Antitumor efficacy of Lf modified daunorubicin plus honokiol liposomes in treatment of brain glioma.
Malignant brain glioma is the most common and aggressive type of primary intracranial neoplasm. Regular chemotherapy cannot eradicate brain glioma cells and the residual glioma cells could form vasculogenic mimicry (VM) channels under hypoxic conditions to provide nutrients for tumor cell invasion. In addition, the existence of the blood-brain barrier (BBB) restricts most antitumor drugs into brain glioma. In this study, we developed a kind of lactoferrin (Lf) modified daunorubicin plus honokiol liposomes to transport antitumor drugs across BBB, eliminate the VM channels and block tumor cell invasion. The evaluations were performed on BBB model, brain glioma cells and glioma-bearing mice. In vitro results showed that the targeting liposomes with suitable physicochemical property could enhance the drug transportation acrossing the BBB, inhibit C6 cells invasion and destroy VM channels. Action mechanism studies indicated that Lf modified daunorubicin plus honokiol liposomes could activate apoptotic enzymes caspase 3 as well as down-regulate VM protein indicators (PI3K, MMP-2, MMP-9, VE-Cadherin and FAK). In vivo results displayed the targeting liposomes improved accumulation in brain tumor tissue and exhibited obvious antitumor efficacy. Therefore, Lf modified daunorubicin plus honokiol liposomes could be used as a potential therapy for treatment of brain glioma.


A study of a fetal heart rate calculation system based on R-R interval.
Fetal electrocardiogram (FECG) can be obtained in a non-invasive manner to monitor fetal growth status. In this study, a fetal heart rate (FHR) calculation system was proposed, which consists of the FECG recorder (MF-HOLTER) and the FECG monitoring software (FECG-MS). The abdomen electrocardiogram (AECG) of pregnant woman is acquired through the MF-HOLTER. The FECG-MS packs the AECG data and calls the FECG separation algorithm to obtain the separated FECG and the fetal QRS (FQRS) position. The FHR is further obtained by calculating the R-R interval value. At the same time, this study proposed a FQRS position correction algorithm to calculate the correct FHR values. In order to verify the accuracy of the FHR calculation, the ECG signal of FLUKE's PS320 FETAL SIMULATOR and clinical data were simultaneously tested. The accuracy rate is over 98% in processing the simulator's data. In processing clinical data, the FHR values obtained by both the system proposed in this study and Monica AN24 are very close, and the difference is less than 1 bpm. The results show that the FHR calculation system is accurate and stable, and has a positive application value and prospect.


Equilibrium, Kinetic, and Thermodynamic Studies on the Adsorption of Cadmium from Aqueous Solution by Modified Biomass Ash.
Natural biomass ash of agricultural residuals was collected from a power plant and modified with hexagonal mesoporous silica and functionalized with 3-aminopropyltriethoxysilane. The physicochemical and morphological properties of the biomass ash were analyzed by ICP-OES, SEM, TEM-EDS, FTIR, and BET analysis. The adsorption behavior of the modified product for Cd2+ in aqueous solution was studied as a function of pH, initial metal concentration, equilibrium time, and temperature. Results showed that the specific surface area of the modified product was 9 times that of the natural biomass ash. The modified biomass ash exhibited high affinity for Cd2+ and its adsorption capacity increased sharply with increasing pH from 4.0 to 6.0. The maximum adsorption capacity was 23.95 mg/g in a pH 5 solution with an initial metal concentration of 50 mg/L and a contact time of 90 min. The adsorption of Cd2+ onto the modified biomass ash was well fitted to the Langmuir model and it followed pseudo-second-order kinetics. Thermodynamic analysis results showed that the adsorption of Cd2+ was spontaneous and endothermic in nature. The results suggest that the modified biomass ash is promising for use as an inexpensive and effective adsorbent for Cd2+ removal from aqueous solution.


Infection with enteric pathogens Salmonella typhimurium and Citrobacter rodentium modulate TGF-beta/Smad signaling pathways in the intestine.
Salmonella and Citrobacter are gram negative, members of Enterobacteriaceae family that are important causative agents of diarrhea and intestinal inflammation. TGF-β1 is a pleiotropic multifunctional cytokine that has been implicated in modulating the severity of microbial infections. How these pathogens alter the TGF-β1 signaling pathways in the intestine is largely unknown. Streptomycin-pretreated C57BL/6J mouse model colonized with S. typhimurium for 8 hours (acute) and 4 days (chronic) infection and FVB/N mice infected with C. rodentium for 6 days were utilized. Results demonstrated an increase in TGF-β1 receptor I expression (p<0.05) in S. typhimurium infected mouse ileum at both acute and chronic post-infection vs control. This was associated with activation of Smad pathways as evidenced by increased phosphorylated (p)-Smad2 and p-Smad3 levels in the nucleus. The inhibitory Smad7 mRNA levels showed a significant up regulation during acute phase of Salmonella infection but no change at 4d post-infection. In contrast to Salmonella, infection with Citrobacter caused drastic downregulation of TGF receptor I and II concomitant with a decrease in levels of Smad 2, 3, 4 and 7 expression in the mouse colon. We speculate that increased TGF-β1 signaling in response to Salmonella may be a host compensatory response to promote mucosal healing; while C. rodentium decreases TGF-β1 signaling pathways to promote inflammation and contribute to disease pathogenesis. These findings increase our understanding of how enteric pathogens subvert specific aspects of the host-cellular pathways to cause disease.


Quantitative estimates of glacial refugia for chimpanzees (Pan troglodytes) since the Last Interglacial (120,000 BP).
Paleoclimate reconstructions have enhanced our understanding of how past climates have shaped present-day biodiversity. We hypothesize that the geographic extent of Pleistocene forest refugia and suitable habitat fluctuated significantly in time during the late Quaternary for chimpanzees (Pan troglodytes). Using bioclimatic variables representing monthly temperature and precipitation estimates, past human population density data, and an extensive database of georeferenced presence points, we built a model of changing habitat suitability for chimpanzees at fine spatio-temporal scales dating back to the Last Interglacial (120,000 BP). Our models cover a spatial resolution of 0.0467° (approximately 5.19 km2 grid cells) and a temporal resolution of between 1000 and 4000 years. Using our model, we mapped habitat stability over time using three approaches, comparing our modeled stability estimates to existing knowledge of Afrotropical refugia, as well as contemporary patterns of major keystone tropical food resources used by chimpanzees, figs (Moraceae), and palms (Arecacae). Results show habitat stability congruent with known glacial refugia across Africa, suggesting their extents may have been underestimated for chimpanzees, with potentially up to approximately 60,000 km2 of previously unrecognized glacial refugia. The refugia we highlight coincide with higher species richness for figs and palms. Our results provide spatio-temporally explicit insights into the role of refugia across the chimpanzee range, forming the empirical foundation for developing and testing hypotheses about behavioral, ecological, and genetic diversity with additional data. This methodology can be applied to other species and geographic areas when sufficient data are available.


Impairment of mitochondrial function of rat hepatocytes by high fat diet and oxidative stress.
Fatty liver disease associated with obesity is an important medical problem and the mechanisms for lipid accumulation in hepatocytes are not fully elucidated yet. Recent findings indicate that mitochondria play an important role in this process. Our data on hepatocytes in which mitochondria are in contact with other cytosolic structures important for their function, extend observations obtained on isolated mitochondria and confirm inhibition of Complex I activity in hepatocytes isolated from rats fed by high fat diet (HFD) compared with controls fed by standard diet (STD). Furthermore we have found that HFD-hepatocytes are more sensitive to the peroxidative stress because under these conditions also Complex II activity is disturbed. Therefore in HFD animals decrease of Complex I activity cannot be compensated by Complex II substrates as in STD hepatocytes. Our data thus indicates that combination of HFD and peroxidative stress potentiates HFD damaging effect of mitochondria because both branches of the respiratory chain (NADH- and flavoprotein-dependent) are disturbed.


Rifaximin versus nonabsorbable disaccharides in the management of hepatic encephalopathy: a meta-analysis.
To compare the positive and negative effects of rifaximin and nonabsorbable disaccharides in patients with hepatic encephalopathy. We used the method recommended by The Cochrane Collaboration to perform a meta-analysis of comparative randomized trials of rifaximin and nonabsorbable disaccharides. Seven randomized controlled trials were identified, but only five trials involving 264 patients met all the inclusion criteria. There was no significant difference between rifaximin and nonabsorbable disaccharides on improvement in patients with hepatic encephalopathy [relative risk (RR) 1.08; 95% confidence interval (CI), 0.85-1.38; P=0.53]. RR was 0.98 (95% CI: 0.85-1.13; P=0.74) for acute hepatic encephalopathy in 157 patients and 0.87 (95% CI: 0.40-1.88; P=0.72) for chronic hepatic encephalopathy in 96 patients, respectively. There was no significant difference between rifaximin and nonabsorbable disaccharides on diarrhea (RR=0.90; 95% CI: 0.17-4.70; P=0.90). However, a significant difference in favor of rifaximin on abdominal pain (RR=0.28; 95% CI: 0.08-0.95; P=0.04) was identified. Rifaximin is not superior to nonabsorbable disaccharides for acute or chronic hepatic encephalopathy in the long-term or short-term treatment except that it may be better tolerated. Further studies on larger populations are required to provide more sufficient evidence for assessment of the use of rifaximin.


Co-operative binding of hsp60 may promote transfer from hsp70 and correct folding of imported proteins in mitochondria [corrected].
I propose that a molecular chaperone hsp60 binds to and dissociates from the unfolded polypeptide or folding intermediate in a positively co-operative manner, but another chaperone hsp70 shows no such co-operativity. This could simply explain the fact that the protein newly imported in the mitochondrial matrix is transferred from hsp70 to hsp60 promotes correct folding of the substrate protein while hsp70 does not.


Clinical and microbiological profiles of human immunodeficiency virus (HIV)-seropositive Brazilians undergoing highly active antiretroviral therapy and HIV-seronegative Brazilians with chronic periodontitis.
This study compares the periodontal clinical profile and the composition of the subgingival microbiota of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative subjects with chronic periodontitis. A total of 172 subjects were distributed into two HIV-seropositive groups (37 chronic periodontitis [H+CP+] and 35 periodontally healthy [H+CP-] individuals) and two HIV-seronegative groups (49 chronic periodontitis [H-CP+] and 51 periodontally healthy [H-CP-] subjects). Subgingival samples were collected from six sites with the deepest probing depth in the periodontitis groups and six random sites in the groups with periodontal health. All HIV-infected patients had undergone highly active antiretroviral therapy (HAART) for at least 2 years. The presence and levels of 33 bacterial species were detected by DNA probes and the checkerboard method. Kruskal-Wallis and Mann-Whitney tests were used to seek for significant differences among and between groups. H-CP+ patients showed significantly more periodontal destruction and inflammation than H+CP+ patients, whereas H+CP- subjects presented a greater percentage of sites with bleeding than H-CP- subjects (P <0.01). Patients who were HIV seronegative showed higher prevalence and levels of most bacterial species than HIV seropositive patients. Periodontal pathogens including Tannerella forsythensis, Porphyromonas gingivalis, Prevotella nigrescens, Eubacterium nodatum, Fusobacterium nucleatum, and Selenomonas noxia were more frequently detected in H-CP+ subjects compared to H+CP+ and controls. In contrast, Enterococcus faecalis and Acinetobacter baumannii were more commonly found in HIV-infected than in non-HIV-infected subjects (P <0.05). Putative periodontal pathogens are more prevalent in the subgingival microbiota of HIV-seronegative patients with chronic periodontitis, whereas species not usually associated with periodontitis are detected in higher frequency in HIV-seropositive subjects under HAART.


Microwave irradiation of pristine multi-walled carbon nanotubes in vacuum.
The goal of the present paper was to study the behavior of commercially available pristine multi-walled carbon nanotubes (MWNTs) under microwave irradiation (exposures up to 200 s) in vacuum, by means of several experimental techniques. An intense glow and heating of the nanotube samples were observed. Raman spectra, scanning electron microscopy (SEM) and scanning tunneling microscopy (STM) images of the processed nanotubes did not show considerable changes as compared to those for pristine MWNTs. Closer structural investigation by means of conventional and high-resolution transmission electron microscopy (TEM and HRTEM, respectively) revealed an increase in the occurrence of open nanotube ends, whereas the sidewalls remained generally unchanged. The possibility of increase in the number of entry ports for gases was verified by employing temperature programmed desorption experiments with mass spectrometric detection (TPD-MS) with pristine and microwave-irradiated MWNTs exposed to atmosphere. The overall adsorption capacity did not change, whereas the rate of adsorption increased roughly by twice for the nanotubes irradiated for 200 s as compared to pristine MWNTs, which is consistent with selective opening of the nanotube ends.


Failure to diagnose: bowel obstruction.
Case histories are based on actual medical negligence claims or medicolegal referrals; however certain facts have been omitted or changed by the author to ensure the anonymity of the parties involved.


Evaluation and treatment of men with biochemical prostate-specific antigen recurrence following definitive therapy for clinically localized prostate cancer.
Early detection and monitoring by serum prostate-specific antigen (PSA) measurement has increased the number of men presenting with potentially curable prostate cancer. Most will choose radical prostatectomy or some form of radiation therapy for treatment, but some will have evidence of biochemical disease recurrence following therapy, shown by a rising PSA level without other clinical evidence of disease. Radical prostatectomy involves the removal of all prostate tissue, causing the serum PSA to decline to undetectable levels within four to six weeks following surgery; a subsequent rise in the serum PSA to a detectable level indicates disease recurrence. Patients should be evaluated to assess whether rising PSA levels indicate local recurrence or early metastatic disease. The advantages of salvage radiation, endocrine therapy, and other treatment modalities in local disease recurrence must be weighed against potential side effects and the resulting decrease in quality of life. Radiation therapy does not immediately eradicate all PSA-producing cells; therefore the persistence of a detectable PSA does not necessarily imply residual cancer, but rising PSA levels indicate treatment failure. Salvage surgery can be performed after radiotherapy for the purpose of removing all viable cancer cells, but should be weighed against a higher incidence of surgical complications; cryoablation offers a less invasive therapeutic modality.


Generation of a phenotypic array of hypothalamic neuronal cell models to study complex neuroendocrine disorders.
Knowledge of how the brain achieves its diverse central control of basic physiology is severely limited by the virtual absence of appropriate cell models. Isolation of clonal populations of unique peptidergic neurons from the hypothalamus will facilitate these studies. Herein we describe the mass immortalization of mouse primary hypothalamic cells in monolayer culture, resulting in the generation of a vast representation of hypothalamic cell types. Subcloning of the heterogeneous cell populations resulted in the establishment of 38 representative clonal neuronal cell lines, of which 16 have been further characterized by analysis of 28 neuroendocrine markers. These cell lines represent the first available models to study the regulation of neuropeptides associated with the control of feeding behavior, including neuropeptide Y, ghrelin, urocortin, proopiomelanocortin, melanin-concentrating hormone, neurotensin, proglucagon, and GHRH. Importantly, a representative cell line responds appropriately to leptin stimulation and results in the repression of neuropeptide Y gene expression. These cell models can be used for detailed molecular analysis of neuropeptide gene regulation and signal transduction events involved in the direct hormonal control of unique hypothalamic neurons, not yet possible in the whole brain. Such studies may contribute information necessary for the strategic design of therapeutic interventions for complex neuroendocrine disorders, such as obesity.


Calorimetric studies of ligands binding to glutathione S-transferase from the malarial parasite Plasmodium falciparum.
Glutathione S-transferase, from the malarial parasite Plasmodium falciparum (PfGST), exerts a protective role in the organism and is thus considered an interesting target for antimalarial drug development. In contrast to other GSTs, it is present in solution as a tetramer and a dimer in equilibrium, which is induced by glutathione (GSH). These properties prevent a calorimetric titration from being conducted upon binding of ligands to this protein's G-site. Thermodynamic characterization can be an optimal strategy for antimalarial drug development, and isothermal titration calorimetry (ITC) is the only technique that allows the separation of the binding energy into both enthalpic and entropic contributions. This information facilitates an understanding of the changes in the drugs' substituents, improving their affinity and specificity. In this study, we have applied a nontypical ITC procedure, based on the dissociation of the ligand-protein complex, to calorimetrically study the binding of the GSH substrate, and the glutathione sulfonate competitive inhibitor, to dimeric PfGST over a temperature range of 15-37 °C. The optimal experimental conditions for applying this procedure have been optimized by studying the dimer to tetramer conversion using size exclusion chromatography. The binding of these ligands to dimeric PfGST is noncooperative, the affinity of glutathione sulfonate being approximately 2 orders of magnitude higher than that of its natural substrate GSH. The binding of both ligands is enthalpically favorable and entropically unfavorable at all the studied temperatures. These results demonstrate that, although PfGST presents differences when compared to other known GSTs, these ligands bind to its dimeric form with a similar affinity and energetic balance. However, in contrast to that of other GSTs, the binding of GSH to protein, in the absence of the ligand, is slow.


Prediction of pre-eclampsia during early pregnancy in primiparas with soluble fms-like tyrosine kinase-1 and placental growth factor.
We hypothesized that pre-eclampsia (PE) can be predicted early in primiparas by measuring serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). All normotensive primiparas attending the antenatal clinics of Aga Khan University Hospital and Aga Khan Hospital for Women, Karachi, Pakistan without any known risk factor for PE were invited to participate in the study. They were divided into two groups based on the development of PE. Their blood samples were collected at 8-15, 16-22, 23-28, 29v34 weeks of pregnancy and once within 1 week of delivery. All samples were analysed for sFlt-1 and PlGF. Six hundred and eleven (46.7%) of 1307 recruited primiparas completed the study according to the protocol. Of these, 39 (6.4%) women developed PE. The difference in serum sFlt-1 was evident as early as 15 weeks of gestation. Higher levels of serum sFlt-1 were present in women who later developed PE. Relatively higher levels of PlGF were observed in non-PE women compared to PE women up to 22 weeks of gestation. However, after 23 weeks of pregnancy, PlGF levels increased in both the groups, but less so in the PE group. Receiver operator characteristics (ROC) curve analysis showed that even in early pregnancy (<15 weeks of gestation), serum sFlt-1 alone has the potential to predict PE with area under the curve (AUC), sensitivity and specificity of 0.81, 75.9 and 72.4, respectively. PE can be predicted in primiparas in the early part of second trimester with serum levels of sFlt-1 and in the later part of second trimester with serum levels of PlGF.


Roentgenographical study of the stability of the cervical spine in children.
A roentgenographical study of the supposedly normal cervical spine in 40 children is reported. At the upper cervical level, the validity of the criteria in the literature (especially the atlantodental distance on the lateral view) was confirmed, and an upper limit was determined for children. A study of the atlantoaxial relationship on the anteroposterior view in neutral position and in lateral position was performed. At the lower cervical level, measurements according to Penning (Am J Roentgenol 1978;30:317-26) and Cattel and Filtzer (J Bone Joint Surg [Am] 1965;47:1295-308) were applied to children and compared level by level at each age. This study allows a better comprehension of the mobility of the cervical spine in children and offers an explanation for suspicious roentgenographical features after trauma.


Innovative, integrative, and interactive in-class activity on metabolic regulation: Evaluating educational impacts.
Medical students tend to have difficulties in developing a holistic view of metabolic pathway and hormone regulation. To address this issue, an interactive activity was implemented for first-year medical students at the School of Medicine, University of Minho, Portugal. Students' previous knowledge on metabolic pathways was evaluated by a pre-test followed by an interactive activity. In the supervised activity, students were challenged to elaborate a diagrammatic representation regarding enzymes, co-factors, and hormonal metabolic regulation in early fasting during the night, as well as in well-fed conditions. The activity was concluded with a post-test to determine the students' learning gains and a few days later students were evaluated by a final exam. Afterwards, students evaluated the activity by filling a questionnaire. Results from four different cohorts showed that the activity resulted in significant learning gains, particularly favoring students who have less prior knowledge. The comparison between the pre-test and the final exam also revealed significant learning gains for low achievers students. On the questionnaires, the majority of the students rated the activity as good or very good. Students agreed that this activity promotes: (a) reactivation of previous knowledge; (b) a better understanding of the interconnections between the metabolic pathways; (c) the application of learned concepts in real scenarios; and (d) sharing knowledge with peers. This study describes an active, unpretentious, and easily implemented activity available for early medical and biochemical curricula.


Monitoring of adverse drug reactions by means of autopsy tissue examination.
Morphologic examination of autopsy tissue specimens was undertaken to establish the incidence of adverse drug reactions in a population of hospitalised patients. By removal of subjective bias recording of adverse reactions, the incidence of toxic tissue manifestations was 33%. In those reactions classified as definitely linked to a specific causative agent males between the ages of 41 and 60 displayed the highest frequency of adverse effects. In the probable and possible categories the incidence of toxic manifestations was equal amongst both sexes and highest in patients over 40 y. Regardless of the type of adverse reaction the most common causative agent identified was alcohol and hepatic tissue was primarily altered morphologically. Unlike the conventional mechanism used to monitor adverse drug reactions, autopsy tissue examination provides a system of measurement of toxic manifestations to both prescription as well as non-prescription compounds.


Species identification and comparative population genetics of four coastal houndsharks based on novel NGS-mined microsatellites.
The common smooth-hound (Mustelus mustelus) is the topmost bio-economically and recreationally important shark species in southern Africa, western Africa, and Mediterranean Sea. Here, we used the Illumina HiSeq™ 2000 next-generation sequencing (NGS) technology to develop novel microsatellite markers for Mustelus mustelus. Two microsatellite multiplex panels were constructed from 11 polymorphic loci and characterized in two populations of Mustelus mustelus representative of its South African distribution. The markers were then tested for cross-species utility in Galeorhinus galeus, Mustelus palumbes, and Triakis megalopterus, three other demersal coastal sharks also subjected to recreational and/or commercial fishery pressures in South Africa. We assessed genetic diversity (NA, AR, HO, HE, and PIC) and differentiation (FST and Dest) for each species and also examined the potential use of these markers in species assignment. In each of the four species, all 11 microsatellites were variable with up to a mean NA of 8, AR up to 7.5, HE and PIC as high as 0.842. We were able to reject genetic homogeneity for all species investigated here except for T. megalopterus. We found that the panel of the microsatellite markers developed in this study could discriminate between the study species, particularly for those that are morphologically very similar. Our study provides molecular tools to address ecological and evolutionary questions vital to the conservation and management of these locally and globally exploited shark species.


International medical graduates: learning for practice in Alberta, Canada.
There is little known about the learning that is undertaken by physicians who graduate from a World Health Organization-listed medical school outside Canada and who migrate to Canada to practice. What do physicians learn and what resources do they access in adapting to practice in Alberta, a province of Canada? Telephone interviews with a theoretical sample of 19 IMG physicians were analyzed using a grounded theory constant comparative approach to develop categories, central themes, and a descriptive model. The physicians described two types of learning: learning associated with studying for Canadian examinations required to remain and practice in the province and learning that was required to succeed at clinical work in a new setting. This second type of learning included regulations and systems, patient expectations, new disease profiles, new medications, new diagnostic procedures, and managing the referral process. The physicians "settled" into their new setting with the help of colleagues; the Internet, personal digital assistants (PDAs), and computers; reading; and continuing medical education programs. Patients both stimulated learning and were a resource for learning. Settling into Alberta, Canada, physicians accommodated and adjusted to their settings with learning activities related to the clinical problems and situations that presented themselves. Collegial support in host communities appeared to be a critical dimension in how well physicians adjusted. The results suggest that mentoring programs may be a way of facilitating settlement.


Inorganic chemoreactive nanosonosensitzers with unique physiochemical properties and structural features for versatile sonodynamic nanotherapies.
The fast development of nanomedicine and nanobiotechnology has enabled the emerging of versatile therapeutic modalities with high therapeutic efficiency and biosafety, among which nanosonosensitizer-involved sonodynamic therapy (SDT) employs ultrasound (US) as the exogenous activation source for inducing the production of reactive oxygen species (ROS) and disease therapy. The chemoreactive nanosonosensitizers are the critical components participating in the SDT process, which generally determine the SDT efficiency and therapeutic outcome. Compared to the traditional and mostly explored organic sonosensitizers, the recently developed inorganic chemoreactive nanosonosensitizers feature the distinct high stability, multifunctionality and significantly different SDT mechanism. This review dominantly discusses and highlights two types of inorganic nanosensitizers in sonodynamic treatments of various diseases and their underlying therapeutic mechanism, including US-activated generation of electrons (e-) and holes (h+) for facilitating the following ROS production and delivery of organic molecular sonosensitizers. Especially, this review proposes four strategies aiming for augmenting the SDT efficiency on antitumor and antibacterial applications based on inorganic sonosensitizers, including defect engineering, novel metal coupling, increasing electric conductivity and alleviating tumor hypoxia. The encountered challenges and critical issues facing these inorganic nanosonosensitzers are also highlighted and discussed for advancing their clinical translations.


Transformational Leadership, Ethical Leadership, and Participative Leadership in Predicting Counterproductive Work Behaviors: Evidence From Financial Technology Firms.
Counterproductive work behaviors are a crucial issue for practice and academic because it influences employees' job performance and career development. The present research conceptualizes Kahn's employee engagement theory and employs transformational leadership, ethical leadership, and participative leadership as its antecedents to predict counterproductive work behaviors through a latent growth model. The present research collected empirical data of 505 employees of fintech businesses in Great China at three waves over 6 months. The findings revealed that as employees perceived higher transformational leadership, ethical leadership, and participative leadership at the first time point, they may demonstrate more positive growths in employee engagement development behavior, which in turn, caused more negative growths in counterproductive work behaviors. The present research stresses a dynamic model of the three leaderships that can alleviate counterproductive work behaviors through the mediating role of employee engagement over time.


Regional anaesthesia and pain management.
Despite recent advances in analgesia delivery techniques and the availability of new analgesic agents with favourable pharmacokinetic profiles, current evidence suggests that postoperative pain continues to be inadequately managed, with the proportion of patients reporting severe or extreme postoperative pain having changed little over the past decade. Regional techniques are superior to systemic opioid agents with regards to analgesia profile and adverse effects in the context of general, thoracic, gynaecological, orthopaedic and laparoscopic surgery. Outcome studies demonstrate that regional analgesic techniques also reduce multisystem co-morbidity and mortality following major surgery in high risk patients. This review will discuss the efficacy of regional anaesthetic techniques for acute postoperative analgesia, the impact of regional block techniques on physiological outcomes, and the implications of acute peri-operative regional anaesthesia on chronic (persistent) postoperative pain.


Increased expression of amyloid precursor protein in oral squamous cell carcinoma.
In our previous study, we identified amyloid precursor protein (APP) in an oral squamous cell carcinoma (OSCC)-enriching subtractive hybridization library. Our present study attempts to define the significance of APP expression in the genesis of OSCC. RT-PCR analysis showed increase in APP mRNA expression for more than 2-fold in 76% of OSCC (n = 55) relative to corresponding non-cancerous matched tissues (NCMT). The majority of esophageal SCCs also had increase in APP mRNA expression. OSCC patients exhibiting increase in APP mRNA expression had significantly lower survival rate compared to patients exhibiting the opposite status. Western blotting analysis identified APP751 and APP770 as the major APP isoforms in oral keratinocytes. A high correlation between mRNA and protein expressions of APP was noted in OSCC/NCMT pairs. Immunohistochemistry further showed a remarkable increase of APP in OSCC tissue relative to NCMT. Treatment with an antisense oligonucleotide against APP reduced cellular and secreted APP as well as growth in an OSCC cell line. Our study provides novel clues that APP expression is involved in the proliferation and carcinogenesis of OSCC. Correlated with such pathogenesis was the survival of its victims. The degree of APP expression could serve as an invaluable marker for oral carcinogenesis.


Localization and function of group III metabotropic glutamate receptors in rat pancreatic islets.
Pancreatic islets contain ionotropic glutamate receptors that can modulate hormone secretion. The purpose of this study was to determine whether islets express functional group III metabotropic glutamate (mGlu) receptors. RT-PCR analysis showed that rat islets express the mGlu8 receptor subtype. mGlu8 receptor immunoreactivity was primarily displayed by glucagon-secreting alpha-cells and intrapancreatic neurons. By demonstrating the immunoreactivities of both glutamate and the vesicular glutamate transporter 2 (VGLUT2) in these cells, we established that alpha-cells express a glutamatergic phenotype. VGLUT2 was concentrated in the secretory granules of islet cells, suggesting that glutamate might play a role in the regulation of glucagon processing. The expression of mGlu8 by glutamatergic cells also suggests that mGlu8 may function as an autoreceptor to regulate glutamate release. Pancreatic group III mGlu receptors are functional because mGlu8 receptor agonists inhibited glucagon release and forskolin-induced accumulation of cAMP in isolated islets, and (R,S)-cyclopropyl-4-phosphonophenylglycine, a group III mGlu receptor antagonist, reduced these effects. Because excess glucagon secretion causes postprandial hyperglycemia in patients with type 2 diabetes, group III mGlu receptor agonists could be of value in the treatment of these patients.


Visualization of electron correlation in autoionizing states above the 3p threshold in magnesium.
The conditional probability density has been calculated for a number of autoionizing states (AIS) in Mg above the 3p threshold. The correlation in such high energy AIS has not been extensively studied and provides insight into the rovibrator behavior of two-electron atoms. The calculations have been done by configuration interaction (CI) with a B-spline basis. This allows for the simultaneous study of the effects of electron correlation and the widths and angular distribution of photoelectrons in multiphoton ionization. The states have been assigned approximate vibrational quantum numbers, and a correlation between the approximate quantum numbers and the photoelectron distribution is observed. Probability distribution for one electron when the other, represented by the small spike, is at its most probable distance from the nucleus. This is a distribution for the doubly-excited 1S(e) state commonly labeled as the 4s2 state.


Medical treatment of hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a common skin disease affecting an estimated 2% of the population. It causes significant symptoms and is notoriously difficult to treat. In this article, the current medical therapy is reviewed. At the present time, therapy appears to be based on an interpretation of the disease as either infectious or a form of acne. The understanding of the pathogenesis of HS suggests that these are not adequate models in order to understand the disease and this may explain the insufficiency of currently available medical treatment. The literature is sparse and there is a shortage of randomised, controlled trials. Three small, randomised, controlled trials have suggested that clindamycin, tetracycline and oestrogens and cyproteroneacetate may have an effect in some patients. Preceiving HS as an inflammatory skin disease suggests the use of general immunosuppressive drugs in the treatment of this condition. This approach, using both traditional immunosupressants and monoclonal antibodies, has been assessed in a small number of patients and appears to have some potential. However, the main source of evidence for this are case series and there is a strong need for more formal studies in this potentially debilitating disease.


Dysregulated resting state functional connectivity and obesity: A systematic review.
Obesity has been variously linked to differences in brain functional connectivity in regions associated with reward, emotional regulation and cognition, potentially revealing neural mechanisms contributing to its development and maintenance. This systematic review summarizes and critically appraises the existing literature on differences in resting state functional connectivity (Rs-FC) between overweight and individuals with obesity in relation healthy-BMI controls. Twenty-nine studies were identified and the results consistently support the hypothesis that obesity is associated with differences in Rs-FC. Specifically, obesity/overweight was consistently associated with (i) DMN hypoconnectivity and salience network hyperconnectivity; (ii) increased Rs-FC between the hypothalamus and reward, limbic and salience networks, and decreased Rs-FC between the hypothalamus and cognitive regions; (iii) increased power within regions associated with inhibition/emotional reasoning; (iv) decreased nodal efficiency, degree centrality, and global efficiency. Collectively, the results suggest obesity is associated with disrupted connectivity of brain networks responsible for cognition, reward, self-referential processing and emotional regulation.


Patient-based surgical outcome tool demonstrating alleviation of symptoms following parathyroidectomy in patients with primary hyperparathyroidism.
This study assessed the impact of parathyroidectomy on the preoperative symptoms of patients with primary hyperparathyroidism (1 degrees HPT) using a surgical outcome tool designed specifically for HPT. The multicenter nature of this study allowed us to validate further this disease-specific outcome tool. 1 degrees HPT patients from Canada, the United States, and Australia filled out the questionnaire preoperatively and postoperatively on day 7 and at 3 and 12 months. The symptoms recorded by the patients were expressed as parathyroidectomy assessment of symptoms (PAS) scores: the higher the score, the more symptomatic is the patient. Quality of Life (QOL) and self-rated health uni-scales were included. Altogether, 203 patients with 1 degrees HPT were enrolled; 27 from center A, 54 from center B, and 122 from center C; 58 nontoxic thyroid patients were enrolled for comparison. The comparison group had no significant change in their PAS scores throughout the study (scores 184, 215, 156, 186). All three centers demonstrated a significant reduction in symptoms following surgery. The median preoperative PAS score from center B patients was 282. Following surgery, PAS scores decreased significantly: 136, 58, 0 (p <0.05). Center C patients had a median preoperative PAS score of 344, decreasing postoperatively to 228 (p <0.05) and continuing to decrease to 190, then 180. Center A also demonstrated a significant reduction in symptoms at 3 months, from 510 preoperatively to 209 (p <0.001). Both QOL and self-rated health improved in the HPT patients, whereas no change was found in the comparison group following surgery. PAS scores are a reliable, disease-specific measure of symptoms seen with HPT. Parathyroidectomy significantly reduces these preoperative symptoms, and this change translated into an improved health-related QOL for the patients.


Female ROMK null mice manifest more severe Bartter II phenotype on renal function and higher PGE2 production.
ROMK null mice with a high survival rate and varying severity of hydronephrosis provide a good model to study type II Bartter syndrome pathophysiology (26). During the development of such a colony, we found that more male than female null mice survived, 58.7% vs. 33.3%. To investigate the possible mechanism of this difference, we compared the survival rates, renal functions, degree of hydronephrosis, as well as PGE(2) and TXB(2) production between male and female ROMK wild-type and null mice. We observed that female ROMK Bartter's mice exhibited lower GFR (0.37 vs. 0.54 ml.min(-1).100 g BW(-1), P < 0.05) and higher fractional Na(+) excretion (0.66% vs. 0.48%, P < 0.05) than male Bartter's. No significant differences in acid-base parameters, urinary K(+) excretion, and plasma electrolyte concentrations were observed between sexes. In addition, we assessed the liquid retention rate in the kidney to evaluate the extent of hydronephrosis and observed that 67% of male and 90% of female ROMK null mice were hydronephrotic mice. Urinary PGE(2) excretion was higher in both sexes of ROMK null mice: 1.35 vs. 1.10 ng/24 h in males and 2.90 vs. 0.87 ng/24 h in females. TXB(2) excretion was higher in female mice in both wild-type and ROMK null mice. The increments of urinary PGE(2) and TXB(2) were significantly higher in female null mice than males, 233.33% vs. 22.74% of PGE(2) and 85.67% vs. 20.36% of TXB(2). These data demonstrate a more severe Bartter phenotype in female ROMK null mice, and higher PGE(2) and TXB(2) production may be one of the mechanisms of this manifestation.


Structural interpretation of vicinal proton-proton coupling constants 3JH alpha H beta in the basic pancreatic trypsin inhibitor measured by two-dimensional J-resolved NMR spectroscopy.
Two-dimensional J-resolved 1H NMR spectroscopy was used to measure the vicinal spin-spin coupling constants 3JH alpha H beta for numerous, previously individually assigned amino acid residues in the basic pancreatic trypsin inhibitor at various temperatures between 30 and 85 degrees JC. An analysis of this data is proposed which enables one to compare the spatial arrangements of individual amino acid side chains in solution and in single crystals of the protein, and which also provides information on the mobility of the side chains in the solution conformation. As a rule, the amino acid side chains in the interior of the protein were found to be locked into unique spatial orientations, with the mobility restricted to rapid rotational fluctuations about this unique value for the dihedral angle chi 1. In most, but not all, instances the data for the interior amino acids indicate identical average conformations for the amino acid side chains in single crystals and in solution. For residues on the protein surface structural rearrangements between crystal and solution appear to be common, and the mobility in the solution conformation may include rapid averaging between two or several distinct, preferentially populated values of chi 1, analogous to the gauche-trans-gauche isomerization in isolated amino acids.


[Hemodynamic effects of the acute administration of captopril in refractory chronic congestive heart failure. Study of 13 patients and review of the literature].
We examined the acute hemodynamic response to Captopril, an oral converting enzyme inhibitor, in 13 patients with chronic congestive heart failure (CHF) refractory to conventional therapy, including other vasodilators. Captopril was administered in four increasing doses of 25, 50, 100 and 150 mg. The cardiac index (Cl) increased significantly (average +22%) in patients with high plasma renin activity (PRA). Pulmonary artery diastolic pressure (PADP) considerably decreased in all patients. A moderate decrease in systemic arterial pressure (SAP) was also observed. The heart rate (HR) did not change. Peak effect occurred 90 minutes after administration for the Cl, 30 to 120 minutes for PADP and SAP. The drug was well tolerated. This study confirms the acute beneficial hemodynamic effects of Captopril in patients with CHF refractory to conventional therapy. The possible mechanisms are discussed and the literature is reviewed.


The effect of proanthocyanidins and chlorhexidine on the bond strength of glass fiber posts to root dentin.
In this study, the influence of different irrigant solutions applied before cementation on the bond strength (BS) of glass fiber posts to root dentin was evaluated. Thirty endodontically treated maxillary canines of similar length were selected and divided into 3 groups (n = 10) according to the irrigant solution used before post cementation: 1% sodium hypochlorite (NaOCl; control), 2% chlorhexidine (CHX), or a 6.5% grape seed extract (GSE) cross-linking agent. After cementation of the posts, the roots were transversely sectioned to create 2 discs (2 mm) for each of the root thirds: coronal, middle, and apical. These discs were submitted to push-out tests (0.5 mm/min) to evaluate the BS between the glass fiber posts and the root dentin. Statistical analysis was performed by a 2-way analysis of variance and a Tukey test (P < 0.05). The failure mode was evaluated in all specimens. Both the CHX and GSE groups presented significantly higher BS values than the control group in all root thirds (P < 0.05). The values of the GSE group were significantly higher than those of the CHX group in all thirds except the apical third (P < 0.05). In the control group, the BS value was highest in the cervical third. There was no significant difference in the BS values between the cervical and middle thirds when CHX was used (P > 0.05); however, the BS value diminished significantly in the apical third (P < 0.05). The highest BS value in the GSE group was found in the middle third. The results showed that the use of either GSE or CHX before adhesive cementation improved the BS of glass fiber posts to root dentin.


A young woman with recurrent lower respiratory tract infection.
Tracheobronchomegaly is a rare congenital abnormality with marked widening of the trachea and major bronchi, in most cases associated with chronic recurrent respiratory tract infection. We present this rare syndrome in a young woman who presented with recurrent respiratory tract infection. She was found to have tracheobronchomegaly on flexible bronchoscopy, which was confirmed with high-resolution computed tomography findings.


Transcriptional regulation of the prothrombin gene in muscle.
Thrombin has been shown to mediate neurite retraction in neurons and synapse elimination at the neuromuscular junction. The presence of prothrombin mRNA has been demonstrated in brain and in muscle, but extra-hepatic regulation of the prothrombin gene has not been investigated. To identify cis-acting DNA elements involved in the expression of the prothrombin gene in muscle, we have isolated and analyzed a 1.3-kilobase pair promoter region of the mouse prothrombin gene. Using a series of transiently transfected plasmid constructs in which gene segments of the prothrombin promoter were linked to the luciferase gene, we have identified a sequence, -302 to -210, essential for prothrombin promoter activity in C2-myotubes. Fine analysis revealed that deletion of nucleotides between -248 and -235 eliminated prothrombin promoter activity in C2-myotubes. Furthermore, electrophoretic mobility shift assays demonstrated that a nuclear factor present in C2-myotubes, but not in C2-myoblasts or HepG2 hepatocytes, specifically binds to the sequence -241 to -225. Substitutional mutation of nucleotides -237 to -231 abolished myotube-specific promoter activity and inhibited the nuclear factor binding. Quantitative reverse transcription polymerase chain reaction demonstrated the expression of prothrombin mRNA in myotubes, but not in myoblasts, of primary, C2, and G8 muscle cells. This result correlates with the lack of prothrombin promoter activity in C2-myoblasts. The data thus suggest that a myotube-specific nuclear factor binds to a cis-acting sequence encompassing the core nucleotides -237 to -231 and plays a critical role in muscle-specific, differentiation-dependent expression of the mouse prothrombin gene.


Loss of cervical lordosis: What is the prognosis?
Neck pain is a diffuse problem with a high incidence and often leads to the more or less appropriate prescription of imaging studies of the cervical spine. In general, this is represented by a magnetic resonance imaging (MRI) scan. Frequently such studies reveal no other significant findings apart from a loss of cervical lordosis either under the form of a simple straightening of the spine or even an inversion of the normal curvature into a kyphosis. Faced with this entity, the clinician is put in front of a series of questions: to which extent such a finding plays a role in the patient's symptoms? If it does what is the role of conservative or even invasive treatment? What are the implications for surgery either for decompressive procedures or corrective procedures? To shed some light on these questions, the authors present a narrative review of the most relevant literature on the topic. Papers examined span from the initial epidemiologic reports out of the pre-MRI and computerized tomography era up to the most recent discussions on cervical sagittal alignment and its implications both for the surgical and nonsurgical patient. In this process, it becomes increasingly clear that we are still far from making any definite statements.


Nutritional Status of People with a Coexisting Chronic Wound and Extended Assessment Using Bioelectrical Impedance.
The diagnosis of malnutrition should be one of the pillars of comprehensive patient care, especially in the case of patients with large wounds, prolonged healing, or comorbidities. The condition for a reliable and accurate nutritional diagnosis is to link it with the parameters of nutritional status assessment at the basic level (anthropometric measurements and clinical assessment) and in depth (biochemical tests and bioelectrical impedance). A prospective study included a sample of 60 patients with coexisting chronic wounds (venous ulcers, diabetic foot syndrome, pressure injury) treated at the Wound Treatment Clinic of Fr. B. Markiewicz Podkarpackie Oncology Center (Poland). The method of estimation and diagnostic survey was used; the research tool was a scientific research protocol consisting of four parts. Self-care capacity was assessed based on the Barthel scale, nutritional status using blood biochemical parameters, and electrical bioimpedance. Wounds were classified according to the extent, depth of tissue structures, and potential infection. Subjects with pressure ulcers had statistically significantly lower fat-free mass component indices compared to those with diabetic foot syndrome and venous ulceration. The subjects with pressure ulcers had significantly lower values of body composition components compared to those with diabetic foot syndrome and venous ulcers. In the group of patients with pressure ulcers, the lowest values of albumin (3.20 g/dL), hemoglobin (10.81 g/dL), and nutritional risk index (NRI) (88.13 pts.) scores were confirmed. Subjects with pressure ulcers with limited self-care presented a non-physiological nutritional status, indicating a risk of malnutrition. Local actions related to wound treatment should be preceded by a general examination, considering the state of augmented nutrition with the use of electrical bioimpedance.


Formulation, characterisation and in vitro studies of doxorubicin-loaded silica-polydimethylsiloxane granules.
The goal was to develop a granule-type formulation, characterised as a long-term, zero-order release delivery system for doxorubicin hydrochloride (DOX) and composed of a sol-gel derived silica-polydimethylsiloxane solid matrix with well-defined microstructures. The preparation of the DOX-loaded granule-type formulation was performed using the sol-gel moulding method. A liquid-form of DOX was added to the sol before moulding. Optical microscopy, X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and N2 adsorption/desorption studies were employed to characterise the obtained formulation. The influence of different drug loads of DOX per granule (136, 336 and 555μg) on the release profiles was assessed on a USP Apparatus 4 dissolution and via UV/Vis end analysis. The in vitro mineralisation of these formulations associated with the nucleation of the apatite layer on their surface was also examined. The semi-ellipse shape and micrometer-size of the DOX-loaded granule-type formulation was successfully obtained. These formulations exhibited a mesoporous structure, uniform pore size distribution and good monodispersity. Following an initial burst, the slow drug release from all formulations followed zero order kinetics under infinite sink conditions for over 70days. Besides the formulation's potential properties as a carrier, the material was also surface-reactive during in vitro mineralisation.


The role of understudied post-translational modifications for the behavior and function of Signal Transducer and Activator of Transcription 3.
The Signal Transducer and Activator of Transcription (STAT) family of transcription factors is involved in inflammation, immunity, development, cancer, and response to injury, among other biological phenomena. Canonical STAT signaling is often represented as a 3-step pathway involving the sequential activation of a membrane receptor, an intermediate kinase, and a STAT transcription factor. The rate-limiting phosphorylation at a highly conserved C-terminal tyrosine residue determines the nuclear translocation and transcriptional activity of STATs. This apparent simplicity is actually misleading and can hardly explain the pleiotropic nature of STATs, the existence of various noncanonical STAT pathways, or the key role of the N-terminal domain in STAT functions. More than 80 post-translational modifications (PTMs) have been identified for STAT3, but their functions remain barely understood. Here, we provide a brief but comprehensive overview of these underexplored PTMs and their role on STAT3 canonical and noncanonical functions. A less tyrosine-centric point of view may be required to advance our understanding of STAT signaling.


[Evaluation of the accuracy of alveolar bone height measurement in vitro by cone beam computed tomography].
To evaluate the accuracy and repeatability of alveolar bone height measurement in vitro by cone beam computed tomography (CBCT), and to provide theoretical application of CBCT in periodontal clinic. Eight dry mandibles with 236 selected markers were scanned by CBCT scanner, and the distance from alveolar ridge crest to cemento-enamel junction were measured on every marker by the images of CBCT. Meanwhile the distances on the dry mandibles were measured directly by vernier caliper. All the data were analyzed by SPSS 13.0 statistics software. There was no significant difference between the two repeated measurements by the CBCT images (P >0.05), and no significant difference were found between the measurement by the CBCT images and by vernier caliperas well (P > 0.05). The CBCT images could demonstrate the three-dimensional relationships between tooth and alveolar bone accurately. As far as the height of alveolar bone measurement was concerned, CBCT show good accuracy and repeatability in vitro.


Regulation Mechanism of MicroRNAs in Non-Small Cell Lung Cancer.
MicroRNAs are small non-coding RNAs with regulatory biological activity, by modulating target genes on epigenetic, transcriptional, post-transciptional and translational levels. Hundreds of reports indicated that miRNAs play important roles in non-small cell lung cancer (NSCLC). Actually, microRNAs are both regulation targets and regulators targeting effector genes. This article reviewed multifaceted role of microRNAs associated to NSCLC, not only targeting to but also targeted by tumor related genes, to help us understand microRNAs related complex regulation networks. Aberrant expressed micoRNAs and their targets were summarized; the statistical results showed that several microRNAs may play key roles by targeting multiple tumor associated targets. On the other hand, Oncogenes and tumor repressors represented by PTEN were also shown to be the most popular targets of microRNAs. Additionally, ZEB1/2 may be a featured pathway in NSCLC, with significant frequency modulated by microRNAs.


Natural Infection of a European Red Squirrel (Sciurus vulgaris) with Francisella tularensis subsp. Holarctica.
Postmortem examination and immunohistochemical and bacteriologic analyses on a free-ranging European red squirrel (Sciurus vulgaris) revealed a systemic infection with Francisella tularensis. Genome sequencing and single-nucleotide polymorphism analysis were consistent with F. tularensis subs. holarctica clade B.45. Tularemia has not previously been reported in this species.


Preparation and characterization of n-hydroxyapatite/PCL-pluronic-PCL nanocomposites for tissue engineering.
In this paper, a new kind of polymeric nanocomposite materials based on nano-hydroxyapatite (n-HA) and PCL-Pluronic-PCL (PCFC) copolymer were prepared by in situ combination method. Firstly, the PCFC copolymer was synthesized by ring-opening polymerization of epsilon-caprolactone initiated by Pluronic (PEG-PPG-PEG); Secondly, n-HA powder were combined with PCFC to form polymeric composites in the presence of hexamethylene diisocyanate (HDI). The obtained composites were characterized by 1H-NMR, FTIR, XRD, TEM, SEM, DTA/TGA, and tensile testing. The results revealed that n-HA could be dispersed into polymer matrix uniformly, and the n-HA/PCFC composite showed great mechanical properties when the content of n-HA was 10 wt%. The microstructure and thermal properties of the composites were discussed in the paper too. The experimental results suggested that this polymeric nanocomposite might have great potential application in the field of tissue engineering.


A Study on Suitability of EAF Oxidizing Slag in Concrete: An Eco-Friendly and Sustainable Replacement for Natural Coarse Aggregate.
Environmental and economic factors increasingly encourage higher utility of industrial by-products. The basic objective of this study was to identify alternative source for good quality aggregates which is depleting very fast due to fast pace of construction activities in India. EAF oxidizing slag as a by-product obtained during the process in steel making industry provides great opportunity to utilize it as an alternative to normally available coarse aggregates. The primary aim of this research was to evaluate the physical, mechanical, and durability properties of concrete made with EAF oxidizing slag in addition to supplementary cementing material fly ash. This study presents the experimental investigations carried out on concrete grades of M20 and M30 with three mixes: (i) Mix A, conventional concrete mix with no material substitution, (ii) Mix B, 30% replacement of cement with fly ash, and (iii) Mix C, 30% replacement of cement with fly ash and 50% replacement of coarse aggregate with EAF oxidizing slag. Tests were conducted to determine mechanical and durability properties up to the age of 90 days. The test results concluded that concrete made with EAF oxidizing slag and fly ash (Mix C) had greater strength and durability characteristics when compared to Mix A and Mix B. Based on the overall observations, it could be recommended that EAF oxidizing slag and fly ash could be effectively utilized as coarse aggregate replacement and cement replacement in all concrete applications.


B700, a melanoma-specific antigen, catalyzes metabolism of prostaglandin E2.
B700 is an albumin-like mouse-melanoma-specific antigen of unknown primary structure and biochemical function. The ability of mouse serum albumin to catalyze weak degradation of prostaglandin E2 has been utilized to compare functional similarities between B700 and mouse serum albumin. Both proteins catalyze the degradation of prostaglandin E2 to prostaglandin A2 and prostaglandin B2. This catalytic ability is related to the amino acid composition of the two proteins within the functional region rather than the 3-dimensional configuration, the activity is not altered upon boiling. The primary prostaglandin E2 metabolite in the presence of mouse serum albumin is prostaglandin B2, while prostaglandin A2 predominates in B700 catalyzed degradations. An additional product, presently unidentified, is produced during B700 catalyzed degradation of prostaglandin E2. Our studies indicate that the B700 protein has weak enzymatic activity for prostaglandin E2 similar to that of albumin. To our knowledge, B700 is the only melanoma antigen for which enzymatic activity has been demonstrated.


Clinical and genetic characteristics in patients with Huntington's disease from China.
Huntington's disease (HD) is a neurodegenerative disease caused by the expansion of unstable CAG repeats in the HTT gene. There are scarce data about HD in China. Fifty-eight HD patients were consecutively recruited and assessed using the Unified HD Rating Scale (UHDRS) motor section and UHDRS behaviour assessment (UHDRS-b). Genetic analyses were also conducted. Thirty-three women and Twenty -five men were diagnosed with a mean age of 46.1 ± 11.2 years and a mean number of CAG triplet repeats 44.6 ± 4.4. CAG triplet repeat number was negatively correlated with age at onset, and positively correlated with UHDRS-b total score, and its subdomains including depressed mood, low self-esteem, anxiety and irritability. On the other hand, negative correlations were identified between age at onset and UHDRS-b total score, and its subdomains include low self-esteem, anxiety, suicidal thought, irritability and apathy. Disease durations were correlated with UHDRS motor scores and anxiety domain of UHDRS-b. This is the largest series of Chinese HD patients with demographic, clinical and genetic data confirms the demographic features of Chinese HD patients are comparable to those in other ethnic backgrounds. CAG triplet repeat number may also predict the severity of behaviour problems in HD patients besides its predication for age of onset.


Disorganization and reorganization of the Golgi complex and the lysosomal system in association with mitosis.
The fate of the Golgi complex and the lysosomal system during mitosis was studied in L929 mouse fibroblasts by staining with wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and transmission electron microscopy. In interphase WGA-HRP stained a circumscribed juxtanuclear region encompassing the stacked Golgi cisternae, the trans Golgi network, secretory vacuoles, endosomes, and lysosomes. As the cells entered prophase, WGA-HRP reactive material was spread around the perimeter of the nucleus. Fine structurally, the Golgi complex was found to be disorganized and its stacks were scattered throughout the cytoplasm together with clusters of lysosomes. At the same time, the trans Golgi network atrophied and secretory vacuoles and endosomes decreased in number. The disperse and structurally modified state of the Golgi complex and the lysosomal system persisted until late telophase, when they were reorganized in a defined region, most frequently on the outside of the nucleus as related to the midbody. The disorganization and reorganization of the Golgi complex and the lysosomal system coincided with the breakdown and rebuilding of the microtubular cytoskeleton, and showed striking similarities to the previously described modifications of these organelles during treatment with and after withdrawal of microtubule-disruptive drugs. Based on the findings, a model is presented that links the division of the Golgi complex and the lysosomal system to the loss of the radiating array of interphase microtubules.


Evidence-Based Cardiovascular Disease Medicines' Availability in Low-Cost Generic Drug Programs in the United States : A Cross-Sectional Study.
Low-cost generic programs (LCGPs) that expand access to affordable cardiovascular disease (CVD) medicines can assist patients in achieving desired cardiovascular outcomes. It is important that LCGPs offer CVD medicines that promote evidence-based prescribing. To evaluate LCGPs' coverage of evidence-based CVD medications using a clinical framework that examines coverage of core treatments, coverage of options with the highest-quality evidence, and the variety of medication options and strengths that create choices and allow dosing titration. Cross-sectional study. Publicly available LCGPs in March and April 2023 in the United States. 19 LCGPs. Proportion of LCGPs that offered evidence-based CVD medicines within a clinical framework for 6 CVDs (atrial fibrillation, heart failure, hyperlipidemia, hypertension, post-acute coronary syndrome secondary prevention, and stable angina) according to 4 availability metrics (breadth, choice, high-quality evidence, and titratability). The availability of CVD medication varied by program, drug, and CVD condition. Some programs had more breadth and choice of coverage for most CVDs (H-E-B, Kroger, Mark Cuban Cost Plus Drug Company, and Walmart), whereas many had more focused coverage and others markedly limited offerings. Nearly all LCGPs offered angiotensin-converting enzyme inhibitors, β-blockers, thiazides, and moderate-intensity statins, but availability was low for higher-cost or lower-use generics (antiplatelets and antiarrhythmics). Core pharmacotherapy coverage and choices were limited for atrial fibrillation and heart failure but widely available for hypertension and hyperlipidemia. In-depth cost analysis was not investigated. Coverage of evidence-based medications for the 6 CVDs investigated varied by LCGP and condition. Because high availability of core CVD pharmacotherapy can enhance optimal disease state management, LCGPs should identify existing limitations in their coverage and continuously revise their formularies to improve the comprehensiveness of CVD medication coverage. None.


Prevalence of cuterebrid parasitism among woodmice in Virginia.
Botfly infestation was analyzed in 1319 small mammals from varied habitats and elevations in upland Virginia, 1972-1974. Adult Cuterebra fontinella were reared from bots infesting the woodmouse (Peromyscus leucopus). Of 651 woodmice, 199 (30.6%) were infested at least once. The season of bot infestation extended from May through November of all years, with peak prevalence (mean 42.2%) in August. Infestation in woodmice was general over a 2000 km2 study area during peak months. Significantly greater prevalence (P less than 0.001) was seen in forested and brushy habitat (39.9%) compared with old fields (2.6%). Higher prevalence (P less than 0.01) was found in males than in females, and in postjuveniles compared to adults. Greatest overall prevalence (39.1%) was in postjuvenile males. Most warble sites (98%) were inguinal, and observations suggested that many infested adults were non-reproductive. Mean burden (1.27) was independent of host age, sex, habitat, and month of capture. Multi-infestations occurred in 23% of the affected mice; maximum burden was six bots. Botflies were absent or negligible in sympatric deermice (P. maniculatus) and twelve other species of rodents and shrews.


[8-[Bis(carboxymethyl)aminomethyl]-6-bromo-7-hydroxycoumarin-4-yl]methyl moieties as photoremovable protecting groups for compounds with COOH, NH2, OH, and C=O functions.
We introduce a variant of coumarin-based photoactivatable protecting groups and use it exemplarily for caging of a carboxylic acid, an amine, a phenol, and a carbonyl compound. The caged compounds are efficiently photolyzed at long-wavelength UV/vis irradiation. Compared to the corresponding (6-bromo-7-hydroxycoumarin-4-yl)methyl (Bhc) derivatives, the novel coumarin-type caged compounds are distinguished by (i) dramatically increased solubilities in aqueous buffers, (ii) lower pK(a) values of the C7 hydroxyl of the coumarin chromophore, thus permitting efficient photorelease at lower pH, and (iii) higher photolysis quantum yields in the case of photoprotected carbonyl compounds. The primary step of the photocleavages occurs with rate constants of about 10(9) s(-1).


Altered expression of metabolic pathways in CLL detected by unlabelled quantitative mass spectrometry analysis.
Chronic lymphocytic leukaemia (CLL) remains the most common incurable malignancy of B cells in the western world. Patient outcomes are heterogeneous and can be difficult to predict with current prognostic markers. Here, we used a quantitative label-free proteomic technique to ascertain differences in the B-cell proteome from healthy donors and CLL patients with either mutated (M-CLL) or unmutated (UM-CLL) IGHV to identify new prognostic markers. In peripheral B-CLL cells, 349 (22%) proteins were differentially expressed between normal B cells and B-CLL cells and 189 (12%) were differentially expressed between M-CLL and UM-CLL. We also examined the proteome of proliferating CLL cells in the lymph nodes, and identified 76 (~8%) differentially expressed proteins between healthy and CLL lymph nodes. B-CLL cells show over-expression of proteins involved in lipid and cholesterol metabolism. A comprehensive lipidomic analysis highlighted large differences in glycolipids and sphingolipids. A shift was observed from the pro-apoptotic lipid ceramide towards the anti-apoptotic/chemoresistant lipid, glucosylceramide, which was more evident in patients with aggressive disease (UM-CLL). This study details a novel quantitative proteomic technique applied for the first time to primary patient samples in CLL and highlights that primary CLL lymphocytes display markers of a metabolic shift towards lipid synthesis and breakdown.


Skin spread from an intracranial glioblastoma: case report and review of the literature.
Extracranial metastases secondary to intracranial neoplasm are extremely rare. The incidence of extraneural metastases of brain tumours is estimated to be less than 0.4%. The authors report a case of postoperative intracranial glioblastoma spreading to the skin in an adult patient. In this case, the radiological images and surgical findings suggest that the potential dissemination mechanism is as a result of infiltration through the surgical wound site. The primary tumour-upon coming into contact with the dura and the skin-mimicked the characteristics of both tissues. This case supports the theory of risk of spread through the durotomy site, although this phenomenon is extremely rare. Both the specific pathogenic mechanisms as well as the ideal and effective management have not been established yet and require further investigation.


Case report: laparoscopic Boari flap.
A Boari flap may be required to bridge long defects of the middle and lower ureter to the bladder. Laparoscopic construction of a Boari flap was performed in a patient with a ureteral stricture secondary to iatrogenic injury. The salient steps performed were spatulation of the transected ureteral end, fashioning of a Boari flap from the bladder, end-to-side anastomosis of the ureter to the flap, placement of a stent with the aid of a suction cannula, and closure of the flap over the stent. A Boari flap can be accomplished laparoscopically with minimal morbidity.


The regulatory impact of RNA-binding proteins on microRNA targeting.
Argonaute is the primary mediator of metazoan miRNA targeting (MT). Among the currently identified >1,500 human RNA-binding proteins (RBPs), there are only a handful of RBPs known to enhance MT and several others reported to suppress MT, leaving the global impact of RBPs on MT elusive. In this study, we have systematically analyzed transcriptome-wide binding sites for 150 human RBPs and evaluated the quantitative effect of individual RBPs on MT efficacy. In contrast to previous studies, we show that most RBPs significantly affect MT and that all of those MT-regulating RBPs function as MT enhancers rather than suppressors, by making the local secondary structure of the target site accessible to Argonaute. Our findings illuminate the unappreciated regulatory impact of human RBPs on MT, and as these RBPs may play key roles in the gene regulatory network governed by metazoan miRNAs, MT should be understood in the context of co-regulating RBPs.


Interfacial Nanostructure and Asymmetric Electrowetting of Ionic Liquids.
In this work, the interfacial nanostructure and electrowetting of ionic liquids having the same 1-ethyl-3-methylimidazolium cation ([EMIm]+) but different anions such as bis(trifluoromethylsulfonyl)imide (TFSI-), trifluoromethylsulfonate (TfO-), methylsulfonate (OMs-), acetate (OAc-), bis(fluorosulfonyl)imide (FSI-), dicyanamide (DCA-), and tris(pentafluorethyl)trifluorphosphat (FAP-) on bare metallic electrodes were investigated. In the investigated voltammetric potential regime, the contact angle versus voltage curve is asymmetric with respect to surface polarity. The electrowetting of the ILs occurs at negative potentials but does not occur at positive potentials. In situ atomic force microscopy (AFM) shows that the IL adopts a multilayered structure at the solid/IL interface, and a cation-rich layer is present in the innermost layer during cathodic polarization. The cations can change their orientation and propagate ahead of the three-phase contact line by diffusion, leading to further spreading on the negatively charged surface. The formation of such a surface layer is also evidenced by X-ray photoelectron spectroscopy. Such a surface diffusion mechanism does not occur during anodic polarization, where anions are enriched. In addition, the influence of substrate, water, and dissolved zinc salts on the electrowetting of ILs was studied. Our findings provide valuable insights for the interfacial nanostructure and the electrowetting of ILs.


Novel dynamic ccaling regime in hole-doped La2CuO4.
Only 3% hole doping by Li is sufficient to suppress the long-range three-dimensional (3D) antiferromagnetic order in La2CuO4. The spin dynamics of such a 2D spin liquid state at T<<J was investigated with measurements of the dynamic magnetic structure factor S(omega,q), using cold neutron spectroscopy, for single crystalline La2Cu0.94Li0.06O4. S(omega,q) peaks sharply at (pi,pi) and crosses over around 50 K from omega/T scaling to a novel low temperature regime characterized by a constant-energy scale. The possible connection to a crossover from the quantum critical to the quantum disordered regime of the 2D antiferromagnetic spin liquid is discussed.


Expression of claudin-4 molecule in canine exocrine pancreatic acinar cell carcinomas.
Claudins, integral membrane proteins are components of the tight junction structures between epithelial and endothelial cells. These transmembrane proteins create a primary barrier to prevent paracellular transport of solutes, and also restrict the lateral diffusion of membrane lipids and proteins to maintain the cellular polarity. The aim of the present study was to characterise the expression pattern of claudin-4 tight junction molecule in canine normal pancreatic tissues and in the well-differentiated and poorly-differentiated pancreatic acinar cell carcinomas in canines. The necropsy samples included canine intact pancreatic tissues, and canine well-differentiated and poorly-differentiated pancreatic acinar cell carcinomas samples. Claudin-4 was detected as an intense lateral membrane labelling of acinar cells in all intact pancreatic tissues. The intact epithelial cells of the different ducts were negative for the claudin-4 molecule. All primary and secondary canine well-differentiated exocrine pancreatic acinar cell carcinoma tissues showed intense apical lateral positivity for the claudin-4 molecule. All primary and secondary poorly-differentiated pancreatic acinar cell carcinoma tissues showed diffusely the loss of claudin-4 expression. Consequently, we hypothesize that the loss of expression of claudin-4 plays a role in the progression of canine pancreatic acinar cell carcinoma and may lead to cellular detachment, disorientation and invasion of these pancreatic cancers. Furthermore, claudin-4 can be used as an immunohistochemical marker to distinguish canine well-differentiated and undifferentiated exocrine pancreatic acinar cell carcinomas.


Validation of a simple liquid chromatographic method for determination and quantitation of residual ivermectin and doramectin in pig liver.
A rapid and quantitative method for the extraction, derivatization, and liquid chromatography with fluorescence detection of ivermectin (IVM) and doramectin (DOM) residues in porcine liver was developed and validated. IVM and DOM were extracted from the liver samples with acetonitrile, the supernatant was evaporated to dryness at 37 degrees C under nitrogen, and the residue was reconstituted in 1-methylimidazole solution. After 2 min at room temperature, IVM and DOM were converted to a fluorescent derivative and then separated on a Hypersil ODS column. The derivatives of IVM and DOM were detected and quantitated with high specificity by fluorescence (excitation: 365 nm, emission: 475 nm). Abamectin was used as an internal standard. The mean extraction efficiencies from fortified samples (15 ng/g) were 75% for IVM and 70% for DOM. The limit of detection was 0.8 ng/g for both IVM and DOM.


Spinal muscular atrophy is not the result of mutations at the beta-hexosaminidase or GM2-activator locus.
The disease locus for the clinically heterogeneous childhood spinal muscular atrophies (SMA) maps to the chromosome 5 subregion, 5q11.2-13.3. The beta-subunit of beta-D-N-acetylhexosaminidase (hexosaminidase) (EC 184.108.40.206) (Hex B) maps to the same region, and the protein required for substrate recognition by this enzyme, GM2-activator protein, likewise maps to chromosome 5. We have investigated the possibility of allelic variation among some forms of SMA and hexosaminidase deficiency. Recombination between the Hex B and SMA loci eliminates this enzyme as a candidate site for defects causing the illness. Furthermore, we show that, despite previous evidence to the contrary, the GM2-activator locus does not map to chromosome 5, thereby eliminating it as a candidate gene for SMA.


Impact of prenatal cold stress on placental physiology, inflammatory response, and apoptosis in rats.
Prenatal cold stress is one of the earliest factors affecting mammalian health, and is associated with neonatal growth retardation and immune dysfunction, thus increasing disease susceptibility. The mechanisms underlying these observations remain unclear; hence, the objective of this study was to elucidate placental responses to cold stress. 60 maternal rats were randomly allocated to either stressed (n = 30) or non-stressed (control, n = 30) treatment conditions and 30 pubs (n=15) were used for the pups analysis. We found that maternal exposure to cold stress resulted in decreased body temperature, increased food intake without body weight gain, and a high level of plasma corticosterone (CORT) between gestational day (GD) 14 and GD21. In addition, gestation cold stress induced the placental expression of heat shock protein 70 (HSP70), IκBα, glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), interferon (IFN) regulatory factor 3 (IRF3), Caspase-3 proteins and altered the ratio of B-cell lymphoma-extra large (Bcl-xL) to Bcl-associated x (Bax) proteins on gestational GD15, GD17, GD19, and GD21, also resulted in the production of interleukin (IL)-1β. Next, gestational cold stress provoked a decrease in plasma GH levels of 21-day-old offspring, and the body weights of offspring were have no differences from postnatal day (PD) 1-21. Taken together, our results indicate that gestational cold stress induces placental apoptosis and the activation of NF-kB via HSP70/TLR4/NF-κB signaling pathways in the placenta, these changes may affect placental function and fetus development.


Emplacement and everyday use of medications in domestic dwellings.
To extend knowledge of relationships between people and domestic settings in the context of medication use, we conducted fieldwork in twenty households in New Zealand. These households contained a range of 'medicative' forms, including prescription drugs, traditional remedies, dietary supplements and enhanced foods. The location and use of these substances within domestic dwellings speaks to processes of emplacement and identity in the creation of spaces for care. Our analysis contributes to current understandings of the ways in which objects from 'outside' the home come to be woven into relationships, identities and meanings 'inside' the home. We demonstrate that, as well as being pharmacological objects, medications are complex, socially embedded objects with histories and memories that are ingrained within contemporary relationships of care and home-making practices.


Comparison of oral health in children aged 5-6 years in the Czech Republic and Yemen.
Dental caries is the most widespread oral disease in the world, with multifactorial aetiology. It hinders not only the ability to eat good food, but also affects perfect speech and well-being. As the disease is almost completely preventable, and at its early stage well treatable, the prevalence of dental caries expresses the lack of public health literacy and skills in dental hygiene, and availability of adequate dental care. Children are especially vulnerable to dental caries, hence the WHO recommends regular monitoring of children's oral health and also appropriate controls for its continual improvement. We describe the part of the study targeted on dental health of Czech (CR) and Yemeni (YE) school children and its association with basic anthropometric markers of their nutrition. Total of 190 children aged 5-6 years (100 from CR and 90 from YE, 111 males, 79 females - 22.5% of the wider study on 5-15 years old children) were involved (after obtaining informed consent from their parents). The sample is not representative. All dental examinations were performed in accordance with the WHO criteria by the same examiner. Each individual tooth, whether primary or permanent, was identified as intact, untreated decayed, extracted or filled. Also, dmft/DMFT indexes for individual children were calculated. Anthropometric measurements were performed by standardized methods and the body mass index (BMI-for-age) was calculated. For the statistical evaluation of differences, the program MedCalc Software Inc., Belgium, was used, especially t-test, Pearson's correlation (rho with 95% confidence interval (CI) and Spearmen's rank correlation coefficient; p-values less than 0.05 were considered significant. Dental caries prevalence and dmft scores (2.12-4.31) were found to be rather high among this age group of children, with no significant differences in relation to gender and country; only 30.0% or less of children were caries free. The decayed component was the major part of the dmft scores, and the evaluation of restorative index (ri%) indicates a high percentage of untreated caries and a high treatment need. Especially in Yemeni children dental caries is wholly untreated (ri 0.0 %), but also in the CR the dental care is rather poor (ri 38-41%). The levels of association(s) between oral health markers (dmft/DMFT) and BMI were inconsistent (both positive and negative), but without statistical significance. The high prevalence of poor dental health in these groups of Czech and Yemeni children and low or even no treatment urge effort to include WHO recommendations for practice into the national health policies. Prevention and control of dental caries can be promoted not only by dentists, targeting children and the whole family and their dental habits and lifestyle, with the cooperation of schools, paediatricians, general practitioners and with gynaecologists targeting new and expectant mothers, to increase their knowledge and skills.


[Diabetes mellitus reduces the expression of SK3 in rat cavernous tissues].
SK3, one of the small conductance calcium-activated potassium channels, is the key substance of the endothelium-derived hyperpolarizing factor (EDHF) passway. This study aimed to investigate the expression of SK3 in the cavernous tissue of rats with diabetes mellitus (DM). Twenty-six DM models were made by injection of streptozocin (STZ) out of 50 male Sprague-Dawley rats, and another 15 that failed to be modeled were included in an STZ group. Ten healthy male rats were taken as blank controls. Eight weeks later, the penile erectile function of the rats was detected by injection of apomorphine (APO) at 80 microg/kg, and the expression of SK3 in the cavernous tissue was determined by RT-PCR and Western blot. Penile erection was observed in 14 (54%) of the 26 DM rat models and in all the rats of the STZ and blank control groups. Both the mRNA and protein expressions of SK3 were significantly lower in the DM (0.50 +/- 0.09 and 0.65 +/- 0.06) than in the STZ (1.15 +/- 0.03 and 1.28 +/- 0.04) and blank control groups (1.21 +/- 0.04 and 1.34 +/- 0.05) (P < 0.05). There were no significant differences between the STZ and blank control groups in either penile erection or mRNA and protein expressions of SK3 (P > 0.05). Diabetes mellitus can significantly reduce erectile function in rats, which may be related to the decreased expression of SK3 in the corpus cavernosum.


DNA methylation patterns and sequence transitions of the CpG island of mouse Hprt during early embryogenesis.
The timing and pattern of methylation of the CpG island in the X-chromosome gene, Hprt, was examined using bisulfite methods to assess the occurrence of DNA cytosine methylation at the onset of X-chromosome inactivation (XCI). The Hprt sequences were extensively methylated in 4.5 dpc blastocysts, and the levels of methylation progressively decreased to 7.5 dpc. Adult patterns of methylation were established in the embryonic tissues after 7.5 dpc. By contrast, methylation continued to decrease in extraembryonic lineages and at 13.5 days was not detectable on the paternal Hprt sequences in the yolk sac endoderm. In the bisulfite-treated coding strand, numerous G to A transitions and CpTpG methylations were observed that were unique to the methylated or nonmethylated Hprt sequences, respectively, in early development.


Frequency of heavy ions in space and their biologically important characteristics.
A review of the galactic cosmic ray energy spectra of heavy ions with Z< or = 28 is presented. Fluxes of these ions within critical body organs of astronauts travelling outside the magnetosphere will be modified from the free space values by fragmentation within the spacecraft and the bodies of the astronauts themselves. The effects of such fragmentation are presented in terms of variations in the particle flux above a given dE/dx at representative depths. Present limitations to the accuracy of such calculations are considered. The validity of dE/dx as a relevant physical parameter for characterizing the biologically important component of the heavy ion radiation environment is discussed.


Pericholecystic adhesions in single v multiple gallstones and their consequences for laparoscopic cholecystectomy.
Adhesions are amongst the common reasons for open conversion of laparoscopic cholecystectomy. It is not clear whether this problem is more common with single or multiple gallstones. The clinical records of 110 patients with chronic cholelithiasis harboring multiple stones in the gallbladder (multiple stone group; MSG) and 45 patients with single stones in the gallbladder (SSG) undergoing laparoscopic cholecystectomy were analyzed for differences in the clinical presentation and outcome with special reference to the incidence of pericholecystic adhesions, size of the stones, and their implications for conversion and complications. Patients in the SSG had a significantly higher incidence of dense pericholecystic adhesions in the region of the porta hepatis (P = 0.003). Eleven patients in the SSG (24.4%) were converted to open cholecystectomy. Dense pericholecystic adhesions around the porta hepatis alone contributed to nine of these conversions (81.8%). The size of the stones was significantly greater (P < 0.001) in those patients of the SSG who required conversion to open cholecystectomy. Thirteen patients of the MSG (11.8%) required conversion to open cholecystectomy. Dense pericholecystic adhesions alone contributed to conversion in four cases (30.7%), and the size of the gallstones was not significantly different (P = 0.981) in patients with or without conversion to open cholecystectomy. There was no difference in the clinical presentation or complications in the two groups of patients. Dense adhesions in the porta hepatis are significantly more common in patients with single stones and are the most common reason for open conversion.


Multi-slice 3D-CTA - an improvement over single slice helical CTA for cerebral aneurysms.
The aim of this study was to demonstrate the utility of volume rendered multi-slice helical three-dimensional CT angiography in patients with cerebral aneurysm when compared with single slice CT angiography and formal digital subtraction angiography. A prototype Toshiba Aquilon multi-slice CT scanner was employed with the following scan conditions: voltage 135 kV; current 300 mA; slice thickness 0.8 mm; scan speed 0.75 sec/cycle; couch speed 1 mm/sec; range 50 mm from foramen magnum; scan pitch 3; three dimensional images were reconstructed using multiple image projections and integral volume rendering algorithms on a Xlink/Xtension workstation. 80 cases of multi-slice CTA for cerebral aneurysm carried out at Fujita University from January 1999 to January 2001 were reviewed. The advantages of multi-slice imaging are illustrated with representative cases of cerebral aneurysm - good demonstration of three dimensional anatomy, appreciation of perforators down to 1 mm in size, delineation of the vessels around the aneurysm complex, relationship between the aneurysm and skull base, information on calcification, thrombus and blebs in the wall and eleven routine views for perusal. Multi-slice CTA is a significant improvement over single slice CTA for cerebral aneurysms. It is our experience the superior and precise images produced by multi-slice technology displays anatomical information not readily available from standard DSA. Multislice 3D-CTA is relatively non-invasive and provides better and adequate detail for surgical planning. The basis of multi-slice CT angiography is described. Multi slice CTA is changing the way cerebral aneurysms are being managed nowadays. New advances in the technology of multi-slice CTA resulting in increased image resolution are outlined.


RNA expression analysis of a congenital intracranial teratoma.
Congenital intracranial tumors are extremely rare and account only for 0.5%-1.5% of brain tumors in children. We report a large intrauterine congenital teratoma in a female fetus at gestation weeks 37, which was diagnosed by detecting the tumor and associated craniomegaly with ultrasonography (US) and magnetic resonance (MR) imaging. The tumor had replaced the cerebral hemispheres and produced prenatal manifestations. Pathologic examination showed an immature teratoma, which was differentiated from all three germ layers. Microarray analysis revealed upregulation of ten genes and downregulation of three genes, as well as upregulation of 41 genes of ribosomal proteins in teratoma cells, compared to normal brain tissue of the patient. The data from the microarray analysis offer not only the potential to help define disease pathogenesis but may also provide clues to identify potential molecular therapeutic targets.


Animal Welfare and Economic Aspects of Using Nurse Sows in Swedish Pig Production.
The number of born piglets per litter has increased in Swedish pig industry, and farmers are struggling to improve piglet survival. A common practice is to make litters more equally sized by moving piglets from large litters to smaller to make sure that all piglets get an own teat to suckle. Litter equalization is not always enough, as many sows have large litters and/or damaged teats, which results in an insufficient number of available teats. One way to solve this problem is to use nurse sows. A nurse sow raises, and weans, her own piglets before receiving a foster litter. The objectives of this study were to address how the use of nurse sows affects the welfare of sows and piglets and to explore how it impacts the contribution margin of pig production in Sweden. A literature search was made to investigate welfare aspects on sows and piglets. As there were few published studies on nurse sows, an expert group meeting was organized. In order to explore the impact on the contribution margin of pig production, a partial budgeting approach with stochastic elements was used for a fictive pig farm. Standard templates for calculating costs and benefits were supplemented with figures from existing literature and the gathered expert opinions. In Sweden, the minimum suckling period is 28 days while published studies involving nurse sows, all from outside of Sweden, weaned the piglets at 21 days. A Swedish nurse sow will thus get longer lactation period which might increase the risk of poor body condition, damaged teats, and shoulder ulcers. This indicates a reduced welfare of the sow and may lead to impaired fertility and increased culling risk. On the other hand, the piglet mortality could be reduced with the use of nurse sows, but the separation and mixing of piglets could be stressful. The partial budgeting suggested that the nurse sow system is slightly more profitable (+6,838 Swedish krona) per farrowing group during one dry and one lactation period compared to the conventional system. The result is, however, highly dependent on the input values, and welfare aspects were not considered in the calculations.


d-wave induced zero-field resonances in dc pi-superconducting quantum interference devices.
A dc pi SQUID consists of a superconducting ring interrupted by two Josephson junctions, one of which carries in equilibrium a pi phase difference, caused, for example, by the d-wave pairing symmetry of the high- T(c) cuprates. If this phase shift is maintained in the voltage state, anomalous resonance currents are expected in the SQUIDs transport characteristics. Here we report the observation of such resonances for high- T(c) dc pi SQUIDs, providing evidence for the influence of the d-wave symmetry on the voltage state of a Josephson junction for frequencies of several tens of GHz.


Predicting Lead-Time RSV-Related Pediatric Hospitalizations From Historic Google Trend Search.
Respiratory syncytial virus (RSV) causes seasonal outbreaks of respiratory tract infections in children, leading to increased emergency department visits and hospitalizations. Although the risk of severe illnesses difficult to predict, the sudden surge in RSV may strain the health care system. Therefore, the objective of this study was to examine the utility of Google Trends search activity on RSV to predict changes in RSV-related hospitalizations in children in the United States in 2019. A retrospective cross-sectional analysis of pediatric hospitalization was conducted using the 2019 HCUP-Kids Inpatient Database. Google Trends search activity for "RSV" was abstracted as a monthly relative interest score for 2019. RSV-related hospitalizations were identified using International Classification of Diseases 9/10 codes. We applied finite distributed lag models to estimate the causal effect over time of historical relative search activity and long-run propensity to calculate the cumulative effect of changes in relative search activity on admission rate. Of the total 102 127 RSV-related pediatric hospitalizations, 90% were in those aged ≤2 years. Admissions were common in males (55%), non-Hispanic Whites (50%), and South region (39%). Across 2o successive months, the cumulative effect of a 1-unit score increase in relative interest was associated with an increase of 140.7 (95% confidence interval, 96.2-185.2; P < .05) RSV-related admissions. Historic Google Trends search activity for RSV predicts lead-time RSV-related pediatric hospitalization. Further studies are needed to validate these findings using regional health systems.