Identification of miR-125b targets involved in acute promyelocytic leukemia cell proliferation.
Acute promyelocytic leukemia (APL) is characterized by the presence of the PML-RARα fusion protein. We have previously found that PML-RARα-regulated miR-125b is highly expressed in APL; however, the characteristics of the regulatory effects and mechanisms of miR-125b involved in APL proliferation have yet to be clarified. In this study, we demonstrate that miR-125b promotes the proliferation of APL cells with the involvement of the PI3K/Akt and MAPK signaling pathways. Furthermore, we identified BTG2, MAP3K11, RPS6KA1 and PRDM1 as putative targets of miR-125b, which we verified using luciferase reporter constructs. Moreover, we demonstrate that the expression of miR-125b targets is downregulated in leukemic cells in patients with APL. Thus, our results provide evidence that miR-125b can modulate multiple oncogenic cell proliferation pathways and may be a novel therapeutic target for APL.


Molecular characterization of mutations affecting expression level and growth rate-dependent regulation of the Escherichia coli zwf gene.
We characterized three cis dominant mutations which elevate glucose 6-phosphate dehydrogenase level. Growth rate-dependent regulation and oxidative stress control of enzyme level were altered by the mutations. DNA sequencing and transcript mapping showed that the "up" mutations created new promoters whose hyperactive expression overrides the normal regulation of the native promoter.


Advanced maternal age and the risk of perinatal death due to intrapartum anoxia at term.
Advanced maternal age is associated with higher risks of intrapartum complications. However, the effect of maternal age on the risk of perinatal death due to these complications is unclear. The aim of the present study was to determine the association between maternal age and delivery-related perinatal death at term. In this retrospective cohort study, birth records of 1,043,002 singleton term infants with cephalic presentation were analysed excluding anomalous and antepartum losses in Scotland between 1985 and 2004. Linked Scottish national registries of pregnancy outcome data and perinatal death data were used. The event was delivery-related perinatal death (ie, intrauterine fetal death during labour or death of the infant in the first 4 weeks of life), plus a subgroup ascribed to intrapartum anoxia. There were 803 delivery-related perinatal deaths, with 490 due to intrapartum anoxia (4.7 per 10,000 births) and 313 (3.0 per 10,000 births) due to non-anoxic causes. Compared to women aged 25-34, women aged 40 and above had a twofold risk of delivery-related perinatal death at term (adjusted OR 2.20, 95% CI 1.42 to 3.40). The excess was explained by increased risk of death due to intrapartum anoxia. Among women in labour at term, age greater than 40 was independently associated with risk of anoxic death among primiparous (adjusted OR 5.34, 95% CI 2.34 to 12.20) and multiparous women (adjusted OR 2.14, 95% CI 0.99 to 4.60). Advanced maternal age is associated with an increased risk of death due to intrapartum anoxia at term.


Dietary Phytase- and Lactic Acid-Treated Cereals Caused Greater Taxonomic Adaptations than Functional Adaptations in the Cecal Metagenome of Growing Pigs.
Phosphorus (P) is an essential nutrient for the gut bacteria and the host. Nevertheless, little information exists that indicates to what extent an improved level of P availability in the small intestine leads to functional adaptations in bacterial metabolic pathways in the large intestine. Therefore, we investigated the changes in the taxonomic and functional bacterial metagenome in cecal digesta of growing pigs fed diets containing phytase and/or cereals treated with 2.5% lactic acid (LA) for 19 days (n = 8/diet) using shotgun metagenome sequencing. The phytase supplementation resulted in strikingly distinct bacterial communities, affecting almost all major bacterial families, whereas functional changes were less dramatic among the feeding groups. While phytase treatment decreased predominant Prevotellaceae levels, it seemed that Clostridiaceae, Ruminococcaceae, and Lachnospiraceae filled the opening metabolic niches (P < 0.05). The LA-treated cereals mediated reduced levels of Bacteroidaceae and increased levels of Veillonellaceae, but those results were mainly seen when the cereals were fed as a single treatment (P < 0.05). In association with the taxonomic alterations, phytase caused changes within the major functional pathways corresponding to amino acid metabolism; translation; membrane transport; folding, sorting, and degradation; and energy metabolism, whereas the LA treatment of cereals resulted in decreased enzymatic capacities within the carbohydrate metabolism and energy metabolism pathways (P < 0.05). Metabolic dependencies corresponding to the starch and sucrose metabolism, glycolysis/gluconeogenesis, and citrate cycle pathways were indicated by diet-associated changes in enzymatic capacities related to short-chain fatty acid, methane, vitamin, and bacterial antigen synthesis. Accordingly, the present results support the idea of the importance of the availability of intestinal P for bacterial metabolism. However, the functional profiles were less different than the taxonomic profiles among the dietary treatment results, indicating a certain degree of metabolic plasticity within the cecal metagenome.IMPORTANCE Dietary strategies (e.g., phytase supplementation and lactic acid [LA] treatment of cereals) used to improve the availability of phytate-phosphorus (P) from pig feed reduce the amount of P flowing into the large intestine, whereas LA treatment-induced changes in nutrient fractions alter the substrate being available to the microbiota. In ruminants, lower intestinal P availability compromises the fibrolytic activity of the microbiome. Here, we report that the functional capacities were less dramatically affected than the taxonomic composition by phytase-supplemented and LA-treated cereals. The bacterial community appeared to be partly capable of functionally compensating for the altered flow of P by replacing taxa with higher P needs by those with lower P needs. Therefore, by acting as mucosal immune stimulants, alterations in microbiota-associated molecular patterns (MAMPs) due to the taxonomic shifts may play a greater role for host physiology and health than functional differences caused by differing intestinal P availabilities, which merits further research.


Endothelial cells promote neural stem cell proliferation and differentiation associated with VEGF activated Notch and Pten signaling.
To investigate whether and how endothelial cells affect neurogenesis, we established a system to co-culture endothelial cells and brain slices of neonatal rat and observed how subventricular zone cells differentiate in the presence of endothelial cells. In the presence of endothelial cells, neural stem cells increased in number, as did differentiated neurons and glia. The augmentation of neurogenesis was reversed by diminishing vascular endothelial growth factor (VEGF) expression in endothelial cells with RNA interference (RNAi). Microarray analysis indicated that expression levels of 112 genes were significantly altered by co-culture and that expression of 81 of the 112 genes recovered to normal levels following RNAi of VEGF in endothelial cells. Pathway mapping showed an enrichment of genes in the Notch and Pten pathways. These data indicate that endothelial cells promote neural stem cell proliferation and differentiation associated with VEGF, possibly by activating the Notch and Pten pathways.


[Epidemiology of liver injuries in 14 district, urban, regional and canton hospitals in Switzerland].
224 patients with liver injuries treated in 14 District and Regional Hospitals over a 10-year period were retrospectively evaluated. The results were compared to those obtained in 175 patients referred to the Central University Clinic "Inselspital", Berne/Switzerland. In all cases the degree of multiple trauma was assessed by the Injury Severity Score (ISS) and the severity of the liver injury by a Liver Injury Score (modified after MOORE). Blunt injury to the abdomen as a result of road traffic accidents, accidents at work or sporting misadventures were responsible for about 80% of all liver injuries. Peritoneal lavage was the main special investigation and was reliable in the diagnosis of haemoperitoneum. Abdominal ultrasonography proved of additional value. It allowed in experienced hands not only the diagnosis of liver injury but also some assessment of the severity of injury. Additional injuries to other abdominal organs can be assessed. By utilizing abdominal ultrasonography (or computed-tomography) liver trauma were managed conservatively in selected stable patients with minor injuries. The overall mortality was 17% in the 224 patients and compares well with the international figures. The results of treatment revealed a low mortality for liver injuries Grades I to III, whether managed in a District or Regional Hospital or in the Central University Clinic. For more severe injuries (Grades IV or V) the prognosis was worse in the District or Regional Hospitals than in the Central University Clinic. 20% of patients with liver injury Grades I to III in stable circulatory condition could be treated conservatively.(ABSTRACT TRUNCATED AT 250 WORDS)


Tributyltin and the Female Hypothalamic-Pituitary-Gonadal Disruption.
The hypothalamic-pituitary-gonadal (HPG) axis is the principal modulator of reproductive function. Proper control of this system relies on several hormonal pathways, which make the female reproductive components susceptible to disruption by endocrine-disrupting chemicals such as tributyltin (TBT). Here, we review the relevant research on the associations between TBT exposure and dysfunction of the female HPG axis components. Specifically, TBT reduced hypothalamic gonadotropin-releasing hormone (GnRH) expression and gonadotropin release, and impaired ovarian folliculogenesis, steroidogenesis, and ovulation, at least in part, by causing abnormal sensitivity to steroid feedback mechanisms and deleterious ovarian effects. This review covers studies using environmentally relevant doses of TBT in vitro (1 ng-20 ng/ml) and in vivo (10 ng-20 mg/kg) in mammals. The review also includes discussion of important gaps in the literature and suggests new avenue of research to evaluate the possible mechanisms underlying TBT-induced toxicity in the HPG axis. Overall, the evidence indicates that TBT exposure is associated with toxicity to the components of the female reproductive axis. Further studies are needed to better elucidate the mechanisms through which TBT impairs the ability of the HPG axis to control reproduction.


Chemical Cartography Approaches to Study Trypanosomatid Infection.
Pathogen tropism and disease tropism refer to the tissue locations selectively colonized or damaged by pathogens, leading to localized disease symptoms. Human-infective trypanosomatid parasites include Trypanosoma cruzi, the causative agent of Chagas disease; Trypanosoma brucei, the causative agent of sleeping sickness; and Leishmania species, causative agents of leishmaniasis. Jointly, they affect 20 million people across the globe. These parasites show specific tropism: heart, esophagus, colon for T. cruzi, adipose tissue, pancreas, skin, circulatory system and central nervous system for T. brucei, skin for dermotropic Leishmania strains, and liver, spleen, and bone marrow for viscerotropic Leishmania strains. A spatial perspective is therefore essential to understand trypanosomatid disease pathogenesis. Chemical cartography generates 3D visualizations of small molecule abundance generated via liquid chromatography-mass spectrometry, in comparison to microbiological and immunological parameters. This protocol demonstrates how chemical cartography can be applied to study pathogenic processes during trypanosomatid infection, beginning from systematic tissue sampling and metabolite extraction, followed by liquid chromatography-tandem mass spectrometry data acquisition, and concluding with the generation of 3D maps of metabolite distribution. This method can be used for multiple research questions, such as nutrient requirements for tissue colonization by T. cruzi, T. brucei, or Leishmania, immunometabolism at sites of infection, and the relationship between local tissue metabolic perturbation and clinical disease symptoms, leading to comprehensive insight into trypanosomatid disease pathogenesis.


Diagnostic Added-Value of Serum CA-125 on the IOTA Simple Rules and Derivation of Practical Combined Prediction Models (IOTA SR X CA-125).
This study aimed to evaluate the diagnostic added-value of serum CA-125 to the International Ovarian Tumor Analysis (IOTA) Simple Rules in order to facilitate differentiation between malignant and benign ovarian tumors before surgery. A secondary analysis of a cross-sectional cohort of women scheduled for surgery in Maharaj Nakorn Chiang Mai Hospital between April 2010 and March 2018 was carried out. Demographic and clinical data were prospectively collected. Histopathologic diagnosis was used as the reference standard. Logistic regression was used for development of the model. Evaluation of the diagnostic added-value was based on the increment of the area under the receiver operating characteristic curve (AuROC). One hundred and forty-five women (30.3%) out of a total of 479 with adnexal masses had malignant ovarian tumors. The model that included information from the IOTA Simple Rules and serum CA-125 was significantly more superior to the model that used only information from the IOTA Simple Rules (AuROC 0.95 vs. 0.89, p < 0.001 for pre-menopause and AuROC 0.98 vs 0.83, p < 0.001 for post-menopause). The IOTA SR X CA-125 model showed high discriminative ability and is potentially useful as a decision tool for guiding patient referrals to oncologic specialists.


Abdominal wall lift. Low-pressure pneumoperitoneum laparoscopic surgery.
A method of abdominal wall lift has been developed and evaluated clinically in this unit during the past 18 months. It permits the conduct of laparoscopic procedures at an intraabdominal pressure of 6-8 mm Hg. The technique was introduced for laparoscopic surgery in patients with preexisting cardiac disease and chronic bronchitis. The procedure, by lifting both the abdominal wall and the falciform ligament together, also elevates the central portion of the liver (segments 3-5), thereby improving the surgical exposure. For this reason it is now also used in fit patients with ptotic livers or hypertrophied quadrate lobes undergoing laparoscopic cholecystectomy and common bile duct exploration, and to facilitate left subhepatic exposure in patients during laparoscopic antireflux surgery and vagotomy.


[Ambulatory and domiciliary cancer chemotherapy with forearm implant catheter system and low-dose CDDP + 5-FU therapy].
Shortening the period of hospitalizations and improving QOL attracting a great deal of attention in the field of medicine recently. Therefore, ambulatory and domiciliary treatment has become more important. This is not an exception in cancer therapy; the conversion from hospital treatment to ambulatory and domiciliary treatment is promoted. However, there is the danger of a lowered QOL as a resistant side effect, when the conventional cancer chemotherapy in the hospital is used as the ambulatory and domiciliary treatment. Recently, low-dose CDDP + 5-FU therapy (LFP therapy) that applies biochemical modulation has been developed for advanced gastrointestinal cancers. This therapy is thought to have a good antitumor effect and slight side effects, so it can be widely used. However, this therapy needs the continuous injection of 5-FU, so the hospital treatment was necessary, and ambulatory treatment was difficult with the usual administration method. Thus, we implanted a forearm central venous catheter system (forearm IVH reservoir), through which we can administer medication safely and conveniently without limiting the patient activity. LFP therapy was attempted in ambulatory and domiciliary treatment. Low-dose FP therapy consisted of 5-FU (160 mg/m2/day every day by continuous infusion) and cisplatin (3 mg/m2/day in 100 ml of normal saline by infusion over 30 minutes on days 1-5/W). Patients were treated for 4 consecutive weeks with a subsequent one-week rest period. The overall response rate was 52.1%. Grade 3 toxicity was observed in 5% of patients. An advantage was that in the ambulatory and domiciliary cancer chemotherapy the hematotoxicity was slight, and LFP therapy could be continued safely. In addition, it was also possible to attempt the improvement in QOL with the forearm IVH reservoir system. LFP therapy using the forearm IVH reservoir system may develop as a standard method of ambulatory and domiciliary cancer chemotherapy in the future.


Diurnal Variation of Urinary Fabry Disease Biomarkers during Enzyme Replacement Therapy Cycles.
Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene encoding the α-galactosidase A enzyme. This enzyme cleaves the last sugar unit of glycosphingolipids, including globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3), and galabiosylceramide (Ga2). Enzyme impairment leads to substrate accumulation in different organs, vascular endothelia, and biological fluids. Enzyme replacement therapy (ERT) is a commonly used treatment. Urinary analysis of Gb3 isoforms (different fatty acid moieties), as well as lyso-Gb3 and its analogues, is a reliable way to monitor treatment. These analogues correspond to lyso-Gb3 with chemical modifications on the sphingosine moiety (-C2H4, -C2H4+O, -H2, -H2+O, +O, +H2O2, and +H2O3). The effects of sample collection time on urinary biomarker levels between ERT cycles were not previously documented. The main objective of this project was to analyze the aforementioned biomarkers in urine samples from seven Fabry disease patients (three treated males, three treated females, and one ERT-naïve male) collected twice a day (morning and evening) for 42 days (three ERT cycles). Except for one participant, our results show that the biomarker levels were generally more elevated in the evening. However, there was less variability in samples collected in the morning. No cyclic variations in biomarker levels were observed between ERT infusions.


[DRB1 * 1454: the common allele of human leukocyte antigen-DRB1 * 14 in Chinese Han populations].
To investigate and compare the distribution of HLA-DRB1 * 14 alleles between the southern and northern Chinese Han populations. Human leukocyte antigen (HLA)-DRB1 alleles of 436 southern and 713 northern Chinese Han bone marrow volunteers were genotyped by polymerase chain reaction (PCR)-sequence-based-typing (SBT) method, among them the DRB1 * 1401/1439/1454 ambiguous allele pairs were identified using DRB1 * 14 high-resolution PCR-sequence specific primer (SSP) kits. Also, the clinic samples previously reported as DRB1 * 1401 were re-genotyped using the same PCR-SSP kits. The allelic distribution of DRB1 * 14 in southern and northern Chinese Han population were compared by chi-square test method. Eighty-one ambiguous allele pairs of DRB1 * 1401/1439/1454 and 54 clinic samples previously reported as DRB1 * 1401 were all identified as DRB1 * 1454. Among the 436 Southern Han donors, six subtypes of DRB1 * 14 allele were observed including DRB1 * 1454 (69.57%), DRB1 * 1402 (1.45%), DRB1* 1403 (1.45%), DRB1 * 1404 (4.35%), DRB1 * 1405 (20.29%) and DRB1 * 1407 (2.90%). In the 713 northern Han donors, a total of seven subtypes were observed including DRB1 * 1454 (35.48%), DRB1 * 1403 (12.90%), DRB1 * 1404 (6.45%), DRB1 * 1405 (37.63%), DRB1 * 1407 (4.30%), DRB1 * 1411 (1.08%) and DRB1 * 1412 (2.15%). DRB1 * 1454 and DRB1 * 1405 were the most common alleles of HLA-DRB1 * 14 in Chinese Han populations. The distribution of HLA-DRB1 * 14 differ significantly between the southern and northern Chinese Han population, while DRB1 * 1405 showed similar distribution pattern in the two populations but DRB1 * 1454 had higher frequency in southern than in northern Chinese Han population.


Morphologic and Aerodynamic Changes of Upper Airway in Pediatric Hemifacial Microsomia Patients Undergoing Distraction Osteogenesis.
Current studies on hemifacial microsomia (HFM) patients undergoing unilateral distraction osteogenesis (DO) mainly confined to description of facial morphology. This study was to investigate the effect of unilateral DO on upper airway in pediatric HFM patients using computational fluid dynamics. The investigators implemented the present retrospective study composed of 20 patients (age 9.5 ± 2.5 years, 11 males, 9 females) with moderate HFM performed unilateral DO on the ramus of mandible. Computational fluid dynamics models of the upper airway were obtained based on the computed tomography data sets which were taken before and 6 months after distraction. Morphologic and aerodynamic parameters were respectively computed and compared at peak inspiration. Paired t-tests were used to compare the differences between the before and after parameters with the significance set at P < 0.05. The authors observed that after DO, oropharynx and nasopharynx were the major expanded regions, average pressure increased in all cross-sections, average velocity decreased significantly except in the superior border of the epiglottis plane, and the airflow resistance significantly reduced in the whole upper airway (P < 0.05). The results indicate that unilateral DO may expand the constricted oropharynx and nasopharynx, obtain a relatively symmetrical airway shape and decrease the airflow resistance which consequently reduce the workload necessary for breathing and facilitate inspiration.


Emergency infusion of catecholamines into bone marrow.
An emergency infusion of catecholamines into the bone marrow of a 6-month-old infant was performed. We believe this is the first report of continuous intraosseous infusion of dopamine hydrochloride and dobutamine hydrochloride. Intraosseous infusions are efficacious and complications are rare. We recommend use of this technique in emergency circumstances when venous access cannot be obtained.


Pathological love: impulsivity, personality, and romantic relationship.
Pathological love (PL)--behavior characterized by providing repetitive and uncontrolled care and attention to the partner in a romantic relationship--is a rarely studied condition, despite not being rare and causing suffering. This study aims at investigating impulsivity, personality, and characteristics related to the romantic relationship in this population. Eighty-nine individuals (50 with PL; 39 individuals with no psychiatric disorder) were compared regarding impulsivity, personality, type of attachment, satisfaction with romantic relationship, and love style. Individuals with PL have higher levels of impulsivity (P<.001; Barratt Impulsiveness Scale), higher self-transcendence, that is, are more unconventional and hold sense of communion with a wider reality (P<.001; Temperament and Character Inventory) and keep dissatisfactory romantic relationships (P<.001; Adapted Relationship Assessment Scale). Individuals with PL present personality traits and relationship aspects that must be taken into account in devising assessment and therapeutic strategies for this population.


Rapid, cell-free assay for membrane-active forms of amyloid-β.
Small oligomers of amyloid beta (Aβ) are suspected to be the key to Alzheimer's disease (AD). However, identifying these toxic species in the background of other similar but nontoxic Aβ aggregates has remained a challenge. Recent studies indicate that Aβ undergoes a global structural transition in an early step of aggregation. This transition is marked by a strong increase in its affinity for cell membranes, which suggests that the resultant oligomers could be the key to Aβ toxicity. Here we use this increased membrane affinity to develop a rapid, quantitative, cell-free assay for these bioactive oligomers. It uses fluorescence correlation spectroscopy of fluorescently labeled Aβ and requires only 30 s of measurement time. We also describe a simpler (though less rapid) assay based on the same principles, which uses a dialysis step followed by conventional fluorescence spectroscopy. Our results potentially provide a much-needed high-throughput assay for AD drug development.


Identifying Plant-Human Disease Associations in Biomedical Literature: A Case Study.
The impact of ethnobotanical data from surveys of traditional medicinal uses ofplants can be enhanced through the validation of biomedical knowledge that may be embedded in literature. This study aimed to explore the use of informatics approaches, including natural language processing and terminology resources, for extracting and comparing ethnobotanical leads from biomedical literature indexed in MEDLINE. Using ethnobotanical data for plant species described in Primary Health Care Manuals of the Micronesian islands of Palau and Pohnpei, the results of this study were done relative to disease concepts from the "Mental, Behavioral And Neurodevelopmental Disorders " ICD-9-CM category. The results from this feasibility study suggest that informatics methods can be used to extract and prioritize relevant ethnobotanical information from biomedical knowledge literature.


Role of Inflammation and Redox Status on Doxorubicin-Induced Cardiotoxicity in Infant and Adult CD-1 Male Mice.
Doxorubicin (DOX) is a topoisomerase II inhibitor commonly used in the treatment of several types of cancer. Despite its efficacy, DOX can potentially cause fatal adverse effects, like cardiotoxicity. This work aimed to assess the role of inflammation in DOX-treated infant and adult mice and its possible link to underlying cardiotoxicity. Two groups of CD-1 male mice of different ages (infants or adults) were subjected to biweekly DOX administrations, to reach a cumulative dose of 18.0 mg/kg, which corresponds approximately in humans to 100.6 mg/m2 for infants and 108.9 mg/m2 for adults a clinically relevant dose in humans. The classic plasmatic markers of cardiotoxicity increased, and that damage was confirmed by histopathological findings in both groups, although it was higher in adults. Moreover, in DOX-treated adults, an increase of cardiac fibrosis was observed, which was accompanied by an increase in specific inflammatory parameters, namely, macrophage M1 and nuclear factor kappa B (NF-κB) p65 subunit, with a trend toward increased levels of the tumor necrosis factor receptor 2 (TNFR2). On the other hand, the levels of myeloperoxidase (MPO) and interleukin (IL)-6 significantly decreased in DOX-treated adult animals. In infants, a significant increase in cardiac protein carbonylation and in the levels of nuclear factor erythroid-2 related factor 2 (Nrf2) was observed. In both groups, no differences were found in the levels of tumor necrosis factor (TNF-α), IL-1β, p38 mitogen-activated protein kinase (p38 MAPK) or NF-κB p52 subunit. In conclusion, using a clinically relevant dose of DOX, our study demonstrated that cardiac effects are associated not only with the intensity of the inflammatory response but also with redox response. Adult mice seemed to be more prone to DOX-induced cardiotoxicity by mechanisms related to inflammation, while infant mice seem to be protected from the damage caused by DOX, possibly by activating such antioxidant defenses as Nrf2.


[A comparative analysis of Socon CS and Socon pedicle screws in view of their use for treatment of osteoporotic fractures of the thoracolumbal spine--a biomechanical study].
To compare the anchorage strength of Socon CS cannulated pedicle screws (B. Braun, Aesculap) with that of Socon screws in human cadaver vertebrae, using pull-out strength testing. Twelve samples involving T12 to L3 vertebrae were prepared and a total of 20 pedicle screws, 10 Socon CS and 10 Socon screws, were inserted in them. All screws were 55 mm in length and 6 mm in diameter. After placement, Socon CS pedicle screws were augmented with bone cement (Cimplant cement application kit, B. Braun, Aesculap). Both Socon CS and Socon screws were subjected to monotonous loading in the testing device ZWICK Z 020-TND with tensile stress applied in the screw axis. We evaluated the magnitude of strength resulting in screw loosening and the relationship between this strength and bone density of the sample. Bone density of measured samples corresponded either to osteopenia, i.e. T-score range of -1 to -2.5 SD (standard deviation) or osteoporosis, i.e. T-score -2.5 SD. The average bone density of all samples corresponded to a T-score of -3.1 SD. Bone-screw linkage was found to be associated with both bone-cement and screw-cement interface. Pull-out strength was significantly higher for the Socon CS than the Socon screws (t-test, p<0.0005). In the Socon screws, the linear correlation between pull-out strength and bone density was significant at a 5% level of statistical significance (p=0.008) while, in the Socon CS screws, it was not significant (p=0.065). The poor quality of osteoporotic bone is responsible for a higher frequency of implant failure due to loosening, particularly when implants developed for healthy bone are used. In this biomechanical study, we tested one of the possibilities of how to reduce the risk of implant failure by pedicle screw augmentation with bone cement. The results of this study confirm the hypothesis that the anchorage of Socon CS cannulated pedicle screws with bone cement augmentation is disrupted by significantly higher pull-out strength than that of Socon screws, when subjected to monotonous loading. However, more clinical studies are needed to evaluate clinical outcomes.


Long intergenic non-coding RNAs regulate human lung fibroblast function: Implications for idiopathic pulmonary fibrosis.
Phenotypic changes in lung fibroblasts are believed to contribute to the development of Idiopathic Pulmonary Fibrosis (IPF), a progressive and fatal lung disease. Long intergenic non-coding RNAs (lincRNAs) have been identified as novel regulators of gene expression and protein activity. In non-stimulated cells, we observed reduced proliferation and inflammation but no difference in the fibrotic response of IPF fibroblasts. These functional changes in non-stimulated cells were associated with changes in the expression of the histone marks, H3K4me1, H3K4me3 and H3K27ac indicating a possible involvement of epigenetics. Following activation with TGF-β1 and IL-1β, we demonstrated an increased fibrotic but reduced inflammatory response in IPF fibroblasts. There was no significant difference in proliferation following PDGF exposure. The lincRNAs, LINC00960 and LINC01140 were upregulated in IPF fibroblasts. Knockdown studies showed that LINC00960 and LINC01140 were positive regulators of proliferation in both control and IPF fibroblasts but had no effect upon the fibrotic response. Knockdown of LINC01140 but not LINC00960 increased the inflammatory response, which was greater in IPF compared to control fibroblasts. Overall, these studies demonstrate for the first time that lincRNAs are important regulators of proliferation and inflammation in human lung fibroblasts and that these might mediate the reduced inflammatory response observed in IPF-derived fibroblasts.


Carbapenem and colistin resistance in children with Enterobacteriaceae infections.
Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging global public health threat. As a reserve agent, colistin has been the drug of choice for the treatment of infections caused by CRE. The aim of this study was to determine the risk factors of carbapenem and colistin-resistant Enterobacteriaceae infections and to investigate the outcomes. We conducted a retrospective study in a single university hospital between the years 2013 and 2017 including 150 patients with Enterobacteriaceae infections. Of 150 Enterobacteriaceae infections, 62 (41%) were carbapenem and 23 (15%) were colistin-resistant. Colistin resistance rates among Enterobacteriaceae species increased from 4% in 2014 to 25% in 2017. The inhospital mortality of the patients with colistin-resistant and with carbapenem-resistant infections were 39% (9/23) and 45% (28/62), respectively. Prior exposure to polyantibiotic therapy for Gram negative bacteria was found as a predictor of CRE (OR = 6.4; 95% CI 3.07-13.6; p = 0.001) infections. The median length of hospital stay prior to positive culture (OR = 1.02; 95%CI, 1.0-1.04; p = 0.003) and history of surgery during the admission (OR = 2.46; 95% CI 1.2-5.1; p = 0.005) were found as the predictors of CRE infections. Underlying necrotizing enterocolitis and/or short-bowel syndrome (OR=6.38; 95%CI 1.16-35; p = 0.033) and mechanical ventilation prior to index culture were found as predictors of colistin resistance (OR = 9.4; 95% CI 2-40.4; p = 0.004). Recognizing the risk factors of carbapenem and colistin resistant Enterobacteriaceae infections is essential in order to conserve carbapenem and colistin since there are no new antibiotics to treat multidrugresistant Enterobacteriaceae infections.


Prevalence of hookworm infection and its association with anemia among patients visiting Fenan Medical Center, East Wollega Zone, Ethiopia.
Data was obtained from all study subjects and blood and fecal specimen were collected from all subjects who apparently volunteer to take part in the study. To determine prevalence of hookworm infection and its association with anemia. METHODS.: A cross-sectional study was conducted from February to April 2007 in Diga District, East Wollega Zone. Hematocrit test was done on all blood samples. All stool specimens were processed with a Kato-thick method and examined for parasites and the density of parasites was determined as eggs per gram of stool (epg). Frequencies and proportions were used for the descriptive analysis of the data and Pearson Chi-square test was used to assess the associations between the demographic characteristics of the study subjects and the findings of the test samples. The overall prevalence of intestinal parasites was 64.9% Hookworm was the predominant (49.7%) intestinal parasite identified among the study participants. The density of hookworm egg ranged from 48 epg to 11,520 epg with mean and median values of 685 and 288 epg respectively. The observed result for hematocrit ranged from 12% to 50% with mean (SD) and median values of 34.6% (4.7) and 36% respectively. The prevalence of anemia is 65.5% among study participants. Among those subjects with hookworm, 83.9% were anemic. On the contrary only 41 (22.5%) study subjects who appeared negative for hookworm on stool examination were anemic. The prevalence of hookworm is higher and it is associated with anemia in East Wollega zone. Therefore intervention strategies should consider the concomitance of hookworm and anemia in the implementations of appropriate prevention and control strategies.


Chemical reaction induced carrier localization in nanometer-thin Al/Ru, Al/Co, and Al/Mo superlattices.
It is well-known that the electrical conductivity of a metallic film reduces dramatically when the film becomes very thin. This effect is mainly attributed to surface scattering of the conducting carriers. In a multilayer structure, interface scattering also reduces the conductance, but chemical reactions at the interfaces can have equal or bigger effects. The extent of chemically induced carrier localization at the metallic interfaces has not been explored or reported. We have grown superlattices consisting of nm-thin, alternating Al and transition-metal layers (Al/Ru, Al/Co and Al/Mo) by magnetron sputtering, and measured the electrical conductance of the superlattices in-situ during the growth. We observed a sharp conductance drop at the start of each transition metal layer and a pause in conduction increase at the start of each Al layer, neither of which is predicted by the surface scattering model. We show that these abnormal conductance changes can be explained by localization of Al free carriers at the interfaces to facilitate the formation of intermetallic bonds. The magnitude of the measured conductance drops suggests that one monolayer of compound is formed at each interface at room temperature. Annealing the superlattices to 300 °C caused a modest decrease in conductance, attributed to further chemical reactions. In contrast, a superlattice involving two fully miscible transition metals, Ru and Co, exhibited no carrier localization, resulting in a conductance more than three times that of superlattices containing Al layers.


Important pharmacokinetic properties of antiepileptic drugs.
The choice of an antiepileptic drug (AED) is guided primarily by efficacy and safety criteria. However, the pharmacokinetic properties of an AED determine its ease of use, i.e., its ability to predictably produce and maintain optimal plasma concentrations. Desirable and clinically important pharmacokinetic properties of an AED include complete or constant bioavailability, slow enteral absorption or availability of a sustained-release formulation, availability of a parenteral formulation for acute treatment, rapid penetration into the brain, a single-compartment volume of distribution, low and nonsaturable protein binding, and linear elimination kinetics, with an elimination half-life of about 24 h. The absence of autoinduction of enzymatic biotransformation, active metabolites, and pharmacokinetic drug interactions is also important. In clinical practice, the most undesirable pharmacokinetic properties are lack of a parenteral formulation, short elimination half-life, nonlinear elimination kinetics, autoinduction of enzymatic biotransformation, and interaction with other drugs. No AED is presently marketed or under development that meets all of the desirable criteria. Some of the newer AEDs, although not "ideal" agents, have pharmacokinetic profiles that are not shared by their predecessors, including elimination exclusively by the kidney, absence of drug interactions, and dose-related bioavailability.


Molecular pathogenesis and histologic and clinical features of extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue type.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type (EMZL) is considered an antigen driven lymphoid malignancy associated with protracted antigenic stimulation by microbial pathogens, auto-antigens or other unknown stimuli, which trigger a sustained lymphoid proliferation at sites normally devoid of lymphoid tissue. With the progression of disease, chromosomal aberrations may occur. They result in aberrant activation of signaling pathways which lead to the lymphoproliferation becoming independent of antigenic stimulation. The nuclear factor κB (NF-κB) pathway plays a central role in the lymphomagenesis of EMZL. Four mutually exclusive chromosomal translocations have been identified that lead to the up-regulation of either BCL10 or MALT1 or the generation of a fusion protein, cIAP2-MALT1, and induce aberrant activation of the NF-κB pathway. In translocation-negative EMZL, inactivation of the global NF-κB inhibitor A20 might play an important role. These genetic abnormalities alone are insufficient for malignant transformation. Other factors, such as cell surface and chemokine receptors and factors involved with immune and inflammatory response, play their own unique role in the development of a malignant EMZL and may determine its unique clinico-pathological presentation. This review provides an overview of the histologic and clinical features of EMZL and discusses the current insights into the molecular mechanisms underlying the development of EMZL.


Mitochondrial DNA Content Is Linked to Cardiovascular Disease Patient Phenotypes.
Background We sought to determine whether mitochondrial DNA (mtDNA) content can be used as markers for 12 key phenotypes among cardiovascular disease patients, and whether these markers are valid across patients with diverse ancestries. Methods and Results DNA was collected from the peripheral blood of 996 cardiovascular disease patients at the Cleveland Clinic. The mtDNA copy number and DNA-level variation were assessed from whole-genome sequence. Patients were also ascertained retrospectively for histories of 10 clinical events, as well as for maximum stenosis and extent of disease at baseline. Self-reported race and maternal ancestry inferred from mtDNA sequence were recorded. MtDNA copy number and overall mtDNA rare variant load were significantly lower in patients with histories of various adverse clinical events, and mtDNA copy number was inversely correlated with extent of disease. Strong associations were also found between absence of rare variants in the genes MT-ATP6 and MT-COII and patient histories of hyperlipidemia and myocardial infarction, respectively. Importantly, associations were not ancestry dependent. Conclusions This study provides evidence that mtDNA copy number in circulation is associated with a variety of cardiovascular disease patient phenotypes. Results also suggest a protective role for some rare inherited mtDNA variants. Overall, the study supports the potential of mtDNA content and abundance as biomarkers in heart disease, in a manner that is valid across diverse ancestries.


Glucose metabolism and proliferation in glia: role of astrocytic gap junctions.
Astrocytes play a well-established role in brain metabolism, being a key element in the capture of energetic compounds from the circulation and in their delivery to active neurons. Their metabolic status is affected in many pathological situations, such as gliomas, which are the most common brain tumors. This proliferative dysfunction is associated with changes in gap junctional communication, a property strongly developed in normal astrocytes studied both in vitro and in vivo. Here, we summarize and discuss the findings that have lead to the identification of a link between gap junctions, glucose uptake, and proliferation. Indeed, the inhibition of gap junctional communication is associated with an increase in glucose uptake due to a rapid change in the localization of both GLUT-1 and type I hexokinase. This effect persists due to the up-regulation of GLUT-1 and type I hexokinase and to the induction of GLUT-3 and type II hexokinase. In addition, cyclins D1 and D3 have been found to act as sensors of the inhibition of gap junctions and have been proposed to play the role of mediators in the mitogenic effect observed. Conversely, in C6 glioma cells, characterized by a low level of intercellular communication, an increase in gap junctional communication reduces glucose uptake by releasing type I and type II hexokinases from the mitochondria and decreases the exacerbated rate of proliferation due to the up-regulation of the Cdk inhibitors p21 and p27. Identification of the molecular actors involved in these pathways should allow the determination of potential therapeutic targets that could lead to the testing of alternative strategies to prevent, or at least slow down, the proliferation of glioma cells.


Highly Sensitive and Selective Detection of Hydrogen Using Pd-Coated SnO2 Nanorod Arrays for Breath-Analyzer Applications.
We report a breath hydrogen analyzer based on Pd-coated SnO2 nanorods (Pd-SnO2 NRs) sensor integrated into a miniaturized gas chromatography (GC) column. The device can measure a wide range of hydrogen (1-100 ppm), within 100 s, using a small volume of human breath (1 mL) without pre-concentration. Especially, the mini-GC integrated with Pd-SnO2 NRs can detect 1 ppm of H2, as a lower detection limit, at a low operating temperature of 152 °C. Furthermore, when the breath hydrogen analyzer was exposed to a mixture of interfering gases, such as carbon dioxide, nitrogen, methane, and acetone, it was found to be capable of selectively detecting only H2. We found that the Pd-SnO2 NRs were superior to other semiconducting metal oxides that lack selectivity in H2 detection. Our study reveals that the Pd-SnO2 NRs integrated into the mini-GC device can be utilized in breath hydrogen analyzers to rapidly and accurately detect hydrogen due to its high selectivity and sensitivity.


Decompaction and biopsy of late mouse morulae: assessment of in-vitro and in-vivo developmental potential.
The present study reports a biopsy technique on decompacted late mouse morulae. Zygotes were collected from hyperstimulated F1 hybrids (C57BL6j females x CBAca males) and cultured in modified Earle's balanced salt solution supplemented with 0.5% bovine serum albumin until the late morula stage (92 h post administration of human chorionic gonadotrophin). Decompaction was obtained by exposure of the embryos to Ca(2+)-Mg(2+)-free phosphate-buffered saline (PBS) or an aqueous solution of ethylene-diaminetetraacetic acid (EDTA) and glycine. Using micromanipulation, a single blastomere was aspirated without removal or softening of the zona. The impact of the different decompaction procedures and the biopsy technique was studied by vital staining, by in-vitro culture up to the early egg-cylinder staged and by the recovery of living mice after transfer to pseudopregnant foster mothers. Our investigations revealed no impact of decompaction and biopsy on immediate viability, as assessed by fluorescein diacetate staining. A significant reduction (P less than 0.05) in the number of mouse morulae that reached the early egg-cylinder stage in vitro was observed after the biopsy procedure. We observed that after this microbiopsy technique, successful pregnancies can be obtained but at a lower percentage compared to controls (P less than 0.01).


Cytotoxic and mutagenic action of 193-nm and 213-nm laser radiation.
To compare the cytotoxic and mutagenic effect of 213-nm and 193-nm laser radiation on cultured mammalian cells. Chinese hamster lung (V79) cells were exposed to 193-nm radiation from an argon fluorine excimer laser or 213-nm radiation from a 5th harmonic Nd:YAG laser. The cytotoxic action of the lasers was compared by determining the number of V79 cell colonies that formed 1 week after irradiating cells with different doses of 193-nm or 213-nm laser radiation or with continuous wave 254-nm radiation. The cytotoxic action of the lasers on primary cultures of human corneal fibroblasts was also compared. The mutagenic potential of the lasers was compared by measuring the number of ouabain or 6-Thioguanine(6TG)-resistant V79 mutants that formed after exposing V79 cells to 193-nm or 213-nm radiation. The dose of 193-nm laser radiation that resulted in 37% survival (D37) of V79 cells was estimated to be 11.3 mJ/cm2 compared to 3.2 mJ/cm2 for 213-nm laser radiation and 1.2 mJ/cm2 for 254-nm UV radiation. The mean number of ouabain-induced mutants induced at the D37 for 193-nm, 213-nm, and 254-nm laser radiation were 28, 166, and 279 mutants/10(7) cells, respectively. Continuous wave 254-nm radiation induced 6TG-resistant colonies, but there was no significant induction of 6TG-resistant mutants by either laser. Although the in vitro data presented herein may or may not be meaningful to humans, the 213-nm Nd:YAG laser was more cytotoxic and mutagenic than the 193-nm excimer laser on cultured mammalian cells but was less cytotoxic and mutagenic than 254-nm radiation.


A Unified Fourth-Order Tensor-Based Smart Community System.
Empowered by the ubiquitous sensing capabilities of Internet of Things (IoT) technologies, smart communities could benefit our daily life in many aspects. Various smart community studies and practices have been conducted, especially in China thanks to the government's support. However, most intelligent systems are designed and built individually by different manufacturers in diverging platforms with different functionalities. Therefore, multiple individual systems must be deployed in a smart community to have a set of functions, which could lead to hardware waste, high energy consumption and high deployment cost. More importantly, current smart community systems mainly focus on the technologies involved, while the effects of human activity are neglected. In this paper, a fourth-order tensor model representing object, time, location and human activity is proposed for human-centered smart communities, based on which a unified smart community system is designed. Thanks to the powerful data management abilities of a high-order tensor, multiple functions can be integrated into our system. In addition, since the tensor model embeds human activity information, complex functions could be implemented by exploring the effects of human activity. Two exemplary applications are presented to demonstrate the flexibility of the proposed unified fourth-order tensor-based smart community system.


[The immunological effects of three doses of a live attenuated hepatitis A vaccine (H2 strain) in 8 years].
To observe the immunological effects of three doses of H2 strain live attenuated hepatitis A vaccine 8 years after the administration and to compare with that of one dose of the vaccine. In a country area, 110 children of 1 to 7 years old susceptible to HAV were screened and administered with one dose of the vaccine, as group B; Group A were 42 children from one of the villages and administered with 3 doses of the vaccine according to 0, 2, 6 month schedule. Blood samples were taken for the children 1, 2, 6, 7, 8, 12, 24, 36 and 96 months after the administrations respectively and detected for anti-HAV antibody. For group B, the sero conversion rate of anti-HAV and GMC reached peak at 92.2% and 126.2 mIU/ml respectively, and then, began to drop with time; For group A, after 2 dose of the vaccine, the sero-conversion rate reached 100%, and the GMC reached peak of 2 739 mIU/ml one month after the third dose at 7 months. So that, group A has a better short-term immunological effects than that of group B. During 36 through 96 months, the anti-HAV positive rate in group B was 75%-71% and 80-89 mIU/ml respectively, and comparatively in group A were 100% and 918.2-480.6 mIU/ml respectively. The differences between group A and B were significantly important. A 3-dose schedule administration of H2 strain live attenuated hepatitis A vaccine has better immunological effects than 1-dose schedule in 8years and further observations are needed.


Haptoglobin phenotypes and in vitro fertilization treatment outcomes.
The haptoglobin (Hp) protein has been implicated in various aspects of reproduction. One possible mechanism is through its effect on angiogenesis. Angiogenesis plays a major role in follicle production. The Hp insertion polymorphism results in the production of Hp proteins denoted Hp 1-1, 2-1, and 2-2, with markedly different angiogenic activities. We sought to determine if the number of oocytes aspirated during in vitro fertilization is related to the Hp type and to compare clinical data and treatment outcomes. We conducted a prospective non-interventional study in an academic in vitro fertilization center serving northern Israel. All patients undergoing in vitro fertilization who agreed to have their haptoglobin phenotype and clinical data evaluated anonymously were included. The main outcome measure was the number of oocytes harvested from each aspiration. The groups did not differ regarding ethnicity or BMI, though women with the Hp1-1 phenotype had a longer duration of infertility (p = 0.037) and a higher gonadotropin requirement (p = 0.024) to achieve the same treatment outcome. Women with mechanical factor infertility were more likely (p = 0.042) to have the Hp 1-1/2-1 phenotypes than the Hp2-2 phenotype. There were no differences in the number of oocytes aspirated or the pregnancy rate. In summary, we could not establish a correlation between Hp phenotype and oocyte number or IVF outcomes though the Hp2-2 phenotype may be protective against mechanical factor infertility. Further studies with a larger sample size, particularly concerning the Hp1-1 phenotype, are required in order to extend these results.


[The diagnostic method of localization of cerebrospinal fluid rhinorrhea by digital video subtraction system].
Demonstration of the exact site of the dural fistula in cerebrospinal fluid rhinorrhea is difficult. Previous reports present the methods of metrizamide cisternography combined with both hypocycloid tomography and computed tomography. But in these methods, direct, dynamic, actual and real-time visualization of the fistula with minimal dose of metrizamide is rather difficult. By using digital video subtraction system (Philips DVI-2CV), we could visualize the direct, dynamic and actual site of fistula with small amount of metrizamide instilled into the suboccipital subarachnoid space with the patient prone position. We report a successful case of traumatic cerebrospinal fluid rhinorrhea drained through the bony defect at the planum sphenoid into the posterior ethmoid sinus. This is the first report to deal with the usefulness of digital video subtraction system for exact localization of cerebrospinal fluid rhinorrhea. We emphasize the usefulness of metrizamide cisternography by the digital video subtraction system combined with the metrizamide computed tomographic cisternography for the precise localization of dural fistula.


Ultrastructural morphology of intermediate forms and forms suggestive of conjugation in the life cycle of Pneumocystis carinii.
The intrapulmonary life cycle of Pneumocystis carinii has been proposed to include asexual reproduction of haploid trophic forms and sexual reproduction to form cysts or ascospores containing 8 intracystic bodies or spores. This study presents the ultrastructural morphology of trophic forms and developing ascospores. Nuclear-associated organelles (NAO) were observed in these various forms and in a binucleated trophozoite. The unique configuration of the nuclei and NAO in this binucleated trophic form were similar to ultrastructural features observed in conjugation of Saccharomyces cerevisiae. NAOs in developing ascospores were present in pairs and were associated with multiple nuclei. In more mature ascospores, NAO were associated with individual spores. The intermediate forms described in this study support an asexual and sexual reproductive process in P. carinii.


Synthesis of 4,5,6,7 and 2,4,5,6,7 Deuterium-labeled Indole-3-Acetic Acid for Use in Mass Spectrometric Assays.
Syntheses are described for tetra and pentadeutero indole-3-acetic acid (IAA) labeled in positions 4, 5, 6, 7 or 2, 4, 5, 6, 7 of the indole moiety. Polydeuterated IAA is proposed as an internal standard for gas chromatographic-mass spectrometric analysis of IAA by selected ion monitoring. Nanogram amounts of IAA may be assayed by monitoring the base peak of IAA at m/z = 130 (134 for d(4)-IAA) and the molecular ion of the methyl ester of IAA at 189 (193 for d(4)-IAA). Deuterium in positions 4, 5, 6, and 7 and, to only a slightly lesser extent, that in position 2 of IAA is retained during alkali treatment, thus permitting use of these compounds as internal standards for assay of IAA released by alkaline hydrolysis of ester and amide conjugates. The use of polydeutero internal standards separates the standards from the "isotope cluster" caused by the normal abundance of heavy isotopes and also permits use of reduced mass resolution, thus leading to a 10-fold increase in sensitivity.Tetradeutero IAA was used as an internal standard for determining free plus ester IAA in alkaline hydrolysates of Zea mays, and showed exact agreement between estimates based on the molecular ion of the methyl ester and those based upon base peak. Application of the method to measuring free IAA in the upper and lower halves of geotropically stimulated Zea shoots showed 61 +/- 4% of the free IAA to be on the lower side.


Conjugate of PAMAM Dendrimer, Doxorubicin and Monoclonal Antibody-Trastuzumab: The New Approach of a Well-Known Strategy.
The strategy utilizing trastuzumab, a humanized monoclonal antibody against human epidermal growth receptor 2 (HER-2), as a therapeutic agent in HER-2 positive breast cancer therapy seems to have advantage over traditional chemotherapy, especially when given in combination with anticancer drugs. However, the effectiveness of single antibody or antibody conjugated with chemotherapeutics is still far from ideal. Antibody⁻dendrimer conjugates hold the potential to improve the targeting and release of active substance at the tumor site. In the present study, we developed and synthesized PAMAM dendrimer⁻trastuzumab conjugates carrying doxorubicin (dox) specifically to cells overexpressing HER-2. ¹HNMR, FTIR and RP-HPLC were used to characterize the products and analyze their purity. Toxicity of PAMAM⁻trastuzumab and PAMAM⁻dox⁻trastuzumab conjugates compared with free trastuzumab and doxorubicin towards HER-2 positive (SKBR-3) and negative (MCF-7) human breast cancer cell lines was determined using MTT assay. Furthermore, the cellular uptake and cellular localization were studied by flow cytometry and confocal microscopy, respectively. A cytotoxicity profile of above mentioned compounds indicated that conjugate PAMAM⁻dox⁻trastuzumab was more effective when compared to free drug or the conjugate PAMAM⁻trastuzumab. Moreover, these results reveal that trastuzumab can be used as a targeting agent in PAMAM⁻dox⁻trastuzumab conjugate. Therefore PAMAM⁻dox⁻trastuzumab conjugate might be an interesting proposition which could lead to improvements in the effectiveness of drug delivery systems for tumors that overexpress HER-2.


Induction of hepatic aneuploidy in vivo by tamoxifen, toremifene and idoxifene in female Sprague-Dawley rats.
Since tamoxifen is efficacious for the prevention of second primary breast neoplasms in humans and has a low reported incidence of acute side effects, several structurally related compounds have been developed for the treatment of breast cancer including toremifene and idoxifene. We have compared the karyotypic alterations that occur after a single per os administration of 35 mg/kg of tamoxifen, toremifene or idoxifene to female Sprague-Dawley rats. One day following treatment, the rats were sacrificed and the hepatocytes isolated and cultured. After 47 h in culture, colcemid was added for 3 h prior to harvest of the hepatocytes for karyotypic evaluation. At least 100 metaphase spreads were examined for each of five rats per treatment. Toremifene resulted in aneuploidy in 50 +/- 7% of the cells examined and idoxifene induced a 57 +/- 4% aneuploidy compared with the 85 +/- 7% level induced by tamoxifen. Since the level of aneuploidy in solvent-treated rats was 3 +/- 3 %, the induction of aneuploidy in at least 50% of the cells from rats treated with tamoxifen, toremifene or idoxifene was highly significant. Analysis of electron micrographs of cultures treated with these antiestrogens demonstrated a range of phenotypes including multipolar spindles in toremifene-treated rats and condensed chromosomes in the presence of an intact nuclear envelope in occasional idoxifene-treated rat hepatocytes. The exclusion of chromosomes from the spindle apparatus and the lagging of some chromosomes on the metaphase plate correlate with the high rate of induction of aneuploidy in the rat liver as determined by karyotypic analysis of hepatocytes from rats treated with these triphenylethylenes.


Deep dermal and subcutaneous canine hemangiosarcoma in the perianal area: diagnosis of perianal mass in a dog.
Tumors of the perianal area occur frequently in dogs, and the two most common tumors are perianal gland adenoma and anal sac adenocarcinoma; others such as mast cell tumor, lymphoma and melanoma can also occur at this site. Diagnostic cytology is a useful technique and is usually used to establish a definitive diagnosis of some tumors in veterinary medicine. This report describes an extremely rare case of a deep dermal and subcutaneous canine hemangiosarcoma in the perianal area. A 13-year-old intact male spaniel was presented for evaluation of a 4 × 4 cm, ulcerated, and hemorrhagic mass presented in the right perianal region. In cytologic evaluation, malignant mesenchymal tumor with inflammation was diagnosed, and incidental heart worm microfilaremia was identified. Based on the cytologic evaluation, a punch biopsy (3 mm, three sites) was conducted under anesthesia and deep dermal and subcutaneous hemangiosarcoma (3 mitotic figures/10 high power field (400×)) was diagnosed by histopathological evaluation. It was also confirmed by immunohistochemistry results for cluster of differentiation 31 (CD31) and factor VIII-related antigen marker. Deep dermal and subcutaneous hemangiosarcoma in the perianal region is a rare condition, and its prognosis is usually poor. Perianal gland adenoma and anal sac adenocarcinoma are the two most common tumors in the perianal region, but other different types of tumors may also occur as in this case; therefore, accurate diagnosis is required using cytology and/or histopathological examination.


Dissection of the superior cerebellar artery: a report of two cases and review of the literature.
Arterial dissections frequently involve the main trunk of the posterior circulation and are recognised as an important cause of stroke in young individuals. However, dissection confined to cerebellar arteries is rare. We encountered two patients with superior cerebellar artery (SCA) dissection. A 37-year-old man presented with dysarthria, right limb ataxia, and severe headache. Magnetic resonance imaging revealed cerebellar infarction in the right SCA territory. Angiography demonstrated stenosis and fusiform dilation of the SCA in the anterior pontine segment. Recovery with antiplatelet treatment was nearly complete. A 45-year-old man was admitted with decreased consciousness after sudden onset of headache. Computed tomography demonstrated subarachnoid haemorrhage with hydrocephalus. Angiography revealed fusiform dilation of the left SCA in the anterior pontine segment. After ventricular drainage, endovascular embolisation was performed without ischaemic complications. The patient's condition improved sufficiently to return to daily life. In our search only four reported cases involved the SCA. Clinical manifestation and treatment for patients with cerebellar arterial dissections are discussed.


Administration of Bacillus subtilis strains in the rearing water enhances the water quality, growth performance, immune response, and resistance against Vibrio harveyi infection in juvenile white shrimp, Litopenaeus vannamei.
In this study, vegetative cell suspensions of two Bacillus subtilis strains, L10 and G1 in equal proportions, was administered at two different doses 10(5) (BM5) and 10(8) (BM8) CFU ml(-1) in the rearing water of shrimp (Litopenaeus vannamei) for eight weeks. Both probiotic groups showed a significant reduction of ammonia, nitrite and nitrate ions under in vitro and in vivo conditions. In comparison to untreated control group, final weight, weight gain, specific growth rate (SGR), food conversion ratio (FCR) and digestive enzymatic activity were significantly greater in the BM5 and BM8 groups. Significant differences for survival were recorded in the BM8 group as compared to the control. Eight weeks after the start of experiment, shrimp were challenged with Vibrio harveyi. Statistical analysis revealed significant differences in shrimp survival between probiotic and control groups. Cumulative mortality of the control group was 80%, whereas cumulative mortality of the shrimp that had been given probiotics was 36.7% with MB8 and 50% with MB5. Subsequently, real-time RT-PCR was employed to determine the mRNA levels of prophenoloxidase (proPO), peroxinectin (PE), lipopolysaccharide- and β-1,3-glucan- binding protein (LGBP) and serine protein (SP). The expression of all immune-related genes studied was only significantly up-regulated in the BM5 group compared to the BM8 and control groups. These results suggest that administration of B. subtilis strains in the rearing water confers beneficial effects for shrimp aquaculture, considering water quality, growth performance, digestive enzymatic activity, immune response and disease resistance.


Polycystic kidney disease associated with cervical arteriovenous shunt and bilateral jugular vein occlusion.
A 59-year-old man with abnormal vascular features (intracranial aneurysm, a cervical arteriovenous shunt, bilateral internal jugular vein occlusions, and left transverse sinus hypoplasia), as well as left optic atrophy was suspected to have familial polycystic kidney disease. The possibility of autosomal dominant polycystic kidney disease complicated by Ehlers-Danlos syndrome type IV due to the coexistence of vasculopathy and polycystic kidneys was considered. However, the negative results of a skin fibroblast culture rendered the diagnosis of Ehlers-Danlos syndrome type IV unlikely. The cause of left optic atrophy in our patient remains unclear although it was suspected to be a secondary consequence of papilledema, which was caused by intracranial hypertension.


Facing Diseases Caused by Trypanosomatid Parasites: Rational Design of Pd and Pt Complexes With Bioactive Ligands.
Human African Trypanosomiasis (HAT), Chagas disease or American Trypanosomiasis (CD), and leishmaniases are protozoan infections produced by trypanosomatid parasites belonging to the kinetoplastid order and they constitute an urgent global health problem. In fact, there is an urgent need of more efficient and less toxic chemotherapy for these diseases. Medicinal inorganic chemistry currently offers an attractive option for the rational design of new drugs and, in particular, antiparasitic ones. In this sense, one of the main strategies for the design of metal-based antiparasitic compounds has been the coordination of an organic ligand with known or potential biological activity, to a metal centre or an organometallic core. Classical metal coordination complexes or organometallic compounds could be designed as multifunctional agents joining, in a single molecule, different chemical species that could affect different parasitic targets. This review is focused on the rational design of palladium(II) and platinum(II) compounds with bioactive ligands as prospective drugs against trypanosomatid parasites that has been conducted by our group during the last 20 years.


Thioredoxin-interacting protein deficiency disrupts the fasting-feeding metabolic transition.
Through a positional cloning approach, the thioredoxin-interacting protein gene (Txnip) was recently identified as causal for a form of combined hyperlipidemia in mice (Bodnar, J. S., A. Chatterjee, L. W. Castellani, D. A. Ross, J. Ohmen, J. Cavalcoli, C. Wu, K. M. Dains, J. Catanese, M. Chu, S. S. Sheth, K. Charugundla, P. Demant, D. B. West, P. de Jong, and A. J. Lusis. 2002. Positional cloning of the combined hyperlipidemia gene Hyplip1. Nat. Genet. 30: 110-116). We now show that Txnip-deficient mice in the fed state exhibit a metabolic profile similar to fasted mice, including increased levels of plasma ketone bodies and free fatty acids, decreased glucose, and increased hepatic expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and acyl-CoA oxidase. Dramatic differences in the expression of key metabolic enzymes were also observed in other tissues, and the fat-to-muscle ratio of Txnip-deficient mice was increased by approximately 40%. We demonstrate an effect of Txnip on the redox status, as the Txnip-deficient mice in the fed state had a significant increase in the ratio of NADH to NAD(+). Surprisingly, we observed that Txnip-deficient mice and wild-type mice had similar levels of thioredoxin activity, suggesting that the effects of Txnip deficiency may be mediated in part by other interactions. These results indicate a role for Txnip in the metabolic response to feeding and the maintenance of the redox status.


Efficacy of Electrical Spinal Cord Stimulation with Neuromodulating Medications: A Systematic Review.
Chronic pain is a prevalent and debilitating problem for millions of people and spinal cord stimulation (SCS) is one option for treatment. It has been shown to have membrane stabilizing properties and is often used in conjunction with medications that are also believed to offer pain control through membrane stabilization. The goal of this review is to analyze the effects of SCS combined with medications to evaluate for augmentative therapeutic effect. Systematic review. A systematic computerized search of the literature was conducted using PubMed, the Cochrane Library, and EMBASE for articles published in English. We report three articles that discuss the potential for augmentative effects of medication in combination with SCS. Located articles related primarily to SCS combined with Gabapentin, TCA, or SNRI. The limited number of articles reflects a need for more investigation in this area. Based on the suspected mechanisms for SCS and neuromodulating medications, there is reason to believe adding these medical therapies may enhance the effects of SCS.


Galectin-3 deficiency prevents concanavalin A-induced hepatitis in mice.
We used concanavalin A (Con A)-induced liver injury to study the role of galectin-3 (Gal-3) in the induction of inflammatory pathology and hepatocellular damage. We tested susceptibility to Con A-induced hepatitis in galectin-3-deficient (Gal-3(-/-)) mice and analyzed the effects of pretreatment with a selective inhibitor of Gal-3 (TD139) in wild-type (WT) C57BL/6 mice, as evaluated by a liver enzyme test, quantitative histology, mononuclear cell (MNC) infiltration, cytokine production, intracellular staining of immune cells, and percentage of apoptotic MNCs in the liver. Gal-3(-/-) mice were less sensitive to Con A-induced hepatitis and had a significantly lower number of activated lymphoid and dendritic cells (DCs) in the liver. The level of tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), and interleukin (IL)-17 and -4 in the sera and the number of TNFα-, IFNγ-, and IL-17- and -4-producing cluster of differentiation (CD)4(+) cells as well as IL-12-producing CD11c(+) DCs were lower, whereas the number of IL-10-producing CD4(+) T cells and F4/80(+) macrophages were significantly higher in livers of Gal-3(-/-) mice. Significantly higher percentages of late apoptotic Annexin V(+) propidium-idodide(+) liver-infiltrating MNCs and splenocytes were observed in Gal-3(-/-) mice, compared to WT mice. Pretreatment of WT C57BL/6 mice with TD139 led to the attenuation of liver injury and milder infiltration of IFNγ- and IL-17- and -4-producing CD4(+) T cells, as well as an increase in the total number of IL-10-producing CD4(+) T cells and F4/80(+) CD206(+) alternatively activated macrophages and prevented the apoptosis of liver-infiltrating MNCs. Gal-3 plays an important proinflammatory role in Con A-induced hepatitis by promoting the activation of T lymphocytes and natural killer T cells, maturation of DCs, secretion of proinflammatory cytokines, down-regulation of M2 macrophage polarization, and apoptosis of MNCs in the liver.


Microcomputer software applied to corneal stromal biometry.
Here we report a new method for image analysis of the corneal stroma. To obtain the biometric characteristics of a given area, we perform three different treatments of the same image. These automated predictions closely match each parameter (length, surface area, etc.), as measured manually by a "blind investigator." Furthermore, to obtain quantifiable, average values, we have increased the number of successive image measurements, which has led to the development of a series of programs designed to optimize automated data handling. Finally, the acquired, calculated parameters are summarized in the form of intermediate tables for each series of images, and as a final summary table incorporating t-test values and permitting comparison between two stromas (e.g., normal and pathological). Multivariate analysis and an ascending hierarchical classification demonstrate the main trends in differences of pathological vs. normal stroma.


The relationship between optic disc area and open-angle glaucoma: the Baltimore Eye Survey.
To determine if eyes with larger optic disc area are more likely to have open-angle glaucoma or to have glaucoma at lower intraocular pressure (IOP). Data were collected from a population-based sample of adults residing in East Baltimore, consisting of demographic information, ocular examinations, automated and static/kinetic visual field tests, IOP as measured by applanation tonometry, and image analysis of the optic disc. Optic disc area was calculated using refractive error to correct magnification. Open-angle glaucoma was defined by visual field and optic disc criteria. One eye from each of 75 patients with glaucoma was compared to those of 3,518 subjects without glaucoma. Although optic disc area was somewhat larger among patients with glaucoma than control subjects, in a regression model adjusting for age, gender, and race, the significance of this difference had a probability of 0.06. Among patients with glaucoma, disc area was not related to IOP level measured at study examination. Disc area is a weak risk factor for open-angle glaucoma. Disc area did not differ between patients with glaucoma who had lower IOP and those who had higher IOP among a group with glaucoma that were identified in a population survey.


Prevalence of Unmet Basic Needs and Association with Diabetes Control and Care Utilization Among Insured Persons with Diabetes.
Unmet basic needs (eg, food insecurity, inadequate housing) are major barriers to diabetes self-management. The purpose of this study was to identify the prevalence of unmet basic needs and examine the association with diabetes control and care utilization among insured persons with diabetes. A total of 4043 adult patients with diabetes were screened for unmet basic needs using Your Current Life Situation, a screener for unmet basic needs, during a clinical encounter or as an online survey, during the study period (January 1, 2016-August 31, 2017). Hemoglobin A1c and care utilization (outpatient, emergency department [ED], hospitalization, diabetes-related prescription refills) were extracted from the electronic health record 12 months prior to screening. The authors compared patients with unmet basic needs to those with no needs on poor diabetes control (ie, A1c ≥8%) and care utilization using multivariable regression models. Of the 4043 patients screened, 25% endorsed ≥1 unmet basic need. In adjusted analyses, the presence of unmet basic needs was associated with an increased likelihood of having an A1c ≥8% (OR = 1.77; 95% CI 1.47, 2.13), more outpatient visits (incidence rate ratio [IRR] = 1.3; 1.2, 1.4), more ED visits (IRR = 2.3; 2.0, 2.6), more hospitalizations (IRR = 1.8; 1.5, 2.2), and more delays in refilling diabetes medication (IRR = 1.21; 1.13, 1.30). Findings indicate that unmet basic needs are highly prevalent, even among an insured patient population, and are associated with poor diabetes-related clinical outcomes and excess utilization. Future studies to determine best strategies to integrate this information into treatment planning are warranted.


Sequential Short Interval Anti-VEGF for the Treatment of Stage 4 Retinopathy of Prematurity.
A 23-month-old girl born at 23 weeks' gestational age with a birth weight of 453 g and retinopathy of prematurity (ROP) stage 4A in 360° and plus disease in both eyes was treated in another institution with laser; her treatment was complicated with two cardiac arrests during the procedure. The patient was referred and treated at 31 weeks with repeated intravitreal bevacizumab injection in both eyes secondary to progressive ROP. Treatment with multiple anti-vascular endothelial growth factor (VEGF) therapy as monotherapy led to the resolution of a retinal detachment and full vascularization of the retina in both eyes. To the best of the authors' knowledge, this is the first description of a patient with stage 4A ROP treated solely with anti-VEGF after failed laser treatment that led to complete resolution of a retinal detachment without surgical intervention. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:159-163.].


Manual hyperinflation in children.
Manual hyperinflation is used in neonatal and pediatric intensive care units to promote expiratory flow bias, but there is no consensus on the benefits of the technique. Thus, a review that presents supporting evidence is necessary. This study aims to review the literature on the manual hyperinflation maneuver in neonatal and pediatric intensive care units to analyze the evidence for this technique in terms of the forms of application (associated with other techniques or not), its safety, the performance of manual resuscitators and the influence of the physical therapist's experience, in addition to evaluating the methodological quality of the identified articles. A search was performed in the following databases: Web of Science, ScienceDirect, PubMedⓇ, Scopus, CINAHL and SciELO. Two researchers independently selected the articles. Duplicate studies were assessed, evaluated by title and abstract and then read in full. The quality of the articles was analyzed using the PEDro scale. Six articles were included, two of which had high methodological quality. The main results provided information on the contribution of the positive end-expiratory pressure valve to increasing lung volumes and the use of chest compressions to optimize expiratory flow bias, the negative influence of operator experience on the increase in peak inspiratory flow, the performance of different manual resuscitators when used with the technique and the safety of application in terms of maintaining hemodynamic stability and increasing peripheral oxygen saturation. The available studies point to a positive effect of the manual hyperinflation maneuver in children who are admitted to intensive care units. Registration PROSPERO: CRD42018108056.


Exact level densities for the harmonic oscillator.
The number of levels of a many-fermion system confined by a harmonic-oscillator potential is computed as a function of excitation energy. Because of its exact nature, the formalism accounts for effects of shell structure on the level density. The method is easily extended to a variety of situations as is illustrated with the inclusion of isospin and deformation effects as well as a calculation of the number of spurious states.


A chemical covalent tactic for bio-thiol sensing and protein labeling agent design.
Discovering novel chemical reactions is important for bioanalysis. Herein, we report a tactic for bio-thiol sensing and protein labeling agent design by the installation of a sulfoxide group onto the skeleton of various fluorophores, and powerfully validate its abilities, which may shed light on the development of specific protein tags to give insight into their biological functions.


N-linked sugar chains of mouse B16 melanoma cells and their low-metastasizing variant selected by wheat germ agglutinin.
The N-linked sugar chains of metastasizing mouse B16 melanoma cells (F1) and their wheat germ agglutinin-resistant variant (Wa4-b1) showing a dramatic decrease in metastasizing and tumorigenic potentials were liberated from their membrane glycoproteins by hydrazinolysis, and their structures were comparatively analysed. The results indicated that both cell lines contain high-mannose-type and bi-, tri- and tetraantennary complex-type oligosaccharides, and their ratios are similar. However, outer chain moieties of tri- and tetraantennary oligosaccharides of the variant are extensively fucosylated, resulting in the formation of X-antigenic determinants, Gal beta 1----4(Fuc alpha 1----3)GlcNAc. Oligosaccharides containing X-antigenic determinants amounted to 71% of the total complex-type oligosaccharides. Fucosylation occurs on every N-acetyllactosamine unit and the number of the determinants ranges from one to three in triantennary oligosaccharides and one to four in tetraantennary oligosaccharides. The determinants occur predominantly in non-sialylated forms, although some are in sialylated forms. Oligosaccharides containing non-sialylated X-antigenic determinants and those containing sialylated X-antigenic determinants are approximately in the ratio 6:1. Since no significant difference was found in the extent of branching of complex-type oligosaccharides of the two cell lines, it is suggested that non-fucosylated outer chains are important for the expression of metastasizing potential by the tumour cells.


5-Lipoxygenase inhibitors: the synthesis and structure-activity relationships of a series of 1-phenyl-3-pyrazolidinones.
A series of analogues of the 5-lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone, 1a) has been prepared via two complementary new synthetic methods. The reaction of various electrophiles with the dianion of 1a or with an N-silylpyrazolidinone anion gave the desired 4-substituted pyrazolidinones (Scheme I and II). A new procedure was developed for the resolution of 4-substituted pyrazolidinones (Scheme V). A regression study on 21 compounds in this series showed a correlation of increased inhibitor potency (pIC50) with increased compound lipophilicity (log P) and with an N-phenyl electronic effect as measured by the 13C NMR chemical shift parameter CNMR1' (R2 = 0.79). The most potent 5-lipoxygenase inhibitor in this series was 4-(ethylthio)-1-phenyl-3-pyrazolidinone (1n) with an IC50 of 60 nM. Another member of this series, 4-(2-methoxyethyl)-1-phenyl-3-pyrazolidinone (1f, IC50 = 0.48 microM), although less potent than 1n, was better tolerated in the whole animal relative to phenidone (1a) and also displayed good oral activity in two models of 5-lipoxygenase inhibition. On the basis of a structure-activity relationship study, a mechanism for the inhibition of 5-lipoxygenase by this class of inhibitors was proposed.


Candesartan cilexetil: an angiotensin II receptor blocker.
To summarize and critique the medical literature on candesartan cilexetil, an angiotensin II receptor blocker (ARB). MEDLINE searches (January 1966-January 1999) and manufacturer prescribing literature were used to identify articles on candesartan cilexetil. Bibliographies were also reviewed for germane articles. Study and review articles describing the chemistry, human pharmacology, pharmacodynamics, pharmacokinetics, placebo-controlled trials, comparative trials, and clinical application of candesartan cilexetil based on the published literature and premarketing clinical trials were reviewed. All literature on the use of candesartan cilexetil for treating hypertension and congestive heart failure were included. ARBs are a new class of drugs with increasing use in treating hypertension. Studies are ongoing to determine the role of these agents in preventing remodeling after myocardial infarction and in patients with congestive heart failure. Candesartan cilexetil is among the newest drugs in the class that includes losartan, irbesartan, and valsartan. Candesartan cilexetil has more than 1000 times more affinity for the angiotensin II, type AT1 receptor ARBs, and the binding affinity and competitive angiotensin II receptor antagonism is stronger than that of losartan. Clinical studies in patients with hypertension have demonstrated that candesartan cilexetil, in doses of 4-16 mg, is more effective in reducing sitting diastolic blood pressure than are placebo and losartan 50 mg. Candesartan cilexetil has demonstrated reductions in blood pressure comparable to those of enalapril, with the rate of adverse events greater in the enalapril group. Dosage adjustments are not necessary in elderly patients or in patients with mild hepatic or renal dysfunction. In diabetic patients, blood glucose, hemoglobinA1c, and serum lipids are not affected. The clinical studies demonstrated that the adverse effect profile of candesartan cilexetil was similar to that of placebo and there were no dose-dependent adverse effects. Candesartan cilexetil provides an alternative antihypertensive therapy that is well tolerated and effective in reducing blood pressure in a wide range of patients. Due to its greater binding affinity to the angiotensin II receptor, candesartan cilexetil appears to have a longer antihypertensive effect than losartan. This may be advantageous in decreasing morbidity and mortality associated with hypertension, although further studies are required to validate this potential advantage.


[Selective reduction of NO over indium catalysts prepared by different methods].
Alumina-supported indium catalysts with different metal loadings were prepared by various methods including impregnation, co-precipitation and sol-gel. Activity tests were carried out on the selective catalytic reduction (SCR) of NO by propene in excess O2 over the catalysts. And the effects of oxygen concentration in reaction gas feed on catalytic activities were examined. The results show that In/Al2O3 catalysts possess high deNO2 activity, and the preparation methods have obvious effects on catalytic activities. The catalysts prepared by co-precipitation or sol-gel method exhibited high NO, conversion to N2 about 90%; the impregnation samples have poor activities, the highest conversion rate not exceeding 60%. The O2 concentration in gas feed has significant effects on the highest conversion rates of NOx reduction and the corresponding reaction temperatures. Along with the increasing of O2 concentration, the temperatures mentioned above declined. The introduction of water into the gas feed depressed greatly the deNO2 activities of In/Al2O3 catalysts. Compared to many other metals as active components of deNOx catalysts, indium has a prominent different behavior that the respective best metal loadings of the catalysts prepared by these three diverse preparation methods have little difference, being all around 1% to approximately 2%.


Laser-guided cervical selective nerve root block with the Dyna-CT: initial experience of three-dimensional puncture planning with an ex-vivo model.
Cervical selective nerve root block (CSNRB) is a well-established, minimally invasive procedure to treat radicular cervical pain. However, the procedure is technically challenging and might lead to major complications. The objective of this study was to evaluate the feasibility of a three-dimensional puncture planning and two-dimensional laser-guidance system for CSNRB in an ex-vivo model. Dyna-CT of the cervical spine of an ex-vivo lamb model was performed with the Artis Zee® Ceiling (Siemens Medical Solutions, Erlangen, Germany) to acquire multiplanar reconstruction images. 15 cervical nerve root punctures were planned and conducted with the syngo iGuide® laser-guidance system. Needle tip location and contrast dye distribution were analyzed by two independent investigators. Procedural, planning, and fluoroscopic time, tract length, and dose area product (DAP) were acquired for each puncture. All 15 punctures were rated as successful with 12 punctures on the first attempt. Total procedural time was approximately 5 minutes. Mean planning time for the puncture was 2.03 (±0.39) min. Mean puncture time was 2.16 (±0.32) min, while mean fluoroscopy time was 0.17 (±0.06) min. Mean tract length was 2.68 (±0.23) cm. Mean total DAP was 397.45 (±15.63) µGy m(2). CSNRB performed with Dyna-CT and the tested laser guidance system is feasible. 3D pre-puncture planning is easy and fast and the laser-guiding system ensures very accurate and intuitive puncture control.


Assembly of the outermost spore layer: pieces of the puzzle are coming together.
Certain endospore-forming soil dwelling bacteria are important human, animal or insect pathogens. These organisms produce spores containing an outer layer, the exosporium. The exosporium is the site of interactions between the spore and the soil environment and between the spore and the infected host during the initial stages of infection. The composition and assembly process of the exosporium are poorly understood. This is partly due to the extreme stability of the exosporium that has proven to be refractive to existing methods to deconstruct the intact structure into its component parts. Although more than 20 proteins have been identified as exosporium-associated, their abundance, relationship to other proteins and the processes by which they are assembled to create the exosporium are largely unknown. In this issue of Molecular Microbiology, Terry, Jiang, and colleagues in Per Bullough's laboratory show that the ExsY protein is a major structural protein of the exosporium basal layer of B. cereus family spores and that it can self-assemble into complex structures that possess many of the structural features characteristic of the exosporium basal layer. The authors refined a model for exosporium assembly. Their findings may have implications for exosporium formation in other spore forming bacteria, including Clostridium species.


[Analyses of risk factors for temporarily inhibited parathyroid hormone secretion of postoperative primary hyperparathyroidism].
Objective: To study relative risk factors for temporarily inhibited parathyroid hormone (PTH) secretion after surgery of primary hyperparathyroidism (PHPT). Methods: Seventy-two cases with PHPT from October 2017 to March 2019 in Beijing Chaoyang Hospital were analyzed retrospectively, including 22 males and 50 females aged from 13 to 83 years old. They were reviewed and divided into a complete inhibition group (24 cases, PTH=0 pg/ml), an incomplete inhibition group (23 cases, 0<PTH<12.4 pg/ml), and a non-inhibition group (25 cases, PTH≥12.4 pg/ml) according to the PTH level on the first day after surgery of PHPT. With the Kruskal-Wallis multi-group rank sum test and the Nemenyi test, preoperative and postoperative biochemical parameters and endocrine indexes, including the preoperative serum levels of calcium, phosphorus, PTH, 25-hydroxyvitamin D, and alkaline phosphatase, as well as the levels of PTH 10 min after focal resection, calcium on the first day after surgery, and PTH on the third day after surgery, were compared among three groups to evaluate potential risk factor for postoperative temporary inhabitation of PTH secretion. The predictive values of various risk factors for postoperative temporary inhibition of PTH secretion were evaluated with ROC curve analysis. Results: Preoperative serum PTH, calcium levels, and serum calcium level on the first day after surgery in the complete inhibition group were higher than those in the non-inhibition group,respectively, with statically significant differences [256.5(141.6,585.3) pg/ml vs. 130.2(92.1,256.6) pg/ml, 2.90(2.69,3.22) mmol/L vs. 2.61(2.50,2.75) mmol/L, 2.23(2.08,2.41) mmol/L vs. 2.12(2.05,2.14) mmol/L, χ(2) were 7.17, 11.90, 8.32, respectively, all P<0.05]. When the preoperative serum calcium level was higher than 2.62 mmol/L (AUC=0.698, 95%CI: 0.57-0.83, P=0.006) or the preoperative PTH level was higher than 115.9 pg/ml (AUC=0.697, 95%CI: 0.58-0.82, P=0.007), patients tended to inhibit completely PTH secretion after operation. Conclusions: Preoperative serum calcium and PTH levels are risk factors for postoperative temporary PTH inhibition in PHPT.


Topical phenytoin treatment of stage II decubitus ulcers in the elderly.
To compare the healing of stage II decubitus ulcers with topically applied phenytoin sodium with two other standard topical treatment procedures in a long-term care setting; and to assess the extent of systemic absorption after topical application in the phenytoin group. Forty-seven nursing home patients with stage II decubitus ulcers were chosen for this study. The patients were matched for age, gender, and size and severity of wounds, and randomly assigned to each treatment group. Clinical assessment of decubitus ulcers was performed at the beginning of treatment and at each dressing change. Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing. Two phenytoin sodium plasma concentrations were to be obtained on all patients in the phenytoin group. Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications (p < or = 0.05). The mean +/- SD time to healing in the phenytoin group was 35.3 +/- 14.3 days compared with 51.8 +/- 19.6 and 53.8 +/- 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively. Healthy granulation tissue in the phenytoin group appeared within two to seven days in all subjects. Patients in the standard treatment groups required six to 21 days to produce new granulation tissue. Serum phenytoin sodium concentrations were nondetectable. No patient withdrew from the study secondary to adverse treatment effects. Both the phenytoin and standard treatment groups showed progress over the study period. However, the phenytoin group demonstrated more rapid results in all aspects of ulcer healing.


This thing called life.
Academic pursuits are inseparable from the medium within which they take place - life. The lives of medical trainees can present many challenges that are independent of academic demands. Poor psychological health has been found to develop in medical trainees. Can medical educators minimize this decline in well-being? Positive education - learning skills for traditional academia and to foster happiness - has been shown to improve students' well-being. This piece considers the application of 'positive education' to medical training. By using this approach, we may optimize the lives of our trainees, potentially enhance learning and improve their academic and personal outcomes.


Effects of supplementation with a phytobiotics-rich herbal mixture on performance, udder health, and metabolic status of Holstein cows with various levels of milk somatic cell counts.
This study evaluated the effects of dietary supplementation of a novel phytobiotics-rich herbal mixture (PRHM) on feed intake, performance, udder health, ruminal fermentation, and plasma metabolites in cows with moderate or high somatic cell counts (SCC) in the milk. Twenty-four Holstein dairy cows (117 ± 26 d in milk and 46.3 ± 4.7 kg of milk/d at the start of the experiment) were blocked by parity and days in milk and split into 2 groups, based on SCC in the milk; 12 cows were with moderate SCC (260,000<SCC <500,000 cells/mL), whereas 12 other cows had high levels of SCC (>500,000 cells/mL) in the milk. Within each SCC group, cows were blocked by milk yield and parity, and were randomly assigned to 2 different feeding regimens. Half of the cows in each SCC group (n=6) were supplemented with PRHM (185 g/cow per day, providing 12.4 g of phenolic compounds per day), and the other half (n=6) were not supplemented in their diets. The experiment lasted 36 d, whereby the first 24 d were used for adaptation to the diets and the last 12 d for sampling. Data showed that supplementation of PRHM decreased somatic cell score in the milk, indicating improved udder health of cows with high initial SCC, but not in cows with moderate SCC. Also, cows supplemented with PRHM consumed more feed DM, produced greater amounts of milk, and showed an improvement of feed utilization efficiency. However, these cows also lost more back-fat thickness during the experiment. Supplementation of PRHM increased fat- and energy-corrected milk yields in cows with high initial SCC, but not in cows with moderate SCC. Supplementation of PRHM decreased milk fat content, whereas other milk components were not affected by PRHM feeding. The PRHM supplementation decreased the acetate-to-propionate ratio in the rumen fluid, but increased β-hydroxybutyrate and cholesterol concentration in the plasma, irrespective of the initial SCC level in the milk. Other plasma metabolites and liver enzymes were not affected by PRHM supplementation. Apparent nutrient digestibility did not differ among treatments. Overall, supplementation of PRHM seems to be an effective strategy to enhance performance and lower SCC, particularly in cows having high SCC levels in the milk. Further research is warranted to evaluate long-term effects of PRHM supplementation, especially with regard to metabolic health status and reproduction.


Progress in dietary behavior change.
Nutrition has important influences on health and mortality. Public response to current dietary guidance is indicated by positive movement on some indicators, notably reductions in calories from fat and in blood cholesterol levels. Downstream case finding and intensive educational and behavioral interventions are often effective for high risk and motivated subjects and for persons with diet-related disease. Midstream environmental changes (e.g., in grocery stores, schools) proffer improved nutritional choices and supports. Individualized dietary counseling has yet to become the norm. Despite recent upstream success in developing broad dietary guidance and improving nutrition labeling policies, numerous avenues remain open for aggressive national policy developments. Emerging studies and continuing improvement in intervention methods, measurement, and research design will help realize the preventive effects of healthful diets.