Identification of Chaetocin as a Potent non-ROS-mediated Anticancer Drug Candidate for Gastric Cancer.
Chaetocin, a natural product extracted from Chaetomium species, possesses anticancer effects in several kinds of tumors. However, it remains unclear whether the potential indication for chaetocin could also include human gastric cancer. We found here that chaetocin induced caspase-dependent and -independent apoptosis in human gastric cancer cell lines, which greatly depended on BID-mediated AIF translocation. Despite not increasing the intercellular ROS levels in gastric cancer cells, chaetocin did cause a reduction in mitochondrial membrane potential probably through its regulation on the expression of Bcl-2 and BAX. Chaetocin could also induce autophagy in gastric cancer cells; blocking autophagy by chloroquine enhanced the cytotoxicity of chaetocin. Chaetocin was further found to suppress the growth of gastric cancer xenograft in nude mice. Therefore, our study provides first evidence that chaetocin has an anticancer efficacy against gastric cancer and the combined use of chaetocin with autophagy inhibitors may enhance the therapeutic effect for gastric cancer. As chronic and exorbitant ROS levels instigate drug resistance, chaetocin, which eradicates gastric cancer cells without increasing ROS levels, may initiate a new line of non-ROS-mediated anti-tumor strategy.


Relationship between Vitamin B12 and Cobalt Metabolism in Domestic Ruminant: An Update.
Cobalt, as a trace element, is essential for rumen microorganisms for the formation of vitamin B12. In the metabolism of mammals, vitamin B12 is an essential part of two enzymatic systems involved in multiple metabolic reactions, such as in the metabolism of carbohydrates, lipids, some amino acids and DNA. Adenosylcobalamin and methylcobalamin are coenzymes of methylmalonyl coenzyme A (CoA) mutase and methionine synthetase and are essential for obtaining energy through ruminal metabolism. Signs of cobalt deficiency range from hyporexia, reduced growth and weight loss to liver steatosis, anemia, impaired immune function, impaired reproductive function and even death. Cobalt status in ruminant animals can be assessed by direct measurement of blood or tissue concentrations of cobalt or vitamin B12, as well as the level of methylmalonic acid, homocysteine or transcobalamin in blood; methylmalonic acid in urine; some variables hematological; food consumption or growth of animals. In general, it is assumed that the requirement for cobalt (Co) is expressed around 0.11 ppm (mg/kg) in the dry matter (DM) diet; current recommendations seem to advise increasing Co supplementation and placing it around 0.20 mg Co/kg DM. Although there is no unanimous criterion about milk production, fattening or reproductive rates in response to increased supplementation with Co, in some investigations, when the total Co of the diet was approximately 1 to 1.3 ppm (mg/kg), maximum responses were observed in the milk production.


Effects of thyroid hormone on regulation of lipolysis and adenosine 3',5'-monophosphate metabolism in 3T3-L1 adipocytes.
We have used cultured 3T3-L1 adipocytes to assess direct effects of T3 on beta-adrenergic-mediated regulation of lipolysis and adenylate cyclase and phosphodiesterase activities. Differentiated 3T3-L1 adipocytes were maintained under four conditions: in the presence of medium containing serum from a hypothyroid calf (hypothyroid medium), hypothyroid medium supplemented with T3 (T3-supplemented hypothyroid medium), medium with serum from a normal calf (control medium), and control medium supplemented with excess T3 (hyperthyroid medium). Compared to the two control groups, i.e. cells maintained in control medium or T3-supplemented hypothyroid medium, cells maintained in hypothyroid medium exhibited lower basal rates of lipolysis and lower sensitivity to isoproterenol. Hyperthyroid cells exhibited higher basal rates of lipolysis and higher sensitivity to isoproterenol. In the presence of maximally effective concentrations of isoproterenol, rates of lipolysis were similar in the four groups. Similarly, basal cAMP content and cAMP accumulation in the presence of isoproterenol were reduced in hypothyroid and increased in hyperthyroid adipocytes compared to those adipocytes maintained in control or T3-supplemented hypothyroid medium. Basal adenylate cyclase activity was similar in the four groups. Sensitivity to isoproterenol and maximal isoproterenol-stimulated cyclase activity were diminished in membrane preparations from hypothyroid adipocytes and increased in preparations from hyperthyroid adipocytes. Cyclase activity in the presence of NaF, however, was similar in preparations from cells maintained in hypothyroid, T3-supplemental hypothyroid, or control medium. NaF-stimulated activity was increased in preparations from hyperthyroid adipocytes. Thyroid status did not affect beta-receptor number of affinity for iodohydroxybenzylpindolol. Compared to control cells or cells maintained in T3-supplemented hypothyroid medium, both soluble and particulate cAMP phosphodiesterase activities were increased in hypothyroid cells and decreased in hyperthyroid cells. These results indicated that in 3T3-L1 adipocytes, some of the effects of thyroid hormone on cAMP content and lipolysis can be explained by alterations in both production and degradation of cAMP.


Current diagnostic methods of HER-2/neu detection in breast cancer with special regard to real-time PCR.
In this study we compare different diagnostic methods to measure HER-2/neu gene amplification in breast cancer with special regard to real-time polymerase chain reaction. Fifty specimens of breast cancer were analyzed, and the use of laser-assisted microdissection prior to PCR was investigated. A total of 38 of 50 cases showed HER-2/neu overexpression in immunohistochemistry. In the 2+ scored group, 2 of 23 cases turned out to be amplified after FISH analysis and 14 of 15 cases in the 3+ group were amplified. Of the 16 amplified cases, 3 initially were measured as nonamplified by real-time PCR but showed amplification after laser capture microdissection. One case showed amplification by PCR but turned out to have only one copy of chromosome 17 by FISH. All 0 or 1+ scored cases were measured as nonamplified both by FISH and PCR. Initial concordance rate between FISH and PCR was 92% and could be increased to 98% using laser-assisted microdissection. FISH and PCR showed high diagnostic accuracy and concordance while immunohistochemistry overestimates amplification within the 2+ scored group. Therefore, either FISH or PCR should be applied in cases scored 2+ by immunohistochemistry. Diagnostic accuracy of PCR can be increased using laser-assisted microdissection.


Froth-Flotation Separation as an Alternative for the Treatment of Soil Enriched with Fluorine Derived from Mica.
Fluorine (F) enrichment originating from natural sources is difficult to remove using chemical washing methods due to the large chemical-resistant residual fraction. This study evaluates the feasibility of using a froth-flotation separation method to remediate soil with a high F concentration caused by mica weathering, and it investigates the optimal conditions for this process, including pH of the slurry, collector dosage, and sample mechanical preparation strategy. The established optimum conditions are pH 3.5, 300 mg/kg collector dosage (tallow amine acetate), which can effectively separate quartz and mica, and a sieving-and-milling strategy that involves discarding particles of size < 0.05 mm, milling those in the range of 0.5-2.0 mm (until < approx. 0.3 mm), and mixing particles with sizes in the range of 0.05-0.5 mm. The target contamination level of 400 mg/kg for the test soil was not met after the first flotation separation process. However, after milling the residue of the first process and subjecting it to a second flotation separation process, the required contamination level was achieved. Consequently, the proposed froth-flotation separation process can be used as a successful alternative technique to remediate F-enriched soils from natural origin that have highly chemical-resistant forms.


Adherence to prophylactic treatment in adult patients with severe hemophilia in Poland.
Patient adherence to a prophylactic regimen is important for optimal benefit of hemophilia treatment. Despite a growing number of adults with hemophilia in Poland receiving secondary prophylaxis, data on adherence to the regimen are limited. The aim of the study was to assess adherence to secondary prophylaxis in Polish adults with severe hemophilia. Patients were recruited in 18 hemophilia treatment centers in Poland. Adherence to prophylaxis was assessed with the Validated Hemophilia Regimen Treatment Adherence Scale Prophylaxis (VERITAS‑Pro) questionnaire. Data on 270 men on the prophylactic regimen (median [interquartile range, IQR] age, 37 [18-75] years; mean [SD], 38.2 [13.3] years) were analyzed. Median (IQR) VERITAS‑Pro score for the study population was 36 (24-76) years; mean (SD), 37.7 (9.9) years, indicating general adherence to the prophylactic regimen. The median subscale scores ranged from 4 for Dosing to 8 for Planning (means, 5.6 and 7.7, respectively). The most pronounced difference in the subscale scores between adherent and nonadherent patients was recorded for Dosing (median, 4 vs 10; mean, 5.3 vs 9.3) and Remembering (median, 5 vs 11; mean, 5.7 vs 10.7). The overall adherence rate was 94%. Our results show a high rate of adherence to hemophilia prophylaxis by Polish adults. Problems with the management of clotting factor stocks and remembering about the injection of the clotting factor were identified as potential barriers to adherence in adults with hemophilia in Poland.


Genetic polymorphism related to ethambutol outcomes and susceptibility to toxicity.
The World Health Organization (WHO) stated that ensuring access to effective and optimal treatment is a key component to eradicate tuberculosis (TB) through the End TB Strategy. Personalized medicine that depends on the genetic profile of an individual is one way to optimize treatment. It is necessary because of diverse drug responses related to the variation in human DNA, such as single-nucleotide polymorphisms (SNPs). Ethambutol (EMB) is a drug widely used as the treatment for Mycobacterium Tuberculosis (Mtb) and/non-tuberculous mycobacteria and has become a potential supplementary agent for a treatment regimen of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. In human genetic polymorphism studies of anti-tuberculosis, the majority focus on rifampicin or isoniazid, which discuss polymorphisms related to their toxicity. Whereas there are few studies on EMB, the incidence of EMB toxicity is lower than that of other first-line anti-TB drugs. To facilitate personalized medicine practice, this article summarizes the genetic polymorphisms associated with alterations in the pharmacokinetic profile, resistance incidence, and susceptibility to EMB toxicity. This study includes 131 total human studies from 17 articles, but only eight studies that held in the low-middle income country (LMIC), while the rest is research conducted in developed countries with high incomes. Personalized medicine practices are highly recommended to maintain and obtain the optimal therapeutic effect of EMB.


Sperm-storage defects and live birth in Drosophila females lacking spermathecal secretory cells.
Male Drosophila flies secrete seminal-fluid proteins that mediate proper sperm storage and fertilization, and that induce changes in female behavior. Females also produce reproductive-tract secretions, yet their contributions to postmating physiology are poorly understood. Large secretory cells line the female's spermathecae, a pair of sperm-storage organs. We identified the regulatory regions controlling transcription of two genes exclusively expressed in these spermathecal secretory cells (SSC): Spermathecal endopeptidase 1 (Send1), which is expressed in both unmated and mated females, and Spermathecal endopeptidase 2 (Send2), which is induced by mating. We used these regulatory sequences to perform precise genetic ablations of the SSC at distinct time points relative to mating. We show that the SSC are required for recruiting sperm to the spermathecae, but not for retaining sperm there. The SSC also act at a distance in the reproductive tract, in that their ablation: (1) reduces sperm motility in the female's other sperm-storage organ, the seminal receptacle; and (2) causes ovoviviparity--the retention and internal development of fertilized eggs. These results establish the reproductive functions of the SSC, shed light on the evolution of live birth, and open new avenues for studying and manipulating female fertility in insects.


Relative age effect in female sport: a diachronic examination of soccer players.
The relative age effect (RAE) is a biased distribution of elite athletes' birthdates, with an overrepresentation of those born at the beginning of the competitive year and an underrepresentation of those born at the end. Despite an abundant literature, the impact of sex on this phenomenon remains neglected by most researchers. This study investigated the whole sample of female soccer players affiliated to the French Soccer Federation for the 2006-2007 season (n=57 892). It first aimed at testing the presence of RAE depending on age. Next, we looked at the birthdates of dropout players during the next season (n=15 285), to test whether relative age accounts for dropout from the activity. The analyses revealed significant differences between the expected and the observed distributions for all age categories. Furthermore, a significantly biased distribution of dropout players' birthdates was found for the <10, <14, and <17 categories. On the whole, dropout players are underrepresented in Q1 and Q2, but overrepresented in Q3 and Q4. This study completes the literature on RAE among females, but the inconsistency of the results calls for more research on this population.


Functional status of peripheral blood T-cells in ischemic stroke patients.
Stroke is a major cause of disability and leading cause of death in the northern hemisphere. Only recently it became evident that cerebral ischemia not only leads to brain tissue damage and subsequent local inflammation but also to a dramatic loss of peripheral blood T-cells with subsequent infections. However, only scarce information is available on the activation status of surviving T cells. This study therefore addressed the functional consequences of immunological changes induced by stroke in humans. For this purpose peripheral blood T-cells were isolated from 93 stroke patients and the expression of activation makers was determined. In addition ex vivo stimulation assays were applied to asses the functionality of T cells derived from blood of stroke patients. Compared to healthy controls, stroke patients demonstrated an enhanced surface expression of HLA-DR (p<0.0001) and CD25 (p = 0.02) on T cells, revealing that stroke leads to T cell activation, while CTLA-4 remained undetectable. In vitro studies revealed that catecholamines inhibit CTLA-4 upregulation in activated T cells. Ex vivo, T cells of stroke patients proliferated unimpaired and released increased amounts of the proinflammatory cytokine TNF-alpha (p<0.01) and IL-6 (p<0.05). Also, in sera of stroke patients HMGB1 concentrations were increased (p = 0.0002). The data demonstrate that surviving T cells in stroke patients remain fully functional and are primed towards a TH1 response, in addition we provide evidence that catecholamine mediated inhibition of CTLA-4 expression and serum HMGB1 release are possible mediators in stroke induced activation of T cells.


[Local and systemic immunity in patients with different course of generalized periodontitis].
The aim of the study was to assess local immunity of oral cavity and system immunity in patients with different course of generalized periodontitis. Immunological parameters of oral mucosa, gingival liquid and blood were evaluated in 99 persons (31 with an intact periodontium, 32 patients with chronic course of periodontal disease and 36 patients with exacerbated periodontal disease). Complex immunological assessment revealed that in periodontal disease the main changes were concentrated in the system of local oral immunity. However, in the patients with exacerbated periodontal disease significant changes were also observed in humoral immunity and in the system of nonspecific protection. Revealed immunological disbalance in patients with different course of periodontal disease requires differentiated immunotherapy.


[A multi-fractionated course of gamma teletherapy in the late stages of cancer of the maxillofacial area and neck].
The results of gamma-beam therapy using a multifractional course in 373 patients with advanced stages of different parts of the maxillofacial area and neck were assessed. The 3-year survival rates among patients with stage IV (83.9%) were 18.8% for cancer of the organs of the oral cavity and 16.8% for cancer of the accessory nasal sinus and nose. Multifractional radiotherapy puts an end to painful symptoms in patients at advanced stages of cancer without causing any noticeable local reactions or deterioration in the patients' general status.


Ring opening of donor-acceptor cyclopropanes with the azide ion: a tool for construction of N-heterocycles.
Invited for the cover of this issue is the group of Ekaterina M. Budynina and Igor V. Trushkov at Lomonosov Moscow State University. The image depicts the diversity of synthetic outcomes that can be achieved by using the ring-opening of donor-acceptor cyclopropanes with the azide ion as a triggering reaction. Read the full text of the article at 10.1002/chem.201405551.


Magnetic face-to-face interaction and electrocommunication in chromium sandwich compounds.
The reaction of [{(C5Me5)CrCl2}2] with [2.2](1,4)cyclophane gave [(C5Me5)Cr{[2.2](1,4)cyclophane}] (1) and [(C5Me5)Cr{[2.2](1,4)cyclophane}Cr(C5Me5)] (2), depending on the reaction conditions. X-ray structure analysis showed 2 to be a ministack which in turn is stacked in the lattice. The chromium atoms are 6.035 A apart, and the distortion of the benzene rings to boat-shaped moieties is less pronounced than in parent [2.2](1,4)cyclophane. The NMR and EPR spectra were consistent with a S=1/2 ground state for 1 and with two interacting S=1/2 centers in 2. Spin density was found in the ligand pi systems, where its sign was negative when the pi system was adjacent to chromium, while on the nonbonded benzene moiety of 1 it was positive. Cyclic voltammograms showed reductions to 1- and 2(2-), as well as oxidations to 1+, 2+, and 2(2+) which were quasireversible, whereas oxidations to 1(2+) and 2(3+) were irreversible. Interaction between the metal ions was revealed by a 260 mV separation of the redox waves belonging to 2+, and 2(2+). Both cations were isolated as [B(C6H5)4]- salts, which in solution decomposed to [2.2](1,4)cyclophane and [(C5Me5)Cr{(eta6-C6H5)B(C6H5)3}] (3). The 1H and 13C NMR spectra of 3 were in accordance with an S=1 ground state. Solid-state magnetic measurements of the dimetallic compounds showed antiferromagnetic interaction with J=-122 cm-1 for 2, J=-31 cm-1 for 2+ (ground state S=1/2), and J=-23.5 cm-1 for 2(2+) (with H=-JS1S2). The decrease of J in the series 2, 2+, and 2(2+) was traced to the number of unpaired electrons and, for the mixed-valent cation 2+, to additional double exchange.


Total laryngectomy - past, present, future.
In a period in which therapeutic approaches for malignant laryngeal tumors are focused on the principle of "organ preservation", total laryngectomy is a well coded surgical procedure, addressed to the advanced laryngeal cancer which is not suitable for conservative techniques or in case of their failure. The main objective of this work is to summarize the important events that have marked the evolution of this surgical technique to the current formula. Also this paper aims to identify, in our own casuistry, some elements of strategy and surgical technique required, in our opinion, for a successful therapeutic intervention. The fundamental significance of the study is that we must learn from the past, perform our surgeries at contemporary standards and look to the future for new solutions and approaches of the advanced laryngeal malignancies.


Calculation of plantar pressure time integral, an alternative approach.
In plantar pressure measurement, both peak pressure and pressure time integral are used as variables to assess plantar loading. However, pressure time integral shows a high concordance with peak pressure. Many researchers and clinicians use Novel software (Novel GmbH Inc., Munich, Germany) that calculates this variable as the summation of the products of peak pressure and duration per time sample, which is not a genuine integral of pressure over time. Therefore, an alternative calculation method was introduced. The aim of this study was to explore the relevance of this alternative method, in different populations. Plantar pressure variables were measured in 76 people with diabetic polyneuropathy, 33 diabetic controls without polyneuropathy and 19 healthy subjects. Peak pressure and pressure time integral were obtained using Novel software. The quotient of the genuine force time integral over contact area was obtained as the alternative pressure time integral calculation. This new alternative method correlated less with peak pressure than the pressure time integral as calculated by Novel. The two methods differed significantly and these differences varied between the foot sole areas and between groups. The largest differences were found under the metatarsal heads in the group with diabetic polyneuropathy. From a theoretical perspective, the alternative approach provides a more valid calculation of the pressure time integral. In addition, this study showed that the alternative calculation is of added value, along peak pressure calculation, to interpret adapted plantar pressures patterns in particular in patients at risk for foot ulceration.


Clinical and histopathological presentation and successful treatment with ciclosporin for canine sarcoidosis: a case report.
Sarcoidosis is a granulomatous disease histologically characterized by naked granulomas in various mammals. Canine sarcoidosis is a rare disease which can cause nonpruritic papule, plaques and nodules on the trunk, neck, face and ear; it is usually treated with corticosteroids. To date, there are no published reports on alternatives to corticosteroids treatment. To report a case of canine cutaneous sarcoidosis successfully treated with oral ciclosporin. An 11-year-old beagle dog was presented with multiple pleomorphic plaques on the lateral thighs and dorsal trunk. Skin punch biopsy specimen were collected and analysed via routine histological examination and immunohistochemistry. After 14 weeks of oral ciclosporin treatment, repeat skin biopsy specimens were collected. Histopathological examination revealed noncaseating epithelioid cell granuloma formation in the dermis. Dermal epithelioid cells were positive for CD18 and Iba1, but not for CD3, CD20 and E-cadherin based on immunohistochemistry findings. Acid-fast bacteria, fungi and Leishmania spp. were not detected by special stains, culture or polymerase chain reaction. An initial two week treatment with immunosuppressive doses of oral prednisolone and doxycycline was not effective. Skin lesions were almost in remission after 14 weeks of oral ciclosporin treatment without adverse events. Histologically, the dermal granulomatous lesions regressed and were replaced by fibrous tissues after ciclosporin treatment. This case report describes the clinical and histopathological presentation including immunohistochemistry and treatment outcome of a case of canine sarcoidosis Ciclosporin may be an effective alternative to corticosteroids for treating canine sarcoidosis.


Analysis for voltammetric responses of molecular-solid tetrathionaphthalene confined on an electrode.
The cyclic voltammetry (CV) of solid-state tetrathionaphthalene (TTN; particles with diameters from a few tens to hundreds of nanometers) confined on electrodes was analyzed quantitatively by considering the inert-zone potential, the thermodynamic and kinetic interactions, and the kinetics of the electrode reaction. Theoretical treatments are applied for clarifying the experimentally accessible corresponding parameters. From the potential of full peak width at half-height current (ΔE(p1/2)) and the peak current (i(p)) for the reversible CV voltammogram obtained at the slowest potential scan rate, the thermodynamic attraction forces in their active materials are evaluated as W = 3.67 ± 0.30 kJ mol(-1) for the (TTN)(0/1+) redox couple. From the shift of peak potential (ΔE(p)) and the changes in ΔE(p1/2) and/or the magnitude of i(p) for the irreversible CV obtained against the moderate potential scan rate, the value of the formal rate constant (k°') regarding surface electrode reaction of the (TTN)(0/1+) couple was evaluated as 0.59 ± 0.10 s(-1). The interaction parameters of W and ΔW[symbol: see text] being related to the thermodynamic and the kinetic interactions of the electrode reaction for the (TTN)(0/1+) couple were also evaluated as 3.39 ± 0.41 kJ mol(-1) and -1.39 ± 0.31 kJ mol(-1), respectively, from analysis for the irreversible CV.


Functionalized calix[4]arenes as potential therapeutic agents.
Calixarenes, composed of phenolic units linked by methylene bridges at the 2,6-positions, represent a versatile class of macrocyclic compounds in supramolecular chemistry that can host small molecules or ions in their well-defined hydrophobic cavities. In recent years, it has been recognized that this class of compounds has the potential to serve as platform for the design of biological active compounds. Therefore, the calixarenes functionalized with different pharmacophoric groups have been synthesized as target structure by many researchers and were further evaluated for their biological activities. Owing to their promising biological activities such as antiviral, antibacterial, antifungal, and anticancer, the functionalized calixarenes are recently receiving increased attention from pharmaceutical/medicinal chemistry community. In this review, we summarize and discuss the synthetic approaches and the biological potential of functionalized calixarenes, mainly focusing on the selected recent studies for a comprehensive and target-oriented information, which could help in the design and synthesis of new therapeutic agents leading to the development of clinically viable drugs based on these macrocyles.


A Hybrid Effectiveness-Implementation Study of a Multi-Component Lighting Intervention for Hospital Shift Workers.
Simple lighting solutions may mitigate the harmful effects of shiftwork. This hybrid effectiveness-implementation study evaluated a multi-component lighting intervention in hospital nurses that included 6500 K architectural lighting in the nurses' station plus optional behavioral components (a lightbox, blueblocker glasses, eyemasks) with instruction about appropriately timed usage. Selective improvements from baseline were observed in on-shift performance, sleep quality, and caffeine consumption in day workers (all p < 0.05); off-shift sleepiness scores improved for night workers (p < 0.05). Further, self-reported measures of quality of life improved for both groups (p < 0.05). Preliminary implementation data from interviews and questionnaires suggest perceived benefits and high acceptability of the intervention.


Efficacy and safety of the six-dose regimen of artemether-lumefantrine in pediatrics with uncomplicated Plasmodium falciparum malaria: a pooled analysis of individual patient data.
Patient data from eight clinical trials were pooled and analyzed to study the efficacy and safety of the six-dose versus four-dose regimen of artemether-lumefantrine (coartemether; Coartem) in children weighing 5-25 kg. A total of 544 patients with uncomplicated P. falciparum malaria (six-dose: 343; four-dose: 201), matched for demographic and baseline characteristics and individual coartemether doses were included in the analysis. Analysis of day 28 cure rate based on the intention-to-treat and evaluable populations yielded corrected cure rates for the six-dose regimen of 93% and 96% compared with 61% and 76%, respectively, for the four-dose regimen (P < 0.0001 for both comparisons). Similarly high cure rates were achieved with the six-dose regimen in non-immune infants weighing as little as 5 kg. The six- and four-dose regimens were equally well tolerated. The main finding of this analysis is that the six-dose regimen of coartemether is safe and more efficacious than the four-dose regimen in children.


Irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer.
Out of every 17-18 individuals in the US, one develops colorectal cancer (CRC) in their lifetime. Of individuals diagnosed with CRC, > 50% present or develop metastatic disease, which, if untreated, is associated with 6-9 months median survival. Although surgical resection is the primary treatment modality for CRC, chemotherapy is the mainstay of treatment for metastatic or unresectable disease. For nearly three decades, 5-fluorouracil (5-FU) has been the chemotherapy of choice for treatment of CRC. However, the response rates to single 5-FU therapy have been suboptimal with an objective tumour response of 10-20%. Attempts have been made to improve the efficacy of 5-FU by either schedule alteration (protracted infusion versus intravenous push) or biochemical modulation with leucovorin (LV). Continuous infusion induced more tumour regression and prolonged the time-to-disease progression with some significant impact on survival (11.3 versus 12.1 months; p < 0.04). 5-FU/LV resulted in a significant increase in overall response rates and in the prolongation of disease-free survival in the adjuvant setting, although severe toxicities represent a major clinical problem. The last 10 years have seen the addition of several new agents such as irinotecan, oxaliplatin, raltitrexed, bevacizumab and cetuximab. The prognosis has significantly improved with the addition of these agents, with median survivals now > 20 months. This review paper focuses on irinotecan, oxaliplatin and raltitrexed when used alone and in combination.


Triple osteotomy of the pelvis in children and adolescents.
To assess the results of Steel triple osteotomy on Developmental hip displacement (DDH) and Legg-Calvé-Perthes Disease (LCPD) cases utilising objective criteria based on measurements. All measurements were done by a co-author in a blind way. What concerns DDH, triple osteotomy was used in all cases in which authors felt to obtain a profit for a patient, so that hips with non-spherical head were operated on, too. On the other hand, as far as the experience with Steel osteotomy in LCPD is very limited, authors used this method presuming to obtain similar effect like with Salter osteotomy in younger patients. 41 Steel osteotomies carried out in 29 cases of developmental dislocation of the hip (DDH), (age ranging 14-23 years) and in 12 cases of Legg-Calvé-Perthes disease (LCPD), (9-12 years of age) have been analysed. The follow-up duration was 4-12 years. Differently to the postulations of Dr. Steel, the inaugurator of triple osteotomy for DDH cases, indications in this study were also extended to aspherical congruencies and even incongruencies in DDH. Besides measuring CE, Sharp angles and Reimer's index, there was used subjectively descriptive classification of both initial conditions and results. The reached medialization and caudalization of the femoral head to Shenton line played an important role at the evaluating classification of the results. All obtained data were processed by the statistical methods to ascertain the influence of the operation. The same measuring methods were used for assessment of LCPD cases. Fisher's exact test has shown the dependence of the results in DDH on the preoperative finding, reflecting the fact, that the triple osteotomy did not improve substantially the parameters of the more distorted hip joints. With the greater degree of joint deformity, the chance to obtain postoperative correction was less. Complete correction in all the DDH group was obtained in 20, partial correction in 7 cases and failure was found in 2 cases. Fisher exact test in LCPD demonstrated that results are not statistically dependent on the initial state. Complete correction in LCPD group was obtained in 10, partial correction in 1 and failure in 1 case. It seems that the indication of Steel triple osteotomy in DDH must be highly well-considered concerning especially the containment of aspherical femoral head. Indication should be based on careful pre-operative planning using dynamic contrast arthrography helping to find the best position of femoral head through the additional femoral osteotomy. Hitherto rare application of Steel osteotomy for LCPD everywhere seems to be little irrespective of the fact that this operation can secure the containment of even deformed femoral head with the perspective of its subsequent remodelling as showed this study. The historical postulate of inaugurator of triple osteotomy, concerning the sphericity of the femoral head as a condition sine qua non, seems to be broken especially in Legg-Calvé-Perthes disease. Even sattle deformity of femoral head can be corrected. What concerns the DDH the greater degree of joint deformity, especially aspherical incongruency brings about the risk of failure of surgical procedure. Nevertheless, in this study five out from seven cases of that degree of distortion obtained at least partial correction.


Correlation between the salivary microbiology and H2 S concentration of the oral cavity.
Hydrogen sulfide (H2 S) is the most important compound causing oral malodor, and its concentration is thought to be closely correlated with oral microorganism activity. Therefore, clarifying the correlation between oral microbes and metabolites is important. This study tested with 16S rRNA gene amplicon and shotgun metagenomic sequencing of oral microorganisms and oral malodor tests. There were different of the microbial taxa between the low and high H2 S groups. And in the high H2 S group, most of the enriched taxa were genera which abundance was correlated with H2 S concentration. Fusobacterium periodonticum and Prevotella nanceiensis were significantly different in coverage breadth and depth and in LPS biosynthesis contributions between the two groups. The contribution of F. periodonticum to sulfur metabolism was significantly different between the two groups, and the relative F. periodonticum abundance was higher in the high H2 S group. The H2 S content is significantly associated with the oral cavity microorganism composition and abundance. Most microorganisms enriched in people with high H2 S levels are associated with oral diseases such as caries and periodontal diseases.


Hemangioblastoma: a study of radiopathologic correlation.
Computerized tomography (CT) scan and operative observations, and histolopathogical findings of 25 cases of intracranial hemangioblastoma were correlated. Solid hemangioblastomas showed a large number of thin-walled capillaries and abundant stromal cells with eosinophilic cytoplasm. Tumors with a cystic component and a mural nodule had a large number of stromal cells with vacuolated cytoplasm and microcysts.


Structure and function of the growth-hormone-releasing hormone receptor.
Growth-hormone-releasing hormone (GHRH) stimulates growth hormone (GH) secretion and GH synthesis and is also thought to cause somatotroph proliferation. Specific high-affinity binding sites for GHRH have been demonstrated on pituitary membranes using iodinated GHRH analogs. The complementary DNA encoding for the human GHRH receptor (GHRH-R) was recently cloned. The open reading frame was shown to extend 1269 bp and thus to encode a protein of 423 amino acids with a predicted molecular weight of 47 kDa. Expression is restricted to specific tissues. Analysis of the genomic structure revealed that the human GHRH-R gene spans 15 kb and consists of 13 exons. The 5'-flanking region of the human GHRH-R gene was recently characterized. Transcriptional regulation of the GHRH-R is discussed in this review. Mechanisms of signal transduction for control of GH transcription and secretion are presented. Furthermore, the role of the GHRH-R in proliferation and differentiation of the somatotrophic pituitary cell as well as in disease is examined.


Sardine peptide with angiotensin I-converting enzyme inhibitory activity improves glucose tolerance in stroke-prone spontaneously hypertensive rats.
An enzymatic hydrolysate of sardine protein (sardine peptide, SP) derived from sardine muscle possesses angiotensin I-converting enzyme (ACE) inhibitory activity. In the present study, we investigated the effect of SP on the blood glucose levels in stroke-prone spontaneously hypertensive rats (SHRSPs). Ten-week-old SHRSPs were assigned to three groups. The control group was given tap water for 4 weeks, while the experimental groups were given water containing SP (1 g/kg/d) or an ACE inhibitor, captopril (8 mg/kg/d). Treatment with SP and captopril decreased ACE activity in the kidney, aorta, and mesentery. There were no differences in fasting blood glucose levels among the three groups, whereas SP and captopril administration significantly suppressed the increase in blood glucose after glucose loading in the control SHRSPs. No difference was observed in plasma insulin levels among the three groups. Thus treatment with captopril and ACE-inhibitory sardine peptides ameliorated the glucose tolerance of this rat strain.


Mothers' and fathers' mind-mindedness influences physiological emotion regulation of infants across the first year of life.
The main aim of this study was to test whether mothers' (n = 116) and fathers' (n = 116) mind-mindedness predicts infants' physiological emotion regulation (heart rate variability; HRV) across the first year of life. Three hypotheses were examined: (a) parents' mind-mindedness at 4 and 12 months predicts infants' HRV at 12 months over and above infants' initial HRV levels at 4 months, (b) mothers' and fathers' mind-mindedness independently predict infant HRV, and (c) the effects of mind-mindedness on infant HRV (partially) operate via parenting behaviour. Infants' HRV was assessed during rest and a stranger approach. Mind-mindedness was assessed by calculating the proportions of appropriate and non-attuned mind-related comments during free-play interactions, and parenting quality was observed at 4 and 12 months in the same interactions. Path analyses showed that mothers' appropriate mind-related comments at 4 and 12 months predicted higher baseline HRV at 12 months, whereas mothers' non-attuned comments predicted lower baseline HRV at 12 months. Similar, but concurrent, relations were found for fathers' appropriate and non-attuned mind-related comments and infant baseline HRV at 12 months. In addition, fathers' appropriate mind-related comments showed an indirect association with infant baseline HRV at 12 months via fathers' parenting quality. With regard to infant HRV reactivity during the stranger approach, mothers' appropriate mind-related comments at 4 months and fathers' non-attuned mind-related comments at 12 months predicted a larger HRV decline during the stranger approach at 12 months. Infants' HRV at 4 months did not predict parents' later mind-mindedness. The results indicate that mothers' and fathers' appropriate and non-attuned mind-related speech uniquely impacts the development of infants' physiological emotion regulation.


Multidisciplinary Progress in Obesity Research.
Obesity is a chronic disease that endangers human health. In recent years, the phenomenon of obesity has become more and more common, and it has become a global epidemic. Obesity is closely associated with many adverse metabolic changes and diseases, such as insulin resistance, type 2 diabetes mellitus, coronary heart disease, nervous system diseases and some malignant tumors, which have caused a huge burden on the country's medical finance. In most countries of the world, the incidence of cancer caused by obesity is increasing year on year. Diabetes associated with obesity can lead to secondary neuropathy. How to treat obesity and its secondary diseases has become an urgent problem for patients, doctors and society. This article will summarize the multidisciplinary research on obesity and its complications.


Transforming growth factor-beta regulates production of proteoglycans by mesangial cells.
Accumulation of glomerular extracellular matrix is a prominent feature of most forms of progressive glomerular disease. Since some growth factors may play a role in extracellular matrix production, we examined the effects of transforming growth factor-beta (TGF-beta), interleukin 1, platelet derived growth factor, and tumor necrosis factor on the production of extracellular matrix components by cultured rat mesangial cells. In control experiments we found that mesangial cells produced two distinct proteoglycans identified as the small chondroitin/dermatan sulfate proteoglycans biglycan (PG I) and decorin (PG II) by showing that their mobility on SDS-PAGE changed upon digestion by chondroitinase ABC, and that they reacted with antibodies raised against synthetic peptides from the core protein sequence of human biglycan and decorin. Exposure to TGF-beta for 48 hours stimulated an 8- to 10-fold increase in the biglycan and decorin bands, and induced a structural change detected as a shift in electrophoretic mobility. TGF-beta did not demonstrably affect the production of other matrix proteins by the mesangial cells. The other growth factors tested had no comparable effect on the production of proteoglycans or other extracellular matrix components by these cells. Our results show that TGF-beta is unique among growth factors in its regulatory effects on mesangial cell proteoglycan production. The release or activation of TGF-beta during glomerular injury could mediate the accumulation of proteoglycans in the extracellular matrix and predispose the kidney to development of glomerulosclerosis.


Tobacco Point-of-Sale Influence on U.S. Adult Smokers.
Prior research has shown that tobacco companies target point-of-sale (POS) marketing to low-income communities. This research assessed the association between demographic characteristics and venue type with purchasing tobacco products in response to marketing. Using Population Assessment of Tobacco and Health (PATH) Study Wave 1 Adult data, this analysis compared promotion awareness and purchase influence among current smokers. Tobacco promotions were more likely to be noticed at convenience stores, gas stations, or tobacco stores than at other outlets. Smokers who bought their cigarettes at these outlets were more likely to purchase a brand other than their usual brand because of marketing. Smokers below the poverty level had greater odds than others to have noticed tobacco ads and to indicate purchase influence. Point-of-sale marketing is effective in garnering the attention of low-income populations and influencing their tobacco purchases. Enforcing retailers' adherence to regulations is vital.


An epidemiological study of snake bite envenomation in Papua New Guinea.
We report a study of 347 patients with snake bite envenomation in Papua New Guinea. The male: female ratio of the victims was 1.6:1 and their mean age was 24.5 years; 26% were children less than 15 years old. In all cases in which the bite site was known (334) the snake had bitten the extremities of the victim, with 71.3% of these bites being on the ankle or below. The patients came from three regions: urban Papua, rural Papua and (mostly rural) New Guinea. Snake bites occurred more frequently during the daytime in all regions, but this pattern was less obvious in New Guinea (P = 0.004), reflecting the predominance of the death adder (Acanthophis antarcticus) in New Guinea and of the taipan (Oxyuranus scutellatus canni) in Papua. Bites were commoner in the rainy season (November to April) in all groups, but this was less noticeable in rural Papua and New Guinea (P = 0.004). This may relate to seasonal activities of the rural population. The female:male ratio for patients from rural areas was higher for those 30 years of age and over than for those under 30 (P = 0.034), probably reflecting the increased gardening workload of older women. The incidence of envenomation and mortality rates after snake bite in Papua appear to have changed little over 25 years. However, increased relative numbers of taipans seem to be occurring in central Papua possibly related to the cane toad (Bufo marinus) and deforestation. We calculate the annual incidence of envenomation and the mortality rate per 100,000 to be 81.8 and 4.3, respectively, for rural central Papua, 21.8 and 2.1 for urban central Papua, and 3.0 and less than 1.0 for the Madang region of New Guinea. The importance of a standard management protocol and of improved first aid are emphasised.


Biodegradation of N-nitrosodimethylamine in aqueous and soil systems.
N-Nitrosodimethylamine (NDMA) was mineralized by microorganisms in aqueous and soil systems. Initial rates of mineralization (micrograms per milliliter per day) were calculated for a wide range of initial concentrations of NDMA (micrograms per milliliter to picograms per milliliter). Log-log plots of the data were fitted with both linear and nonlinear least-squares analyses; however, linear models provided better fits for the kinetic data in all cases. The slopes of the linear fits were not significantly different than 1.0 (P < 0.05); thus, first-order reaction kinetics were in effect over the range of concentrations tested, and saturation kinetics were not achieved. Rate constants (day) and total percent mineralized increased with decreasing initial concentrations of NDMA. Rates of mineralization were reduced in aqueous systems when supplemental carbon was available, whereas in soils, percentages of organic matter and supplemental carbon had little effect on rates of mineralization. Implications of these results for predictions of rates and threshold limits of mineralization activity in natural systems are discussed. A laboratory scale simulated trickling filter containing an activated charcoal bed provided a suitable environment for mineralization of NDMA at concentrations of 50 and 100 mug/ml on a continuous basis. NDMA was not toxic to natural populations of microorganisms at concentrations up to 10 mg/ml. Using high-pressure liquid chromatography coupled with radioactivity detection, we identified formaldehyde and methylamine as intermediates produced during the biodegradation of NDMA.


Ras and Rap1 activation of PLCepsilon lipase activity.
Phosphoinositide-specific phospholipase C (PLC) plays a pivotal role in signal transduction from various receptor molecules on the plasma membrane. PLCepsilon is characterized by possession of two Ras/Rap-associating (RA) domains and a CDC25 homology domain acting as a guanine nucleotide exchange factor for Rap1. Our recent studies using PLCepsilon-deficient mice have suggested that PLCepsilon plays crucial roles in cardiac semilunar valvulogenesis downstream of the EGF receptor, as well as in chemical carcinogen-induced skin tumor development downstream of Ha-Ras. Stimulation of cultured mammalian cells with growth factors induces translocation of PLCepsilon from the cytoplasm to the plasma membrane and to the Golgi apparatus through direct association at its RA domains with the GTP-bound forms of Ras and Rap1, respectively. These results suggest that growth factor stimulation activates PLCepsilon by means of Ras and/or Rap1. However, growth factor-induced activation of the PLCepsilon lipase activity cannot be measured accurately because of simultaneous activation of PLCgamma through receptor-dependent phosphorylation. In this article, we introduce two methods to assay Ras- or Rap1-dependent activation of PLCepsilon lipase activity, with special emphasis on the use of cells expressing a mutant platelet-derived growth factor receptor lacking the PLCgamma-binding sites.


[Tissue blood flow of the sigmoid colon for safe anastomosis following ligation of the inferior mesenteric artery].
We examined the tissue blood flow (TBF) of the sigmoid colon to determine which level of inferior mesenteric artery. In 13 patients, TBF of the sigmoid colon was measured in the control state and the clamped state, in which the inferior mesenteric artery (IMA), left colic artery and the rectal were wall clamped. In the clamped state, means of TBF at 10 cm and 15 cm distal to the descend-sigmoid junction were 1.87 +/- 0.77 and 1.10 +/- 0.40, respectively. Mean of TBF at 15 cm was significantly lower than that at 10 cm. In conclusion, TBF which is enough for safe anastomosis reaches as far as 10 cm distal from the descend-sigmoid junction after ligation of IMA. Anastomosis at this level in anterior resection of the rectum is safe in concerning with TBF.


The different roles of two distinct Fc gamma receptors on guinea pig macrophages in the phagocytosis of sensitized sheep erythrocytes.
The functional roles of two distinct types of Fc gamma receptors (Fc gamma 1/gamma 2R specific for both IgG1 and IgG2, and Fc gamma 2R specific for IgG2 alone) on the surface of guinea pig macrophages in the phagocytosis of sensitized sheep erythrocytes (EA) were investigated by the use of two Fab's of monoclonal anti-Fc gamma 1/gamma 2R and anti-Fc gamma 2R antibodies. The binding and subsequent ingestion of IgG1 antibody-sensitized erythrocytes (EA gamma 1) by macrophages were completely inhibited by anti-Fc gamma 1/gamma 2R Fab', indicating that the reactions are mediated only by Fc gamma 1/gamma 2R. On the other hand, the binding and subsequent ingestion of IgG2 antibody-sensitized erythrocytes (EA gamma 2) were substantially inhibited by anti-Fc gamma 2R Fab', but not by anti-Fc gamma 1/gamma 2R Fab'. The inhibitory activities of anti-Fc gamma 2R Fab' were dependent upon the amount of IgG2 antibody bound on erythrocytes; increasing the amount of bound IgG2 antibody from 0.15 to 0.91 micrograms/2 X 10(8) erythrocytes resulted in a decrease in the inhibition of binding of EA gamma 2 by anti-Fc gamma 2R Fab' from 50 to 0%, and also a decrease in the inhibition of ingestion of EA gamma 2 from 100 to 50%.(ABSTRACT TRUNCATED AT 250 WORDS)


Comprehensive genome-scale metabolic model of the human pathogen Cryptococcus neoformans: A platform for understanding pathogen metabolism and identifying new drug targets.
Introduction: The fungal priority pathogen Cryptococcus neoformans causes cryptococcal meningoencephalitis in immunocompromised individuals and leads to hundreds of thousands of deaths per year. The undesirable side effects of existing treatments, the need for long application times to prevent the disease from recurring, the lack of resources for these treatment methods to spread over all continents necessitate the search for new treatment methods. Methods: Genome-scale models have been shown to be valuable in studying the metabolism of many organisms. Here we present the first genome-scale metabolic model for C. neoformans, iCryptococcus. This comprehensive model consists of 1,270 reactions, 1,143 metabolites, 649 genes, and eight compartments. The model was validated, proving accurate when predicting the capability of utilizing different carbon and nitrogen sources and growth rate in comparison to experimental data. Results and Discussion: The compatibility of the in silico Cryptococcus metabolism under infection conditions was assessed. The steroid and amino acid metabolisms found in the essentiality analyses have the potential to be drug targets for the therapeutic strategies to be developed against Cryptococcus species. iCryptococcus model can be applied to explore new targets for antifungal drugs along with essential gene, metabolite and reaction analyses and provides a promising platform for elucidation of pathogen metabolism.


MicroRNAs in atherosclerosis and lipoprotein metabolism.
MicroRNAs (miRNA) are mediators of post-transcriptional gene expression that likely regulate most biological pathways and networks. The study of miRNAs is a rapidly emerging field; recent findings have revealed a significant role for miRNAs in atherosclerosis and lipoprotein metabolism, which will be described in this review. The discovery of miRNA gene regulatory mechanisms contributing to endothelial integrity, macrophage inflammatory response to atherogenic lipids, vascular smooth muscle-cell proliferation, and cholesterol synthesis are described. Furthermore, recent evidence suggests that miRNAs may play a role in mediating the beneficial pleiotropic effects observed with statin-based lipid-lowering therapies. New modifications to miRNA mimetics and inhibitors, increasing targeting efficacy and cellular uptake, will likely enable future therapies to exploit miRNA gene regulatory networks. At this time, the applicability and full potential of miRNAs in clinical practice is unknown. Nonetheless, recent advances in miRNA delivery and inhibition hold great promise of a tremendous clinical impact in atherosclerosis and cholesterol regulation.


Impact of Diabetes on Perioperative Complications in Patients Undergoing Elective Total Shoulder Arthroplasty.
Diabetes has been associated with negative outcomes following orthopaedic surgery. While previous studies have reported on diabetes-associated complications in shoulder arthroplasty, those cohorts were heterogeneous in terms of patient population, nature of elective surgery, and arthroplasty type. Given that the number of elective total shoulder arthroplasties (TSAs) performed has grown substantially in volume and is predicted to rise even further, it is important to recognize the role that diabetes may play in developing in-hospital complications within a more homogenous sample of patients undergoing elective TSA. The Nationwide Inpatient Sample (NIS) was searched for the year 2012 to identify all patients undergoing elective TSA. Patients with diabetes were identified, and differences regarding demographics and in-hospital outcomes were compared to non-diabetics using multivariate logistic regression. A total of 44,050 patients underwent elective total shoulder arthroplasty (TSA) in 2012. Diabetic patients tended to be older, of minority racial status, and had a greater medical comorbidity burden. When controlling for preoperative factors and comorbidities, diabetes was an independent risk factor for non-home bound discharge (OR 1.285; 95% CI 1.093-1.509, p = 0.002), length of stay in 75th percentile (OR 1.390; 95% CI 1.233-1.567, p < 0.001), total charges in the 75th percentile (OR 1.136; 95% CI 1.006-1.283, p = 0.040), and postoperative acute renal failure (OR 1.460; 1.002-2.128, p = 0.048). Diabetes was associated with marginal increases in non-home bound discharge, length of stay, and total charges, following elective TSA. Subgroup analysis revealed that diabetic patients undergoing reverse total shoulder arthroplasty (rTSA) have higher comorbidity burden and worse outcomes than diabetic patients undergoing anatomic total shoulder arthroplasty (aTSA).


Unilateral suppression of pharyngeal motor cortex to repetitive transcranial magnetic stimulation reveals functional asymmetry in the hemispheric projections to human swallowing.
Inhibitory patterns of repetitive transcranial magnetic stimulation (rTMS) were applied to pharyngeal motor cortex in order to establish its role in modulating swallowing activity and provide evidence for functionally relevant hemispheric asymmetry. Healthy volunteers underwent single pulse TMS before and for 60 min after differing intensities of 1 Hz rTMS (n = 9, 6 male, 3 female, mean age 34 +/- 3 years) or theta burst stimulation (TBS) (n = 9, 6 male, 3 female, mean age 37 +/- 4 years). Electromyographic responses recorded from pharynx and hand were used as a measure of cortico-motor pathway excitability. Swallowing behaviour was then examined with a reaction time protocol, before and for up to 60 min after the most effective inhibitory protocol (1 Hz) applied to each hemisphere. Interventions were conducted on separate days and compared to sham using ANOVA. Only high intensity 1 Hz rTMS consistently suppressed pharyngeal motor cortex immediately and for up to 45 min (-34 +/- 7%, P < or = 0.001). Adjacent hand and contralateral pharyngeal motor cortex showed no change in response (-15 +/- 12%, P = 0.14 and 15 +/- 12%, P = 0.45, respectively). When used to unilaterally disrupt each hemisphere, rTMS to pharyngeal motor cortex with the stronger responses altered normal (-12 +/- 3%, P < or = 0.001) and fast (-9 +/- 4%, P < or = 0.009) swallow times, not seen following rTMS to the contralateral cortex or after sham. Thus, suppression of pharyngeal motor cortex to rTMS is intensity and frequency dependent, which when applied to each hemisphere reveals functionally relevant asymmetry in the motor control of human swallowing.


Superantigenic Activation of Human Cardiac Mast Cells.
B cell superantigens, also called immunoglobulin superantigens, bind to the variable regions of either the heavy or light chain of immunoglobulins mirroring the lymphocyte-activating properties of classical T cell superantigens. Protein A of Staphylococcus aureus, protein L of Peptostreptococcus magnus, and gp120 of HIV are typical immunoglobulin superantigens. Mast cells are immune cells expressing the high-affinity receptor for IgE (FcεRI) and are strategically located in the human heart, where they play a role in several cardiometabolic diseases. Here, we investigated whether immunoglobulin superantigens induced the activation of human heart mast cells (HHMCs). Protein A induced the de novo synthesis of cysteinyl leukotriene C4 (LTC4) from HHMCs through the interaction with IgE VH3+ bound to FcεRI. Protein L stimulated the production of prostaglandin D2 (PGD2) from HHMCs through the interaction with κ light chains of IgE. HIV glycoprotein gp120 induced the release of preformed (histamine) and de novo synthesized mediators, such as cysteinyl leukotriene C4 (LTC4), angiogenic (VEGF-A), and lymphangiogenic (VEGF-C) factors by interacting with the VH3 region of IgE. Collectively, our data indicate that bacterial and viral immunoglobulin superantigens can interact with different regions of IgE bound to FcεRI to induce the release of proinflammatory, angiogenic, and lymphangiogenic factors from human cardiac mast cells.


Gait propulsion in patients with facioscapulohumeral muscular dystrophy and ankle plantarflexor weakness.
Facioscapulohumeral muscular dystrophy is a slowly progressive hereditary disorder resulting in fatty infiltration of eventually most skeletal muscles. Weakness of trunk and leg muscles causes problems with postural balance and gait, and is associated with an increased fall risk. Although drop foot and related tripping are common problems in FSHD, gait impairments are poorly documented. The effect of ankle plantarflexor involvement on gait propulsion has never been addressed. In addition to ankle plantarflexion, gait propulsion is generated through hip flexion and hip extension. Compensatory shifts between these propulsion sources occur when specific muscles are affected. Such a shift may be expected in patients with FSHD since the calves may show early fatty infiltration, whereas iliopsoas and gluteus maximus muscles are often spared for a longer time. In the current study, magnetic resonance imaging was used to assess the percentage of unaffected calf, iliopsoas and gluteus maximus muscles. Joint powers were analyzed in 10 patients with FSHD at comfortable and maximum walking speed to determine the contribution of ankle plantarflexor, hip flexor and hip extensor power to propulsion. Associations between muscle morphology, power generation and gait speed were assessed. Based on multivariate regression analysis, ankle plantarflexor power was the only factor that uniquely contributed to the explained variance of comfortable (R(2)=80%) and maximum (R(2)=86%) walking speed. Although the iliopsoas muscles were largely unaffected, they appeared to be sub-maximally recruited. This submaximal recruitment may be related to poor trunk stability, resulting in a disproportionate effect of calf muscle affliction on gait speed in patients with FSHD.


Treatment Satisfaction and Medication Adherence Among Hypertensive Patients Seeking Care in Selected Hospitals in Ibadan, Nigeria.
Poor adherence to hypertension treatment is a major health-related problem, and a significant risk factor for complications, disability and hypertension associated mortality. There is a paucity of evidence on the impact of treatment satisfaction on medication adherence among hypertensive patients in Nigeria. This study aimed to determine the association between treatment satisfaction and medication adherence among hypertensive patients in Ibadan, Nigeria. A descriptive cross-sectional study was conducted, wherein hypertensive patients were consecutively recruited from 5 hospitals in Ibadan, Nigeria. A pre-tested, interviewer-administered questionnaire was used to collect data. Medication adherence was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8), and treatment satisfaction using the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM). Descriptive statistics were computed for all variables. Bivariate analysis was carried out using chi-square test, and multivariate analysis using binary logistic regression. Sensitivity analysis was conducted to adjust for unmeasured binary confounders. Statistical significance was set at p < 0.05 for a 2-tailed. A total of 342 respondents with the mean age of 59.6 ± 12.6 years participated in the study. The overall prevalence of medication adherence was 35.1% (MMAS-8 scores = 8). Treatment satisfaction (AOR=2.03, 95% CI: 1.21-3.43) was independently associated with medication adherence. Sensitivity analysis revealed that the observed association between treatment satisfaction and medication adherence was unlikely to be due to unmeasured confounding variables. Medication adherence was low, and treatment satisfaction independently increases medication adherence. Treatment satisfaction strategies should be part of any treatment intervention packages in this population.


Perceptions of rural school mental health services: a focus group study.
The presence of emotional or behavioural disorders has an impact on academic achievement. Access to behavioural health services is a challenge, particularly in rural communities. School-based mental health services have been recognised as an effective means of addressing the needs of students with emotional or behavioural disorders. This qualitative focus group study explored the service needs, gaps, and barriers to mental health services. Themes related to time, space, family engagement, and education for teachers and caregivers emerged from the focus groups.


Impaired oculo-motor behaviour affects both reading and scene perception in neglect patients.
Unilateral spatial neglect (USN) is a common neuropsychological disorder following a right-sided brain lesion. Although USN is mostly characterized by symptoms involving the left hemispace, other symptoms are not left lateralized. Recently, it was shown that patients with neglect dyslexia, a reading disturbance that affects about 40% of USN patients, manifest a non-lateralized impairment of eye movement behaviour in association with their reading deficit when they read aloud and perform non-verbal saccadic tasks (Primativo et al., 2013). In the present paper, we aimed to demonstrate that the eye movement impairment shown by some USN patients reflects a more general oculo-motor disorder that is not confined to orthographic material, the horizontal axis or constrained saccadic tasks. We conjectured that inaccurate oculo-motor behaviour in USN patients indicates the presence of a reading deficit. With this aim we evaluated 20 patients, i.e., 10 right-sided brain-damaged patients without neglect and 10 patients affected by USN. On the basis of the patients' eye movement patterns during a scene exploration task, we found that 4 out of the 10 USN patients presented an abnormal oculo-motor pattern. These same four patients (but not the others) also failed in performing 5 different saccadic tasks and produced neglect dyslexia reading errors in both single words and texts. First, we show that a large proportion of USN patients have inaccurate eye movement behaviour in non-reading tasks. Second, we demonstrate that this exploratory deficit is predictive of the reading impairment. Thus, we conclude that the eye movement deficit prevents reading and impairs the performance on many other perceptual tests, including scene exploration. The large percentage of patients with impaired eye-movement pattern suggests that particular attention should be paid to eye movement behaviour during the diagnostic phase in order to program the best rehabilitation strategy for each patient.


Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Can Predict the Severity in COVID-19 Patients from Ethiopia: A Retrospective Study.
Coronaviruses are a broad family of pathogens that can cause mild to severe respiratory illnesses. Due to a strong inflammatory response and a weak immunological response, viral pneumonia inflammation, like Coronavirus Disease 2019 (COVID-19), displays an unbalanced immune response. Therefore, circulating biomarkers of inflammation and the immune system can serve as reliable predictors of a patient's prognosis for COVID-19. Hematological ratios are reliable markers of inflammation that are frequently utilized in pneumonia, primarily in viral infections with low cost in developing countries. To examine the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in predicting the severity of COVID-19 patients. An institutional-based retrospective study was done on 105 hospitalized COVID-19 patients at the University of Gondar comprehensive specialized referral hospital, Northwest Ethiopia. The laboratory evaluations that were gathered, evaluated, and reported on included the total leucocyte count (TLC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count (AMC), NLR, LMR, and PLR. The Kruskal-Wallis test and Wilcoxon matched-pairs signed test were used to see whether there were any differences between the continuous variables. Receiver operating curve (ROC) analysis was used to determine the appropriate cut-off values for NLR, PLR, and LMR. P-value <0.05 was considered a statistically significant association. ANC, NLR, and PLR were highest in the critical group (p = 0.001), while this group had the least ALC and LMR (p = 0.001). We calculated the optimal cut-off values of the hematological ratios; NLR (8.4), LMR (1.4), and PLR (18.0). NLR had the highest specificity and sensitivity, at 83.8% and 80.4%, respectively. Our research showed that NLR and PLR were good indicators of severity in COVID-19. However, our findings indicate that MLR is not a reliable predictor.


The European experience.
This article presents an overview of past and current experiences with time division multiple assess-based (Global System for Mobil Communication) mobile telephones in Europe as seen by the European Hearing Instrument Manufacturers Association. Initial fear of widespread interference problems for hearing aid users in general owing to use of a new generation of mobile telephones seems unjustified. The background for the International Electrotechnical Commission 118-13 standard for measuring interference is described. No solution to complete elimination of interference problems resulting from direct contact between hearing aids and mobile telephones has yet been found. Several reports on the subjects are cited, and new work on measurement standards for near-field situations is mentioned.


Galvanic Skin Response Features in Psychiatry and Mental Disorders: A Narrative Review.
This narrative review is aimed at presenting the galvanic skin response (GSR) Biofeedback method and possibilities for its application in persons with mental disorders as a modern form of neurorehabilitation. In the treatment of mental disorders of various backgrounds and courses, attention is focused on methods that would combine pharmacological treatment with therapies improving functioning. Currently, the focus is on neuronal mechanisms which, being physiological markers, offer opportunities for correction of existing deficits. One such indicator is electrodermal activity (EDA), providing information about emotions, cognitive processes, and behavior, and thus, about the function of various brain regions. Measurement of the galvanic skin response (GSR), both skin conductance level (SCL) and skin conductance responses (SCR), is used in diagnostics and treatment of mental disorders, and the training method itself, based on GSR Biofeedback, allows for modulation of the emotional state depending on needs occurring. Summary: It is relatively probable that neurorehabilitation based on GSR-BF is a method worth noticing, which-in the future-can represent an interesting area of rehabilitation supplementing a comprehensive treatment for people with mental disorders.


[The transfection and expression of IL-1ra gene to the rabbit cornea in situ via cation polymer mediation].
To investigate the efficiency and safety of transfection of PEGFP-IL-1ra plasmid via cation polymer mediation (poly-ethylenimine, PEI) by injection into the corneal stroma. Human IL-1ra cDNA fragments were cloned by RT-PCR. Plasmid PEGFP-hIL-1ra recombinants were constructed and transferred into corneal endothelial cells (CEC) via cation polymer mediation. Expression of IL-1ra mRNA and IL-1ra was detected by green fluorescent protein (GFP) and Western-blotting. In the experiment group, 20 microl preparation containing 10 microg plasmid PEGFP-hIL-1ra recombinants and PEI-in-vivo was injected into the corneal stroma of Wistar rats (n = 30). Equivalent PEI-in-vivo solution was injected into another 15 corneas as the controls. Corneas were harvested at different time points (day 1, 3, 6, 14 and 21) after injection. The changes of tissue structure and function after IL-1ra in situ transfection were studied by HE staining, transmission electron microscopy, trypan blue-alizarin red staining and immunohistochemistry. The location and intensity of IL-1ra-GFP fusion protein expression were monitored by fluorescence microscopy. The size of the RT-PCR product of hIL-1ra fragments was approximately 500 bp in agarose gel electrophoresis. Restrictive enzyme digestion analysis of PstI, BamHI and DNA sequence analysis showed that expression of plasmid PEGFP-hIL-1ra recombinants had been constructed successfully. Twelve hours after the transfection of PEGFP-hIL-1ra, GFP fluorescence was detected in 10% - 15% endothelial cells. IL-1ra protein (RMW: 44,000) was detected by Western-blotting. In PEGFP-hIL-1ra treated group, fluorescence was appeared at day 1 in cornea basal epithelial cells, peaked at day 6 in whole cornea, began to weaken at day 14, and only weak fluorescence remained in cornea epithelial cells at day 21. No fluorescence appeared in the control group. No significant pathologic changes could be found in HE stained cornea tissues in both transfected group and the controls. p63 immunocytochemical staining in cornea epithelium was positive in both groups. Trypan blue-alizarin red staining confirmed that there was no damage in cornea endothelial cells. IL-1ra-GFP granules could be found by transmission electron microscope in every layer of cornea in the transfected group, but none in the controls. There was no impairment in the ultrastructure of cells in both groups. By direct injection of PEGFP-hIL-1ra into corneal stroma and mediated by cation polymer, IL-1ra genes could be transferred and expressed in corneal tissue efficiently and safely, and might provide a novel technique of gene transfection to cornea in situ.


Serotonin promotes exploitation in complex environments by accelerating decision-making.
Fast responses can provide a competitive advantage when resources are inhomogeneously distributed. The nematode Caenorhabditis elegans was shown to modulate locomotion on a lawn of bacterial food in serotonin (5-HT)-dependent manners. However, potential roles for serotonergic signaling in responding to food discovery are poorly understood. We found that 5-HT signaling in C. elegans facilitates efficient exploitation in complex environments by mediating a rapid response upon encountering food. Genetic or cellular manipulations leading to deficient serotonergic signaling resulted in gradual responses and defective exploitation of a patchy foraging landscape. Physiological imaging revealed that the NSM serotonergic neurons responded acutely upon encounter with newly discovered food and were key to rapid responses. In contrast, the onset of responses of ADF serotonergic neurons preceded the physical encounter with the food. The serotonin-gated chloride channel MOD-1 and the ortholog of mammalian 5-HT1 metabotropic serotonin receptors SER-4 acted in synergy to accelerate decision-making. The relevance of responding rapidly was demonstrated in patchy environments, where the absence of 5-HT signaling was detrimental to exploitation. Our results implicate 5-HT in a novel form of decision-making, demonstrate its fitness consequences, suggest that NSM and ADF act in concert to modulate locomotion in complex environments, and identify the synergistic action of a channel and a metabotropic receptor in accelerating C. elegans decision-making.


Human becoming-guided patient-centered care: A new model transforms nursing practice.
Nurses working on an orthopedic surgery and rheumatology unit in a large teaching hospital in Canada participated in a 24-month research project to evaluate what happens when nurses are provided 20% of their time for the purpose of learning and self-development. Half of the teaching-learning was aligned with the commitment of the organization to advance patient-centered care, and in particular patient-centered care guided by the nursing theory, human becoming. The other half was self-directed by nurse participants according to their learning interests and self-development priorities. The purpose of this column is to describe the teaching-learning and mentoring processes in which the nurses were engaged and to highlight the subsequent changes in nursing practice that have happened on the unit from the perspectives of nurse participants.


Transrectal ultrasonography and operative selection for early carcinoma of the rectum.
Transrectal ultrasonography (TRUS) supplements clinical evaluation of early carcinoma of the rectum in selecting patients for local operative therapy, such as transanal excision (TAE). This study was done to evaluate the accuracy of ultrasonographic staging of tumor depth (T stage) in patients with suspected early carcinoma of the rectum, to compare ultrasonographic with clinical T-staging accuracies within this patient group, to determine if any specific tumor characteristics (configuration, size, location) predispose toward ultrasonographic T-staging inaccuracy, and to examine the role of TRUS in operative selection for patients with early carcinoma of the rectum. Between April 1990 and December 1992, 62 patients with primary carcinoma of the rectum underwent ultrasonographic staging (uT), whereby three uT4, 27 uT3, 24 uT2 and eight uT1 carcinomas were identified. Of the 32 patients with suspected intramural (uT1 or uT2) disease, 27 underwent prompt operative excision or resection at our institution, allowing comparative histopathologic staging. In this highly selected patient subset, uT1 staging was correct in all instances; uT2 staging was incorrect in 45 percent of instances, with 30 percent having unpredicted transmural penetration. Ultrasonographic and clinical staging accuracies were quantitatively similar, and no tumor characteristics were consistently associated with ultrasonographic imprecision. Among patients with clinically suspected early carcinoma of the rectum, the decision to perform TAE is supported by ultrasonographic T1 staging. By contrast, the decision to perform TAE cannot be based solely on ultrasonographic T2 staging, because of the possibility for transmural penetration of tumor.


[Frontiers in vitamin D; basic research and clinical application. Vitamin D deficiency, insufficiency and sufficiency].
In November 2010, IOM (Institute of Medicine) of USA issued a report on DRI (Dietary Reference Intakes) for calcium and vitamin D, which challenged then widespread view among many in US that vitamin D sufficiency is defined by serum 25 (OH) D level more than 30 ng/mL. The IOM report concluded serum 25 (OH) D level of 20 ng/mL would be sufficient for 97.5% of general healthy population, and recommended vitamin D intake much lower than that had been believed among many experts. After much discussion, disputes, in July 2011, American Endocrine Society issued a guideline for Vitamin D deficiency, which contrasted to IOM report in many aspects. In this article, differences between those two guidelines are reviewed and current issues surrounding vitamin D deficiency/sufficiency are discussed.


Negotiating collaborative agreements: Interprofessional collaboration in a Norwegian welfare context.
Interprofessional collaboration among welfare services is a policy objective promoted to ensure successful service provision to people with complex needs. In the Nordic region, people who are not in education, employment, or training often have challenging life situations requiring help from a multitude of services. In Norway, significant political and institutional efforts focus on implementing policies that support collaboration. However, we know little about how service workers formalize joint efforts. In this study, I used institutional ethnography to explore how interprofessional collaboration was constructed through negotiations of collaborative agreements among leaders of welfare services and how such negotiations are consequential for collaborative practices. I explored two cases of negotiations initiated by the leader of the Norwegian Labor and Welfare Administration. The negotiations were with the local child welfare and protection services and Refugee services, focusing on the transition of care regarding youth and refugees. The data includes two collaborative agreements between the services, an observation of the negotiation of one agreement, and 10 interviews with leaders and staff. Results show that collaboration is constructed based on holistic service provision. The negotiations, however, do not result in such collaborative practices, but are characterized by the demarcation of responsibilities and work.


Size, demography, ownership profiles, and identification rate of the owned dog population in central Italy.
The One Health paradigm recognizes that information on infectious diseases, zoonosis and related predictors in animal populations is essential. Pets live in close contact with humans and interact with wild animals, but the lack of reliable information on pet population size, demography and ownership profiles is a constant worldwide. Reliable data must be made available in order to address proper public health policies regarding the design of surveillance plans, the management of canine welfare and stray dog phenomenon, the control of dog behaviour-related problems, and the livestock/wildlife endangerment. Dog identification & registration (I&R) have become mandatory in most European countries in recent years, but the process is far from being widely accomplished, thus resulting in an underestimation of the real canine population. To date, data on the completeness of Dog Registries is very limited. A cross-sectional survey through 630 face-to-face questionnaires was performed with the aim of investigating the dog population size, demography, ownership profiles, and the I&R rate in central Italy. Logistic regression models investigated risk factors with the following outcome variables: dog presence into the Dog Registry, veterinary care frequency, and dog ownership. The present study identified that the dog population is higher than previously reported in Italy and in Europe, whilst lower compared to countries with a poor Human Development Index (a statistic composite index of life expectancy, education, and per capita income indicators used by United Nation). Almost half of the interviewed people (47%) owned at least one dog, totalling 315 dogs. The mean number of dogs per household was 0.7 and 1.5 per dog-owning household. The Bayesian model estimated 481,294 (95% CI: 470,860-491,978) dogs (90 dogs/km2; human:dog ratio 9.0, 95% CI: 8.8-9.2) suggesting that a high density of people does not limit the dog ownership. Dogs resulted predominant among pets. The majority of dogs were males, crossbred, acquires as a gift, lived in rural areas, outdoors and attended a veterinary visit 1-2 times per year. The percentage of neutered dogs were higher in females (55%) than in males (8%). Only 75.3% (95% CI: 73.6-76.9) of the dogs were correctly identified and registered. The Dog Registry completeness increased during the first decades after its establishment, but no improvement has been made afterwards. The dogs correctly identified and registered were more likely to be purebred, neutered, lived in urban areas and visited a veterinarian frequently. Several strategies are recommended to encourage I&R, including promoting responsible dog ownership, engaging private veterinarians and dog breeders, and establishing an effective control system. The present study identified also that the dog source and the kind of feeding were variables associated with the veterinary care frequency. Owning a dog was associated with living in rural areas and the presence of children. The present study reported the poor presence of reliable predictors for the dog ownership. This is the first study to provide an estimate of the canine population abundance, characteristics, and ownership profiles in a European large metropolitan area.


Dimensional Transformation of Molecular Magnetic Materials.
Two-dimensional (2D) magnetic layered materials have revolutionized size dependent magnetism to manipulate spin-based devices. However, it has been challenging to artificially create 2D magnetic materials from three-dimensional (3D) crystal structures with a variety of material groups. Here, we present the dimensionality manipulation via cation exchange of a 3D Prussian blue analogue [RbMnFe(CN)6] toward a 2D magnetic sheet [(K,Rb)(V,Mn)(Cr,Fe)(CN)6] with the magnetic ordering temperature rising from 12 to 330 K. Such a 2D magnetic sheet achieves crystalline V-Cr coordination in the Prussian blue lattice with pronounced anisotropy and stimuli responsiveness. The pressure dependent magnetic tunability of such 2D networks is predicted using first-principles calculations and demonstrated using the phase transitions of the hydrogel. This previously unobserved phenomenon of dimensional manipulation of a bulk crystal structure provides a rational strategy to expand the diversity and chemical compositions of 2D molecular magnetic material libraries.


Neuroinflammation in Sepsis: Molecular Pathways of Microglia Activation.
Frequently underestimated, encephalopathy or delirium are common neurological manifestations associated with sepsis. Brain dysfunction occurs in up to 80% of cases and is directly associated with increased mortality and long-term neurocognitive consequences. Although the central nervous system (CNS) has been classically viewed as an immune-privileged system, neuroinflammation is emerging as a central mechanism of brain dysfunction in sepsis. Microglial cells are major players in this setting. Here, we aimed to discuss the current knowledge on how the brain is affected by peripheral immune activation in sepsis and the role of microglia in these processes. This review focused on the molecular pathways of microglial activity in sepsis, its regulatory mechanisms, and their interaction with other CNS cells, especially with neuronal cells and circuits.


Studies on the mechanism of alloxan-diabetes potentiation of carbon tetrachloride-induced liver necrosis.
Carbon tetrachloride (CCl4)-induced liver necrosis in alloxan diabetic rats is markedly more intense than in controls as established by determination of isocitric dehydrogenase activity in plasma or by histological techniques. The covalent binding (CB) of CCl4 reactive metabolites to liver microsomal lipids is higher in alloxan diabetic rats than in controls. Cytochrome c reductase activity remains unchanged in alloxan diabetic rats. All the alterations described above observed in the diabetic animals are reverted by insulin administration. CCl4-induced lipid peroxidation of microsomal lipids, in contrast, is equally intense in controls than in alloxan diabetic animals and it is not modified by insulin treatment. Body temperature in alloxan diabetic animals treated with CCl4 is lower than in controls treated with the hepatotoxin. Results suggest that part of the enhanced necrogenic response of the liver observed in alloxan diabetic rats is due to increased CB to liver cell constituents but available evidence from the present and another work suggest that increased susceptibility of the liver from alloxan diabetic animals play a major role in the potentiation of CCl4 deleterious effects.


Organizational factors associated with screening for military sexual trauma.
This exploratory study investigated organizational factors associated with receipt of military sexual trauma (MST) screening during an early timeframe of the Veterans Health Administration's (VHA) implementation of the universal MST screening policy. The sample consisted of all VHA patients eligible for MST screening in fiscal year 2005 at 119 VHA facilities. Analyses were conducted separately by gender and by user status (i.e., new patients to the VHA health care system in FY 2005 and continuing users who had previously used the VHA health care system in the past year). Multivariate generalized estimating equations were used to assess the effects of facility-level characteristics and adjusted for person-level covariates. Facility-level mandatory universal MST screening policies were associated with increased odds of receiving MST screening among new female patients and both continuing and new male patients: Odds ratio (OR), 2.87 (95% confidence interval [CI], 1.39-5.89) for new female patients; OR, 8.15 (95% CI, 2.93-22.69) for continuing male patients; and OR, 4.48 (95% CI, 1.79-11.20) for new male patients. Facility-level audit and feedback practices was associated with increased odds of receiving MST screening among new patients: OR, 1.91 (95% CI, 1.26-2.91) for females and OR, 1.86 (95% CI, 1.22-2.84) for males. Although the facility-level effect for women's health clinic (WHC) did not emerge as significant, patient-level effects indicated that among these facilities, women who used a WHC had greater odds of being screened for MST compared with women who had not used a WHC: OR, 1.79 (95% CI, 1.18-2.71) for continuing patients and OR, 2.20 (95% CI, 1.59-3.04) for new patients. This study showed that facility policies that promote universal MST screening, as well as audit and feedback practices at the facility, significantly improved the odds of patients receiving MST screening. Women veterans' utilization of a WHC was associated with higher odds of receiving MST screening. This study provides empirical support for the use of policies and audit and feedback practices which the VHA has used since the implementation of the MST screening directive to encourage compliance with VHA's MST screening policy and is likely associated with the present-day success in MST screening across all VHA facilities.


Herpes Simplex Mastitis in an Adolescent Woman: Clinical and Ultrasound Features.
Herpetic mastitis is extremely rare, and its imaging findings remain unclear. We report a case of herpes simplex mastitis in an adolescent woman and describe the clinical and ultrasound features. The patient showed unilateral nipple and areolar skin thickening and axillary lymphadenopathy on B-mode ultrasonography. Doppler ultrasonography revealed multiple linear and branching blood flows in the areolar area. The lesion was verified as herpes simplex mastitis via a skin biopsy. This report shows that the radiologic features of herpes simplex mastitis may be similar to those of Paget's disease because of localized nipple and areolar skin thickening and increased vascularity.


Effects of Freezing Method and Antioxidants on Lipid Oxidation in Turkey Sausage 1.
Rosemary oleoresin (200 ppm) was compared to a commercial antioxidant mixture of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) (200 ppm) and citric acid in frozen and freeze dried breakfast sausages prepared with 18% mechanically deboned turkey meat. Analysis for malondialdehyde (MDA) revealed that both antioxidant treatments inhibited lipid oxidation during 5 weeks of storage. Rosemary oleoresin was comparable in activity to the commercial antioxidant mixture in the freeze dried products but not in the frozen products. Fatty acid analysis at the beginning and the end of storage revealed a selective decrease in certain long chain polyunsaturated fatty acids which was not related to treatment. Sensory analysis yielded a strong preference for the frozen sausages which was attributable to the poorer texture of the freeze dried sausages rather than to flavor deterioration.


Evaluation of chemoradiotherapy with carbon ions and the influence of p53 mutational status in the colorectal carcinoma cell line HCT 116.
Heavy ion therapy has shown promising results in the treatment of recurrent colorectal carcinoma. The present study evaluates the effect of five different cytostatic agents in combination with radiotherapy with carbon (C12) ions and photons in two isogenic colorectal cancer cell lines differing in p53 status. Clonogenic survival analyses were performed using the human colon cancer cell lines HCT 116 wt and the isogenic p53 deficient cell line HCT 116 p53 -/-. Single photon doses (6 MV X-rays) up to 10 Gy were applied using a linear accelerator. Carbon ion irradiation up to 3 Gy was performed at the Heidelberg Ion-Beam Therapy Center with the horizontal beamline delivering an extended Bragg peak with an average linear energy transfer of 103 keV/µm. Five different cytostatic agents were applied in combinations with photon and carbon ion radiotherapy. Both cell lines showed a similar response to photons and carbon ions, whereas treatment with carbon ions resulted in a superior relative biological efficiency. Irinotecan and paclitaxel alone showed high toxicity in the treatment of wildtype cells. A notable difference was observed on the cell death of p53 -/- cell lines. Here, single treatment with paclitaxel and gemcitabine resulted in good response rates. Combinations of carbon ions with gemcitabine, irinotecan or paclitaxel revealed high response rates. After irradiation with carbon ions and temozolomide, cell survival rates depended on p53 status, with a decreased survival rate in wildtype cells. Irinotecan and paclitaxel are an effective treatment for HCT 116 wt cells, whereas HCT 116 cells with p53 deficiency can be treated successfully with paclitaxel and gemcitabine. Combined treatment modalities with carbon ions and chemotherapy provide great effectiveness that may offer new treatment opportunities for recurrent colorectal cancer in the future.


Properties of a novel polydatin-β-d-glucosidase from Aspergillus niger SK34.002 and its application in enzymatic preparation of resveratrol.
Resveratrol and its glucoside polydatin are the main stilbenes in Polygonum cuspidatum. Resveratrol has become the subject of intensive research over the past two decades owing to its outstanding pharmacological properties. However, its lower concentration in plants compared to polydatin limits its application. In this study, the polydatin-β-d-glucosidase (PBG) that hydrolyzes the β-d-glucosyl residue of polydatin with release of resveratrol was purified to homogeneity and characterized. The molecular weight of PBG was estimated to be 125 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 128 kDa by size-exclusion chromatography- multi-angle laser light scattering/ultraviolet/refractive index. The optimal PBG activity was observed at 70 °C and pH 4.5. The enzyme showed around 50% stability at 60 °C for 12 h and residual activity was over 80% at pH 3.0-5.0. Ca(2+) , Mg(2+) , Mn(2+) , Zn(2+) , Ba(2+) , Ni(2+) , Co(2+) and Cu(2+) ions had no significant effect on the enzyme activity. The PBG presented higher affinity to polydatin (Km = 0.74 mmol L(-1) ) than p-nitrophenyl-β-d-glucopyranoside (Km = 2.9 mmol L(-1) ) and cellobiose (Km = 8.9 mmol L(-1) ). With this enzyme, nearly all polydatin in P. cuspidatum was converted to resveratrol. Although several β-D-glucosidases (BGLs) have been obtained from other sources, PBG is distinguished from other BGLs by its outstanding thermal stability and high catalytic efficiency. © 2015 Society of Chemical Industry.


[Population based study on periodontal conditions and socioeconomic determinants in adults in the city of Guarulhos (SP), Brazil, 2006].
This study described the prevalence of periodontal conditions and assessed its association with social, economical and behavioral variables in adults aged 35 to 44 years old, residents in the city of Guarulhos, State of Sao Paulo, 2006. This study was a population based survey with cluster sampling. Data collecting and exams were done at houses drew at random. The Community Periodontal Index was used to assess the periodontal condition. Data analysis used EPIINFO 6 and STATA 10 softwares. The assessment of association used the prevalence ratio (PR), as calculated by Poisson regression models with complex sampling and weighted sample adjustments. The total number of people was 263 in 237 domiciles. In the multivariate model, the prevalence of gingival bleeding and dental calculus was significantly associated to being male (PR=1.12, p=0.04), smoking (PR=1.11, p=0.01), school level of less than eight years of study (PR=1.14, p=0.01), and who have not received dental care for more than two years (PR=1.19, p<0.01). As for the presence of periodontal pocket, associated factors were smoking (PR=1.71, p=0.02) and who have not received dental care for more than 2 years (PR=1.97, p=0.03). We observed a higher prevalence (62.7%) of individuals with gingival bleeding and dental calculus in relation to the presence of shallow or deep periodontal pockets (26,6%). As shallow pockets are reversible, their treatment may be resolute in programs of primary dental care.


Intrinsic cardiac rate regulation in the anaesthetized rabbit.
Intrinsic cardiac regulation, the direct effect of changes in right atrial pressure on heart rate, was examined in rabbits under chloralose/urethane anaesthesia. Autonomic influences on the cardiac pacemaker were eliminated by cervical vagotomy and intravenous propranolol. Right atrial transmural pressure was monitored as the difference between right atrial and pleural pressures. Blood volume expansion (5-15%) increased right atrial transmural pressure and heart rate and produced a sinus arrhythmia associated with respiration-linked fluctuations in right atrial transmural pressure. The gain of intrinsic cardiac rate regulation was calculated as 0.96 +/- 0.24 beats min-1 mmHg-1 at a heart rate of 218 +/- 6 beats min-1 (values as the mean +/- SEM, n = 12). When heart rate was reduced by electrical stimulation of the peripheral end of the right vagus nerve, gain increased to 2.25 +/- 0.57 and 4.61 +/- 1.6 beats min-1 mmHg-1 at heart rates of 180 +/- 4 and 130 +/- 4 beats min-1, respectively (n = 6 and n = 10; P < 0.05 compared with pre-stimulation values). During vagally-induced bradycardia, rapid infusion of blood into the left superior vena cava produced a brief marked cardiac acceleration. We conclude that right atrial pressure has a small direct influence on heart rate, and this is enhanced by background cardiac parasympathetic stimulation.


Forward Genetics Approach Reveals a Mutation in bHLH Transcription Factor-Encoding Gene as the Best Candidate for the Root Hairless Phenotype in Barley.
Root hairs are the part of root architecture contributing significantly to the root surface area. Their role is particularly substantial in maintaining plant growth under stress conditions, however, knowledge on mechanism of root hair differentiation is still limited for majority of crop species, including barley. Here, we report the results of a map-based identification of a candidate gene responsible for the lack of root epidermal cell differentiation, which results in the lack of root hairs in barley. The analysis was based on the root hairless barley mutant rhl1.b, obtained after chemical mutagenesis of spring cultivar 'Karat'. The rhl1 gene was located in chromosome 7HS in our previous studies. Fine mapping allowed to narrow the interval encompassing rhl1 gene to 3.7 cM, which on physical barley map spans a region of 577 kb. Five high confidence genes are located within this region and their sequencing resulted in the identification of A>T mutation in one candidate, HORVU7Hr1G030250 (MLOC_38567), differing the mutant from its parent variety. The mutation, located in the 3' splice-junction site, caused the retention of the last intron, 98 bp long, in mRNA of rhl1.b allele. This resulted in the frameshift, the synthesis of 71 abnormal amino acids and introduction of premature STOP codon in mRNA. The mutation was present in the recombinants from the mapping population (F2rhl1.b × 'Morex') that lacked root hairs. The candidate gene encodes a bHLH transcription factor with LRL domain and may be involved in early stages of root hair cell development. We discuss the possible involvement of HORVU7Hr1G030250 in this process, as the best candidate responsible for early stages of rhizodermis differentiation in barley.