Trends for incidence of hospitalization and death due to GI complications in the United States from 2001 to 2009.
Studies from the 1990s through mid-2000s report variable decreases in upper gastrointestinal (UGI) complications and differ regarding changes in lower gastrointestinal (LGI) complications. We determined incidence and case fatality of hospitalizations for GI complications in the United States over the past decade. We used a national inpatient database to calculate yearly projections from 2001-2009 for incidence and case fatality of hospitalizations with primary discharge diagnoses of UGI and LGI complications (bleeding, perforation, and obstruction) and of undefined GI bleeding. Age/sex-adjusted incidence of GI complications decreased non-significantly from 236.1 to 223.7/100,000 population from 2001-2009. Components were UGI complications (85.0 to 66.0/100,000), LGI complications (100.3 to 104.4/100,000), and undefined bleeding (50.8 to 53.3/100,000). Decreases were seen in UGI bleeding (78.4 to 60.6/100,000), peptic ulcer bleeding (48.7 to 32.1/100,000), LGI bleeding (41.8 to 35.7/100,000), and colonic diverticular bleeding (30.4 to 23.9/100,000), whereas LGI obstruction increased (55.0 to 66.0/100,000). Age/sex-adjusted case fatality decreased from 3.78 to 2.70%. 2009 case fatality rates were 2.45% for UGI bleeding, 3.00% for undefined bleeding, 1.47% for LGI bleeding, 2.30% for LGI obstruction, 10.7% for UGI perforation, and 16.0% for LGI perforation. Case fatality increased with age, but was 3.54% in patients >75 years with bleeding or obstruction. Hospitalizations for UGI complications are decreasing in the United States owing to a decrease in UGI bleeding. LGI complications are relatively stable, with a decrease in LGI bleeding and a larger increase in LGI obstruction. Case fatality owing to bleeding or obstruction is low, increasing with age but remaining <5% even in the elderly.


Antibiofilm and antimicrobial activity of Lactobacillus cell free supernatant against Pseudomonas aeruginosa isolated from burn wounds.
The present study investigated the antimicrobial and anti-biofilm effects of indigenous Lactobacillus probiotic strains on Pseudomonas aeruginosa isolated from burn wound infection in laboratory conditions. The effect of 7 probiotic strains isolated from infant faeces on the pathogenicity factors of P. aeruginosa, including protease, elastase, antibiofilm and antipyocyanin was measured. Also, diffusion methods in the well and micro broth dilution were used to evaluate the antimicrobial activity of probiotics. All tests were performed in triplicate. A negative control and a positive control were used for each test. SPSS version 22 software was used for statistical analysis, and a p < 0.05 was considered statistically significant. A total of 30 clinical isolates of P. aeruginosa were isolated. The elastolytic activity of P. aeruginosa isolates decreased after adding Cell free supernatant (CFS) of each Lactobacillus. L1, L4, L5, and L6 strains had a 100% inhibitory effect on pathogen isolates. L3 and L7 strains had the lowest inhibitory effect. The inhibitory effect of CFS extracted from lactobacilli on protease production by P. aeruginosa. L1, L4, L5, and L6 strains had an inhibitory effect on all tested isolates. L2, L3, and L7 strains had a less inhibitory effect. L4 strain had the highest inhibitory effect on pyocyanin production by P. aeruginosa (50%), followed by L5 (43.3%), L1 (40%), and L6 (23.3%) strains. L3 and L7 strains had no inhibitory effect on the pyocyanin production of P. aeruginosa isolates. It was found that the CFS of 4 isolates (L1, L4, L5, and L6) was the most active extract and had a 100% inhibitory effect against biofilm formation of all P. aeruginosa strains. The L3 strain had the least inhibitory effect against the biofilm formation of pathogens. Overall, this study showed that probiotics could be promising alternatives to combat the pathogenicity of P. aeruginosa in burn wounds.


Legionella bacteria and water systems in health care premises.
Legionnaires' disease (Legionellosis) is a bacterial pneumonia that acquired its name following an outbreak of pneumonia among army veterans attending an American Legion convention in Philadelphia in 1976. The previously undiscovered bacterium that caused this form of pneumonia was therefore named Legionella. There are more than 45 species of Legionella bacteria and these are natural inhabitants of water supplies throughout the world (Fliermans, 1981). About half of these have been associated with infection, although the most common cause of Legionnaires' disease is Legionella pneumophila, which is the causative strain in around 90 per cent of cases (Fields et al, 2002).


Atypical presentations of dementia of the Alzheimer type.
Seven patients who eventually met established criteria for dementia of the Alzheimer type are described to illustrate the variety of atypical clinical presentations of this disorder. The value of a careful history, examination, and follow up in reaching the earliest possible diagnosis is emphasized. In the event of the development of adequate therapy this information will become essential in proper management of these patients.


Respiratory viral infections in adults.
Respiratory viral infections in adults cause significant morbidity and mortality, especially in high-risk patients. The impact of influenza virus, rhinoviruses, and respiratory syncytial virus in immunocompromised cancer patients and in asthma and chronic bronchitis patients has been documented in recent publications. Cytomegalovirus pneumonia continues to be a major cause of morbidity and mortality in transplant recipients. Newer rapid diagnostic tests and the use of polymerase chain reaction technology have provided better understanding of the causes and epidemiology of acute respiratory illness in adults. The approved neuraminidase inhibitors for influenza viruses and the nonapproved capsid inhibitors of rhinoviruses may be useful in treating high-risk individuals. The inactivated influenza vaccine has been shown to benefit healthy adults and to be safe in asthmatic adults and children.


Anticipatory child fostering and household economic security in Malawi.
While there is a rich literature on the practice of child fostering in sub-Saharan Africa, little is known about how fostering impacts receiving households, as few studies consider household conditions both before and after fostering. Despite the fact that circumstances surrounding fostering vary, the literature's key distinction of fostering is often drawn along the simple line of whether or not a household is fostering a child. This paper argues that anticipation of fostering responsibilities, in particular, is a useful dimension to distinguish fostering experiences for receiving households. This paper examines the relationship between receiving a foster child and subsequent changes in household wealth. Particular emphasis is placed on how these changes are conditioned by differing levels of anticipation of the fostering event. This study uses data from Tsogolo la Thanzi (TLT), a longitudinal survey in Balaka, Malawi. Using data from 1754 TLT respondents, fixed effects pooled time-series models are estimated to assess whether and how receiving a foster child changes household wealth. This paper demonstrates the heterogeneity of fostering experiences for receiving households. The results show that households that anticipate fostering responsibilities experience a greater increase in household wealth than both households that do not foster and those that are surprised by fostering. Households that anticipate fostering responsibilities exhibit the greatest increase in household wealth. While fostering households that do not anticipate fostering responsibilities may not experience these gains, there is no evidence to indicate that such households are negatively impacted relative to households that do not foster. This finding suggests that additional childcare responsibilities may not be as detrimental to African households as some researchers have feared.


Docetaxel-Induced Systemic Sclerosis with Internal Organ Involvement Masquerading as Congestive Heart Failure.
Systemic sclerosis, or scleroderma, is a complex medical disorder characterized by limited or diffuse skin thickening with frequent involvement of internal organs such as lungs, gastrointestinal tract, or kidneys. Docetaxel is a chemotherapeutic agent which has been associated with cutaneous side effects. An uncommon cutaneous side effect of docetaxel is scleroderma-like skin changes that extend from limited to diffuse cutaneous systemic sclerosis. Several case reports have been published regarding the association of docetaxel and systemic sclerosis. However, those reports demonstrated the association between docetaxel and scleroderma-like skin changes without internal organ involvement. Here, we report a case of systemic sclerosis with pulmonary arterial hypertension and a microangiopathic kidney involvement induced by docetaxel chemotherapy. After an exhaustive literature review, this could be the first case of docetaxel-induced systemic sclerosis involving internal organs.


[The problem of infection in measuring brain ventricle pressure].
Catheters for ventriculometry were implanted into the lateral ventricles of 71 neurosurgical patients. Clinical symptoms of meningitis were recorded from 5.6 per cent of them. A positive bacterial culture was obtained in one case. Reference is made to the risk of infection, and prophylactic antibiotic treatment is advocated.


Angiogenesis and fibroblast proliferation precede formation of recurrent tumors after radiation therapy in nude mice.
Recently, the combination of ionizing radiation with inhibitors of angiogenesis has been reported to improve tumor eradication compared to treatment with irradiation alone. However, the mechanisms of this effect have not been defined. For this purpose [corrected] we established a non-small cell lung cancer model in nude mice. Tumor vascularization was visualized in vivo by MRI using gadolinium-DTPA as contrast agent. Further, cryosections were produced as close as possible to the MRI slice positions. Since we were interested in examining the formation of a recurrent tumor, irradiation was performed with a single fraction of 4 Gy. This dose caused a partial remission followed by recurrent tumor growth 25 to 35 days after therapy. The process of partial remission as well as formation of the recurrent tumor was examined in 28 nude mice analysing the following parameters: (i) contrast agent enhancement using high-resolution MRI, (ii) proliferation of tumor cells and fibroblasts using Ki-67 immunohistochemistry and (iii) formation of microvessels using CD31 immunohistochemistry. The latter analyses led to differentiation of three stages. Stage 1 (day 1 to day 15 after irradiation) was characterized by increasing areas of dead cell mass in hematoxylin-eosin-stained slides that corresponded to a decrease in tumor cell proliferation as well as contrast agent enhancement in MRI. The percentage of Ki-67-positive tumor cells decreased from initially 45.1% +/- 6.0% (mean +/- standard deviation) to 1.4% +/- 1.2% (mean +/- standard deviation) on day 15. Stage 2 (day 6 to day 20 after irradiation; overlapping with stage 1) was characterized by proliferation of fibroblasts leading to formation of fibrotic septae with abundant microvessels. Already during late stage 2, MRI identified new contrast agent enhancing areas. Stage 3 (day 20 to day 40 after irradiation) was characterized by new tumor cell proliferation. Interestingly, tumor cells almost exclusively proliferated in the direct neighbourhood of the fibrotic septae that had been formed in stage 2. Obviously, proliferation of fibroblasts and blood vessels was a condition prior to formation of recurrent tumor tissue. Thus, our results are in contrast with the view that tumors or recurrent tumors begin as avascular masses that later induce neovascularization. With respect to clinical practice, our results suggest that: (i) adjuvant anti-angiogenic therapy should not be limited to the day of irradiation but should cover a critical period until day 5 to day 20 after radiotherapy, (ii) adjuvant therapy should also include inhibition of fibroblast proliferation and (iii) MRI can identify a recurrent tumor 10 to 15 days before occurrence of new tumor growth.


Characterization of adhesion zones in E. coli cells.
After plasmolysis of Escherichia coli cells, the adhesion zones were characterized using the cytochemical PTA and SP procedures which stain peptidoglycan and lipopolysaccharides (LPS) respectively. A PTA-stained layer was detected at the adhesion sites. This layer was visualized irrespective of the electron microscopy procedure used. Also, using SP staining an outer membrane in which LPS molecules were asymmetrically distributed, was observed.


Markers of slow-healing peptic ulcer in the elderly. A study on 1,052 ranitidine-treated patients.
Little is known about ulcer outcome in the elderly. The aims of the present paper were to establish whether risk factors of slow-healing peptic ulcer can be demonstrated in the elderly and whether clinical differences exist between ulcer patients whose age of onset of the disease was before or after 65 years old. The short-term, open study, involving 1052 elderly patients (over 65 years) in 37 gastroenterology centers throughout Italy aimed to compare two schedules of ranitidine treatment: 150 mg twice daily versus 300 mg at bedtime. As nonsignificant differences were found between these two schedules, the sample was considered as a whole. It included 319 gastric ulcer (GU) patients, 699 duodenal ulcer (DU) patients, and 34 concomitant GU and DU cases. Ninety-three patients dropped out of the trial; 79/294 GU, 138/635 DU, and 10/30 GU+DU were found still unhealed after four weeks and 20 GU, 15 DU, and 1 GU+DU remained so after eight weeks. Statistical analysis was performed using likelihood-ratio and Pearson's chi-squared tests and Cox's models. Univariate analysis showed that the indicators of slow-healing GU were ulcer size (P = 0.002) and persisting ulcer symptoms (P = 0.0001); indicators of slow-healing DU were ulcer size (P = 0.0001), persisting ulcer symptoms (P = 0.0001), alcohol (P = 0.0003), and NSAID (P = 0.0088) consumption. DU patients taking antiplatelet drugs have significantly better results after four weeks and worse results after eight weeks (P = 0.0352).(ABSTRACT TRUNCATED AT 250 WORDS)


Fostering study crafting to increase engagement and reduce exhaustion among higher education students: A randomized controlled trial of the STUDYCoach online intervention.
The study demands-resources framework states that study demands increase exhaustion and study resources increase engagement. Study crafting describes a student's proactive adaption to demands and resources. To date, no intervention in the higher education context has aimed to foster study crafting. Accordingly, this study developed and evaluated the STUDYCoach online intervention, which aimed to increase engagement and reduce exhaustion by promoting study crafting. The study was a randomized controlled trial with a waiting-list control group. All participants (N = 209) completed a questionnaire before (T1) and after (T2) the intervention and at a 20-week follow-up (T3). Participants in the intervention group (n = 149) used the STUDYCoach over three consecutive weeks. Results showed that overall study crafting, decreasing hindering demands, and engagement significantly increased in the intervention group compared to the control group after the intervention. All effects remained stable at follow-up. Notably, exhaustion decreased significantly in the intervention group from T1 to T3 and T2 to T3. Study crafting mediated the intervention's effect on engagement and exhaustion. Our study extends the study demands-resources framework and the literature on job crafting by confirming that study crafting interventions can be effective in higher education.


Transcriptomic and Metabolomic Analyses Provide Insights into the Pathogenic Mechanism of the Rice False Smut Pathogen Ustilaginoidea virens.
Rice false smut, caused by the fungal pathogen Ustilaginoidea virens, is a worldwide rice fungal disease. However, the molecular mechanism of the pathogenicity of the fungus U. virens remains unclear. To understand the molecular mechanism of pathogenesis of the fungus U. virens, we performed an integrated analysis of the transcriptome and metabolome of strongly (S) and weakly (W) virulent strains both before and after the infection of panicles. A total of 7932 differential expressed genes (DEGs) were identified using transcriptome analysis. Gene ontology (GO) and metabolic pathway enrichment analysis indicated that amino acid metabolism, autophagy-yeast, MAPK signaling pathway-yeast, and starch and sucrose metabolism were closely related to the pathogenicity of U. virens. Genes related to pathogenicity were significantly upregulated in the strongly virulent strain, and were ATG, MAPK, STE, TPS, and NTH genes. However, genes involved in the negative regulation of pathogenesis were significantly downregulated and contained TOR kinase, TORC1, and autophagy-related protein genes. Metabolome analysis identified 698 differentially accumulated metabolites (DAMs), including 13 categories of organic acids and derivatives, lipids and lipid-like molecules, organoheterocyclic compounds. The significantly enriched pathways of DAMs mainly included amino acids and carbohydrates, and they accumulated after infection by the S strain. To understand the relevance of DEGs and DAMs in the pathogenicity of U. virens, transcriptomic and metabolomic data were integrated and analyzed. These results further confirmed that the pathogenesis of U. virens was regulated by DEGs and DAMs related to these four pathways, involving arginine and proline metabolism, lysine biosynthesis, alanine, aspartate and glutamate metabolism, and starch and sugar metabolism. Therefore, we speculate that the pathogenicity of U. virens is closely related to the accumulation of amino acids and carbohydrates, and to the changes in the expression of related genes.


Case of bilateral retinal neovascularization associated with chronic idiopathic myelofibrosis.
We report a case of bilateral peripheral retinal neovascularization and chronic idiopathic myelofibrosis in a 69-year-old man. Ophthalmic examination revealed peripheral retinal nonperfusion with retinal neovascularization in both eyes and vitreous hemorrhage in the right eye. Fluorescein angiography of both eyes showed a marked midperipheral and peripheral avascular retina temporally with arteriovenous anastomosis and sea-fan neovascularizations. Blood tests showed pancytopenia and teardrop-shaped red blood cells, and bone marrow examination showed hypocellular marrow with severe fibrosis. The neovascularization was regressed following pars plana vitrectomy in the right eye and scatter laser photocoagulation in the left. The results suggest that peripheral retinal vessel occlusion and neovascularization may be associated with idiopathic myelofibrosis.


Analysis of parotid glands of primary Sjögren's syndrome patients using proteomic technology reveals altered autoantigen composition and novel antigenic targets.
Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration, destruction of the salivary and lacrimal glands and production of autoantibodies against a variety of cellular proteins. The aberrant immune response against these autoantigens may begin or extend to other proteins that are not yet defined. Several studies have shown that autoantibody production is taking place in the affected salivary glands. In the present study, using proteomic approaches, we aimed to: (a) identify new autoantigens in the salivary glands of primary SS (pSS) patients and (b) evaluate the epigenetic changes of known autoantigens. Total parotid gland extracts of pSS patients were analysed using two-dimensional gel electrophoresis, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot with pSS patients' sera or purified autoantibodies and immunoprecipitation using homologous IgG. Identification of the unknown proteins was performed using mass spectrometry (MS). Immunoblot analysis on two-dimensional gels using purified anti-La/SSB antibodies revealed that pSS salivary glands contain high levels of post-translationally modified La/SSB autoantigen, while the native form of the protein is recognized faintly, in contrast to normal controls. Moreover, salivary glands of pSS patients contain post-translationally modified actin that becomes immunogenic in the microenviroment of the affected tissue. The alteration of the physicochemical properties of self-proteins could thus contribute to the break of immune tolerance against them.


Identification of a novel redox-sensitive gene, Id3, which mediates angiotensin II-induced cell growth.
Reactive oxygen species, such as superoxide (O(2)(-)), are involved in the abnormal growth of various cell types. Angiotensin II (Ang II) is one of the most potent inducers of oxidative stress in the vasculature. The molecular events involved in Ang II-induced proliferation of vascular smooth muscle cells (VSMCs) are only partially understood. Ang II as well as xanthine/xanthine oxidase (X/XO) led to enhanced DNA synthesis and proliferation of VSMCs. The effect of Ang II was abolished by diphenylene iodonium. Consequently, VSMCs were incubated with X/XO, and modulation of gene expression was monitored by differential display, leading to the identification of a novel redox-sensitive gene, the dominant-negative helix-loop-helix protein Id3, which was upregulated within 30 minutes by X/XO and Ang II. Superoxide dismutase but not catalase inhibited this effect. Overexpression of antisense Id3 via transfection in VSMCs completely abolished Ang II- and X/XO-induced cell proliferation. Ang II, X/XO, and overexpression of sense Id3 downregulated protein expression of p21(WAF1/Cip1), p27(Kip1), and p53. Overexpression of antisense Id3 abrogated the effect of Ang II on the expression of p21(WAF1/Cip1), p27(Kip1), and p53. Ang II and overexpression of sense Id3 caused hyperphosphorylation of the retinoblastoma protein. Ang II-induced phosphorylation of the retinoblastoma protein was decreased by overexpression of antisense Id3. Ang II induces proliferation of VSMCs via production of superoxide, which enhances the expression of Id3. Id3 governs the downstream mitogenic processing via depression of p21(WAF1/Cip1), p27(Kip1), and p53. These findings reveal a novel redox-sensitive pathway involved in growth control.


[Ethical dilemmas of contemporary psychiatry].
Ethics in the contemporary psychiatry, as well as in medicine in general, is based on the two core ethical traditions: deontological and theological. Good ethical decision takes into the consideration both traditions, and is preceded with ethical dilemmas to provide the best possible care to the patients in that moment. In the article are presented most recent research results of the literature about ethical dilemmas in psychiatry. Ethical dilemmas in everyday practice as well as compliance with the patients, psychiatric consultations, informed consent, treatment of personality disorders, pharmacological investigations, forensic psychiatry, forced hospitalisation, promotion of mental health, and dealing with the stigma of the mental diseases are showed in the article. The authors emphasize the necessity of constant questioning of ethical dilemmas in the contemporary psychiatry, because of the special status of psychiatry as a potentially risky field in practice, and because of intensive pharmacological investigations in psychiatric patients.


Clinical presentation of patients with eosinophilic inflammation of the esophagus.
Allergic eosinophilic esophagitis (AEE) is defined by a dense infiltrate of eosinophils within the esophageal mucosa and the absence of pathological gastroesophageal reflux. To characterize a pediatric population with AEE to determine if AEE can be diagnosed based on history; to compare patients with varying degrees of esophageal eosinophilic inflammation to determine if moderate esophageal inflammation is part of a continuum of AEE. Medical records of 112 patients with eosinophils on esophageal biopsy specimens were reviewed. Patients were grouped according to eosinophils per high power field (eos/hpf): group 1 (1-5 eos/hpf, n = 31), group 2 (6-14 eos/hpf, n = 13), and group 3 (> or =15 eos/hpf, n = 68) and compared. University Children's Hospital. Children and adolescents with eosinophils on esophageal mucosal biopsy specimens. Analysis of clinical information. Clinical characterization of patients with esophageal eosinophilia. There was no significant difference in patient demographics. Patients in groups 2 and 3 had multiple food allergens identified. Patients in group 3 with a positive type I allergic response were significantly younger than those with a negative response (mean, 4.6 years old vs mean, 8.5 years old; P = .0065). In group 2, 3 of 13 patients responded histologically to acid-suppressive therapy, whereas 6 patients had improved histology with corticosteroids; 4 of these 6 patients had not responded histologically to acid-suppression. Retrospective study. History and clinical presentation were not useful in predicting the severity of histologic esophageal inflammation in this cohort. Patients with moderate esophageal eosinophilia (group 2) exhibited a variable response to medical therapy.


Rare events via multiple reaction channels sampled by path replica exchange.
Transition path sampling (TPS) was developed for studying activated processes in complex systems with unknown reaction coordinate. Transition interface sampling (TIS) allows efficient evaluation of the rate constants. However, when the transition can occur via more than one reaction channel separated by a high barrier, TPS and TIS are ineffective in sampling both channels. The combination of replica exchange with TIS can overcome this problem. This work shows how, by including both the backward and forward reactions, the corresponding rate constants, as well as the free energy barrier can be computed in a single simulation. The method is illustrated on a two dimensional potential using the Langevin dynamics. In addition, a simpler algorithm based on only forward shooting from the interfaces is shown to give equally accurate results, and forms a bridge between the transition interface and the forward flux sampling methods. The diffusive behavior of the replicas can be used to assess the quality of the choice of the order parameter used for the interfaces.


Murine delayed type hypersensitivity is suppressed by Ascaris suum extract.
We studied the suppressive effect of an Ascaris suum extract on delayed-type hypersensitivity (DTH) reactions to ovalbumin (OVA) and to Bacillus Calmette-Guerin (BCG). The ability of mice to develop DTH reactions to both antigens was suppressed when an immunizing dose of the antigen was given subcutaneously together with the Ascaris extract. Partial or complete suppression of the response to OVA was obtained by the use of 400 or 1000 micrograms of Ascaris extract, respectively. The response to BCG, on the other hand, was totally suppressed by 400 micrograms of extract.


"It's My Responsibility, But…" A Qualitative Study of Perpetrators' Understanding of Child Sexual Abuse.
The present study looked at child sexual abuse (CSA) from the perpetrator's perspective, focusing on precursors to, sustaining mechanisms, and inhibitors of CSA. Individuals serving sentences for sexual abuse of children under the age of 16 were interviewed (N = 8). A qualitative design using interpretative phenomenological analysis was employed. Negative childhood events such as poly-victimization, poor social skills, loneliness, and insecure sexual identity were reported as predisposing elements. Abuse was sustained due to a strong conviction of not being responsible for doing anything wrong. Respondents conveyed few salient inhibitors for the abuse, though not wanting to physically harm the child was often cited as important. Implications for the prevention of CSA in risk groups suggest the need to increase the understanding of children from a child's perspective, changing conceptions leading to disavowal of adult responsibility toward children, strengthening social competency, integration into a social context, and increasing knowledge about the harmful consequences of CSA.


Metal behavior and soil quality changes induced by the application of tailor-made combined biochar: An investigation at pore water scale.
The remediation performance of biochar varies based on the biomass used for its production. Further innovation involves developing tailor-made biochar by combining different raw materials to compensate for the limitations of pure biochar. Therefore, tailor-made combined biochar produced from the co-pyrolysis of pig manure and invasive Japanese knotweed (P1J1), as well as biochars produced from these feedstocks separately, i.e., pure pig manure (PM) and pure Japanese knotweed (JK), were applied to Pb and As contaminated soil to evaluate the biochar-induced changes on soil properties, microbial activity, DOM, and metal and metalloids solubility at the soil pore water scale. Biochar application reduced soluble Pb, whereas enhanced the As mobility; the increased soil pH after biochar addition played a fundamental role in reducing the Pb solubility, as revealed by their significant negative correlation (r = -0.990, p < 0.01). In contrast, the release of dissolved P strongly influenced As mobilization (r = 0.949, p < 0.01), especially in P-rich PM and P1J1 treatments, while JK showed a marginal effect in mobilizing As. Soils treated with PM, P1J1, and JK mainly increased Gram-negative bacteria by 56 %, 52 %, and 50 %, respectively, compared to the control. Fluorescence excitation-emission matrix spectroscopy combined with parallel factor analysis identified three components in pore water DOM, C1 (long wavelength humic-like), C2 (short wavelength humic-like), and C3 (protein-like), which were dominant respectively in the P1J1, JK, and PM-added soil. A principal component analysis (PCA) confirmed that the PM and P1J1 had similar performance and were more associated with releasing P and Mg and specific DOM components (C1 and C3). Meanwhile, P1J1 supplemented soil OM/OC and K, similar to JK. The results of this study suggest that combined biochar P1J1 can comprehensively enhance soil quality, embodying the advantages of pure PM and JK biochar while overcoming their shortcomings.


Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation.
Melanoma is the deadliest form of commonly encountered skin cancer, and has fast propagating and highly invasive characteristics. Pim-3, a highly expressed oncogene in melanoma, is a highly conserved serine/threonine kinase with various biological activities, such as proliferation-accelerating and anti-apoptosis effects on cancer progression. However, whether Pim-3 regulates melanoma metastasis has not been determined. Here, we constructed a Pim-3-silencing short hairpin RNA (sh-Pim-3), a TLR7-stimulating ssRNA and a dual-function vector containing a sh-Pim-3 and a ssRNA, and transfected them into the B16F10 melanoma cell line to investigate the effects of Pim-3 on migration and invasion in melanoma. We found that sh-Pim-3 inhibited B16F10 cell migration and invasion in vitro. In a tumor-bearing mouse model, sh-Pim-3 significantly downregulated pulmonary metastasis of B16F10 melanoma cell in vivo. Mechanistically, sh-Pim-3 inhibited metastasis by regulating the expression of genes related to epithelial-mesenchymal transition (EMT). Further study revealed that by promoting the phosphorylation of STAT3 (signal transducer and activator of transcription 3), Pim-3 induced the expression of Slug, Snail, and ZEB1, which enhanced EMT-related changes and induced melanoma migration and invasion. Our study suggests that Pim-3 is a potential effective target for melanoma therapy.


Neurovascular ultrasound in emergency settings: diagnostic and therapeutic aspects.
Neurovascular ultrasound is a non-invasive, portable and fast imaging method that, when performed by an experienced neurosonologist, offers reliable and reproducible information on the morphological and hemodynamic status of cervical and intracranial vessels. To review the available evidence regarding the use of this tool in the approach to acute stroke. Neurovascular ultrasound can be used in one of two ways: diagnostic and therapeutic. Considering the low recanalization rates of internal carotid artery and proximal medial cerebral artery occlusions with intravenous recombinant tissue plasminogen activator (r-tPA), neurovascular ultrasound used shortly in Emergency Department may help to select patients that could benefit from endovascular therapy. Moreover, ultrasound monitorization during intravenous r-tPA treatment allows the analysis of the pattern of arterial recanalization. Cervical ultrasound allows the assessment of the stenosis degree and the composition/surface of an arterial plaque that could, for instance, reveal earlier a candidate for carotid intervention. Finally, the therapeutic potential of ultrasound is also being investigated. Sonothrombolysis and sonolysis, that combine ultrasound technology with r-tPA and use exclusively the ultrasound to lyse the clot, respectively, showed promising results. Neurovascular ultrasound has greatly expanded to assume an important role in the study of cerebrovascular disorders.


The use of recombinant human bone morphogenetic protein 2 (rhBMP-2) to promote spinal fusion in a nonhuman primate anterior interbody fusion model.
A study on the efficacy of recombinant human bone morphogenetic protein 2 (rhBMP-2) in a nonhuman primate anterior interbody fusion model. To investigate the efficacy of rhBMP-2 with an absorbable collagen sponge carrier to promote spinal fusion in a nonhuman primate anterior interbody fusion model. RhBMP-2 is an osteoinductive growth factor capable of inducing new bone formation in vivo. Although dosage studies using rhBMP-2 have been performed on species of lower phylogenetic level, they cannot be extrapolated to the primate. Dosage studies on nonhuman primates are essential before proceeding with human primate application. Six female adult Macaca mulatta (rhesus macaque) monkeys underwent an anterior L7-S1 interbody lumbar fusion. All six sites were assigned randomly to one of two fusion methods: 1) autogenous bone graft within a single freeze-dried smooth cortical dowel allograft cylinder (control) or 2) rhBMP-2-soaked absorbable collagen sponges within a single freeze-dried smooth cortical dowel allograft cylinder also soaked in rhBMP-2. The animals underwent a baseline computed tomography scan followed by 3- and 6-month postoperation scans. Anteroposterior and lateral radiographs of the lumbosacral spine were performed monthly. After the monkeys were killed, the lumbar spine fusion sites were evaluated. Histologic evaluation of all fusion sites was performed. The three monkeys receiving rhBMP-2-soaked collagen sponges with a freeze-dried allograft demonstrated radiographic signs of fusion as early as 8 weeks. The control animals were slower to reveal new bone formation. The computed tomography scans revealed extensive fusion of the L7-S1 lumbar vertebrae in the group with rhBMP-2. A pseudarthrosis was present in two of the control animals. This study was able to document the efficacy of rhBMP-2 with an absorbable collagen sponge carrier and a cortical dowel allograft to promote anterior interbody fusion in a nonhuman primate model at a dose of 0.4 mg per implant site (1.5 mg/mL concentration). The late of new bone formation and fusion with the use of rhBMP-2 and cortical dowel allograft appears to be far superior to that of autogenous cancellous iliac crest graft with cortical dowel allograft.


[Headache and teeth].
Headache, facial pain and toothache are poorly localized and irradiate in distant areas. Thus, toothache often causes facial pain and headache, but, in turn, it can also be mimicked by several forms of these disorders, in particular by a myoarthropathy of the masticatory system, a migraine, a tension-type headache, a neuropatic pain and a trigeminal neuralgia. The atypical odontalgia is a nonodontogenic form of toothache that is difficult to diagnose; therefore, it leads to a number of invasive dental procedures which normally worsen the pain condition. The atypical odontalgia can often be solely diagnosed by means of a diagnostic block. Headache and facial pain can also be caused by a myoarthropathy of the masticatory system. This disorder is often misdiagnosed, because the signs and symptoms are not pathognomonic, and they are frequently present also in healthy individuals. The disorder has a good prognosis, the therapy is generally simple and follows the treatment principles for chronic musculoskeletal disorders. The burning-mouth syndrome is an other poorly understood form of intraoral pain that occurs primarily in postmenopausal females. Several etiologic factors have been described, but treatment based on one or more of these factors is often ineffective. Spontaneous remission occurs in about half of the patients after several years.


Molecular profiling of CD34+ cells identifies low expression of CD7, along with high expression of proteinase 3 or elastase, as predictors of longer survival in patients with CML.
Although most patients with chronic myeloid leukemia (CML) have the same initial molecular abnormality, the BCR-ABL fusion gene, the duration of chronic phase (CP) varies widely. To identify the possible molecular basis of this heterogeneity, we studied CD34+ cells collected at diagnosis from 68 patients with CML-CP. By using oligonucleotide microarray screening, we performed gene-expression profiling on 2 subsets of patients, one comprising patients with an "aggressive disease" who developed blastic transformation (BT) within 3 years of diagnosis (n = 10) and, at the other extreme, patients with an "indolent disease" whose BT occurred 7 or more years from diagnosis (n = 9). This screening revealed 20 genes differentially expressed in patients with aggressive and indolent disease, which were validated by quantitative reverse transcriptase/polymerase chain reaction (Q-RT/PCR). A multivariate Cox regression model identified the combination of low CD7 expression with high expression of proteinase 3 or elastase as associated with longer survival in the complete cohort of 68 patients. This differential pattern of gene expression probably reflects the intrinsic heterogeneity of the disease; if so, assessing expression levels of selected genes at diagnosis may be valuable in predicting duration of survival in patients treated with imatinib and the newer tyrosine kinase inhibitors.


Functional diversity of inhibitors tackling the differentiation blockage of MLL-rearranged leukemia.
The chromosomal rearrangements of the mixed-lineage leukemia gene MLL (KMT2A) have been extensively characterized as a potent oncogenic driver in leukemia. For its oncogenic function, most MLL-fusion proteins exploit the multienzyme super elongation complex leading to elevated expression of MLL target genes. High expression of MLL target genes overwrites the normal hematopoietic differentiation program, resulting in undifferentiated blasts characterized by the capacity to self-renew. Although extensive resources devoted to increased understanding of therapeutic targets to overcome de-differentiation in ALL/AML, the inter-dependencies of targets are still not well described. The majority of inhibitors potentially interfering with MLL-fusion protein driven transformation have been characterized in individual studies, which so far hindered their direct cross-comparison. In our study, we characterized head-to-head clinical stage inhibitors for BET, DHODH, DOT1L as well as two novel inhibitors for CDK9 and the Menin-MLL interaction with a focus on differentiation induction. We profiled those inhibitors for global gene expression effects in a large cell line panel and examined cellular responses such as inhibition of proliferation, apoptosis induction, cell cycle arrest, surface marker expression, morphological phenotype changes, and phagocytosis as functional differentiation readout. We also verified the combination potential of those inhibitors on proliferation and differentiation level. Our analysis revealed significant differences in differentiation induction and in modulating MLL-fusion target gene expression. We observed Menin-MLL and DOT1L inhibitors act very specifically on MLL-fused leukemia cell lines, whereas inhibitors of BET, DHODH and P-TEFb have strong effects beyond MLL-fusions. Significant differentiation effects were detected for Menin-MLL, DOT1L, and DHODH inhibitors, whereas BET and CDK9 inhibitors primarily induced apoptosis in AML/ALL cancer models. For the first time, we explored combination potential of the abovementioned inhibitors with regards to overcoming the differentiation blockage. Our findings show substantial diversity in the molecular activities of those inhibitors and provide valuable insights into the further developmental potential as single agents or in combinations in MLL-fused leukemia.


Theoretical characterization of alpha-helix and beta-hairpin folding kinetics.
By means of the conformational free energy surface and corresponding diffusion coefficients, as obtained by long time scale atomistic molecular dynamics simulations (mus time scale), we model the folding kinetics of alpha-helix and beta-hairpin peptides as a diffusive process over the free energy surface. The two model systems studied in this paper (the alpha-helical temporin L and the beta-hairpin prion protein H1 peptide) exhibit a funnel-like almost barrierless free energy profile, leading to nonexponential folding kinetics matching rather well the available experimental data. Moreover, using the free energy profile provided by Muñoz et al. [Muñoz et al. Nature 1997, 390: 196-199], this model was also applied to reproduce the two-state folding kinetics of the C-terminal beta-hairpin of protein GB1, yielding an exponential folding kinetics with a time constant (approximately 5 micros) in excellent agreement with the experimentally observed one (approximately 6 micros). Finally, the folding kinetics obtained by solving the diffusion equation, considering either a one-dimensional or a two-dimensional free energy surface, are also compared in order to understand the relevance of the possible kinetic coupling between conformational degrees of freedom in the folding process.


Listener expertise and sound identification influence the categorization of environmental sounds.
The influence of listener's expertise and sound identification on the categorization of environmental sounds is reported in three studies. In Study 1, the causal uncertainty of 96 sounds was measured by counting the different causes described by 29 participants. In Study 2, 15 experts and 15 nonexperts classified a selection of 60 sounds and indicated the similarities they used. In Study 3, 38 participants indicated their confidence in identifying the sounds. Participants reported using either acoustical similarities or similarities of the causes of the sounds. Experts used acoustical similarity more often than nonexperts, who used the similarity of the cause of the sounds. Sounds with a low causal uncertainty were more often grouped together because of the similarities of the cause, whereas sounds with a high causal uncertainty were grouped together more often because of the acoustical similarities. The same conclusions were reached for identification confidence. This measure allowed the sound classification to be predicted, and is a straightforward method to determine the appropriate description of a sound.


American Society of Hematology.
We review key sessions on Hodgkin's lymphoma, diffuse large B-cell lymphoma, thromboembolism, hemophilia, sickle cell disease, and chronic lymphocytic leukemia.


Agent and nature of childhood injury and initial care provided at the community level in Ibadan, Nigeria.
Daily home interviews-examinations were carried out for a period of three months to obtain information on the agent (object) involved, nature (diagnosis) and care provided to children aged zero to 19 years, following accidental injury, in Idikan community, Ibadan. During the study period, 1286 injuries were recorded involving all the 436 children in the study community. Rocky outcrops, chairs, broken bottles, tables, knives and glasses were the major agents of injuries (91.0%). Puncture wounds, lacerations, haematomas, sprains and dislocations constituted most of the nature of injury (96.5%). All injuries were minor injuries (AIS = 1). Relatives-neighbours were responsible for managing majority of the injuries. Only seven (0.6%) injuries were seen by a nurse-physician in a health facility. Specific individual-community health education as well as health service and environmental modification measures are suggested. This study has also shown that community based data on injury provides more precise information required for the development of injury prevention and care programmes at the primary care level.


Tinnea gombea (Lamiaceae), a new species from the Sudanian savanna region, Nigeria based on integrative evidence.
Tinnea gombea, endemic to the Sudan savanna grasslands in northern Nigeria, is described and illustrated. We used integrative evidence from morphological characters, ecology and molecular phylogenetic data. The new species is morphologically and ecologically similar to T. barteri and T. aethiopica, but can be readily delimited from these taxa by unique characters including a subshrub growth habit, leaves alternate to subopposite, blades lanceolate, apically acuminate, inflorescences raceme, bearing solitary flowers in upper leaf and bract axils, lilac to purplish dusky flowers and the inflated fruits dehiscent. The distribution and habitat of T. gombea are also distinctive, being restricted to the Sudan savanna, while the two most similar species are widespread in tropical Africa. Additionally, molecular phylogenetic assessments using nrITS and chloroplast trnL-F, matK and rbcL support the placement of T. gombea as a distinct species. Tinnea gombea is here assessed as Critically Endangered due to its small population size and restriction to a small area lacking conservation prioritization.


Theoretical investigation of electronic and optical properties of nitrogen doped triangular shaped graphene quantum dots.
The electronic and optical properties of graphene quantum dots can be significantly tailored by doping it with heteroatoms, thus extending its potential applications. In this work, we have employed time-dependent density functional theory to systematically explore the effect of introduction of nitrogen atoms in varying concentration at pyridinic and graphitic configuration in armchair and zigzag-edged triangular shaped graphene quantum dots (TQDs) of different sizes. Our results indicate that the electronic band-gap in these N-doped systems can be effectively tuned by varying the configuration as well as concentration of dopants and nature of edge-termination. The variation of electronic band-gap is critically determined by the localized/delocalized nature of molecular orbitals and presence of additional energy levels due to dopant nitrogen atoms. However, the significance of these extra energy levels in modulating the optical properties (appearance of characteristic N-dopant absorption peaks) becomes conspicuous only for specific configuration and concentration of nitrogen atoms. In addition, our studies have attributed the strong dependence of blue/red-shift of absorption spectra and variation in the peak profile to position as well as concentration of dopant atoms and edge-termination pattern. Further, it is observed that the effect of increasing size of TQDs on the strength of most intense absorption peak of pyridinic N-doped TQDs is remarkably different from graphitic N-doped systems. This selective manipulation of optical properties in TQDs due to different N-doping pattern can open up new frontiers for rational design of novel optoelectronic devices.


Embryonic loss in mares. Incidence, possible causes, and diagnostic considerations.
Fertilization rates were similar for normal and subfertile mares, and much of the difference in fertility between normal and subfertile mares was due to embryonic loss. Fertilization rate estimates for mares ranged from 71 to 96 per cent. The incidence of embryonic loss detected by ultrasonography between Days 11 and 50 was approximately 9 per cent for normal mares, and the estimated incidence of embryonic loss before Day 14 was also 9 per cent. Therefore, the estimated incidence of embryonic loss in normal mares between fertilization and Day 50 is approximately 18 per cent (Fig. 1). In subfertile mares, the corresponding estimate for embryonic loss between fertilization and Day 50 is 80 per cent, with most embryonic losses occurring before Day 14 in subfertile mares (Fig. 1). The high rate of early embryonic loss in subfertile mares could be related to embryonic defects, oviductal environment, or uterine environment. Oviductal embryos from subfertile mares were less viable than embryos from normal mares; therefore, embryonic defects were important in early embryonic losses in subfertile mares. These defects might be inherent within the embryo or might arise from the early oviductal environment. The uterine environment of subfertile mares was adequate to support normal embryos in early gestation; however, the relationship between the uterine environment and the increased metabolic demands of the conceptus in the late embryonic or early fetal periods requires further study. The uterine environment is also altered in mares with endometritis; therefore, endometritis may also be an important factor in embryonic loss in some mares. Uterine-induced luteolysis, as well as the effect of the pathogen or the resulting inflammation, may lead to embryonic loss. An increased susceptibility of some subfertile mares to endometritis could result in embryonic loss secondary to a postcoital endometritis that persists until the embryo reaches the uterus at Days 5 or 6 postovulation. Although progesterone is critical to embryonic survival, the cause-and-effect relationship between progesterone and spontaneous embryonic loss remains unclear. Reduced progesterone concentrations could be related to endometritis, failure of maternal pregnancy recognition, or luteal insufficiency. Progesterone supplementation may be indicated for some mares, but the value of exogenous progesterone for prevention of spontaneous embryonic loss has not been critically tested. A number of other factors have been associated with embryonic loss in mares.(ABSTRACT TRUNCATED AT 400 WORDS)


Intragenic amplification and formation of extrachromosomal small circular DNA molecules from the PIP gene on chromosome 7 in primary breast carcinomas.
The PIP gene is expressed in exocrine glands and, in pathologic conditions, in breast cysts and breast cancers exhibiting apocrine features. It is localized on the long arm of chromosome 7, a region frequently alterated in mammary tumors. We previously described an abnormal restriction pattern of the PIP gene in 33% of prostate carcinomas analyzed. Here, we analyze the structure of the PIP gene in primary breast carcinomas. We report that part of the 3' end, including exon 3, intron C, two-thirds of exon 4 and a small portion of intron B, is amplified and involved in the formation of extrachromosomal spcDNA molecules in 3/14 (21.4%) breast cancers analyzed. The involvement of a well-defined intragenic region of a gene in the formation of spcDNA appears to be unprecedented. Since spcDNA has been suggested to serve as an enhancer of genetic instability, the PIP gene may be the target of genomic variability processes in breast cancer.


Feasibility of Peripheral Artery CT Angiography under 70 kV with 50 ml Contrast Medium on the Third-generation Dual-source CT.
Objective To evaluate the feasibility of peripheral artery CT angiography (CTA)under 70 kV with 50 ml contrast medium on the third-generation dual-source CT. Methods Totally 82 patients who were equally randomized into two groups:70 kV group:the scan was performed under 70 kV tube voltage+50 ml iopromide on the third-generation dual-source CT;and 100 kV group:the scan was performed under 100 kV tube voltage+90 ml iopromide on the second-generation dual-source CT. The CT number of abdominal aorta,bilateral common iliac arteries,common femoral arteries,superficial femoral arteries,popliteal arteries and arteries of the calf were measured and contrast to noise ratio(CNR),signal to noise ratio(SNR)were calculated. The image quality was compared between these two groups. Results The dose-length product was (195.8±46.9)mGy·cm in 70 kV group,which was significantly lower than that in 100 kV group (461.6±57.9)mGy·cm,and was decreased by 57% (t=-22.848,P=0.000). Compared with the 100 kV group,the CT number of the proximal abdominal aorta in 70 kV group was significantly lower(t=-2.502,P=0.014),while the CT number of superficial femoral arteries (t=3.053,P=0.003)and popliteal arteries (t=4.013,P=0.000)was much higher in 70 kV group. SNR and CNR of proximal abdominal aorta,distal abdominal aorta,bilateral common iliac arteries,common femoral arteries,superficial femoral arteries,popliteal arteries and arteries of the calf were significantly lower in 70 kV group than those in 100 kV group (all P<0.05). The artifacts in abdominal aorta (t=2.893,P=0.000)and feet arteries (t=3.776,P=0.000)were higher in 70 kV group than those in 100 kV group,the enhancement of abdominal aorta (t=-1.000,P=0.002)and feet arteries (t=2.893,P=0.010)were lower in 70 kV group,the enhancement of femoral-popliteal arteries (t=-1.000,P=0.000)and arteries of calf (t=4.261,P=0.000)were higher in 70 kV group. Compared with the 100 kV group,the image noise in aorta (t=2.048,P=0.044),femoral-popliteal arteries (t=8.370,P=0.000),arteries of the calf (t=8.315,P=0.000)and feet arteries (t=7.202,P=0.000)were higher in 70 kV group. Conclusion Compared to conventional scan protocol,using 70 kV tube voltage with 50 ml contrast medium to perform peripheral artery CTA can assure the image quality and meanwhile remarkably reduce the radiation dose and the use of contrast medium.


What If a Resident or Medical Student Is Raped? Hospitals' and Academic Medical Centers' Title IX Obligations.
Title IX of the Education Amendments of 1972 protects medical students and residents from all forms of sexual discrimination, including sexual harassment and assault. Hospitals that train residents as well as medical students must follow Title IX mandates, including investigating and addressing all reports of sexual discrimination, harassment, or violence. While these processes can help eliminate potential barriers to women in medical training, the pressure to participate in an internal investigation can discourage some medical students and residents from seeking help. Hospitals should work closely with university Title IX officials to design and implement effective policies and procedures to both prevent and address all types of sexual discrimination as well as to support trainees who have been victimized.


Proteus syndrome.
Proteus syndrome is a rare congenital hamartomatous entity. We report some new findings in a boy with this syndrome, in addition to the classical clinical and radiological features of subcutaneous masses, partial gigantism of hands and feet, bony abnormalities, and epidermal nevi. We also discuss how to reach a definitive diagnosis by using an established rating scale.


Stressors influence work ability in different age groups of nursing professionals: 2-year follow-up.
Work stressors influence work ability - WA - and increasing age is associated with functional aging. We sought to establish whether work stressors differentially influence WA in young and aging nursing professionals. A cohort (2009-2011) composed of 304 workers at a hospital in Sao Paulo responded questionnaires Effort-Reward Imbalance (ERI), Job Stress Scale (JSS), Work-Related Activities That May Contribute To Job-Related Pain and/or Injury (WRAPI) and Work Ability Index (WAI). Changes in perceived exposure to stressors in each age group (< 45 and ≥ 45 years old) were compared to delta-WAI (difference between initial and final WAI score) by means of the Mann-Whitney test. There was a worsening in WAI (p = 0.609) without difference between the groups. WA impairment was associated with intensification of stressors ERI (p = 0.004), overcommitment (p = 0.002), social support (p = 0.014) and WRAPI (p = 0.004) among the younger workers, but with poorer ERI (p = 0.047) only among the older ones. While among the younger workers WA was influenced by the intensification of various stressors, in the case of the older ones it was influenced by effort-reward imbalance only, indicating that interventions should be differentiated according to age groups.


Induction of type C viruses in cultured guinea pig cells.
Particles morphologically resembling type C viruses were activated by bromodeoxyuridine (BUdR; 10(-4) M) treatment of cultured guinea pig cells. Virus particles were isolated from the cells of normal and leukemic strain 2 and random-bred guinea pigs (adult and embryonic). Immature virus particles with electron-lucent cores were found in the cytoplasmic matrix. The mature particles with electron-dense cores were found outside the cells and some appeared in the process of budding from the plasma membrane. The peak of virus production was observed within 4 days of BUdR treatment. When compared to the amount of virus produced in darkness, visible light enhanced virus production, whereas exposure of BUdR-treated cells to UV light either had no effect or inhibited virus production. Virus particles had a density of 1.16 gm/ml, possessed an oncornavirus-specific reverse transcriptase, and contained a large-molecular-weight RNA (65-70S) which dissociated into 36S subunits after heat denaturation. The BUdR-activated virus particles, therefore, possessed the morphological, biophysical, and biochemical characteristics of type C oncornaviruses.


Influenza Virus and Glycemic Variability in Diabetes: A Killer Combination?
Following the 2009 H1N1 influenza virus pandemic, numerous studies identified the striking link between diabetes mellitus and influenza disease severity. Typically, influenza virus is a self-limiting infection but in individuals who have a pre-existing chronic illness, such as diabetes mellitus, severe influenza can develop. Here, we discuss the latest clinical and experimental evidence for the role of diabetes in predisposing the host to severe influenza. We explore the possible mechanisms that underlie this synergy and highlight the, as yet, unexplored role that blood glucose oscillations may play in disease development. Diabetes is one of the world's fastest growing chronic diseases and influenza virus represents a constant and pervasive threat to human health. It is therefore imperative that we understand how diabetes increases influenza severity in order to mitigate the burden of future influenza epidemics and pandemics.


Homologies in the structures of bull seminal plasma acrosin inhibitors and comparison with other homologous proteinase inhibitors of the Kazal type.
After determination of the amino-acid sequence of a further acrosin inhibitor isolated from bull seminal plasma, the primary structures of the three seminal inhibitors known so far were compared with other homologous structures of protein-protein inhibitors. From the matrix of minimal base changes, a high divergence in the evolution of the seminal inhibitors can be seen. Inhibitors from bull seminal plasma show even a higher degree of relationship to dog submandibular gland inhibitor domain II and the 3rd domain of quail ovomucoid than to acrosin inhibitor from boar seminal plasma.


Conservative non-instrumental treatment of benign prostatic hyperplasia.
This paper critically reviews the clinical effects in benign prostatic hyperplasia (BPH) patients that can be achieved with the presently available medical treatment options. The classes of drugs that are reviewed include: 5-alpha-reductase inhibitors, alpha-blockers, cholesterol-lowering agents and phytotherapeutic drugs. Only double-blind placebo-controlled studies with a duration of at least 3 months that have reported symptomatic changes and changes in flow rate in a quantitative fashion have been included. Studies that exclusively included selected groups of patients such as hypertensives or non-hypertensives have been excluded. The results of the clinical trials that are reviewed in this paper often show improvements in symptom score and maximum flow rate in the patients taking the active drug. These improvements are often statistically significantly better than the improvements seen in the placebo groups. However, taking into account that the symptomatic and the flow rate improvements achieved are below the level of perception in most of these trials, there seems to be no convincing evidence that medical treatment of BPH with the presently available drugs is also clinically more effective than placebo.


Field, laboratory, and X-ray absorption spectroscopic studies of mercury accumulation by water hyacinths.
We have studied water hyacinth (Eichhornia crassipes), a non-native nuisance plant found in the in San Francisco Bay Delta region, for its potential to phytoremediate mercury. Mercury is a common contaminant in San Francisco Bay Area waters because of gold mining activities. In this study, speciation of mercury in hyacinth roots and shoots, rates of mercury uptake by hyacinths in the laboratory, and mercury levels near the Big Break Region in the Delta were studied. In the speciation studies, Hg L3 edge X-ray absorption spectroscopic analysis of Hg model compounds and water hyacinth roots and shoots revealed that Hg was initially bound ionically to oxygen ligands in roots, most likely to carboxylate groups, and was bound covalently to sulfur groups in shoots. In laboratory uptake studies, we found that water hyacinths grown in 1 ppm Hg and one-quarter strength Hoagland's solution accumulated a maximum of 0.20 ppm in shoots and 16.0 ppm in roots, both reaching maximum concentrations after approximately 16 days. Mercury concentrations were found to be 0.26 +/- 0.20 ppm in the water and 0.86 +/- 1.70 ppm in sediment at Big Break. It was proposed that water hyacinths have the potential to phytoremediate mercury in the water at Big Break if the current herbicide treatments are replaced by physical removal.


Evaluation of clinical validity of an S-1 dosage formula based on renal function using data of the SPIRITS and the G-SOX trials.
The aim of this study was to evaluate clinical validity of the S-1 dosage formula based on body surface area (BSA) and creatinine clearance (CLcr) to achieve the target area under the concentration-time curve of 5-FU, which we had developed and refined in each prospective pharmacokinetic study. The recommended dose determined by the refined formula was assessed using data of the SPIRITS (S-1 vs. S-1 plus cisplatin [SP]) and the G-SOX (SP vs. S-1 plus oxaliplatin [SOX]) trials. Nine hundred and thirty-eight patients in these trials were classified into three groups according to their actual S-1 starting doses compared with the recommended doses (under-dosed, <recommended dose; equal-dosed, =recommended dose; over-dosed, >recommended dose). The patients in the under-dosed group in both trials showed similar tendencies: male, younger, higher BSA, and higher CLcr. The incidence of any grade neutropenia was significantly greater in the over-dosed group compared with the equal-dosed group in the S-1 and the SOX arms. The hazard ratios (HR) of overall survival (OS) (under-dosed vs. equal-dosed) were 1.361 (S-1 arm), 1.259 (SP arm) in the SPIRITS trial, and 1.381 (SOX arm), 0.999 (SP arm) in the G-SOX trial. Multivariate analysis in all the patients demonstrated that OS of the over-dosed group was equivalent (HR 1.002, 95% confidence interval [CI] 0.850-1.182, p = 0.980) and that of the under-dosed group was inferior (HR 1.267, 95% CI 1.005-1.597, p = 0.045) to the equal-dosed group. It is suggested that the refined S-1 dosage formula can recommend optimal dose in terms of safety and efficacy.


Optimizing claims payment for successful risk management.
Disputed claims and delayed payments are among the principal sources of provider and vendor dissatisfaction with managed care payment systems. Timely and accurate claims-payment systems are essential to ensure provider and vendor satisfaction, fiscal stability, and regulatory compliance. A focused analysis of conditions contributing to late payment of claims can disclose problems in provider, vendor, or payer operational and billing procedures, contracting processes, information systems, or human resources management. Resolution of these conditions equips claims-processing staff with tools to resolve problem claims promptly, thereby lowering costs.


Zebrafish pten Genes Play Relevant but Distinct Roles in Antiviral Immunity.
The PTEN (phosphatase and TENsin homolog on chromosome 10) gene encodes a bifunctional phosphatase that acts as a tumor suppressor. However, PTEN has been implicated in different immune processes, including autophagy, inflammation, regulation of natural killer (NK) cell cytolytic activity and type I interferon responses. Unlike mammals, zebrafish possess two pten genes (ptena and ptenb). This study explores the involvement of both zebrafish pten genes in antiviral defense. Although ptena-/- and ptenb-/- larvae were more susceptible to Spring viremia of carp virus (SVCV), the viral replication rate was lower in the mutant larvae than in the wild-type larvae. We observed that both mutant lines showed alterations in the transcription of numerous genes, including those related to the type I interferon (IFN) system, cytolytic activity, autophagy and inflammation, and some of these genes were regulated in opposite ways depending on which pten gene was mutated. Even though the lower replication rate of SVCV could be associated with impaired autophagy in the mutant lines, the higher mortality observed in the ptena-/- and ptenb-/- larvae does not seem to be associated with an uncontrolled inflammatory response.


Elevated concentrations of ethanol in plasma do not suppress voluntary ethanol consumption in C57BL mice.
The 24-hr patterns of ethanol intake and resulting concentrations of ethanol in plasma are described for male C57BL/6J mice given free access to water and a 10% v/v solution of ethanol. Animals treated with the alcohol dehydrogenase inhibitor 4-methylpyrazole developed peak plasma concentrations of 116 +/- 20 mg/100 ml, while controls given daily injections of saline exhibited peak plasma concentrations of 11 +/- 7 mg/100 ml. Ethanol consumption as measured by total daily intake and preference was not significantly different in the two groups of mice. The absence of an effect on ethanol consumption despite a tenfold difference in peak plasma levels suggests that concentrations of circulating ethanol within the range observed do not limit voluntary consumption of ethanol.


Dynamics of noninvasively estimated microvascular O2 extraction during ramp exercise.
Utilization of near-infrared spectroscopy (NIRS) in clinical exercise testing to detect microvascular abnormalities requires characterization of the responses in healthy individuals and theoretical foundation for data interpretation. We examined the profile of the deoxygenated hemoglobin signal from NIRS {deoxygenated hemoglobin + myoglobin [deoxy-(Hb+Mb)] approximately O(2) extraction} during ramp exercise to test the hypothesis that the increase in estimated O(2) extraction would be close to hyperbolic, reflecting a linear relationship between muscle blood flow (Q(m)) and muscle oxygen uptake (Vo(2)(m)) with a positive Q(m) intercept. Fifteen subjects (age 24 +/- 5 yr) performed incremental ramp exercise to fatigue (15-35 W/min). The deoxy-(Hb+Mb) response, measured by NIRS, was fitted by a hyperbolic function [f(x) = ax/(b + x), where a is the asymptotic value and b is the x value that yields 50% of the total amplitude] and sigmoidal function {f(x) = f(0) + A/[1 + e(-(-c+dx))], where f(0) is baseline, A is total amplitude, and c is a constant dependent on d, the slope of the sigmoid}, and the goodness of fit was determined by F test. Only one subject demonstrated a hyperbolic increase in deoxy-(Hb+Mb) (a = 170%, b = 193 W), whereas 14 subjects displayed a sigmoidal increase in deoxy-(Hb+Mb) (f(0) = -7 +/- 7%, A = 118 +/- 16%, c = 3.25 +/- 1.14, and d = 0.03 +/- 0.01). Computer simulations revealed that sigmoidal increases in deoxy-(Hb+Mb) reflect a nonlinear relationship between microvascular Q(m) and Vo(2)(m) during incremental ramp exercise. The mechanistic implications of our findings are that, in most healthy subjects, Q(m) increased at a faster rate than Vo(2)(m) early in the exercise test and slowed progressively as maximal work rate was approached.


Control of scroll wave turbulence in a three-dimensional reaction-diffusion system with gradient.
In this paper, we summarize our recent experimental and theoretical works on observation and control of scroll wave (SW) turbulence. The experiments were conducted in a three-dimensional Belousov-Zhabotinsky reaction-diffusion system with chemical concentration gradients in one dimension. A spatially homogeneous external forcing was used in the experiments as a control; it was realized by illuminating white light on the light sensitive reaction medium. We observed that, in the oscillatory regime of the system, SW can appear automatically in the gradient system, which will be led to spatiotemporal chaos under certain conditions. A suitable periodic forcing may stabilize inherent turbulence of SW. The mechanism of the transition to SW turbulence is due to the phase twist of SW in the presence of chemical gradients, while modulating the phase twist with a proper periodic forcing can delay this transition. Using the FitzHugh-Nagumo model with an external periodic forcing, we confirmed the control mechanism with numerical simulation. Moreover, we also show in the simulation that adding temporal external noise to the system may have the same control effect. During this process, we observed a new state called "intermittent turbulence," which may undergo a transition into a new type of SW collapse when the noise intensity is further increased. The intermittent state and the collapse could be explained by a random process.


Protective effect of liposomal gentamicin against systemic acute murine brucellosis.
Liposomes of the stable multilamellar type, which previously demonstrated great efficiency in antibiotic transport [Vitas et al: Antimicrob Agents Chemother 1996;40:146-151] were used in this study as carriers of gentamicin for treatment of mice lethally infected with Brucella abortus. Treatment with gentamicin in positively charged liposomes produced a protective effect when it was administered 1 day after lethal challenge (70% of protection). On the other hand, the use of free gentamicin or in liposomes with a negative net charge did not produce a protective effect. Moreover, the results reported here also indicated that cationic liposomes themselves had a therapeutic effect on the course of the infection (up to 50% of protection). In conclusion, we observed that cationic liposomal encapsulation of gentamicin resulted in an enhancement of the therapeutic activity of free gentamicin in this mouse model of acute infection.


The evolving role of neurosurgery for central nervous system metastases in the era of personalized cancer therapy.
Recent therapeutic advances involving the use of systemic targeted treatments and immunotherapeutic agents in patients with advanced cancers have translated into improved survival rates. Despite the emergence of such promising pharmacological therapies and extended survival, the frequency of metastases in the central nervous system has steadily increased. Effective medical and surgical therapies are available for many patients with brain metastases and need to be incorporated into multi-disciplinary care protocols. The role of neurosurgeons is evolving within these multi-disciplinary care teams. Surgical resection of brain metastases can provide immediate relief from neurological symptoms due to large lesions and provides the histopathological diagnosis in cases of no known primary malignancy. In situations where immunotherapy is part of the oncological treatment plan, surgery may be proposed for expeditious relief of edema to remove the need for steroids. In patients with multiple brain metastases and mixed response to therapeutics or radiosurgery, tumour resampling allows tissue analysis for druggable targets or to distinguish radiation effects from progression. Ventriculo-peritoneal shunting may improve quality of life in patients with hydrocephalus associated with leptomeningeal tumour dissemination and may allow for time to administer more therapy thus prolonging overall survival. Addressing the limited efficacy of many oncological drugs for brain metastases due to insufficient blood-brain barrier penetrance, clinical trial protocols in which surgical specimens are analysed after pre-surgical administration of therapeutics offer pharmacodynamic insights. Comprehensive neurosurgical assessment remains an integral element of multi-disciplinary oncological care of patients with brain metastases and is integral to tumour biology research and therapeutic advancement.


[Clinical study of rhG-CSF (KRN8601) in patients with myelodysplastic syndrome].
A clinical study of rhG-CSF (KRN8601) in patients with myelodysplastic syndrome (MDS) was performed to investigate the hematopoietic effects and the increase of neutrophils. The rhG-CSF was administered daily by intravenous infusion over 30 min. to 21 patients with MDS (PARA = 11, RAEB = 4, RAEB in T = 6). The dose was escalated stepwise from 50 to 400 microgram/m2 every week. Within one week to 26 days after commencement of rhG-CSF administration, the increases of absolute neutrophil counts in peripheral blood were observed in all patients. Treatment with rhG-CSF enhanced normal marrow myeloid cell differentiation and maturation in 3 of 9 PARA patients and in 3 of 4 RAEB patients. None of patients changed to acute leukemia attributable to rhG-CSF, but one of RAEB patient and two of RAEB in T patients progressed to leukemic phase in 21 days or two months after treatment. Minor side effects or abnormal laboratory findings were observed in 3 patients (14.3%). These results suggested that treatment with rhG-CSF was well tolerated and effective for improving the neutropenia between 50 to 400 micrograms/m2 in patients with MDS.


Plasmacytoma of the clivus: a case report.
A 60-year-old male presented with headache and diplopia for 2 months. Computed tomography of the head showed a heterogeneously enhancing expansile lytic lesion in clival region. The patient underwent surgery and histopathological examination revealed it to be plasmacytoma of the clivus. The multiple myeloma work-up was negative. Solitary plasmacytoma localized to the skull base is extremely rare. Prior to this, only three case reports of plasmacytoma of the clivus have been described in the English literature.


Produced β-hydroxybutyrate after β-hydroxy-β-methylbutyrate (HMB) administration may contribute HMB function in mice.
β-Hydroxy-β-methylbutyrate (HMB) is an intermediate in the metabolism of the branched-chain amino acid leucine. HMB has several demonstrated effects on skeletal muscle function, some of which are contradictory. In addition, the effect of exogenous HMB intake on the levels of intermediate metabolites is not known. Therefore, we investigated changes in HMB metabolites after oral HMB administration in mice. First, ICR mice were treated with either distilled water or HMB (0.215 g/10 mL/kg). Sampling was performed at 0, 1, 6, 12, and 24 h after administration. Next, ICR mice were given distilled water or HMB (0.215 g/10 mL/kg/d) for 10 d. Mice given HMB shown a significant increase in liver β-methylcrotonyl-CoA and increased β-hydroxybutyrate in plasma and the gastrocnemius muscle 1 h after HMB administration. Mice administered HMB for 10 d showed significantly decreased food intake and body weight; however, the relative weight of the gastrocnemius muscle was significantly increased. These results may be attributed to an increase in β-hydroxybutyrate resulting from exogenous HMB, since β-hydroxybutyrate inhibits food intake and suppresses skeletal muscle catabolism. In conclusion, β-hydroxybutyrate, a metabolite of HMB, was found to play an important role in the function of HMB.


Effects of Fadrozole (CGS 16949A) and Letrozole (CGS 20267) on the inhibition of aromatase activity in breast cancer patients.
Fadrozole Hydrochloride (CGS 16949A) and Letrozole (CGS 20267), are two of the newest non-steroidal, orally active aromatase inhibitors currently being evaluated as second line treatment of patients with hormone dependent forms of metastatic breast cancer. In a phase I clinical efficacy study, we examined the ability of these two imidazole derivatives to suppress the synthesis of estrogen in a cohort of postmenopausal patients with metastatic breast cancer. Both medications at relatively low doses were potent and rapid inhibitors of aromatase activity as evidenced by their ability to suppress the level of blood and urine estradiol and estrone as well as blood estrone sulfate in these patients. Letrozole appeared to be the more potent of the two, with over 95% suppression of both plasma and urinary estrogens observed within 2 weeks of therapy. Letrozole appeared to be more selective than Fadrozole in inhibiting aromatase activity in that no compromise in cortisol and aldosterone output was evident with Letrozole therapy at all of the doses tested, a compromise clearly seen with Fadrozole. The inhibition of aromatase activity by these imidazole derivatives as second line therapy for patients with hormone dependent breast cancer appears to be a favorable alternative form of hormone ablative therapy and holds considerable promise for the treatment of this malignancy.


Morphological Integration of the Orbital Region in a Human Ontogenetic Sample.
Most studies on craniofacial morphology have focused on adult individuals, but patterns of variation are the outcome of genetic and epigenetic variables that interact throughout ontogeny. Among cranial regions, the orbits exhibit morphological variation and occupy an intermediate position between neurocranial and facial structures. The main objective of this work was to analyze postnatal ontogenetic variation and covariation in the morphology of the orbital region in a cross-sectional series of humans from 0 to 31 years old. Landmarks and semilandmarks were digitized on the orbital rim, as well as in neighboring neural and facial structures. Data were analyzed using geometric morphometrics. Results indicated that orbital size increases during the first years of postnatal life, while the shape of the orbital aperture does not change significantly with age. In general, the pattern and magnitude of shape covariation do not vary markedly during postnatal life although some subtle shifts were documented. Additionally, the shape of the orbital aperture is more related to the anterior neurocranium than to zygomatic structures, even when the allometry is adjusted. Although we expected some influence from postnatal craniofacial growth and from some functional factors, such as mastication, on the development of the orbits, this assumption was not completely supported by our results. As a whole, our findings are in line with the prediction of an early influence of the eyes and extraocular tissues on orbital morphology, and could be interpreted in relation to processes promoting early neural development that coordinately affects orbital traits and the neurocranial skeleton.


Mass spectrometric identification of urinary and plasma metabolites of 6-(6'-carboxyhexyl)-7-n-hexyl-1,3-diazaspiro-[4-4]-nonan-2,4-dione, a new cytoprotective agent.
The compound IBI-P-01028, or R,S-cis-6-(6'-carboxyhexyl)-7-trans-n-hexyl-1,3-diazaspiro-[4-4]-nona n-2,4- dione, is a new cytoprotective agent under development. To study the metabolites of this compound in laboratory animals, we administered it to dogs and rats, and analyzed extracts from dog and rat urine, and from dog plasma, by GC-MS. The metabolic profiles were different in the rat and dog. In the dog (plasma and urine), one metabolite was found, and in the rat urine two other metabolites were found. The unmetabolized drug was found only in the dog plasma and urine.


Bone morphogenetic protein-6 is expressed in nonparenchymal liver cells and upregulated by transforming growth factor-beta 1.
Bone morphogenetic protein-6 (BMP-6) is a member of the TGF-beta superfamily, which controls growth and differentiation during embryogenesis and acts as an osteoinductive factor in the adult organism. In order to gain further insights into the role of BMP-6, the present study analyzed the expression pattern of BMP-6 in adult rat tissues with special emphasis to the liver, since TGF-beta 1, another member of the TGF-beta superfamily, has been shown to play a fundamental role in liver physiology. Rat BMP-6-coding cDNAs were generated by homology cloning using RT-PCR and displayed 89.6 and 83.4% homology to mouse and human BMP-6, respectively. By Northern blotting BMP-6-specific transcripts 3.7 kb in size were detected in major amounts in lung and in minor quantities in spleen, kidney, heart, brain, and liver. Among the different hepatic cell populations tested BMP-6 expression was confined to nonparenchymal liver cells, namely rat hepatic stellate cells (HSC) and Kupffer cells (KC). During primary culture BMP-6 expression was increased in HSC but declined in KC. Interestingly, TGF-beta 1 stimulated BMP-6 expression of HSC especially at an early time point of culture, while interferon-gamma downregulated BMP-6 expression. The detection of BMP-6 transcripts in the liver, the cell-type-restricted expression pattern, and its regulation propose that, in addition to its osteoinductive properties, BMP-6 might play a role in liver growth and differentiation, in particular after tissue damage.


Reinforcement Learning With Multiple Relational Attention for Solving Vehicle Routing Problems.
In this article, we study the reinforcement learning (RL) for vehicle routing problems (VRPs). Recent works have shown that attention-based RL models outperform recurrent neural network-based methods on these problems in terms of both effectiveness and efficiency. However, existing RL models simply aggregate node embeddings to generate the context embedding without taking into account the dynamic network structures, making them incapable of modeling the state transition and action selection dynamics. In this work, we develop a new attention-based RL model that provides enhanced node embeddings via batch normalization reordering and gate aggregation, as well as dynamic-aware context embedding through an attentive aggregation module on multiple relational structures. We conduct experiments on five types of VRPs: 1) travelling salesman problem (TSP); 2) capacitated VRP (CVRP); 3) split delivery VRP (SDVRP); 4) orienteering problem (OP); and 5) prize collecting TSP (PCTSP). The results show that our model not only outperforms the learning-based baselines but also solves the problems much faster than the traditional baselines. In addition, our model shows improved generalizability when being evaluated in large-scale problems, as well as problems with different data distributions.


Non-thermal nanoelectroablation of UV-induced murine melanomas stimulates an immune response.
Non-thermal nanoelectroablation therapy completely ablates UV-induced murine melanomas. C57/BL6-HGF/SF transgenic mice were exposed to UV radiation as pups and began to develop visible melanomas 5-6 months later. We have treated 27 of these melanomas in 14 mice with nanosecond pulsed electric field (nsPEF) therapy delivering 2000 electric pulses each 100 ns long and 30 kV/cm at a rate of 5-7 pulses per second. All nanoelectroablated melanoma tumors began to shrink within a day after treatment and gradually disappeared over a period of 12-29 days. Pyknosis of nuclei was evident within 1 h of nsPEF treatment, and DNA fragmentation as detected by TUNEL staining was evident by 6 h after nsPEF treatment. In a melanoma allograft system, nsPEF treatment was superior to tumor excision at accelerating secondary tumor rejection in immune-competent mice, suggesting enhanced stimulation of a protective immune response by nsPEF-treated melanomas. This is supported by the presence of CD4(+) -T cells within treated tumors as well as within untreated tumors located in mice with other melanomas that had been treated with nanoelectroablation at least 19 days earlier.


Description of the larva and pupa of Limnephilus hamifer Flint 1963 (Trichoptera, Limnephilidae) from Costa Rica.
The larva and pupa of Limnephilus hamifer Flint 1963 are described and illustrated for the first time. The description is based on material collected and reared from the Cerro de la Muerte mountain range in Costa Rica, and from additional specimens deposited at the Zoological Museum of the University of Costa Rica. The distribution of this species is restricted to high mountain areas of Costa Rica and Panamá and constitutes the most southern distribution of the genus on the American continent.


Synaptic organization of visual space in primary visual cortex.
How a sensory stimulus is processed and perceived depends on the surrounding sensory scene. In the visual cortex, contextual signals can be conveyed by an extensive network of intra- and inter-areal excitatory connections that link neurons representing stimulus features separated in visual space. However, the connectional logic of visual contextual inputs remains unknown; it is not clear what information individual neurons receive from different parts of the visual field, nor how this input relates to the visual features that a neuron encodes, defined by its spatial receptive field. Here we determine the organization of excitatory synaptic inputs responding to different locations in the visual scene by mapping spatial receptive fields in dendritic spines of mouse visual cortex neurons using two-photon calcium imaging. We find that neurons receive functionally diverse inputs from extended regions of visual space. Inputs representing similar visual features from the same location in visual space are more likely to cluster on neighbouring spines. Inputs from visual field regions beyond the receptive field of the postsynaptic neuron often synapse on higher-order dendritic branches. These putative long-range inputs are more frequent and more likely to share the preference for oriented edges with the postsynaptic neuron when the receptive field of the input is spatially displaced along the axis of the receptive field orientation of the postsynaptic neuron. Therefore, the connectivity between neurons with displaced receptive fields obeys a specific rule, whereby they connect preferentially when their receptive fields are co-oriented and co-axially aligned. This organization of synaptic connectivity is ideally suited for the amplification of elongated edges, which are enriched in the visual environment, and thus provides a potential substrate for contour integration and object grouping.


Maternal methylmercury exposure during early-life periods adversely affects mature enamel structure of offspring rats at human exposure levels: a concern for oral health.
Although there are many studies on the health effects of methylmercury (MeHg) toxicity during in utero and early development, little is known about its effects on mineralized tissues present in the oral cavity, such as enamel structure. Therefore, this study evaluated the effects of MeHg exposure on the physico-chemical, ultrastructural and functional properties of mature tooth enamel. Specifically, we studied offspring of mothers exposed to MeHg during the prenatal and postnatal periods which are the developmental stages associated with tooth enamel formation. Female rats were exposed to MeHg at a dose of 40 μg/kg/day for 42 days of pregnancy and lactation. The enamel of offspring was analyzed by (1) Fourier Transform Infrared Spectroscopy and Raman to assess physicochemical composition, (2) Scanning Electron Microscopy for ultrastructural evaluation, (3) Transmitted Polarizing Light Microscopy for analysis of the enamel extracellular matrix, and (4) resistance and hardness were evaluated by microhardness. The results showed that MeHg exposure during this sensitive enamel formation period induced changes in inorganic and organic content and enamel prisms ultrastructure alterations and disturbed the organic extracellular matrix due to a decreased enamel strength. These novel findings establish for the first time that maternal exposure to MeHg pre and postnatal promoted relevant changes in mature enamel of their offspring rats.


Commentary on Bowe et al, "The State of the Otolaryngology Match: A Review of Applicant Trends, 'Impossible' Qualifications, and Implications".
An objective evidence-based review of the metrics used to evaluate applicants entering our field ultimately found these figures to have upward trends without any major correlation to performance in residency. The rise of these metrics coincides with a yearly drop in senior applicants, and in 2017, nearly 10% of programs did not match their contingent. The causes of unmatched spots must be examined to ensure that the field of otolaryngology can continue to grow and attract medical students who will excel in our field. Considerations into revising the applicant selection process, early introduction and mentorship within the otolaryngology field, and changes to the current otolaryngology interview process are discussed.


Garlic attenuates nitric oxide production in rat cardiac myocytes through inhibition of inducible nitric oxide synthase and the arginine transporter CAT-2 (cationic amino acid transporter-2).
It is now accepted that allicin, the main biologically active compound in garlic, exhibits antioxidant activity. The present study was designed to test the hypothesis that the antioxidant activity of garlic can be partially attributed to the inhibition of nitric oxide (NO) production by cytokine-induced NO synthase (iNOS). Cardiac myocytes cultured from neonatal Wistar rats were stimulated by lipopolysaccharide (LPS) and incubated for 24 h with various concentrations of allicin. This resulted in marked inhibition of nitrite production. Interestingly, a low concentration of allicin (10 microM) was significantly more potent in abrogating the effect of LPS on nitrite production than a higher concentration (40 microM). Allicin decreased steady-state iNOS mRNA levels, and this effect was maximal when a lower concentration was used (10 microM compared with 40 microM). In order to explore additional effects of allicin on NO generation that might counteract the effect on iNOS, we assessed the effects of higher allicin concentrations on arginine transport. Allicin inhibited the uptake of 1 mM extracellular arginine in a concentration-dependent manner. The expression of the two arginine transporters that are expressed in cardiac myocytes [CAT-1 (cationic amino acid transporter-1) and CAT-2] was studied using reverse transcription-PCR. A concentration of 200 microM allicin abolished the expression of CAT-2 mRNA, 100 microM significantly attenuated it, whereas 50 microM had no effect. Allicin had no effect on steady-state CAT-1 mRNA levels. Our results suggest that allicin inhibits iNOS activity through two different mechanisms: at lower concentrations it decreases iNOS mRNA levels, whereas at higher concentrations it inhibits arginine transport through down-regulation of CAT-2 mRNA.


Spontaneous Magnetic Skyrmions in Single-Layer CrInX3 (X = Te, Se).
The realization of magnetic skyrmions in nanostructures holds great promise for both fundamental research and device applications. Despite recent progress, intrinsic magnetic skyrmions in two-dimensional lattice are still rarely explored. Here, using first-principles calculations and Monte Carlo simulations, we report the identification of spontaneous magnetic skyrmions in single-layer CrInX3 (X = Te, Se). Because of the joint effect of broken inversion symmetry and strong spin-orbit coupling, inherent large Dzyaloshinskii-Moriya interaction occurs in both systems, endowing the intriguing Néel-type skyrmions. By further imposing moderate magnetic field, the skyrmion phase can be obtained and is stable within a wide temperature range. Particularly for single-layer CrInTe3, the size of skyrmions is sub-10 nm and the skyrmion phase can be maintained at an elevated temperature of ∼180 K. In addition, the phase diagrams of their topological spin textures under the variation of magnetic parameters of D, J, and K are mapped out.


[Scrofuloderma. a clinical case].
Scrofuloderma is a form of colliquative cutaneous tuberculosis resulting from the spread of an underlying focus, generally represented by lymphnodes; osteoarticular tubercular locations or epididimus locations can also lead to ulcerative cutaneous involvement. We report the case of a female patient aged 12 who had been in Italy for 15 days following her arrival from Marocco. In the left clavicular region she presented an ulcerated lesion with palpable lymphnodes on the corresponding side of the neck. Histopathological examination of one of the involved lymphnodes suggested a mycobacteriosis; differential diagnosis was carried out between MAIS (M. avium, M. intracellulare, M. scrofulaceum) group mycobacteria infection and tuberculosis. Bacteriological research in the lymphnode of alcohol-acid resistant bacilli gave a negative result, while cultural examination and protein chain reaction pointed to M. tuberculosis. The patient was subjected to combined treatment based on rifampycin, isoniazide, etambutolol and pyrazinamide. At the present time, tuberculosis is an important public health problem in developing countries. In western countries such as the United Kingdom, which have been open to immigration for a longer time, scrofuloderma is present with higher prevalence in immigrants from Asia and Africa; in these immigrant populations, this tubercular form involves a wide age segment between the ages of 10 and 50. In the autochthonous population the highest incidence is in subjects aged more than 50. In Italy too, extra-communitary immigration has also contributed, with a delay compared to other western countries, to bring tuberculosis back into the public eye after a period of decades during which it was wrongly considered to have disappeared.


Immunohistochemical analysis of pRb2/p130, VEGF, EZH2, p53, p16(INK4A), p27(KIP1), p21(WAF1), Ki-67 expression patterns in gastric cancer.
Although the considerable progress against gastric cancer, it remains a complex lethal disease defined by peculiar histological and molecular features. The purpose of the present study was to investigate pRb2/p130, VEGF, EZH2, p53, p16(INK4A), p27(KIP1), p21(WAF1), Ki-67 expressions, and analyze their possible correlations with clinicopathological factors. The expression patterns were examined by immunohistochemistry in 47 patients, 27 evaluated of intestinal-type, and 20 of diffuse-type, with a mean follow up of 56 months and by Western blot in AGS, N87, KATO-III, and YCC-2, -3, -16 gastric cell lines. Overall, stomach cancer showed EZH2 correlated with high levels of p53, Ki-67, and cytoplasmic pRb2/p130 (P < 0.05, and P < 0.01, respectively). Increased expression of EZH2 was found in the intestinal-type and correlated with the risk of distant metastasis (P < 0.05 and P < 0.01, respectively), demonstrating that this protein may have a prognostic value in this type of cancer. Interestingly, a strong inverse correlation was observed between p27(KIP1) expression levels and the risk of advanced disease and metastasis (P < 0.05), and a positive correlation between the expression levels of p21(WAF1) and low-grade (G1) gastric tumors (P < 0.05), confirming the traditionally accepted role for these tumor-suppressor genes in gastric cancer. Finally, a direct correlation was found between the expression levels of nuclear pRb2/p130 and low-grade (G1) gastric tumors that was statistically significant (P < 0.05). Altogether, these data may help shed some additional light on the pathogenetic mechanisms related to the two main gastric cancer histotypes and their invasive potentials.