Molecular mechanisms of cyclosporin A inhibition of the cytokine-induced matrix metalloproteinase-9 in glomerular mesangial cells.
The effects of the immunosuppressants cyclosporin A (CsA) and tacrolimus (FK506) on the IL-1beta-induced matrix metalloproteinase-9 (MMP-9) were investigated. Impairment of the protease-antiprotease balance contributes to renal fibrosis, which is observed collectively under long-term treatment with either immunosuppressant. It is demonstrated that CsA, in contrast to FK506, reduced the IL-1beta-induced MMP-9 content in conditioned media of mesangial cells, which coincides with a reduction in the cytokine-induced MMP-9 mRNA level. Similar to FK506, the VIVIT peptide, a specific inhibitor of the nuclear factor of activated T cells, did not affect the cytokine-induced MMP-9 level. Moreover, CsA caused a dose-dependent inhibition on the IL-1beta-induced luciferase activity of a 1.3-kb MMP-9 promoter fragment. Concomitant, electrophoretic mobility shift assay revealed that CsA selectively inhibits the cytokine-induced DNA binding of activator protein-1 and NF-kappaB. The effects on NF-kappaB binding were accompanied by a marked reduction in the nuclear content of the p65 subunit of NF-kappaB. Accordingly, CsA specifically impaired the IL-1beta-triggered degradation of inhibitory NF-kappaB. The suppressive effects by CsA on MMP-9 expression were accompanied by a reduction in the cytokine-induced phosphorylation of p42/p44 and c-Jun N-terminal Kinase (JNK). It is interesting that only the JNK inhibitor SP600125 impaired the cytokine-triggered MMP-9 level, suggesting that CsA, via inhibition of the JNK pathway, negatively interferes with the NF-kappaB-dependent transcriptional control of MMP-9. Interference with MMP-9 transcription may account for the accumulation of extracellular matrix underlying the high fibrotic potential of CsA during anti-inflammatory therapies with calcineurin inhibitors.


Feasibility and safety of redo laparoscopic repair of recurrent inguinal hernia following previous endolaparoscopic repair.
Laparoscopic redo inguinal hernia (LRIH) repairs are fraught with challenges as the pre-peritoneal space is violated due to previous surgery and the presence of mesh. The purpose of this study was to present the feasibility and safety of LRIH in a series of patients with recurrent inguinal hernia following previous endolaparoscopic repair and present technical experiences and clinical outcomes in this subset of patients. This was a retrospective study from a prospective database of 16 patients who underwent LRIH between March 2014 and December 2020. The decision to do a redo laparoscopic surgery was undertaken after a detailed discussion with the patient. The operative details, challenges faced and tips to overcome difficulties have been explained in detail. Out of 16 patients (mean age 49.5 years, all men), 15 underwent laparoscopic redo trans-abdominal pre-peritoneal (TAPP) mesh repair and 1 underwent laparoscopic enhanced-view totally extra-peritoneal (eTEP) mesh repair. The mean operating time was 68.5 min for unilateral, 115 min for bilateral TAPP and 90 min for eTEP. The main contributing factors for recurrences were mesh migration, insufficient size of the mesh and inadequate fixation. There was no conversion to open repair. The duration of stay was 1-2 days. There was no documented re-recurrence during the follow-up period of 2-9 years. Based on our experience, redo laparoscopic inguinal hernia mesh repair after previous endolaparoscopic repair is feasible, effective and safe in experienced hands.


Probing the mechanisms of extracellular vesicle biogenesis and function in cancer.
Tumor cells interact with each other, and their surroundings, using a variety of mechanisms to promote virtually all aspects of cancer progression. One such form of intercellular communication that has been attracting considerable attention from the cancer community and the pharmaceutical industry in recent years involves the ability of cancer cells to generate multiple distinct types of non-classical secretory vesicles, generally referred to as extracellular vesicles (EVs). Microvesicles (MVs) represent one of the major classes of EVs and are formed as a result of the outward budding and fission of the plasma membrane. The other main class of EVs is exosomes, which are generated when multivesicular bodies fuse with the cell surface and release their contents into the extracellular space. Both MVs and exosomes have been shown to contain bioactive cargo, including proteins, metabolites, RNA transcripts, microRNAs, and DNA that can be transferred to other cancer cells and stimulate their growth, survival, and migration. However, cancer cell-derived EVs also play important roles in helping re-shape the tumor microenvironment to support tumor expansion and invasive activity, dampen immune responses, as well as enter the circulation to help promote metastatic spread. Here, we provide an overview of what is currently known regarding how the different classes of EVs are generated and contribute to various cancer cell phenotypes. Moreover, we highlight how some of the unique properties of EVs are being used for the development of novel diagnostic and clinical applications.


Pancreatic diseases: evaluation with MR cholangiopancreatography.
Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive diagnostic modality capable of producing high-quality images of the biliary tree and pancreatic duct. We evaluated the MRCP capability of depicting the normal pancreatic duct and, based on data achieved, studied the usefulness in the pathologic pancreatic duct. MRCP was performed in 42 patients without any pancreatic lesion and in 162 patients with pancreatic diseases, including congenital anomalies of biliary tree and pancreatic duct. Results were compared with endoscopic retrograde cholangiopancreatography (ERCP) in 93 patients. The visualization of the pancreatic duct and its branches and the presence or absence of dilatation, stenosis, and filling defects were recorded. All images were interpreted retrospectively and blindly by three radiologists. Among control patients, the main pancreatic duct (MPD) was depicted in the head, body, and tail of the pancreas in 41 (98%), 39 (93%), and 31 (74%), and accessory pancreatic duct and secondary branches in the head, body, and tail of the pancreas were depicted in 11 (26%), eight (19%), four (10%), and two (5%) of these patients. Compared with ERCP, MRCP overestimated the stenosis of MPD and underestimated the dilatation of the branches and filling defects in the pancreatic duct in pancreatic diseases, especially pancreatitis. However, MRCP was distinctly advantageous over ERCP in diagnosing mucin-producing tumor of the pancreas, cystic lesions, and depicting the whole, including the part distal to the obstructed site. Four of the eight cases of pancreas divisum, and 10 of the 12 cases of anomalous pancreaticobiliary duct union also were demonstrated. MRCP can accurately demonstrate the normal pancreatic duct as well as various pancreatic duct abnormalities, including congenital anomalies of the biliary tree and pancreatic duct.


The spectrum of cardiovascular disease in children with predialysis chronic kidney disease.
Cardiovascular disease is the major cause of mortality in adults and children on chronic dialysis and in adults after kidney transplantation. Cardiovascular disease burden and cardiovascular mortality are high in adults with chronic kidney disease. The early development of cardiovascular disease risk factors, some of which are modifiable, largely explain this phenomenon. Limited data are available on the prevalence of chronic kidney disease in children, the prevalence of cardiovascular disease in children with chronic kidney disease, and the prevalence of cardiovascular disease risk factors in these patients. This article summarizes the current knowledge of the prevalence of cardiovascular disease and of cardiovascular disease risk factors in pediatric patients with predialysis chronic kidney disease. Long-term prospective studies are needed to determine the impact of early identification and treatment of cardiovascular disease and its risk factors on the natural history of cardiovascular disease in children with chronic kidney disease.


Sulfonamide-based 4-anilinoquinoline derivatives as novel dual Aurora kinase (AURKA/B) inhibitors: Synthesis, biological evaluation and in silico insights.
Aurora kinases (AURKs) were identified as promising druggable targets for targeted cancer therapy. Aiming at the development of novel chemotype of dual AURKA/B inhibitors, herein we report the design and synthesis of three series of 4-anilinoquinoline derivatives bearing a sulfonamide moiety (5a-d, 9a-d and 11a-d). The % inhibition of AURKA/B was determined for all target quinolines, then compounds showed more than 50% inhibition on either of the enzymes, were evaluated further for their IC50 on the corresponding enzyme. In particular, compound 9d displayed potent AURKA/B inhibitory activities with IC50 of 0.93 and 0.09 µM, respectively. Also, 9d emerged as the most efficient anti-proliferative analogue in the US-NCI anticancer assay toward the NCI 60 cell lines panel, with broad spectrum activity against different cell lines from diverse cancer subpanels. Docking studies, confirmed that, the sulfonamide SO2 oxygen was involved in a hydrogen bond with Lys162 and Lys122 in AURKA and AURKB, respectively, whereas, the sulfonamide NH could catch hydrogen bond interaction with the surrounding amino acid residues Lys141, Glu260, and Asn261 in AURKA and Lys101, Glu177, and Asp234 in AURKB. Furthermore, N1 nitrogen of the quinoline scaffold formed an essential hydrogen bond with the hinge region key amino acids Ala213 and Ala173 in AURKA and AURKB, respectively.


Enhanced performance in deep-ultraviolet laser diodes with an undoped BGaN electron blocking layer.
Aluminum-rich p-AlGaN electron blocking layers (EBLs) are typically used for preventing overflow of electrons from the active region in AlGaN-based deep ultraviolet (DUV) laser diode (LD). However, these cannot effectively prevent electron leakage and form barrier layers, which affects the hole injection efficiency. Herein, the traditional p-AlGaN EBL in LD is replaced with an undoped BGaN EBL. The undoped BGaN EBL LD increases the effective barrier height of the conduction band to prevent the leakage of electrons and decreases the energy loss caused by the polarization induced electric field, enhancing the hole injection. The slope efficiency of the undoped BGaN EBL LD is 289% higher than that of the highly doped AlGaN EBL LD, and its threshold current is 51% lower. Therefore, the findings of this study provide insights for solving the problems of electron leakage and insufficient hole injection in high-performance and undoped EBL DUV LDs.


The polybasic region of Rho GTPases defines the cleavage by Yersinia enterocolitica outer protein T (YopT).
Pathogenic Yersinia strains evade the innate immune responses of the host by producing effector proteins ( Yersinia outer proteins [Yops]), which are directly injected into mammalian cells by a type III secretion system (TTSS). One of these effector proteins (YopT) disrupts the actin cytoskeleton of the host cell resulting in cell rounding. YopT is a cysteine protease that cleaves Rho proteins directly upstream of the post-translationally modified cysteine. Thereby, it releases the GTPases from the membrane leading to inactivation. Small GTPases are modified by isoprenylation of the cysteine of the CAAX box, cleavage of the -AAX tripeptide, and methylation of the cysteine. We have shown that isoprenylation and the endoproteolytic cleavage of the tripeptide of Rho GTPases are essential for YopT-induced cleavage, whereas carboxyl methylation is not required. In the present study, we post-translationally modified RhoA, Rac, Cdc42, and several mutants in vitro and characterized the YopT-induced cleavage with recombinant YopT. We show that farnesylated RhoA is a preferred substrate of YopT compared with the geranylgeranylated GTPase. Geranylgeranylated RhoA, however, is the preferred substrate for YopT-catalyzed cleavage with a threefold faster turnover rate over Rac and Cdc42. Moreover, our data indicate that the composition of the polybasic region of the GTPases defines the specificity and efficiency of the YopT-induced cleavage, and that a space between the polybasic stretch of amino acids at the C terminus and the CAAX box enhances the turnover rate of YopT-catalyzed cleavage.


[Study on the T cell functions induced by anti-CD3mAb in chronic pulmonary heart disease].
We studied the T lymphocyte transformation and IL-2's functions induced by anti-CD3 mAb in 42 cases of CPHD. The T lymphocyte transformation, activity of IL-2 and expression of IL-2R were determined by 3H-TDR incorporation, bioassay and immunoabsorption methods. The results showed that PBL transformation and activity of IL-2 were decreased in the patients of acute exacerbation stage more than those in controls and remission stage (P < 0.05 or P < 0.01); activity of IL-2 in the patients of remission stage was close to that in controls (P > 0.05), but PBL transformation was still less than that in controls (P < 0.01); Expression of IL-1R were increased in the patients more than in controls (P < 0.01). G.I of anti-CD3mAb and PHA stimulating PBL proliferation showed positive correlation (P < 0.01), activity of IL-2 and expression of IL-2R were not correlated (P > 0.05). The results showed that extrinsic IL-2 could enhance PBL proliferations induced by anti-CD3mAb, especially in CPHD patients.


Quantifying the responses of biological indices to rare macroinvertebrate taxa exclusion: Does excluding more rare taxa cause more error?
Including or excluding rare taxa in bioassessment is a controversial topic, which essentially affects the reliability and accuracy of the result. In the present paper, we hypothesize that biological indices such as Shannon-Wiener index, Simpson's index, Margalef index, evenness, BMWP (biological monitoring working party), and ASPT (Average Score Per Taxon) respond differently to rare taxa exclusion. To test this hypothesis, a benthic macroinvertebrate data set based on recent fifteen-year studies in China was built for suppositional plot analyses. A field research was conducted in the Nansi Lake to perform related analyses. The results of suppositional plot simulations showed that Simpson's index placed more weight on common taxa than any other studied indices, followed by Shannon-Wiener index which remained a high value with the exclusion of rare taxa. The results indicated that there was not much of effect on Simpson's index and Shannon-Wiener index when rare taxa were excluded. Rare taxa played an important role in Margalef index and BMWP than in other indices. Evenness showed an increase trend, while ASPT varied inconsistently with the exclusion of rare taxa. Results of the field study also indicated that rare taxa had few impacts on the Shannon-Wiener index. By examining the relationships between the rare taxa and biological indices in our study, it is suggested that including the rare taxa when using BMWP and excluding them in the proposed way (e.g., fixed-count subsampling) to calculate Shannon-Wiener index and Simpson's index could raise the efficiency and reduce the biases in the bioassessment of freshwater ecosystems.


PLASTICITY OF JAW AND SKULL MORPHOLOGY IN THE NEOTROPICAL CICHLIDS GEOPHAGUS BRASILIENSIS AND G. STEINDACHNERI.
I examined plasticity of jaw and skull morphology induced by feeding different diets in two species of the neotropical cichlid genus Geophagus. The two species possess different modes of development, which affect the size at which young begin feeding. I hypothesized that the difference in size at first feeding could lead to a difference in the amount of change inducible in the two species. The young of the substrate-spawning species, G. brasiliensis, which begin feeding at a smaller size, were predicted to be more plastic than those of the mouthbrooding species, G. steindachneri. The two diets used to induce differences were brine shrimp nauplii and chironomid larvae. Numerous measures of the jaw and skull differed significantly between groups fed the two diets but the amount of plasticity induced was small and would not present a problem for taxonomists. Contrary to my prediction, both the magnitude and pattern of plasticity induced in the two species was similar. Thus, mode of parental care and the size at which young begin feeding do not affect the degree of plasticity. Fish fed brine shrimp nauplii were longer in oral jaw region, but were shorter and shallower in the area behind the oral jaws. An additional group of G. brasiliensis was fed flake food to compare the results of this study to other studies. The differences in measures between fish fed brine shrimp diets and flake food diets were greater than those between fish fed brine shrimp and chironomid larvae. A possible role of plasticity for enhancing rather than retarding morphological evolution is discussed.


miR-188-5p regulates proliferation and invasion via PI3K/Akt/MMP-2/9 signaling in keloids.
Keloids (KDs) and hypertrophic scars (HSs), two forms of pathological scars, seriously affect the physical and psychological health of patients. Despite many similarities with HSs, KDs are characterized by invasion and a high rate of recurrence after surgery, features they share in common with tumors. The underlying molecular mechanisms of this phenomenon have not been fully elucidated. In this study, we used microRNA (miRNA) array analysis to search for invasion-associated miRNAs in KDs. The expression of miR-188-5p in KDs, HSs, normal skin (NS) tissues, and cell lines was measured by quantitative real-time polymerase chain reaction. Furthermore, cell proliferation, migration, and invasion were detected in KD fibroblasts (KFs) and HS fibroblasts (HSFs), and interrelated proteins were ascertained by western blot analysis. It was found that miR-188-5p was significantly decreased in KD tissue compared with HS and NS tissues. Upregulated expression of miR-188-5p suppressed KF proliferation, migration, and invasion; and decreased expression of miR-188-5p also promoted HSF proliferation, migration, and invasion. The protein levels of MMP-2, MMP-9, PI3K, and p-Akt in miR-188-5p mimic-transfected KFs were repressed. In contrast, after transfection with miR-188-5p inhibitor, the protein levels of MMP-2, MMP-9, PI3K, and p-Akt were higher than the control in HSFs. Treatment with PI3K/Akt inhibitor LY294002 in KFs with miR-188-5p inhibitor did not further reduce their proliferation, migration, and invasion. The upregulation of MMP-2 and MMP-9 by miR-188-5p inhibitor could be abolished by LY294002. These findings together demonstrate a tumor-suppressive role of miR-188-5p in KD proliferation and invasion via PI3K/Akt/MMP-2/9 signaling, indicating that miR-188-5p may be a potential prognostic marker and therapeutic target for KDs.


Pain after cardiac surgery: a prospective cohort study of 1-year incidence and intensity.
Persistent chest pain may originate from cardiac surgery. Conflicting results have been reported on the incidence of persistent poststernotomy pain with considerable discrepancies between the retrospective reports and the one prospective study conducted to assess this pain. Therefore, the authors conducted a follow-up survey for the first 12 months after cardiac surgery in 213 patients who had a sternotomy. The authors performed a prospective inquiry of acute and chronic poststernotomy pain both before and after cardiac surgery. Two hundred thirteen coronary artery bypass patients received a questionnaire preoperatively, 4 days postoperatively, and 1, 3, 6, and 12 months postoperatively. All patients were asked about their expectations, their preferences, and the location and intensity of postoperative pain. The return rates for the postal questionnaires were 203 (95%) and 186 (87%) after 1 and 12 months, respectively. Patients experienced more pain postoperatively at rest than they had expected to preoperatively. At rest, the worst actual postoperative pain was 6 (0-10), and the worst expected pain as assessed preoperatively was 5 (0-10) (P = 0.013). The worst reported postoperative pain was severe (numeric rating scale score 7-10) in 49% at rest, in 78% during coughing, and in 62% of patients on movement. One year after the operation, 26 patients (14%) reported mild chronic poststernotomy pain at rest, 1 patient (1%) had moderate pain, and 3 patients (2%) had severe pain. Upon movement, persistent pain was even more common: 45 patients (24%) had mild, 5 patients (3%) had moderate, and 7 patients (4%) had severe pain. Patients who experienced moderate to severe acute postoperative pain also reported any chronic poststernotomy pain (numeric rating scale score 1-10) more frequently. Although common, the incidence of persistent pain after sternotomy was lower than previously reported. Also, reassuringly, 1 year after surgery this pain was mostly mild in nature both at rest and on movement.


Atrial and ventricular vulnerability in a patient with the Wolff-Parkinson-White syndrome.
An electrophysiologic study was carried out in a patient with the Wolff-Parkinson-White syndrome and a history of spontaneous atrial fibrillation but with no evidence of organic cardiac disease. A single induced premature ventricular depolarization resulted in ventricular tachycardia followed by ventricular fibrillation. Similarly, atrial pacing or premature atrial stimulation resulted in frequent episodes of atrial fibrillation or flutter. The atrial and ventricular effective refractory periods were 180 ms and less than 160 ms, respectively, at a driven cycle length of 480 ms. Intravenous administration of procainamide resulted in lengthening of the refractory periods and failure to induce either atrial or ventricular arrhythmias with pacing. In most patients with enhanced atrioventricular nodal or accessory atrioventricular nodal by-pass, the mechanism of ventricular tachycardia is related to an inordinately rapid ventricular response during supraventricular arrhythmias. In our patient, a unique mechanism was apparent: atrial and ventricular vulnerability to fibrillation was associated with extremely short myocardial effective refractory periods. The relationship of this finding to sudden cardiac death bears further study.


Characteristics of abdominal obesity in persons with spinal cord injury.
To investigate the characteristics of community-dwelling spinal cord injury (SCI) persons with obesity, including diet, socioeconomic factors, weight reduction method, and frequency of body weight and abdominal circumference measurements. We developed a questionnaire based on 'the Fourth Korea National Health and Nutrition Examination Survey, 2009'. A total of 371 community-dwelling SCI persons were enrolled in this study. Inclusion criteria were SCI persons older than 20 years with more than 1 year elapsed since the injury. Trained investigators visited SCI persons' home to complete the questionnaire and measure abdominal obesity (AO) as defined by the waist circumference. Prevalence of AO was 29.2% in SCI persons and 27.4% in the general population (GP), showing no significant difference. Education showed correlation with AO in both SCI persons and the GP. The injury level, type of injury and income did not show any correlation with AO in SCI persons. Only 28.8% and 48.8% of SCI persons measured their waist circumference and body weight within the past year, respectively. Also, SCI persons with AO thought that their body was less obese compared to persons with AO in the GP (p<0.001). The method of weight reduction was diet modification in 53.6% of SCI persons with AO, which was higher than 37.1% of persons with AO in the GP. In SCI persons, obesity perception as well as socioeconomic factors correlated with AO, but these were not relevant factors in the GP. Therefore, development of a specific and intensive weight control program for SCI persons is necessary.


Influence of systemic inflammation on efficiency of antiplatelet therapy in PAOD patients.
Recently it was shown that inflammation adversely influences results obtained from the platelet function analyzer system, PFA-100, hypothesizing that inflammation could confound interpretation of platelet function results. We investigated the clinical relevance of these results in patients with peripheral arterial occlusive disease (PAOD), with and without signs of systemic inflammation. In 98 PAOD patients, all treated with acetyl-salicylic acid (ASA), we obtained PFA-100 values upon stimulation with epinephrine. C-reactive protein (CRP) values were investigated as indicator for systemic inflammation. Mean CRP levels were elevated in 23 patients (23%). There was no difference of mean PFA-100 results between patients with elevated CRP levels and those without. Our results indicate that the effect of ASA on platelet aggregation, as measured by the PFA-100, is not relevantly influenced in PAOD patients with elevated CRP.


High-Impact Performance and Thermal Properties of Polyimine Nanocomposites Reinforced by Silicon Carbide Nano-Whiskers.
Polymer nanocomposites, which combine the advantages of polymers and fillers, are widely used in the field of automobile and aviation. Polyimine (PI) is an emerging thermoset material with remarkable properties, such as malleability, recyclability, and self-healing. Silicon carbide nano-whiskers (SiCw), as a cheap and high-hardness filler material, are chosen to enhance the properties of polyimine matrix. Silicon carbide nano-whisker-reinforced polyimine (PI-SiCw) nanocomposites were successfully fabricated by heat pressing, which was confirmed by FTIR and XPS tests. According to the results of mechanical tests, the mechanical properties of PI-SiCw nanocomposites were obviously improved. For example, with the addition of 0.5% SiCw, bending strength and bending elongation at break can be simultaneously increased by 33% and 148%, respectively. Surprisingly, the impact strength of PI-SiCw nanocomposites with 2% SiCw was increased by 154% compared to the matrix. SEM and EDS tests showed that the evenly distributed SiCw in the polyimine matrix enhanced the mechanical properties of PI-SiCw nanocomposites according to the mechanism of whiskers pulling out and the bridging principle. According to the TGA test results, the PI composites with SiCw retain a higher weight percentage at 800 °C. The reason was the combined effect of the good thermal stability of SiCw and their strong interactions with the PI matrix. As a result, introducing SiCw into the PI matrix imparts a slight improvement in thermal stability. This article presents an avenue of cost-effective research to enhance the mechanical properties of polyimine composites.


The ameba Balamuthia mandrillaris feeds by entering into mammalian cells in culture.
Microscopic observations of live cultures of the pathogenic ameba Balamuthia mandrillaris and mammalian cells showed that amebic feeding involved the invasion of the pseudopodia, and/or the whole ameba into the cells. The ameba, recognized by their size and flow of organelles in the cytosol, was seen to extend the tip of a pseudopodium into the cytoplasm of a cell where it moved about leaving visible damage when retracted. In rounded cells, whole amebas were seen to enter into and move around before exiting a cell and then remain quiescent for hours. The invaded mammalian cells retained their turgidity and excluded vital dyes until only their denuded nuclei remained. The cytoplasm of the cells was consumed first, then the nuclei, but not their mitotic chromosomes. The feeding pattern of four isolates of B. mandrillaris, two from humans and two from soil samples, was by amebic invasion into the mammalian cells. The resulting ameba population included cysts, amebas on the surface, and free-floating amebas as individuals or in dense-packed clusters. There was no morphologic indication of a cytopathic change in the mammalian cells before their invasion by the amebas. Feeding by cell invasion is a distinctive feature of B. mandrillaris.


[Association of genetic polymorphisms of COMT gene with psychiatric disorders].
The enzyme catechol-O-methyltransferase (COMT) transfers a methyl group from S-adenosylmethionine to the benzene ring of catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the COMT gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. This review focuses on the association between the genetic polymorphisms of COMT gene and psychiatric disorders.


Intermediate results of Buechel Pappas unconstrained uncemented total ankle replacement for osteoarthritis.
We present the functional and radiological results after implantation of thirty five uncemented Buechel Pappas total ankle replacements by an independent surgeon. All consecutive uncemented Buechel Pappas total ankle replacements were performed by the senior author (MSA) between 1990 and 2005. All ankle replacements were performed for osteoarthritis. The patients were assessed clinically and radiologically. The average follow-up period is five years. Nine female patients and 25 male patients with an average age of 69(58-84) were enrolled. One patient died before follow-up. Ninety seven percent of patients were happy with their operation and ninety seven percent thought it was successful. Sixty six percent of patients had no, or occasional pain. All patients were mobile and forty five percent of patients required no walking aids. Only three percent of patients required two walking aids. The American Orthopaedic Foot and Ankle Society Score was 73.3(54-100) at follow-up, compared to 34.6(20-56) pre-operatively (p < 0.001). One prosthesis was revised. Two fractured medial malleoli occurred and no deep infections were noted. Buechel Pappas Uncemented Total Ankle replacement, performed by an independent surgeon, can give intermediate results comparable to data published by the designer. Patient selection is paramount. Our data compares well with results from other uncemented total ankle replacements.


Can serotonin and fluoxetine levels in plasma and platelets predict clinical response in depression?
We describe the clinical response and the area under the concentration-time curve (AUC) of fluoxetine and serotonin levels in plasma and platelets in 10 depressive patients treated with 20 mg/day of fluoxetine for 30 days. Depression severity was assessed at baseline and after treatment by the Hamilton Rating Scale for Depression (HAM-D). "Good clinical response" was defined as a decrease of 50% or more of the total HAM-D score compared with baseline. Using this measure, patients were thus classified as "responders" or "nonresponders." For both groups we describe the AUC of fluoxetine and serotonin levels in plasma and platelets at baseline and after 30 days of treatment. We found different trends of biochemical parameters in the examined groups. In fact, after treatment responders showed, in comparison with nonresponders, higher levels of fluoxetine in platelets and lower levels in plasma; responders also showed lower concentrations of serotonin in platelets and higher concentrations in plasma.


Occurrence and Trophic Transfer of Polychlorinated Naphthalenes (PCNs) in the Arctic and Antarctic Benthic Marine Food Webs.
Information about the occurrence and trophic transfer of polychlorinated naphthalenes (PCNs) in polar ecosystems is vital but scarce. In this study, PCNs were analyzed in benthic marine sediment and several biological species, collected around the Chinese polar scientific research stations in Svalbard in the Arctic and South Shetland Island in Antarctica. Total PCNs in biota ranged from 28 to 249 pg/g of lipid weight (lw) and from 11 to 284 pg/g lw in the Arctic and Antarctic regions, respectively. The concentrations and toxic equivalent (TEQ) of PCNs in polar marine matrices remained relatively low, and the compositions were dominated by lower chlorinated homologues (mono- to trichlorinated naphthalenes). Trophic magnification factors (TMFs) were calculated for congeners, homologues, and total PCNs in the polar benthic marine food webs. Opposite PCN transfer patterns were observed in the Arctic and Antarctic regions, i.e., trophic dilution and trophic magnification, respectively. This is the first comprehensive study of PCN trophic transfer behaviors in remote Arctic and Antarctic marine regions, providing support for further investigations of the biological trophodynamics and ecological risks of PCNs.


The effect of intravenously administered dexmedetomidine on perioperative hemodynamics and isoflurane requirements in patients undergoing abdominal hysterectomy.
The effects of two doses of dexmedetomidine (0.3 or 0.6 micrograms.kg-1), fentanyl 2.0 micrograms.kg-1, or saline as a single intravenous bolus administered 10 min prior to the induction of anesthesia were assessed in double-blind, randomized study in 96 women undergoing abdominal hysterectomy. In each patient, anesthesia was induced with thiopental 4.0 mg.kg-1, and after the effect of succinylcholine had dissipated, isoflurane 0.3% end-tidal concentration in 70% nitrous oxide was begun to maintain anesthesia. The isoflurane concentration was adjusted to maintain blood pressure and heart rate within 20% of preoperative values, and fentanyl was given if the end-tidal isoflurane concentration exceeded 1.5%. In all groups, blood pressure and heart rate increased after tracheal intubation. However, the increase in blood pressure and heart rate was significantly less in the higher dexmedetomidine (0.6 micrograms.kg-1) group than in the saline group (P less than 0.01). Also, the postintubation increase in heart rate was significantly less (P less than 0.05) in the dexmedetomidine 0.6 micrograms.kg-1 group (increase of 18 +/- 3 beats per min) compared to the fentanyl group (increase of 26 +/- 3 beats per min). In patients receiving dexmedetomidine 0.3 micrograms.kg-1, the increase in blood pressure or heart rate did not differ from that of the saline group. The mean end-tidal isoflurane concentration was significantly less in the women receiving the higher dose of dexmedetomidine (0.35%) than in those receiving saline (0.47%) or fentanyl (0.48%), although the reduction was not clinically important.(ABSTRACT TRUNCATED AT 250 WORDS)


Development of Peptide-Based Vaccines for Cancer.
Peptides cancer vaccines are designed based on the epitope peptides that can elicit humoral and cellular immune responses targeting tumor-associated antigens (TAAs) or tumor-specific antigens (TSAs). In order to develop a clinically safe and more effective vaccine for the future, several issues need to be addressed, and these include the selection of optimal antigen targets, adjuvants, and immunization regimens. Another emerging approach involves the use of personalized peptide-based vaccines based on neoantigens to enhance antitumor response. Rationally designed combinatorial therapy is currently being investigated with chemotherapeutic drugs or immune checkpoint inhibitor therapies to improve the efficacy. This review discusses an overview of the development of peptide-based vaccines, the role of adjuvants, and the delivery systems for peptide vaccines as well as combinatorial therapy as potential anticancer strategies.


Gallium-sulfide supertetrahedral clusters as building blocks of covalent organic-inorganic networks.
The synthesis and characterization of novel covalent organic-inorganic architectures containing organically functionalized supertetrahedra is described. The structures of these unique materials consist of one-dimensional zigzag chains or of honeycomb-type layers, in which gallium-sulfide supertetrahedral clusters and dipyridyl ligands alternate.


Short double-stranded RNAs with an overhanging 5' ppp-nucleotide, as found in arenavirus genomes, act as RIG-I decoys.
Arenavirus RNA genomes are initiated by a "prime and realign" mechanism, such that the initiating GTP is found as a single unpaired (overhanging) nucleotide when the complementary genome ends anneal to form double-stranded (ds) RNA panhandle structures. dsRNAs modeled on these structures do not induce interferon (IFN), as opposed to blunt-ended (5' ppp)dsRNA. This study examines whether these viral structures can also act as decoys, by trapping RIG-I in inactive dsRNA complexes. We examined the ability of various dsRNAs to activate the RIG-I ATPase (presumably a measure of helicase translocation on dsRNA) relative to their ability to induce IFN. We found that there is no simple relationship between these two properties, as if RIG-I can translocate on short dsRNAs without inducing IFN. Moreover, we found that (5' ppp)dsRNAs with a single unpaired 5' ppp-nucleotide can in fact competitively inhibit the ability of blunt-ended (5' ppp)dsRNAs to induce IFN when co-transfected into cells and that this inhibition is strongly dependent on the presence of the 5' ppp. In contrast, (5' ppp)dsRNAs with a single unpaired 5' ppp-nucleotide does not inhibit poly(I-C)-induced IFN activation, which is independent of the presence of a 5' ppp group.


Korean Scutellaria baicalensis Georgi flavonoid extract induces mitochondrially mediated apoptosis in human gastric cancer AGS cells.
Korean Scutellaria baicalensis Georgi has been widely used in Korean folk medicines for its range of medicinal benefits, including its anticancer effect. The aim of the present study was to investigate the underlying molecular mechanism of action of a flavonoid extract from Korean Scutellaria baicalensis Georgi (FSB) on AGS human gastric cancer cells (gastric adenocarcinoma) in which FSB exhibits an anticancer effect. Treatment of AGS cells with FSB significantly inhibited cell viability in a concentration-dependent manner. Furthermore, FSB significantly increased the proportion of cells in sub-G1 phase, and Annexin V and Hoechst 33258 fluorescent staining confirmed the apoptotic cell death. Furthermore, western blotting results identified that treatment of AGS cells with FSB significantly downregulated the expression of caspase family members, namely procaspases 3 and 9, and poly(ADP-ribose) polymerase (PARP), and subsequently upregulated cleaved caspase 3 and cleaved PARP. It was observed that FSB treatment significantly decreased the mitochondrial membrane potential of AGS cells. In addition, the ratio of the mitochondrion-associated proteins B cell lymphoma 2-associated X protein and B cell lymphoma extra large was upregulated. The results of the present study provide novel insight into the underlying molecular mechanism of the anticancer effects of FSB on AGS human gastric cancer cells and indicate that FSB may be an alternative chemotherapeutic agent for the treatment of gastric cancer.


Advances in the development of wire mesh reactor for coal gasification studies.
In an effort to further understand the coal gasification behavior in entrained-flow gasifiers, a high pressure and high temperature wire mesh reactor with new features was recently built. An advanced LABVIEW-based temperature measurement and control system were adapted. Molybdenum wire mesh with aperture smaller than 70 mum and type D thermocouple were used to enable high carbon conversion (>90%) at temperatures >1000 degrees C. Gaseous species from wire mesh reactor were quantified using a high sensitivity gas chromatography. The material balance of coal pyrolysis in wire mesh reactor was demonstrated for the first time by improving the volatile's quantification techniques.


[Remarks on configuration frequency analysis].
The "Konfigurationsfrequenzanalyse" (KFA) is a method proposed by Lienert to detect syndromes. Using examples we criticize the definition of a syndrome used for a KFA, and we thus criticize the interpretation of the results of a KFA. Furthermore, we describe briefly a backward selection procedure of multiplicative models for contingency tables. This procedure may be used to find simple patterns of association for several symptoms.


Nemaline myopathy: reclassification of previously reported variants according to ACMG guidelines, and report of novel genetic variants.
Nemaline myopathy (NM) is a heterogeneous genetic neuromuscular disorder characterized by rod bodies in muscle fibers resulting in multiple complications due to muscle weakness. NM patients and their families could benefit from genetic analysis for early diagnosis, carrier and prenatal testing; however, clinical classification of variants is subject to change as further information becomes available. Reclassification can significantly alter the clinical management of patients and their families. We used the newly published data and ACMG/AMP guidelines to reassess NM-associated variants previously reported by clinical laboratories (ClinVar). Our analyses on rare variants that were not canonical loss-of-function (LOF) resulted in the downgrading of ~29% (28/97) of variants from pathogenic or likely-pathogenic (P/LP) to variants of uncertain significance (VUS). In addition, we analyzed the splicing effect of variants identified in NM patients by clinical laboratories or research, using an accurate in silico prediction tool that applies a deep-learning network. We identified 55 rare variants that may impact splicing (cryptic splicing). We also analyzed six new NM families and identified eight variants in NEB and ACTA1, including three novel variants: homozygous pathogenic c.164A > G (p.Tyr55Cys), and homozygous likely pathogenic c.980T > C (p.Met327Thr) in ACTA1, and heterozygous VUS c.18694-3T > G in NEB. This study demonstrates the importance of reclassifying variants to facilitate more definitive "calls" on causality or no causality in clinical genetic testing of patients with NM. Reclassification of ~150 variants is now available for improved clinical management, risk counseling and screening of NM patients.


The roles of bile acids and applications of microencapsulation technology in treating Type 1 diabetes mellitus.
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the loss of glycemic control. Recent studies have shown significant inflammation and disturbed bile acid homeostasis, associated with T1DM. Bile acids are endogenously produced as a result of cholesterol catabolism in the liver and solely metabolized by gut microflora. This review investigates their potential oral delivery in T1DM using targeted delivery and encapsulation technologies. A sensitive and selective search was carried out using different search engines and databases. Keywords used included diabetes mellitus, bile acids and inflammation. To conclude, bile acids have a significant impact on diabetes symptoms and, when microencapsulated, may be used as an adjunct therapy to supplement T1DM treatment.


Severe allergic contact dermatitis to two different continuous glucose monitoring devices in a patient with glycogen storage disease type 9b.
Continuous glucose monitoring (CGM) systems are of great value for patients with disorders of impaired glucose homeostasis, including glycogen storage diseases. We report on an 8-year-old girl with glycogen storage disease type 9b who developed severe allergic contact dermatitis to two different continuous glucose monitoring systems, FreeStyle® Libre and Dexcom® G6. Our case highlights the impact of sensitization for pediatric patients, the urgent need for open labeling of components by pharmaceutical and device manufacturers, and the need for avoidance of skin sensitizers in medical devices.


Up-regulation of Fas ligand (FasL) mRNA expression in peripheral blood mononuclear cells (PBMC) after major surgery.
FasL, which is expressed mainly on activated lymphocytes, can induce apoptosis (programmed cell death) of cells which express Fas. Fas/FasL interaction is primarily beneficial in maintaining immunological and physiological homeostasis by eliminating unnecessary cells. Dysregulation of the interaction, however, leads to tissue damage. We investigated how Fas/FasL levels changed after major surgery. The major aim of this study was to elucidate the involvement of the Fas/FasL system in postoperative inflammation. The investigation involved 10 patients admitted to the intensive care unit after surgery. Although the percentage of Fas+ cells and the amount of Fas expression tended to increase, there was no significant difference between pre- and post-operative samples. In contrast, the levels of FasL mRNA were dramatically up-regulated after operation. Post-operative C-reactive protein (CRP) levels increased and correlated well with FasL levels (r=0.91, P<0.01). Lymphocyte counts decreased after operation and were inversely proportional to FasL levels (r=0.58, P < 0.05). These results suggest that the enhanced FasL expression is likely to be related to systemic inflammatory responses induced during the perioperative period. FasL up-regulation may be involved in the aggravation of tissue damage, including lymphocytopenia, in the early post-operative period.


Temperature sensitivity of the human cardiac pacemaker during exercise.
The temperature sensitivity of the human cardiac pacemaker was investigated during exhaustive exercise. From graded runs to exhaustion, we established the relationship between maximum exercise heart rate (HRmax) and rectal temperature (Tr). After warm-up periods of varying intensity and duration, four male subjects completed 4 to 6 runs each, each run performed on a separate day. For every subject there was a strong linear correlation between HRmax and Tr (r = 0.79 to 0.96). Various measures of the temperature sensitivity were: linear sensitivity, 8.8 +/- 4.3 beats min-1.degrees C-1; Q10, 1.6 +/- 0.4 and the Arrhenius constant, mu, 35.9 +/- 16.6 kJ.mol-1. At HRmax the value for linear temperature sensitivity was similar to, but the values for Q10 and mu lower than, those observed previously for intrinsic heart rate. Sympathetic influence on the cardiac pacemaker during exercise may cause this reduction, by shifting the pacemaker location to cells with a lower temperature sensitivity, or by altering a rate-limiting step determining the diastolic pacemaker potential.


Highly Uniform and Conducting Single-Walled Carbon Nanotube Thin Films via Controlling the Dewetting Phenomenon.
Carbon nanotubes (CNTs) have received substantial attention as alternatives to indium tin oxide for the production of transparent conductors. However, problems associated with the dewetting of liquid thin films have hindered the reliable fabrication of networked conducting CNT films via solution-based processes. In this study, the dewetting of liquid thin films containing single-walled carbon nanotubes (SWCNTs) on substrates is successfully retarded by simply adding ethylene glycol to the SWCNT dispersion, and highly uniform SWCNT thin films are obtained using the meniscus-dragging deposition (MDD) method. The dewetting-free coating conditions for the uniform SWCNT films are determined by calculating the dewetting and drying times of the liquid thin films formed by the MDD method. When the dewetting time was 2.5 times longer than the drying time of the liquid thin layers, uniform SWCNT films are formed over the entire substrates without breakage or rupture of the films. In addition, the transmittance and sheet resistance of the transparent SWCNT films are easily controlled over a wide range by varying the coating parameters.


[Acupoint stimulation as a smoking cessation therapy].
The purpose of this article was to review the literature on the effectiveness of stopping smoking through acupoint stimulation. Topics of interest included traditional Chinese medicine theory, acupoints selected for use in smoking cessation therapies, and the effectiveness and outcomes of acupoint stimulation therapies targeting smoking cessation. It is hoped that this article provides valuable knowledge and information on an alternative smoking cessation approach to give medical professionals additional options when assisting patients to quit smoking.


Promotion of micrometastasis proliferation in a rat rhabdomyosarcoma model by epidermal growth factor.
Using a rat rhabdomyosarcoma 9-4/0, we investigated the role of epidermal growth factor (EGF) in tumor dissemination. In vitro, we detected high-affinity EGF receptors on tumor cells and stimulation of their proliferation by EGF. When injected iv, EGF-pretreated cells demonstrated an increased capacity to form lung colonies and to invade lymphatic tissue. In vivo, EGF treatment led to increased metastatic spread of subcutaneous tumors. When primary tumors were ablated, and the treatment was given from the time of graft until ablation (seeding step), no effect on metastatic spread was noticed. When treatment was given from the time of ablation until death (growth step), EGF increased the number of lung metastases and of invaded lymph node sites.


Echocardiographic decision-making for replacement surgery in mitral valve prolapse.
The clinical usefulness of M-mode echocardiography for predicting severe mitral regurgitation (MR) requiring valve replacement was assessed in 16 men and 10 women with mitral valve prolapse (MVP) as sole primary cardiac disorder. From left ventricular (LV) angiography, MR was classified as none to moderate (8 cases, group A) or severe (18 cases, group B). At echocardiography, increased LV end-diastolic and end-systolic and left atrial (LA) dimensions, corrected for body-surface area, distinguished group B from group A, with the best validities for LA and LV end-diastolic values. The mean echocardiographic LV fractional shortening and ejection fraction (EF) and the angiographic EF were similar in both groups. Echocardiographic and angiocardiographic LV EF correlated poorly, the former usually overestimating the latter. LV end-diastolic and mean pulmonary capillary wedge pressures were highest in group B, and the latter correlated with echocardiographic LA size. Mitral valve replacement was subsequently performed on 15 of the 18 group B patients. M-mode echocardiography is a valuable adjuvant to clinical assessment of MVP for predicting MR severity and for time-planning of cardiac catheterization or mitral valve surgery.


New insights into the phenotypic covariance structure of the anthropoid cranium.
In complex organisms, suites of non-random, highly intercorrelated phenotypic traits, organized according to their developmental history and forming semi-autonomous units (i.e. modules), have the potential to impose constraints on morphological diversification or to improve evolvability. Because of its structural, developmental and functional complexity, the cranium is arguably one of the best models for studying the interplay between developmental history and the need for various parts of a structure to specialize in different functions. This study evaluated the significance of two specific types of developmental imprints in the adult anthropoid cranium, those imposed by ossification pattern (i.e. ossification with and without a pre-existing cartilaginous phase) and those imposed by tissue origin (i.e. tissues derived principally from neural-crest vs. those derived from paraxial mesoderm). Specifically, this study tests the hypothesis that the face and the basicranium form two distinct modules with higher within-unit trait integration magnitudes compared with the cranium as a whole. Data on 12 anthropoid primate species were collected in the form of 20 three-dimensional landmarks digitized on cranial surface models that sample the basicranium as well as regions of functional importance during feeding [corrected]. The presence of a significant modularity imprint in the adult cranium was assessed using a between-region within-species comparison of multivariate correlations (RV coefficients) obtained with partial least-squares, using within-module within-species eigenvalue variance (EV), and using cluster analyses and non-metric multidimensional scaling. In addition to addressing the validity of the cranial modularity hypothesis in anthropoids, this study addressed methodological aspects of the interspecific comparison of morphological integration, namely the effect of sample size and the effect of landmark number on integration magnitudes. Two methodological findings that are of significance to research in morphological integration are that: (i) a smaller sample size increases integration magnitude, but preserves the pattern of variation of integration magnitudes from block to block within species; and that (ii) the number of landmarks per cranial block does not significantly impact block integration magnitude measured as EV. Results from the analyses testing for cranial modularity imprints in the adult anthropoid cranium show that some facial landmarks covary more strongly with basicranial landmarks than with other facial landmarks. Cluster methods, non-metric multidimensional scaling and, to an extent, RV results show that the rostral and the zygomatic landmarks covary more strongly with the basicranial landmarks than they do with the molar landmarks. However, the rostral-zygomatic-basicranial block, the molar block, the facial block, the basicranial block and the other analyzed cranial and facial blocks are not more integrated than the cranium. Thus, the morphological variation in the adult anthropoid cranium is not significantly constrained by at least two of the potential developmental sources of its covariance structure.


Quality of life assessment in patients treated for metastatic cutaneous squamous cell carcinoma of the head and neck.
Treatment for metastatic cutaneous head and neck squamous cell carcinoma is usually multimodal and associated with morbidity. This study aimed to evaluate the impact of treatment on patients' quality of life. Cross-sectional survey of 42 patients (35 men, 7 women) at least 6 months after metastatic cutaneous head and neck squamous cell carcinoma treatment, using two standardised quality of life questionnaires: the Functional Assessment of Cancer Therapy - Head and Neck questionnaire and the Facial Disability Index, with statistical analysis to identify potential predictors of outcome. Female gender correlated with significantly lower Facial Disability Index physical function scores (p = 0.017). Alcohol consumption correlated with significantly better scores for Functional Assessment social well-being (p = 0.016), general total score (p = 0.041) and overall total score (p = 0.033), and for Facial Disability Index physical function (p = 0.034). Marital status, education, employment, chemotherapy, time from last treatment, parotidectomy and facial nerve sacrifice did not affect quality of life. The commonest patient complaints were dry mouth (76 per cent), altered voice quality and strength (55 per cent), and physical appearance (45 per cent). Female gender predicts worse quality of life, while alcohol consumption (versus none) predicted for better quality of life.


Inhibitory control and moral emotions: relations to reparation in early and middle childhood.
This study examined links between inhibitory control, moral emotions (sympathy and guilt), and reparative behavior in an ethnically diverse sample of 4- and 8-year-olds (N = 162). Caregivers reported their children's reparative behavior, inhibitory control, and moral emotions through a questionnaire, and children reported their guilt feelings in response to a series of vignettes depicting moral transgressions. A hypothesized meditation model was tested with inhibitory control relating to reparative behavior through sympathy and guilt. In support of this model, results revealed that high levels of inhibitory control were associated with high levels of reparative behavior through high levels of sympathy and guilt. However, the mediation of inhibitory control to reparation through guilt was significant for 4-year-olds only. Results are discussed in relation to the temperamental, regulatory, and affective-moral precursors of reparative behavior in early and middle childhood.


Ecological Factors in Human Development.
Urie Bronfenbrenner (1992) helped developmental psychologists comprehend and define "context" as a rich, thick multidimensional construct. His ecological systems theory consists of five layers, and within each layer are developmental processes unique to each layer. The four articles in this section limit the exploration of context to the three innermost systems: the individual plus micro- and macrolayers. Rather than examine both the physical features and processes, the articles tend to focus solely on processes associated with a niche. Processes explored include social identity development, social network dynamics, peer influences, and school-based friendship patterns. The works tend to extend the generalization of extant theory to the developmental experience of various minority group experiences.


Human Rights Law and the Defence of Mental Impairment.
This article provides an overview of recent scholarship calling for the defence of mental impairment to be abolished on the grounds that it breaches international human rights law. It outlines how differing interpretations of the United Nations Convention on the Rights of Persons with Disabilities (CRPD) suggest that arguments for abolition will continue to be contested. On a practical level, no Australasian law reform body has called for the abolition of the defence and it seems unlikely that government policy will shift towards this in the absence of such a recommendation from these bodies. However, highlighting the obligations on States Parties to the CRPD to ensure the right to equal treatment before the law necessitates a careful consideration of whether the defence of mental impairment is still fit for purpose.


Hydro-bio-geo-socio-chemical interactions and the sustainability of residential landscapes.
Residential landscapes are essential to the sustainability of large areas of the United States. However, spatial and temporal variation across multiple domains complicates developing policies to balance these systems' environmental, economic, and equity dimensions. We conducted multidisciplinary studies in the Baltimore, MD, USA, metropolitan area to identify locations (hotspots) or times (hot moments) with a disproportionate influence on nitrogen export, a widespread environmental concern. Results showed high variation in the inherent vulnerability/sensitivity of individual parcels to cause environmental damage and in the knowledge and practices of individual managers. To the extent that hotspots are the result of management choices by homeowners, there are straightforward approaches to improve outcomes, e.g. fertilizer restrictions and incentives to reduce fertilizer use. If, however, hotspots arise from the configuration and inherent characteristics of parcels and neighborhoods, efforts to improve outcomes may involve more intensive and complex interventions, such as conversion to alternative ecosystem types.


The cooked meat derived genotoxic carcinogen 2-amino-3-methylimidazo[4,5-b]pyridine has potent hormone-like activity: mechanistic support for a role in breast cancer.
The cooked meat-derived heterocyclic amine 2-amino-3-methylimidazo[4,5-b]pyridine (PhIP) is activated by CYP1A2 to the N-hydroxy metabolite, then esterified by acetyl transferase and sulfur transferase into unstable DNA-reactive products that can lead to mutation. The genotoxicity of PhIP has been implicated in its carcinogenicity. Yet, CYP1A2-null mice are still prone to PhIP-mediated cancer, inferring that alternative mechanisms must be operative in tumor induction. PhIP induces tumors of the breast, prostate, and colon in rats and lymphoma in mice. This profile of carcinogenicity is indicative of hormonal involvement. We recently reported that PhIP has potent estrogenic activity inducing transcription of estrogen (E2)-regulated genes, proliferation of E(2)-dependent cells, up-regulation of progesterone receptor, and stimulation of mitogen-activated protein kinase signaling. In this report, we show for the first time that PhIP at doses as low as of 10(-11) mol/L has direct effects on a rat pituitary lactotroph model (GH3 cells) and is able to induce cell proliferation and the synthesis and secretion of prolactin. This PhIP-induced pituitary cell proliferation and synthesis and secretion of prolactin can be attenuated by an estrogen receptor (ER) inhibitor, implying that PhIP effects on lactotroph responses are ERalpha mediated. In view of the strong association between estrogen, progesterone, prolactin, and breast cancer, the PhIP repertoire of hormone-like activities provides further mechanistic support for the tissue-specific carcinogenicity of the chemical. Furthermore, the recent epidemiology studies that report an association between consumption of cooked red meat and premenopausal and postmenopausal human breast cancer are consonant with these observations.


Immobilization of Pt Nanoparticles via Rapid and Reusable Electropolymerization of Dopamine on TiO2 Nanotube Arrays for Reversible SERS Substrates and Nonenzymatic Glucose Sensors.
Inspired by mussel-adhesion phenomena in nature, polydopamine (PDA) coatings are a promising route to multifunctional platforms for decorating various materials. The typical self-polymerization process of dopamine is time-consuming and the coatings of PDA are not reusable. Herein, a reusable and time-saving strategy for the electrochemical polymerization of dopamine (EPD) is reported. The PDA layer is deposited on vertically aligned TiO2 nanotube arrays (NTAs). Owing to the abundant catechol and amine groups in the PDA layer, uniform Pt nanoparticles (NPs) are deposited onto the TiO2 NTAs and can effectively prevent the recombination of electron-hole pairs generated from photo-electrocatalysis and transfer the captured electrons to participate in the photo-electrocatalytic reaction process. Compared with pristine TiO2 NTAs, the as-prepared Pt@TiO2 NTA composites exhibit surface-enhanced Raman scattering sensitivity for detecting rhodamine 6G and display excellent UV-assisted self-cleaning ability, and also show promise as a nonenzymatic glucose biosensor. Furthermore, the mussel-inspired electropolymerization strategy and the fast EPD-reduced nanoparticle decorating process presented herein can be readily extended to various functional substrates, such as conductive glass, metallic oxides, and semiconductors. It is the adaptation of the established PDA system for a selective, robust, and generalizable sensing system that is the emphasis of this work.


Derlin2 protein facilitates HRD1-mediated retro-translocation of sonic hedgehog at the endoplasmic reticulum.
Endoplasmic reticulum-associated degradation (ERAD) is an important system that eliminates misfolded proteins from the ER. Three derlins have been implicated in this process, but their precise function remains unknown. In this study, we report that although both derlin1 and derlin2 are capable of binding the ERAD-specific ubiquitin ligase HRD1, they associate with the HRD1-containing complex with different affinities. Accordingly, these derlins have nonredundant functions in ERAD with derlin2 being an essential functional partner for HRD1-mediated ERAD of SHH and NHK. We show that derlin2, but not derlin1 or derlin3, is required for ERAD of both glycosylated and nonglycosylated SHH, as well as NHK. Derlin2 appears to act at a post-targeting step for HRD1-dependent retro-translocation. Without derlin2, the assembly of HRD1 into a functional retro-translocation homo-oligomer proceeds normally, and substrate targeting to the HRD1 complex also occurs. However, the ERAD substrate SHH-C is largely trapped inside the ER lumen. These observations raise the possibility that derlin2 may regulate the movement of substrates through the HRD1-containing retro-translocon. Our study is the first to report that derlin2 functions with HRD1 in ERAD of certain substrates independent of their glycosylation status. The mammalian ERAD system may require multiple derlins that each functions with a distinct E3 partner to eliminate a specific subset of substrates. This is different from the model in Saccharomyces cerevisiae, in which Hrd1p alone is sufficient for retro-translocation.


Spin pumping with coherent elastic waves.
We show that the resonant coupling of phonons and magnons can be exploited to generate spin currents at room temperature. Surface acoustic wave pulses with a frequency of 1.55 GHz and duration of 300 ns provide coherent elastic waves in a ferromagnetic thin-film-normal-metal (Co/Pt) bilayer. We use the inverse spin Hall voltage in the Pt as a measure for the spin current and record its evolution as a function of time and external magnetic field magnitude and orientation. Our experiments show that a spin current is generated in the exclusive presence of a resonant elastic excitation. This establishes acoustic spin pumping as a resonant analogue to the spin Seebeck effect.


Intestinal cytokine response of commercial source broiler chicks to Salmonella typhimurium infection.
Development of molecular-based immunotherapeutic strategies for controlling Salmonella Typhimurium (ST) infection in poultry requires a better understanding of intestinal and cecal cytokine responses. Accordingly, an experiment was conducted to measure changes in intestinal cytokine expression when commercial source broiler chickens were challenged with a nalidixic acid-resistant ST. Ross broiler chicks were nonchallenged with ST (control treatment) or challenged by orally giving 7.8 x 10(6) cfu at 4 d of age (STC treatment). Each treatment consisted of 4 replicate pens with 14 chicks per pen. Expression levels of proinflammatory cytokines, interferon-gamma, and antiinflammatory interleukin (IL)-10 were determined at 5 and 10 d postchallenge (PC). Intestinal flushes were also collected from each treatment at 7 d PC to estimate IgA and IgG. Results showed an upregulation in IL-1beta mRNA in STC chicks at 5 d PC. By 10 d PC, the expression of IL-1beta was further increased and accompanied by an upregulation of IL-6 and interferon-gamma mRNA, whereas IL-10 mRNA expression decreased. It was concluded that ST induced an intestinal mucosal inflammatory response in commercial source broiler chicks less than 2 wk of age.


Clinical pattern of females with crystal-induced arthritis: gout and pseudogout.
Of the 228 patients with crystal-induced arthritis (194 cases of gouty arthritis, 34 cases of pseudogout) seen between 1976 and 1985 at the Medical Service of Chulalongkorn hospital in Bangkok, 46 of them or 20.2 per cent of the total were female. The females with crystal-induced arthritis included 22 cases of gouty arthritis and 24 cases of pseudogout. Pseudogout was seen more commonly than gouty arthritis during the 10-year period. Both types exhibited a similar pattern with regard to late onset of disease at age 60 or more (75% of the cases with pseudogout and 54% of those with gouty arthritis), monoarticular arthritis as the initial manifestation (83.3% of those with pseudogout and 59.1% of those with gouty arthritis), intermittent pattern (54.2% of those with pseudogout and 86.4% of those with gouty arthritis) and the presence of precipitating factors (37.5% of those with pseudogout and 45.5% of those with gouty arthritis). However, different patterns were observed with regard to the joint of involvement: the knee joint was the most commonly involved joint in pseudogout (75%) but the ankle joint was seen in cases of gouty arthritis (86.4%). Podagra was not observed in cases of pseudogout, although in 22.7% of the patients with gouty arthritis, it was the initial manifestation of the disease. In subsequent attacks of arthritis, monoarticular arthritis (61.5%) and knee joint involvement (75%) were the main features of pseudogout. Oligoarticular arthritis (63.2%) and ankle joint involvement (86.4%) were the main feature of gouty arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)


[Coronary blood flow during stochastic stimulation of the canine heart].
Changes of mechanical activity and coronary blood flow induced by haphazard uncorrelated sequence of stimuli, were studied in the dog heart. The total coronary blood flow did not differ from one during determined regimen of the same mean frequency. Whereas relative contribution of systolic coronary flow increased and that of diastolic one decreased. The analysis of phasic blood flow in coronary vessels during potentiated and extrasystolic contractions, was performed.


Corticospinal Excitability Is Lower During Eccentric Than Concentric Cycling in Men.
How corticospinal excitability changes during eccentric locomotor exercise is unknown. In the present study, 13 volunteers performed 30-min strenuous concentric and eccentric cycling bouts at the same power output (60% concentric peak power output). Transcranial magnetic and electrical femoral nerve stimulations were applied at exercise onset (3rd min) and end (25th min). Motor-evoked potentials (MEPs) amplitude was measured for the rectus femoris (RF) and vastus lateralis (VL) muscles with surface electromyography (EMG) and expressed as a percentage of maximal M-wave amplitude (MMAX). EMG amplitude 100 ms prior to MEPs and the silent period duration were calculated. There was no change in any neural parameter during the exercises (all P > 0.24). VL and RF MMAX were unaffected by exercise modality (all P > 0.38). VL MEP amplitude was greater (26 ± 11.4 vs. 15.2 ± 7.7% MMAX; P = 0.008) during concentric than eccentric cycling whereas RF MEP amplitude was not different (24.4 ± 10.8 vs. 17.2 ± 9.8% MMAX; P = 0.051). While VL EMG was higher during concentric than eccentric cycling (P = 0.03), RF EMG showed no significant difference (P = 0.07). Similar silent period durations were found (RF: 120 ± 30 ms; VL: 114 ± 27 ms; all P > 0.61), but the silent period/MEP ratio was higher during eccentric than concentric cycling for both muscles (all P < 0.02). In conclusion, corticospinal excitability to the knee extensors is lower and relative silent period longer during eccentric than concentric cycling, yet both remained unaltered with time.


TBHQ Attenuates Neurotoxicity Induced by Methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT Signaling Pathways.
Methamphetamine (METH) leads to nervous system toxicity. Long-term exposure to METH results in damage to dopamine neurons in the ventral tegmental area (VTA), and depression-like behavior is a clinical symptom of this toxicity. The current study was designed to investigate whether the antioxidant tertiary butylhydroquinone (TBHQ) can alleviate neurotoxicity through both antioxidative stress and antiapoptotic signaling pathways in the VTA. Rats were randomly divided into a control group, a METH-treated group (METH group), and a METH+TBHQ-treated group (METH+TBHQ group). Intraperitoneal injections of METH at a dose of 10 mg/kg were administered to the rats in the METH and METH+TBHQ groups for one week, and METH was then administered at a dose that increased by 1 mg/kg per week until the sixth week, when the daily dosage reached 15 mg/kg. The rats in the METH+TBHQ group received 12.5 mg/kg TBHQ intragastrically. Chronic exposure to METH resulted in increased immobility times in the forced swimming test (FST) and tail suspension test (TST) and led to depression-like behavior. The production of reactive oxygen species (ROS) and apoptosis levels were increased in the VTA of animals in the METH-treated group. METH downregulated Nrf2, HO-1, PI3K, and AKT, key factors of oxidative stress, and the apoptosis signaling pathway. Moreover, METH increased the caspase-3 immunocontent. These changes were reversed by treatment with the antioxidant TBHQ. The results indicate that TBHQ can enhance Nrf2-induced antioxidative stress and PI3K-induced antiapoptotic effects, which can alleviate METH-induced ROS and apoptosis, and that the crosstalk between Nrf2 and PI3K/AKT is likely the key factor involved in the protective effect of TBHQ against METH-induced chronic nervous system toxicity.


Proteins specified by herpes simplex virus. V. Purification and structural proteins of the herpesvirion.
We are reporting a procedure for the purification of herpes simplex enveloped nucleocapsids (virions), an evaluation of the purification procedure and the results of analyses of the virion proteins by high-resolution acrylamide gel electrophoresis. The data may be summarized as follows. (i) The procedure for the purification of virions consists of careful extraction of cytoplasm to prevent nuclear breakage, separation of enveloped nucleocapsids from soluble proteins and membrane vesicles by rate zonal centrifugation of cytoplasmic extracts through dextran 10 gradients, treatment with urea to dissociate virus-debris aggregates, and, lastly, separation of virions from naked nucleocapsids and free membranes by isopycnic flotation in discontinuous sucrose gradients. (ii) Purity was evaluated in three ways, i.e., electron microscopic examination, analysis of purified virions produced in cells labeled with amino acids before infection, and analysis of purified virions from artificial mixtures of infected and labeled, uninfected cells. The extent of purification was 120-to 200-fold with respect to host proteins. Residual contaminants were identified as host and viral constituents of membrane vesicles. Residual host proteins are very likely contaminants and not structural components of the virion. (iii) Analyses by staining and autoradiography of structural proteins of purified virions in 6, 7, 8.5, 9, and 14% acrylamide gels revealed 24 bands of proteins and glycoproteins made and labeled after infection. Co-electrophoresis of viral proteins with six known standards ranging from 25,700 to 220,000 daltons in molecular weight in 6, 7, 8.5, and 9% acrylamide gels indicate that viral proteins range from 25,000 to 275,000 daltons. The sum of the molecular weights of viral proteins is 2,580,000 daltons. Assuming that messenger transcription is asymmetric and noncomplementary, this corresponds to 47% of the genetic information of the virus. (iv) The nonionic detergent NP-40 removes from purified virions some nonglycosylated proteins and a large fraction of the glycosylated proteins. It leaves behind traces of the envelope visible in the electron microscope as well as some glycoproteins thought to be in the envelope.


[The roles of AC/A ratio and other ocular motor parameters in the induction of late-onset myopia].
This study was to explore ocular motor parameters (accommodation and convergence) in late myopia onset and development. Eleven Emm (emmetrope), 14 S.M. (stable late-onset myopia), and 9 P.M. (progressing late-onset myopia) were include in this study. Phoria at distance and near, positive and negative relative accommodation (NRA/PRA), accommodative convergence and accommodation response were measured. Response AC/A ratio of P.M. was higher than that of Emm or S.M. (P < 0.05); But statistically AC/A ratio was not significant difference (P > 0.05). Accommodation response (3.00 D) of Emm was higher than P.M and S.M (P < 0.05). There was significant difference in phoria in near between LOM and Emm, but none in that of distance. There was no significant difference in NRA. However, PRA of LOM was lower than that of the Emm (P < 0.05). Ocular motor parameters are important in LOM onset and development. Response AC/A ratio (not calculated AC/A ratio) is one of key parameters among them, Response AC/A ratio is the highest in P.M, which indicates out of focus of retinal image in the developing LOM.


A safe and effective way for reduction of temporomandibular joint dislocation.
Anterior dislocation of the temporomandibular joint (TMJ) is a common problem which demands immediate reduction to relieve the discomfort. The most popular technique is to put the operator's thumbs over the molar teeth of the patient and push the dislocated jaw downward and backward. This maneuver takes a lot of effort and usually needs sedation. Failure to reduction is not uncommon. Furthermore, the physician has to take the risk of being bitten and disease transmission. A novel method for reduction of the dislocated TMJ via extraoral route is presented, based on the observation that once the mandible is dislocated anteriorly, the coronoid process and anterior border of the ramus can be palpated easily over the cheek. By applying steady pressure over this prominent part, the anteriorly dislocated mandible can be reduced easily. From May 2000 to July 2005, there were 7 anterior mandible dislocations treated successfully by this method in Chang Gung Memorial Hospital. None of the patients need any adjuvant medication for sedation or relaxation. This technique is simple and effective, and the physicians are spared from the risk of bite trauma and unexpected disease transmission.


Increased mammographic breast density in acromegaly: quantitative and qualitative assessment.
Mammographic density is a strong independent risk factor for breast cancer, whose prevalence in acromegaly is still controversial. To compare breast density in premenopausal acromegalic patients and controls and to determine whether density correlated with disease duration, GH, and IGF1 levels. A prospective study involving 30 patients and 60 controls matched for age and body mass index. A quantitative computer-aided mammographic density estimation (MDEST) and a qualitative blind evaluation by two experienced radiologists using the breast imaging reporting and data system (BI-RADS) was performed. Totally, 60 (acromegaly) and 120 (controls) craniocaudal and mediolateral oblique mammograms were evaluated in both patients and controls. Breast density. Patients showed a significantly (P<0.01) increased mammographic breast density with both methods (MDEST: 0.33 ± 0.21% and BI-RADS category: 2.81 ± 0.78) in comparison with controls (MDEST: 0.26 ± 0.19% and BI-RADS category: 2.35 ± 0.61). The agreement between the two methods and inter-observer agreement between the two radiologists were excellent (k=0.63 and k=0.85). In patients grouped according to disease activity (17 controlled and 13 uncontrolled) and medical therapy (15 treated and 15 untreated), no differences were found. All these groups had significantly increased mammographic breast density compared with controls (P<0.01). A positive correlation was found between mammographic breast density, IGF1 values and disease duration (r=0.29 and r=0.39), whereas it was not found with GH (r=-0.02). Mammographic breast density in premenopausal acromegalic patients is significantly higher than controls and positively correlated with IGF1 and disease duration.


Effects of knee sleeves on coordination of lower-limb segments in healthy adults during level walking and one-leg hopping.
The evaluation of multisegment coordination is important in gaining a better understanding of the gait and physical activities in humans. Therefore, this study aims to verify whether the use of knee sleeves affects the coordination of lower-limb segments during level walking and one-leg hopping. Eleven healthy male adults participated in this study. They were asked to walk 10 m on a level ground and perform one-leg hops with and without a knee sleeve. The segment angles and the response velocities of the thigh, shank, and foot were measured and calculated by using a motion analysis system. The phases between the segment angle and the velocity were then calculated. Moreover, the continuous relative phase (CRP) was calculated as the phase of the distal segment subtracted from the phase of the proximal segment and denoted as CRPTS (thigh-shank), CRPSF (shank-foot), and CRPTF (thigh-foot). The root mean square (RMS) values were used to evaluate the in-phase or out-of-phase states, while the standard deviation (SD) values were utilized to evaluate the variability in the stance and swing phases during level walking and in the preflight, flight, and landing phases during one-leg hopping. The walking velocity and the flight time improved when the knee sleeve was worn (p < 0.05). The segment angles of the thigh and shank also changed when the knee sleeve was worn during level walking and one-leg hopping. The RMS values of CRPTS and CRPSF in the stance phase and the RMS values of CRPSF in the preflight and landing phases changed (p < 0.05 in all cases). Moreover, the SD values of CRPTS in the landing phase and the SD values of CRPSF in the preflight and landing phases increased (p < 0.05 in all cases). These results indicated that wearing a knee sleeve caused changes in segment kinematics and coordination.


Antibodies to nuclear lamin proteins in liver disease.
Sera of patients with autoimmune liver disease contained antibodies reactive with nuclear lamins. These antigens were identified in immunoblotting experiments, using isolated nuclei, nuclear matrices, nuclear lamina-pore complexes and purified lamins as antigen source. The lamins were, furthermore, characterized by 2-dimensional gel electrophoresis. Antibodies to nuclear lamins were found in 75 per cent of the active lupoid hepatitis cases, but not in patients with inactive disease. Anti-lamin antibodies were detected in 8 per cent of primary biliary cirrhosis sera. The autoimmune liver disease sera recognized predominantly the nuclear lamins A/C, and less frequently the lamins A/B/C or lamin B.


Do resonance-assisted intramolecular halogen bonds exist without a charge transfer and a σ-hole?
To analyze the properties and mechanisms of six types of intramolecular resonance-assisted halogen bonds (Br···O, Cl···O, F···O, Br···O, Cl···S and F···S), we have chosen the five-membered closed ring system X-C1R1=C3R2-C2R3=Y (X = Br, Cl & F; Y = O & S) of unsaturated compounds with the substituents NO2, CH3 and H. A total of 78 structures were investigated by quantum chemical calculations at the MP2/aug-cc-pVTZ level of theory. A molecular electrostatic potential (MESP) map reveals that the cusp point of the σ-hole was not utilized but the belt point was used for all these intramolecular halogen-bonding interactions, indicating that all are electrostatic interactions. The halogen-bonding angle is below 100° with the strongest interactions. The value of the nucleus-independent chemical shift (NICS (1)) reflects the changes and efficiency of resonance in all structures with a long bond. The presence of all interactions was proved by the bond critical point (BCP) and analyzed through its electron density, Laplacian of electron density and ellipticity parameter. The linear-probability correlation between the difference of the sum of the van der Waals radius and the non-covalent bond length (∑vdW-L) and the electron density of the BCP was reported. 2D and 3D-NCI (non covalent interactions) plots show that halogen-bonding interactions are a mixed type of interactions with an attractive term. Natural bond orbital (NBO) analysis clearly indicates that the halogen bond lacks charge transfer and orbital overlapping through non-interacting lobes.


Effect of cigarette smoking on experimental microvascular anastomoses.
Cigarette smoking has been shown to cause cutaneous vasoconstriction, a decrease in digital blood flow, impaired wound healing, and it was implicated as a cause of failure of microvascular anastomoses in replanted digits. The subject of the following study was to assess the effect of cigarette smoking on experimental microvascular anastomoses. Twenty Sprague-Dawley male rats weighting 200 to 250 grams were divided into groups of ten. Both the experimental and the control groups were acclimatized to a Maddox/ORNL rat smoke inhalation exposure system for six days prior to operation. At this time they were anesthetized and bilateral femoral artery end to end anastomoses were performed by two surgeons, using standard microsurgical techniques. After a recovery period of 24 hours, both groups were started on a smoking/sham-smoking regime for 12 to 13 days. After this time they were anesthetized again, the femoral artery anastomoses were checked for patency in vivo and excised for histological evaluation. Five cm3 of blood was drawn from each animal to be analyzed for the presence of nicotine and its metabolites, and the rats were sacrificed. All the anastomoses in both groups were patent at the time of exploration and no histological difference could be demonstrated between the two groups. The radioimmunoassay of nicotine and cotinine showed large amounts in the smokers, and none in the nonsmokers.


Reproducibility of maximum aerobic power (VO2max) among soccer players using a modified heck protocol.
To determine the degree of reproducibility of maximum oxygen consumption (VO2max) among soccer players, using a modified Heck protocol. 2 evaluations with an interval of 15 days between them were performed on 11 male soccer players. All the players were at a high performance level; they were training for an average of 10 hours per week, totaling 5 times a week. When they were evaluated, they were in the middle of the competitive season, playing 1 match per week. The soccer players were evaluated on an ergometric treadmill with velocity increments of 1.2 km.h-1 every 2 minutes and a fixed inclination of 3% during the test. VO2max was measured directly using a breath-by-breath metabolic gas analyzer. The maximum running speed and VO2max attained in the 2 tests were, respectively: (15.6 +/- 1.1 vs. 15.7 +/- 1.2 km.h-1; [P = .78]) and (54.5 +/- 3.9 vs. 55.2 +/- 4.4 ml.kg-1.min-1; [P = .88]). There was high and significant correlation of VO2max between the 2 tests with a 15-day interval between them [r = 0.97; P < .001]. The modified Heck protocol was reproducible, and the 15-day interval between the ergospirometric testing was insufficient to significantly modify the soccer players' VO2max values.


Calcium Homeostasis and Muscle Energy Metabolism Are Modified in HspB1-Null Mice.
Hsp27-encoded by HspB1-is a member of the small heat shock proteins (sHsp, 12-43 kDa (kilodalton)) family. This protein is constitutively present in a wide variety of tissues and in many cell lines. The abundance of Hsp27 is highest in skeletal muscle, indicating a crucial role for muscle physiology. The protein identified as a beef tenderness biomarker was found at a crucial hub in a functional network involved in beef tenderness. The aim of this study was to analyze the proteins impacted by the targeted invalidation of HspB1 in the Tibialis anterior muscle of the mouse. Comparative proteomics using two-dimensional gel electrophoresis revealed 22 spots that were differentially abundant between HspB1-null mice and their controls that could be identified by mass spectrometry. Eighteen spots were more abundant in the muscle of the mutant mice, and four were less abundant. The proteins impacted by the absence of Hsp27 belonged mainly to calcium homeostasis (Srl and Calsq1), contraction (TnnT3), energy metabolism (Tpi1, Mdh1, PdhB, Ckm, Pygm, ApoA1) and the Hsp proteins family (HspA9). These data suggest a crucial role for these proteins in meat tenderization. The information gained by this study could also be helpful to predict the side effects of Hsp27 depletion in muscle development and pathologies linked to small Hsps.


The surface properties and antigen-presenting function of hepatic non-parenchymal cells.
Hepatic endothelial cells and Kupffer cells have been isolated after pronase digestion of mouse liver and separated by density-gradient centrifugation on Percoll. The endothelial cells had a central round nucleus with a pale cytoplasm which contained non-specific esterase. They had Fc receptors but no Ia antigen, C3 receptor or phagocytic ability. In contrast, the phagocytic Kupffer cell had an initial rounded appearance and possessed Fc and C3 receptors and Ia antigens. Kupffer cells were capable of functioning as antigen-presenting cells as shown by their ability to reconstitute a secondary in vitro antibody in spleen cell cultures depleted of adherent cells. This function was genetically restricted. There was progressive loss of antigen-presenting function of Kupffer cells as time in culture increased. This appeared to be related to the loss of Ia antigen. Hepatic endothelial cells did not restore the antibody response in macrophage-depleted spleen cell cultures. The experiments show that Kupffer cells can function as antigen-presenting cells in a secondary antibody response in vitro and that this function is not due to the presence of endothelial cells in the isolated sinus lining cells.


Reevaluating the Long-Term Impact of In Utero Exposure to the 1918 Influenza Pandemic.
Almond (2006) argues that in utero exposure to the 1918 influenza pandemic reduced the 1919 birth cohort's adult socioeconomic status (SES). We show that this cohort came from lower-SES families, which is incompatible with Almond's cohort-comparison identification strategy. The adult SES deficit is reduced after background characteristics are controlled for; it is small and statistically insignificant in models that include household fixed effects. Replicating Almond's state-level dose-response analysis, we find no evidence in census data that influenza exposure reduced adult SES. Evidence from a city-level dose-response analysis on educational attainment using WWII enlistees from 287 cities is mixed.


Diurnal fluctuation in the number of hypocretin/orexin and histamine producing: Implication for understanding and treating neuronal loss.
The loss of specific neuronal phenotypes, as determined by immunohistochemistry, has become a powerful tool for identifying the nature and cause of neurological diseases. Here we show that the number of neurons identified and quantified using this method misses a substantial percentage of extant neurons in a phenotype specific manner. In mice, 24% more hypocretin/orexin (Hcrt) neurons are seen in the night compared to the day, and an additional 17% are seen after inhibiting microtubule polymerization with colchicine. We see no such difference between the number of MCH (melanin concentrating hormone) neurons in dark, light or colchicine conditions, despite MCH and Hcrt both being hypothalamic peptide transmitters. Although the size of Hcrt neurons did not differ between light and dark, the size of MCH neurons was increased by 15% in the light phase. The number of neurons containing histidine decarboxylase (HDC), the histamine synthesizing enzyme, was 34% greater in the dark than in the light, but, like Hcrt, cell size did not differ. We did not find a significant difference in the number or the size of neurons expressing choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme, in the horizontal diagonal band (HBD) during the dark and light conditions. As expected, colchicine treatment did not increase the number of these neurons. Understanding the function and dynamics of transmitter production within "non-visible" phenotypically defined cells has fundamental implications for our understanding of brain plasticity.


An integrated microfluidic system for the isolation and detection of ovarian circulating tumor cells using cell selection and enrichment methods.
Gynecological cancer is difficult to be diagnosed at early stages. The relatively high mortality rate has been a serious issue accordingly. We herein reported a diagnosis method by using circulating tumor cells (CTCs) which have been extensively explored as a potential tool for diagnostics and prognostics of ovarian cancers. Nonetheless, the detection of CTCs still remains a challenge because of the difficulty in isolating them from whole blood samples since they are shed into the vasculature from primary tumors and circulate irregularly in the bloodstream in extremely low concentrations. In this work, we reported a new, integrated microfluidic system capable of (1) red blood cells lysis, (2) white blood cell (WBC) depletion via a negative selection process, and (3) capture of target cancer cells from whole blood samples using aptamer-binding technology. Furthermore, this is the first time that an aptamer was used to capture ovarian cancer cells owing to its high affinity. The new microfluidic chip could efficiently perform the entire process in one hour without human intervention at a high recovery rate and a low false positive detection rate when compared with antibody-based systems. A high recovery rate for the isolation of CTCs within a short period of time has been reported when compared to the traditional negative or positive selection approach by using traditional antibody biomarkers. More importantly, "false positive" results from WBCs could be significantly alleviated due to the high specificity of the cancer cell-specific aptamers. The developed integrated microfluidic system could be promising for the isolation and detection of CTCs, which could be used for early diagnosis and prognosis of cancers.


Development of a web-based executive functioning intervention for adolescents with epilepsy: The Epilepsy Journey.
Youth with epilepsy exhibit significant deficits in executive functioning (EF), yet there are few interventions to improve EF for adolescents. The aims of the current study were to develop an individually-tailored intervention, called Epilepsy Journey, to improve aspects of EF through an iterative, patient-centered process including focus groups and usability testing. Five adolescents and caregivers participated in focus groups. This input was used to develop ten learning modules based on subscales of the Behavioral Rating Inventory of Executive Functions and key issues that may impact EF in adolescents. Six adolescents participated in usability testing and a usability expert conducted a heuristic evaluation. Demographic information, chart reviews and measures of EF were also completed. Focus group participants and their parents reported difficulties with memory, attention, organization, monitoring, initiation, impulsivity, emotional control, sleep, awareness in schools and managing stress. They also identified successful strategies to address memory and organizational difficulties. Usability testing of the resultant Epilepsy Journey modules revealed problems with navigation and identified features that promoted usability, including progress bars and interactive modules. Program modifications were made after each usability trial resulting in a relatively brief, interactive and readily navigable program. Perceived utility was high with all but one participant. Participants rated the content as helpful and indicated they would recommend Epilepsy Journey to others. Feedback from the focus group and usability testing yielded a feasible, acceptable, relevant and user-friendly web-based intervention for adolescents with epilepsy. The Epilepsy Journey program will be further tested in an open pilot with adolescents with epilepsy and associated EF deficits.


Interaction of oestrogen and peroxisome proliferator-activated receptors with apolipoprotein(a) gene enhancers.
A high plasma concentration of lipoprotein(a) [Lp(a)] confers an increased risk for the development of coronary heart disease. Hormones, such as oestrogen, are some of the few compounds known to reduce plasma Lp(a) levels. A putative enhancer region, located at the DHII DNase I hypersensitive site approx. 28 kb upstream of the apolipoprotein(a) [apo(a)] gene, contains a number of sequences similar to the binding half-sites for nuclear hormone receptors, such as the oestrogen receptor and the peroxisome proliferator-activated receptor (PPAR). The 180 bp core DHII enhancer increased the activity of the apo(a) promoter by over 7-fold in reporter-gene assays in HepG2 cells in vitro. Almost 60% of this increase was lost in the presence of co-transfected oestrogen receptor and oestrogen. In contrast, co-transfection with PPARalpha increased the effect of the DHII enhancer on apo(a) transcriptional activity by approx. 70% and could overcome the inhibitory effect of the oestrogen receptor on apo(a) transcription. Gel mobility-shift assays showed that oestrogen receptor protein bound to one half of a sequence corresponding to a predicted oestrogen receptor response element. PPARalpha also bound to this site and competed with oestrogen receptors for binding. In addition, PPARalpha bound to a separate site that comprised part of a direct repeat of nuclear hormone receptor half-sites. The results suggest that nuclear hormones affect plasma Lp(a) concentrations by binding to the sequences within the DHII enhancer, thereby altering the amount by which the enhancer increases the transcription of the apo(a) gene.


Rupture of the triceps tendon associated with steroid injections.
Rupture of the triceps mechanism is an uncommon injury that has been recognized with increasing frequency in recent years. It has been proposed that such injuries commonly accompany fractures of the radial head and must be actively evaluated in the presence of such a fracture. We present a unique case of isolated rupture of the triceps tendon in an athlete who was lifting weights. This case was complicated by a history of olecranon bursitis that had been treated with numerous local steroid injections, as well as a history of anabolic steroid abuse. Both systemic steroids and local injections may predispose tendons to rupture. Triceps tendon ruptures may result in uniformly good to excellent results if recognized and treated surgically. This case also serves as a reminder of the risks of treating inflamed tissues with local steroid injections, especially in strength athletes who place high demands on their musculoskeletal structures. Finally, this case documents a second case of triceps mechanism rupture in an athlete who has abused anabolic steroids. A study by Hunter et al. suggests that oral steroid abuse may be associated with detrimental effects on the mechanical properties of connective tissue, demonstrating another negative effect of anabolic steroid use in athletes.


Digit Memory Test: unequivocal cerebral dysfunction and suspected malingering.
The Digit Memory Test (DMT) (Hiscock & Hiscock, 1989), a forced-choice test for detecting malingering, was administered to 27 patients with unequivocal cerebral dysfunction, 5 patients with postconcussional syndrome, 6 suspected malingerers and 10 normal controls. Results indicate that, even in patients with severe, but static cerebral dysfunction and unequivocal memory disorder, DMT performance is between 95% to 100% correct. By contrast, the 6 patients in whom malingering was seriously considered performed at a level much below the other three groups (74% correct) but not significantly below chance. The DMT may be helpful in evaluating patients suspected of malingering even when they do not score significantly below chance.