotics bacillaene and difficidin or oxydifficidin, respectively. In addition, B. subtilis OKB105 (pheA sfp(0)), a transformant of the B. subtilis 168 derivative JH642, was shown to produce bacillaene, demonstrating that the pksX gene cluster directs the synthesis of that polyketide. The GenBank accession numbers for gene clusters pks1(bae), pks2, and pks3(dif) are AJ 634060.2, AJ 6340601.2, and AJ 6340602.2, respectively.


Depolarization of dehydroergosterol in phospholipid bilayers.
The behavior in phospholipid bilayers of low concentrations of dehydroergosterol, a fluorescent cholesterol mimic, has been examined by fluorometry and calorimetry. In contrast to many fluorescent membrane probes, dehydroergosterol shows a decrease in fluorescence anisotropy when the matrix phospholipid goes from the liquid-crystalline to the gel state. This was observed in three systems in which the matrix lipid was either dipalmitoyl- or dimyristoylphosphatidylcholine or dilauroylphosphatidylethanolamine. The decrease in anisotropy is the result of a large increase in the fluorescence life time of dehydroergosterol in these bilayer systems which is probably the result of thermal quenching of dehydroergosterol by neighboring molecules. The rotation of dehydroergosterol in these bilayers can be described in terms of the thermal coefficient of frictional resistance offered by the environment (Weber et al. (1984) Biochemistry 23, 6785-6788). The thermal coefficients are observed to change abruptly at the onset and completion temperatures of the gel to liquid-crystalline phase transition temperatures of the three matrix phospholipids. These changes are, however, much smaller than are the corresponding changes in the thermal coefficient observed for the fluorescent probe diphenylhexatriene in dilauroylphosphatidylethanolamine bilayers. The difference in behavior of the two fluorescent probes may be the result of lateral phase separation of dehydroergosterol similar to that reported for cholesterol in similar systems.


Evaluation of Ocotea puberula bark powder (OPBP) as an effective adsorbent to uptake crystal violet from colored effluents: alternative kinetic approaches.
The Ocotea puberula bark powder (OPBP) was evaluated as an effective adsorbent for the removal of crystal violet (CV) from colored effluents. OPBP was characterized and presented a surface with large cavities, organized as a honeycomb. The main functional groups of OPBP were O-H, N-H, C=O, and C-O-C. The adsorption of CV on OPBP was favorable at pH 9 with a dosage of 0.75 g L-1. The Avrami model was the most suitable to represent the adsorption kinetic profile, being the estimated equilibrium concentration value of 3.37 mg L-1 for an initial concentration of 50 mg L-1 (CV removal of 93.3%). The equilibrium was reached within 90 min. The data were better described by the Langmuir isotherm, reaching a maximum adsorption capacity of 444.34 mg g-1 at 328 K. The Gibbs free energy ranged from - 26.3554 to - 27.8055 kJ mol-1, and the enthalpy variation was - 11.1519 kJ mol-1. The external mass transfer was the rate-limiting step, with Biot numbers ranging from 0.0011 to 0.25. Lastly, OPBP application for the treatment of two different simulated effluents was effective, achieving a removal percentage of 90%.


Recyclable waste Dry-cell batteries derived carbon dots (CDs) for detection of Two-fold metal ions and degradation of BTB dye.
In modern era, electronic wastes are one of the major threats around us, most of them are reused with less efficiency instead of re-usage, and conversion into valuable products is highly recommended. In this work, we report an innovative approach for the synthesis of highly photoluminescent CDs from waste dry-cell batteries through one-step hydrothermal treatment for the detection and degradation of environmental pollutants. The as-prepared CDs were studied by X-ray photoelectron spectroscopy (XPS), HR-TEM studies, X-ray diffractometer (XRD), Raman spectrometer, FTIR spectroscopy, UV-visible spectrophotometer, and spectrofluorometric measurements. The calculated quantum yield for synthesized CDs was around 13 %. The CDs have uniform particle size distribution, strong photoluminescent behavior, and possess high stability against various environmental conditions. Also, CDs display the selective and sensitive detection of Cr6+ and Co2+ and ions with a detection limit of around 0.11 µM and 0.10 µM respectively. The possible mechanism of CDs was also examined. Moreover, the photocatalytic activity of CDs with Bromothymol Blue (BTB) dye was studied. The degradation efficiency of BTB dye can be achieved at around 84 % over 180 min under the irradiation of direct sunlight in presence of H2O2. To date, it's the first time we have recycled waste dry-cell batteries into CDs as an effective probe for the detection and decomposition of environmental pollution. Furthermore, this work provides not only an easier route to make good quality and improved photoluminescent CDs from waste material like used batteries and also paves way for the reconversion of global treating waste. Finally, the outstanding detection capability with multiple properties of as-prepared CDs provides various environmental applications like the detection of pollutants and carcinogenic polluted water treatment.


Association Between Parental Supply of Alcohol and Later Adolescent Alcohol Use in a Highly Permissive Context.
Many children and adolescents get their first experience with alcohol in a family setting. Evidence suggests that parental supply of alcohol is a risk factor for drinking later in life. However, most of the previous studies have been conducted in Western countries. The Czech Republic has among the highest alcohol consumption per capita, including among adolescents, and providing their own children with sips of alcohol is widely considered by parents to be a good way to introduce children to safe drinking. This study examined whether the parental supply of alcohol is associated with later use among adolescents in an Eastern European alcohol-permissive context. The sample included children (49% female) assessed at age 11 (n = 2,202) and age 15 (n = 1,279) from the European Longitudinal Study of Parents and Children (ELSPAC). The outcome was adolescent alcohol use at age 15, reported by adolescents and pediatricians. Predictors included different sources of alcohol (parents, family member, friend, own supply, or other sources) reported by adolescent at age 11. Parental supply of alcohol consistently emerged as a robust longitudinal predictor of adolescent alcohol use, with adjusted odds ratios of self-reported and pediatrician-reported frequent drinking at age 15 of 2.34 [1.19, 4.44] and 2.37 [1.02, 5.47], respectively. It also mediated the association between parental drinking and adolescent alcohol use. Parental supply of alcohol is an important risk factor for later adolescent alcohol use in the high alcohol-permissive population of the Czech Republic, suggesting that the association might not be context dependent.


Characteristics of Cancer-Related Fatigue and Concomitant Sleep Disturbance in Cancer Patients.
Cancer patients often experience cancer-related fatigue (CRF) and sleep disturbances due to cancer and cancer treatment, and symptoms can persist long after treatment. Despite these common occurrences, few studies simultaneously characterize CRF and sleep architecture among cancer patients. The objective was to characterize CRF and the sleep architecture of patients seen in a CRF clinic and sleep clinic at the University of Texas MD Anderson Cancer Center. CRF Clinic medical records were retrospectively reviewed from September 1, 2006, to September 30, 2010, for self-reported performance status, fatigue, pain, sleep disturbance, depression, anxiety, and sleepiness (n = 219). Polysomnography results were recorded for those referred for additional sleep consultation (n = 39). Notably, patients often reported fatigue, sleep disturbance, excessive daytime sleepiness, and a majority of patients referred for a sleep consultation were diagnosed with obstructive sleep apnea (n = 33). The results highlight the promise of an interdisciplinary collaboration between dedicated a CRF clinic and sleep clinic to conduct effective assessments to identify treatable CRF and sleep disorders.


Nutritional status, sarcopenia, gastrointestinal symptoms and quality of life after gastrectomy for cancer - A cross-sectional pilot study.
Gastrointestinal (GI) symptoms, malabsorption, reduced food intake and weight loss are common sequela of gastrectomy. This can result in malnutrition with a subsequent prolonged recovery, reduced physical functioning and deteriorated quality of life (QoL). Few studies have investigated the relationship between GI-symptoms, QoL and malnutrition in long-term survivors of gastric cancer. Therefore, we assess nutritional status, GI-symptoms and QoL 2-5 years after gastrectomy for malignancy. A cross-sectional, pilot study was carried out in patients who underwent total or subtotal gastrectomy at Oslo University Hospital between 2012 and 2016, who had not experienced disease recurrence. Subjects above 85 years were excluded. The nutritional status of the patients fell into three groups by a score of subjective global assessment (SGA)-A, B, and C. Muscle mass was measured by body composition by bioelectrical impedance analysis and muscle strength was measured by handgrip strength (HGS). Dietary intake was assessed by repeated 24-h dietary recalls. GI-symptoms and QoL were assessed using GI-Symptom Rating Scale (GSRS) and the SF-36 questionnaire. 21 patients were included. Mean (SD) weight loss was 12.8% (11.6) from preoperative status to follow up. Percentage weight loss was larger after total gastrectomy compared with subtotal gastrectomy (17.9% (12.3) vs. 6.6% (7.1) (p = 0.03)). A low mean intake of energy and protein was reported compared to dietary recommendations for the general Nordic population and intake in a national dietary survey. All of the patients were classified as pre-sarcopenic, and 5% as sarcopenic. Persistent weight loss >10% was observed in 45% of the subjects and these were in risk of malnutrition. Subjects with malnutrition had higher GSRS score for the abdominal pain syndrome (p = 0.042) and lower SF-36 scores for bodily pain (p = 0.01) and vitality (p = 0.02) compared with those without malnutrition. A high prevalence of weight loss, and pre-sarcopenia was observed. Malnutrition as assessed by SGA was associated with more GI-Symptoms and reduced QoL scores. Further studies with larger number of participants are needed to verify our findings.


Immunological recovery of thymectomized and sham-thymectomized lethally irradiated mice reconstituted with syngeneic bone marrow cells.
Immunological functions of lethally irradiated mice reconstituted with syngeneic bone marrow cells recover after 5--6 weeks. In mice that had been thymectomized before irradiation and reconstitution, T-cell function is deficient but the B-cell function is preserved.


Tumor environment changed by combretastatin derivative (Cderiv) pretreatment that leads to effective tumor targeting, MRI studies, and antitumor activity of polymeric micelle carrier systems.
To evaluate effect of a vascular disrupting agent, a combretastatin derivative (Cderiv), on tumor targeting for polymeric micelle carrier systems, containing either a diagnostic MRI contrast agent or a therapeutic anticancer drug. Cderiv was pre-administered 72 h before polymeric micelle MRI contrast agent injection. Accumulation of the MRI contrast agent in colon 26 murine tumor was evaluated with or without pretreatment of Cderiv by ICP and MRI. Significantly higher accumulation of the MRI contrast agent was found in tumor tissues when Cderiv was administered at 72 h before MRI contrast agent injection. T(1)-weighted images of the tumor exhibited substantial signal enhancement in tumor area at 24 h after the contrast agent injection. In T(1)-weighted images, remarkable T(1)-signal enhancements were observed in part of tumor, not in whole tumor. These results indicate that Cderiv pretreatment considerably enhanced the permeability of the tumor blood vessels. Antitumor activity of adriamycin encapsulated polymeric micelles with the Cderiv pretreatment suppressed tumor growth in 44As3 human gastric scirrhous carcinoma-bearing nude mice. Pretreatment of Cderiv enhanced tumor permeability, resulting in higher accumulation of polymeric micelle carrier systems in solid tumors.


Pancreas and islet cell transplantation.
Transplantation of the pancreas or islet cells constitutes surgical treatment for patients with type 1 diabetes mellitus. Pancreas transplantation is now an established procedure for the surgical treatment of diabetes mellitus. Islet cell transplantation has the potential to be the procedure of choice once it becomes more routine because of the minimal surgery involved. Included in this chapter are the pathophysiology of diabetes, rationale for transplantation, and the surgical procedure itself.


Mycobacterium tuberculosislpdC, Rv0462, induces dendritic cell maturation and Th1 polarization.
Mycobacterium tuberculosis, the etiological factor of pulmonary tuberculosis, causes significant morbidity and mortality worldwide. Activation of host immune responses for containment of mycobacterial infections involves participation of innate immune cells, such as dendritic cells (DCs). In this study, we demonstrated that the gene encoding lipoamide dehydrogenase C (lpdC) from M. tuberculosis, Rv0462, induce maturation and activation of DCs involved in the MAPKs signaling pathway. Moreover, Rv0462-treated DCs activated naïve T cells, polarized CD4(+) and CD8(+) T cells to secrete IFN-γ in syngeneic mixed lymphocyte reactions, which would be expected to contribute to Th1 polarization of the immune response. Our results suggest that Rv0462 can contribute to the innate and adaptive immune responses during tuberculosis infection, and thus modulate the clinical course of tuberculosis.


MR imaging-based volumetry in patients with early-treated phenylketonuria.
Our purpose was to specify the most severely affected brain structures in early treated phenylketonuria regarding volume loss and establish possible correlations between volume loss and plasma levels of phenylalanine (Phe). In 31 patients with early treated phenylketonuria and in 27 healthy volunteers, we acquired volumetric MR imaging data. Serum Phe concentrations at different times were measured as well. Semiautomatic volumetric postprocessing of the cerebellum, cerebrum (supratentorial brain tissue), hippocampus, intracranial volume, lateral ventricles, nucleus caudatus, nucleus lentiformis, pons, and thalamus, as well as the two-dimensional extension of the corpus callosum, was performed using the software BRAINS2. For each separate brain structure, the relative differences between the normal and the phenylketonuria group (delta(rel)) were calculated. The cerebrum, corpus callosum, hippocampus, intracranial volume, and pons were significantly smaller in patients with phenylketonuria than in healthy patients. The volume of the lateral ventricles was significantly larger in patients with phenylketonuria than in healthy ones. The most severely affected structures were the pons (delta(rel) = 16%), hippocampus (delta(rel) = 14.5%), cerebrum (delta(rel) = 13%), and corpus callosum (delta(rel) = 10%). No significant differences were found for the basal ganglia, cerebellum, and thalamus. There were no significant correlations found between the volume of any of the different brain structures and the metabolic parameters. The most severely affected brain structures in early-treated patients with phenylketonuria regarding volume loss are the cerebrum, corpus callosum, hippocampus, and pons.


Five-Year-Olds' Systematic Errors in Second-Order False Belief Tasks Are Due to First-Order Theory of Mind Strategy Selection: A Computational Modeling Study.
The focus of studies on second-order false belief reasoning generally was on investigating the roles of executive functions and language with correlational studies. Different from those studies, we focus on the question how 5-year-olds select and revise reasoning strategies in second-order false belief tasks by constructing two computational cognitive models of this process: an instance-based learning model and a reinforcement learning model. Unlike the reinforcement learning model, the instance-based learning model predicted that children who fail second-order false belief tasks would give answers based on first-order theory of mind (ToM) reasoning as opposed to zero-order reasoning. This prediction was confirmed with an empirical study that we conducted with 72 5- to 6-year-old children. The results showed that 17% of the answers were correct and 83% of the answers were wrong. In line with our prediction, 65% of the wrong answers were based on a first-order ToM strategy, while only 29% of them were based on a zero-order strategy (the remaining 6% of subjects did not provide any answer). Based on our instance-based learning model, we propose that when children get feedback "Wrong," they explicitly revise their strategy to a higher level instead of implicitly selecting one of the available ToM strategies. Moreover, we predict that children's failures are due to lack of experience and that with exposure to second-order false belief reasoning, children can revise their wrong first-order reasoning strategy to a correct second-order reasoning strategy.


Profiling of the antibody response to attenuated LC16m8 smallpox vaccine using protein array analysis.
Concerns about bioterrorism and outbreaks of zoonotic orthopoxvirus require safe and efficacious smallpox vaccines. We previously reported the clinical efficacy and safety profiles of LC16m8, a live, attenuated, cell culture-derived, smallpox vaccine, examined in over 3000 healthy Japanese adults with various vaccination histories. In this study, serum of approximately 200 subjects pre and post LC16m8 vaccination were subjected to a vaccinia virus-specific protein array to evaluate the proteome-wide immunogenicity. The relationships between antigen-specific antibodies and plaque reduction neutralization titers were analyzed. LC16m8 induced antibodies to multiple vaccinia antigens in primary-vaccinated individuals and yielded effective booster responses in previously vaccinated individuals, demonstrating similar antibody profiles to those reported for other vaccinia virus strains. Several immunodominant antigens were indicated to be important for neutralization of the intracellular mature virion. The similarity of antibody profiles between LC16m8 and other smallpox vaccine strains supports the immunogenicity and protective efficacy of LC16m8.


Trans-Cis Kinetic Study of Azobenzene-4,4'-dicarboxylic Acid and Aluminium and Zirconium Based Azobenzene-4,4'-dicarboxylate MOFs.
Metal organic frameworks (MOFs) are porous hybrid crystalline materials that consist of organic linkers coordinated to metal centres. The trans-cis isomerisation kinetics of the azobenzene-4,4'-dicarboxylic acid (AZB(COOH)2) precursor, as well as the Al3+ (Al-AZB)- and Zr4+ (Zr-AZB)-based MOFs with azobenzene-4,4'-dicarboxylate linkers, are presented. The photo-isomerization in the MOFs originates from singly bound azobenzene moieties on the surface of the MOF. The type of solvent used had a slight effect on the rate of isomerization and half-life, while the band gap energies were not significantly affected by the solvents. Photo-responsive MOFs can be classified as smart materials with possible applications in sensing, drug delivery, magnetism, and molecular recognition. In this study, the MOFs were applied in the dye adsorption of congo red (CR) in contaminated water. For both MOFs, the UV-irradiated cis isomer exhibited a slightly higher CR uptake than the ambient-light exposed trans isomer. Al-AZB displayed a dye adsorption capacity of over 95% for both the UV-irradiated and ambient light samples. The ambient light exposed Zr-AZB, and the UV irradiated Zr-AZB had 39.1% and 44.6% dye removal, respectively.


Phase I and pharmacologic study of 72-hour infused 5-fluorouracil in man.
The relationships between the administered dose, clearance, and the toxicity spectrum of 5-fluorouracil (5-FU) administered as 72-hour constant infusion have been studied in 21 patients with advanced cancer. This was done as a pilot study for possible future combination using 5-FU as a radiosensitizer. Individual patients tolerated up to 65 mg/kg/24 hours, but serious toxicity appeared once as low as 35 mg/kg. Limiting toxicity proved to be "mixed" with upper intestinal symptoms (nausea and vomiting), stomatitis, and central nervous system signs all occurring in various patients. Central nervous system effects (both cerebellar and vomiting) proved as troublesome as stomatitis. There was only a general link between the administered dose and the subsequent toxicity grade, but a reasonably quantitative relationship emerged when the serum 5-Fu levels obtained and the degree of patient toxicity were compared. The clearance of 5-FU was confirmed to be nonlinear over the entire dose range studied (25-65 mg/kg/24 hours), consistent with a two-compartment model of drug metabolism. One compartment appears to be systemic (extra-hepatic) metabolism (probably anabolic removal) which is saturated at just below 15 mg/kg/day. Doses above that level lead to drug accumulation. No steady state was reached, contrary to previous reports. At the higher infusion rates, clearance progressively approaches that predicted by the assumption that the second compartment is splanchnic blood flow and catabolism. While 5-FU can be administered as a 72-hour infusion as one possible schedule for use as a single agent or for combined modality studies, CNS effects are quite troublesome in comparison to longer infusions to toxicity.


Elucidating Drivers for Variations in the Explosive Human Immunodeficiency Virus Epidemic Among People Who Inject Drugs in Pakistan.
Pakistan's explosive human immunodeficiency virus (HIV) epidemic among people who inject drugs (PWID) varies widely across cities. We evaluated possible drivers for these variations. Multivariable regression analyses were undertaken using data from 5 national surveys among PWID (n = 18 467; 2005-2017) to determine risk factors associated with variations in city-level HIV prevalence. A dynamic HIV model was used to estimate the population-attributable fraction (PAF; proportion of HIV infections prevented over 10 years when that risk factor is removed) of these risk factors to HIV transmission and impact on HIV incidence of reducing their prevalence. Regression analyses suggested that city-level HIV prevalence is strongly associated with the prevalence of using professional injectors at last injection, heroin use in last month, and injecting ≥4 times per day. Through calibrating a model to these associations, we estimate that the 10-year PAFs of using professional injectors, heroin use, and frequent injecting are 45.3% (95% uncertainty interval [UI], 4.3%-79.7%), 45.9% (95% UI, 8.1%-78.4%), and 22.2% (95% UI, 2.0%-58.4%), respectively. Reducing to lowest city-level prevalences of using professional injectors (2.8%; median 89.9% reduction), heroin use (0.9%; median 91.2% reduction), and frequent injecting (0.1%; median 91.8% reduction) in 2020 reduces overall HIV incidence by 52.7% (95% UI, 6.1%-82.0%), 53.0% (95% UI, 11.3%-80.2%), and 28.1% (95% UI, 2.7%-66.6%), respectively, over 10 years. Interventions should focus on these risk factors to control Pakistan's explosive HIV epidemic among PWID, including a concomitant expansion of high-coverage needle/syringe provision, opioid substitution therapy, and antiretroviral therapy.


Mycotic aneurysm of the distal thoracic aorta after botulinum toxin injection for esophageal dysmotility.
Endoscopic injection of botulinum toxin is a common method to treat esophageal dysmotility and achalasia. Patients undergoing this procedure who subsequently present with abdominal or back pain and constitutional symptoms should be evaluated for possible complications of the procedure, including occult esophageal perforation, mediastinitis, and mycotic aneurysm of the thoracic aorta. The case described herein illustrates the importance of serial imaging in a patient with persistent symptoms after botulinum toxin injection to identify and to treat occult aortic inoculation leading to mycotic aneurysm before sepsis and aortic rupture ensue with their attendant morbidity and mortality risks.


Structural comparison of human C4A3 and C4B1 after proteolytic activation by C1s.
The fourth component of human complement is an essential part of the classical and lectin pathways performing multifunctional roles in both host defense and immune regulation. C4 is the most polymorphic member of the complement proteins, and complete deficiency is strongly associated with autoimmune disease, especially, systemic lupus erythematosus (SLE). Of the two C4 genes C4A, but not C4B, null alleles have been implicated as important independent disease susceptibility genes occurring in more than half of SLE patients. Whether and how this deficiency contributes to the development or pathology remains unclear. We do know that activation of C4 by C1s cleaves the thioester bond, thus inducing a conformational change that exposes numerous ligand-binding sites involved in functional activity. Structural comparison, among many other tools, plays an important role in predicting function. In this report, the tertiary structures of C4A and C4B were compared using near and far-UV circular dichroism, ANS fluorescence, site-specific monoclonal antibodies and isoelectric focusing. Negligible differences in the native proteins were found. However, the activated proteins were dissimilar in secondary and tertiary structure that was accompanied by significant differences in charge distribution and surface hydrophobicity. These conformational differences, together with known acceptor preferences, have functional implications for the association between C4A null alleles and SLE.


Relationship between the degree of poverty and the IgE response to Ascaris infection in slum children.
We examined a group of urban slum children in Caracas, Venezuela, and demonstrated the relationship that exists between poverty, conditions of hygiene and the prevalence of helminth infection. Concordant with the high prevalence of helminth infection in these children, the total serum levels of immunoglobulin E (IgE) and blood eosinophilia were elevated and were directly related to the degree of poverty and lack of sanitary facilities. However, in contrast, the reverse pattern was observed for the specific allergic response to these parasites. Thus, the immediate hypersensitivity skin test reactivity to Ascaris antigens, and the serum levels of specific anti-Ascaris IgE antibody, were lowest in the poorest children, who had the highest prevalence of helminth infection and the highest total IgE levels. As allergic-type reactions may participate in protective mechanisms against helminths, these results suggest that poverty and poor sanitary conditions may, by influencing the IgE response, compromise the resistance of such children to parasitic infections.


Bypass surgery for the prevention of ischemic stroke: current indications and techniques.
Although most ischemic strokes are thromboembolic in origin and their management is endovascular or medical, some are haemodynamic in origin and their management may be surgical. We reviewed bypass indications, patient selection and surgical techniques used in our current practice. Extracranial-intracranial (EC-iC) bypass with superior temporal artery-to-middle cerebral artery (STA-MCA) bypass, high-flow interposition grafts and reconstructive techniques were used to treat patients with symptomatic ischemia. During a 13-year period, 152 bypasses were performed for ischemia in 129 patients. Specific diagnoses included: (1) internal carotid artery (iCA) occlusion (58 bypasses); (2) MCA occlusion and, rarely, high-grade MCA stenosis (22 bypasses); (3) vertebrobasilar atherosclerotic steno-occlusive disease (2 bypasses); (4) moyamoya disease (65 bypasses); and (5) ischemic complications after aneurysm treatment (5 bypasses). of the 152 bypasses, 137 were conventional STA-MCA bypasses. fourteen patients had high-flow bypasses that included 4 "double-barrel" STA-MCA bypasses, 6 bypasses with interposition grafts to the cervical carotid artery, 2 subclavian artery-to-MCA bypasses, 1 MCA-to-posterior cerebral artery (PCA) bypass and 1 aorto-carotid bypass. The bypass patency rate was 96.1%. Bypass surgery for the prevention of ischemic stroke is safe and elegant techniques have been developed. Patients with athero-occlusive disease, ischemic symptoms and haemodynamic insufficiency have significant risk of stroke if managed medically or left untreated. However, surgical intervention lacks supporting evidence from the recent Carotid occlusion Surgery Study (CoSS). Patients will be caught in a difficult position between a dismal natural history and an unproven surgical intervention. Clinicians must individualise their management until additional data are published or further consensus develops.


Palladium-catalyzed mono- and double-carbonylation of indoles with amines controllably leading to amides and α-ketoamides.
A novel and efficient double-carbonylation of indoles with primary or secondary amines to yield indole-3-α-ketoamides has been developed and bioactive molecules could be one-pot synthesized using the current methodology, which could also be selectively switched to mono-carbonylation to afford indole-3-amides only by a slight modification of reaction conditions.


Optimally designed theranostic system based folic acids and chitosan as a promising mucoadhesive delivery system for encapsulating curcumin LbL nano-template against invasiveness of breast cancer.
Curcumin is a potential candidate in cancer therapy due to its ability to inhibit many signalling pathways at the same time of exposure because of its unique content of aromatic ring, B diketone, olefinic linker, and O methoxy phenolic groups. Its applications in biomedical therapy is limited because of its sensitivity, and its rapid degradation. In the current study, curcumin inserted into polyelectrolyte pairs (protamine and dextran) and then was functionalized by folic acid conjugated chitosan used for the first time, as theranostic system. Such this strategy allows to improve its mucoadhesion and penetration that increases their accumulation inside cancer cells. CUR-LbL NPs were then used to investigate drug release inside Human Mammary Carcinoma (MCF-7 cell lines) after their incubations for 3 h, 6 h and 24 h. Flow cytometry indicated that the percentages of apoptosis, necrosis and cell cycle arrest were increased significantly in MCF-7 cell lines treated by CUR-LbL NPs. Furthermore, SEM image showed many debris in the section of MCF-7 treated by CUR-LbL NPs. Here, it can be summarized that curcumin functionalized by multi-layered polyelectrolyte capsules can be used as a model to study the fate of the adsorbed nanocarriers and to investigate the drug release inside cells.


Characterization of GRK5 as a novel regulator of rhabdomyosarcoma tumor cell growth and self-renewal.
Rhabdomyosarcoma (RMS) is the most common soft-tissue pediatric sarcoma. Clinical outcomes for RMS patients with relapsed or metastatic disease remain poor. Treatment options remain limited, presenting an urgent need for novel therapeutic targets. Using a high-throughput siRNA screen against the human kinome, we identified GRK5, a G-protein receptor kinase, as a novel regulator of RMS tumor cell growth and self-renewal. Through functional assays in vitro and in vivo, we show that GRK5 regulates cell cycle in a kinase-independent manner to promote RMS tumor cell growth. NFAT1 expression is regulated by GRK5 in a kinase independent manner, and loss of NFAT1 phenocopies GRK5 loss-of-function effects on the cell cycle alterations. Self-renewal of tumor propagating cells (TPCs) is thought to give rise to tumor relapse. We show that loss of GRK5 results in a significant reduction of RMS self-renewal capacity in part due to increased cell death. Treatment of human RMS xenografts in mice with CCG-215022, a GRK5-selective inhibitor, results in reduced tumor growth and self-renewal in both major subtypes of RMS. GRK5 represents a novel therapeutic target for the treatment of RMS.


Comparative ultrastructure of thyroid, tongue and eyelid lesions in the neuroma phenotype of medullary carcinoma of the thyroid: association of amyloid with fibroblasts in thyroid tumor and in mucosal neuromas.
Electron-microscopic and histochemical studies of thyroid tumor, tongue neuromas and eyelid neuromas from the lesions of a patient with medullary thyroid carcinoma were compared. In the thyroid tumor, a significant number of the C cells showed heterogeneity of granule types; no C cells, however, were identified in the tongue and eyelid neuromas. Amyloid was clearly shown by Congo red staining in the thyroid neoplasm and in the tongue neuromas. In all tissues, amyloid fibrils were found to be ultrastructurally closely associated with fibroblasts. These fingings suggest that the fibroblast rather than the C cell may have played the important role in the deposition of amyloid in this patient's thyroid carcinoma.


A new method for culturing human hair follicle cells on floating mixed collagen membranes.
A new method for culturing human hair follicle cells without a biological feeder layer has been developed. Dispersed hair follicle cells obtained from plucked hairs have been successfully grown on floating mixed collagen membranes (collagen types I and IV) and have reached a confluent state. They could be subcultured up to twice. Differentiation of the cells was maintained throughout a month in culture. Stratification of the cells and continuous epithelial pavement formation were seen, as in cultured epidermal keratinocytes.


Preperitoneal Pelvic Packing is Associated With Increased Risk of Venous Thromboembolism.
Preperitoneal pelvic packing (PPP) is an important intervention for control of severe pelvic hemorrhage in blunt trauma patients. We hypothesized that PPP is associated with an increased incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE). A retrospective cohort analysis of blunt trauma patients with severe pelvic fractures (AIS ≥4) using the 2015-2017 American College of Surgeons-Trauma Quality Improvement Program database was performed. Patients who underwent PPP within four hours of admission were matched to patients who did not using propensity score matching. Matching was performed based on demographics, comorbidities, injury- and resuscitation-related parameters, vital signs at presentation, and initiation and type of prophylactic anticoagulation. The rates of DVT and PE were compared between the matched groups. Out of 5129 patients with severe pelvic fractures, 157 (3.1%) underwent PPP within four h of presentation and were matched with 157 who did not. No significant differences were detected between the two matched groups in any of the examined baseline variables. Similarly, mortality and end-organ failure rates were not different. However, PPP patients were significantly more likely to develop DVT (12.7% versus 5.1%, P = 0.028) and PE (5.7% versus 0.0%, P = 0.003). PPP in severe pelvic fractures secondary to blunt trauma is associated with an increased risk of DVT and PE. A high index of suspicion and a low threshold for screening for these conditions should be maintained in patients who undergo PPP.


Lytic transglycosylase MltG cleaves in nascent peptidoglycan and produces short glycan strands.
Bacteria encase their cytoplasmic membrane with peptidoglycan (PG) to maintain the shape of the cell and protect it from bursting. The enlargement of the PG layer is facilitated by the coordinated activities of PG synthesising and -cleaving enzymes. In Escherichia coli, the cytoplasmic membrane-bound lytic transglycosylase MltG associates with PG synthases and was suggested to terminate the polymerisation of PG glycan strands. Using pull-down and surface plasmon resonance, we detected interactions between MltG from Bacillus subtilis and two PG synthases; the class A PBP1 and the class B PBP2B. Using in vitro PG synthesis assays with radio-labelled or fluorophore-labelled B. subtilis-type and/or E. coli-type lipid II, we showed that both, BsMltG and EcMltG, are lytic tranglycosylases and that their activity is higher during ongoing glycan strand polymerisation. MltG competed with the transpeptidase activity of class A PBPs, but had no effect on their glycosyltransferase activity, and produced glycan strands with a length of 7 disaccharide units from cleavage in the nascent strands. We hypothesize that MltG cleaves the nascent strands to produce short glycan strands that are used in the cell for a yet unknown process.


Repeat resection for recurrence of pulmonary artery intimal sarcoma.
Pulmonary artery intimal sarcomas (PAIS) are vascular sarcomas of mesenchymal origin and are exceedingly rare. Here, we detail a 57-year-old female who presents with worsening dyspnea and computed tomography scan findings consistent with a pulmonary embolus, however, upon examination in the operating room for emergent embolectomy, was found to have a PAIS. This case report highlights this rare illness and management decisions that can optimize care of these patients.


The origin of protein and fatty yolk in Rana pipiens. III. Intramitochondrial and primary vesicular yolk formation in frog oocytes.
The precise origin of the primary yolk precursor complex or primary vesicular yolk is obscure but in its earliest recognizable stage it is a typical multivesicular body which first acquires a moderately electron-dark matrix. Following this, an extremely electron-dark amorphous material, the yolk protein, appears within the precursor. This yolk protein increases in amount as the yolk vesicle grows and by the time the precursors are about 1 micrometer in diameter this protein is partly to almost completely crystalline. Yolk originating within mitochondrial cristae unlike that in the yolk precursor complexes is crystalline from its earliest appearance. Intracristae mitochondrial yolk crystals have a spacing of 70--85 A. Their molecular organization appears in some sections as electron-dark lamellae and in others as light cylinders surrounded by an electron-dark matrix.


Robert Bentley Todd's contribution to cell theory and the neuron doctrine.
Robert Bentley Todd, who is best remembered for "Todd's paralysis," made many more important contributions to neurology and neuroscience, including the concept of brain electricity and electrical discharges in epilepsy. He was also a pioneering microscopist and we here review his neurohistological studies and his contributions to the application of Schwann's (1839) cell theory to the nervous system and the later neuron doctrine, as described in his textbook The Descriptive and Physiological Anatomy of the Brain, Spinal Cord and Ganglions (Todd, 1845), his Cyclopaedia of Anatomy and Physiology (1847) and his joint textbook with William Bowman The Physiological Anatomy and Physiology of Man (1845). Writing in the mid-1840s, Todd acknowledged that the "vesicles" he observed corresponded to the earlier descriptions of "globules" or "kugeln" by Valentin and which Schwann first interpreted as cell bodies. Todd was among the first to recognize that nerve cell bodies were in continuity with axons ("axis cylinders"), sometimes associated with "the white substance of Schwann" ("tubular" fibers), or sometimes without ("gelatinous" fibers). He also described continuous nerve cell branching processes, later called dendrites. He was the first to recognize the insulating properties of Schwann's "white substance" (myelin) to facilitate conduction. Influenced by his contemporary, Faraday, Todd was also the first to develop the functional concept of dynamic polarization ("nervous polarity") to explain nerve cell conduction.


Cerebral blood flow in adolescents with drug-naive, first-episode major depressive disorder: An arterial spin labeling study based on voxel-level whole-brain analysis.
The major depressive disorder (MDD) can be a threat to the health of people all over the world. Although governments have developed and implemented evidence-based interventions and prevention programs to prevent MDD and maintain mental health in adolescents, the number of adolescents with this condition has been on the rise for the past 10 years. A total of 60 adolescents were recruited, including 32 drug-naive adolescents with first-episode MDD and 28 healthy controls (HCs). Alterations in the intrinsic cerebral activity of the adolescents with MDD were explored using arterial spin labeling (ASL) while differences in the regional cerebral blood flow (rCBF) of the two groups were assessed based on voxel-based whole-brain analysis. Finally, correlations between the regional functional abnormalities and clinical variables were investigated for adolescents with MDD. Compared with HCs, MDD patients had a lower rCBF in the left triangular part of the inferior frontal gyrus (IFGtriang) but a higher one in the right Precental gyrus (PreCG). Negative correlations were also noted between the CBF in the left IFGtriang and the Hamilton depression scale (HAMD) scores of MDD patients. Elucidating the neurobiological features of adolescent patients with MDD is important to adequately develop methods that can assist in early diagnosis, precaution and intervention.


Cost-effectiveness of integrated disease management for high risk, exacerbation prone, patients with chronic obstructive pulmonary disease in a primary care setting.
We evaluate the cost-effectiveness of the 'Best Care' integrated disease management (IDM) program for high risk, exacerbation prone, patients with chronic obstructive pulmonary disease (COPD) compared to usual care (UC) within a primary care setting from the perspective of a publicly funded health system (i.e., Ontario, Canada). We conducted a model-based, cost-utility analysis using a Markov model with expected values of costs and outcomes derived from a Monte-Carlo Simulation with 5000 replications. The target population included patients started in GOLD II with a starting age of 68 years in the trial-based analysis. Key input parameters were based on a randomized control trial of 143 patients (i.e., UC (n = 73) versus IDM program (n = 70)). Results were shown as incremental cost per quality-adjusted life year (QALY) gained. The IDM program for high risk, exacerbation prone, patients is dominant in comparison with the UC group. After one year, the IDM program demonstrated cost savings and improved QALYs (i.e., UC was dominated by IDM) with a positive net-benefit of $5360 (95% CI: ($5175, $5546) based on a willingness to pay of $50,000 (CAN) per QALY. This study demonstrates that the IDM intervention for patients with COPD in a primary care setting is cost-effective in comparison to the standard of care. By demonstrating the cost-effectiveness of IDM, we confirm that investment in the delivery of evidence based best practices in primary care delivers better patient outcomes at a lower cost than UC.