Morusin exerts anti-cancer activity in renal cell carcinoma by disturbing MAPK signaling pathways.
Renal cell carcinoma (RCC) has gradually become a severe type of kidney malignant tumor, which warrants an urgent need for highly efficacious therapeutic agents. Morusin, a typical prenylated flavonoid, has been revealed to possess anticarcinogenic effects against several cancers by inhibiting cell proliferation and tumorigenesis. Cells proliferation was examined by CCK-8. Migration assays were performed using a 24-well transwell chamber. Apoptotic cells were detected using the Annexin V PE/7-AAD apoptosis detection kit. Cell cycle analysis was carried out by flow cytometry. Western blotting and quantitative real time (qRT) PCR were used to exam the change of target gene in mRNA and protein level. Nude mouse xenograft experiments were performed to identify vivo function of morusin. Here, we evaluated the effect of morusin against RCC. We treated three RCC cell lines, 769-P, 786-O, and OSRC-2, with morusin to study its effects on cell growth, migration, apoptosis, cell cycle and cancer-related pathways. Additionally, we assessed the effects of morusin on tumor growth using a nude mouse model. Morusin could inhibit cell growth and migration, induce cell apoptosis and downregulate apoptosis-related proteins, and disturb the cell cycle arrest in the G1 phase. Additionally, morusin could suppress RCC tumorigenesis in vivo. Moreover, mitogen-activated protein kinase (MAPK) signal pathways were found to be involved in morusin-induced anti-cancer activity. P-p38 and P-JNK levels were up-regulated by morusin, while the ERK phosphorylation level was down-regulated. Our results show that morusin could inhibit the growth of RCC cells in vitro and in vivo through MAPK signal pathways. Thus, morusin could be a potential anti-cancer agent for RCC.


Molecular Defensive Mechanism of Echinacea purpurea (L.) Moench against PAH Contaminations.
The understanding of the molecular defensive mechanism of Echinacea purpurea (L.) Moench against polycyclic aromatic hydrocarbon (PAH) contamination plays a key role in the further improvement of phytoremediation efficiency. Here, the responses of E. purpurea to a defined mixture of phenanthrene (PHE) and pyrene (PYR) at different concentrations or a natural mixture from an oilfield site with a history of several decades were studied based on transcriptomics sequencing and widely targeted metabolomics approaches. The results showed that upon 60-day PAH exposure, the growth of E. purpurea in terms of biomass (p < 0.01) and leaf area per plant (p < 0.05) was negatively correlated with total PAH concentration and significantly reduced at high PAH level. The majority of genes were switched on and metabolites were accumulated after exposure to PHE + PYR, but a larger set of genes (3964) or metabolites (208) showed a response to a natural PAH mixture in E. purpurea. The expression of genes involved in the pathways, such as chlorophyll cycle and degradation, circadian rhythm, jasmonic acid signaling, and starch and sucrose metabolism, was remarkably regulated, enhancing the ability of E. purpurea to adapt to PAH exposure. Tightly associated with transcriptional regulation, metabolites mainly including sugars and secondary metabolites, especially those produced via the phenylpropanoid pathway, such as coumarins, flavonoids, and their derivatives, were increased to fortify the adaptation of E. purpurea to PAH contamination. These results suggest that E. purpurea has a positive defense mechanism against PAHs, which opens new avenues for the research of phytoremediation mechanism and improvement of phytoremediation efficiency via a mechanism-based strategy.


[Transmission and course of parasitemia of Babesia microti (Hannover I strain) in the bank vole (Clethrionomys glareolus) and field vole (Microtus agrestis)].
In Germany only M. agrestis has been found to be naturally infected with B. microti while in other European countries several rodent species were found as mammalian hosts. In the laboratory C. glareolus got easily infected by German strains of B. microti, if parasitized blood was inoculated. But results of this method are not transferable to natural conditions. Therefore this study was carried out. It was to prove whether C. glareolus is susceptible to B. microti transmitted by nymphs of I. ricinus, or not. To compare the results, M. agrestis was infected in the same way. Both of them proved to be susceptible. The parasitaemia lasted for months. In the beginning the rate of parasitaemia reached 2%, then decreased below 0.1%. The course of infection was variable. In blood smears B. microti could not be detected at all times, so that in field trials the infection rate in mice will often be underestimated. A connection between parasitaemia and gravidity or lactation was not observed under laboratory conditions.


Activation of Phenyl 4-(2-Oxo-3-alkylimidazolidin-1-yl)benzenesulfonates Prodrugs by CYP1A1 as New Antimitotics Targeting Breast Cancer Cells.
Prodrug-mediated utilization of the cytochrome P450 (CYP) 1A1 to obtain the selective release of potent anticancer products within cancer tissues is a promising approach in chemotherapy. We herein report the rationale, preparation, biological evaluation, and mechanism of action of phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs) that are antimicrotubule prodrugs activated by CYP1A1. Although PAIB-SOs are inert in most cells tested, they are highly cytocidal toward several human breast cancer cells, including hormone-independent and chemoresistant types. PAIB-SOs are N-dealkylated into cytotoxic phenyl 4-(2-oxo-3-imidazolidin-1-yl)benzenesulfonates (PIB-SOs) in CYP1A1-positive cancer cells, both in vitro and in vivo. In conclusion, PAIB-SOs are novel chemotherapeutic prodrugs with no equivalent among current antineoplastics and whose selective action toward breast cancer is tailored to the characteristic pattern of CYP1A1 expression observed in a large percentage of human breast tumors.


Inhibition of α-glucosidase, α-amylase, and aldose reductase by potato polyphenolic compounds.
Diabetes mellitus is a chronic disease that is becoming a serious global health problem. Diabetes has been considered to be one of the major risks of cataract and retinopathy. Synthetic and natural product inhibitors of carbohydrate degrading enzymes are able to reduce type 2 diabetes and its complications. For a long time, potatoes have been portrayed as unhealthy for diabetic patients by some nutritionist due to their high starch content. However, purple and red potato cultivars have received considerable attention from consumers because they have high levels of polyphenolic compounds that have potent antioxidant activities. In this study, we screened the total phenolics (TP) and total anthocyanins (TA) and analyzed the phenolic and anthocyanin compounds in selected potato cultivars and advanced selections with distinct flesh colors (purple, red, yellow and white). Purple and red potato cultivars had higher levels of TP and TA than tubers with other flesh colors. Chlorogenic acid is the predominant phenolic acid, and major anthocyanin is composed of the derivatives of petunidin, peonidin, malvidin and pelargonidin. We tested the potential inhibitory effect of potato extracts on the activities of α-amylase and α-glucosidase, which were targeted to develop antidiabetic therapeutic agents. We also measured inhibitory effect of potato extracts on aldose reductase (AR) which is a key enzyme that has been a major drug target for the development of therapies to treat diabetic complications. Purple flesh tubers extract showed the most effective inhibition of α-amylase, α-glucosidase, and aldose reductase with IC50 values 25, 42, and 32 μg/ml, respectively. Kinetic studies showed that anthocyanins are noncompetitive inhibitors of these enzymes, whereas phenolic acids behaved as mixed inhibitors for α-amylase and α-glucosidase and noncompetitive inhibitors for AR. This study supports the development of a positive and healthful image of potatoes, which is an important issue for consumers.


Study of the proximate and mineral composition of different Nigerian yam chips, flakes and flours.
Yam (Dioscorea spp) is an essential tuber crop for hundreds of millions of people in many African, Asian and South American countries. Considering in particular Southwest Nigeria, chips, flakes and flours are amongst the most common shelf-stable traditionally-processed yam products. This paper reports a systematic study on the proximate (moisture, protein, carbohydrate, fibre, fat, ash and gross energy) and mineral composition of these three food commodities sold in Nigerian markets. Results showed no significant differences in the moisture, crude protein and fibre content of all samples (10.0-12.3, 2.7-4.3 and 1.3-2.0 wt%, respectively). Gross energy was also comparable for all yam derived food items (between 3300 and 3507 kcal/kg), contradicting the common belief that yam flakes have lower nutritional value than chips and flours. Considering the mineral composition, Ca, Mg, P and K were the predominant macronutrients. Micronutrients such as Zn, Co, Mn and Cu were also detected. Significant differences existed between products, and their various sources (markets). Principal component analysis showed a direct correlation between ash content of the samples and the assessed macronutrients, irrespective of the market, or the seller of the commodities. This study confirmed that yam derived food stuffs have an adequate nutritional composition, irrespective of their form and/or origin.


Distribution of postganglionic parasympathetic fibers originating in the pterygopalatine ganglion in the maxillary and ophthalmic nerve branches of the trigeminal nerve; HRP and WGA-HRP study in the guinea pig.
The distribution of the postganglionic parasympathetic fibers originating in the pterygopalatine ganglion (PTPG) has been traced in the guinea pig by means of the HRP and WGA-HRP methods. The greatest number of labeled cells were observed when WGA-HRP was injected in the lacrimal gland. After applying HRP to all the ramifications of the maxillary and ophthalmic divisions of the trigeminal nerve, labeled neurons were found in the PTPG. Numerous PTPG fibers were detected in the ethmoidal and sphenopalatine nerves. The presence of PTPG fibers in the supraorbital, infratrochlear, zygomaticotemporal, zygomaticofacial-inferior palpebral, sphenopalatine and infraorbital-superior alveolar nerves has not hitherto been reported in mammals.


Iron causes interactions of TAK1, p21ras, and phosphatidylinositol 3-kinase in caveolae to activate IkappaB kinase in hepatic macrophages.
We recently discovered a novel signaling phenomenon involving a rapid and transient rise in intracellular low molecular weight iron complex(es) in activation of IkappaB kinase (IKK) in hepatic macrophages. We also showed direct treatment with ferrous iron substitutes for this event to activate IKK. The present study used this model to identify upstream kinases responsible for IKK activation. IKK activation induced by iron is abrogated by overexpression of a dominant negative mutant (DN) for transforming growth factor beta-activated kinase-1 (TAK1), NF-kappaB-inducing kinase, or phosphatidylinositol 3-kinase (PI3K) and by treatment with the mitogen-activated protein kinase (MAPK) kinase-1 (MEK1) inhibitor. Iron increases AKT phosphorylation that is prevented by DNTAK1 or DNp21ras. Iron causes ERK1/2 phosphorylation that is attenuated by DN-PI3K, prevented by DNp21ras, but unaffected by DNTAK1. Iron-induced TAK1 activity is not affected by the PI3K or MEK1 inhibitor, suggesting TAK1 is upstream of PI3K and MEK1. Iron increases interactions of TAK1 and PI3K with p21ras as demonstrated by co-immunoprecipitation and co-localization of these proteins with caveolin-1 as shown by immunofluorescent microscopy. Finally, filipin III, a caveolae inhibitor, abrogates iron-induced TAK1 and IKK activation. In conclusion, MEK1, TAK1, NF-kappa-inducing kinase, and PI3K are required for iron-induced IKK activation in hepatic macrophages and TAK1, PI3K, and p21ras physically interact in caveolae to initiate signal transduction.


Beta-defensins activate macrophages and synergize in pro-inflammatory cytokine expression induced by TLR ligands.
Our previous studies indicated that mouse beta defensin 14 (mBD14, Defb14), a newly identified member of the beta-defensin super family, interacts with the chemokine receptors CCR2 and CCR6. In this study we report that pre-stimulation of primary mouse macrophages with mBD14 results in a synergistic, enhanced expression of pro-inflammatory cytokines and chemokines induced by TLR ligand re-stimulation. Experiments using specific inhibitors of G(i)-protein-coupled receptor signaling provide evidence that this effect seems to be mediated by a G(i)-protein-coupled receptor expressed on bone marrow derived macrophages. However, using primary macrophages derived from CCR6- and CCR2-deficient mice clearly demonstrated that the enhanced pro-inflammatory cytokine and chemokine expression is independent of the chemokine receptors CCR6 and CCR2. Additionally, signaling pathway analysis indicated that mBD14 is capable of inducing MAPK ERK1/2 phosphorylation and the induction of CD86 and F4/80 expression in bone marrow-derived macrophages after mBD14 stimulation. Collectively, our data indicate that β-defensins activate primary macrophages and enhance pro-inflammatory responses by using G(i)PCRs in order to support inflammatory reactions induced by TLR ligands.


Diagnostic glenohumeral arthroscopy fails to fully evaluate the biceps-labral complex.
The purpose of this study was to define the limits of diagnostic glenohumeral arthroscopy and determine the prevalence and frequency of hidden extra-articular "bicipital tunnel" lesions among chronically symptomatic patients. Eight fresh-frozen cadaveric specimens underwent diagnostic glenohumeral arthroscopy with percutaneous tagging of the long head of the biceps tendon (LHBT) during maximal tendon excursion. The percentage of visualized LHBT was calculated relative to the distal margin of subscapularis tendon and the proximal margin of the pectoralis major tendon. Then, a retrospective review of 277 patients who underwent subdeltoid transfer of the LHBT to the conjoint tendon were retrospectively analyzed for lesions of the biceps-labral complex. Lesions were categorized by anatomic location (inside, junctional, or bicipital tunnel). Inside lesions were labral tears. Junctional lesions were LHBT tears visualized during glenohumeral arthroscopy. Bicipital tunnel lesions were extra-articular lesions hidden from view during standard glenohumeral arthroscopy. Seventy-eight percent of LHBT were visualized relative to the distal margin of the subscapularis tendon and only 55% relative to the proximal margin of the pectoralis major tendon. No portion of the LHBT inferior to the subscapularis tendon was visualized. Forty-seven percent of patients had hidden bicipital tunnel lesions. Scarring was most common and accounted for 48% of all such lesions. Thirty-seven percent of patients had multiple lesion locations. Forty-five percent of patients with junctional lesions also had hidden bicipital tunnel lesions. The only offending lesion was in the bicipital tunnel for 18% of patients. Diagnostic glenohumeral arthroscopy fails to fully evaluate the biceps-labral complex because it visualizes only 55% of the LHBT relative to the proximal margin of the pectoralis major tendon and did not identify extra-articular bicipital tunnel lesions present in 47% of chronically symptomatic patients. Level IV, therapeutic case series and cadaveric study.


Incorporation of a fluorous diazirine group into phosphatidylinositol 4,5-bisphosphate to illustrate its interaction with ADP-ribosylation factor 1.
Phosphatidylinositides are one family of the most versatile signaling molecules in cells, yet how they interact with different proteins to regulate biological processes is not well understood. Towards a general strategy to identify phosphatidylinositide-protein interactions, a fluorous diazirine group has been incorporated into phosphatidylinositol 4,5-bisphosphate (PIP(2)). The modified PIP(2) was effectively cleaved by phospholipase C, one signaling protein that utilizes PIP(2) as its endogenous substrate. Upon light illumination, the PIP(2) probe effectively crosslinks with small GTPase ADP-ribosylation 1 to form a complex, suggesting that the probe might be suitable to identify PIP(2)-interacting proteins on the proteome level.


Soft Tissue Masses of Hand: A Radio-Pathological Correlation.
Aim. To evaluate soft tissue masses of the hand with magnetic resonance imaging (MRI) and ultrasonography (USG) and to correlate imaging findings with pathological findings. Material and Methods. Thirty-five patients with soft tissue masses of the hand were evaluated with high resolution USG and contrast enhanced MRI of the hand, prospectively over a period of 2.5 years. The radiological diagnosis was then compared with cytology/histopathology. Results. There were a total of 19 (55%) females. The mean age was 27.45 ± 14.7 years. Majority (45%) of cases were heteroechoic. Four cases were predominantly hyperechoic. These were later diagnosed as lipomas. Four cases were anechoic (diagnosed as ganglions). Only four lesions showed hyperintense signal on T1-weighted images. Out of these, 3 were lipomas and one was cavernous haemangioma. Three lesions were hypointense on T2-weighted images. All these lesions were diagnosed as giant cell tumor of the tendon sheath. A correct diagnosis was possible on MRI in 80% of cases (n = 28). Conclusion. MRI provides specific findings for diagnosis of certain soft tissue lesions of the hand. Ultrasonography allows accurate diagnosis of hemangioma/vascular malformations. However, in most conditions, imaging findings are nonspecific and diagnosis rests on pathologic evaluation.


Association of Vitamin D With Stress Fractures: A Retrospective Cohort Study.
Vitamin D is an essential, fat-soluble nutrient that is a key modulator of bone health. Despite the gaining popularity throughout published medical studies, no consensus has been reached regarding a serum vitamin D level that will guarantee adequate skeletal health in a patient with an increased functional demand. The purpose of the present investigation was to examine the serum concentrations of vitamin D in patients with confirmed stress fractures. A total of 124 patients were included in our retrospective cohort study. Of the 124 patients, 53 had vitamin D levels measured within 3 months of diagnosis. An association was seen in patients with a stress fracture and vitamin D level measured, as 44 (83.02%) of the 53 patients had a serum 25-hydroxyvitamin D level <40 ng/mL. Although an association was seen at our institution in patients with stress fractures and a serum vitamin D concentration <40 ng/mL, a larger and prospective investigation is warranted to further understand the effect of vitamin D level and stress fracture prevention in an active, nonmilitary population.


Knowledge, attitude and experience of menopause.
To determine the knowledge and attitude of women towards menopause and to investigate the symptoms experienced by postmenopausal women. It was a cross sectional survey based on sample of convenience. Study was conducted at out patient department of Isra university hospital from 1st January 2005 to 31st December 2006. Total 863 women of age 42 to 80 years were interviewed in office of out patient department. A semi structured questionnaire was used to collect data. Data analysis done by computer software statistical program for social sciences (SPSS) version 11.0. Mean age of respondents was 55.05, Menopause was natural in 727 (84.24%) women and 136 (15.75%) had surgical menopause. 680 (78.79%) women had little knowledge about menopause, while 137 (15.8%) women knew about effects and symptom of menopause. 680 (78.79%) women considered menopause as a natural process, while 183 (21.2%) perceived it as a disease, 720 (83.42%) women were happy about cessation of menses and they did not want to have menses again, while 143 (16.57%) women wanted to have menses again. These women were of age 45 to 58 years and 85 (59.4%) were uneducated. Frequently reported symptoms were Backache in 653 (75.66%), body aches, 576 (66.74%) and Insomnia in 544 (63.44%) women. Vasomotor symptoms (Hot Flushes and Night Sweats) were reported by 513 (59.4%) and 390 (45.19%) respectively. Short loss of memory was reported by 536 (62.10%) women. 318 (36.84%) women were bothered by menopausal symptoms but only 275 (31.86%) has consulted doctor. 649 (75.20%) women were not taking any medicine for symptoms, 08 (0.926%) were taking Herbs, 10 (1.15%) were on HRT and 196 (22.71%) women were taking analgesics and Ca supplements off and on. Hypertension and Diabetes Mellitus was present in 180 (20.85%), 215 (24.9%) women respectively. Majority of our women were unaware of menopausal symptoms and its health effects. Most of them considered it as a natural process of aging, though bothered by symptoms but did not go for consultation due to lack of awareness and poverty.


Dairy farm demographics and management factors that played a role in the re-emergence of brucellosis on dairy cattle farms in Fiji.
Little is published on risk factors associated with bovine brucellosis in Pacific island communities. The 2009 re-emergence of bovine brucellosis in Fiji enabled us to do an interview-based questionnaire survey of 81 farms in the Wainivesi locality of the Tailevu province on the main island of Fiji to investigate what risk factors could have played a role in the re-emergence of the disease. The survey was conducted on 68 farms that had no positive cases of bovine brucellosis and on 13 farms in the same area where cattle had returned a positive result to the Brucella Rose Bengal test. Descriptive statistical methods were used to describe the demographic data while univariate analysis and multivariate logistic regression were used to evaluate the association between the selected risk factors and the presence of brucellosis on the farms at the time of the outbreak. The demographics of Fijian dairy farms are presented in the article and the biosecurity implications of those farming systems are discussed. Two risk factors were strongly associated with farms having brucellosis, and these were history of reactor cattle to brucellosis and or bovine tuberculosis on the farm (OR = 29, P ≤ 0.01) and farms that practised sharing of water sources for cattle within and with outside farms (OR = 39, P ≤ 0.01). Possible reasons why these were risk factors are also discussed. The potential risks for human health was also high as the use of personal protective equipment was low (15%). A high proportion of farmers (62%) could not recognise brucellosis thus contributing to the low frequency of disease reports (44%) made. The article also highlights other important risk factors which could be attributed to farming practices in the region and which could contribute to public health risks and the re-emergence of diseases.


The Mycoplasma-derived macrophage-activating 2-kilodalton lipopeptide triggers global immune activation on nasal mucosa-associated lymphoid tissues.
A better knowledge on how immune responses are initiated in mucosal tissues would facilitate the design of new mucosal vaccines, as well as improve our understanding on host defense against infection. We investigated the mechanisms of adjuvanticity of the Mycoplasma-derived macrophage-activating 2-kDa lipopeptide (MALP-2), which binds to the heterodimer formed by the Toll-like receptors 2 and 6 (TLR2 and -6), at the level of the murine nasal mucosa-associated lymphoid tissues (NALT). TLR2 expression analysis demonstrated that several cell types from the nasal cavity were able to overexpress this receptor, either constitutively (such as B cells) or after stimulation (i.e., T cells). MALP-2 stimulated a strong B-cell activation. In addition, the antigen presentation capacity of dendritic cells was improved after in vivo loading with antigen in the presence of MALP-2. We also observed an up-regulated expression of activation markers and adhesion molecules on T cells, suggesting that they have enhanced responsiveness and interaction potential. Quantitative reverse transcription-PCR analysis showed that MALP-2 administration resulted in the stimulation of a proinflammatory cascade. We observed an early up-regulated expression of IP-10, MCP-1, MCP-3, MIP-1alpha, MIP-2, and CCR-2 which was reversed within 36 h. The obtained results demonstrated that MALP-2 creates a reversible local microenvironment which promotes effective priming of T and B cells in the NALT.


Sudden Cardiac Death in Athletes.
There are clear health benefits to exercise; even so, patients with cardiac conditions who engage in exercise and athletic competition may on rare occasion experience sudden cardiac death (SCD). This article reviews the epidemiology and common causes of SCD in specific athlete populations. There is ongoing debate about the optimal mechanism for SCD prevention, specifically regarding the inclusion of the ECG and/or cardiac imaging in routine preparticipation sports evaluation. This controversy and contemporary screening recommendations are also reviewed.


Modern trends in animal venom research - omics and nanomaterials.
Animal venom research is a specialized investigation field, in which a number of different methods are used and this array is constantly expanding. Thus, recently emerged omics and nanotechnologies have already been successfully applied to venom research. Animal venoms have been studied for quite a long time. The traditional reductionist approach has been to isolate individual toxins and then study their structure and function. Unfortunately, the characterization of the venom as a whole system and its multiple effects on an entire organism were not possible until recent times. The development of new methods in mass spectrometry and sequencing have allowed such characterizations of venom, encompassing the identification of new toxins present in venoms at extremely low concentrations to changes in metabolism of prey organisms after envenomation. In particular, this type of comprehensive research has become possible due to the development of the various omics technologies: Proteomics, peptidomics, transcriptomics, genomics and metabolomics. As in other research fields, these omics technologies ushered in a revolution for venom studies, which is now entering the era of big data. Nanotechnology is a very new branch of technology and developing at an extremely rapid pace. It has found application in many spheres and has not bypassed the venom studies. Nanomaterials are quite promising in medicine, and most studies combining venoms and nanomaterials are dedicated to medical applications. Conjugates of nanoparticles with venom components have been proposed for use as drugs or diagnostics. For example, nanoparticles conjugated with chlorotoxin - a toxin in scorpion venom, which has been shown to bind specifically to glioma cells - are considered as potential glioma-targeted drugs, and conjugates of neurotoxins with fluorescent semiconductor nanoparticles or quantum dots may be used to detect endogenous targets expressed in live cells. The data on application of omics and nanotechnologies in venom research are systematized concisely in this paper.


The RNA antiterminator causes transcription pausing in the leader region of the tryptophan operon.
In vitro transcription studies with a trp leader DNA template derived from a double deletion mutant of Serratia marcescens revealed that the transcription complex pauses synthesis of part of the RNA antiterminator, structure 2:3. Pausing was enhanced by NusA protein and was dependent on the concentration of UTP in the transcription reaction mixture. A weak antiterminator pause also was detected during transcription of the wild-type S. marcescens trp leader template in the presence of NusA protein and 1 microM UTP. Transcription pausing following synthesis of the antiterminator also was observed in a cell-free transcription-translation system. Antiterminator-induced pausing may play an important role in vivo by delaying synthesis of RNA segment 4. This delay may influence basal level control in cells with an excess of tryptophan. In addition, formation of the antiterminator pause structure may introduce a more stringent tryptophan starvation requirement for RNA polymerase to read through the attenuator.


Bursting pressure in anastomotic healing in experimentally induced colitis in rats.
Experimental studies on healing of colonic anastomosis have been thoroughly investigated. However, clinical parameters of the healing process of anastomosis in the inflamed colon has not yet been reported. In the present study, healing of anastomosis in trinitrobenzene-sulfonic acid-induced colitis in rats was assessed by measuring the bursting pressure and bursting wall tension. On postoperative day 4, bursting pressure and bursting wall tension were significantly lower (P < 0.001) in rats with colitis with or without anastomosis and normal colon with anastomosis, compared with normal colon without anastomosis. On postoperative day 7, bursting pressure and bursting wall tension of normal colon with anastomosis approached that of normal colon without anastomosis. However, bursting pressure and bursting wall tension of rats with colitis with or without anastomosis remained significantly lower (P < 0.001) than the latter. Furthermore, unlike rats without colitis in which perforation occurred mostly at the anastomotic line, the bursting site in colitic rats was predominantly away from the anastomotic line. These results suggest that in surgery for inflammatory bowel disease, it is the adjoining inflamed bowel wall that is vulnerable to be perforated in response to increasing intraluminal pressure rather than the anastomosis that is braced by the sutures.


High death anxiety and ambiguous loss: Lessons learned from teaching through the COVID-19 pandemic.
For gerontological educators, topics such as mortality, loss, and end-of-life issues often emerge or are central in their courses. However, teaching in the era, and aftermath, of the COVID-19 pandemic has heightened the salience of death and loss, raising questions about best practices and teaching pedagogies to support student learning amidst a global crisis. This qualitative study utilized written narratives collected during the pandemic from students enrolled in an undergraduate thanatology course. Content analysis of written narratives (n = 44) revealed three themes that can help inform strategies to best support student learning during challenging times. Participants desired more flexibility; compassion and understanding; and more targeted resources and socioemotional support. Results have immediate implications for educators teaching during the pandemic and for years to come. We provide recommendations for teaching and learning support, as well as advocate for more university and community-based thanatology and gerontology education offerings.


Cervical pedicle screw fixation in 100 cases of unstable cervical injuries: pedicle axis views obtained using fluoroscopy.
The authors conducted a study to introduce the imaging technique in which pedicle axis views are obtained using fluoroscopy to match the screw entry point with pedicle orientation and to report the clinical results and safety of cervical pedicle screw fixation (PSF) in patients treated for unstable cervical injuries. One hundred consecutive patients with unstable cervical injuries underwent PSF in which the authors used fluoroscopic imaging to acquire pedicle axis views. There were 87 men and 13 women whose mean age was 42.5 years. The accuracy of PS placement was examined postoperatively using axial computed tomography (CT) and oblique radiography. Screw malpositioning was classified either as screw exposure (< 50% of the screw outside the pedicle) or pedicle perforation (> 50% of the screw outside the pedicle boundaries). The mean operative time was 97.6 minutes, and the mean estimated blood loss was 221 ml. Local vertebral alignment around the injured segment measured 6.0 degrees of kyphosis preoperatively and 6.7 degrees of lordosis postoperatively. Solid posterior bone fusion was achieved in all but three patients who died shortly after surgery. There was no secondary dislodgment of instrumentation in 95% of these 97 cases. Of the 419 cervical PSs, 43 (10.3%) were of the screw-exposure type and 17 (4.0%) of the pedicle-perforation type. There were two surgery-related complications: one penetration of a probe into the vertebral artery and one radiculopathy. There were six postoperative complications: two cases of instrumentation failure associated with loss of correction, three cases of correction loss (> 10 degrees), and one case of deep wound infection. Solid posterior fusion without secondary dislodgment of hardware was demonstrated in 95% of the cases. The incidence of complications associated with cervical PSF was not high. Postoperative CT scanning showed that 17 (4.0%) of 419 screws perforated the pedicle. It appears that fluoroscopy performed using pedicle axis views improves the accuracy and safety of cervical PS insertion.


Increase in decorin and biglycan in Duchenne Muscular Dystrophy: role of fibroblasts as cell source of these proteoglycans in the disease.
Fibrosis is a common pathological feature observed in muscles of patients with Duchenne muscular dystrophy (DMD). Biglycan and decorin are small chondroitin/dermatan sulfate proteoglycans in the muscle extracellular matrix (ECM) that belong to the family of structurally related proteoglycans called small leucine-rich repeat proteins. Decorin is considered an anti-fibrotic agent, preventing the process by blocking TGF-beta activity. There is no information about their expression in DMD patients. We found an increased amount of both proteoglycans in the ECM of skeletal muscle biopsies obtained from DMD patients. Both biglycan and decorin were augmented in the perimysium of muscle tissue, but only decorin increased in the endomysium as seen by immunohistochemical analyses. Fibroblasts were isolated from explants obtained from muscle of DMD patients and the incorporation of radioactive sulfate showed an increased synthesis of both decorin and biglycan in cultured fibroblasts compared to controls. The size of decorin and biglycan synthesized by DMD and control fibroblasts seems to be similar in size and anion charge. These findings show that decorin and biglycan are increased in DMD skeletal muscle and suggest that fibroblasts would be, at least, one source for these proteoglycans likely playing a role in the muscle response to dystrophic cell damage.


Recognition of EBV plasma membrane protein expressed on murine cells after gene transfer.
The immune response to B lymphocytes infected with Epstein-Barr virus (EBV) prevents their overgrowth in normal humans. A murine model is now described for analyzing the T cell immune response to Epstein-Barr virus genes expressed in murine lymphoblasts by gene transfer. In mice, a 60,000 dalton virus-encoded protein characteristically found in the plasma membrane of latently infected human lymphocytes readily induces both proliferative and cytolytic T lymphocytes specific for both the EBV protein and murine major histocompatibility proteins. Longterm cultures of L3T4+ cells, some of which were cytolytic, were found to be restricted by H-2I-Ed and the latent membrane protein. Similarly, Lyt-2+ cells were cytolytic and were restricted by H-2Ld and the lymphocyte membrane protein gene product. The similarity in murine and human effector cell responses suggests that this is a useful experimental model, and the EBV latent infection membrane protein may be an important antigen in the immune restriction of growth transformed latently infected lymphocytes.


Targeted knockout of the gene OsHOL1 removes methyl iodide emissions from rice plants.
Iodine deficiency represents a public health problem worldwide. To increase the amount of iodine in the diet, biofortification strategies of plants have been tried. They rely on the exogenous administration of iodine to increase its absorption and accumulation. However, iodine is not stable in plants and can be volatilized as methyl iodide through the action of specific methyltransferases encoded by the HARMLESS TO OZONE LAYER (HOL) genes. The release of methyl iodide in the atmosphere represents a threat for the environment due to its ozone depletion potential. Rice paddies are among the strongest producers of methyl iodide. Thus, the agronomic approach of iodine biofortification is not appropriate for this crop, leading to further increases of iodine emissions. In this work, we used the genome editing CRISPR/Cas9 technology to knockout the rice HOL genes and investigate their function. OsHOL1 resulted a major player in methyl iodide production, since its knockout abolished the process. Moreover, its overexpression reinforced it. Conversely, knockout of OsHOL2 did not produce effects. Our experiments helped elucidating the function of the rice HOL genes, providing tools to develop new rice varieties with reduced iodine emissions and thus more suitable for biofortification programs without further impacting on the environment.


Versatile octave-spanning soliton crystals with high conversion efficiency in a Si3N4 microresonator.
Microresonator-based soliton crystals are a key recent advancement in the study of the rich nonlinear dynamics of soliton states. The soliton crystals are self-organized temporal pulses filling the microresonator cavity and have strong comb lines with wide spacing making them of great interest in many potential applications such as communication and meteorology. However, achieving a broad spectrum, tunable repetition rates, and high conversion efficiency are still a challenge. Here, we report the deterministic generation of versatile octave-spanning soliton crystals with various repetition rates via avoided mode crossings. In addition, we investigate the conversion efficiency of the obtained soliton crystals and achieved above ∼50% in one of the devices with a suitable coupling. Our results pave the way for accessing coherent broad and tunable on-chip soliton crystals, thus requiring a rigorous and viable microcavity design to engineer the desired mode coupling position.


Pre-Assault Personality Predicts the Nature of Adverse Outcomes Among Sexual Assault Victims.
Exposure to sexual assault results in ongoing harms for women. After an assault, some women engage in higher levels of externalizing behaviors, such as problem drinking, and others experience higher levels of internalizing dysfunction, such as symptoms of anxiety and depression. We sought to understand the role of premorbid factors on the different post-assault experiences of women. We studied 1,929 women prospectively during a period of high risk for sexual assault (the first year of college): women were assessed in July before arriving at college and in April near the end of the school year. A premorbid personality disposition to act impulsively when distressed (negative urgency) interacted positively with sexual assault experience to predict subsequent increases in drinking behavior; a premorbid personality disposition toward internalizing dysfunction positively interacted with sexual assault experience to predict increased symptoms of anxiety and depression. Women with different personalities tend to experience different forms of post-assault consequences.


[Post anthrax vaccine delayed hypersensitivity. II--delayed hypersensitivity in humans vaccinated against anthrax].
To detect cell immunity characterized by delayed postvaccination hypersensitivity to anthrax in man and assess its dynamics, vaccination using unencapsulated live anthrax vaccine was performed in 668 healthy volunteers. Vaccination was performed either by scarification (n = 172), subcutaneous injection (n = 202), or low-dose (n = 202) or high-dose (n = 83) inhalation. The anthraxin intradermal tests were performed in each patient at various times during the year following vaccination (D7, D15, D90, D180, D365). This study confirm that, regardless of the mode of administration, the vaccine induces cell-mediated immunity in man, as determined by positive anthraxine skin test. The incidence of positive tests decreases with time regardless of the mode of vaccination. After one year, the test remained positive in 34.8% of subjects vaccinated by subcutaneous injection, 37.5% vaccinated by low-dose inhalation, 34.2% vaccinated by high-dose inhalation, and 22.4% vaccinated by scarification. These findings are in agreement with those obtained in clinical epidemiological studies documenting the effectiveness of encapsulated live anthrax vaccine in man.


[Surgical anatomy of the peri-insular association tracts. Part I.The superior longitudinal fascicle system].
To study the peri-insular association tract anatomy and define the permissible anatomical boundaries for resection of glial insular tumors with allowance for the surgical anatomy of the peri-insular association tracts. In an anatomic study of the superior longitudinal fascicle system (SLF I, SLF II, SLF III, arcuate fascicle), we used 12 anatomical specimens (6 left and 6 right hemispheres) prepared according to the Klingler's fiber dissection technique. To confirm the dissection data, we used MR tractography (HARDI-CSD-tractography) of the conduction tracts, which was performed in two healthy volunteers. Except the SLF I (identified in 7 hemispheres by fiber dissection), all fascicles of the SLF system were found in all investigated hemispheres by both fiber dissection and MR tractography. The transcortical approach to the insula through the frontal and (or) parietal operculum is associated with a significant risk of transverse transection of the SLF III fibers passing in the frontal and parietal opercula. The most optimal area for the transcortical approach to the insula is the anterior third of the superior temporal gyrus that lacks important association tracts and, consequently, a risk of their injury. The superior peri-insular sulcus is an intraoperative landmark for the transsylvian approach, which enables identification of the SLF II and arcuate fascicle in the surgical wound. Detailed knowledge of the peri-insular association tract anatomy is the prerequisite for neurosurgery in the insular region. Our findings facilitate correct identification of both the site for cerebral operculum dissection upon the transcortical approach and the intraoperative landmarks for locating the association tracts in the surgical wound upon the transsylvian approach to the insula.


Spontaneous corneal perforation post cataract surgery.
A 69-year-old female was referred for bilateral cataracts. Best-corrected visual acuity was 6/12 oculus dexter (OD) and 6/18 oculus sinister (OS). On examination, tear film breakup time was 8 s, signifying mild dry eyes; otherwise was unremarkable. The patient underwent uneventful left cataract surgery. At a 1 month postoperative examination vision was 6/9. The left cornea was dry with extensive punctuate epithelial erosions. There was no lagophthalmos. Lubricants were started to both eyes. The authors proceeded with right cataract surgery. Postoperative preservative free drops were given. She failed to attend an earlier than routine 2 week postoperative examination. Four weeks postoperatively, the vision was 2/60. She was incompliant with the lubricant drops. Biomicroscopic examination showed a sterile painless paracentral corneal perforation with iris plugging, Seidel's negative. She was started on steroid drops and lubricants. A lower lid punctual plug was inserted. The best corrected vision at 4 months was 6/18 OD and 6/6 OS.


Magnetic circular dichroism of peralkylated tetrasilane conformers.
Magnetic circular dichroism (MCD) of five peralkylated tetrasilanes (1-5) conformationally constrained to angles ranging from nearly 0 degrees to 180 degrees and of the open chain tetrasilane Si(4)Me(10) (6) shows a clear conformational dependence and permits the detection of previously hidden transitions. In the tetrasilane CH(2)Si(4)Me(8) (1), with the smallest dihedral angle, comparison of MCD with absorption spectra reveals four low-energy electronic transitions. In the tetrasilanes 2-4, three distinct transitions are apparent. In tetrasilanes 5 and 6, MCD reveals the very weak transition that has been predicted to be buried under the first intense peak and to which the anomalous thermochromism of 6 and other short-chain oligosilanes has been attributed.


Anatomic Considerations for Injection of the Lateral Atlanto-Axial Joint.
We aimed to define the potential complications of intra-articular steroid injections into the lateral C1-2 articulations and safety margins to the relevant structures. A total of 488 contrast-enhanced computed tomography angiogram (CTA) "arch to vertex" studies were retrospectively reviewed for theoretical intersection of the vertebral artery or thecal sac and distance of the named structures from the anticipated/theoretical trajectory of injection into the lateral C1-C2 joint. Patients were 60.4±15.8 years old and 55.5% male. In total, seven vertebral arteries and 11 thecal sac theoretical intersections were found. In cases without a direct intersection, the distance from the trajectory (range) was 0.71±0.18 (0.22-1.44) cm to the vertebral artery and 0.6±0.22 (0.14-1.8) cm to the thecal sac. Although injection of steroid into the lateral C1-C2 articulation for pain management has historically been reported to carry risk of severe complications due to close proximity and location variability of surrounding structures, our study quantifies the potential risk of such injections. Further, our analysis suggests that preprocedural imaging should be considered.


Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis.
Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation. To elucidate the related mechanism, mRNA levels of inflammatory cytokines and immunomodulatory receptors in the transplanted grafts were measured using quantitative RT-PCR. The lung graft tissue from the rats that received MSCs post-surgically was protected from acute rejection significantly better than that from the untreated controls. Notably, the rats administered MSCs twice after surgery exhibited the least signs of rejection, with a markedly upregulated mRNA level of PD-L1 and a downregulated mRNA level of IL-17A. This study assessed MSC protection of lung allografts from acute rejection by modulating T cell activity via enforced expression of PD-L1 in transplants and downregulation of IL-17A.


Bipartite graph analyses reveal interdomain LGT involving ultrasmall prokaryotes and their divergent, membrane-related proteins.
Based on their small size and genomic properties, ultrasmall prokaryotic groups like the Candidate Phyla Radiation have been proposed as possible symbionts dependent on other bacteria or archaea. In this study, we use a bipartite graph analysis to examine patterns of sequence similarity between draft and complete genomes from ultrasmall bacteria and other complete prokaryotic genomes, assessing whether the former group might engage in significant gene transfer (or even endosymbioses) with other community members. Our results provide preliminary evidence for many lateral gene transfers with other prokaryotes, including members of the archaea, and report the presence of divergent, membrane-associated proteins among these ultrasmall taxa. In particular, these divergent genes were found in TM6 relatives of the intracellular parasite Babela massiliensis.


Pharmacogenomics: Driving Personalized Medicine.
Personalized medicine tailors therapies, disease prevention, and health maintenance to the individual, with pharmacogenomics serving as a key tool to improve outcomes and prevent adverse effects. Advances in genomics have transformed pharmacogenetics, traditionally focused on single gene-drug pairs, into pharmacogenomics, encompassing all "-omics" fields (e.g., proteomics, transcriptomics, metabolomics, and metagenomics). This review summarizes basic genomics principles relevant to translation into therapies, assessing pharmacogenomics' central role in converging diverse elements of personalized medicine. We discuss genetic variations in pharmacogenes (drug-metabolizing enzymes, drug transporters, and receptors), their clinical relevance as biomarkers, and the legacy of decades of research in pharmacogenetics. All types of therapies, including proteins, nucleic acids, viruses, cells, genes, and irradiation, can benefit from genomics, expanding the role of pharmacogenomics across medicine. Food and Drug Administration approvals of personalized therapeutics involving biomarkers increase rapidly, demonstrating the growing impact of pharmacogenomics. A beacon for all therapeutic approaches, molecularly targeted cancer therapies highlight trends in drug discovery and clinical applications. To account for human complexity, multicomponent biomarker panels encompassing genetic, personal, and environmental factors can guide diagnosis and therapies, increasingly involving artificial intelligence to cope with extreme data complexities. However, clinical application encounters substantial hurdles, such as unknown validity across ethnic groups, underlying bias in health care, and real-world validation. This review address the underlying science and technologies germane to pharmacogenomics and personalized medicine, integrated with economic, ethical, and regulatory issues, providing insights into the current status and future direction of health care. SIGNIFICANCE STATEMENT: Personalized medicine aims to optimize health care for the individual patients with use of predictive biomarkers to improve outcomes and prevent adverse effects. Pharmacogenomics drives biomarker discovery and guides the development of targeted therapeutics. This review addresses basic principles and current trends in pharmacogenomics, with large-scale data repositories accelerating medical advances. The impact of pharmacogenomics is discussed, along with hurdles impeding broad clinical implementation, in the context of clinical care, ethics, economics, and regulatory affairs.


An estimation of the sensitivity of in vitro translation using two-dimensional gel analysis.
Poly (A+ mRNA species, isolated from 100-day-old rat brain, were analysed by in vitro translation and two-dimensional gel electrophoresis. The synthesis of selected protein species was compared to actin on the basis of [35S]methionine incorporation. The estimated molar abundance of translation products varied from abundant species at 0.78% of the total to several are species, detectable below the 0.02% level. If these synthesis rates reflect the abundance of particular mRNAs in the mixture, this sensitivity limit compares well with accepted values using differential cDNA screening techniques. This analysis provides evidence that in vitro translation methodology is able to detect rarer mRNA species than is usually expected--these include similar abundance classes to library screening procedures.


Synthesis of Imine-Naphthol Tripodal Ligand and Study of Its Coordination Behaviour towards Fe(III), Al(III), and Cr(III) Metal Ions.
A hexadentate Schiff base tripodal ligand is synthesized by the condensation of tris (2-aminoethyl) amine with 2-hydroxy-1-naphthaldehyde and characterized by various spectroscopic techniques like UV-VIS, IR, NMR, MASS, and elemental analysis. The solution studies by potentiometric and spectrophotometric methods are done at 25 ± 1°C, µ = 0.1 M KCl, to calculate the protonation constants of the ligand and formation constants of metal complexes formed by the ligand with Fe(III), Al(III), and Cr(III) metal ions. The affinity of the ligand towards Fe(III) is compared with deferiprone (a drug applied for iron intoxication) and transferrin (the main Fe(III) binding protein in plasma). Structural analysis of the ligand and the metal complexes was done using semiempirical PM6 method. Electronic and IR spectra are calculated by semiempirical methods and compared with experimental one.


Fatness in relation to substrate oxidation during exercise.
The aim of this study was to test the hypothesis that differences in fuel utilisation during exercise, determined by muscle fibre-type profile, are an aetiological factor for obesity as proposed by Wade et al. (Lancet 1990, 335, 805-8). An investigation was carried out of relationships between body fatness (assessed by skinfolds, densitometry and dual X-ray absorptiometry) and fuel utilisation represented by the respiratory exchange ratio (RER, assessed by indirect calorimetry) during three cycle ergometer exercises. Exercise 1 was an exact replication of the Wade protocol (fixed 100 Watt load and unstandardised with respect to antecedent diet and activity). Exercises 2 (fasted) and 3 (fed) were highly standardised and adjusted to represent the same relative workload for each subject (45% VO2max). The subjects were 37 randomly-selected untrained men. None of the exercises yielded significant correlations between fatness and RER. The results refute the initial hypothesis linking substrate oxidation and body fatness. Inspection of the body composition data for Wade's subjects reveals that they were abnormally lean. This suggests that their findings may have been confounded by coincident correlations between fitness and fatness, and may not represent a true causal relationship.


Reference right atrial function determined by steady-state free precession cardiovascular magnetic resonance.
There is agreement that measurements of atrial volumes and ejection fraction (EF) are superior to atrial diameters for accurate determination of atrial size, follow up studies and prognosis. However, reference values for right atrial volumes and EF for cardiovascular magnetic resonance (CMR) have not been established but are crucial to identify patients with impaired right atrial function. Atrial function was studied in 70 healthy subjects (52+/-16 years, 38 male) with both the standard short axis method (SA) and the area-length method (AL) using steady-state free precession gradient-echo cine imaging (SSFP). Intraobserver, interobserver (n=70) and interstudy (n=10) variability was assessed for both methods. Maximal volumes, minimal volumes and EF for SA and AL were 101.0+/-30.2 mL, 50.3+/-19 mL and 47.2+/-8.3%, and 103.2+/-32.6 mL, 50.8+/-20.2 mL and 51.4+/-9.2%, respectively. Maximal volumes, minimal volumes and EF were higher with AL than with SA (mean difference: 2.2+/-4.6 mL, 3.5+/-3.5 mL and 2.8+/-2.8%, respectively). Atrial function measurements were not related to gender (p>or=0.387) and age (rho<or=0.16) with either method. Intraobserver, interobserver and interstudy variability for volumes and EF was lower for SA compared to AL, with narrower limits of agreement. Analysis was faster with AL than with SA (62+/-18 s versus 7+/-2 minutes). Normal ranges for right atrial function vary significantly between methods. AL is faster, but less reproducible than SA. Appropriate reference ranges should be used to differentiate normal from abnormal right atrial function.


A survivin-ran complex regulates spindle formation in tumor cells.
Aberrant cell division is a hallmark of cancer, but the molecular circuitries of this process in tumor cells are not well understood. Here, we used a high-throughput proteomics screening to identify novel molecular partners of survivin, an essential regulator of mitosis overexpressed in cancer. We found that survivin associates with the small GTPase Ran in an evolutionarily conserved recognition in mammalian cells and Xenopus laevis extracts. This interaction is regulated during the cell cycle, involves Ran-GTP, requires a discrete binding interface centered on Glu65 in survivin, and is independent of the Ran effector Crm1. Disruption of a survivin-Ran complex does not affect the assembly of survivin within the chromosomal passenger complex or its cytosolic accumulation, but it inhibits the delivery of the Ran effector molecule TPX2 to microtubules. In turn, this results in aberrant mitotic spindle formation and chromosome missegregation in tumor, but not normal, cells. Therefore, survivin is a novel effector of Ran signaling, and this pathway may be preferentially exploited for spindle assembly in tumor cells.


Carotid Plaque Morphology and Ischemic Vascular Brain Disease on MRI.
Vulnerable carotid plaque components are reported to increase the risk of cerebrovascular events. Yet, the relation between plaque composition and subclinical ischemic brain disease is not known. We studied, in the general population, the association between carotid atherosclerotic plaque characteristics and ischemic brain disease on MR imaging. From the population-based Rotterdam Study, 951 participants underwent both carotid MR imaging and brain MR imaging. The presence of intraplaque hemorrhage, lipid core, and calcification and measures of plaque size was assessed in both carotid arteries. The presence of plaque characteristics in relation to lacunar and cortical infarcts and white matter lesion volume was investigated and adjusted for cardiovascular risk factors. Stratified analyses were conducted to explore effect modification by sex. Additional analyses were conducted per carotid artery in relation to vascular brain disease in the ipsilateral hemisphere. Carotid intraplaque hemorrhage was significantly associated with the presence of cortical infarcts (OR, 1.9; 95% confidence interval, 1.1-3.3). None of the plaque characteristics were related to the presence of lacunar infarcts. Calcification was the only characteristic that was associated with higher white matter lesion volume. There was no significant interaction by sex. The presence of carotid intraplaque hemorrhage on MR imaging is independently associated with MR imaging-defined cortical infarcts, but not with lacunar infarcts. Plaque calcification, but not vulnerable plaque components, is related to white matter lesion volume.


Inhibitory Effect of Lychee Seed Saponins on Apoptosis Induced by Aβ25-35 through Regulation of the Apoptotic and NF-κB Pathways in PC12 Cells.
Neuronal apoptosis plays a critical role in the pathogenesis of Alzheimer's disease (AD). Previous studies have shown that lychee seed saponins (LSS), isolated and extracted from traditional Chinese medicine lychee seeds, possess many beneficial activities including anti-oxidation, anti-diabetes, anti-AD, etc. In the present study, we established an in vitro neuronal apoptotic model of PC12 cells induced by Aβ25-35 and studied the effect of LSS on apoptosis by the methods of Hoechst 33342/propidium iodide (PI) fluorescence double staining, Annexin V/PI double staining, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL). We also investigated the effects of LSS on mitochondria membrane potential, the expressions of Bcl-2 and Bax proteins, and the mRNA expression and the nuclear translocation of NF-κBp65 in PC12 cells. The results showed that LSS markedly inhibited apoptosis, improved the mitochondria membrane potentials, upregulated the expression of Bcl-2 protein, downregulated the expression of Bax protein, and decreased the mRNA expression and nuclear translocation of NF-κBp65 in PC12 cells. The study demonstrated that LSS significantly inhibited apoptosis induced by Aβ25-35 via regulation of the apoptotic and NF-κB pathways in PC12 cells. Therefore, LSS has the potential to be developed as a novel agent or nutrient supplement for the prevention and/or treatment of AD.


"DEPHENCE" system-a novel regimen of therapy that is urgently needed in the high-grade serous ovarian cancer-a focus on anti-cancer stem cell and anti-tumor microenvironment targeted therapies.
Ovarian cancer, especially high-grade serous type, is the most lethal gynecological malignancy. The lack of screening programs and the scarcity of symptomatology result in the late diagnosis in about 75% of affected women. Despite very demanding and aggressive surgical treatment, multiple-line chemotherapy regimens and both approved and clinically tested targeted therapies, the overall survival of patients is still unsatisfactory and disappointing. Research studies have recently brought some more understanding of the molecular diversity of the ovarian cancer, its unique intraperitoneal biology, the role of cancer stem cells, and the complexity of tumor microenvironment. There is a growing body of evidence that individualization of the treatment adjusted to the molecular and biochemical signature of the tumor as well as to the medical status of the patient should replace or supplement the foregoing therapy. In this review, we have proposed the principles of the novel regimen of the therapy that we called the "DEPHENCE" system, and we have extensively discussed the results of the studies focused on the ovarian cancer stem cells, other components of cancer metastatic niche, and, finally, clinical trials targeting these two environments. Through this, we have tried to present the evolving landscape of treatment options and put flesh on the experimental approach to attack the high-grade serous ovarian cancer multidirectionally, corresponding to the "DEPHENCE" system postulates.


[Promoting Self-Regulation of Adolescents in School Through Mindfulness].
Promoting Self-Regulation of Adolescents in School Through Mindfulness. Evaluation of the Mindfulness Training "8-sam" Mindfulness describes the psychological process of purposely bringing one's attention to the present experiences with an accepting, non-judgmental attitude. As such, it has attracted increasing interest in educational institutions. The present study aims to evaluate a mindfulness training for adolescents in a German high school. For this purpose, the program "8-sam" has been developed. Feasibility, acceptance and efficacy of this four-week training were examined in a sample of 48 ninth-grade students. Self-ratings of mindfulness, chronic stress, emotion regulation and health, as well as behavioral measures of attention and mind-wandering of the intervention group (n = 22) were compared to the wait control group (n = 24) before, immediately and 6 weeks after the training. As indicated by self-designed evaluation questionnaires, the training proved to be well accepted and implementable at school. The intervention group showed less mind-wandering after the training than the control group. The findings offer implications for future research and the application of mindfulness trainings in schools. Implementing mindfulness in the daily school routine promises to support self-regulatory processes and thus, strengthen the resilience of children and adolescents.


Effect of physical therapy intervention on thickness and ratio of the sternocleidomastoid muscle and head rotation angle in infants with congenital muscular torticollis: A randomized clinical trial (CONSORT).
Early diagnosis as well as treatment is important in management of congenital muscular torticollis (CMT). The purpose of this study was to find an effective physical therapy modality to improve the sternocleidomastoid (SCM) muscle thickness, the ratio of the SCM muscle thickness on the affected side to that on the non-affected side (A/N ratio), and head rotation in infant under 3 months of age diagnosed with CMT. A single-blind, randomized clinical trial was conducted. Participants were assigned in one of the 3 study groups through randomization. The treatment was performed 3 times a week for 30 minutes until the head tilt was ≤5 degrees. Group 1 was treated by handling for active or active-assist movement, group 2 was treated with passive stretching, and group 3 was treated with thermotherapy. For general characteristics, a χ2 test and 1-way analysis of variance were used. Intragroup differences were analyzed using a paired t test, and intergroup differences were analyzed using an age-adjusted analysis of covariance. After the intervention, there was no significant difference between groups in terms of SCM thickness on the affected side and A/N ratio (P > .05). Degree of head rotation on the affected side showed significant differences between groups (P < .05), with Group 2 showing significantly better results than group 1 and group 3 (P < .05, both). Passive stretching treatment was more effective than other treatments of this study for improvement in degree of head rotation in CMT infants under 3 months of age. The trial is registered at the Institutional Review Board of Sahmyook University (IRB number, 2-7001793-AB-N-012019103HR) and the Clinical Research Information Service (CRiS; registry number, KCT0004862).


First draft genome assembly and identification of SNPs from hilsa shad ( Tenualosa ilisha) of the Bay of Bengal.
Background: Hilsa shad ( Tenualosa ilisha), a widely distributed migratory fish, contributes substantially to the economy of Bangladesh. The harvest of hilsa from inland waters has been fluctuating due to anthropological and climate change-induced degradation of the riverine habitats. The whole genome sequence of this valuable fish could provide genomic tools for sustainable harvest, conservation and productivity cycle maintenance. Here, we report the first draft genome of T. ilisha from the Bay of Bengal, the largest reservoir of the migratory fish. Methods: A live specimen of T. ilisha was collected from the Bay of Bengal. The whole genome sequencing was performed by the Illumina HiSeqX platform (2 × 150 paired end configuration). We assembled the short reads using SOAPdenovo2 genome assembler and predicted protein coding genes by AUGUSTUS. The completeness of the T. ilisha genome assembly was evaluated by BUSCO (Benchmarking Universal Single Copy Orthologs). We identified single nucleotide polymorphisms (SNPs) by calling them directly from unassembled sequence reads using discoSnp++. Results: We assembled the draft genome of 710.28 Mb having an N50 scaffold length of 64157 bp and GC content of 42.95%. A total of 37,450 protein coding genes were predicted of which 29,339 (78.34%) were annotated with other vertebrate genomes. We also identified 792,939 isolated SNPs with transversion:transition ratio of 1:1.8. The BUSCO evaluation showed 78.1% completeness of this genome. Conclusions: The genomic data generated in this study could be used as a reference to identify genes associated with physiological and ecological adaptations, population connectivity, and migration behaviour of this biologically and economically important anadromous fish species of the Clupeidae family.


Localization and characterization of gastrin/cholecystokinin-like immunoreactivity in the central nervous system of Aplysia californica.
Gastrin/cholecystokinin-like immunoreactivity (G/CCK-LI) was localized by immunocytochemistry in neurons in the central nervous system of Aplysia californica. Neuronal cell bodies were specifically immunostained in the buccal, cerebral, pedal, and abdominal ganglia but not in the pleural ganglia. Neural G/CCK-LI processes were observed in the neuropil of all ganglia and connectives and in some but not all of the peripheral nerves examined. Somata containing G/CCK-LI ranged from 15 to 200 micron in diameter. Ganglionic G/CCK-LI was most efficiently extracted in neutral or basic solutions and consisted mainly of a substance eluting in a volume corresponding to a peptide of between 8 and 17 amino acid residues on gel filtration. This G/CCK-LI diluted in parallel to mammalian gastrin in radioimmunoassays using two antisera differing in their specificities for the bioactive COOH-terminal region of mammalian G/CCK. We conclude that G/CCK-LI is distributed widely in the central and peripheral nervous systems of Aplysia californica and that this immunoreactivity probably represents a small peptide which is similar but not identical to mammalian gastrins and cholecystokinins at the functionally critical COOH terminus.


Regulating Ionizing Radiation Based on Metrics for Evaluation of Regulatory Science Claims.
This article attempts to reconcile differences within the relevant scientific community on the effect of exposure to low levels of ionizing radiation notably the applicability of linear nonthreshold (LNT) process at exposures below a certain limit. This article applies an updated version of Metrics for Evaluation of Regulatory Science Claims (MERSC) derived form Best Available Regulatory Science (BARS) to the arguments provided by the proponents and opponents of LNT. Based on BARS/MERSC, 3 categories of effects of exposure to ionizing radiation are identified. One category (designated as S) consists of reproducible and undisputed adverse effects. A second category (designated as U) consists of areas where the scientific evidence for potential adverse effects includes uncertainties. The scientific evidence in the U category leads to a threshold. In contrast, the scientific foundation of the third category (designated as P) is questionable, as the scientific evidence indicates that adverse effects of the exposure at this level are not only questionable but may be helpful. This article claims that the third area is the domain of policy makers including regulators. This article describes Jeffersonian Principle that categorizes the affected community into specialists, knowledgeable nonspecialists, and the general public. Based on Jeffersonian Principle, the relevant scientific information, particularly the U and P areas, must be translated into a language that at a minimum is understandable to the knowledgeable group. Once this process is completed, the policy makers including regulators may select exposure limits based on their judgment.


Ultrastructural autoradiographic studies of the early vasoproliferative response in tumor angiogenesis.
The early local vasoproliferative response induced by live tumor cells and an extract derived from such cells was studied in rat subcutaneous tissue by means of electron microscopy and ultrastructural autoradiography after local injections of tritium-labeled thymidine. DNA synthesis was localized in endothelial cells, pericytes, and perivascular cells 6 to 8 hours after exposure to 10(6) live Walker ascites tumor cells. At this time, DNA-synthesizing endothelial cells in parent vessels exhibited a continuous basement membrane and could not be readily differentiated, ultrastructurally, from control endothelium. At 48 to 50 hours, the number of labeled cells increased and there was ultrastructural evidence of regenerating endothelium: marked increase in ribosomes and endoplasmic reticulum, scarce or absent pinocytotic vesicles, attenuated or discontinuous basement membrane and marked irregularities in cytoplasmic surfaces. Labeled endothelial cells were present in parent vessels, as well as along newly formed sprouts. Autoradiographic and ultrastructural findings after tumor extract or live tumor cells at 48 hours were similar. Evidence was also presented that cells which were recognizable as pericytes, by ultrastructural criteria and by their localization within the basement membrane, were capable of DNA synthesis and mitosis.


The effect of intravenous injection of purified human tissue thromboplastin in rats.
As a background for the development and testing of phospholipase C in the therapy of post-traumatic and post-surgical intravascular coagulation, highly purified tissue thromboplastin was injected i.v. into rats. The levels of factor V, VII, VIII and blood platelets and the activity of the intrinsic coagulation pathway in general (the cephalin test) were followed. Histological examination of pulmonary, kidney and liver tissue was carried. The dose-response was highly dependent on the injection rate. A marked activation of factor VII and a fall in the activities of factors V and VIII as well as in thrombocyte counts were observed. Very few or no thrombi were seen beyond the pulmonary circulation. The main changes (fibrin-containing thrombi and platelet aggregates) were observed in the lungs during the first 15 min after injection. Atter 15 min virtually no thrombi or platelet aggregates could be detected. The effect of tissue thromboplastin was counteracted by large doses of antithrombin III.


RAC1P29S Induces a Mesenchymal Phenotypic Switch via Serum Response Factor to Promote Melanoma Development and Therapy Resistance.
RAC1 P29 is the third most commonly mutated codon in human cutaneous melanoma, after BRAF V600 and NRAS Q61. Here, we study the role of RAC1P29S in melanoma development and reveal that RAC1P29S activates PAK, AKT, and a gene expression program initiated by the SRF/MRTF transcriptional pathway, which results in a melanocytic to mesenchymal phenotypic switch. Mice with ubiquitous expression of RAC1P29S from the endogenous locus develop lymphoma. When expressed only in melanocytes, RAC1P29S cooperates with oncogenic BRAF or with NF1-loss to promote tumorigenesis. RAC1P29S also drives resistance to BRAF inhibitors, which is reversed by SRF/MRTF inhibitors. These findings establish RAC1P29S as a promoter of melanoma initiation and mediator of therapy resistance, while identifying SRF/MRTF as a potential therapeutic target.


Internal fixation of fractured ribs in neonatal foals with nylon cable tie using a modified technique.
Nylon cable tie has been shown to be an effective and economical method for fixing fractured ribs in the neonatal foal. This article describes a modification of the previously described technique. Under general anesthesia, the fractured ribs were exposed and a hole was drilled in the dorsal and ventral fragments. The fracture was not reduced, leaving the fragments overriding each other. The nylon cable tie was passed through the hole in the dorsal fragment from the external surface of the rib. The free end of the cable tie was then passed through the hole in the ventral fragment from the external surface of the rib and the tie was tightened. This technique was used in 4 neonatal foals with no complications. The modification of the original technique represents a method to minimize soft tissue trauma, implant failure, and complications.


Aging and survival of cutaneous microvasculature.
The growth and turnover of blood vessels in the skin is fundamental in normal development, wound repair, hair follicle cycling, tumor cell metastasis, and in many different states of cutaneous pathology. Whereas many investigations are focused on mechanisms of angiogenesis in the skin, the influence of cellular aging and replicative senescence (i.e., the inability, after a critical number of population doublings, to replicate) on microvascular remodeling events has received relatively less attention. In this article, we review the clinical and pathologic relationships associated with cutaneous vascular aging and update current knowledge of endothelial cell survival characteristics. A hypothesis is presented in which endothelial cell aging and survival are linked to molecular mechanisms controlling cell proliferation, quiescence, apoptosis, and cellular senescence. We review recent results demonstrating how activation of telomerase in human dermal microvascular endothelial cells affects their durability both in vitro and in vivo and conclude by linking these studies with current concepts involving endothelial cell precursors, control of postnatal somatic cell telomerase activity, and murine model systems.


Centrosome-attracting body: a novel structure closely related to unequal cleavages in the ascidian embryo.
The mechanism of unequal cleavage is one of the most intriguing subjects in cell biology. Previous studies of unequal cleavage have focused on a limited number of organisms such as yeasts, nematodes, sea urchins and annelids. The cleavage pattern of the ascidian embryo is invariant. In the ascidian embryo, the posterior-most blastomeres divide unequally in three successive cleavages. In the present study, it was shown that the ascidian embryo provides another good experimental system with which to analyze the mechanism of unequal cleavage. A novel structure, designated as CAB (centrosome-attracting body), which was found specifically in the unequally cleaving blastomeres was described. In the course of unequal cleavages, first, a thick microtubule bundle appeared between CAB and one of the centrosomes. Then with the shortening of the microtubule bundle, the nucleus with the centrosome was drawn toward CAB, situated at the posterior cortex of the blastomere. Finally, a cleavage furrow formed in the middle of the asymmetrically located mitotic apparatus and produced two blastomeres of different size, generating a smaller cell that inherits CAB. The CAB seemed to play an essential role in the unequal cleavages in the ascidian embryo.


Current bioremediation practice and perspective.
The use of microbes to clean up polluted environments, bioremediation, is a rapidly changing and expanding area of environmental biotechnology. Although bioremediation is a promising approach to improve environmental conditions, our limited understanding of biological contribution to the effect of bioremediation and its impact on the ecosystem has been an obstacle to make the technology more reliable and safer. Providing fundamental data to resolve these issues, i.e., the behavior of the target bacteria directly related to the degradation of contaminants and the changes in microbial communities during bioremediation, has been a challenge for microbiologists since many environmental bacteria cannot yet be cultivated by conventional laboratory techniques. The application of culture-independent molecular biological techniques offers new opportunities to better understand the dynamics of microbial communities. Fluorescence in situ hybridization (FISH), in situ PCR, and quantitative PCR are expected to be powerful tools for bioremediation to detect and enumerate the target bacteria that are directly related to the degradation of contaminants. Nucleic acid based molecular techniques for fingerprinting the 16S ribosomal DNA (rDNA) of bacterial cells, i.e., denaturing gradient gel electrophoresis (DGGE) and terminal restriction fragment length polymorphism (T-RFLP), enable us to monitor the changes in bacterial community in detail. Such advanced molecular microbiological techniques will provide new insights into bioremediation in terms of process optimization, validation, and the impact on the ecosystem, which are indispensable data to make the technology reliable and safe.


Enzymo- and immunocytochemical analyses of the differentiation of liver cells in the prenatal mouse.
Differentiation of the endodermal cells of the mouse liver was studied enzymo- and immunocytochemically by analyzing the cellular localization of alphafoetoprotein (AFP), glycogen, and alkaline phosphatase (ALP) and 5'-nucleotidase (5'-Nase) activities. 1. In 8.5-day foetuses, AFP appears in some endodermal cells of the anterior intestinal portal region. The cells of the cranial diverticulum contain much AFP at 9.5 days, while those of the caudal diverticulum contain less AFP. 2. In 9.5- to 15.5-day foetuses, hepatocytes are intensely fluorescent for AFP. After 16.5 days less-positive hepatocytes increase in number. AFP is still present in a few hepatocytes of 14-day-old postnatal mice. ALP and 5'-Nase activities appear in a small proportion of hepatocytes at 13.5 and 14.5 days of embryonal life, respectively. At 15.5 days, many hepatocytes possess these enzyme activities, and initiate accumulation of glycogen. AFP-containing hepatocytes type I (gestation day 9.5-16.5) successively acquire ALP and 5'-Nase activities and accumulate glycogen, and then differentiate into hepatocytes type II after gestation day 17.5. 3. Endodermal cells constituting lumen structures in the liver trabeculae are the precursor of the intrahepatic bile duct cells. They possess much AFP, but no glycogen and no ALP activity, and are similar to hepatocytes type I. Since immature hepatic duct cells also possess much AFP, but no glycogen, and no ALP and 5'-Nase activities, they are similar to endodermal cells of the lumen structures. Therefore, that the endodermal cells of the lumen structures are the intermediate cells between hepatocytes type I and hepatic duct cells may be conceivable.


Theophylline-induced endothelium-dependent vasodilation is mediated by increased nitric oxide release and phosphodiesterase inhibition in rat aorta.
This study aimed to examine the endothelial dependence of vasodilation induced by the phosphodiesterase inhibitor theophylline in isolated rat thoracic aortas and elucidate the underlying mechanism, with emphasis on endothelial nitric oxide (NO). The effects of various inhibitors and endothelial denudation on theophylline-induced vasodilation, and the effect of theophylline on vasodilation induced by NO donor sodium nitroprusside, cyclic guanosine monophosphate (cGMP) analog bromo-cGMP, and β-agonist isoproterenol in endothelium-denuded aorta were examined. The effects of theophylline and sodium nitroprusside on cGMP formation were also examined. We examined the effect of theophylline on endothelial nitric oxide synthase (eNOS) phosphorylation and intracellular calcium levels. Theophylline-induced vasodilation was greater in endothelium-intact aortas than that in endothelium-denuded aortas. The NOS inhibitor, NW-nitro-L-arginine methyl ester; non-specific guanylate cyclase (GC) inhibitor, methylene blue; and NO-sensitive GC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one inhibited theophylline-induced vasodilation in endothelium-intact aortas. Theophylline increased the vasodilation induced by sodium nitroprusside, bromo-cGMP, and isoproterenol. Theophylline increased cGMP formation in endothelium-intact aortas, and sodium nitroprusside-induced cGMP formation in endothelium-denuded aortas. Moreover, theophylline increased stimulatory eNOS (Ser1177) phosphorylation and endothelial calcium levels, but decreased the phosphorylation of inhibitory eNOS (Thr495). These results suggested that theophylline-induced endothelium-dependent vasodilation was mediated by increased endothelial NO release and phosphodiesterase inhibition.


Stress responses at the endometrial-placental interface regulate labyrinthine placental differentiation from trophoblast stem cells.
Development can happen in one of two ways. Cells performing a necessary function can differentiate from stem cells before the need for it arises and stress does not develop. Or need arises before function, stress develops and stress signals are part of the normal stimuli that regulate developmental mechanisms. These mechanisms adjust stem cell differentiation to produce function in a timely and proportional manner. In this review, we will interpret data from studies of null lethal mutants for placental stress genes that suggest the latter possibility. Acknowledged stress pathways participate in stress-induced and -regulated differentiation in two ways. These pathways manage the homeostatic response to maintain stem cells during the stress. Stress pathways also direct stem cell differentiation to increase the first essential lineage and suppress later lineages when stem cell accumulation is diminished. This stress-induced differentiation maintains the conceptus during stress. Pathogenic outcomes arise because population sizes of normal stem cells are first depleted by decreased accumulation. The fraction of stem cells is further decreased by differentiation that is induced to compensate for smaller stem cell populations. Analysis of placental lethal null mutant genes known to mediate stress responses suggests that the labyrinthine placenta develops during, and is regulated by, hypoxic stress.


Renal scarring is associated with nonsecretion of blood type antigen in children with primary vesicoureteral reflux.
Nonsecretor status of blood type antigen has been associated with higher risk of urinary tract infection (UTI) in women. However its implication in the modern management for pediatric UTI remains unclear. We evaluate the impact of secretor status on clinical course in children with primary vesicoureteral reflux (VUR). From 1998 to 2002, 382 cases of primary VUR presented to our institute and were treated either surgically or nonoperatively in accordance with the American Urological Association guideline. Of these potential candidates 128 patients and their guardians volunteered to be entered into the study. Antiseptic swabs to collect saliva were sent to them. The secretor status was determined using the hemagglutination inhibition assay from the eluted saliva on the swabs and medical records of responders were evaluated retrospectively. Secretor status was not associated with gender, VUR grade, presentation, history of breakthrough UTI, laterality of VUR and conservative vs surgical treatment. However, nonsecretor status weakly correlated with decreased split renal function and significantly correlated with the presence of focal renal scarring (40.9% vs 21.7% for children with and without scarring, respectively) as determined by technetium dimercapto-succinic acid renal scan. These results demonstrate that secretor status represents unrecognized host disposition that affects the clinical course of primary VUR. Further study is needed to determine the significance of secretor status for clinical management and pathophysiology of VUR.


Thiol-reactive (co)polymer scaffolds comprising organic arsenical acrylamides.
Novel, well-defined organic arsenical homopolymers (Đ = 1.10-1.40) have been synthesised via RAFT polymerisation. Copolymerisation of the As-functional monomer with dimethylacrylamide yielded non-toxic polymer scaffolds (Đ ≈ 1.10) that could be manipulated in response to pH and undergo sequential reduction and substitution in the presence of thiols including cysteine and glutathione.


[Infrared coagulation of the lung. Initial experimental and clinical results].
With regard to the good results which were found using the infrared coagulator (IRC) in hemostasis of liver and spleen experimental and clinical investigations of the lung were performed. Animal experiments elucidated the necessity of ligation of greater vessels as well as bronchi. Secure plugging of lung tissue was also possible following increased positive pressure respiration. A mean maximal extend of necrosis of 3 mm was measured. Clinical use in 11 patients proved secure plugging of tissue due to IRC application. Drainages could be removed within 4 days without appearance of broncho-pleural fistulas.


The effects of low doses of ranitidine on intragastric acidity in healthy men.
H2-receptor antagonists are becoming widely available as over-the-counter medications for the treatment of heartburn and excess gastric acidity. To determine the effects of single low doses of ranitidine on intragastric acidity. Intragastric pH was measured for 9 h after lunch in five studies involving 24 healthy male volunteers. Antacid was given to all subjects on day 1. They then received single oral doses of a study drug 45 min after lunch on four separate occasions: placebo and either ranitidine 25 mg, 75 mg or 125 mg were given double-blind according to a predetermined randomization schedule. During both of the post-dosing time periods (0-5 h and 5-9 h) there were significant decreases in integrated intragastric acidity for each ranitidine dose compared with placebo (P < 0.0001). There was a significant linear relationship between dose and integrated intragastric acidity with a greater decrease in acidity with increasing ranitidine doses (P < 0.0001). Compared with placebo, time with pH > 3 was significantly greater for ranitidine 75 mg and 125 mg (P < 0.001), but not ranitidine 25 mg. Results with the antacid were similar to placebo. Using low doses of ranitidine (25, 75 or 125 mg) there was a dose-related decrease in intragastric acidity for 9 h after dosing. A single dose of antacid did not decrease intragastric acidity significantly.


Impact of the protocol proposed by the American Society for Gastrointestinal Endoscopy in patients at high risk of choledocholithiasis, in Puebla Regional Hospital ISSSTE in Mexico.
Choledocholithiasis is one of the main complications of cholelithiasis with a prevalence in the Mexican population of 14%. The management through the guide proposed by the American Society for Gastrointestinal Endoscopy (ASGE) in 2010 can support the surgeon for the timely resolution of the pathology. To determine that the guide proposed by ASGE for the management of choledocholithiasis in patients with "high risk" reduces the complications of this pathology. A comparative, retrospective case-control study was conducted from January 1, 2015 to December 31, 2017. We included patients who were stratified at high risk of choledocholithiasis according to the ASGE guidelines. They were divided into 2 groups: the case group (diagnosis by ASGE guidelines) was submitted directly to endoscopic retrograde cholangiopancreatography (ERCP), the second group (no ASGE) followed the protocol of performing computed tomography, magnetic cholangioresonance, and finally ERCP. Of 61 patients with choledocholithiasis, the following groups were compared: the appearance of cholangitis, the complications after ERCP, time of ERCP, days of hospital stay and mortality. Obtaining significant difference in: "complications post ERCP" group ASGE 3/35 (9%), group no ASGE 8/26 (30.7%) with OR of 0.2 (0.05 - 0.9 IC 95%) and a p = 0.03; "Cholangitis" group ASGE 2/35 (5.7%), group no ASGE 8/26 (30-7%) with ORP 0.13 (0.03-0.71 IC 95%) and p = 0.009. In our setting, the use of the ASGE guideline reduces the presence of cholangitis and post-ERCP complications.


tortuga refines Notch pathway gene expression in the zebrafish presomitic mesoderm at the post-transcriptional level.
We have identified the zebrafish tortuga (tor) gene by an ENU-induced mutation that disrupts the presomitic mesoderm (PSM) expression of Notch pathway genes. In tor mutants, Notch pathway gene expression persists in regions of the PSM where expression is normally off in wild type embryos. The expression of hairy/Enhancer of split-related 1 (her1) is affected first, followed by the delta genes deltaC and deltaD, and finally, by another hairy/Enhancer of split-related gene, her7. In situ hybridization with intron-specific probes for her1 and deltaC indicates that transcriptional bursts of expression are normal in tor mutants, suggesting that tor normally functions to refine her1 and deltaC message levels downstream of transcription. Despite the striking defects in Notch pathway gene expression, somite boundaries form normally in tor mutant embryos, although somitic mesoderm defects are apparent later, when cells mature to form muscle fibers. Thus, while the function of Notch pathway genes is required for proper somite formation, the tor mutant phenotype suggests that precise oscillations of Notch pathway transcripts are not essential for establishing segmental pattern in the presomitic mesoderm.


Dopamine action in the substantia nigra pars reticulata: iontophoretic studies in awake, unrestrained rats.
Dopamine (DA) neurons located in the substantia nigra pars compacta release DA not only via axonal terminals, affecting neurotransmission within the striatum, but also via dendrites, some of which densely protrude into the substantia nigra pars reticulata (SNr). Although the interaction of dendritically released DA with somatodendritic autoreceptors regulates DA cell activity, released DA may also affect SNr neurons. These cells, however, lack postsynaptic DA receptors, making it unclear how locally released DA modulates their activity. Although previous work in brain slices suggests that DA might modulate the activity of GABA inputs, thus affecting SNr neurons indirectly, it remains unclear how increased or decreased DA release might affect these cells exposed to normal afferent inputs. To explore this issue, we examined the effects of iontophoretic DA and amphetamine on SNr neurons in awake, unrestrained rats. DA had no consistent effects on SNr cells but amphetamine, known to induce DA release, dose-dependently inhibited most of them. This effect was blocked by SCH23390, a selective D1 receptor blocker, which itself strongly increased neuronal discharge rate. As GABA input is a major factor regulating the activity of SNr neurons, our data suggest that dendritically released DA, by interacting with D1 receptors on striato-nigral and pallido-nigral afferents, is able to decrease this input, thus releasing SNr neurons from tonic, GABA-mediated inhibition. Surprisingly, a full DA receptor blockade (SCH23390 + eticlopride) did not result in the expected increase in SNr discharge rate, suggesting that other mechanisms are responsible for behavioral abnormalities following acute disruption of DA transmission.


Impact of High-Voltage Discharge After-Treatment Technology on Diesel Engine Particulate Matter Composition and Gaseous Emissions.
Diesel particulate matter (DPM) and oxides of nitrogen (NOx) are the emissions from diesel engines (compression ignition engines) of the most concern and are currently strictly regulated. In this work, we present an alternative diesel emission control technique to assist in further emission reduction. An experiment-oriented study on diesel engine emission abatement using low-power, low-frequency, high-voltage discharge (HVD) treatment was carried out in a laboratory-scale reactor with whole diesel engine exhaust gas. A dielectric barrier discharge (DBD) reactor was used in direct contact with diesel exhaust gas at atmospheric temperature with an input energy density between 200 and 400 J/L. An investigation of the direct effect of the high-voltage discharge reactor on the diesel exhaust gas treatment was carried out to characterize both diesel particle and gaseous emissions. The proposed HVD system demonstrated up to 95% particulate matter reduction by mass or 64% reduction by number, and 63% reduction of the diesel soot particle geometrical mean diameter by HVD-generated O3 oxidation. Thermogravimetric analysis revealed the significant change in the diesel soot compositions and oxidation characteristics. HVD-treated particulate matter demonstrated a lower reactivity in comparison to untreated soot. Gas composition analysis indicated the generation of free radicals (e, O, OH, O3, and N) by the HVD system, as mainly indicated by the increase of the NO2/NO ratio and concentration of CO and O2. The pattern of CO2 reduction while CO and O2 increased indicated the dissociation of CO2 by HVD. Free radicals generated by HVD directly affected DeNO, DeNOx, NO2/NO ratio, and CO and CO2 selectivities.


Algal populations controlled by fish herbivory across a wave exposure gradient on southern temperate shores.
Consumers that forage across habitats can affect communities by altering the abundance and distribution of key species. In marine communities, studies of trophic interactions have generally focused on the effects of herbivorous and predatory invertebrates on benthic algae and mussel populations. However, large mobile consumers that move across habitats, such as fishes, can strongly affect community dynamics through consumption of habitat-dominating species, but their effects often vary over environmental gradients. On temperate rocky shores, herbivorous fishes are generally a small part of the fish fauna compared to the tropics, and there is sparse evidence that they play a major direct role in algal community dynamics, particularly of large brown algae that dominate many reefs. In New Zealand, however, a wide-ranging herbivorous fish, Odax pullus, feeds exclusively on macroalgae, including Durvillaea antarctica, a large low-intertidal fucoid reaching 10 m in length and 70 kg in mass. In four experiments we tested the extent of fish herbivory and how it was affected by algal canopy structure across a gradient of wave exposure at multiple sites. Exclusion experiments showed that fish impacts greatly reduced the cover and biomass of Durvillaea and that these effects decreased with increasing wave stress and algal canopy cover, effectively restricting the alga to exposed conditions. Almost all plants were entirely removed by fish where there was a sparse algal canopy in sheltered and semi-exposed sites, but there was significantly less grazing in exposed sites. Recruit Durvillaea beneath canopies were less affected by fish grazing, but they grew slowly. Successful natural recruitment, therefore, occurred almost exclusively on exposed shores outside canopies where many plants escaped severe grazing, and growth to maturity was far greater than elsewhere. Such large and direct impacts on the local and regional distribution of large brown algal populations by mobile vertebrate consumers are rare and were mediated by an environmental gradient and plant density, both of which interact with algal demographics. The study highlights that, even though herbivorous fish diversity may be low, the impacts of particular species may still be high, even in cool temperate waters where fish herbivory is usually considered to be minimal.