Effects of recombinant human adenovirus type 5 combined with transarterial chemoembolization on postoperative metastasis and recurrence of hepatocellular carcinoma patients.
Postoperative recurrence is currently the main factor affecting the long-term survival of hepatocellular carcinoma (HCC) patients. The folinic acid, fluorouracil, and oxaliplatin (FOLFOX) regimen with transarterial chemoembolization (TACE) is a commonly used postoperative chemotherapy strategy, but its effect is still limited. The aim of this study was to analyze the effects of recombinant human adenovirus type 5 (rhAd5) combined with TACE on postoperative metastasis and recurrence of HCC. Patients with HCC undergoing surgical treatment were collected and divided into the rhAd5 group and control group according to whether rhAd5 was performed. The rhAd5 group was combined with rhAd5 treatment based on TACE. The recurrence and metastasis rates of the two participant groups were compared. The changes of liver function, kidney function, blood routine, and adverse reactions during treatment were analyzed. The basic data of the two groups were not significantly different (P>0.05). The recurrence and metastasis rates of rhAd5 group participants were significantly lower than those of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the rhAd5 group and control group (P>0.05). There were no significant differences in the incidences of adverse reactions between the rhAd5 group and control group (P>0.05). The combination of FOLFOX and rhAd5 after surgery can significantly inhibit the occurrence of metastasis and recurrence of HCC patients, improve progression free survival, and has certain safety.


The Concept, Status Quo and Forensic Pathology of Karoshi.
"Karoshi" originates from Japan's economic take-off period in the 1960s and 1970s. It is generally believed that overwork lead to the accumulation of fatigue, which triggers the outbreak of potential diseases, and results in sudden death. Karoshi causes great harm to both the community and families because it occurs primarily in 30 to 60 year old young adults. Japan put Karoshi into the category of industrial injury for the first time in 2001 and started to undertake a series of studies in the sociological and pathological fields. However, there is a tremendous gap in the forensic pathological diagnosis domain. In China, research on Karoshi started from the 1990s and is closely related to the reform and opening up policy as well as economic development. According to the incomplete statistics, 600 thousand people die from overwork each year in China, the highest in the world. Karoshi has become one of the most serious social problems in China at the present stage, thus a systematic study in the sociology and forensic pathology fields is urgently required. This paper summarizes the past and present status of Karoshi, and puts forward the problems that need attention during the judicial expertise of Karoshi from forensic pathology perspective.


Surgical management of GIST and intra-abdominal visceral leiomyosarcomas.
Intra-abdominal visceral sarcomas are a rare group of mesenchymal tumors that require the use of distinct surgical principles and a multidisciplinary approach in order to optimize treatment. Surgery remains the only potentially curative treatment. Management and outcomes vary for the different sarcomas arising from viscera. This review will summarize the current treatment strategies for the two most common visceral sarcomas, leiomyosarcomas, and gastrointestinal stromal tumors.


Intraductal carcinoma of the prostate without invasive carcinoma on needle biopsy: emphasis on radical prostatectomy findings.
Limited information is available on radical prostatectomy findings in men with intraductal carcinoma of the prostate on needle core biopsy in the absence of invasive prostate cancer. From the consulting files of one of us we identified 83 men in whom biopsy showed only intraductal prostate cancer. Followup was available in 66 cases. We reviewed slides in 21 radical prostatectomy cases. Treatment was radical prostatectomy in 23 men, radiation therapy in 15, hormone therapy in 8 and radiation plus hormone therapy in 15 while 5 underwent no treatment or repeat biopsy. Of the 21 radical prostatectomies available for review findings revealed pathological stage pT3a in 8 (38%), pT3b in 3 (13%), pT2 in 8 (38%) and intraductal carcinoma without identifiable invasive cancer in 2 (10%). One patient with pT3a had a positive lymph node at surgery. Average Gleason score was 7.9. Three patients (14%) experienced post-prostatectomy biochemical failure and another (5%) had bone metastases 2.5 years after prostatectomy. In 15 prostatectomies (71%) there was extensive intraductal carcinoma, defined as greater than 10% of tumor being intraductal, including the 2 cases of intraductal carcinoma only. Of the 19 prostatectomies with invasive adenocarcinoma 16 (84%) were conventional acinar adenocarcinoma, 2 (11%) ductal adenocarcinoma, and 1 (5%) mixed ductal and acinar adenocarcinoma. At radical prostatectomy men in whom prior biopsies showed only intraductal carcinoma of the prostate typically have high grade (Gleason score 7 or greater) invasive adenocarcinoma and most have advanced stage disease (pT3). Definitive therapy is recommended in men with intraductal carcinoma of the prostate on needle biopsy even in the absence of pathologically documented invasive prostate cancer.


Clinical significance and molecular characterization of nonsporulating molds isolated from the respiratory tracts of bronchopulmonary mycosis patients with special reference to basidiomycetes.
Nonsporulating molds (NSMs), especially basidiomycetes, have predominantly been reported as human pathogens responsible for allergic and invasive disease. Their conventional identification is problematic, as many isolates remain sterile in culture. Thus, inconclusive culture reports might adversely affect treatment decisions. The clinical significance of NSMs in pulmonary mycoses is poorly understood. We sequenced the internal transcribed spacer (ITS) region and D1/D2 domain of the larger subunit (LSU) of 52 NSMs isolated from respiratory specimens. The basidiomycetes were the predominant NSMs, of which Schizophyllum commune was the most common agent in allergic bronchopulmonary mycosis (ABPM), followed by Ceriporia lacerata in invasive fungal disease. Porostereum spadiceum, Phanaerochaete stereoides, Neosartorya fischeri, and Marasmiellus palmivorus were the other molds observed. Application of ITS and LSU region sequencing identified 92% of the isolates. The antifungal susceptibility data revealed that all basidiomycetes tested were susceptible to amphotericin B and resistant to caspofungin, fluconazole, and flucytosine. Except for 3 isolates of S. commune and a solitary isolate of M. palmivorus, all basidiomycetes had low MICs for itraconazole, posaconazole, and voriconazole. Basidiomycetes were isolated from patients with ABPM, invasive pulmonary mycosis/pneumonia, or fungal balls. In addition, the majority of the basidiomycetes were isolated from patients with chronic respiratory disorders who were sensitized to one of the basidiomycetous fungi and demonstrated precipitating antibodies against the incriminating fungi, indicating an indolent tissue reaction. Thus, isolation of basidiomycetes from the lower respiratory tract could be significant, and it is important to monitor these patients in order to prevent subsequent lung damage.


Sexual dimorphism in ritualized agonistic behaviour, fighting ability and contest costs of Sus scrofa.
Sexual selection has driven sexual dimorphism in agonistic behaviour in many species. Agonistic behaviour is fundamentally altered by domestication and captivity, but it is unclear whether ancestral sex differences remain. We aimed to evaluate the effect of sex on agonistic behaviour, fighting ability and contest costs. We studied this in domestic pigs (Sus scrofa) where aggression compromises welfare, and sexual dimorphism in aggression has been inconclusively demonstrated. Behaviour and physiology of 827 male and female juvenile pigs were studied during resident-intruder tests and dyadic contests at various ages, while accounting for the relative body weight difference between the opponents. Males won in 79% of contests against females, even when at a large weight disadvantage. The effect of sex increased with age, with males having a 138 times higher likelihood of winning than females when 13 weeks old. In dyadic contests, males invested more time in non-damaging agonistic display behaviour and took longer before escalating into damaging aggression. Males showed ritualized display that included foaming from the mouth and piloerection of the neck hair, which was nearly always absent in females. Contest costs in terms of contest duration, blood lactate and skin lesions where higher for males, especially when fighting another male. Profound sex differences were present for agonistic behaviour, fighting ability and contest costs, and became more pronounced as animals got older. Males invested more in ritualized display before escalating into costly fights, whereas females attacked sooner but also terminated contests more rapidly and with fewer costs. The sexual dimorphism in agonistic behaviour in juvenile domestic pigs is in line with the evolutionary relevance for females' maternal defence and males' competition for females.


Self-Rated Executive Function and Health-Related Quality of Life in Young Adults With Persistent Post-Concussion Symptoms: A Cross-Sectional Study.
To assess self-reported executive dysfunction in young adult patients with persistent post-concussion symptoms (PCS) 2-6 months post-injury, and the association with self-reported Health-Related Quality of Life (HRQoL). This cross-sectional study carried out in a hospital setting was a secondary analysis of data from a separate randomized trial testing the effect of a novel intervention, "Get going After concussIoN " (GAIN), for persistent PCS. Patients (18-30 years) were recruited from a clinical cohort of patients with a hospital diagnosis of concussion or referred by primary care physicians. Main measures were The Behaviour Rating Inventory of Executive Function-Adult Version providing two index scores, that is, the Metacognitive Index (MI) and the Behavioural Regulation Index (BRI), and the Quality of Life after Brain Injury-Overall Scale. Compared with normative data, patients had elevated scores (i.e., worse functioning) on both the MI and the BRI. In linear regression analysis, the MI score, but not the BRI score, was negatively associated with self-reported HRQoL (MI: slope = -.27, 95% confidence interval, CI [-.53, -.02], p = .03; BRI: slope = -.19, 95% CI [-.49, .13], p = .24), suggesting a positive association of subjective executive dysfunction and lower HRQoL. However, the association was attenuated after adjustment for self-reported psychological distress (MI: slope = -.09, 95% CI [-.34, .17], p = .51). Self-reported executive dysfunction is common in young adult patients with persistent PCS, but not strongly associated with decreased HRQoL after adjusting for concurrent psychological distress.


English-as-an-Additional-Language Nursing Student Support Group: Student Leadership and Engagement.
Hermeneutic phenomenology was used to explore the perceived impact of student engagement and leadership opportunities on English-as-an-additional-language (EAL) student success. Participant interviews revealed insight into the lived experiences of EAL students completing undergraduate nursing education in a secondary language. Research findings revealed: a) the importance of student engagement and leadership opportunities, b) the influence of student engagement and leadership opportunities on mental well-being, c) accessible student engagement and leadership opportunities for EAL students, and d) future ambitions encouraged by student engagement and leadership opportunities.


Drug treatment in acute porphyria.
The acute hepatic porphyrias are rare pharmacogenetic diseases inherited as autosomal dominant conditions of low penetrance. The genetic defect is a 50% deficiency of an enzyme of the haem biosynthetic pathway. Patients may develop 'neurovisceral attacks' which include severe abdominal pain, neuropsychiatric manifestations and potentially fatal respiratory paralysis. Attacks occur generally after puberty, are much commoner in females and may be precipitated by endogenous hormonal changes, dieting, alcohol, severe infections, and many drugs. Treatment includes analgesia, early administration of haem, and general supportive measures. Patients are at greater risk of a severe attack on first presentation since an abdominal emergency may be simulated and inappropriate medication, including that for general anaesthesia may exacerbate the crisis. The urine should be tested for raised porphobilinogen, which is pathognomonic of the acute attack, if there is the slightest doubt about diagnosis. The genotype of blood relatives of index cases must be determined so that carriers may avoid drug and other precipitants. Some drugs have been established as safe or unsafe by clinical use, but information about many drugs is not available or is based only on their properties in rodents or in tissue culture systems. The relevance of these to the human condition remains controversial, but drugs shown to be porphyrinogenic in animal systems should be avoided if there is a known safe alternative. Where it is essential to use a drug not known to be safe, close biochemical and clinical observation may warn of an impending attack.


DRIFTS-based multivariate calibration and prediction of low-concentration polymorphic impurities in multiple lots of an active pharmaceutical ingredient, and outlier criteria.
Mixtures of two polymorphic impurities with one lot of the desired form of an Active Pharmaceutical Ingredient (API), mostly binary mixtures, with up to 2% wt/wt of an impurity, were used for multivariate modeling via Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectra. The two obtained cross-validated models, significantly differing in accuracy, were used to predict the concentrations of these impurities in independent API lots. The predictions were found to be biased and with outliers, as revealed by the Q residuals criterion but not the other two outlier criteria. Updating the models with the spectra from the mixtures using multiple API lots produced very different calibration results: the model of the impurity with the strong IR response became noticeably worse, while the model of the impurity with less responsive IR signal changed only marginally. The updated models performed much better in the prediction as the bias for both polymorphs was reduced and the outlier-related issues mostly disappeared.


Impact of Lay-Administered CPR on Survival Rates.
Sudden death accounts for between 20%-25% of all "new" coronary events. Until prevention is better understood, the best and most effective treatment is the rapid provision of resuscitative measures which "buy time" until definitive care can be provided. Factors positively associated with length of survival are: age, time from collapse to CPR; and time from collapse to CPR, combined with time to definitive care. Preliminary reports on the functional status of survivors are also promising. Canadians should readdress CPR as a vital factor influencing out-of-hospital cardiac arrest survival rates and necessitating administration by lay persons.


Isotope-exchange enhancement studies of Escherichia coli glutamine synthetase.
Isotope-exchange enhancement studies, a variation on positional isotope-exchange enhancement as described by Raushel and Garrard [Raushel, F. M., & Garrard, L. J. (1984) Biochemistry 23, 1791-1795], are used to establish the point in the biosynthetic reaction of Escherichia coli glutamine synthetase at which gamma-glutamyl phosphate is formed. In these experiments, the behavior of the reverse biosynthetic reaction, i.e., the reaction of ADP, L-glutamine, and phosphate to form NH4+, L-glutamate, and ATP, is examined as a function of the concentration of ammonium ion. By varying the concentration of NH4+, the ratio of the velocity of isotope exchange to the velocity of net reaction, as measured by the rate of 18O depletion from labeled phosphate and the rate of production of L-glutamate, respectively, can be modulated in a mechanism-dependent manner. Evidence is presented demonstrating the presence of a branch point in the mechanism. The enzyme-ATP-glutamate complex may partition in two ways, one involving binding of ammonium ion and the other involving the chemical transformation to form the enzyme-ADP-gamma-glutamyl phosphate complex. The alternate pathways then rejoin upon formation of the enzyme-ADP-NH4+-gamma-glutamyl phosphate complex. Because of the branch point, there is no absolute requirement that ammonium ion be absent or present in order for the formation of gamma-glutamyl phosphate to occur. At high concentrations of ammonia, one pathway through the branch can be eliminated, effectively making that portion of the pathway ordered, with ATP, L-glutamate, and NH4+ binding consistent with our previously reported steady-state kinetic mechanism [Meek, T. D., & Villafranca, J. J. (1980) Biochemistry 19, 5513-5519].


Impact of the prolactin levels in breast cancer: a systematic review and meta-analysis.
Prolactin (PRL) acts stimulating the mammary glands development, and its deregulation has been associated to the emergence of several types of tumors, including breast cancer. Breast cancer represents the most prevalent malignancy in women, and the second cause of death in several countries. This tumor can be arise due to several molecular alterations, among them PRL has been the object of increasing interest from researchers worldwide. To assess the association between elevated levels of plasma prolactin and breast cancer development. A total of 158 studies were found in search databases (48 from PubMed, 69 from Scopus, 88 from Cochrane, 25 from Embase and 10 retrieved from the gray literature) after removing duplicates. Of these, 104 studies were excluded after title and abstract reading, and 54 studies were then read in full, of which only 14 were selected for this review because they had evaluated the association between PRL and breast cancer. Meta-analysis was carried out using the relative risk (RR), mean and standard deviation, confidence interval (95% CI), and the total number of patients for each study. Fixed- and random-effect models were used as applicable and, for the analysis. The meta-analysis showed a positive association between elevated levels of PRL and breast cancer occurrence (RR 1.26; 95%CI 1.15-1.37). Additionally, the patient sub-group analyses showed a positive association between PRL and invasive breast cancer (1.42; 1.24-1.60), ER+/PR+ (1.49; 1.23-1.75), and post-menopausal status (1.29; 1.16-1.43). The results showed a positive association between plasma prolactin levels and breast cancer, especially in women with ER+/PR + tumors, of post-menopausal age and those with invasive cancer.


The association of human papillomavirus type 16 E6 and E7 antibodies with stage of cervical cancer.
Previous investigators have reported higher HPV type 16 antibody positivity among cervical cancer patients than among healthy women. The objective of this study was to determine the association of HPV 16 antibody levels with the stage of cervical cancer. Pretreatment tumor biopsies and sera were obtained from 137 newly diagnosed cervical cancer patients residing in Mexico. Using peptide ELISA and radioimmunoprecipitation assay (RIPA), HPV 16 E6- and E7-specific antibodies were measured. By ELISA, elevated antibody titers to HPV 16 E6 and E7 were detected in 16.8 and 32.8% of the women, respectively. While sera positivity did not differ by disease stage, the mean absorbance in the E7-positive sera was 0.42, 0.62, 0.91, and 0.81 for stages I to IV, respectively. Using RIPA, anti-E6 and E7 positivity was demonstrated in 46.7 and 38.7% of the females, respectively. Although no difference across disease stage was detected for E6, increasing proportions of positivity to E7 with stage of disease was detected. The rates for increasing disease stage were 0.14, 0.37, 0.40, and 0.67. Sera from the 6-month postradiation follow-up examinations of a small group of patients demonstrated a statistically significant decrease in antibody positivity from pretreatment positivity to HPV 16 E6 (n = 14; P = 0.01) and HPV 16 E7 (n = 20; P = 0.0001) using ELISA. These data suggest that HPV 16 E7 antibody positivity may be associated with stage of cervical cancer. Such immune parameters may be applicable to disease staging, monitoring of recurrence and, perhaps, diagnosis. Further investigation into the relationship of HPV 16 E6 and E7 antibodies with stage of cervical cancer and response to therapy is warranted.


The thalamic low-threshold Ca²⁺ potential: a key determinant of the local and global dynamics of the slow (<1 Hz) sleep oscillation in thalamocortical networks.
During non-rapid eye movement sleep and certain types of anaesthesia, neurons in the neocortex and thalamus exhibit a distinctive slow (<1 Hz) oscillation that consists of alternating UP and DOWN membrane potential states and which correlates with a pronounced slow (<1 Hz) rhythm in the electroencephalogram. While several studies have claimed that the slow oscillation is generated exclusively in neocortical networks and then transmitted to other brain areas, substantial evidence exists to suggest that the full expression of the slow oscillation in an intact thalamocortical (TC) network requires the balanced interaction of oscillator systems in both the neocortex and thalamus. Within such a scenario, we have previously argued that the powerful low-threshold Ca(2+) potential (LTCP)-mediated burst of action potentials that initiates the UP states in individual TC neurons may be a vital signal for instigating UP states in related cortical areas. To investigate these issues we constructed a computational model of the TC network which encompasses the important known aspects of the slow oscillation that have been garnered from earlier in vivo and in vitro experiments. Using this model we confirm that the overall expression of the slow oscillation is intricately reliant on intact connections between the thalamus and the cortex. In particular, we demonstrate that UP state-related LTCP-mediated bursts in TC neurons are proficient in triggering synchronous UP states in cortical networks, thereby bringing about a synchronous slow oscillation in the whole network. The importance of LTCP-mediated action potential bursts in the slow oscillation is also underlined by the observation that their associated dendritic Ca(2+) signals are the only ones that inform corticothalamic synapses of the TC neuron output, since they, but not those elicited by tonic action potential firing, reach the distal dendritic sites where these synapses are located.


Patient Attitudes Toward Transplantation as Preferred Treatment Modality in Different Stages of Renal Disease.
Kidney transplantation is generally considered to be the best treatment for end-stage renal disease. Not every patient can be operated, but many of suitable patients refuse this possibility. We aimed to explore the attitudes of patients with chronic kidney disease towards renal replacement therapies to recognize motives, thoughts, and feelings concerning accepting or refusing the treatment. We studied the attitudes towards the illness and the treatment, the appearance of depression, and the disease burden during different stages of the disease. For this study we implemented a questionnaire that we developed (which has been described in an earlier publication of this journal) with 99 pre-dialysis patients, 99 dialysis patients, and 87 transplantation patients. We completed the attitude questionnaire designed by our team to include disease burden and depression questionnaires. We used discriminant analysis to describe different stages of the disease. There was a significant difference in the following factors between the three patient groups: accepting the new kidney, lack of confidence in transplantation therapy, fear of surgery, accepting self-responsibility in recovery, dependency on the transplanted kidney, confidence in recovery, subjective burden of dialysis, and denial of personal responsibility in maintaining the transplanted kidney. Significant differences were also detected in these three groups regarding the level of depression and disease burden: we measured the highest value among the dialysis patients, and the lowest value among the pre-dialysis patients. Comparing patients accepting and refusing transplantation, we found a correlation between the refusal of transplantation and the attitudes towards the illness and treatment. Most patients remain unmotivated to change treatment modality and refuse transplantation. Misbelief about transplantation shows a correlation with the motive of refusal. Dissemination of information may facilitate a change in the situation.


Magnetic fields (MF) of 50 Hz at 1.2 microT as well as 100 microT cause uncoupling of inhibitory pathways of adenylyl cyclase mediated by melatonin 1a receptor in MF-sensitive MCF-7 cells.
Magnetic fields (MF) of 60 Hz at 1.2 microT were previously shown to inhibit the antiproliferative effect of melatonin on MCF-7 cells (Liburdy,R.P., 1993, J. Pimeal Res. 14, 89-97). In addition, three laboratories (Blackman,C.F. and Benane,S.G., 1998; Luben,R.A. and Morgan,A.P., 1998; Morris,J.E., Chrisler,W.B., Miller,D.L., Sasser,L.B. and Anderson,L.E., 1998; 20th Annual Meeting of the Bioelectromagnetics Society, At. Pete Beach, FL) independently reported results consistent with this finding. In this study, we investigated the molecular basis of the biological effects of MF using MCF-7 cells. Only 1a melatonin receptors were identified by the [125I]melatonin binding assay and RT-PCR analysis. Moreover, preceding exposures to MF of 100 microT for 3, 5 and 7 days blocked the melatonin-induced inhibition of cAMP accumulation in a time-dependent manner, while none of the melatonin receptor functions or GTPase and adenylyl cyclase activities were affected. Estrogen-evoked cell proliferation was not altered by MF either. Exposure to 1.2 microT MF exerted the same effects on the melatonin-signaling pathway as that to 100 microT. Thus, this is the first study to provide evidence that MF may cause uncoupling of signal transduction from melatonin receptors to adenylyl cyclase.


The N-terminal transmembrane domain (TMD0) and a cytosolic linker (L0) of sulphonylurea receptor define the unique intrinsic gating of KATP channels.
ATP-sensitive potassium (K(ATP)) channels comprise four pore-forming Kir6 and four regulatory sulphonylurea receptor (SUR) subunits. SUR, an ATP-binding cassette protein, associates with Kir6 through its N-terminal transmembrane domain (TMD0). TMD0 connects to the core domain of SUR through a cytosolic linker (L0). The intrinsic gating of Kir6.2 is greatly altered by SUR. It has been hypothesized that these changes are conferred by TMD0. Exploiting the fact that the pancreatic (SUR1/Kir6.2) and the cardiac (SUR2A/Kir6.2) K(ATP) channels show different gating behaviours, we have tested this hypothesis by comparing the intrinsic gating of Kir6.2 with the last 26 residues deleted (Kir6.2Delta26) co-expressed with SUR1, S1-TMD0, SUR2A and S2-TMD0 at -40 and -100 mV (S is an abbreviation for SUR; TMD0/Kir6.2Delta26, but not TMD0/Kir6.2, can exit the endoplastic reticulum and reach the cell membrane). Single-channel kinetic analyses revealed that the mean burst and interburst durations are shorter for TMD0/Kir6.2Delta26 than for the corresponding SUR channels. No differences were found between the two TMD0 channels. We further demonstrated that in isolation even TMD0-L0 (SUR truncated after L0) cannot confer the wild-type intrinsic gating to Kir6.2Delta26 and that swapping L0 (SUR truncated after L0)between SUR1 and SUR2A only partially exchanges their different intrinsic gating. Therefore, in addition to TMD0, L0 and the core domain also participate in determining the intrinsic gating of Kir6.2. However, TMD0 and L0 are responsible for the different gating patterns of full-length SUR1 and SUR2A channels. A kinetic model with one open and four closed states is presented to explain our results in a mechanistic context.


Dopamine regulates cell cycle regulatory proteins via cAMP, Ca(2+)/PKC, MAPKs, and NF-kappaB in mouse embryonic stem cells.
This study examined the effect of dopamine on DNA synthesis and its related signal cascades in mouse embryonic stem (ES) cells. Dopamine inhibited DNA synthesis in both a dose- and time-dependent manner. Dopamine, SKF 38393 (D1 receptor agonist), and quinpirole (D2 receptor agonist) decreased the level of [(3)H]-thymidine incorporation. The level of cyclic adenosine 3, 5-monophosphate (cAMP) was increased by SKF 38393 but not by quinpirole. The protein kinase C (PKC) protein was translocated from the cytosolic fraction to the membrane compartment by dopamine. Dopamine also increased [Ca(2+)](i), which was blocked by EGTA (an extracellular Ca(2+) chelator), BAPTA-AM (an intracellular Ca(2+) chelator), nifedipine (a L-type Ca(2+) channel blocker), SQ 22536 [an adenylyl cyclase (AC) inhibitor] and neomycin [a phospholipase C (PLC) inhibitor]. Dopamine, SKF 38393, and quinpirole increased the level of p44/42 mitogen-activated protein kinases (MAPKs), p38 MAPK, and stress-activated protein kinase/Jun-N-terminal kinase (SAPK/JNK) phosphorylation. Dopamine also increased level of H(2)O(2) formation and activated the transcription factor family NF-kappaB. Moreover, SKF 38393, quinpirole, and dopamine inhibited cell cycle regulatory proteins, which is consistent with the change in the level of [(3)H]-thymidine incorporation observed. The dopamine-induced decrease in cyclin E, cyclin-dependent protein kinase-2 (CDK-2), and cyclin D1, CDK-4 were blocked by pertussis toxin (G protein inhibitor), SQ 22536, neomycin, bisindolylmaleimide I (PKC inhibitor), SB 203580 (p38 MAPK inhibitor), PD 98059 (p44/42 inhibitor), and SP 600125 (SAPK/JNK inhibitor). In conclusion, dopamine inhibits DNA synthesis in mouse ES cells via the cAMP, Ca(2+)/PKC, MAPKs, and NF-kappaB signaling pathways.


Zbtb20 deficiency causes cardiac contractile dysfunction in mice.
The zinc-finger protein ZBTB20 regulates development and metabolism in multiple systems, and is essential for postnatal survival in mice. However, its potential role in the cardiovascular system remains undefined. Here, we demonstrate that ZBTB20 is critically involved in the regulation of cardiac contractility and blood pressure in mice. At the age of 16 days, the relatively healthy Zbtb20-null mice exhibited hypotension without obvious change of heart rate or other evidence for heart failure. Moreover, Zbtb20 deletion led to a marked reduction in heart size, left ventricular wall thickness, and cell size of cardiomyocytes, which was largely proportional to the decreased body growth. Notably, echocardiographic and hemodynamic analyses showed that cardiac contractility was greatly impaired in the absence of ZBTB20. Mechanistically, ZBTB20 deficiency decreased cardiac ATP contents, and compromised the enzyme activity of mitochondrial complex I in heart as well as L-type calcium current density in cardiomyocytes. Furthermore, the developmental activation of some mitochondrial function-related genes was significantly attenuated in Zbtb20-null myocardium, which included Hspb8, Ckmt2, Cox7a1, Tfrc, and Ogdhl. Put together, these results suggest that ZBTB20 plays a crucial role in the regulation of heart development, energy metabolism, and contractility.


Property tax and inter-municipal migration in Canada: a multivariate test of the Tiebout hypothesis.
"This paper tests the causal ordering between property taxes and inter-municipal migration, using both bivariate and multivariate methods. Empirical results, based on annual data for post-war Canada (1940-84), support the Tiebout-Tullock hypothesis, which implies that differential local tax [systems] and public services induce intercommunity migration, inter alia. Local spending and taxation are not therefore fully capitalized in property values."


Two-photon absorption in three-dimensional chromophores based on [2.2]-paracyclophane.
A series of alpha,omega-bis donor substituted oligophenylenevinylene dimers held together by the [2.2]paracyclophane core were synthesized to probe how the number of repeat units and through-space delocalization influence two-photon absorption cross sections. Specifically, the paracyclophane molecules are tetra(4,7,12,15)-(4'-dihexylaminostyryl)[2.2]paracyclophane (3R(D)), tetra(4,7,12,15)-(4' '-(4'-dihexylaminostyryl)styryl)[2.2]paracyclophane (5R(D)), and tetra(4,7,12,15)-(4' "-(4' '-(4'-dihexylaminostyryl)styryl)styryl)[2.2]paracyclophane (7R(D)). The compounds bis(1,4)-(4'-dihexylaminostyryl)benzene (3R) and bis(1,4)-(4' '-(4'-dihexylaminostyryl)styryl)benzene (5R) were also synthesized to reveal the properties of the "monomeric" counterparts. The two-photon absorption cross sections were determined by the two-photon induced fluorescence method using both femtosecond and nanosecond pulsed lasers as excitation sources. While there is a red shift in the linear absorption spectra when going from the "monomer" chromophore to the paracyclophane "dimer" (i.e., 3R --> 3R(D), 5R --> 5R(D)), there is no shift in the two-photon absorption maxima. A theoretical treatment of these trends and the dependence of transition dipole moments on molecular structure rely on calculations that interfaced time-dependent density functional theory (TDDFT) techniques with the collective electronic oscillator (CEO) program. These theoretical and experimental results indicate that intermolecular interactions can strongly affect B(u) states but weakly perturb A(g) states, due to the small dipole-dipole coupling between A(g) states on the chromophores in the dimer.


Predictors of dropout in an outpatient treatment for problem drinkers including cognitive-behavioral therapy and the opioid antagonist naltrexone.
This study investigated predictors of dropout in an outpatient treatment program for problem drinking that included individual cognitive-behavioral therapy combined with naltrexone. Specifically, we investigated whether sociodemographic factors, severity of alcohol dependence, history of problem drinking, or intensity of alcohol craving assessed at the beginning of the treatment predicted dropout from an outpatient program among a sample of 372 patients (65% male). We also investigated whether the effectiveness of the treatment (the change in alcohol consumption and symptoms of alcohol craving) or adherence to naltrexone was related to dropout. Predictors of dropout were investigated using an analysis of covariance with the number of attended treatment sessions as an independent variable. Our results demonstrated that the treatment entry factors predictive of dropout were younger age, lower severity of alcohol dependence, better ability to resist and control alcohol use, and lower obsession with alcohol. In addition, those who dropped out were more likely to begin the program by abstaining from alcohol and had lower adherence to naltrexone use than those who completed the program. The length of stay for treatment was not related to change in alcohol consumption. Patients with less severe alcohol-related problems may lack motivation for treatment, specifically cognitive-behavioral therapy and naltrexone. These patients may benefit more from less intensive treatments.


Scanning Auger Microscopy Studies of Silane Films Grown on Plasma-Modified HOPG Surfaces.
The growth of silane films on plasma oxidized highly oriented pyrolytic graphite (HOPG) surfaces has been studied using wet chemical deposition of propyltrimethoxysilane (PTMS) and propyldimethylmethoxysilane (PDMMS). Scanning Auger microscopy (SAM) and X-ray photoelectron spectroscopy (XPS) were used to investigate the chemical composition and morphology of the silane films. The effects of several deposition parameters were examined, including the necessity of oxidation of the HOPG surface, addition of water with the silane, and rinsing before curing. The optimal conditions needed to create a complete uniform film differ for the two silanes due to differences in their structures. Both silanes require an oxidized HOPG surface for a film to grow, the addition of water with PTMS results in a thicker film, while the addition of water with PDMMS decreases the film growth. Rinsing of both samples before curing removes physisorbed species, leaving only the covalently bonded film on the surface.


A nitrogen-doped graphene/carbon nanotube nanocomposite with synergistically enhanced electrochemical activity.
A new kind of nitrogen-doped graphene/carbon nanotube nanocomposite can be synthesized by a facile hydrothermal process under mild conditions, which exhibits synergistically enhanced electrochemical activity for the oxygen reduction reaction. This research provides a new route to access a metal-free electrocatalyst with high activity under mild conditions.


Mg doping affects dislocation core structures in GaN.
Aberration-corrected scanning transmission electron microscopy was used to investigate the core structures of threading dislocations in undoped GaN films with both high and low dislocation densities, and in a comparable high dislocation density Mg-doped GaN film. All a-type dislocations in all samples have a 5/7-atom core structure. In contrast, most (a+c)-type dislocations in undoped GaN dissociate due to local strain variations from nearby dislocations. In contrast, Mg doping prevents (a+c)-type dislocation dissociation. Our data indicate that Mg affects dislocation cores in GaN significantly.


Identification of F-box only protein 7 as a negative regulator of NF-kappaB signalling.
The nuclear factor κB (NF-κB) signalling pathway controls important cellular events such as cell proliferation, differentiation, apoptosis and immune responses. Pathway activation occurs rapidly upon TNFα stimulation and is highly dependent on ubiquitination events. Using cytoplasmic to nuclear translocation of the NF-κB transcription factor family member p65 as a read-out, we screened a synthetic siRNA library targeting enzymes involved in ubiquitin conjugation and de-conjugation for modifiers of regulatory ubiquitination events in NF-κB signalling. We identified F-box protein only 7 (FBXO7), a component of Skp, Cullin, F-box (SCF)-ubiquitin ligase complexes, as a negative regulator of NF-κB signalling. F-box protein only 7 binds to, and mediates ubiquitin conjugation to cIAP1 and TRAF2, resulting in decreased RIP1 ubiquitination and lowered NF-κB signalling activity.


The ColE1 unidirectional origin acts as a polar replication fork pausing site.
Co-orientation of replication origins is the most common organization found in nature for multimeric plasmids. Streptococcus pyogenes broad-host-range plasmid pSM19035 and Escherichia coli pPI21 are among the exceptions. pPI21, which is a derivative of pSM19035 and pBR322, has two long inverted repeats, each one containing a potentially active ColE1 unidirectional origin. Analysis of pPI21 replication intermediates (RIs) by two-dimensional agarose gel electrophoresis and electron microscopy revealed the accumulation of a specific RI containing a single internal bubble. The data obtained demonstrated that initiation of DNA replication occurred at a single origin in pPI21. Progression of the replicating fork initiated at either of the two potential origins was transiently stalled at the other inversely oriented silent ColE1 origin of the plasmid. The accumulated RIs, containing an internal bubble, occurred as a series of stereoisomers with different numbers of knots in their replicated portion. These observations provide one of the first functional explanations for the disadvantage of head-to-head plasmid multimers with respect to head-to-tail ones.


Primary dental care: time to revise the definition?
There have been several definitions of primary dental care over the last 20 years and while each was written to reflect the requirements of the time, most provide a conflicting description. This paper examines past definitions of primary dental care in the context of recent developments in UK dentistry and critically describes possible new definitions.


[A preliminary study on the mechanism of against human tongue cancer cell line].
Inverted phase contrast microscope and transmission electron microscope examination reveals that, tumor-draining lymphnode lymphocytes (DNL) conjugated with tumor cells very tightly at 12 hours co-culture. The DNL cell nucleus was seen positioned away from the target cells, whereas the cell mitochondria granules were oriented toward the point of contact with the target cells. The injured target cell had a highly condensed cytoplasm and chromatin and formation of cytoplasmic blebs, which were consistent with an apoptotic cell death rather than with a lytic or necrotic cell death. The mechanism was exocytosis of granules containing a pore-forming protein. Holes formed in the target cell's membrane may allow a lethal substance to enter and to induce its death via an apoptotic mechanism.


Advancing interprofessional education through the use of high fidelity human patient simulators.
Modern medical care increasingly requires coordinated teamwork and communication between healthcare professionals of different disciplines. Unfortunately, healthcare professional students are rarely afforded the opportunity to learn effective methods of interprofessional (IP) communication and teamwork strategies during their education. The question of how to best incorporate IP interactions in the curricula of the schools of health professions remains unanswered. We aim to solve the lack of IP education in the pharmacy curricula through the use of high fidelity simulation (HFS) to allow teams of medical, pharmacy, nursing, physician assistant, and social work students to work together in a controlled environment to solve cases of complex medical and social issues. Once weekly for a 4-week time period, students worked together to complete complex simulation scenarios in small IP teams consisting of pharmacy, medical, nursing, social work, and physician assistant students. Student perception of the use of HFS was evaluated by a survey given at the conclusion of the HFS sessions. Team communication was evaluated through the use of Communication and Teamwork Skills (CATS) Assessment by 2 independent evaluators external to the project. The CATS scores improved from the HFS sessions 1 to 2 (p = 0.01), 2 to 3 (p = 0.035), and overall from 1 to 4 (p = 0.001). The inter-rater reliability between evaluators was high (0.85, 95% CI 0.71, 0.99). Students perceived the HFS improved: their ability to communicate with other professionals (median =4); confidence in patient care in an IP team (median=4). It also stimulated student interest in IP work (median=4.5), and was an efficient use of student time (median=4.5). The use of HFS improved student teamwork and communication and was an accepted teaching modality. This method of exposing students of the health sciences to IP care should be incorporated throughout the curricula.


Antibiotic susceptibility pattern of nosocomial isolates of staphylococcus aureus in a tertiary care hospital, Nepal.
Methicillin resistant Staphylococcus aureus (MRSA), the most common cause of nosocomial infection has been a major cause of morbidity and mortality around the world. They are normally resistant to most of the antibiotics used in clinical practice. This study has been carried out to find out the resistance pattern among S. aureus. During November 2007 to June 2008, clinical samples from patients with nosocomial infection were processed for culture and sensitivity following standard methodology in microbiology laboratory, Tribhuvan University teaching hospital, Kathmandu, Nepal. Among 149 Staphylococcus aureus isolates, highest resistance was observed against Penicillin (91.94%) followed by Fluoroquinolone (61.74%), Erythromycin (52.94%), Gentamicin (46.98%), Cotrimoxazole (42.95%), Tetracycline (40.94%) and others, whereas susceptibility was observed maximum against Chloramphenicol (94.85%) followed by Rifampicin (92.61%), Tetracycline (59.06%), Cotrimoxazole (57.04%), and others. None of the isolates were resistant to Vancomycin and Teicoplanin. Of these isolates 44.96 % of the isolates were Methicillin resistant S. aureus (MRSA). Resistance to Penicillin, Fluoroquinolone, Erythromycin, Gentamicin, Co-trimoxazole and Tetracycline were associated significantly with MRSA isolates (chi2= 8.779, p<0.05, chi2= 74.233, p<0.05, chi2= 84.2842, p<0.05, chi2= 108.2032, p<0.05, chi2= 88.1512, p<0.05 and chi2= 79.1876, p<0.05 respectively). Although most of the Methicillin sensitive S. aureus (MSSA) isolates were susceptible to both Rifampicin and Chloramphenicol, only Rifampicin susceptibility was significantly associated with them (chi2= 10.1299, p<0.05). Among three Biochemical tests for the detection of beta lactamase detection namely chromogenic, iodometric and acidimetric test, chromogenic test method had highest sensitivity and specificity. Since MRSA comprised a greater part of S. aureus isolates and were multi-resistant, patients infected by such strains should be identified and kept in isolation for hospital infection control and treated with second line of drug like vancomycin.


Yeasts in the Sugiyamaella clade associated with wood-ingesting beetles and the proposal of Candida bullrunensis sp. nov.
During a survey of yeasts associated with wood-ingesting insects, six strains of the Sugiyamaella clade were isolated from the gut of passalid and tenebrionid beetles and the decayed wood inhabited by them. Phylogeny based on rRNA gene sequences placed these yeasts as members of Sugiyamaella smithiae, Sugiyamaella americana, Candida lignohabitans and a novel species closely related to Su. americana. The only strain of the novel species, EH008(T), could be unquestionably distinguished from its relatives by DNA sequences and other taxonomic characteristics. Ascospore production was not observed under the laboratory conditions tested. Therefore, this novel species is proposed as Candida bullrunensis sp. nov. (type strain EH008(T) = ATCC MYA-4660(T) = CBS 11840(T)).


Dynamic expression of neurotrophic factor receptors in postnatal spinal motoneurons and in mouse model of ALS.
Neurotrophic factors support the survival of spinal motoneurons (MNs) and have been considered as strong candidates for treating motoneuron diseases. However, it is unclear if the right combination of neurotrophic factor receptors is present in postnatal spinal MNs. In this study, we show that the level of c-ret expression remains relatively stable in embryonic and postnatal spinal MNs. In contrast, the mRNA and protein of GFRalpha1 and -2 are progressively down-regulated in postnatal life. By 3 and 6 months of age, both receptors are barely detectable in spinal MNs. The down-regulation of GFRalpha1 appears accelerated in transgenic mice expressing mutant SOD1(G93A). Despite the progressive loss of GFRalpha1 and -2, phosphorylation of c-ret shows no detectable reduction on tyrosine residues or on serine 696. In addition to the GFRalpha subunits, expression of TrkB also shows a dynamic change. During embryogenesis, there is twice as much full-length TrkB as the truncated TrkB isoform. However, this ratio is reversed in postnatal spinal cord. Expression of the mutant SOD1(G93A) appears to have no effect on the TrkB receptor ratio. Taken together, our data indicate that the expression of neurotrophic factor receptors, GFRalpha1, -2, and TrkB, is not static, but undergoes dynamic changes in postnatal spinal MNs. These results provide insights into the use of neurotrophic factors as therapeutic agents for ALS.


Helicobacter pylori infection and the prevention of peptic ulcer with proton pump inhibitors in elderly subjects taking low-dose aspirin.
The role of Helicobacter pylori infection on the risk of low-dose aspirin-related gastroduodenal damage and on the efficacy of the prevention therapy in elderly chronic users of low-dose aspirin is still controversial. To evaluate in symptomatic elderly chronic users of low-dose aspirin: (1) the association between H. pylori infection and the prevalence of upper gastrointestinal lesions; and (2) the effect of H. pylori infection on the efficacy of proton pump inhibitors in the prevention of aspirin-related gastroduodenal lesions. Two hundred and forty-five symptomatic elderly who were taking aspirin 75-300 mg daily, at least during the last 3 months, were evaluated by endoscopy. A structured interview was carried out to evaluate gastrointestinal symptoms and the use of proton pump inhibitors. H. pylori infection was diagnosed according to histology and the rapid urease test on gastric biopsies. One hundred and twelve patients were H. pylori-positive and 133 patients were H. pylori-negative. A significantly higher prevalence of peptic ulcers was observed in H. pylori-positive than in H. pylori-negative subjects (36.6% versus 15.8%, P = 0.0002). The use of proton pump inhibitors was associated with a significant decreased risk of peptic ulcer both in H. pylori-positive (absolute risk reduction, ARR = -36.2, 95% confidence interval: -51.2 to -21.3, P < 0.001) and H. pylori-negative patients (ARR = -12.6, 95% confidence interval: -23.9 to -1.2, P = 0.03). However, the number of patients who needed to be treated in order to gain a reduction of one peptic ulcer (number needed to treat, NnT) was lower in H. pylori-positive than in H. pylori-negative patients (NnT = 3 versus 8). In symptomatic elderly chronic users of low-dose aspirin, H. pylori infection may influence the prevalence of peptic ulcers and the cost-effectiveness of the proton pump inhibitor prevention therapy.


Liquid nebulization: emerging technologies conference summary.
Most physicians and respiratory therapists are knowledgeable of the use of aerosolized drugs, but many are less familiar with the performance characteristics of the nebulizer. In fact, the general opinion is that the performance of the nebulizer is relatively unimportant. However, there is accumulating evidence that the nebulizer itself does make a difference. The decision to replace a good performing nebulizer with a poor performing nebulizer may decrease the delivered dose in half or more. Although this is less important for routine bronchodilator therapy, it may make a big difference with newer aerosolized drugs. Increasingly, the Food and Drug Administration is approving drugs to be used with a specific nebulizer brand and new nebulizer designs are becoming available for use with these drugs. There are several reasons why I think this conference was important. First, new aerosol drug formulations are becoming available and these will require better performing nebulizers. Second, we as clinicians need to be knowledgeable of the newer generations of nebulizers so that we can make informed purchase decisions. Third, and perhaps most important, we must gain an increased appreciation for aerosol therapy as a science. The proceedings of this conference do much to synthesize the current state-of-the art related to new nebulizer systems. This provides, in a complete and cogent manner, the scientific basis for which clinicians can improve their knowledge of the new generation of nebulizers.


Postoperative spirometry after laparoscopy for lower abdominal or upper abdominal surgical procedures.
In this prospective study, we have compared women undergoing laparoscopic cholecystectomy, laparoscopic gynaecological surgery and laparoscopic minor gynaecological procedures (diagnostic, tubal, ligation) (n = 10 in each group) to determine if lower abdominal laparoscopy results in less postoperative pulmonary dysfunction than upper abdominal laparoscopy. Pulmonary testing was performed before operation, and 3 and 6 h after operation, on the first and second days after surgery. After operation, a significant reduction in forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow rate occurred after laparoscopic cholecystectomy at each time. There were no significant changes after minor gynaecologic laparoscopy, whereas laparoscopic gynaecological surgery resulted in minor pulmonary dysfunction on the day of surgery only. We conclude that postoperative pulmonary function was less impaired after gynaecological laparoscopy than after laparoscopic cholecystectomy. This study suggests that the site of surgery is an important determinant of lung dysfunction after laparoscopy.


Intracellular localization of keratinocyte Fas ligand explains lack of cytolytic activity under physiological conditions.
Acquired Fas ligand (FasL)-mediated cytolytic activity of human keratinocytes causes the massive keratinocyte cell death that occurs during toxic epidermal necrolysis, a deadly adverse drug eruption. Under normal conditions keratinocyte apoptosis is a rare event in the epidermis although keratinocytes express the death receptor Fas and its ligand. Here we have investigated why this is so. We show that Fas, FasL, Fas-associated death domain, and caspase-8 mRNA are detectable in the epidermis, primary keratinocyte cultures, and keratinocyte cell line and that Fas protein is expressed in keratinocytes of all subcorneal layers of the epidermis, whereas FasL is only expressed in the basal and first suprabasal layers. Coexpression of Fas and FasL therefore occurs in basal and suprabasal keratinocytes. In vitro, keratinocytes are killed by recombinant FasL in a dose-dependent manner, but they are unable to kill Fas-sensitive target cells despite FasL expression. Analysis of keratinocyte culture supernatants and treatment of keratinocytes with metalloproteinase inhibitors excluded cell surface expression of FasL and rapid metalloproteinase-mediated cleavage of cell surface FasL. Fluorescence-activated cell sorter, confocal microscopical, and electron microscopical analysis revealed that keratinocyte FasL is localized intracellularly predominantly associated to intermediate filaments. These data suggest that the observed inability of keratinocyte FasL to induce apoptosis under physiological conditions is due to its cellular localization and also indicate that intermediate filaments may be involved in regulating the subcellular localization of FasL.


General Enhancement of Spatial Hearing in Congenitally Blind People.
Vision is thought to support the development of spatial abilities in the other senses. If this is true, how does spatial hearing develop in people lacking visual experience? We comprehensively addressed this question by investigating auditory-localization abilities in 17 congenitally blind and 17 sighted individuals using a psychophysical minimum-audible-angle task that lacked sensorimotor confounds. Participants were asked to compare the relative position of two sound sources located in central and peripheral, horizontal and vertical, or frontal and rear spaces. We observed unequivocal enhancement of spatial-hearing abilities in congenitally blind people, irrespective of the field of space that was assessed. Our results conclusively demonstrate that visual experience is not a prerequisite for developing optimal spatial-hearing abilities and that, in striking contrast, the lack of vision leads to a general enhancement of auditory-spatial skills.


Behavioral characterization of wild derived male mice (Mus musculus musculus) of the PWD/Ph inbred strain: high exploration compared to C57BL/6J.
PWD/Ph is an inbred mouse strain derived from wild mice trapped in central Czech Republic. These mice are of the Mus musculus musculus subspecies, whose ancestors separated from those of Mus musculus domesticus about one million years ago. There is a high degree of variation in the genomic sequence and a wide range of phenotypes between PWD/Ph and standard laboratory inbred mouse strains, the genomes of which are principally Mus musculus domesticus in origin, making PWD/Ph mice an useful resource for complex trait research. As a first step in taking advantage of this resource, a preliminary characterization of the behavior of PWD/Ph mice was performed. Groups of 10 PWD/Ph and C57BL/6J male mice were tested in the open field, novel object exploration task and Morris water maze. PWD/Ph were marginally more anxious than C57BL/6J mice in the open field but subsequently displayed much higher levels of exploration and lower anxiety than C57BL/6J mice following introduction of a novel object. As C57BL/6J itself is rated as highly explorative among classical inbred strains, PWD/Ph probably represents an extreme among mouse strains for this specific behavior. PWD/Ph and C57BL/6J mice differed in their water escape training profiles in the Morris water maze, perhaps reflecting different motivational factors. However, there were no differences in overall cognitive ability (spatial learning) as both groups learned to find the hidden platform and performed equally well when the location of the platform was changed. This is the first quantification of the behavior of PWD/Ph mice and the results are promising for the potential of the consomic panel currently being generated with PWD/Ph and C57BL/6J as a tool for the molecular dissection of behavior.


Updating hippocampal representations: CA2 joins the circuit.
The hippocampus integrates the encoding, storage and recall of memories, binding the spatio-temporal and sensory information that constitutes experience and keeping episodes in their correct context. The rapid and accurate processing of such daunting volumes of continuously changing data relies on dynamically assigning different aspects of mnemonic processing to specialized, interconnected networks corresponding to the anatomical subfields of dentate gyrus (DG), CA3 and CA1. However, differentially processed information ultimately has to be reintegrated into conjunctive representations, and this is unlikely to be achieved by unidirectional, sequential steps through a DG-CA3-CA1 loop. In this Review, we highlight recently discovered anatomical and physiological features that are likely to necessitate updates to the hippocampal circuit diagram, particularly by incorporating the oft-neglected CA2 region.


Neuronal post-stroke plasticity in the adult.
Contrary to what previously believed, recent research advances have demonstrated that the adult brain has a certain capacity for plastic reorganization and self-repair after a lesion such as cerebrovascular accidents. The mechanisms subtending post-stroke recovery are probably complex and operating at different levels, from molecular to synaptic to anatomical reorganization. The integrated use of functional neuroimaging techniques, by overcoming the limitations of each specific methodology is likely to shed much light on plasticity mechanisms. In this review we discuss the neuroanatomy and neurophysiology possibly underlying reorganization of the central nervous system, as well as the experimental evidence of "in vivo" post-stroke plasticity. Better understanding of these mechanisms can provide neurorehabilitation with powerful tools in designing and implementing new therapeutic approaches to stroke patients both in the acute and the chronic stages after a brain tissue lesion has occurred and stabilized.


End-to-side anastomosis in complex tracheal resection and reconstruction: a case series study.
The development of current anesthetic and surgical techniques has increased the success rate of complex tracheal resection and reconstruction. End-to-end anastomosis is the prevailing method, while the end-to-side approach has also been reported to be practical and suitable. The current study aimed to demonstrate the feasibility and advantages of the end-to-side anastomosis method in specific cases. We summarized 6 cases of patients with tracheobronchial tumors who received different end-to-side airway reconstructions in our center. Their clinical features and surgical procedures were also described. Postoperative follow-up was conducted to monitor their complications and prognosis. Among the patients involved in the study, 2 patients with tumors involving the bronchus intermedius received auto-lung transplantations under general anesthesia, 3 patients with tumors involving the lower trachea and carina underwent reconstruction under non-intubated combined anesthesia, and 1 patient with left main bronchus (LMB) involvement received surgery under venoarterial extracorporeal membrane oxygenation (VA ECMO)-supported non-intubated anesthesia. The surgical procedures were completed successfully without surgical or anesthetic incidents. Patients 1 and 2 underwent auto-lung transplantation with distal stumps and trachea end-to-side anastomosis (right lower lobe and right basal segment). Patients 3 and 4 received right main bronchus (RMB) to lateral trachea reconstruction, while Patients 5 and 6 underwent LMB to tracheal wall anastomosis. Anastomotic buttressing was performed using the thymus and mediastinal tissue. The patients were discharged within 2 weeks of the operation. No severe postoperative complications were reported, with the exception of Patient 5, who required a prolonged intensive care unit (ICU) stay with antibiotics due to pneumonia. Anastomotic necrosis, dehiscence, or stenosis were not observed in the postoperative bronchoscopy. End-to-side anastomosis is a feasible and effective surgical method in airway reconstructions. This method facilitates tension-free anastomosis, which is crucial for surgical prognosis and decreasing complications. The reported cases had ideal surgical results during follow-up. The long-term outcomes of the end-to-side method require further evaluation.


Fault Diagnosis of Permanent Magnet DC Motors Based on Multi-Segment Feature Extraction.
For permanent magnet DC motors (PMDCMs), the amplitude of the current signals gradually decreases after the motor starts. Only using the signal features of current in a single segment is not conducive to fault diagnosis for PMDCMs. In this work, multi-segment feature extraction is presented for improving the effect of fault diagnosis of PMDCMs. Additionally, a support vector machine (SVM), a classification and regression tree (CART), and the k-nearest neighbor algorithm (k-NN) are utilized for the construction of fault diagnosis models. The time domain features extracted from several successive segments of current signals make up a feature vector, which is adopted for fault diagnosis of PMDCMs. Experimental results show that multi-segment features have a better diagnostic effect than single-segment features; the average accuracy of fault diagnosis improves by 19.88%. This paper lays the foundation of fault diagnosis for PMDCMs through multi-segment feature extraction and provides a novel method for feature extraction.


Distribution of incorporated, synthetic cytokinins in ribosomal RNA preparations from tobacco callus.
The distribution of incorporated synthetic cytokinins (N(6)-[8-(14)C]benzyladenine ([8-(14)C]bzl(6)Ade) and N(6)[8-(14)C]furfuryladenine ([8-(14)C]fr(6)Ade) in ribosomal RNA prepared from tobacco callus (Nicotiana tabacum L. var. Wis. No. 38) grown in the presence of one of these for 25 or 26 days has been studied. The rRNA of tissue supplied with [8-(14)C]bzl(6)Ade or [8-(14)C]fr(6)Ade was fractionated by methylated albumin-Kieselguhr column chromatography and preparative gel electrophoresis, respectively. In each case about 80% of the incorporated cytokinin was recovered as the ribonucleoside [8-(14)C]bzl(6)A or [8-(14)C]fr(6)A in the rRNA peak after the fractionations. [8-(14)C]fr(6)A was found associated with both the 18S and 25S rRNA components in quantities roughly proportional to their 260 nm absorbance. This pattern of apparently nonspecific association was not affected by prior denaturation of the RNA with formamide.The distribution of [8-(14)C]fr(6)A moieties in mono- and oligonucleotides derived from combined treatment of [8-(14)C]fr(6)Ade-labeled rRNA with ribonuclease T(1) and pancreatic ribonuclease A was measured by fractionating the digest on a DEAE-cellulose column in the presence of 7 m urea and determining the [8-(14)C]fr(6)A content in each fraction. The [8-(14)C]fr(6)A content in the oligonucleotides varied from 46 to 210 mumol/mol of adenosine (A). The mol ratio of [8-(14)C]fr(6)A to A was three to four times greater for oligonucleotides containing uridine or cytidine ([A](n)Up or [A](n)Cp) than for those containing quanosine ([A](n)Gp).


Proteomic identification of hair cell repair proteins in the model sea anemone Nematostella vectensis.
Sea anemones have an extraordinary capability to repair damaged hair bundles, even after severe trauma. A group of secreted proteins, named repair proteins (RPs), found in mucus covering sea anemones significantly assists the repair of damaged hair bundle mechanoreceptors both in the sea anemone Haliplanella luciae and the blind cavefish Astyanax hubbsi. The polypeptide constituents of RPs must be identified in order to gain insight into the molecular mechanisms by which repair of hair bundles is accomplished. In this study, several polypeptides of RPs were isolated from mucus using blue native PAGE and then sequenced using LC-MS/MS. Thirty-seven known polypeptides were identified, including Hsp70s, as well as many polypeptide subunits of the 20S proteasome. Other identified polypeptides included those involved in cellular stress responses, protein folding, and protein degradation. Specific inhibitors of Hsp70s and the 20S proteasome were employed in experiments to test their involvement in hair bundle repair. The results of those experiments suggested that repair requires biologically active Hsp70s and 20S proteasomes. A model is proposed that considers the function of extracellular Hsp70s and 20S proteasomes in the repair of damaged hair cells.


From pre-ovulatory follicle palpation to the challenge of twin pregnancies: Clinical reflections following one million gynaecological examinations in dairy cows.
Based on experimental studies and extensive field-scale experience, this review offers new proposals for: (i) elevating the success of modern insemination procedures, (ii) emphasizing features of a pre-ovulatory follicle in the context of optimum insemination timing, (iii) overcoming heat stress and its consequences using physiological processes or endocrine protocols, (iv) establishing a viable pregnancy or early pregnancy loss and (v) the challenge of twin pregnancies. In conclusion, the fertility of high-yielding dairy cows can be further improved.


Contact or Collision Sport History, Repetitive Neurotrauma, and Patient-Reported Outcomes in Early to Midadulthood.
Data on the early to midlife effects of repetitive neurotrauma on patient-reported outcomes have been delimited to homogeneous samples of male athletes without comparison groups or accounting for modifying factors such as physical activity. To determine the effect of contact or collision sport participation and repetitive neurotrauma on patient-reported outcomes among early to middle-aged adults. Cross-sectional study. Research laboratory. A total of 113 adults (53 [46.9%] men, 60 [53.1%] women; age = 34.88 ± 11.80 years) in 4 groups: (1) physically inactive individuals with no repetitive head impact (RHI) exposure (NON); (2) noncontact sport athletes and nonathletes with no RHI exposure who were currently physically active (NCA); (3) former high-risk sport athletes with an RHI history who were physically active (HRS); and (4) former rugby players with prolonged RHI exposure who remained physically active. The 12-Item Short-Form Health Survey (SF-12), Apathy Evaluation Scale-self-rated version (AES-S), Satisfaction With Life Scale (SWLS), and Sport Concussion Assessment Tool-5th Edition (SCAT5) Symptom and Symptom Severity Checklist. The NON group had worse self-rated physical function than the NCA group as assessed by the SF-12 physical component summary (P = .03) and worse self-rated apathy (AES-S) and satisfaction with life (SWLS) than the NCA (P = .03 for both) and HRS groups (P = .03 and P = .040, respectively). We observed no group differences for self-rated mental health (SF-12 mental component summary; P = .26) or symptoms (SCAT5; P = .42). Career duration was not associated with any patient-reported outcomes. A history of contact or collision sport participation and career duration did not negatively affect patient-reported outcomes in physically active, early to middle-aged adults. However, physical inactivity status was negatively associated with patient-reported outcomes in these individuals in the absence of an RHI history.


Antibody-dependent enhancement of coxsackievirus B3 infection of primary CD19+ B lymphocytes.
Coxsackievirus B3 (CVB3) is associated with several different acute and chronic forms of human disease, including myocarditis, aseptic meningitis, and pancreatitis. Moreover, CVB3 also infects immune cells like CD19+ B lymphocytes, but the viral uptake mechanism into these cells is not well understood. Therefore, primary murine and human CD19+ B cells were isolated by magnetic-activated cell separation technology and analyzed for virus receptor expression, antibody-dependent enhancement of viral infection, and different cellular surface proteins, that might be involved in mechanisms of viral uptake. Western blot analysis of these cells revealed no significant expression of the coxsackievirus-adenovirus receptor CAR. But incubation of CVB3 with serum dilutions, which exhibited binding but not neutralizing characteristics, increased viral uptake and replication significantly in a dose-dependent manner. Viral entry was reduced when Fc portions of immunoglobulins were blocked by protein A treatment. Moreover, the classical complement system rather than Fc-gamma-receptor-mediated mechanisms could be involved in viral uptake. Taken together, these data suggest an antibody-dependent enhancement of CVB3 infection of primary murine and human CD19+ B cells.


Suspected cardiac syncope in elderly patients: use of the 12-lead electrocardiogram to select patients for holter monitoring.
Results of 24-hour Holter monitoring in elderly patients are often unhelpful, since the prevalence of asymptomatic arrhythmias increases and their prognostic significance is unclear. We investigated the value of the resting electrocardiogram (ECG) in predicting significant findings on 24-hour Holter recordings in those suspected of having cardiac syncope. To see whether the resting 12-lead ECG can be used as a screening tool to select elderly patients suspected of having cardiac syncope for 24-hour ECG monitoring. Comparison of resting 12-lead ECGs and 24-hour Holter tapes in 145 consecutive elderly outpatients suspected of having a cardiac cause for falls, dizziness, or syncope. Four of 30 normal ECGs (13%) showed an abnormality on Holter monitoring as compared with 55 of the 115 abnormal ECGs (47.8%; chi = 11.7143, p < 0.005). In the 'normal' group the 4 abnormal Holter recordings all showed short runs of supraventricular tachycardia, and no intervention resulted. The 115 abnormal resting ECGs showed either ischaemia (n = 27), dysrhythmia (n = 28), sinus bradycardia (n = 22), or conduction defects (n = 38). The 55 of these which showed abnormalities on Holter recordings occurred mostly where the resting ECG showed dysrhythmia (n = 14/28; 50%), bradycardia (n = 19/22; 86.4%), and conduction defect (n = 17/38; 44.7%). Seven patients had complete heart block on Holter, and all had conduction defects on resting ECG (p < 0.0004). Fifteen patients had pauses of longer than 3 s on Holter; all had conduction defect, bradycardia, or dysrhythmias on resting ECG (p < 0.0045). Sixteen patients were paced because of complete heart block or pauses on Holter recordings, and all had either bradycardia or conduction defects on resting ECG, resulting in complete resolution of their symptoms. Patients with suspected cardiac syncope and normal resting ECGs are unlikely to reveal significant abnormalities on single 24-hour Holter monitoring. Cardiac event recorder or prolonged Holter monitoring may be required in patients with strong clinical history. Those with abnormal ECGs, in particular sinus bradycardia and conduction defects, are highly likely to have significant abnormalities on 24-hour ECG monitoring.


A Comparative Study of the Wound Healing Properties of Moist Exposed Burn Ointment (MEBO) and Silver Sulphadiazine.
Burns expose the deeper tissues of the skin or body to invasive microbes. Topical preparations for treating burn wounds, to be useful, should ideally have antibiotic power and promote healing. Silver compounds have been the mainstay of topical burn treatment for decades. However, most chemical substances retard wound healing. Several natural agents such as honey and moist exposed burn ointment (MEBO) are believed to protect wounds from infection and promote healing without causing any of the adverse effects of purified chemicals. In this study, we compared the wound healing properties of MEBO, a herbal preparation of Chinese origin, with silver sulphadiazine (SSD), a long-standing conventional burn dressing. Ten adult Sprague Dawley rats were divided into two groups. They were housed in separate cages and received partial-thickness burn wounds on their dorsal skin. They were then treated with MEBO and SSD. The wounds were inspected daily until day 8, when all the animals were sacrificed, perfused with normal saline, and had their wounds excised and prepared for histology. It was found that animals in both groups were well preserved. No clinical infections occurred. Wound healing was at an advanced stage by day 8 in all the animals. Clinical and histological examination showed that the two agents gave the animals comparable protection and healing possibilities. It is concluded that MEBO is a suitable and efficacious alternative to conventional silver-based topical therapies for treating partial-thickness burn wounds.


Anaphylactoid reactions to vitamin K.
Anaphylactoid reactions in patients receiving intravenously administered vitamin K have been reported in the literature. To summarize the known data on anaphylactoid reactions from administration of vitamin K, we reviewed all published and unpublished reports of this adverse reaction. Published reports were obtained through medline (1966--1999) and EMBASE (1971--1999) searches of the English language literature and review of references from identified case reports. Unpublished reports were obtained using the Spontaneous Reporting System Adverse Reaction database of the United States Food and Drug Administration (FDA) between August 1968 and September 1997. All adverse drug reactions to vitamin K were categorized by route of drug administration, dose and standard adverse reaction code. In the FDA reports, we defined anaphylactoid reactions as any adverse drug reaction coded as either anaphylaxis, allergic reaction, apnea, dyspnea, death, heart arrest, hypotension, shock or vasodilatation. Additionally, all fatal and life-threatening FDA reported reactions were reviewed to determine if they could represent an anaphylactoid reaction missed by the above definition. The literature review uncovered a total of 23 cases (3 fatal) of anaphylactoid reactions from intravenous vitamin K. The FDA database contained a total of 2236 adverse drug reactions reported in 1019 patients receiving vitamin K by all routes of administration. Of the 192 patients with reactions reported for intravenous vitamin K, 132 patients (69 %) had a reaction defined as anaphylactoid, with 24 fatalities (18 %) attributed to the vitamin K reaction. There were 21 patients with anaphylactoid reactions and 4 fatalities reported with doses of intravenous vitamin K of less than 5 mgs. For the 217 patients with reactions reported due to vitamin K via a non-intravenous route of administration, 38 patients had reactions meeting the definition of anaphylactoid (18 %), with 1 fatality (3 %) attributed to the drug. The absolute risk of an anaphylactoid reaction to intravenous vitamin K cannot be determined by this study, but the relatively small number of documented cases despite widespread use of this drug suggest that the reaction is rare. Anaphylactic reactions and case fatality reports were found even when intravenous vitamin K was given at low doses by slow dilute infusion. The pathogenesis of this reaction is unknown and may be multifactorial with etiologies including vasodilation induced by the solubilizing vehicle or immune-mediated processes. We conclude that use of intravenous vitamin K should be limited to patients with serious hemorrhage due to a coagulopathy that is secondary to a relative or absolute deficiency of vitamin K.


Functional electrical stimulation training on functional capacity and blood pressure variability in a centenarian woman: case study.
Functional electrical stimulation (FES) is a rehabilitation method that can revert alterations provoked by aging, such as reductions in functional capacity and modifications on blood pressure variability (BPV). To evaluate the training effects of FES on functional capacity and BPV in a centenarian woman. A 101-year-old woman without previous disease underwent FES training for 12 weeks, with three 40 min sessions/week. FES was applied at a frequency of 20 Hz with a 0.5 ms pulse, 5 s contraction time, 10 s relaxation time, the maximum tolerable intensity and with progressive overload. Functional capacity was assessed with a six-minute walk test (6MWT) and proximal lower limb strength was assessed with a sit-and-stand test (STST). BPV was measured by continuous recording of pulse pressure and calculated by spectral analysis. All variables were measured before and after FES training. After training there was a 70% increase in distance walked in the 6MWT, a 300% increase in the number of STST repetitions, an 8 mmHg reduction in systolic blood pressure (SBP) and a 4 mmHg reduction in diastolic blood pressure (DBP) and mean blood pressure (MBP). Reductions in SBP (11.8 mmHg²), DBP (2.3 mmHg²) and MBP (6.0 mmHg²) variability were also observed. Three months of FES training improved functional capacity and BPV in a centenarian woman.


Plant biology in reduced gravity on the Moon and Mars.
While there have been numerous studies on the effects of microgravity on plant biology since the beginning of the Space Age, our knowledge of the effects of reduced gravity (less than the Earth nominal 1 g) on plant physiology and development is very limited. Since international space agencies have cited manned exploration of Moon/Mars as long-term goals, it is important to understand plant biology at the lunar (0.17 g) and Martian levels of gravity (0.38 g), as plants are likely to be part of bioregenerative life-support systems on these missions. First, the methods to obtain microgravity and reduced gravity such as drop towers, parabolic flights, sounding rockets and orbiting spacecraft are reviewed. Studies on gravitaxis and gravitropism in algae have suggested that the threshold level of gravity sensing is around 0.3 g or less. Recent experiments on the International Space Station (ISS) showed attenuation of phototropism in higher plants occurs at levels ranging from 0.l g to 0.3 g. Taken together, these studies suggest that the reduced gravity level on Mars of 0.38 g may be enough so that the gravity level per se would not be a major problem for plant development. Studies that have directly considered the impact of reduced gravity and microgravity on bioregenerative life-support systems have identified important biophysical changes in the reduced gravity environments that impact the design of these systems. The author suggests that the current ISS laboratory facilities with on-board centrifuges should be used as a test bed in which to explore the effects of reduced gravity on plant biology, including those factors that are directly related to developing life-support systems necessary for Moon and Mars exploration.


MRI of Transcallosal White Matter Helps to Predict Motor Impairment in Multiple Sclerosis.
Background Altered callosal integrity has been associated with motor deficits in patients with multiple sclerosis (MS), but its contribution to disability has, to the knowledge of the authors, not been investigated by using multiparametric MRI approaches. Purpose To investigate structural and functional interhemispheric MRI substrates of global disability at different milestones and upper limb motor impairment in MS. Materials and Methods In this cross-sectional study, healthy control patients and patients with MS (between January 1, 2008, and December 31, 2016) were retrospectively selected from our hospital database. Clinical assessment included Expanded Disability Status Scale (EDSS), nine-hole peg test, and digital finger tapping test. By using structural and resting-state functional MRI sequences, probabilistic tractography of hand corticospinal tract fibers, and transcallosal fibers between hand-motor cortices (hereafter, referred to as hand-M1), supplementary motor areas (SMAs), premotor cortices (PMCs), and voxel-mirror homotopic connectivity (VMHC) were analyzed. Random forest analyses identified the MRI predictors of clinical disability at different milestones (EDSS scores of 3.0, 4.0, 6.0) and upper limb motor impairment (nine-hole peg test and finger tapping test z scores < healthy control patients 5th percentile). Results One-hundred thirty healthy control patients (median age, 39 years; interquartile range, 31-50 years; 70 women) and 340 patients with MS (median age, 43 years; interquartile range, 33-51 years; 213 women) were studied. EDSS 3.0 predictors (n = 159) were global measures of atrophy and lesions together with damage measures of corticospinal tracts and transcallosal fibers between PMCs and SMAs (accuracy, 86%; P = .001-.01). For EDSS 4.0 (n = 131), similar predictors were found in addition to damage in transcallosal fibers between hand-M1 (accuracy, 89%; P = .001-.049). No MRI predictors were found for EDSS 6.0 (n = 70). Nine-hole peg test (right, n = 161; left, n = 166) and finger tapping test (right, n = 117; left, n = 111) impairments were predicted by damage in transcallosal fibers between SMAs and PMCs (accuracy range, 69%-77%; P = .001-.049). VMHC abnormalities did not explain clinical outcomes. Conclusion Structural, not functional, abnormalities at MRI in transcallosal premotor and motor white matter fibers predicted severity of global disability and upper limb motor impairment in patients with multiple sclerosis. The informative role of such predictors appeared less evident at higher disability levels. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Barkhof and Pontillo in this issue.


Contributions of working muscle to whole body lipid metabolism are altered by exercise intensity and training.
To evaluate the contribution of working muscle to whole body lipid oxidation, we examined the effects of exercise intensity and endurance training (9 wk, 5 days/wk, 1 h, 75% Vo(2 peak)) on whole body and leg free fatty acid (FFA) kinetics in eight male subjects (26 +/- 1 yr, means +/- SE). Two pretraining trials [45 and 65% Vo(2 max) (45UT, 65UT)] and two posttraining trials [65% of pretraining Vo(2 peak) (ABT), and 65% of posttraining Vo(2 peak) (RLT)] were performed using [1-(13)C]palmitate infusion and femoral arteriovenous sampling. Training increased Vo(2 peak) by 15% (45.2 +/- 1.2 to 52.0 +/- 1.8 ml.kg(-1).min(-1), P < 0.05). Muscle FFA fractional extraction was lower during exercise (EX) compared with rest regardless of workload or training status ( approximately 20 vs. 48%, P < 0.05). Two-leg net FFA balance increased from net release at rest ( approximately -36 micromol/min) to net uptake during EX for 45UT (179 +/- 75), ABT (236 +/- 63), and RLT (136 +/- 110) (P < 0.05), but not 65UT (51 +/- 127). Leg FFA tracer measured uptake was higher during EX than rest for all trials and greater during posttraining in RLT (716 +/- 173 micromol/min) compared with pretraining (45UT 450 +/- 80, 65UT 461 +/- 72, P < 0.05). Leg muscle lipid oxidation increased with training in ABT (730 +/- 163 micromol/min) vs. 65UT (187 +/- 94, P < 0.05). Leg muscle lipid oxidation represented approximately 62 and 30% of whole body lipid oxidation at lower and higher relative intensities, respectively. In summary, training can increase working muscle tracer measured FFA uptake and lipid oxidation for a given power output, but both before and after training the association between whole body and leg lipid metabolism is reduced as exercise intensity increases.


Path integral analysis of Jarzynski's equality: analytical results.
We apply path integrals to study nonequilibrium work theorems in the context of Brownian dynamics, deriving in particular the equations of motion governing the most typical and most dominant trajectories. For the analytically soluble cases of a moving harmonic potential and a harmonic oscillator with a time-dependent natural frequency, we find such trajectories, evaluate the work-weighted propagators, and validate Jarzynski's equality.


[Interaction of beta-adrenergic agents with the plasma membranes of the myocardium].
The initial stage of interaction of beta-adrenomimetics and beta-adrenoblockers with specific membrane binding sites is characterized by different patterns of thermodynamic parameters. Administration of isadrin results in a decrease of entropy and enthalpy, which reflects the primary binding reaction and agonist-specific receptor isomerization to the conformational form activating adenylate cyclase. Anaprilin and alpheprol do not change the receptor conformation and participate only in the primary binding reaction which is marked by a decrease in enthalpy and a rise of entropy in the course of interaction of beta-adrenoblockers with specific membrane binding sites. The different patterns of thermodynamic parameters under the effect of beta-adrenomimetics and beta-adrenoblockers on plasma membranes are explained by the different influence of these substances on the mobility of membrane lipids, i.e. on the viscosity of plasma membranes.


Incinerator ash characterization - Implications for elevated temperature landfills.
The occurrence of temperatures in municipal solid waste (MSW) landfills in excess of 55 °C is a problem that has gained much attention in the solid waste industry, both domestically and globally. Facilities which frequently experience such temperatures are termed Elevated Temperature Landfills (ETLFs). Ash, both MSW incinerator ash (MSWIA) and coal combustion ash (CCA), when co-disposed with unburned MSW, can provide constituents which are able to partake in abiotic exothermic reactions that may develop or sustain elevated temperatures. These reactions include hydration and carbonation, as well as the oxidation and corrosion of metals commonly found in ash. In this study, sixteen ash samples from across the U.S. were characterized by using X-ray diffraction (XRD), X-ray fluorescence (XRF), and scanning electron microscopy coupled with X-ray energy dispersive spectroscopy (SEM/XEDS) to identify complex mineral and glassy phases enriched in calcium, silicon, aluminum, and iron. The high-temperature incineration of MSW and coal feedstocks, along with weathering processes impacting these ashes, yield a heterogenous material capable of generating appreciable heat given the right conditions. Additionally, a simple model was developed and, using ash compositions obtained via XEDS, a value termed relative heat potential (RHP) was estimated for each sample. Results show that CCAs may be expected to generate roughly 15 % more heat than MSWIAs when deposited in landfills due to their greater aluminum content.


An fMRI Study of Local Synchronization in Different Subfrequency Bands during the Continuous Feedback of Finger Force.
Conventional functional magnetic resonance imaging (fMRI) studies on motor feedback employ periodical blocked paradigm which does not allow frequency analysis of brain activity. Here, we carried out an fMRI study by using a continuous paradigm, that is, continuous (8 min) feedback of finger force. Borrowing an analytic method widely used in resting-state fMRI studies, that is, regional homogeneity (ReHo), we compared the local synchronization in some subfrequency bands between real and sham feedback, and the subbands were defined as Slow-6 (0.0-0.01 Hz), Slow-5 (0.01-0.027 Hz), Slow-4 (0.027-0.073 Hz), Slow-3 (0.073-0.198 Hz), and Slow-2 (0.198-0.25 Hz). Our results revealed that the five subfrequency bands of brain activity contributed to the changes of ReHo between real and sham feedback differently, and, more importantly, the changes in basal ganglia were only manifested in Slow-6, implicating the fact that ReHo in ultraslow band may be associated with the functional significance of BG, that is, motor control. These findings provide novel insights into the neural substrate underlying motor feedback, and properties of the ultraslow band of local synchronization deserve more attention in future explorations.


The accuracy of head and neck carcinoma sentinel lymph node biopsy in the clinically N0 neck.
Sentinel lymph node (SLN) biopsy originally was described as a means of identifying lymph node metastases in malignant melanoma and breast carcinoma. The use of SLN biopsy in patients with oral and oropharyngeal squamous cell carcinoma and clinically N0 necks was investigated to determine whether the pathology of the SLN reflected that of the neck. Patients undergoing elective neck dissections for head and neck squamous cell carcinoma accessible to injection were enrolled into our study. Sentinel lymph node biopsy was performed after blue dye and radiocolloid injection. Preoperative lymphoscintigraphy and the perioperative use of a gamma probe identified radioactive SLNs; visualization of blue stained lymphatics identified blue SLNs. A neck dissection completed the surgical procedure, and the pathology of the SLN was compared with that of the remaining neck dissection. Sentinel lymph node biopsy was performed on 40 cases with clinically N0 necks. Twenty were pathologically clear of tumor and 20 contained subclinical metastases. SLNs were found in 17 necks with pathologic disease and contained metastases in 16. The sentinel lymph node was the only lymph node containing tumor in 12 of 16. The SLN, in head and neck carcinomas accessible to injection without anesthesia, is an accurate reflector of the status of the regional lymph nodes, when found in patients with early tumors. Sentinel lymph nodes may be found in clinically unpredictable sites, and SLN biopsy may aid in identifying the clinically N0 patient with early lymph node disease. If SLNs cannot be located in the neck, an elective lymph node dissection should be considered.


Crystal structure of bis-(4-nitro-aniline-κN (1))(5,10,15,20-tetra-phenyl-por-phy-rin-ato-κ(4) N)cobalt(III) chloride di-chloro-methane monosolvate.
The reaction of [Co(III)(TPP)Cl] (TPP is the dianion of 5,10,15,20-tetra-phenyl-porphyrin) with an excess of 4-nitro-aniline in di-chloro-methane leads to the title compound, [Co(III)(C44H28N4)(C6H6N2O2)2]Cl·CH2Cl2. The Co(III) ion lies on an inversion centre and is octa-hedrally coordinated by two N atoms of the NH2 groups of the two 4-nitro-aniline trans-axial ligands and four pyrrole N atoms of the porphyrin. The asymmetric unit contains one half of the [Co(III)(TPP)(4-nitro-aniline)2](+) ion complex, one chloride counter-ion (lying on a twofold rotation axis) and one half di-chloro-methane solvent mol-ecule, where the C atom lies on a twofold rotation axis. The average equatorial Co-N(pyrrole) distance (Co-Np) is 1.982 (2) Å and the axial Co-N(4-nitro-aniline) bond length is 2.006 (2) Å. The crystal packing is stabilized by an N-H⋯Cl hydrogen bond between the N atom of the amino group of the 4-nitro-aniline axial ligand and the chloride counter-ion. The supra-molecular architecture is further stabilized by weak C-H⋯π inter-actions.


Whole Genome Sequencing Reveals Potential New Targets for Improving Nitrogen Uptake and Utilization in Sorghum bicolor.
Nitrogen (N) fertilizers are a major agricultural input where more than 100 million tons are supplied annually. Cereals are particularly inefficient at soil N uptake, where the unrecovered nitrogen causes serious environmental damage. Sorghum bicolor (sorghum) is an important cereal crop, particularly in resource-poor semi-arid regions, and is known to have a high NUE in comparison to other major cereals under limited N conditions. This study provides the first assessment of genetic diversity and signatures of selection across 230 fully sequenced genes putatively involved in the uptake and utilization of N from a diverse panel of sorghum lines. This comprehensive analysis reveals an overall reduction in diversity as a result of domestication and a total of 128 genes displaying signatures of purifying selection, thereby revealing possible gene targets to improve NUE in sorghum and cereals alike. A number of key genes appear to have been involved in selective sweeps, reducing their sequence diversity. The ammonium transporter (AMT) genes generally had low allelic diversity, whereas a substantial number of nitrate/peptide transporter 1 (NRT1/PTR) genes had higher nucleotide diversity in domesticated germplasm. Interestingly, members of the distinct race Guinea margaritiferum contained a number of unique alleles, and along with the wild sorghum species, represent a rich resource of new variation for plant improvement of NUE in sorghum.


Preserved C-peptide levels in overweight or obese compared with underweight children upon diagnosis of type 1 diabetes mellitus.
We hypothesized that overweight or obese children might develop type 1 diabetes mellitus (T1DM) early despite residual beta-cell function. Factors independently associated with preservation of C-peptide level were analyzed. We retrospectively reviewed the medical data of 135 children aged 2.1-16.5 years with autoimmune T1DM. Body mass index (BMI), pubertal stage, and glycosylated hemoglobin (HbA1c) and C-peptide levels were evaluated. Patients were assigned to underweight (22.2%), normal weight (63.7%), and overweight or obese (14.1%) groups according to their BMI. Preservation of serum C-peptide levels (≥0.6 ng/mL) was found in 43.0% of subjects. With increasing BMI, the proportions of children with preserved C-peptide levels increased from 33.3% to 41.9% to 63.2%, with marginal significance (P=0.051). Interaction analysis indicated no effect of BMI score on age at onset associated with serum C-peptide levels. The lower the C-peptide level, the younger the age of onset (P<0.001), after adjustment for BMI z-score and HbA1c level. However, no significant relationship between BMI z-score or category and onset age was evident. Upon multivariate-adjusted modeling, the odds that the C-peptide level was preserved increased by 1.2 fold (P=0.001) per year of life, by 3.1 folds (P=0.015) in children presenting without (compared to with) ketoacidosis, and by 5.0 folds (P=0.042) in overweight or obese (compared to underweight) children. Overweight or obese children had slightly more residual beta-cell function than did underweight children. However, we found no evidence that obesity temporally accelerates T1DM presentation.


Application of an efficient strategy based on liquid-liquid extraction, high-speed counter-current chromatography, and preparative HPLC for the rapid enrichment, separation, and purification of four anthraquinones from Rheum tanguticum.
This study presents an efficient strategy based on liquid-liquid extraction, high-speed counter-current chromatography, and preparative HPLC for the rapid enrichment, separation, and purification of four anthraquinones from Rheum tanguticum. A new solvent system composed of petroleum ether/ethyl acetate/water (4:2:1, v/v/v) was developed for the liquid-liquid extraction of the crude extract from R. tanguticum. As a result, emodin, aloe-emodin, physcion, and chrysophanol were greatly enriched in the organic layer. In addition, an efficient method was successfully established to separate and purify the above anthraquinones by high-speed counter-current chromatography and preparative HPLC. This study supplies a new alternative method for the rapid enrichment, separation, and purification of emodin, aloe-emodin, physcione, and chrysophanol.


Increased cell compaction can augment the resistance of HT-29 human colon adenocarcinoma spheroids to ionizing radiation.
One of the most important questions in tumor biology is the understanding of the mechanisms responsible for the resistance of cancer cells to radiotherapy. In the present study, the possible role played by cell-cell interactions in determining the response of tumor cells to ionizing radiation was investigated. HT-29 colon adenocarcinoma spheroids were irradiated with a dose of 15 Gy in two different stages of growth characterized by diverse degrees of compaction: loosely organized spheroids (early spheroids) and compacted spheroids (late spheroids). Morphological analyses demonstrated that late spheroids were less damaged than early spheroids. Moreover, analyses of the cell cycle and cell death showed that ionizing radiation induced necrosis in early spheroids and apoptosis in late ones. From these results it can be concluded that late, compacted spheroids are more resistant to ionizing radiation than early, loose spheroids. In order to understand the mechanisms regulating this compaction-induced resistance of late spheroids, E-cadherin/beta-catenin complex expression and distribution were analyzed. In late spheroids, E-cadherin/beta-catenin complexes were shown to be tethered to the cytoskeleton, and since this organization has been demonstrated to strengthen cell-cell adhesion in other systems, it can be postulated that the same is true in HT-29 spheroids. In conclusion, it can be hypothesized that compaction of HT-29 spheroids is mediated by the reorganization of E-cadherin/beta-catenin complexes on the plasma membrane and that this compaction may be responsible for the increase in resistance of HT-29 spheroids to ionizing radiation.