Synthesis of indolizidinone analogues of cytotoxic alkaloids: monocyclic precursors are also active.
Readily available proline derivatives can be transformed in just two steps into analogues of cytotoxic phenanthroindolizidine alkaloids. The key step uses a sequential radical scission-oxidation-alkylation process, which yields 2-substituted pyrrolidine amides. A second process effects the cyclization to give the desired alkaloid analogues, which possess an indolizidine core. The major and minor isomers (dr 3:2 to 3:1) can be easily separated, allowing their use to study structure-activity relationships (SAR). The process is versatile and allows the introduction of aryl and heteroaryl groups (including biphenyl, halogenated phenyl, and pyrrole rings). Some of these alkaloid analogues displayed a selective cytotoxic activity against tumorogenic human neuronal and mammary cancer cells, and one derivative caused around 80% cell death in both tumor lines at micromolar doses. The cytotoxicity of some monocyclic precursors was also studied, being comparable or superior to the bicyclic derivatives.


Kordiimonas sediminis sp. nov., isolated from a sea cucumber culture pond.
A marine bacterium, designated strain N39(T), was isolated from a sediment sample collected at a sea cucumber culture pond in Weihai, China. Cells of strain N39(T) were observed to be Gram-stain negative, facultatively anaerobic, motile rods showing catalase and oxidase negative reactions. Strain N39(T) was found to grow optimally at pH 8.0-8.5, 35-37 °C and in the presence of approximately 3.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain N39(T) belongs to the genus Kordiimonas in the family Kordiimonadaceae, appearing closely related to Kordiimonas lacus JCM 16261(T) (95.9 %), Kordiimonas aquimaris MEBiC06554(T) (95.1 %), Kordiimonas gwangyangensis JCM 12864(T) (94.2 %) and Kordiimonas aestuarii 101-1(T) (93.8 %). Ubiquinone 10 (Q-10) was found to be the major respiratory quinone. The dominant cellular fatty acids were identified as iso-C17:1 ω9c, iso-C17:0, iso-C15:0 and C17:1 ω6c. The predominant polar lipids were found to be phosphatidylglycerol, phosphatidylethanolamine and diphosphatidylglycerol. The DNA G + C content of strain N39(T) is 50.8 %. On the basis of genotypic, chemotaxonomic and phenotypic data, strain N39(T) is concluded to represent a novel species within the genus Kordiimonas, for which the name Kordiimonas sediminis sp. nov. is proposed. The type strain is N39(T) (=KCTC 42590(T) = MCCC 1H00112(T)).


Genetic Analysis of Patients With Sickle Cell Anemia and Stroke Before 4 Years of Age Suggest an Important Role for Apoliprotein E.
Ischemic stroke is a devastating complication affecting children with sickle cell anemia. Genetic factors are likely to be important in determining the risk of stroke but are poorly defined. We have studied a cohort of 19 children who had an overt ischemic stroke before 4 years of age. We predicted genetic determinants of stroke would be more prominent in this group. We performed whole exome sequencing on this cohort and applied 2 hypotheses to our variant filtering. First, we looked for strong, potentially mono- or oligogenic variants for ischemic stroke, and second, we considered that more common polygenic variants will be enriched in our cohort. Candidate variants emerging from both strategies were validated in a cohort of 283 patients with sickle cell anemia and known pediatric cerebrovascular outcomes. We used principal component analysis in this cohort to control for relatedness and population substructure. Our primary finding was that the Apoliprotein E genotypes ε2/ε4 and ε4/ ε4, defined by the interplay of rs7412 and rs429358, were associated with increased stroke risk, with an odds ratio of 4.35 ([95% CI, 1.85-10.0] P=0.0011) for ischemic stroke in the validation cohort. We also found that rs2297518 in NOS (NO synthase) 2 (odds ratio, 2.25 [95% CI, 1.21-4.19]; P=0.014) and rs2230123 in signal transducer and activator of transcription (odds ratio, 2.60 [95% CI, 1.30-5.20]; P=0.009) both had increased odds ratios for ischemic stroke, although these two variants were below the threshold for statistical significance after correction for multiple testing. These data identify new loci for future functional investigations into cerebrovascular disease in sickle cell anemia. Based on African population reference allele frequencies, the Apoliprotein E genotypes would be present in about 10% of children with sickle cell anemia and represent a genetic risk factor that is potentially modifiable by both dietary and pharmaceutical manipulation of its dyslipidemic effects.


Multiple system atrophy: a prototypical synucleinopathy for disease-modifying therapeutic strategies.
Despite active fundamental, translational and clinical research, no therapeutic intervention has yet shown convincing effects on disease progression in Parkinson's disease (PD) patients. Indeed, several disease-modification trials failed or proved to be inconclusive due to lack of consistency between clinical rating scales and putative surrogate markers of disease progression, or confounding symptomatic effects of the tested compound. Multiple system atrophy (MSA) is a rapidly progressing orphan disorder leading to severe motor disability within a few years. Together with PD and dementia with Lewy bodies (DLB), MSA belongs to the synucleinopathies, a group of neurodegenerative disorders characterized by the abnormal accumulation of alpha-synuclein. Crucial milestones have been reached for successfully conducting clinical intervention trials in a large number of patients with MSA. In this personal view, we will review evidence, and discuss why MSA could prove the most relevant clinical model for assessing treatments that target mechanisms operating in all synucleinopathies.


Understanding atomic bonding and electronic distributions of a DNA molecule using DFT calculation and BOLS-BC model.
Deoxyribonucleic acid (DNA) is an important molecule that has been extensively researched, mainly due to its structure and function. Herein, we investigated the electronic behavior of the DNA molecule containing 1008 atoms using density functional theory. The bond-charge (BC) model shows the relationship between charge density and atomic strain. Besides, the model mentioned above is combined with the bond-order-length-strength (BOLS) notion to calculate the atomic cohesive energy, the bond energy, and the local bond strain of the DNA chain. Using the BOLS-BC model, we were able to obtain information on the bonding features of the DNA chain and better comprehend the associated properties of electrons in biological systems. Consequently, this report functions as a theoretical reference for the precise regulation of the electrons and the bonding states of biological systems.


Survey of KI, WU, MW, and STL Polyomavirus in Cancerous and Non-Cancerous Lung Tissues.
The pathogenesis of the human polyomavirus (PyV) KI, WU, MW, and STL has not been elucidated yet. Respiratory transmission is suggested, but the site of the replication, tissue, and cell tropism is not clarified. KIPyV and WUPyV DNA and/or antigen were detected in normal lung tissues previously by others. In fact, a KIPyV DNA sequence was found in lung cancer samples. Up to date, there is no publication about the DNA prevalence of MWPyV and STLPyV neither in normal nor in cancerous lung tissues. The aim of the present study was to examine the DNA prevalence of these polyomaviruses in cancerous and non-cancerous lung tissue samples, in order to study the possible site for viral replication and/or persistence, and the potential association of these viruses with lung carcinogenesis as well. 100 cancerous and 47 non-cancerous, formalin-fixed paraffin-embedded lung tissue samples were studied for KIPyV, WUPyV, MWPyV, and STLPyV by real-time PCR. Neither of the viruses was found in samples from small-cell, non-small-cell (adenocarcinoma, squamous-cell carcinoma and large-cell neuroendocrine lung cancer), mixed-type and non-differentiated lung carcinoma, and non-cancerous lung tissues (from patients with pneumonia, emphysema and fibrosis).


The treatment of advanced cystadenocarcinoma of the ovary with gestronol and continuous oral cyclophosphamide.
Fifty-four patients with advanced cystadenocarcinoma of the ovary were treated with gestronol (Depostat), 200 mg/week, by intramuscular injection and continuous oral cyclophosphamide, the dose of the latter being varied to maintain the patient's white cell count at about 1.5 x 10(9)/l. A combined partial and complete remission rate of 76 per cent was obtained. The length of survival depended upon the type of remission and the type of remission was markedly affected by the amount of tumour removed at initial laparotomy.


The blood cells of the freshwater snail Planorbis corneus (Gastropoda, Pulmonata).
A study of the morphology and behaviour (cell adherence and spreading, in vitro phagocytosis and rosette formation) of blood cells of Planorbis corneus, revealed the presence of two cell types: the spreading haemocyte and the round haemocyte. Results obtained with vinblastine confirmed that these cell forms are distinct cell types and not different maturational stages of a single cell type.


Degeneration and the chemical composition of the human lumbar intervertebral disc.
Fifteen lumbar spines were collected postmortem. The intervertebral discs were assigned morphological grades and were analyzed for water, collagen, and proteoglycan. In order of increasing degeneration, five grade 0, four grade 1, 45 grade 2, 12 grade 3A, and nine grade 3B discs were identified. The proteoglycan concentration fell progressively with increasing grade, although the concentrations of each component overlapped extensively among the grades. Grade 2 discs showed no consistent differences from adjacent grade 3A or 3B discs in the same spine. All discs in seven of the eight spines with grade 3A or 3B discs and all discs in three spines with no grade 3A or 3B discs had proteoglycan concentrations below 52 mg/g fresh weight. Four of five spines with at least one disc of proteoglycan concentration above this value contained no grade 3A or 3B discs. These observations support the hypothesis that low proteoglycan concentrations in all the discs of a spine precede degeneration.


Loss of DNA copy number of 10q is associated with aggressive behavior of leiomyosarcomas: a comparative genomic hybridization study.
Leiomyosarcomas (LMS) account for 10-20% of all soft tissue sarcomas. We analyzed 10 primary, 5 metastatic, and 2 recurrent extrauterine LMS. Genomic imbalances were detected in 15 out of the 17 tumors. The most common regions of loss were 13q (59%, 10 of 17), 10q (59%, 10 of 17), 2q (35%, 6 of 17), and 16q (29%, 5 of 17). The most common region of gain was 5p (35%, 6 of 17). High-level gain of DNA copy number was detected in 6p and 17p. Loss of function of tumor suppressor genes or the activation of oncogenes (or both of these factors) resulting from these copy number changes might play an important role in the development of extrauterine LMS. Large tumors and tumors with metastasis showed 10q deletions. Gain of 5p was detected only in G3 tumors. These findings are consistent with our earlier study on uterine LMS and indicate that loss of 10q and gain of 5p are associated with an aggressive behavior of LMS. A larger series of cases is needed to confirm these results.


Effect of the preoperative assessment of the anteroposterior diameters of the spinal canal and dural area on the efficacy of oblique lumbar interbody fusion in patients with lumbar spinal stenosis.
The purpose of this study was to quantify the degree of lumbar spinal stenosis by assessing the anterior and posterior vertebral canal diameter and dural area, determine the sensitivity of the anterior and posterior spinal canal diameter, dural area and dural occupying rate in predicting the postoperative efficacy of oblique lumbar interbody fusion (OLIF) for patients with single-stage lumbar spinal stenosis, and identify the corresponding indicators suggesting that OLIF surgery should not be performed. In a retrospective analysis of patients who had previously undergone OLIF surgery in our hospital, we included a total of 104 patients with lumbar spinal stenosis who had previously undergone single-stage surgery in our hospital. Three independent observers were employed to measure the anterior and posterior diameter of the spinal canal (AD, mm), dural area (CSA, mm2), the spinal canal area (SCA, mm2), and the ratio of the dural area to the spinal canal area (DM, %) at the disc level with the most severe stenosis on MRI. According to the values of AD and CSA in preoperative MRI, patients were divided into three groups: A, B, and C (Group A: AD > 12 and 100 < CSA ≤ 130, group B: Except A and C, group C: AD ≤ 10 and CSA ≤ 75). Preoperative and postoperative clinical outcome scores (Japanese Orthopaedic Association [JOA] score, VAS score, modified Macnab standard) of 104 patients were statistically. There were significant differences in the preoperative and postoperative clinical correlation scores among the mild, moderate and severe lumbar spinal stenosis groups. The improvement rate of the post treatment JOA score, the difference between the preoperative and postoperative VAS score, and the modified Macnab standard were compared pairwise. There was no statistical significance in the improvement rate of the post treatment JOA score, the difference between the preoperative and postoperative VAS score, and the modified Macnab standard between Group A and Group B (P = 0.125, P = 0.620, P = 0.803). There were statistically significant differences between Group A and Group C and between Group B and Group C in the improvement rate of the JOA score, the difference in the pre- and postoperative VAS score, and the modified Macnab standard. The anterior and posterior vertebral canal diameter and dural area are sensitive predictors of the postoperative efficacy of OLIF surgery for single-stage lumbar spinal stenosis. Moreover, when the anterior and posterior vertebral canal diameter was less than 6.545 mm and the dural area was less than 34.43 mm2, the postoperative effect of OLIF surgery was poor. All the patients with mild, moderate, and severe lumbar spinal stenosis achieved curative effects after OLIF surgery. Patients with mild and moderate lumbar spinal stenosis had better curative effects, and there was no significant difference between them, while patients with severe lumbar spinal stenosis had poor curative effects. Both the anteroposterior diameter of the spinal canal and the dural area of the spinal canal were sensitive in predicting the curative effect of OLIF surgery for single-stage lumbar spinal stenosis. When the anterior and posterior vertebral canal diameter was less than 6.545 mm and the dural area was less than 34.43 mm2, the postoperative effect of OLIF surgery was poor.


Occipito-transtentorial approach for falcotentorial meningiomas: how I do it.
Falcotentorial meningiomas are rare tumors that arise at the junction of the dural folds of the tentorium and falx cerebri, at the junction of the vein of Galen with the straight sinus with possible extensions along the course of the straight sinus. Surgery of falcotentorial meningiomas remains challenging due to the intimate neurovascular relationships in the posterior incisural space. We describe the key steps of the occipito-transtentorial approach for falcotentorial meningiomas with a video illustration. The surgical anatomy is described along with the advantages and limitations of this approach. The occipito-transtentorial approach offers good surgical exposure and outcomes in carefully selected patients harboring falcotentorial meningiomas. Precise understanding of the relationship between the tumor and the internal cerebral veins, basal veins, and vein of Galen should be thoroughly analyzed as these structures may be infiltrated or displaced.


Extrapulmonary Surfactant Therapy: Review of Available Data and Research/Development Issues.
Since the discovery of surfactant, a large amount of knowledge has been accumulated about its biology and pharmacology. Surfactant is the cornerstone of neonatal respiratory critical care, but its proteins and phospholipids are produced in various tissues and organs, with possible roles only partially similar to that played in the alveoli. As surfactant research is focused mainly on its respiratory applications, knowledge about the possible role of surfactant in extrapulmonary disorders has never been summarized. Here we aim to comprehensively review the data about surfactant biology and pharmacology in organs other than the lung, especially focusing in the more promising surfactant extrapulmonary roles. We also review any preclinical or clinical data available about the therapeutic use of surfactant in these contexts. We offer a summary of knowledge and research/development milestones, as possible useful guidance for researchers of multidisciplinary background.


Evidence that 1 per cent Meshushit ointment prevents progressive dermal ischaemia of experimental deep partial skin thickness burns: a preliminary, quantitative controlled study.
This study quantitatively assessed the topical effects of Meshushit, a new herbal compound, on the healing process of experimental deep partial skin thickness burns over 27 days. To symmetrical circular burns were inflicted on the back of 15 animals by aluminium templates. The Meshushit and its control vehicle containing 0.1 per cent gentamycin or the control vehicle plus antibiotic alone, were applied topically to randomly selected burns at equal time intervals. Epithelialization and contraction were assessed on postburn days 6, 10, 15, 18, 22 and 27 using a computerized planimeter. The newly formed granulation tissue was assessed histologically on postburn day 27, while the hair follicles were counted in the same sections. Student's t test was used to differentiate the rates of contraction and epithelialization; hair follicle counts and the thickness of the newly formed granulation tissue. None of the animals died during the experiment. The epithelialization and contraction rates did not differ significantly between the test groups. The Meshushit-treated wounds showed a significantly thicker granulation tissue layer as compared to its control (828.72 +/- 46.39 microns vs. 540.78 +/- 37.81 microns, P less than 0.01). The count of hair follicles was significantly higher in the Meshushit-treated burns (23.38 +/- 1.84 vs. 3.76 +/- 0.35, P less than 0.001). It is concluded that the herbal Meshushit ointment enhanced the newly formed granulation tissue and preserved better the hair follicles in the present burn wound model. It is suggested that these findings are due to the preservation of the dermal microcirculation.


Acetalized starch-based nanoparticles stabilized acid-sensitive Pickering emulsion as a potential antitumor drug carrier.
Pickering emulsions are attracting increased attention owing to their therapeutic applications. However, the slow-release property of Pickering emulsions and the in vivo solid particle accumulation caused by the solid particle stabilizer film limit their applications in therapeutic delivery. In this study, drug-loaded, acid-sensitive Pickering emulsions were prepared using acetal-modified starch-based nanoparticles as stabilizers. The acetalized starch-based nanoparticles (Ace-SNPs) not only act as a solid-particle emulsifier to stabilize Pickering emulsions but also exhibit acid sensitivity and degradability, conducive to the destabilization of Pickering emulsions to release the drug and reduce the effect of particle accumulation in an acidic therapeutic environment. In vitro drug release profiles show that 50 % of curcumin was released in 12 h in an acidic medium (pH 5.4), whereas only 14 % of curcumin was released in 12 h at higher pH (7.4), indicating that the Ace-SNP stabilized Pickering emulsion possess good acid-responsive release characteristics in acidic environments. Moreover, acetalized starch-based nanoparticles and their degradation products showed good biocompatibility, and the resulting curcumin-loaded Pickering emulsions exhibited significant anticancer activity. These features suggest that the acetalized starch-based nanoparticle-stabilized Pickering emulsion has the potential for application as an antitumor drug carrier to enhance therapeutic effects.


Microbe-Responsive Proteomes During Plant-Microbe Interactions Between Rice Genotypes and the Multifunctional Methylobacterium oryzae CBMB20.
Rice is colonized by plant growth promoting bacteria such as Methylobacterium leading to mutually beneficial plant-microbe interactions. As modulators of the rice developmental process, Methylobacterium influences seed germination, growth, health, and development. However, little is known about the complex molecular responsive mechanisms modulating microbe-driven rice development. The application of proteomics to rice-microbe interactions helps us elucidate dynamic proteomic responses mediating this association. In this study, a total of 3908 proteins were detected across all treatments of which the non-inoculated IR29 and FL478 share up to 88% similar proteins. However, intrinsic differences appear in IR29 and FL478 as evident in the differentially abundant proteins (DAPs) and their associated gene ontology terms (GO). Successful colonization of M. oryzae CBMB20 in rice resulted to dynamic shifts in proteomes of both IR29 and FL478. The GO terms of DAPs for biological process in IR29 shifts in abundance from response to stimulus, cellular amino acid metabolic process, regulation of biological process and translation to cofactor metabolic process (6.31%), translation (5.41%) and photosynthesis (5.41%). FL478 showed a different shift from translation-related to response to stimulus (9%) and organic acid metabolic acid (8%). Both rice genotypes also showed a diversification of GO terms due to the inoculation of M. oryzae CBMB20. Specific proteins such as peptidyl-prolyl cis-trans isomerase (A2WJU9), thiamine thiazole synthase (A2YM28), and alanine-tRNA ligase (B8B4H5) upregulated in IR29 and FL478 indicate key mechanisms of M. oryzae CBMB20 mediated plant growth promotion in rice. Interaction of Methylobacterium oryzae CBMB20 to rice results in a dynamic, similar, and plant genotype-specific proteomic changes supporting associated growth and development. The multifaceted CBMB20 expands the gene ontology terms and increases the abundance of proteins associated with photosynthesis, diverse metabolic processes, protein synthesis and cell differentiation and fate potentially attributed to the growth and development of the host plant. The specific proteins and their functional relevance help us understand how CBMB20 mediate growth and development in their host under normal conditions and potentially link subsequent responses when the host plants are exposed to biotic and abiotic stresses.


Comparative polarized-light and electron microscopic studies of changes in the structure of the intercalate disc following various experimental lesions.
The intercalate disc was studied following various traumatizing interference (cyanide, carbon monoxide poisoning, intermittent coronary perfusion, nitrogen perfusion, intermittent hypoxic loading, direct electric trauma). The most frequent alterations were the separation, vesicular transformation and loss of electron-dense material of the fascia adherens and occludens of the junctions. In extreme situations the lysis of filaments joining to the junctions and the rupture of the membrane was observed. Total desintegration of the intercalate disc was rarely encountered probably due to the high adhesive capacity of desmosomes. Topooptical reactions were found suitable to detect functional changes.


IVIM DW-MRI of autoimmune pancreatitis: therapy monitoring and differentiation from pancreatic cancer.
To evaluate IVIM DW-MRI for changes in IVIM-derived parameters during steroid treatment of autoimmune pancreatitis (AIP) and for the differentiation from pancreatic cancer (PC). Fifteen AIP-patients, 11 healthy patients and 20 PC-patients were examined with DWI-MRI using eight b-values (50, 100, 150, 200, 300, 400, 600, 800). 12 AIP-patients underwent follow-up examinations during treatment. IVIM-parameters and ADC800-values were tested for significant differences and an ROC analysis was performed. The perfusion fraction f was significantly lower in patients with AIP at the time of diagnosis (10.5 ± 4.3 %) than in patients without AIP (20.7 ± 4.3 %). In AIP follow-up, f increased significantly to 17.1 ± 7.0 % in the first and 21.0 ± 4.1 % in the second follow up. In PC, the f-values were lower (8.2 ± 4.0 %, n.s.) compared to initial AIP and were significantly lower compared to first and second follow-up examination. In the ROC-analysis AUC-values for f were 0.63, 0.88 and 0.98 for differentiation of PC from initial, first and second follow up AIP-examination. The found differences in f between AIP, AIP during steroid treatment and pancreatic cancer suggest that IVIM-diffusion MRI could serve as imaging biomarker during treatment in AIP-patients and as a helpful tool for differentiation between PC and AIP. • MRI is used for follow-up examinations during therapy in AIP-patients • IVIM-DWI-MRI offers parameters which reflect perfusion and true diffusion • IVIM-parameters are helpful for differentiation between AIP and pancreatic cancer • IVIM-parameters could serve as an imaging biomarker during steroid treatment.


Hypoxia-mediated regulation of mitochondrial transcription factors in renal epithelial cells: implications for hypertensive renal physiology.
Kidneys have a high resting metabolic rate and low partial pressure of oxygen due to enhanced mitochondrial oxygen consumption and ATP production needed for active solute transport. Heightened mitochondrial activity leads to progressively increasing hypoxia from the renal cortex to the renal medulla. Renal hypoxia is prominent in hypertensive rats due to increased sodium reabsorption within the nephrons, which demands higher energy production by oxidative phosphorylation (OXPHOS). Consequently, spontaneously hypertensive rats (SHR) display greater oxygen deficiency (hypoxia) than normotensive Wistar Kyoto rats (WKY). Here, we sought to investigate the expression of key proteins for mitochondrial biogenesis in SHR and WKY, and study the regulation of mitochondrial transcription factors (mtTFs) under in vitro hypoxic conditions in renal epithelial cells. We report that renal expressions of hypoxia-inducible factor-1-alpha (HIF-1α), peroxisome proliferator-activated receptor-gamma coactivator-1-alpha (PGC-1α), mtTFs, and OXPHOS proteins are elevated in SHR compared to WKY. In addition, our experiments in cultured kidney cells demonstrate that acute hypoxia augments the expression of these genes. Furthermore, we show that the transcripts of HIF-1α and mtTFs are positively correlated in various human tissues. We reveal, for the first time to our knowledge, that HIF-1α transactivates mtTF genes by direct interaction with their promoters in rat kidney epithelial cells (NRK-52E) under acute hypoxia. Concomitant increases in the mitochondrial DNA and RNA, and OXPHOS proteins are observed. Taken together, this study suggests that hypoxia within the renal epithelial cells may enhance mitochondrial function to meet the energy demand in proximal tubular cells during prehypertensive stages in kidneys of young SHR.


OCA7 is a melanosome membrane protein that defines pigmentation by regulating early stages of melanosome biogenesis.
Mutations in C10orf11 (oculocutaneous albinism type 7 [OCA7]) cause OCA, a disorder that presents with hypopigmentation in skin, eyes, and hair. The OCA7 pathophysiology is unknown, and there is virtually no information on the OCA7 protein and its cellular function. Here, we discover that OCA7 localizes to the limiting membrane of melanosomes, the specialized pigment cell organelles where melanin is synthesized. We demonstrate that OCA7 is recruited through interaction with a canonical effector-binding surface of melanosome proteins Rab32 and Rab38. Using newly generated OCA7-KO MNT1 cells, we show OCA7 regulates overall melanin levels in a melanocyte autonomous manner by controlling melanosome maturation. Importantly, we found that OCA7 regulates premelanosome protein (PMEL) processing, impacting fibrillation and the striations that define transition from melanosome stage I to stage II. Furthermore, the melanosome lumen of OCA7-KO cells displays lower pH than control cells. Together, our results reveal that OCA7 regulates pigmentation through two well-established determinants of melanosome biogenesis and function, PMEL processing, and organelle pH.


Multimodality assessments of wild-type transthyretin cardiac amyloidosis with no ventricular hypertrophy.
While patients with transthyretin cardiac amyloidosis (ATTR-CA) typically present with concentric or asymmetric hypertrophy, a small percentage of ATTR-CA is known to present with 'atypical' cardiac morphologies such as eccentric hypertrophy or even no hypertrophy. However, detailed report of multimodality assessments of ATTR-CA with no ventricular hypertrophy is lacking. Herein, we report detailed multimodality assessments of an 81-year-old Japanese woman with heart failure and history of carpal tunnel syndrome and lumbar canal stenosis, presenting no ventricular hypertrophy and negative 99m technetium-pyrophosphate scintigraphy, who was eventually diagnosed as having wild-type ATTR-CA. Our case highlights the role of multimodality assessments for early diagnosis of ATTR-CA in patients with atypical cardiac morphologies and also emphasizes the limitations of bone scintigraphy and the importance of considering ATTR-CA in patients with non-cardiac manifestations of ATTR amyloidosis.


Effect of pH on xylitol production by Candida species from a prairie cordgrass hydrolysate.
Using hydrolysates of the North American prairie grass prairie cordgrass buffered at pH 4.5, 5.0, 5.5 or 6.0, xylitol production, xylitol yield, cell biomass production and productivity were investigated for three strains of yeast Candida. Of the three strains, the highest xylitol concentration of 20.19 g xylitol (g xylose consumed)-1 and yield of 0.89 g xylitol (g xylose consumed)-1 were produced by Candida mogi ATCC 18364 when grown for 120 h at 30° C on the pH 5.5-buffered hydrolysate-containing medium. The highest biomass level being 7.7 g cells (kg biomass)-1 was observed to be synthesized by Candida guilliermondii ATCC 201935 after 120 h of growth at 30° C on a pH 5.5-buffered hydrolysate-containing medium. The highest xylitol specific productivity of 0.73 g xylitol (g cells h)-1 was determined for C. guilliermondii ATCC 20216 after 120 h of growth at 30°C on a pH 5.0-buffered hydrolysate-containing medium. Xylitol production and yield by the three Candida strains was higher on prairie cordgrass than what was previously observed for the same strains after 120 h at 30° C when another North American prairie grass big bluestem served as the plant biomass hydrolysate indicating that prairie cordgrass may be a superior plant biomass substrate.


[Effect of yin zhi huang on bilirubin excretion in animals with unconjugated hyperbilirubinemia].
Yin Zhi Huang (YZH) given stomach perfusion daily for three days in rabbits accelerated plasma clearance of infused unconjugated bilirubin. A similar but less dramatic effect could be obtained by using YZH or phenobarbital i. p. daily for three days in rats employing simultaneously with the method of bile duct ligation, plasma indirect bilirubin levels was lower but hepatic bilirubin content and plasma direct bilirubin levels were higher in both YZH and phenobarbital treated rats than those in the control animals. These observations suggested that YZH and phenobarbital shared a common mechanism of acting in lowering the indirect bilirubin levels of serum.


Genetic diversity and origin of Chinese cattle revealed by mtDNA D-loop sequence variation.
To determine the origin and genetic diversity of Chinese cattle, we analyzed the complete mtDNA D-loop sequences of 84 cattle from 14 breeds/populations from southwest and west China, together with the available cattle sequences in GenBank. Our results showed that the Chinese cattle samples converged into two main groups, which correspond to the two species Bos taurus and Bos indicus. Although a dominant lineage was clearly discerned in both B. taurus and B. indicus mtDNAs, network analysis of the lineages in each of the two species further revealed multiple clades that presented regional difference. The B. taurus samples in China could be grouped into clades T2, T3, and T4, whereas B. indicus harbored two clades I1 and I2. Age estimation of these discerned clades showed a time range of 14,100-44,500 years before present (YBP). The phylogenetic pattern of Chinese cattle was consistent with the recently described cattle matrilineal pool from northeast Asia, but suggested that B. indicus contributed more to the cattle from south and southwest China. The genetic diversity of Chinese cattle varied among the breeds studied.


Microbial diversity response in thallium polluted riverbank soils of the Lanmuchang.
Thallium (Tl) is a toxic element, but little is known about microbial communities' response to TI mobilization and sequestration. Here, we characterize the microbial communities and their feedbacks to Tl-pollution in riverbank soils to understand the distribution of microbial metal tolerance. These soils have been affected by pollution sourced from a Tl-rich mineralized area in Lanmuchang, Guizhou, China. In all studied soil samples, Proteobacteria, Acidobacteria, and Actinobacteria were revealed relatively in higher abundance at the phylum level. The results indicated that a number of microbial communities including Gemmatimonadetes, and Actinobacteria were correlated with total Tl, suggesting potential roles of these microbes to Tl tolerance. The patterns of phylogenetic beta-diversity in studied samples showed a high diversity of the microbial community in soils with high Tl concentrations. Sequence analysis of microbial community indicated that most of the environmental parameters in soils were associated with the major phylogenetic groups such as Gemmobacteria, Bryobacteria, Proteobacteria, Actinobacteria, Firmicutes, and Rhodobacteria. Some species of microbes, Nocardioides (genus), Actinomycetales (Order), Ralstonia (phyla) and Sphingomonas (genus) might are tolerant of Tl. These results provide direction to the microbial communities in the presence of elevated Tl concentration in Lanmuchang and shed light on bioremediation of Tl polluted locations.


A de novo splice site mutation in EHMT1 resulting in Kleefstra syndrome with pharmacogenomics screening and behavior therapy for regressive behaviors.
Kleefstra syndrome (KS) is a rare autosomal dominant developmental disability, caused by microdeletions or intragenic mutations within the epigenetic regulator gene EHMT1 (euchromatic histone lysine N-methyltransferase 1). In addition to common features of autism, young adult regressive behaviors have been reported. However, the genetic downstream effects of the reported deletions or mutations on KS phenotype have not yet been completely explored. While genetic backgrounds affecting drug metabolism can have a profound effect on therapeutic interventions, pharmacogenomic variations are seldom considered in directing psychotropic therapies. In this report, we used next-generation sequencing (exome sequencing and high-throughput RNA sequencing) in a patient and his parents to identify causative genetic variants followed by pharmacogenomics-guided clinical decision-making for making positive changes toward his treatment strategies. The patient had an early autism diagnosis and showed significant regressive behaviors and physical aberrations at age 23. Exome sequencing identified a novel, de novo splice site variant NM_024757.4: c.2750-1G>T in EHMT1, a candidate gene for Kleefstra syndrome, in the patient that results in exon skipping and downstream frameshift and termination. Gene expression results from the patient showed, when compared to his parents, there was a significant decreased expression of several reported gene variants associated with autism risk. Further, using a pharmacogenomics genotyping panel, we discovered that the patient had the CYP2D6 nonfunctioning variant genotype *4/*4 that results in very low metabolic activity on a number of psychotropic drugs, including fluvoxamine which he was prescribed. As reported here, a change in psychotropic drugs and intense behavior therapies resulted in a significant reversal of the regressive behaviors and physical aberrations. These results demonstrate an individualized approach that integrated genetic information and behavior therapies, resulting in a dramatic improvement in regressive behaviors associated with KS.


Mycobacterial MCE proteins as transporters that control lipid homeostasis of the cell wall.
Mammalian cell entry (mce) genes are not only present in genomes of pathogenic mycobacteria, including Mycobacterium tuberculosis (the causative agent of tuberculosis), but also in saprophytic and opportunistic mycobacterial species. MCE are conserved cell-wall proteins encoded by mce operons, which maintain an identical structure in all mycobacteria: two yrbE genes (A and B) followed by six mce genes (A, B, C, D, E and F). Although these proteins are known to participate in the virulence of pathogenic mycobacteria, the presence of the operons in nonpathogenic mycobacteria and other bacteria indicates that they play another role apart from host cell invasion. In this respect, more recent studies suggest that they are functionally similar to ABC transporters and form part of lipid transporters in Actinobacteria. To date, most reviews on mce operons in the literature discuss their role in virulence. However, according to data from transcriptional studies, mce genes, particularly the mce1 and mce4 operons, modify their expression according to the carbon source and upon hypoxia, starvation, surface stress and oxidative stress; which suggests a role of MCE proteins in the response of Mycobacteria to external stressors. In addition to these data, this review also summarizes the studies demonstrating the role of MCE proteins as lipid transporters as well as the relevance of their transport function in the interaction of pathogenic Mycobacteria with the hosts. Altogether, the evidence to date would indicate that MCE proteins participate in the response to the stress conditions that mycobacteria encounter during infection, by participating in the cell wall remodelling and possibly contributing to lipid homeostasis.


Delayed retroperitoneal arterial hemorrhage after inferior vena cava (IVC) filter insertion: case report and literature review of caval perforations by IVC filters.
Transvenous placement of inferior vena cava (IVC) filters has become commonplace in selected patients with deep venous thrombosis (DVT) and pulmonary embolism (PE). IVC filters have been shown to have excellent therapeutic efficacy and low complication rates. Penetration of the IVC by filter hooks or struts has been reported and commonly noted to be inconsequential. We report a laceration of a lumbar artery by a stainless steel Greenfield (SSG) filter strut that resulted in a near fatal hemorrhage, and review the world literature on caval perforation by IVC filters.


Corticospinal involvement in patients with a portosystemic shunt due to liver cirrhosis: a MEP study.
Hepatic myelopathy (HM) is a rare complication of chronic liver diseases usually associated with a portosystemic shunt, causing a progressive spastic paraparesis, and is likely to be overlooked. Thirteen patients with liver cirrhosis associated with surgical or spontaneous portosystemic shunts were studied to determine the frequency and gravity of HM. Six patients exhibited clear-cut signs of spinal cord involvement and four of them exhibited varying degrees of disability. Neurological examination did not reveal any abnormalities in the other patients. Motor evoked potentials (MEPs) were measured in all patients; in five of them the examinations were done before and after orthotopic liver transplantation (OLT). The patients with clinical signs of spinal cord involvement exhibited severe neurophysiological abnormalities, whereas milder but unequivocal MEP abnormalities were found in four of the seven patients with normal clinical examination. The clinical and neurophysiological features of patients with slight MEP abnormalities improved after OLT, whereas the patients with a more advanced stage of disease (severe MEPs abnormalities) did not. Our findings indicate that MEP studies may disclose an impairment of the corticospinal pathways even before HM is clinically manifest and provide evidence that early diagnosis of HM and subsequent immediate liver transplantation have to be recommended.


Endometrial cancer.
Endometrial cancer is the most common gynaecological cancer in high income countries and its incidence is rising globally. Although an ageing population and fewer benign hysterectomies have contributed to this trend, the growing prevalence of obesity is the major underlying cause. Obesity poses challenges for diagnosis and treatment and more research is needed to offer primary prevention to high-risk women and to optimise endometrial cancer survivorship. Early presentation with postmenopausal bleeding ensures most endometrial cancers are cured by hysterectomy but those with advanced disease have a poor prognosis. Minimally invasive surgical staging and sentinel-lymph-node biopsy provides a low morbidity alternative to historical surgical management without compromising oncological outcomes. Adjuvant radiotherapy reduces loco-regional recurrence in intermediate-risk and high-risk cases. Advances in our understanding of the molecular biology of endometrial cancer have paved the way for targeted chemotherapeutic strategies, and clinical trials will establish their benefit in adjuvant, advanced, and recurrent disease settings in the coming years.


Predator identity dominates non-consumptive effects in a disease-impacted rocky shore food web.
Predicting the effects of predator diversity loss on food webs is challenging, because predators can both consume and induce behavioral responses in their prey (i.e., non-consumptive effects or NCEs). Studies manipulating predator diversity and investigating NCEs are rare, especially in marine systems. Recently, a severe outbreak of sea star wasting syndrome (SSWS) on the west coast of North America resulted in unprecedented declines of the sea star Pisaster ochraceus. We investigated the consequences of Pisaster loss on an abundant grazer, the black turban snail Tegula funebralis, through NCEs. We combined a laboratory experiment and field surveys to examine the importance of identity vs. diversity in a predator assemblage (Pisaster, crabs, and octopuses) on Tegula behavior, feeding, and growth. Laboratory and field results indicated that predator identity, not diversity, drives Tegula behavior and causes NCEs. Mesocosm treatments with Pisaster caused greater NCEs on Tegula than assemblages without Pisaster. Tegula's distribution in the field, which is driven primarily by anti-predator behavior, was strongly associated only with Pisaster abundance, and not with the abundance of crabs, octopuses, and other predatory sea stars (Leptasterias spp.). We conclude that Pisaster primarily drives Tegula vertical distribution and may be having strong NCEs on Tegula on northern California rocky shores. Furthermore, predator diversity in northern California does not provide functional redundancy, in terms of NCEs on Tegula, to buffer the system from Pisaster loss. Thus, predator-induced vertical distributions and grazing suppression may not be maintained in areas where Pisaster populations are reduced or slow to recover from SSWS.


Clinical and ultrasonography follow-up of five cases of calcinosis cutis successfully treated with intralesional sodium thiosulfate.
Calcinosis cutis (CC) is characterized by deposit of calcium salts in the skin and subcutaneous tissue; its clinical presentation consists of indurated painful nodules, which can ulcerate and become superinfected. CC treatment remains a challenge, yet successful treatment with intralesional (IL) sodium thiosulfate (STS) has been reported in several CC subtypes. Herein we are reporting on a case series of 5 patients with CC successfully treated with IL-STS. We describe the 18-22 MHz ultrasound characteristics of the lesions and on follow-up after treatment. Ultrasound imaging was useful in guiding IL-STS injections and confirming response to treatment.


Further evidence for calcium permeability of non-NMDA receptor channels in hippocampal neurons.
We have previously suggested that kainic acid (KA) increases the fluorescence of a fluoroprobe for Ca2+ via activation of the non-NMDA (N-methyl-D-aspartic acid) receptor in cultured hippocampal cells. The present study provides further evidence to support this suggestion. KA and NMDA increased the fluorescence occasionally in different subcellular loci of a single cell for each agonist, excluding the possibility that KA activated the NMDA receptor. KA elevated fluorescence in the cell whose membrane was voltage-clamped, thus eliminating possible Ca2+ entry through voltage-dependent channels. A monophasic response to KA was found to occur in the cells identified immunochemically as neurons. Even when the cells were cultured at different embryonic stages, KA responsiveness reached a peak at a rather fixed timepoint through the total age of neurons, while NMDA responsiveness continued to increase. This suggests that the Ca(2+)-permeable non-NMDA receptor is expressed according to a genetic schedule, but not to an artifactual effect of cell culture.


Protective effect of leg fat against cardiovascular risk factors in obese premenopausal women.
While the relationship between abdominal fat and cardiovascular risk (CVR) factors is well established, the possible protective role of peripheral fat against these factors has received less attention, particularly in severely obese individuals. The principal aim of this study was to analyse the relationship, if any, among amount of leg fat, CVR factors and body mass index (BMI) in obese premenopausal women. Subjects were 80 obese premenopausal women. Body composition was measured by dual energy X-ray absorptiometry (DEXA); CVR factors (blood pressure, plasma lipids, glucose) were determined and anthropometric measurements (waist and hip circumferences) taken. In severely obese women (BMI>40 kg/m(2)) leg fat correlated negatively with CVR factors, whereas metabolic parameters were not significantly different from those of subjects with BMI<40 kg/m(2). Leg fat seems to play a protective role against CVR factors in severely obese premenopausal women.


Liquid platelet-rich fibrin promotes the regenerative potential of human periodontal ligament cells.
To compare the biological effect of PRP and liquid-PRF on human periodontal ligament cells (hPDLCs) in vitro. The liquid-PRF was processed with centrifugation at 700 g for 3 min, and PRP was processed according to Curasan's protocol. Migration and proliferation assay were performed by a scratch/Transwell assay and a CCK-8 assay, respectively. To investigate hPDLC differentiation, alkaline phosphatase (ALP) assay, Alizarin Red S staining, and gene expression level detection of Runx2, Col1a1, and OCN were conducted. Furthermore, cells cultured with lipopolysaccharide (LPS) to induce an inflammation condition were utilized to investigate the impact of liquid-PRF on inflammatory resolution. Either PRP or liquid-PRF can promote proliferation, migration of hPDLCs, and osteogenic differentiation of hPDLCs. It was noteworthy that liquid-PRF demonstrated a significantly higher ability to promote the biological differentiation and mineralization of hPDLCs compared with PRP. Lastly, when hPDLCs were incubated with LPS, cells cultured with liquid-PRF showed significantly lower mRNA expression levels of inflammatory genes. Liquid-PRF notably promoted hPDLC activity and attenuated the inflammatory state induced by LPS.


Sequence of the neuraminidase gene of influenza virus A/Tokyo/3/67 and previously uncharacterized monoclonal variants.
A full-length cDNA copy of the neuraminidase (NA) gene of influenza strain A/Tokyo/3/67 was cloned into the plasmid pBR322, and the nucleotide sequence of the gene was determined. In addition, the sequence changes in six variants of A/Tokyo/3/67 selected with various monoclonal antibodies (Ab) to the NA were determined by dideoxy sequencing of the vRNA. In five of the monoclonal variants, a single change occurred, resulting in an amino acid substitution at residue 344. Arginine in the parent virus changed to every amino acid possible with a single nucleotide change. In another variant, arginine at position 253 changed to serine, a change that also occurred in field strains. All variants so far sequenced that were selected by monoclonal Ab to A/Tokyo/3/67 virus changed at position 344, except one which changed at residue 368. Both of these positions are in clusters of residues that vary considerably in field strains, the clusters being 344-347 and 368-370. Analysis of the three-dimensional crystal structure of the NA of A/Tokyo/3/67 shows that these clusters are directly adjacent on the protein, and likely comprise a single antigenic site. A total of three or four antigenic sites have been proposed for the NA protein, based on antigenic mapping with monoclonal Ab [R. G. Webster, V. S. Hinshaw , and W. G. Laver (1982) Virology 117, 93-104]. Variants selected by Ab to Tokyo/67 NA all change in this single antigenic site, whereas variants selected by Ab to other strains change in other regions. It is possible that, although there may be three or four antigenic sites on the NA molecule, there may be a single, dominant antigenic site for each strain.


Epidemiology chapter.
This chapter outlines the epidemiology of brucellosis in the Russian Federation and in five countries bordering Russia. Since the Soviet Union's dissolution, Russia and the newly formed independent republics have failed to maintain policies to control brucellosis and other zoonotic diseases. Many of these republics, due to weak animal control and prevention systems and dangerous food preparation practices, are still burdened with the human cost of brucellosis. The final summary of this section provides an example of the successful transboundary cooperative efforts between Arizona and Mexico, which could be applied to the situation between Russia and the bordering independent republics.


New methods for the synthesis of N-benzoylated uridine and thymidine derivatives; a convenient method for N-debenzoylation.
An improved procedure for the synthesis of N-benzoyl-2',3'-O-isopropylidene uridine via one-step selective N-benzoylation of 2',3' -O-isopropylidene uridine has been developed. An efficient synthetic route to N-benzoyl thymidine via initial tribenzoylation, followed by selective hydrolysis of the benzoates is also described. De-N-benzoylation of N-benzoylated thymidine and uridine derivatives can be conveniently effected under neutral conditions, by heating with benzyl alcohol.


Reduction of cocaine place preference in mice lacking the protein phosphatase 1 inhibitors DARPP 32 or Inhibitor 1.
Modulation of protein phosphorylation by dopamine is thought to play an important role in drug reward. Protein phosphatase-1 (PP-1) is known to mediate some of the changes in neuronal signaling that occur following activation of the dopaminergic system. Two endogenous inhibitors of PP-1 are dopamine and cyclic 3', 5' adenosine monophosphate-regulated phosphoprotein (DARPP-32) and Inhibitor-1 (I-1). Knockout mice lacking one or both of these PP-1 inhibitors were tested for responses to cocaine using in vivo amperometry and conditioned place preference. Presynaptic dopaminergic function appears to be unaffected by these mutations because stimulation-evoked changes in extracellular dopamine levels were unchanged between wild type mice and mice lacking one or both of these PP-1 inhibitors. In contrast, conditioned place preference to cocaine is reduced in mice lacking DARPP-32, I-1, or both phosphoproteins. This does not appear to be due to a learning deficit because mice lacking both DARPP-32 and I-1 show normal passive avoidance learning. These data imply that increased PP-1 function as a result of deficits in DARPP-32 or I-1 is sufficient to decrease the rewarding properties of cocaine. Furthermore, the mechanism for this altered cocaine place preference does not involve alteration of dopamine release or reuptake.


Carboxypeptidase-B-like processing of the C-terminus of glucagon-like peptide-2 in pig and human small intestine.
We developed specific, C-terminal radioimmunoassays for three proglucagon (PG) fragments: PG 151-158, PG 151-160 and PG 126-159 (glucagon-like peptide-2 (GLP-2] in order to determine the exact C-terminal sequence of the newly isolated GLP-2 in man and pig. The antigens and the antisera showed no mutual cross-reactivity. By gel filtration of extracts of pig and human small intestine, the immunoreactivity eluting at the position of GLP-2 was identified by the radioimmunoassays for glucagon-like peptide-2 (PG 126-159) and for PG 151-158, whereas the assay for PG 151-160 was completely negative. We conclude that the C-terminal amino acid residue of pig and human ileal GLP-2 is PG 158. Thus the basic residues, PG 159 and 160 are removed during its processing in the small intestine.


Hookworms of dogs and cats.
Hookworms are probably the most faithful intestinal parasites of dogs and cats. Infecting all ages, they are life-threatening to the very young and potentially so to the fully mature hookworm-resistant host. Discussed in this article are the diagnosis of hookworm infection, the life cycle of hookworms, the cutaneous and intestinal manifestations of hookworm infection and disease, and the treatment and prevention of infection.


Pediatric nonalcoholic fatty liver disease: a multidisciplinary approach.
Nonalcoholic fatty liver disease (NAFLD) is a multifactorial condition, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with or without fibrosis. NAFLD affects both adults and children who present with particular risk factors, including obesity, sedentary lifestyle and/or a predisposing genetic background. The escalation of the prevalence of NAFLD in children worldwide is a worrying phenomenon because this disease is closely associated with the development of both cirrhosis and cardiometabolic syndrome in adulthood. The etiopathogenesis of primary NAFLD in children is unknown; however, considerable knowledge about the mechanisms of liver damage that occur during disease progression has been gathered over the past 30 years. Understanding the pathogenetic mechanisms, together with the histological pattern, provide the basis to characterize potential early predictors of the disease, suitable noninvasive diagnostic tools and design novel specific treatments and possible management strategies. Despite a few clinical trials on the use of antioxidants combined with lifestyle intervention for NAFLD that showed encouraging results, to date, no treatment guidelines exist for children with NAFLD. In this Review, we provide an overview of current concepts in epidemiology, histological features, etiopathogenesis, diagnosis and treatment of NAFLD in children and adolescents.


Comparison of different software implementations for spatial disease mapping.
Disease mapping is a scientific field that aims to understand and predict disease risk based on counts of observed cases within small regions of a study area of interest. Hierarchical model-based approaches that borrow information from neighbouring areas via conditional autoregressive (CAR) random effects on the local disease rates have gained a lot of popularity, thanks to the readily implemented Markov chain Monte Carlo methods. Nowadays, many software implementations to model risk distributions exist. Many of these applications differ, to varying degrees, in the underlying methodology. This paper provides an in-depth comparison between analysis results, coming from R-packages CARBayes, R2OpenBUGS, NIMBLE, R2BayesX, R-INLA, and RStan. We investigate CAR models typically used in disease mapping for spatially discrete count data. Data about diabetics in children and young adults in Belgium are used in a case study, while simulation studies are undertaken to assess software performance in different settings.


Lesions of the anterior temporal stem and the performance of delayed match-to-sample and visual discriminations in monkeys.
Resection of the medial temporal lobes in humans produces an anterograde amnesia in which past memories are seemingly intact, but the ability to form new memories is compromised. Efforts to reproduce these symptoms in animals have relied extensively on the delayed non-match-to-sample (DNMS) and the delayed match-to-sample (DMS) tasks. DNMS deficits have been found with combined damage to the amygdala and hippocampus, but not to the adjacent white matter (the temporal stem) that connects the temporal cortex to other brain areas. DMS deficits are, however, produced by lesions to either the anteroventral temporal cortex or the orbital frontal cortex. These two areas are interconnected through the anterior temporal stem. The present study examined the hypothesis that an anterior temporal stem lesion would impair DMS in monkeys. The anterior extreme of the temporal stem was transected in 4 Macaca fascicularis and resulted in a powerful deficit on DMS at all delays. Postoperative retention of preoperatively learned visual discriminations and postoperative learning of new visual discriminations were not reliably impaired.


Atomic-level description of protein-lipid interactions using an accelerated membrane model.
Peripheral membrane proteins are structurally diverse proteins that are involved in fundamental cellular processes. Their activity of these proteins is frequently modulated through their interaction with cellular membranes, and as a result techniques to study the interfacial interaction between peripheral proteins and the membrane are in high demand. Due to the fluid nature of the membrane and the reversibility of protein-membrane interactions, the experimental study of these systems remains a challenging task. Molecular dynamics simulations offer a suitable approach to study protein-lipid interactions; however, the slow dynamics of the lipids often prevents sufficient sampling of specific membrane-protein interactions in atomistic simulations. To increase lipid dynamics while preserving the atomistic detail of protein-lipid interactions, in the highly mobile membrane-mimetic (HMMM) model the membrane core is replaced by an organic solvent, while short-tailed lipids provide a nearly complete representation of natural lipids at the organic solvent/water interface. Here, we present a brief introduction and a summary of recent applications of the HMMM to study different membrane proteins, complementing the experimental characterization of the presented systems, and we offer a perspective of future applications of the HMMM to study other classes of membrane proteins. This article is part of a Special Issue entitled: Membrane proteins edited by J.C. Gumbart and Sergei Noskov.


Assessment of the abuse potential of acetorphan, an enkephalinase inhibitor.
The discriminative stimulus properties, reinforcing effects and physical dependence potential of acetorphan, a parenterally-active enkephalinase (E.C. 126.96.36.199) inhibitor, were assessed in the present studies. Rats trained to discriminate 2 mg/kg morphine from saline did not generalize to acetorphan at any dose tested (5-50 mg/kg). Acetorphan also had minimal reinforcing effects in rhesus monkeys. When acetorphan was substituted for cocaine, one dose (300 micrograms/kg per inj.) maintained responding somewhat above the range of vehicle values in only two of the four monkeys tested. In physical dependence studies, acetorphan also failed to produce opioid-like effects. In morphine-dependent monkeys and rats, acetorphan failed to suppress withdrawal. Additionally, there were no overt withdrawal signs observed following the termination of chronic acetorphan infusion in the rat. Together, these results indicate that acetorphan appears to have minimal abuse potential.


Prenatal exposure to passive smoking and duration of breastfeeding in nonsmoking women: Krakow inner city prospective cohort study.
The relationship between tobacco smoking in pregnancy and breastfeeding is of public health importance. The present birth cohort study provided the opportunity to investigate whether the negative relationship between passive smoking measured by the cotinine concentrations in maternal blood at delivery and breastfeeding in postpartum could also be confirmed in nonsmoking mothers. The study sample included 441 healthy pregnant women who were recruited in the first and second trimester of pregnancy. Enrollment included only nonsmoking women of the age of 18-35 years with singleton pregnancies, without illicit drug use and free from chronic diseases. After delivery, breastfeeding duration was defined using the answers recorded in the interviews with mothers conducted every 3 months. An infant was considered to be fully breastfed when breast milk was the only source of nourishment. Any breastfeeding was defined as an infant's being fully breastfed or receiving both breast milk and formula, with or without solids. In the statistical analysis only total duration of breastfeeding up to 6 months was considered for both forms of breastfeeding. Subjects were categorized into environmental tobacco smoke (ETS) exposure groups according to maternal blood cotinine level at delivery or self-reported exposure to ETS during pregnancy. The adjusted relative risk of discontinuation of any breastfeeding after infant's first 6 months was more than two times higher (OR = 2.42; 95% CI: 1.42-4.14) in women whose blood cotinine level at delivery was above 75th percentile of cotinine distribution (>0.15 ng/mL); the corresponding risk of discontinuation of full breastfeeding was OR = 1.71; 95% CI: 1.03-2.82. Estimated relative risk of discontinuation of any breastfeeding based on self-reported ETS was also significant but much less marked; the corresponding risk of discontinuation of full breastfeeding was insignificant. The results obtained support the hypothesis that ETS may affect breastfeeding duration and support the avoidance of passive smoking as a necessary additional measure for breastfeeding promotion.


Endoscopic management of gastrojejunocolic fistula after endoscopic gastrojejunostomy.
Video 1Endoscopic repair of gatstrojejunocolic fistala using tandem stent placement with a long covered metal stent.


Nerve fibre morphometry: a comparison of techniques.
This study compared different approaches to measuring nerve axon and fibre diameters and areas from transverse sections. A mock photomicrograph and mock tissue section, each with 100 identical, circular 'fibres' was constructed. Three measurement protocols were investigated: (A) circular approximation from minimum diameter; (B) circular approximation from the mean of orthogonal diameters; and (C) calculation of diameter and area from a digitized circumference. For each protocol, all 100 fibres on the photomicrograph were repeatedly measured using a digitizing tablet. Similarly, the fibres on the mock tissue section were measured using a digitizing tablet and microscope with camera lucida. The variance for these data was calculated. Protocols were compared on the basis of variability and the amount of digitizing time required. For diameter measurements, protocol B showed significantly lower variability than A or C (P less than 0.05), with only a modest increase in digitizing time over A. For area measurements, protocols B and C showed significantly lower variability than A (P less than 0.05), again with a modest increase in digitizing time. Measurements made using the microscope and camera lucida showed significantly lower variability than those made from the photomicrograph, but took more time. These data suggest that for diameter measurements, a mean of orthogonal diameters approach is best, and that for area measurements, a traced circumference approach is best as it is more flexible than the orthogonal diameter approach. While the microscope and camera lucida setup is more time-consuming to use, it eliminates the need for photomicrograph production.


Economic development and multiple air pollutant emissions from the industrial sector.
This study analyzed the relationship between economic growth and emissions of eight environmental air pollutants (carbon dioxide (CO2), methane (CH4), nitrous oxide (N2O), nitrogen oxide (NOx), sulfur oxide (SOx), carbon monoxide (CO), non-methane volatile organic compound (NMVOC), and ammonia (NH3)) in 39 countries from 1995 to 2009. We tested an environmental Kuznets curve (EKC) hypothesis for 16 individual industry sectors and for the total industrial sector. The results clarified that at least ten individual industries do not have an EKC relationship in eight air pollutants even though this relationship was observed in the country and total industrial sector level data. We found that the key industries that dictated the EKC relationship in the country and the total industrial sector existed in CO2, N2O, CO, and NMVOC emissions. Finally, the EKC turning point and the relationship between economic development and trends of air pollutant emissions differ among industries according to the pollution substances. These results suggest inducing new environmental policy design such as the sectoral crediting mechanism, which focuses on the industrial characteristics of emissions.


Exaggerated systolic blood pressure response to exercise: a normal variant or a hyperdynamic phase of essential hypertension?
This study examines the left ventricular function (by first-pass radionuclide angiography with a multicrystal gamma camera) at rest and during symptom-limited upright exercise in 27 normal subjects (group 1), 25 normotensive subjects with exaggerated systolic blood pressure response to exercise (greater than 200 mm Hg) (group 2) and 25 patients with essential hypertension and no associated coronary artery disease (group 3). There were no significant differences between groups 1 and 2 in exercise tolerance, heart rate, total vascular resistance, left ventricular ejection fraction and end-systolic volume. However, the exercise cardiac index and systolic blood pressure were significantly higher in group 2 (P less than 0.02). Compared to group 3, the subjects in group 2 had higher exercise heart rate (P less than 0.0001), cardiac index (P less than 0.0001), systolic blood pressure (P less than 0.0001) and left ventricular ejection fraction (P less than 0.0001) and lower exercise total vascular resistance (P less than 0.0002) and end-systolic volume (P less than 0.01). Thus, the hemodynamic profile in subjects with exaggerated systolic blood pressure response to exercise differs from that of essential hypertension; it may represent a supernormal response.


Multifocal Inflammatory Pseudotumor of the Temporal Bone, Maxillary Sinus, and Orbit.
This is the first report of multifocal inflammatory pseudotumor (IPT) involving the temporal bone, orbit and paranasal sinus, and the use of rituximab as adjunctive therapy in multifocal temporal bone IPT. We describe a 46-year-old man with orbital and maxillary sinus IPT, whose disease progressed despite radiation and steroid burst. He then developed contralateral mastoid disease, otalgia, aural fullness, and hearing loss. He was initiated on rituximab and prednisone therapy. Mastoidectomy with near-total tumor removal was accomplished and histopathology confirmed IPT. A literature review was also performed. Tumor regression or recurrence. Despite disease progression after radiation and steroids, his orbital, sinus, and mastoid disease improved after surgery, steroids, and rituximab. A review of four other previously reported cases of multifocal disease involving the temporal bone suggest that multifocal disease may be a more aggressive entity with higher recurrence rate compared with solitary disease. Although surgery and steroids are typically recommended, there is currently no consensus treatment recommendation. Multifocal IPT of the temporal bone is a rare but aggressive entity for which surgery and steroid combination therapy should be first line treatment. We suggest rituximab may be an effective adjunctive treatment particularly for recurrent disease or where systemic therapy may be favored.


The physiology of ex vitro pineapple (Ananas comosus L. Merr. var MD-2) as CAM or C3 is regulated by the environmental conditions: proteomic and transcriptomic profiles.
Proteomic and transcriptomic profiles of key enzymes were monitored in pineapple plants propagated under C3 and CAM-inducing metabolisms to obtain insight into the CAM-facultative metabolism and the relationship of CAM plants with oxidative stress. Pineapple is one of the most important tropical crops worldwide. The use of temporary immersion bioreactors for the first stages of pineapple propagation enables precise control of plant growth, increases the rate of plant multiplication, decreases space, energy and labor requirements for pineapple plants in commercial micropropagation. Once the plantlets are ready to be taken from the reactors, they are carefully acclimatized to natural environmental conditions, and a facultative C3/CAM metabolism in the first 2 months of growth is the characteristic of pineapple plants, depending on environmental conditions. We subjected two sets of micropropagated pineapple plants to C3 and CAM-inducing environmental conditions, determined by light intensity/relative humidity (respectively 40 μmol m−2 s−1/85 % and 260 μmol m−2 s−1/50 %). Leaves of pineapple plants grown under CAM-inducing conditions showed higher leaf thickness and more developed cuticles and hypodermic tissue. Proteomic profiles of several proteins, isoenzyme patterns and transcriptomic profiles were also measured. Five major spots were isolated and identified, two of them for the first time in Ananas comosus (OEE 1; OEE 2) and the other three corresponding to small fragments of the large subunit of Rubisco (LSU). PEPC and PEPCK were also detected by immunobloting of 2DE at the end of both ex vitro treatments (C3/CAM) during the dark period. Isoenzymes of SOD and CAT were identified by electrophoresis and the transcript levels of OEE 1 and CAT were associated with CAM metabolism in pineapple plants.


[Communication and Networking - Results of the Working Group 8 of the Forum Future Public Health, Berlin 2016].
Steady changes in society present challenges to constructive cooperation between stakeholders in the diverse PH landscape of Germany through individualism, globalisation, medical progress, digitalisation, etc. Working group 8 therefore suggests that the PH community should build new internal structures, in order to be able to respond jointly to external challenges, facilitate networking amongst the actors and speak with one voice, when needed. The suggestion is to establish an office that has the task to organise further meetings, harmonize written joint statements and moderate the dialogue amongst peers.


Prioritising risk pathways of complex human diseases based on functional profiling.
Analysis of the biological pathways involved in complex human diseases is an important step in elucidating the pathogenesis and mechanism of diseases. Most pathway analysis approaches identify disease-related biological pathways using overlapping genes between pathways and diseases. However, these approaches ignore the functional biological association between pathways and diseases. In this paper, we designed a novel computational framework for prioritising disease-risk pathways based on functional profiling. The disease gene set and biological pathways were translated into functional profiles in the context of GO annotations. We then implemented a semantic similarity measurement for calculating the concordance score between a functional profile of disease genes and a functional profile of pathways (FPP); the concordance score was then used to prioritise and infer disease-risk pathways. A freely accessible web toolkit, 'Functional Profiling-based Pathway Prioritisation' (FPPP), was developed (http://bioinfo.hrbmu.edu.cn/FPPP). During validation, our method successfully identified known disease-pathway pairs with area under the ROC curve (AUC) values of 96.73 and 95.02% in tests using both pathway randomisation and disease randomisation. A robustness analysis showed that FPPP is reliable even when using data containing noise. A case study based on a dilated cardiomyopathy data set indicated that the high-ranking pathways from FPPP are well known to be linked with this disease. Furthermore, we predicted the risk pathways of 413 diseases by using FPPP to build a disease similarity landscape that systematically reveals the global modular organisation of disease associations.


Is Modified Condylotomy a Better Surgical Option Compared With High-Condylar Shave With Eminectomy in Improving Symptoms of Internal Derangement of Temporomandibular Joint?
A proper anatomical disc-condyle position is a prerequisite to prevent progressive deteriorating changes within the temporomandibular joint. Surgery becomes the primary treatment option for patients who do not recover with nonoperative management. The present study aimed to compare the clinical outcome of 2 different surgical procedures in patients with internal derangement of the temporomandibular joint. A prospective clinical cohort study was conducted among patients presenting to outpatient department of Oral and Maxillofacial Surgery at Maulana Azad Institute of Dental Sciences. The study sample was alternatively allocated into 2 treatment groups; Group I: modified condylotomy (MC) and Group II: high-condylar shave with eminectomy (HCSE). The primary outcome variables included pain on function, tenderness on palpation, and maximum mouth opening. The secondary outcome variables included joint sounds, jaw deviation on opening, maximum protrusive jaw movement, maximum ipsilateral jaw movement, and maximum contralateral jaw movement. The covariates were age, sex of the patient, duration of illness, the diagnosis based on Wilkes's staging, and the laterality (whether unilateral or bilateral). Descriptive, comparative, and regression analyses were conducted. Twenty-one patients with Wilkes Stage II, III, and IV were included in the study (MC: 10 patients and HCSE: 11 patients). The mean age of the study sample was 32.67 (±11.66) years. Among 21 patients recruited in our study, 18 were females. It was observed that after 1-year follow-up, patients in Group I had significantly lower pain on function (0.30 ± 0.48) compared with Group II (3.00 ± 1.18). (P < .001). Similarly, tenderness on palpation was significantly decreased in Group I (0.80 ± 0.48) compared with Group II (2.45 ± 0.93; P < .001). Joint sounds were significantly lower in Group I (1.20 ± 0.63) compared with Group II (2.27 ± 0.90) after 1 year (P < .001). Maximum protrusive jaw movement and maximum ipsilateral jaw movement were significantly higher in Group I compared with Group II after 1 year. MC is a comparatively better surgical procedure than HCSE in patients with internal derangement of the TMJ.


Proliferative activity of acoustic neurilemomas without neurofibromatosis determined by monoclonal antibody MIB 1.
Microscopic sections obtained from paraffin blocks of 30 consecutive neurilemomas stored in 1989 were investigated immunohistochemically with the new monoclonal antibody MIB 1 directed against recombinant parts of Ki-67 antigen. The immunohistochemical staining was carried out on dewaxed microwave-oven-processed paraffin sections of formalin-fixed tumour tissues. The labelling index (LI) obtained was below 1% in 21 cases, 1-3% in 7 cases and more than 3% in 2 cases. There was no correlation between the LI and the age of the patients or the tumour size. The major advantage of MIB 1 over previous immunohistochemical methods is its usefulness in long preserved sections which are ideal for retrospective studies.


Association between prenatal exposure to metal mixtures and early childhood allergic diseases.
The association between prenatal exposure to the metal mixture and allergic diseases is poorly understood. We aimed to explore the individual effect and the combined effect of prenatal exposure to vanadium (V), chromium (Cr), nickel (Ni), arsenic (As), cadmium (Cd), thallium (Tl), and lead (Pb) on early childhood allergic diseases based on a birth cohort study that included 628 mother-infant pairs. Metals were measured in maternal urine samples collected in the first, second, and third trimesters. Children were prospectively followed up at age 4 years to collect information on allergic rhinitis, wheeze, and eczema status. By applying logistic regression models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR), the different statistical analyses revealed urinary metals were only associated with early childhood allergic rhinitis. The averaged prenatal As exposure was significantly associated with an increased OR for allergic rhinitis in both single-metal (OR = 2.04, 95% CI: 1.35, 3.07) and multiple-metal logistic regression models (OR = 1.78, 95% CI: 1.15, 2.78). The WQS index of mixed metal exposure was positively associated with allergic rhinitis (OR = 1.66, 95% CI: 1.26, 2.19), and As and Tl had the largest weights in the WQS index (weighted 0.51 and 0.29, respectively). The BKMR analysis also showed the overall effect of the metal mixture was significantly associated with allergic rhinitis when all the metals were at their 55th percentile or above, compared to their 50th percentile. The effect of As and Tl on the risk of allergic rhinitis was significant when all of the other metals were fixed at the specific percentiles. Our findings suggest that prenatal co-exposure to higher levels of the seven metals increases the risk of allergic rhinitis in children, and As and Tl may contribute most to the combined risk.


Two-Dimensional Gel Electrophoresis Image Analysis via Dedicated Software Packages.
Analyzing two-dimensional gel electrophoretic images is supported by a number of freely and commercially available software. Although the respective program is highly specific, all the programs follow certain standardized algorithms. General steps are: (1) detecting and separating individual spots, (2) subtracting background, (3) creating a reference gel and (4) matching the spots to the reference gel, (5) modifying the reference gel, (6) normalizing the gel measurements for comparison, (7) calibrating for isoelectric point and molecular weight markers, and moreover, (8) constructing a database containing the measurement results and (9) comparing data by statistical and bioinformatic methods.


In vitro cell perfusion. I. System for continuous observation of cells and analysis of perfusion fluid suitable for isolated mast cell and macrophage studies.
A system is described in which cells are perfused continuously with appropriate medium while simultaneously recording any change in cell morphology together with assay of released products (enzymes and mediators) following immunologic or non-immunologic perturbation. The released products in the perfusate are monitored continuously by automated fluorimetric assay procedures. The system is particularly applicable to investigate or toxicological studies of isolated mast cells or cultured macrophages.


PpNrg1 is a transcriptional repressor for glucose and glycerol repression of AOX1 promoter in methylotrophic yeast Pichia pastoris.
The regulator in glycerol repression of Pichia pastoris AOX1 promoter (P AOX1 ) is still unclear. A Cys2His2 zinc finger transcriptional repressor PpNrg1 localized to nucleus and participated in the repression of P AOX1 in P. pastoris in glucose and glycerol. Quantitative real-time PCR revealed that PpNrg1 repressed expression of numerous genes involved in methanol utilization and peroxisome biogenesis in 0.02 % glucose and 1 % (v/v) glycerol. Electrophoretic mobility shift assay and DNase I footprinting assay revealed that PpNrg1 bound to five sites of P AOX1 , including two binding sites of PpMxr1, which is an indispensable activator of P AOX1 in P. pastoris. Transcriptional repressor PpNrg1 suppresses P AOX1 in glucose and glycerol by directly binding to five sites of P AOX1 , including two binding sites of transcriptional activator PpMxr1.


Polypyrrole-Coated Zinc Ferrite Hollow Spheres with Improved Cycling Stability for Lithium-Ion Batteries.
Here, ZnFe2 O4 double-shell hollow microspheres are designed to accommodate the large volume expansion during lithiation. A facile and efficient vapor-phase polymerization method has been developed to coat the ZnFe2 O4 hollow spheres with polypyrrole (PPY). The thin PPY coating improves not only the electronic conductivity but also the structural integrity, and thus the cycling stability of the ZnFe2 O4 hollow spheres. Our work sheds light on how to enhance the electrochemical performance of transition metal oxide-based anode materials by designing delicate nanostructures.


Epidemiology of suicidal behaviours amongst school-going adolescents in post-conflict Sierra Leone.
Children and young people living in post-conflict contexts are at an increased risk of suicidal behaviours (ideations and attempts). Not much is known about the extent of suicidal behaviours amongst adolescents in most notable post-conflict countries in sub-Saharan Africa, including Sierra Leone. We performed a secondary analysis of data from the 2017 Sierra Leone World Health Organisation Global School-based Student Health Survey conducted amongst students in secondary schools nationwide. We estimated the 12-month prevalence and performed bivariable and multivariable analyses to assess the correlates of suicidal behaviours. Of the 2,798 analytic sample, 14.6% (males = 15.1%, females = 14.0%) reported suicidal ideation, and the 12-month prevalence estimate of suicide attempt was 19.6% (male = 20.9%, females =17.8%). The factors associated with suicidal behaviours were multi-layered. While no statistically significant gender association with suicide ideation or attempt was observed at the personal level, being aged 18 or older, loneliness, and health risk behaviours (cannabis use, and leisure time sedentary behaviour) were associated with increased odds of suicidal behaviours. Within the family context, parental monitoring was associated with increased odds of suicidal ideation, but parental supervision was associated with reduced odds of suicide ideation. The cross-sectional nature of the data did not support causal inferences. Taken together, professional mental healthcare would be helpful in treating adolescent emotional problems (e.g., depression and loneliness) related to suicidal behaviours; but prevention and intervention programmes targeted at addressing adolescent health risk behaviours, and familial and interpersonal problems may yield more favourable outcomes.


Liver transplantation in primary biliary cirrhosis.
The proportion of patients who undergo liver transplantation for primary biliary cirrhosis (PBC) is steadily declining. This decline is partly from the increasing number of patients undergoing transplantation for other indications, but also perhaps because of the effect of ursodeoxycholic acid (UDCA) on the natural history of this condition. Nevertheless, patients who have PBC still constitute approximately 11% of all patients undergoing transplantation for cirrhosis. The prognosis after transplantation is excellent, with an approximately 80% 5-year survival reported by most large centres. Liver transplantation also significantly improves quality of life in survivors. The disease may recur after surgery in up to one third of patients, but recurrence has not been shown to have a significant effect on patients' survival in the medium term.


A homeodomain leucine zipper gene from Craterostigma plantagineum regulates abscisic acid responsive gene expression and physiological responses.
A subset of homeodomain leucine zipper proteins (HDZip) play a role in regulating adaptation responses including developmental adjustment to environmental cues in plants. Here we report the structural and functional characterisation of a dehydration responsive nuclear-targeted HDZip transcriptional regulator, CpHB-7. DNA-protein interaction studies suggest that CDeT6-19, a known ABA and dehydration responsive dehydrin gene, is a potential target gene of CpHB-7 in the desiccation-tolerant plant Craterostigma plantagineum. Transgenic plants that ectopically express CpHB-7 display reduced sensitivity towards ABA during seed germination and stomatal closure. Expression analysis reveals that genes with induced or repressed expression in CpHB-7 ectopic expression lines are either mostly repressed or induced by ABA, drought or salt treatment respectively, thus demonstrating that CpHB-7 modifies ABA-responsive gene expression as a negative regulator. CpHB-7 gene expression is also linked to early organ development, leading to the suggestion that CpHB-7 is functionally similar to the Arabidopsis transcription factor, ATHB-6.


Oleoyl-estrone does not alter hypothalamic neuropeptide Y in Zucker lean and obese rats.
Female Zucker lean and obese rats were treated for 14 days with 3.5 micromol/kg oleoyl-estrone (OE) in liposomes (Merlin-2). After 0, 3, 6, 10, and 14 days of treatment, the rats were killed and hypothalamic nuclei (lateral preoptic, median preoptic, paraventricular, ventromedial and arcuate) were used for neuropeptide Y (NPY) radioimmunoassay. In 14 days, OE decreased food intake by 26% in lean and 38% in obese rats and energy expenditure by 6% in lean and 47% in obese rats; the body weight gap between controls and treated rats becoming -17.8% of initial b.wt. in the lean and -13.6% in the obese rats. Obese rats showed higher NPY levels in all the nuclei than the lean rats. Despite a negative energy balance and decreased food intake, there were practically no changes in NPY with OE treatment. The results indicate that oleoyl-estrone does not act through NPY in its control of either food intake or thermogenesis in lean and genetically obese rats.


Pure red cell aplasia following pernicious anemia.
A rare case of pure red cell aplasia (PRCA) in association with pernicious anemia is reported. A 40-year-old man presented with typical clinical and laboratory features of pernicious anemia and received intramuscular injections of vitamin B12, with satisfactory response. Anemia recurred 6 months later despite continued therapy, and the patient was noted to have PRCA, which was treated successfully with two courses of high-dose bolus methylprednisolone therapy. His peripheral mononuclear cells before the therapy suppressed colony formation of early erythroid precursors (BFU-E) from normal bone marrow; such a suppressive effect was not found after recovery from anemia.


Emergency irradiation of 3.4Gy/2f in pineal gland germinoma patients with symptomatic hydrocephalus.
Surgical interventions including ventriculostomy and ventriculo-peritoneal shunt were usually administrated in pineal germ cell tumor patients with symptomatic hydrocephalus. Considering higher sensitivity of germinoma to anti-tumor therapy, we explored emergency irradiation as non-invasive measure in this situation. Data of 35 germinoma patients with symptomatic hydrocephalus who received emergency irradiation of 3.4 Gy/2f were studied retrospectively. The maximum width of frontal horn and the minimum width of trunk of corpus callosum (TCC) were measured to evaluate hydrocephalus changing. Besides, mean deviation (MD) of Humphrey perimetry was employed to evaluate visual field defect. Correlations between hydrocephalus changing and clinical factors, including age, percentage of tumor regression, radiographic re-evaluation interval, and serum beta-human chorionic gonadotropin (β-HCG) level, were analyzed. The median maximum diameter and volume of pineal lesions was 27 mm (range 10-55 mm) and 6.5cm3 (range 0.4-74.1 cm3), respectively. At median 8 days after irradiation, the median percentage of tumor remission was 55% (range 10-100%). The median maximum width of FN and the median minimum width of TCC were 11.6 mm and 39.0 mm, and 8.0 mm and 31.4 mm, before and after irradiation, respectively. The improvement of both parameters reached significant level (p < 0.001). However, none clinical factor was found to have correlation with their improvement. In 14 patients with paired data of pre- and post-irradiation MD, its change did not reach the significant level for both eyes. All patients successfully received subsequent chemoradiotherapy without surgical intervention. Emergency irradiation of 3.4 Gy/2f was an effective non-invasive measure to relief hydrocephalus in pineal germinoma patients.


Phenotypic and transcriptional analysis of Saccharomyces cerevisiae during wine fermentation in response to nitrogen nutrition and co-inoculation with Torulaspora delbrueckii.
Nitrogen content of grape musts strongly impacts on fermentation performance and wine metabolite production. As nitrogen is a limiting nutrient in most grape musts, nitrogen supplementation is a common practice that ensures yeast growth during fermentation. However, preferred nitrogen sources -as ammonium- repress the genes related to alternative nitrogen sources consumption, usually involved in aromatic compounds production. Here, we describe the effect of high ammonium doses in Saccharomyces cerevisiae fermentation performance and wine properties, and how it is affected by yeast co-inoculation in mixed (S. cerevisiae + Torulaspora delbrueckii) fermentations. In addition, an RNA-seq analysis allowed us to study the S. cerevisiae transcriptional response to ammonium nutrition and yeast interaction, demonstrating that T. delbrueckii presence affects the global S. cerevisiae transcriptional response, reducing ammonium effects at both phenotypic -fermentation kinetics and metabolite production- and transcriptional levels, under experimental conditions.


Patients' attitudes toward health care providers collecting information about their race and ethnicity.
Experts recommend that health care providers (HCPs) collect patients' race/ethnicity, but HCPs worry that this may alienate patients. To determine patients' attitudes toward HCPs collecting race/ethnicity data. Cross-sectional survey. General Internal Medicine patients (n=220). Perceived importance of having HCPs collect race/ethnicity data, their concerns about this, comfort level providing this information, and reactions to 4 statements explaining the rationale for collecting this. Approximately 80% somewhat or strongly agreed that HCPs should collect information on patients' race/ethnicity. However, 28% had significant discomfort (score 5 or less on 10-point scale) reporting their own race/ethnicity to a clerk, and 58% were somewhat or very concerned that this information could be used to discriminate against patients. Compared with whites, blacks, and Hispanics felt less strongly that HCPs should collect race/ethnicity data from patients (P=.04 for both pairwise comparisons), and blacks were less comfortable reporting their own race/ethnicity than whites (P=.03). Telling patients that this information would be used for monitoring quality of care improved comfort more than telling patients that the data collected (a) was mandated by others, (b) would be used to guide staff hiring and training, and (c) would be used to ensure the patient got the best care possible. Most patients think HCPs should collect information about race/ethnicity, but many feel uncomfortable giving this information, especially among minorities. Health care providers can increase patients' comfort levels by telling them this will be used to monitor quality of care.


Whole-heart coronary MR angiography using image-based navigation for the detection of coronary anomalies in adult patients with congenital heart disease.
The purpose of this study was to evaluate a recently developed two-dimensional (2D) image-based navigation approach (iNAVG+C ) combined with respiratory bellows gating for CMRA in patients with congenital heart disease. Nine healthy volunteers (mean age 32 ± 6 years [standard deviation]) and 29 patients (28 ± 9 years) were scanned on a 1.5 Tesla clinical scanner using iNAV(G+C) motion compensated T2prepared CMRA, and the conventional 1D NAV approach. Scan time was recorded for each CMRA scan. An image quality score was given to each coronary artery from (0, uninterpretable; to 4, excellent image quality). Additionally, vessel sharpness of each coronary artery was measured. Average scan time was significantly shorter (P < 0.01) using the proposed iNAVC+G approach (7:57 ± 1:34) compared with 1D NAV (9:15 ± 3:02). Improved visual scores of the right coronary artery (iNAV(G+C) : 4,3,4 (median, 25th percentile, 75th percentile) versus 1D NAV: 3,3,4; P < 0.001) and left anterior descending artery (iNAV(G+C) : 3,3,4 versus 1D NAV: 3,2,3; P < 0.001) were obtained using iNAV(G+C) compared with 1D NAV as well as an increased vessel sharpness of the right coronary artery (iNAV(G+C) : 65.3% ± 6.6% (mean ± standard deviation) versus 1D NAV: 60.2% ± 11.4%; P < 0.05) and left anterior descending artery (iNAV(G+C) : 63.2% ± 6.7% versus 1D NAV: 58.3% ± 9.5%; P < 0.05). Image-based navigation in combination with respiratory bellows gating allows for more robust suppression of respiratory motion artifacts for whole-heart CMRA compared with conventional 1D NAV as images can be acquired in a shorter time and with improved image quality.


Protective effect of ovalbumin-flavonoid hydrogel on thrombolytic activity and stability of nattokinase.
The protective effect of ovalbumin-flavonoids (naringenin, genistein, naringin, puerarin, and daidzein) hydrogels on the thrombolytic activity and stability of nattokinase were investigated. The results suggested that flavonoids promoted the gelation of ovalbumin solution, which was not able to form hydrogel at the same concentration upon heating. The nattokinase/ovalbumin-naringenin hydrogel had the strongest hardness and springiness. All nattokinase/ovalbumin-flavonoids hydrogels were more elastic than viscous. After in vitro digestion, the thrombolytic capacities of all nattokinase/ovalbumin-flavonoids hydrogels were significantly higher than that of free nattokinase. Moreover, nattokinase/ovalbumin-flavonoids hydrogels showed higher thermal and pH stability than free nattokinase. Fluorescence spectroscopy and molecular docking analysis revealed that the main interactions between nattokinase and daidzein, nattokinase and genistein were mainly hydrogen bond, while the main interactions between nattokinase and naringin, nattokinase and puerarin, nattokinase and naringenin were hydrophobic interaction. This research suggested that nattokinase/ovalbumin-flavonoids had great potential for applications in the treatment of thrombus.


Stereo-EEG tailored resection in a child with presumed perinatal post-stroke epilepsy: The complex organization of epileptogenic zone.
Only a few studies have focused on tailored resection in post-stroke epilepsy, in which hemispherectomy and hemispherotomy are the most recognized treatments. We describe the case of a patient with drug-resistant, presumed perinatal, post-stroke epilepsy and moderate right hemiparesis. The seizures were stereotyped, both spontaneous and induced by sudden noises and somatosensory stimuli. Considering the discordant anatomic-electro-clinical data - left perisylvian malacic lesion with electrical onset over the left mesial fronto-central leads - and the patient's functional preservation, SEEG was performed. SEEG revealed sub-continuous abnormalities in the perilesional regions. Several seizures were recorded, with onset over the premotor area, rapidly involving the motor and insular-opercular regions. We decided for a combined surgical approach, SEEG-guided radiofrequency thermocoagulation, on the fronto-mesial structure but also on the central operculum, followed by resective surgery including only the fronto-mesial structures. The SEEG allowed to localize the epileptogenic zone far away from the anatomical lesion but connected to part of it. A combined surgical approach tailored on SEEG results allowed a good outcome (Engel Ib) without additional deficits.


Assignment of the GDH loci to human chromosomes 10q23 and Xq24 by in situ hybridization.
More precise localisations of the glutamate dehydrogenase gene (GLUD) to chromosome 10q23 and of the pseudogene GLUDP1 to X q24 are proposed.


Impact of Free-Breathing Phase-Contrast MRI on Decision-Making in Fontan Surgical Planning.
Fontan surgical planning ranks proposed surgical options according to their hemodynamics assessed by computational fluid dynamic (CFD) modeling. CFD commonly utilizes blood flow acquired under breath-holding (BH) conditions. Ignoring the free-breathing (FB) effect on blood flow waveforms may impact the ranking of surgical options. This study investigates such a potential impact by including ten Fontan patients who had blood flow acquisitions under both BH and FB conditions. A virtual surgery platform was used to generate two surgical options for each patient: (1) a traditional Fontan conduit and (2) a Y-graft. These options were ranked based on clinically relevant hemodynamic metrics: power loss (PL) and hepatic flow distribution (HFD). No difference was found in the ranking of options between using FB and BH flow acquisitions. The findings indicated that decision-making is not affected by the types of flow acquisition for Fontan surgical planning.