Comparison of wholemount dissection methods for neuronal subtype marker expression in the mouse myenteric plexus.
Accurately reporting the identity and representation of enteric nervous system (ENS) neuronal subtypes along the length of the gastrointestinal (GI) tract is critical to advancing our understanding of ENS control of GI function. Reports of varying proportions of subtype marker expression have employed different dissection techniques to achieve wholemount muscularis preparations of myenteric plexus. In this study, we asked whether differences in GI dissection methods could introduce variability into the quantification of marker expression. We compared three commonly used methods of ENS wholemount dissection: two flat-sheet preparations that differed in the order of microdissection and fixation and a third rod-mounted peeling technique. We also tested a reversed orientation variation of flat-sheet peeling, two step-by-step variations of the rod peeling technique, and whole-gut fixation as a tube. We assessed marker expression using immunohistochemistry, genetic reporter lines, confocal microscopy, and automated image analysis. We found no significant differences between the two flat-sheet preparation methods in the expression of calretinin or neuronal nitric oxide synthase (nNOS) as a proportion of total neurons in ileum myenteric plexus. However, the rod-mounted peeling method resulted in decreased proportion of neurons labeled for both calretinin and nNOS. This method also resulted in decreased transgenic reporter fluorescent protein (tdTomato) for substance P in distal colon and choline acetyltransferase (ChAT) in both ileum and distal colon. These results suggest that labeling among some markers, both native protein and transgenic fluorescent reporters, is decreased by the rod-mounted mechanical method of peeling. The step-by-step variations of this method point to mechanical manipulation of the tissue as the likely cause of decreased labeling. Our study thereby demonstrates a critical variability in wholemount muscularis dissection methods.


Fungal-derived xenobiotic exhibits antibacterial and antibiofilm activity against Staphylococcus aureus.
Staphylococcus aureus is an opportunistic pathogen, responsible for superficial and invasive infections both in nosocomial and community-acquired settings. The incidences of infection have become more problematic attributable to emerging drug resistance and biofilm formation. These challenges suggest the need for new antimicrobial agents against S. aureus. In present work, we purified a fungal xenobiotic (FI3) which elicits a potent antimicrobial activity against a list of tested microbes including methicillin sensitive (MSSA) and methicillin resistance (MRSA) S. aureus. The cell growth of MSSA and MRSA were completely ceased with the 1× minimum inhibitory concentration (MIC); 32 µg/mL and 128 µg/mL, respectively. The cell viability severely decreased within 90 min, due to disturbance of membrane homeostasis. This bactericidal effect was enhanced at lower pH (pH 4) with a speculation to retain positive charge. The FI3 potently disrupts biofilm adherence at 64 µg/mL and found to be a safe with no toxic effect on mammalian tissue. FI3 also leads to increase the potency of tested antibiotics. Taken together, we established that FI3 has a potent antimicrobial activity against tested microbes and safer to human tissue. It may be proven a leading molecule for the treatment of bacterial infections.


Endogenous tissue plasminogen activator enhances fibrinolysis and limits thrombus formation in a clinical model of thrombosis.
Using a clinical model of deep arterial injury, we assessed the ability of exogenous and endogenous tissue plasminogen activator (t-PA) to limit acute in situ thrombus formation. Ex vivo thrombus formation was assessed in the Badimon chamber at low and high shear rates in 2 double-blind randomized cross-over studies of 20 healthy volunteers during extracorporeal administration of recombinant t-PA (0, 40, 200, and 1000 ng/mL) or during endogenous t-PA release stimulated by intra-arterial bradykinin infusion in the presence or absence of oral enalapril. Recombinant t-PA caused a dose-dependent reduction in thrombus area under low and high shear conditions (P<0.001 for all). Intra-arterial bradykinin increased plasma t-PA concentrations in the chamber effluent (P<0.01 for all versus saline) that was quadrupled in the presence of enalapril (P<0.0001 versus placebo). These increases were accompanied by an increase in plasma D-dimer concentration (P<0.005 for all versus saline) and, in the presence of enalapril, a reduction in thrombus area in the low shear (16±5; P=0.03) and a trend toward a reduction in the high shear chamber (13±7%; P=0.07). Using a well-characterized clinical model of coronary arterial injury, we demonstrate that endogenous t-PA released from the vascular endothelium enhances fibrinolysis and limits in situ thrombus propagation. These data support a crucial role for the endogenous fibrinolytic system in vivo and suggest that continued exploration and manipulation of its therapeutic potential are warranted.


Carotid stenting with cerebral protection: first clinical experience using the PercuSurge GuardWire system.
To study the feasibility and safety of carotid angioplasty and stenting using a new cerebral protection device that temporarily occludes the distal internal carotid artery (ICA). Forty-eight high-risk patients (39 men, mean age 69.1 +/- 8 years, range 54 to 86) with 53 ICA stenoses underwent percutaneous angioplasty and stenting via the femoral approach under cerebral protection afforded by a 0.014-inch GuardWire balloon occlusion device. Mean stenosis was 82.1% +/- 9.65% (range 70 to 96) and mean lesion length was 16.0 +/- 7.5 mm (range 6 to 50). Thirty-three (62%) lesions were calcified, and 38 (72%) were ulcerated. Thirty-two (60%) of the lesions were asymptomatic. With the occlusion balloon inflated in the distal ICA, the lesion was dilated and stented. The area was cleaned by aspiration and flushed via an aspiration catheter advanced over the wire. Blood samples were collected from the external carotid artery (ECA) and analyzed to measure the size and number of particles collected. Computed tomography and neurological examinations were performed the day after the procedure. Immediate technical success was achieved in all patients with the implantation of 38 Palmaz stents, 8 Expander stents, and 11 Wallstents. Carotid occlusion was well tolerated in all patients but 1 who had multiple, severe carotid lesions and poor collateralization. Mean cerebral flow occlusion time was 346 +/- 153 seconds during predilation and 303 +/- 143 seconds during stent placement. Total mean flow occlusion time was 542 +/- 243 seconds. One immediate neurological complication (transient amaurosis) occurred in a patient who had an anastomosis between the external carotid (EC) and ICA territories. Debris was removed in all patients with a mean 0.8-mm diameter catheter. Cerebral protection with the GuardWire device is easy, safe, and effective in protecting the brain from cerebral embolism. Larger studies are warranted.


Economic-environmental assessment of silvo-pastoral systems in Colombia: An ecosystem service perspective.
Cattle production in Colombia has an important social and economic role but causes considerable environmental impacts, such as deforestation and greenhouse gas emissions by ruminants, particularly methane. Thus, technological innovations aimed at reducing these impacts must focus on both economic and environmental sustainability. Silvo-pastoral systems (SPS) offer productivity increases while generating environmental benefits and ecosystem services and are therefore at the center of debate around sustainable production alternatives. The objective of this article is to evaluate the economic-environmental performance of two proposed SPS for a cattle fattening system for the Colombian context: (i) Urochloa brizantha cv. Toledo and (ii) Urochloa hybrid cv. Cayman, both in association with Leucaena leucocephala trees for browsing and shade provision. They are compared with the respective base scenarios of only using the grasses in monocultures. The study consists of a financial analysis, which estimates potential profitability increases in beef production in the SPS, and an environmental evaluation, which estimates the monetary values of microclimatic regulation and reduction of methane emissions. The value of methane emission reductions is then integrated into a combined economic-environmental evaluation. Results show that both SPS improve the profitability indicators of the production system and reduce the probability of economic loss. Likewise, the reduction of methane emissions in the SPS is estimated at US$6.12 per cattle, and the economic value of microclimatic regulation at US$2,026 per hectare.


Novel, nano-sized, liposome-encapsulated polyamidoamine dendrimer derivatives facilitate tumour targeting by overcoming the polyethylene glycol dilemma and integrin saturation obstacle.
Drug delivery systems (DDSs) commonly employ arginine-glycine-aspartic acid (RGD) peptides with polyethylene glycol (PEG)-dependent enhanced permeability and retention (EPR) effect to optimise tumour-targeting. However, the PEG dilemma and integrin saturation obstacle are major challenges. To address these issues, we constructed a novel, nano-sized DDS by encapsulating doxorubicin (DOX)-loaded folic acid derivatives of polyamidoamine dendrimer (PAMAM G5.0) in cyclic RGD-tyrosine-lysine pentapeptide (c[RGDyK])-modified liposomes (RGD-SL[FND/DOX]), prepared using thin-film hydration, film-dispersion and hydration-sonication. The liposomes were PEGylated, sterically stabilised and pH-sensitive. In vitro, RGD-SL[FND/DOX] showed pH-sensitive holistic FND/DOX release, and pH-dependent uptake and cytotoxicity in human cancer KB cells. At pH 7.4, RGD-SL[FND/DOX] demonstrated greater cellular uptake and cytotoxicity than relevant control formulations (except FND/DOX) did, although this advantage disappeared at pH 6.5. In vivo, RGD-SL[FND/DOX] inhibited S180 sarcoma xenografted tumour growth in Kunming mice more effectively than FND/DOX did. These findings demonstrate the feasibility of constructing double-stage tumour-targeting nano-sized DDSs such as RGD-SL[FND/DOX]. c[RGDyK] and the EPR effect, facilitated by the particle size (about 110 nm) and PEGylation, helped to target the DDS to the tumour tissue, while the subsequent pH-dependent release of FND/DOX and folic acid-mediated endocytosis specifically targeted the tumour cells, thereby overcoming the PEG dilemma and integrin saturation obstacle.


Systematic review of persistent pain and psychological outcomes following traumatic musculoskeletal injury.
Persistent pain and psychological distress are common after traumatic musculoskeletal injury (TMsI). Individuals sustaining a TMsI are often young, do not recover quickly, and place a large economic burden on society. The aim of this systematic review is to determine (1) the incidence of persistent pain following TMsI, (2) the characteristics of pain, characterized by injury severity and type, and (3) risk and protective factors associated with persistent pain following TMsI. A systematic search of electronic databases (MEDLINE(®), PubMed(®), Embase, and PsycINFO(®)) was conducted for prospective, interventional, or noninterventional studies measuring the incidence of pain associated with TMsI. The search revealed 4388 studies. Eleven studies examined persistent pain and met inclusion criteria. Pain was assessed using a validated measure of pain intensity or pain presence in six studies. Persistent pain was reported by all studies at variable time points up to 84 months postinjury, with wide variation among studies in pain intensity (ie, from mild to very severe) and pain incidence at each time point. The incidence of pain decreased over time within each study. Two studies found significant relationships between injury severity and persistent pain. Frequently cited predictive factors for persistent pain included: symptoms of anxiety and depression, patient perception that the injury was attributable to external sources (ie, they were not at fault), cognitive avoidance of distressing thoughts, alcohol consumption prior to trauma, lower educational status, being injured at work, eligibility for compensation, pain at initial assessment, and older age. The evidence from the eleven studies included in this review indicates that persistent pain is prevalent up to 84 months following traumatic injury. Further research is needed to better evaluate persistent pain and other long-term posttraumatic outcomes.


[Development of mother sporocysts of Echinostoma caproni (Trematoda: Echinostomatidae)].
New data on the migration and development of Echinostoma caproni mother sporocysts in two mollusk species of the genus Biomphalaria are obtained. It is confirmed, that the formation of primary and second generative cells takes place only as a result of undifferentiated cells' proliferation and following differentiation of some of them. These processes in miracidium, as well as in the parasitic stage of mother sporocyst, take place in a special organ, germinal mass, which occupies caudal position in both cases. The supposition of the role of germinal mass as the universal centre of multiplication and development of generative elements in all generations of Echinostoma caproni parthenites is confirmed. It is established, that mother sporocysts do not relize their reproductive potential completely, and the degree of its realization depends on the conditions arising in the host organism.


Smoking and effect of chemotherapy in small cell lung cancer.
The relationship between smoking habits and outcome of treatment was studied in 154 patients with small cell lung cancer (SCLC) who received combination chemotherapy. Thirty-two patients had stopped smoking at least 6 months before the initiation of treatment or had never smoked (NS), 51 patients stopped smoking less than 6 months prior to the start of treatment (SS) and 71 patients continued to smoke during the treatment period (CS). Life table analysis of overall survival showed no significant heterogeneity among the groups (p greater than 0.7). Chi-square test for trend in survival yielded 0.23 (p greater than 0.6) with the longest survival in SS and CS patients, and the shortest survival in NS patients. Corresponding analysis of time to progression showed similar results, with a non-significant heterogeneity (p greater than 0.5) and trend (p greater than 0.4) among the three groups, with the CS patients doing best. In the whole series the disease-free two-year survival rate was higher in the CS patients than in the SS and NS patients (p = 0.04). The results do not imply that continued smoking during chemotherapy in SCLC has unfavourable effects on the outcome of treatment.


Parental marital disruption and intergenerational transfers: an analysis of lone elderly parents and their children.
Although one of the most marked demographic trends observed over the twentieth century is the increased rate of divorce, relatively little research has explored the effects of these changing marital patterns in the context of an aging society. Using a sample of lone elderly parents and their adult children, we analyze the direct and indirect effects of marital disruption on four important dimensions of intergenerational transfers: coresidence, financial assistance, adult children's provision of informal care, and parental purchase of paid care. Our findings suggest that divorce has deleterious effects on intergenerational transfers, particularly for elderly fathers. Remarriage further reduces exchange. Our results reveal that parents engage in lower levels of transfers with stepchildren relative to biological children. Moreover, intergenerational transfers are sensitive to characteristics of biological children but not to those of stepchildren. Taken together, these results suggest that exchange at the end of the life course continues to be adversely affected by marital disruption.


Thermal imaging as a biometrics approach to facial signature authentication.
A new thermal imaging framework with unique feature extraction and similarity measurements for face recognition is presented. The research premise is to design specialized algorithms that would extract vasculature information, create a thermal facial signature and identify the individual. The proposed algorithm is fully integrated and consolidates the critical steps of feature extraction through the use of morphological operators, registration using the Linear Image Registration Tool and matching through unique similarity measures designed for this task. The novel approach at developing a thermal signature template using four images taken at various instants of time ensured that unforeseen changes in the vasculature over time did not affect the biometric matching process as the authentication process relied only on consistent thermal features. Thirteen subjects were used for testing the developed technique on an in-house thermal imaging system. The matching using the similarity measures showed an average accuracy of 88.46% for skeletonized signatures and 90.39% for anisotropically diffused signatures. The highly accurate results obtained in the matching process clearly demonstrate the ability of the thermal infrared system to extend in application to other thermal imaging based systems. Empirical results applying this approach to an existing database of thermal images proves this assertion.


[Effect of polyvinylpyridine-N-oxide on the state of phagocyte-lymphoid elements in aseptic inflammation].
Cytochemical study of NAD-diaphorase and acid phosphatase (mitochondria and lysosomes markers) in the cells of the abdominal cavity exudate with aseptic inflammation and additional action of polyvinylpyridne-N-oxide with molecular weight in the range of from 2000 to 150 000 formed a background for demonstrating the possibility of stabilizing by means of the latter compound of mitochondrial and lysosomal membranes of macrophages, neutrophils and lymphocytes. The most pronounced stabilizing effect is produced by polyvinylpyridine-N-oxide with a molecular weight of 50 000 with its intramuscular introduction in a dose of 100 mg/kg.


Somatostatin, an inhibitor of ACTH secretion, decreases cytosolic free calcium and voltage-dependent calcium current in a pituitary cell line.
Somatostatin is a neurohormone peptide that inhibits a variety of secretory responses in different cell types. We have investigated the effects of somatostatin on calcium current and intracellular free calcium in AtT-20 cells, a pituitary tumor line in which the inhibitory actions of this peptide have been well characterized. At concentrations similar to those that inhibit adrenocorticotropic hormone (ACTH) release, somatostatin and its analogs reduced the levels of intracellular free calcium (as measured by the Quin-2 technique). Nifedipine and other blockers of voltage-dependent calcium channels also reduced cytosolic calcium levels. The effects of somatostatin and nifedipine were not additive, suggesting that somatostatin might inhibit calcium channels. Experiments using the whole-cell patch-clamp technique showed that somatostatin reduces voltage-dependent calcium current. The effects of somatostatin on cytosolic calcium and calcium current appear to be independent of its ability to reduce secretagogue-stimulated cAMP accumulation in these cells. We propose that the somatostatin-induced decrease in cytosolic calcium concentrations and the voltage-dependent calcium current are one of the mechanisms by which somatostatin suppresses ACTH release in AtT-20 cells.


The prescription of psychotropic medications for patients discharged from a psychiatric emergency service.
Considerable debate exists about the value and wisdom of initiating "definitive" pharmacotherapies, particularly antidepressants, in the psychiatric emergency setting. We evaluated the nature and prevalence of medication prescriptions for patients discharged from an urban psychiatric emergency service and the extent to which pharmacotherapy initiation was predictive of follow-through with aftercare. Records were reviewed for 675 consecutive individuals evaluated and discharged from a community-based psychiatric emergency service over a 3-month period (January 2003-March 2003). Information was obtained regarding diagnoses, past and current treatments, and demographic and clinical features, as well as outcomes for the subgroup of patients who received aftercare appointments within the institutional system. Fifty-five percent of psychiatric emergency service visits resulted in discharge, with psychotropic drug prescriptions given to about 30% of this group. Prescriptions most often included antidepressants (64%), benzodiazepines (25%), nonbenzodiazepine sedatives (20%), anti-psychotics (18%), and mood stabilizers (10%). After controlling for potential confounders, the decision to prescribe was significantly associated with a clinical diagnosis of major depressive disorder or bipolar disorder and the preexisting use of psychotropic medications. Nonprescribing occurred most often in discharged patients who had suicidal ideation, substance abuse or dependence, and an existing outpatient psychiatrist. Follow-up emergency service and new outpatient appointments were more often given to patients discharged with a prescription, but follow-through with aftercare was not more likely in this group. Psychiatrists in an emergency service prescribe antidepressants or other major psychotropics for about one third of discharged patients, rarely in the presence of suicidality or substance abuse or dependence, and with little evidence that initiating such medications in the emergency setting promotes more successful bridging to outpatient treatment.


Epidemiology and management of painful procedures in children in Canadian hospitals.
Children being cared for in hospital undergo multiple painful procedures daily. However, little is known about the frequency of these procedures and associated interventions to manage the pain. We undertook this study to determine, for children in Canadian hospitals, the frequency of painful procedures, the types of pain management interventions associated with painful procedures and the influence of the type of hospital unit on procedural pain management. We reviewed medical charts for infants and children up to 18 years of age who had been admitted to 32 inpatient units at eight Canadian pediatric hospitals between October 2007 and April 2008. We recorded all of the painful procedures performed and the pain management interventions that had been implemented in the 24-hour period preceding data collection. We performed descriptive and comparative (analysis of variance, χ(2)) analyses. Of the 3822 children included in the study, 2987 (78.2%) had undergone at least one painful procedure in the 24-hour period preceding data collection, for a total of 18 929 painful procedures (mean 6.3 per child who had any painful procedure). For 2334 (78.1%) of the 2987 children who had a painful procedure, a pain management intervention in the previous 24 hours was documented in the chart: 1980 (84.8%) had a pharmacologic intervention, 609 (26.1%) a physical intervention, 584 (25.0%) a psychologic intervention and 753 (32.3%) a combination of interventions. However, for only 844 (28.3%) of the 2987 children was one or more pain management interventions administered and documented specifically for a painful procedure. Pediatric intensive care units reported the highest proportion of painful procedures and analgesics administered. For less than one-third of painful procedures was there documentation of one or more specific pain management interventions. Strategies for implementing changes in pain management must be tailored to the type of hospital unit.


[The biochemical characteristics of the sperm in patients with varicocele].
Biochemical evaluation of ejaculates from males suffering from varicocele provided evidence on reduced fertility of their gametes mainly due to these cells hypoactivity consequent to insufficient generation of energy supplied during fructose oxidation. Lowered intensity of fructose oxidation in gamete mitochondria led to lactate accumulation in line with ultrastructural derangement of the flagellum and mitochondria with inhibition of dehydrogenases activity. Morphological abnormalities of the gametes are attributed to impaired gametogenesis in reproductive system of men with varicocele.


Rubella immunization. Persistence of antibody four years after a large-scale field trial.
A long-term comparative field trial of three live, attenuated rubella vaccines (HPV-77 DE-5, HPV-77 DK-12, and Cendehill) was initiated in 1969 on the islands of Kauai and Hawaii in the state of Hawaii. Rubella hemagglutination-inhibition (HI) tests on prevaccination serum specimens from 7,931 children in the two study areas indicated an overall susceptibility to rubella of nearly 70%. The rates of seroconversion of 5,153 seronegative subjects to HPV-77 DE-5, HPV-77 DK-12, and Cendehill vaccine were 97.5%, 99.9%, and 99.8%, respectively. Over the subsequent four-year follow-up period, during which time natural exposure to rubella was minimal, the percent decline of geometric mean titers did not vary substantially among the three vaccine groups and measured about twofold for all three. A total of only 28 vaccines (0.7%) who seroconverted to one of the vaccines in 1969 lost all measurable antibody by 1974. Measurable antibody persisted in more than 98% of all vaccinees over the four-year period. Reinfection, thought possibly to be an important factor in maintaining titers, did not occur frequently in the study population and could not be related to outbreaks of disease.


Hemorrhagic cholecystitis and hemobilia: two infrequent complications of systemic lupus erythematosus.
the patients affected by systemic lupus erythematosus (SLE) often suffer gastrointestinal symptoms. The differential diagnosis should contemplate pathology of the gall bladder. We present the case of a patient with hemorrhagic lithiasic cholecystitis and hemobilia. 24 year old female diagnosed with SLE under treatment with Sintrom®, Dacortin® and Dolquine® that presented acute lithiasic cholecystitis and hemobilia with a distal calculus. Cholecystectomy and aperture of the ductus choledochus were performed allowing to confirm the hemobilia and to extract the calculus. The treatment of cholecystitis in the patients with SLE is controversial due to the fact that most reviewed cases have been solved with cholecystectomy, or in other cases with conservative treatment with corticosteroids. We believe that the presence of cholelithiasis in a patient with SLE with pain on the right hypochondrium and ultrasound confirming the suspicion of cholecystitis demands a surgical treatment since the cause may be vascular, lithiasic or combined. Besides, the possible complications will not respond to pharmaceutical treatment.


Comparing COVID-19 and influenza: Epidemiology, clinical characteristics, outcomes and mortality in the ICU.
Several authors have compared COVID-19 infection with influenza in the ICU. This study aimed to compare the baseline clinical profiles, care procedures, and mortality outcomes of patients admitted to the intensive care unit, categorized by infection status (Influenza vs. COVID-19). Retrospective observational study. Data were extracted from the Toulouse University Hospital from March 2014 to March 2021. To compare survival curves, we plotted the survival at Day-90 using the Kaplan-Meier curve and conducted a log-rank test. Additionally, we performed propensity score matching to adjust for confounding factors between the COVID-19 and influenza groups. Furthermore, we use the CART model for multivariate analysis. The study included 363 patients admitted to the ICU due to severe viral pneumonia: 152 patients (41.9 %) with influenza and 211 patients (58.1 %) with COVID-19. COVID-19 patients exhibited a higher prevalence of cardiovascular risk factors, whereas influenza patients had significantly higher severity scores (SOFA: 10 [6-12] vs. 6 [3-9], p<0.01 and SAPS II: 51 [35-67] vs. 37 [29-50], p<0.001). Overall mortality rates were comparable between the two groups (27.6 % (n = 42) in the influenza group vs. 21.8 % (n = 46) in the COVID-19 group, p=NS). Mechanical ventilation was more commonly employed in the influenza group (76.3 % (n = 116) vs. 59.7 % (n = 126), p<0.001); however, COVID-19 patients required longer durations of mechanical ventilation (18 [9-29] days vs. 13 [5-24] days, p<0.006) and longer hospital stays (23 [13-34] days vs. 18.5 [9-34.5] days, p = 0.009). The CART analysis revealed that the use of extra renal replacement therapy was the most influential prognostic factor in the influenza group, while the PaO2/FiO2-PEEP ratio played a significant role in the COVID-19 group. Despite differences in clinical presentation and prognostic factors, the mortality rates at 90 days, after adjusting for confounding factors, were similar between COVID-19 and influenza patients.


Compensatory collateral circles in vertebral and carotid artery occlusion.
The obstructive disease of the supraaortic trunks has considerable clinical importance. Patients with the same grade of obstruction can display a wide spectrum of symptoms. Apart from the grade, etiology and localization of the obstruction, the presence of collateral circles plays an essential role in the determination of the symptoms. We selected all asymptomatic patients, undergoing a diagnostic investigation with EchoColorDoppler in a period of 13 years, in whom an occlusion of the common carotid artery, of the internal carotid artery or of the vertebral artery was present, and we studied the compensatory collateral circles. We considered 8 subjects affected by common carotid occlusion, 66 subjects with internal carotid occlusion and 24 subjects with vertebral artery occlusion. In the 8 subjects affected by common carotid occlusion, before the bifurcation, the collateral circle was realized by the superior thyroid arteries through the supraisthmic thyroid artery. All of the 66 subjects with internal carotid disease showed collateral circles through the ophthalmic branches and through the communicating arteries. In the 24 subjects with vertebral artery occlusion, the compensatory collateral circle was realized by the cervical, costocervical and occipital branches. In conclusion, the presence of an adequate hemodynamic compensation through a collateral circle represents an important positive prognostic factor and can avoid invasive procedures, thus avoiding possible complications.


A beta-naphthaleneimide-modified terthiophene exhibiting charge transfer and polarization through the short molecular axis. Joint spectroscopic and theoretical study.
We present a new terthiophene derivative substituted at the thienyl beta positions with a naphthalenediimide functionalization. The UV-vis absorption and emission spectroscopic properties as well as the electrochemical properties have been discussed to describe its electronic structure. The vibrational Raman data are used to inspect the molecular architecture. All of the experimental data are supported by quantum chemical calculations with different approaches. A close comparison with other terthiophenes available in the literature is conducted, always stressing the effect of the relative orientation of the donor and acceptor groups either with long-axis or short-axis polarizations. The electronic structure of the molecule has been understood in terms of the HOMO-LUMO absolute energy values. A considerable reduction of the band gap from the constituting units to the studied molecule is detected, although electronic interaction is not optimal for this configuration. Fluorescence quenching is interpreted by the possibility of intersystem crossing and internal conversion. Finally, Raman spectroscopy gives additional information of the distribution of conjugation along the molecular domain, of subtle conformational effects, and of the intermolecular interaction by means of temperature-dependent Raman data. This study provides guidelines for controlling the electronic structure and for exploring new strategies pursuing improved dyes.


Terpenoid biosynthesis and the stereochemistry of enzyme-catalysed allylic addition-elimination reactions.
Allylic addition-elimination reactions are widely used in the enzyme-catalysed formation of terpenoid metabolites. It has earlier been shown that the isoprenoid chain elongation reaction catalysed by farnesyl pyrophosphate synthase involving successive condensations of dimethylallyl pyrophosphate (DMAPP) and geranyl pyrophosphate (GPP) with isopentenyl pyrophosphate (IPP) corresponds to such an SE' reaction with net syn stereochemistry for the sequential electrophilic addition and proton elimination steps. Studies of the enzymic cyclization of farnesyl pyrophosphate (FPP) to pentalenene have now established the stereochemical course of two additional biological SE' reactions. Incubation of both (9R)- and (9S)-[9-3H,4,8-14]FPP with pentalenene synthase and analysis of the resulting labelled pentalenene has revealed that H-9re of FPP becomes H-8 of pentalenene, while H-9si undergoes net intramolecular transfer to the adjacent carbon, becoming H-1re (H-1 alpha) of pentalenene, as confirmed by subsequent experiments with [10-2H, 11-13C]FPP. These results correspond to net anti-stereochemistry in the intramolecular allylic addition-elimination reaction. The stereochemical course of a second SE' reaction has now been examined by analogous incubations of (4S,8S)-[4,8-3H,4,8-14C]FPP and (4R,8R)-[4,8-3H, 4.8-14C]FPP with pentalenene synthase. Determination of the distribution of label in the derived pentalenenes showed stereospecific loss of the original H-8si proton. Analysis of the plausible conformation of the presumed reaction intermediates revealed that the stereochemical course of the latter reaction cannot properly be described as either syn or anti, since cyclization and subsequent double bond formation require significant internal motions to allow proper overlap of the scissile C-H bond with the developing carbocation.


Cleavage at met-x bonds by cyanogen bromide.
INTRODUCTIONSelective cleavage of a protein by cyanogen bromide generates a small number of relatively large peptide fragments. This protocol describes protein cleavage with cyanogen bromide, using ~100-fold molar excess of cyanogen bromide over the methionine. The reaction is performed under mild acidic conditions (e.g., 70% formic acid), under nitrogen, and in the dark. All reagents are volatile and can be readily removed by lyophilization.


DNA damage induces p53-dependent BRCA1 nuclear export.
The tumor suppressor gene BRCA1 plays an important role in the response to DNA damage. BRCA1 function is regulated by a variety of mechanisms including transcriptional control, phosphorylation, and protein-protein interactions. Recent studies have shown that BRCA1 is a nuclear-cytoplasmic shuttle protein. Its subcellular localization is controlled by a nuclear localization signal-mediated nuclear import via the importin receptor pathway and a nuclear export signal-facilitated nuclear export through a CRM1-dependent pathway. Using the human breast cancer cell line, MCF7, the subcellular distribution of BRCA1 was assessed by immunohistochemical staining and Western blotting analyses of fractionated subcellullar extracts. Ionizing radiation stimulated BRCA1 nuclear export in a dose-dependent manner. This DNA damage-induced BRCA1 nuclear export utilized a CRM1-dependent mechanism and also required wild-type p53, whose function was abrogated by the E6 protein in MCF7 cells. In addition, the dependence on p53 was confirmed using a second cell type operating a tetracycline-inducible system. The effect of ionizing radiation on BRCA1 export was observed in every phase of the cell cycle, although BRCA1 localization did vary between the G(1), S, and G(2)/M phases. These results imply that, in addition to ATM-, ATR-, and Chk2-dependent phosphorylations, cytoplasmic relocalization of BRCA1 protein is a mechanism whereby BRCA1 function is regulated in response to DNA damage.


Efficacy of Hybrid Tetrahydrobenzo[d]thiazole Based Aryl Piperazines D-264 and D-301 at D₂ and D₃ Receptors.
In elucidating the role of pharmacodynamic efficacy at D3 receptors in therapeutic effectiveness of dopamine receptor agonists, the influence of study system must be understood. Here two compounds with D3 over D2 selectivity developed in our earlier work, D-264 and D-301, are compared in dopamine receptor-mediated G-protein activation in striatal regions of wild-type and D2 receptor knockout mice and in CHO cells expressing D2 or D3 receptors. In caudate-putamen of D2 knockout mice, D-301 was ~3-fold more efficacious than D-264 in activating G-proteins as assessed by [(35)S]GTPγS binding; in nucleus accumbens, D-301 stimulated G-protein activation whereas D-264 did not. In contrast, the two ligands exerted similar efficacy in both regions of wild-type mice, suggesting both ligands activate D2 receptors with similar efficacy. In D2 and D3 receptor-expressing CHO cells, D-264 and D-301 appeared to act in the [(35)S]GTPγS assay as full agonists because they produced maximal stimulation equal to dopamine. Competition for [(3)H]spiperone binding was then performed to determine Ki/EC50 ratios as an index of receptor reserve for each ligand. Action of D-301, but not D-264, showed receptor reserve in D3 but not in D2 receptor-expressing cells, whereas dopamine showed receptor reserve in both cell lines. Gαo1 is highly expressed in brain and is important in D2-like receptor-G protein coupling. Transfection of Gαo1 in D3- but not D2-expressing CHO cells led to receptor reserve for D-264 without altering receptor expression levels. D-301 and dopamine exhibited receptor reserve in D3-expressing cells both with and without transfection of Gαo1. Altogether, these results indicate that D-301 has greater intrinsic efficacy to activate D3 receptors than D-264, whereas the two compounds act on D2 receptors with similar intrinsic efficacy. These findings also suggest caution in interpreting Emax values from functional assays in receptor-transfected cell models without accounting for receptor reserve.


Tissue engineering solutions for tendon repair.
Tendon injuries range from acute traumatic ruptures and lacerations to chronic overuse injuries, such as tendinosis. Even with improved nonsurgical, surgical, and rehabilitation techniques, outcomes following tendon repair are inconsistent. Primary repair remains the standard of care. However, repaired tendon tissue rarely achieves functionality equal to that of the preinjured state. Poor results have been linked to alterations in cellular organization within the tendon that occur at the time of injury and throughout the early stages of healing. Enhanced understanding of the biology of tendon healing is needed to improve management and outcomes. The use of growth factors and mesenchymal stem cells and the development of biocompatible scaffolds could result in enhanced tendon healing and regeneration. Recent advances in tendon bioengineering may lead to improved management following tendon injury.


Effect of alpha-phenyl-N-tert-butyl nitrone (PBN) on fetal cerebral energy metabolism during intrauterine ischemia and reperfusion in rats.
The objective of the present study was to explore whether a free radical spin trap agent, alpha-phenyl-N-tert-butyl nitrone (PBN), influences bioenergetic failure induced in the 20-day-old fetal brain by 30 min of intrauterine ischemia in Wistar rats. Fetal brains were frozen in situ at the end of ischemia and after 1, 2, and 4 h of recirculation for analysis of ATP, ADP, AMP, and lactate. PBN or vehicle was given 1 h after recirculation. Tissue oxygen tension was evaluated in placental and fetal cerebral tissues throughout the whole periods of 30 min of ischemia and 4 h of recirculation. Ischemia was associated with a decrease in ATP concentration and an increase in lactate concentration (p < 0.001). Recirculation (1 and 2 h) led to a recovery of ATP concentration, but continued reflow (4 h) was associated with a secondary deterioration of high-energy phosphates (p < 0.01). Lactate concentration increased during this recovery period. This deterioration was prevented by PBN (p < 0.05). After 30 min of ischemia, tissue oxygen tension in placenta and fetal brain decreased to about 30% and 50% of control, respectively. However, recirculation brought about a recovery of oxygen delivery. The results indicate that although during the early time period after ischemia fetal cerebral energy metabolism is maintained by an acceleration of the anaerobic glycolytic rate, secondary deterioration of cellular bioenergetic state develops in the immature fetal brain. This deterioration may be due to mitochondrial dysfunction, which may be induced by oxygen-derived free radicals, and not by compromised microcirculation.


Sexual size dimorphism in the evolutionary context of facultative paedomorphosis: insights from European newts.
Sexual size dimorphism (SSD) is a key evolutionary feature that has been studied in many organisms. In a wide range of species, this pattern is more complex because of polymorphism within each sex. However, it is not known whether the magnitude and direction of SSD could be affected by alternative developmental trajectories within sexes. Our aim was to test whether an intrasexual polymorphism, facultative paedomorphosis (a process in which the development of somatic and gonadal tissues differs in alternative morphs), could affect SSD variation patterns in European newts. We report here the first evidence that SSD varies depending on the paedomorphic or metamorphic ontogenetic pathway. In species with a consistent female-biased SSD, paedomorphosis decreased the SSD level, but did not affect its direction. In species with moderate female-biased SSD or variable SSD patterns, paedomorphosis changed the magnitude, or both the magnitude and the direction, of SSD. Our study highlights the importance of developmental processes for shaping SSD patterns in populations in which contrasting life-history pathways evolved. European newts express different SSD patterns depending on their developmental pathway (i.e., metamorphosis versus paedomorphosis), as well as their species and population. These findings emphasize the importance of studying alternative morphotypes, which are found in a wide range of animal groups, to understand the evolution of SSD.


Pre-Transplant Screening for Latent Adenovirus in Donors and Recipients.
Human adenoviruses are frequent cause of slight self-limiting infections in immune competent subjects, while causing life-threatening and disseminated diseases in immunocompromised patients, particularly in the subjects affected by acquired immunodeficiency syndrome and in bone marrow and organ transplant recipients. Here, infections interest lungs, liver, encephalon, heart, kidney and gastro enteric tract. To date, human adenoviruses comprise 51 serotypes grouped into seven species, among which species C especially possesses the capability to persist in infected tissues. From numerous works, it emerges that in the recipient, because of loss of immune-competence, both primary infection, via the graft or from the environment, and reactivated endogenous viruses can be responsible for transplantation related adenovirus disease. The transplants management should include the evaluation of anti-adenovirus pre-transplant screening similar to that concerning cytomegalovirus. The serological screening on cytomegalovirus immunity is currently performed to prevent viral reactivation from grafts and recipient, the viral spread and dissemination to different organs and apparatus, and potentially lethal outcome.


Transcriptional impact of dietary methionine restriction on systemic inflammation: relevance to biomarkers of metabolic disease during aging.
Calorie restriction (CR) without malnutrition increases lifespan and produces significant improvements in biomarkers of metabolic health. The improvements are attributable in part to effects of CR on energy balance, which limit fat accumulation by restricting energy intake. Normal age-associated increases in adiposity and insulin resistance are associated with development of a systemic proinflammatory state, while chronic CR limits fat deposition and expression of inflammatory markers. Dietary methionine restriction (MR) has emerged as an effective CR mimetic because it produces a comparable extension in lifespan. MR also reduces adiposity through a compensatory increase in energy expenditure that effectively limits fat accumulation, but essentially nothing is known about the effects of MR on systemic inflammation. Here, we review the relationships between these two interventions and discuss their transcriptional impact. In addition, using tissues from rats after long-term consumption of CR or MR diets, transcriptional profiling was used to examine retrospectively the systems biology of 59 networks of molecules annotated to inflammation. Transcriptional effects of both diets occurred primarily in white adipose tissue and liver, and the responses to MR were far more robust than those to CR. The primary transcriptional targets of MR in both liver and white adipose tissue were phagocytes and macrophages, where expression of genes associated with immune cell infiltration and quantity was reduced. These findings support the conclusion that anti-inflammatory responses produced by CR and MR are not strictly dependent upon reduced adiposity but are significantly influenced by the metabolic mechanisms through which energy balance is altered.


tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans.
Transmembrane channel-like (TMC) genes encode a broadly conserved family of multipass integral membrane proteins in animals. Human TMC1 and TMC2 genes are linked to human deafness and required for hair-cell mechanotransduction; however, the molecular functions of these and other TMC proteins have not been determined. Here we show that the Caenorhabditis elegans tmc-1 gene encodes a sodium sensor that functions specifically in salt taste chemosensation. tmc-1 is expressed in the ASH polymodal avoidance neurons, where it is required for salt-evoked neuronal activity and behavioural avoidance of high concentrations of NaCl. However, tmc-1 has no effect on responses to other stimuli sensed by the ASH neurons including high osmolarity and chemical repellents, indicating a specific role in salt sensation. When expressed in mammalian cell culture, C. elegans TMC-1 generates a predominantly cationic conductance activated by high extracellular sodium but not by other cations or uncharged small molecules. Thus, TMC-1 is both necessary for salt sensation in vivo and sufficient to generate a sodium-sensitive channel in vitro, identifying it as a probable ionotropic sensory receptor.


Training of manual actions improves language understanding of semantically related action sentences.
Conceptual knowledge accessed by language may involve the reactivation of the associated primary sensory-motor processes. Whether these embodied representations are indeed constitutive to conceptual knowledge is hotly debated, particularly since direct evidence that sensory-motor expertise can improve conceptual processing is scarce. In this study, we sought for this crucial piece of evidence, by training naive healthy subjects to perform complex manual actions and by measuring, before and after training, their performance in a semantic language task. Nineteen participants engaged in 3 weeks of motor training. Each participant was trained in three complex manual actions (e.g., origami). Before and after the training period, each subject underwent a series of manual dexterity tests and a semantic language task. The latter consisted of a sentence-picture semantic congruency judgment task, with 6 target congruent sentence-picture pairs (semantically related to the trained manual actions), 6 non-target congruent pairs (semantically unrelated), and 12 filler incongruent pairs. Manual action training induced a significant improvement in all manual dexterity tests, demonstrating the successful acquisition of sensory-motor expertise. In the semantic language task, the reaction times (RTs) to both target and non-target congruent sentence-picture pairs decreased after action training, indicating a more efficient conceptual-semantic processing. Noteworthy, the RTs for target pairs decreased more than those for non-target pairs, as indicated by the 2 × 2 interaction. These results were confirmed when controlling for the potential bias of increased frequency of use of target lexical items during manual training. The results of the present study suggest that sensory-motor expertise gained by training of specific manual actions can lead to an improvement of cognitive-linguistic skills related to the specific conceptual-semantic domain associated to the trained actions.


Assessment of different screw augmentation techniques and screw designs in osteoporotic spines.
This is an experimental study on human cadaver spines. The objective of this study is to compare the pullout forces between three screw augmentation methods and two different screw designs. Surgical interventions of patients with osteoporosis increase following the epidemiological development. Biomechanically the pedicle provides the strongest screw fixation in healthy bone, whereas in osteoporosis all areas of the vertebra are affected by the disease. This explains the high screw failure rates in those patients. Therefore PMMA augmentation of screws is often mandatory. This study involved investigation of the pullout forces of augmented transpedicular screws in five human lumbar spines (L1-L4). Each spine was treated with four different methods: non-augmented unperforated (solid) screw, perforated screw with vertebroplasty augmentation, solid screw with vertebroplasty augmentation and solid screw with balloon kyphoplasty augmentation. Screws were augmented with Polymethylmethacrylate (PMMA). The pullout forces were measured for each treatment with an Instron testing device. The bone mineral density was measured for each vertebra with Micro-CT. The statistical analysis was performed with a two-sided independent student t test. Forty screws (10 per group and level) were inserted. The vertebroplasty-augmented screws showed a significant higher pullout force (mean 918.5 N, P = 0.001) than control (mean 51 N), the balloon kyphoplasty group did not improve the pullout force significantly (mean 781 N, P > 0.05). However, leakage occurred in some cases treated with perforated screws. All spines showed osteoporosis on Micro-CT. Vertebroplasty-augmented screws, augmentation of perforated screws and balloon kyphoplasty augmented screws show higher pullout resistance than non-augmented screws. Significant higher pullout forces were only reached in the vertebroplasty augmented vertebra. The perforated screw design led to epidural leakage due to the position of the perforation in the screw. The position of the most proximal perforation is critical, depending on screw design and proper insertion depth. Nevertheless, using a properly designed perforated screw will facilitate augmentation and instrumentation in osteoporotic spines.


Transcriptomic analysis at organ and time scale reveals gene regulatory networks controlling the sulfate starvation response of Solanum lycopersicum.
Sulfur is a major component of biological molecules and thus an essential element for plants. Deficiency of sulfate, the main source of sulfur in soils, negatively influences plant growth and crop yield. The effect of sulfate deficiency on plants has been well characterized at the physiological, transcriptomic and metabolomic levels in Arabidopsis thaliana and a limited number of crop plants. However, we still lack a thorough understanding of the molecular mechanisms and regulatory networks underlying sulfate deficiency in most plants. In this work we analyzed the impact of sulfate starvation on the transcriptome of tomato plants to identify regulatory networks and key transcriptional regulators at a temporal and organ scale. Sulfate starvation reduces the growth of roots and leaves which is accompanied by major changes in the organ transcriptome, with the response being temporally earlier in roots than leaves. Comparative analysis showed that a major part of the Arabidopsis and tomato transcriptomic response to sulfate starvation is conserved between these plants and allowed for the identification of processes specifically regulated in tomato at the transcript level, including the control of internal phosphate levels. Integrative gene network analysis uncovered key transcription factors controlling the temporal expression of genes involved in sulfate assimilation, as well as cell cycle, cell division and photosynthesis during sulfate starvation in tomato roots and leaves. Interestingly, one of these transcription factors presents a high identity with SULFUR LIMITATION1, a central component of the sulfate starvation response in Arabidopsis. Together, our results provide the first comprehensive catalog of sulfate-responsive genes in tomato, as well as novel regulatory targets for future functional analyses in tomato and other crops.


Sustained store-operated calcium entry utilizing activated chromatin state leads to instability in iTregs.
Thymus-originated tTregs and in vitro induced iTregs are subsets of regulatory T cells. While they share the capacity of immune suppression, their stabilities are different, with iTregs losing their phenotype upon stimulation or under inflammatory milieu. Epigenetic differences, particularly methylation state of Foxp3 CNS2 region, provide an explanation for this shift. Whether additional regulations, including cellular signaling, could directly lead phenotypical instability requires further analysis. Here, we show that upon TCR (T cell receptor) triggering, SOCE (store-operated calcium entry) and NFAT (nuclear factor of activated T cells) nuclear translocation are blunted in tTregs, yet fully operational in iTregs, similar to Tconvs. On the other hand, tTregs show minimal changes in their chromatin accessibility upon activation, in contrast to iTregs that demonstrate an activated chromatin state with highly accessible T cell activation and inflammation related genes. Assisted by several cofactors, NFAT driven by strong SOCE signaling in iTregs preferentially binds to primed-opened T helper (TH) genes, resulting in their activation normally observed only in Tconv activation, ultimately leads to instability. Conversely, suppression of SOCE in iTregs can partially rescue their phenotype. Thus, our study adds two new layers, cellular signaling and chromatin accessibility, of understanding in Treg stability, and may provide a path for better clinical applications of Treg cell therapy.


Aggressive behavior of the white-eye mutant crickets, Gryllus bimaculatus.
Aggressive behavior of white-eye mutant crickets was investigated and compared with that of wild-type crickets. In the dark, wild-type pairs performed long-lasting fights with significantly higher aggressive levels compared to those in the light. In contrast, fights between two white-eye mutants were not significantly different with those between two wild-type crickets both in duration and the aggressive levels. Ethograms of aggressive behavior showed that the mutants could show typical sequentially escalating fight with the same behavioral categories as the wild-type crickets. These results indicate that the white-eye mutants are able to express normal aggressive behavior.


ZIP kinase triggers apoptosis from nuclear PML oncogenic domains.
PML oncogenic domains (PODs), also referred to as nuclear dot 10 bodies, Kreb's bodies, or nuclear bodies, represent nuclear structures implicated in the regulation of a variety of cellular processes, including transcription, tumor suppression, and apoptosis. ZIP kinase (ZIPK) is a proapoptotic protein kinase with homology to DAP kinase, a protein kinase implicated in apoptosis. We show here that ZIPK is present in PODs, where it colocalizes with and binds to proapoptotic protein Daxx. Arsenic trioxide (As(2)O(3)) and gamma interferon (IFN-gamma), which accentuate POD formation, increased the association of ZIPK with PODs. In contrast, the kinase-inactive ZIPK resides in nuclei with a diffuse pattern and significantly prevents the association of Daxx with PODs, implying that ZIPK recruits Daxx to PODs via its catalytic activity. ZIPK also binds and phosphorylates proapoptotic protein Par-4. Association of ZIPK with Daxx was enhanced by coexpression of Par-4. Activation of caspases and induction of apoptosis were also observed in cells overexpressing these proteins. Conversely, small-interfering RNA-mediated reduction of ZIPK, Daxx, or Par-4 expression decreased activation of caspase and apoptosis induced by As(2)O(3) and IFN-gamma. These results suggest that ZIPK, in collaboration with Daxx and Par-4, mediates a novel nuclear pathway for apoptosis.


The role of driving factors in historical and projected carbon dynamics of upland ecosystems in Alaska.
It is important to understand how upland ecosystems of Alaska, which are estimated to occupy 84% of the state (i.e., 1,237,774 km2 ), are influencing and will influence state-wide carbon (C) dynamics in the face of ongoing climate change. We coupled fire disturbance and biogeochemical models to assess the relative effects of changing atmospheric carbon dioxide (CO2 ), climate, logging and fire regimes on the historical and future C balance of upland ecosystems for the four main Landscape Conservation Cooperatives (LCCs) of Alaska. At the end of the historical period (1950-2009) of our analysis, we estimate that upland ecosystems of Alaska store ~50 Pg C (with ~90% of the C in soils), and gained 3.26 Tg C/yr. Three of the LCCs had gains in total ecosystem C storage, while the Northwest Boreal LCC lost C (-6.01 Tg C/yr) because of increases in fire activity. Carbon exports from logging affected only the North Pacific LCC and represented less than 1% of the state's net primary production (NPP). The analysis for the future time period (2010-2099) consisted of six simulations driven by climate outputs from two climate models for three emission scenarios. Across the climate scenarios, total ecosystem C storage increased between 19.5 and 66.3 Tg C/yr, which represents 3.4% to 11.7% increase in Alaska upland's storage. We conducted additional simulations to attribute these responses to environmental changes. This analysis showed that atmospheric CO2 fertilization was the main driver of ecosystem C balance. By comparing future simulations with constant and with increasing atmospheric CO2 , we estimated that the sensitivity of NPP was 4.8% per 100 ppmv, but NPP becomes less sensitive to CO2 increase throughout the 21st century. Overall, our analyses suggest that the decreasing CO2 sensitivity of NPP and the increasing sensitivity of heterotrophic respiration to air temperature, in addition to the increase in C loss from wildfires weakens the C sink from upland ecosystems of Alaska and will ultimately lead to a source of CO2 to the atmosphere beyond 2100. Therefore, we conclude that the increasing regional C sink we estimate for the 21st century will most likely be transitional.


Old and new antiarrhythmic drugs for converting and maintaining sinus rhythm in atrial fibrillation: comparative efficacy and results of trials.
In managing atrial fibrillation (AF), the main therapeutic strategies include rate control, termination of the arrhythmia, and the prevention of recurrences and thromboembolic events. Safety and efficacy considerations are important in optimizing the choice of an antiarrhythmic drug for the treatment of AF. Recently approved antiarrhythmics, such as dofetilide, and promising investigational drugs, such as azimilide and dronedarone, may change the treatment landscape for AF. For medical conversion of recent-onset AF, class IC antiarrhythmic drugs, administered as an oral bolus, have been demonstrated to be the most efficacious pharmacologic conversion agents. Intravenous ibutilide and oral dofetilide both have efficacies superior to placebo in controlled trials for converting persistent AF. Comparative trials in paroxysmal AF have demonstrated that flecainide, propafenone, quinidine, and sotalol are equally effective in preventing recurrences of AF. Amiodarone has been demonstrated to be more efficacious than propafenone or sotalol in the Canadian Trial of Atrial Fibrillation. In persistent AF, twice-daily dofetilide has been shown to be as or more effective than low-dose sotalol given twice daily for the maintenance of sinus rhythm in patients with AF. Trials have demonstrated that subjective adverse effects are less frequent with class IC drugs, sotalol, and dofetilide compared with such drugs as quinidine. In patients without structural heart disease, flecainide, propafenone, and D,L-sotalol are the initial drugs of choice, given their reasonable efficacy, low incidence of subjective side effects, and lack of significant end-organ toxicity. Treating AF in patients with left ventricular dysfunction can be difficult because of associated electrophysiologic derangements, potential proarrhythmic concerns, and negative inotropic effects of antiarrhythmics. Some data exist suggesting that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can prevent AF either by preventing atrial dilation and stretch-induced arrhythmias or by blocking the renin-angiotensin system. In post-myocardial infarction patients, D,L-sotalol, dofetilide, and amiodarone-and in congestive heart failure patients, amiodarone and dofetilide-have demonstrated neutral effects on survival in controlled trials. In the Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy (CHF-STAT), amiodarone lowered the frequency of AF development and improved left ventricular ejection fraction over time. In CHF-STAT, there was lower mortality in patients who converted from AF to sinus rhythm. Dofetilide decreased rehospitalization for congestive heart failure in the Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) trials. Neutral effects on survival and favorable hemodynamics have positioned amiodarone and dofetilide as the antiarrhythmics of choice in patients with left ventricular dysfunction. In post-myocardial infarction patients, sotalol is an additional agent to consider for treatment of AF in this setting.


Diagnostic and prognostic role of HBME-1, galectin-3, and β-catenin in poorly differentiated and anaplastic thyroid carcinomas.
Thyroid cancer represents the first endocrine malignant neoplasm, accounting for 1% of human malignancy. The majority of which are well-differentiated cancer representing up to 90% of thyroid cancer and pursuing a favorable clinical course. The groups of poorly differentiated thyroid cancer (PDC) and anaplastic thyroid cancer (ATC) have a poor outcome and need a strict clinical surveillance. Thirty-four cases including 23 PDC/insular cancer and 9 ATC were examined for the expression of an immunohistochemical panel made up by HBME-1, galectin-3, and β-catenin and correlated either with histologic prognostic parameters or the overall surveillance. HBME-1 and galectin-3 were expressed in 100% of the PDC/insular cases and in none of the ATC cases. The data for β-catenin pointed out an 80% expression (12/15) in the PDCs and only a focal and nonspecific positivity in the ATCs. A β-catenin-positive expression was found in all patients with a worse outcome/death and in the presence of vascular invasion and metastatic disease. All 3 PDC patients with β-catenin negativity are alive, whereas only 41% (5/12) are alive in the β-catenin-positive group. Our data set up the idea that PDC represents an intermediate step in the biological process of dedifferentiation of thyroid tumors toward ATC. This shift is underlined by the β-catenin expression, which seems to be related to a worse prognostic behavior. HBME-1 and galectin-3 show a similar pattern in PDC compared with well-differentiated carcinoma, whereas they are not expressed, as well as β-catenin, in anaplastic carcinomas.


Investigation of possible age effects on meiotic chromosomal recombination and segregation in Armenian hamster spermatocytes.
Male Armenian hamsters were evaluated for age effects upon meiotic recombination and aneuploidy incidence. Primary spermatocytes from young and old animals revealed similar chiasma frequencies. The incidence of terminal-type chiasmata in sex bivalents was also measured and found to be unaffected by age. Percentages of univalents and of hyperploid metaphase II cells were evaluated by chromosome groups based upon individual chromosome morphologies. Regardless of age, the larger dichiasmate chromosomes were seldom observed as univalents, or as extra chromosomes in hyperploid cells. The monochiasmate small autosomes and sex chromosomes revealed univalent frequencies approximating to 5.5-6.5% in animals from both age groups. However, only the small autosomes appeared to be significantly implicated in hyperploidy. Although still a rare event, metaphase II hyperploidy was significantly increased in older animals (0.9% incidence in young and 2.4% in old hamsters). The events leading to higher aneuploidy levels in older male Armenian hamsters are not clear. A role for reduced meiotic recombination as a function of age cannot be ruled out in the present study. However, there was no support for this hypothesis, and consideration of other possible mechanisms of age effects to increase aneuploidy levels is indicated.


[Dosimetry of short-ranged radionuclides].
More and more targeted radiotherapies (TRT) are carried out with pure beta-emitters such as 90Y. Normally fixed activities are administered without considering the individual biokinetics increasing the risk of under- or overdosing. In addition, it would be helpful to obtain additional data on dose-response relationships for further optimization of TRTs. Therefore, post-therapeutic dosimetry using quantitative imaging becomes more important. For an optimization of TRTs additional aspects such as the changing dose rate and radiobiological considerations need to be taken into account. This paper provides an overview on bremsstrahlung imaging modalities after therapies with pure beta-emitters. In addition, new dosimetric methods are described which consider dose rate and fractionation of treatment.


Bone marrow cytological findings in 4 dogs and a cat with hemophagocytic syndrome.
Hemophagocytic syndrome or hemophagic histiocytosis was diagnosed in 4 dogs and 1 cat by evaluation of bone marrow aspirate smears. One of the dogs had a suspected infection with canine parvovirus and a confirmed infection with Salmonella spp, 2 dogs had presumptive diagnoses of myeloproliferative and lymphoproliferative disease, respectively, and 1 dog died without a diagnosis. The cat had hepatic lipidosis and lesions compatible with feline calicivirus infection. All animals had cytopenias involving 2 or more cell lines, and fragmented erythrocytes in the blood, along with mild to moderate increases in the number of macrophages in the bone marrow. Numerous marrow macrophages contained phagocytized hematopoietic cells. Other cytological features of the bone marrow were variable in each patient, but the degree of response in the blood was inadequate, even in those with bone marrow hyperplasia. The phagocytosis of hematopoietic elements did not appear to be caused by a primary immune disorder, but rather by the inappropriate activation of normal macrophages secondary to infectious, neoplastic, or metabolic diseases. These findings suggest that hemophagocytic syndrome may be an important factor in the development of cytopenias; the data also support the cytological evaluation of bone marrow aspirates as an aid in the diagnosis of hemophagocytic syndrome.


Monitoring the influence of toxic compounds on microbial denitrifying biofilm processes.
Microelectrode measurements were conducted to obtain nitrate, pH and redox potential profiles within anoxic denitrifying biofilms. The influence of a toxic organic compound (acid orange 7) on biofilm microprofiles was also monitored using microelectrodes. The data provide evidence that the denitrifying biofilms were stratified into an anoxic layer and an anaerobic layer. The anaerobic zone might provide a niche for the biodegradation of recalcitrant organic compounds in biofilms. It was found that acid orange 7 and its biodegradation byproducts had only a slight impact on biofilm nitrate, pH and redox potential profiles.


Adrenal myelolipoma, cholelithiasis and calcified spleen: retrospective diagnosis of sickle cell anemia using a novel triad of abdominal imaging findings.
Sickle cell anemia is an inherited abnormality of the globin chain with very high prevalence in the Indian subcontinent. A significant proportion of these patients present late in life and are at a risk of complications like acute chest syndrome and painful episodes till a definitive diagnosis is reached and appropriate treatment is started . We report a novel triad of abdominal imaging findings which is not reported in literature until now and which may suggest a diagnosis of sickle cell anemia in retrospect. Patients with this triad of abdominal findings should be suspected to have an underlying hemoglobinopathy and should be referred for further hematological workup. Although in our case the patient was diagnosed to have sickle cell anemia depending on the abnormal morphology of red cells and hemoglobin electrophoresis, it should be remembered that this triad of findings may be seen in other hemoglobinopathies which induce a state of chronic anemia.


[Effect of ethanol on structural and functional characteristics of rat brain cortical membranes in vitro].
When finding the mechanism of the in vitro ethanol membrane action it was established that alcohol in moderate concentrations enhanced the inactivation of the rat brain cortex Na+, K(+)-ATPase after modification of the microsomal fraction by phospholipase A2 from cobra venom. It is supposed that ethanol sensitivity is determined by the structural state of the functional protein-lipid enzyme complexes in membrane. The decrease of the intrinsic tryptophan fluorescence of the membrane proteins and fluorescence of the probe 1-anilinonaphthalene-8-sulfonate (both without and under membrane surface charge shielding) in the presence of ethanol was revealed. It is concluded, that conformational changes of the membrane polar surface area coincide with the enzyme inactivation by ethanol.


Effect of operating and sampling conditions on the exhaust gas composition of small-scale power generators.
Small stationary diesel engines, like in generator sets, have limited emission control measures and are therefore responsible for 44% of the particulate matter (PM) emissions in the United States. The diesel exhaust composition depends on operating conditions of the combustion engine. Furthermore, the measurements are influenced by the used sampling method. This study examines the effect of engine loading and exhaust gas dilution on the composition of small-scale power generators. These generators are used in different operating conditions than road-transport vehicles, resulting in different emission characteristics. Experimental data were obtained for gaseous volatile organic compounds (VOC) and PM mass concentration, elemental composition and nitrate content. The exhaust composition depends on load condition because of its effect on fuel consumption, engine wear and combustion temperature. Higher load conditions result in lower PM concentration and sharper edged particles with larger aerodynamic diameters. A positive correlation with load condition was found for K, Ca, Sr, Mn, Cu, Zn and Pb adsorbed on PM, elements that originate from lubricating oil or engine corrosion. The nitrate concentration decreases at higher load conditions, due to enhanced nitrate dissociation to gaseous NO at higher engine temperatures. Dilution on the other hand decreases PM and nitrate concentration and increases gaseous VOC and adsorbed metal content. In conclusion, these data show that operating and sampling conditions have a major effect on the exhaust gas composition of small-scale diesel generators. Therefore, care must be taken when designing new experiments or comparing literature results.


Hodgkin's disease: successful dissemination of high technology treatment throughout the United States.
In the 1950s and 1960s, concepts of the curability of Hodgkin's disease were changing due to a better understanding of the natural history of the disease and major technical innovations for evaluating the extent of disease and treating it with radiation therapy. The Patterns of Care Study in the United States of national practice and of selected referral centres has been analysed to determine the extent of the adoption or dissemination of our concepts of best current management into the United States practice as a whole. A favourable overall level of compliance has been noted, while the National Cancer Institute-funded Cancer Centers and Radiation Therapy Oncology Group (RTOG) facilities show the best process compliance. University facilities, large practices and full-time practitioners consistently outperform their counterparts in community practices, small practices and part-time practices. Despite these generalizations, we have observed poorly performing facilities in all strata of practice that require that the quality be assessed on an individual facility basis.


Meprin A impairs epithelial barrier function, enhances monocyte migration, and cleaves the tight junction protein occludin.
Meprin metalloproteases are highly expressed at the luminal interface of the intestine and kidney and in certain leukocytes. Meprins cleave a variety of substrates in vitro, including extracellular matrix proteins, adherens junction proteins, and cytokines, and have been implicated in a number of inflammatory diseases. The linkage between results in vitro and pathogenesis, however, has not been elucidated. The present study aimed to determine whether meprins are determinative factors in disrupting the barrier function of the epithelium. Active meprin A or meprin B applied to Madin-Darby canine kidney (MDCK) cell monolayers increased permeability to fluorescein isothiocyanate-dextran and disrupted immunostaining of the tight junction protein occludin but not claudin-4. Meprin A, but not meprin B, cleaved occludin in MDCK monolayers. Experiments with recombinant occludin demonstrated that meprin A cleaves the protein between Gly(100) and Ser(101) on the first extracellular loop. In vivo experiments demonstrated that meprin A infused into the mouse bladder increased the epithelium permeability to sodium fluorescein. Furthermore, monocytes from meprin knockout mice on a C57BL/6 background were less able to migrate through an MDCK monolayer than monocytes from their wild-type counterparts. These results demonstrate the capability of meprin A to disrupt epithelial barriers and implicate occludin as one of the important targets of meprin A that may modulate inflammation.


My various thoughts on actin.
An enormous amount of research has been performed to characterize actin dynamics. Structural biology investigations have determined the localization of main chains and their changes coupled with G (Globular)-F (Filamentous) transformation of actin, whereas local thermal fluctuations that may be caused by free rotations of the tips of side chains are not yet fully investigated. This paper argues if the entropy change of actin accompanied by the G-F transformation is simply attributable to the changes in hydration. It took almost 10 years to understand that the actin filament is semi-flexible. This flexibility was visually confirmed as the development of optical microscope techniques, and the direct observation of actin severing events in the presence of actin binding proteins became possible. Finally, I expect the deep understanding of actin dynamics will lead to the elucidation of self-assembly mechanisms of the living creature.


Depression: some proposals for future research.
The argument has been advanced that pathological states of anxiety and mania are both characterized by a failure on the part of the patient to attach appropriate levels of significance to changes occurring in the immediate environment. There is, it is suggested, a tendency for environmental features to be regarded as important even though, viewed objectively, they may have little relevance to the patient and his needs. Depression, it is further proposed, may be viewed as an extreme defense reaction to the intense anxiety which results from attaching too much significance to environmental events. In depressive state, patients are often characterised by their lowered responsiveness to stimulation and their lack of interest in, or concern about, their surroundings: it may be that, in such state, information processing has been blocked or reduced. The daytime drowsiness of the depressed patients, as well as his night-time sleep disturbance and the frequently observed recurrent or cyclic nature of certain kinds of depressed state, suggest that this blocking of sensory processing may be brought about by the involuntary intervention of mechanisms responsible, under normal circumstances, for sleep induction. This view of the nature of depression has been recast into the form of five potentially testable hypotheses. Speculation is always easy; providing convincing demonstrations that those speculations are reasonable is less easy. It is in the nature of psychological investigation that laboratory-based studies distort and may even destroy the phenomena about which information is sought, and many a perfectly reasonable theory has foundered upon the rocks of translation into experimental terms. In those areas of psychology which have implications for psychiatry and the conceptualisation of psychopathological states, this danger is particularly evident: psychiatric syndromes are complex, variable, and have social referrents, but laboratory experiments are limited in their capacity to reflect all these attributes, and consequently they may never provide really adequate tests of a theory about a psychiatric state. We have to try to come to terms with this apparent impasse--in the first place by being circumspect in translating psychiatric concepts into experimental terms, and secondly by exercising caution in interpreting the results to which the experiments give rise. More importantly, however, we have to accept the essential inadequacy of the majority of experimental paradigms in psychiatric research and to regard theorizing--even when it is not linked to explicitly testable hypotheses--as having inherent value.


The isolation of wheat germ nuclei and some aspects of their glycolytic metabolism.
1. A procedure for isolating nuclei of the wheat germ in non-aqueous media has been described. 2. Such nuclei were shown to constitute about 50 per cent of the protoplasmic mass and to have a ribonucleic acid content of an order equivalent to that of the cytoplasm. 3. Studies of the distribution of the enzymes-aldolase, phosphoglyceraldehyde dehydrogenase, enolase, and pyruvate kinase-have revealed that the nuclei are the most vigorous sites of glycolytic activity. 4. Analysis of the DPN content of the nuclei in calf tissues-liver, pancreas, and heart-pointed to the probability that glycolytic activity is a characteristic common to many nuclei. 5. The significance of glycolytic activity to nuclear function has been discussed and some suggestive comparisons made between the two energy-yielding systems of glycolytic and oxidative phosphorylation.


The DNA damage response--repair or despair?
The term "the DNA damage response" (DDR) encompasses a sophisticated array of cellular initiatives set in motion as cells are exposed to DNA-damaging events. It has been known for over half a century that all organisms have the ability to restore genomic integrity through DNA repair. More recent discoveries of signal transduction pathways linking DNA damage to cell cycle arrest and apoptosis have greatly expanded our views of how cells and tissues limit mutagenesis and tumorigenesis. DNA repair not only plays a pivotal role in suppressing mutagenesis but also in the reversal of signals inducing the stress response. If repair is faulty or the cell is overwhelmed by damage, chances are that the cell will despair and be removed by apoptosis. This final fate is determined by intricate cellular dosimeters that are yet to be fully understood. Here, key findings leading to our current view of DDR are discussed as well as potential areas of importance for future studies.


Semen washing procedures do not eliminate human papilloma virus sperm infection in infertile patients.
To determine the effectiveness of three sperm washing protocols for removing human papillomavirus (HPV)-infected cells from semen samples of infertile patients. Cross-sectional clinical study. Andrology and microbiology sections at a university hospital. A group of 32 infertile patients positive for semen HPV, detected with polymerase chain reaction (PCR) and in-situ hybridization in sperm and exfoliated cells. Semen analysis and in-situ hybridization for HPV detection were performed before and after sperm washing, discontinuous Ficoll gradients, and swim-up protocols. Statistical analysis was performed with a two-tailed Student's t-test. Evaluation of sperm parameters and presence of HPV, performed in semen samples before and after procedures of sperm selection. All native samples showed the presence of infected sperm with a mean percentage of positivity (24.7% ± 8.9%) higher than exfoliated cells (13.8% ± 4.3%). Fifteen samples had HPV DNA on sperm and exfoliated cells. Sperm washing centrifugation showed no changes in the number of infected samples and in the percentage of infected cells. Ficoll and swim-up protocols induced a slight reduction in the number of infected samples (30 and 26, respectively). This study demonstrated that conventional sperm selection rarely eliminates HPV sperm infection. More attention should be paid to the reproductive health of infected patients because, not only can HPV be transmitted, but it may also have a negative effect on development of the fetus.


Ginger reserves testicular spermatogenesis and steroidogenesis in difenoconazole-intoxicated rats by conducting oxidative stress, apoptosis and proliferation.
Difenoconazole, a triazole fungicide, can induce reproductive toxicity in aquatic species, but the probable mechanisms of this hazard in mammals are not formally reported. Here, we have examined the possible ameliorative efficiency of the ginger aqueous extract against the reproductive toxicity of difenoconazole in male rats. Thirty-six animals were equally divided into six groups: control, ginger aqueous extract (50 mg/kg), difenoconazole (15 mg/kg), difenoconazole (30 mg/kg) and ginger co-treated with two doses of difenoconazole. Difenoconazole markedly decreased sperm count, motility and normality percentage, together with the Johnson score. Difenoconazole also significantly reduced serum testosterone, luteinizing hormone and follicle-stimulating hormone levels, as well as the activities of testicular steroidogenic acute regulatory protein and 17 β-hydroxysteroid dehydrogenases. Furthermore, difenoconazole brought a significant decrease in the testicular activity of catalase, but it increased the activity of glutathione peroxidase. Moreover, difenoconazole upregulated the testicular transcripts of Bax and caspase-3, increased Ki-67 immunoreactivity and induced histoarchitecture alterations plus DNA damage. Remarkably, ginger co-treatment preserved sperm toxicity, restored hormone profiles, increased steroidogenic activity and prevented oxidative injury-promoted testicular apoptosis. In conclusion, phenolic acids and flavonoids of ginger can reserve spermatogenesis and steroidogenesis in difenoconazole-intoxicated rats by improving testicular redox status, inhibiting apoptosis and refining proliferation capacity.


Why Ecosystem Management Can't Work Without Social Science: An Example from the California Northern Spotted Owl Controversy
It is increasingly obvious that social science, while not a sufficient condition for making ecosystem management effective, is a necessary condition. A social science typology of ecosystems is developed, applied, and shown to have substantial and unexpected implications for the practice of ecosystem management. Ecologists and environmental scientists, in particular, will find some conclusions uncomfortable. The application involves a case material from the California northern spotted owl controversy.KEY WORDS: Ecosystem management; Social science; Adaptive management; Top-down versus bottom-up planning; Outside-in versus inside-out planning


Identification of NDUFAF1 in mediating K-Ras induced mitochondrial dysfunction by a proteomic screening approach.
Increase in aerobic glycolysis and mitochondrial dysfunction are important biochemical features observed in human cancers. Recent studies suggest oncogenic K-Ras can cause suppression of mitochondrial respiration and up-regulation of glycolytic activity through a yet unknown mechanism. Here we employed proteomic approach and used a K-RasG12V inducible cell system to investigate the impact of oncogenic K-Ras on mitochondria and cell metabolism. Mitochondria isolated from cells before and after K-Ras induction were subjected to protein analysis using stable isotope labeling with amino acids (SILAC) and liquid chromatography coupled with mass spectrometry (LC-MS). 70 mitochondrial proteins with significant expression alteration after K-Ras induction were identified. A majority of these proteins were involved in energy metabolism. Five proteins with significant decrease belong to mitochondrial respiratory chain complex I. NADH dehydrogenase 1 alpha subcomplex assembly factor 1 (NDUFAF1) showed most significant decrease by 50%. Such decrease was validated in primary human pancreatic cancer tissues. Knockdown of NDUFAF1 by siRNA caused mitochondrial respiration deficiency, accumulation of NADH and subsequent increase of glycolytic activity. Our study revealed that oncogenic K-Ras is able to induce significant alterations in mitochondrial protein expression, and identified NDUFAF1 as an important molecule whose low expression contributes to mitochondrial dysfunction induced by K-Ras.


Iron Acquisition of Urinary Tract Infection Escherichia coli Involves Pathogenicity in Caenorhabditis elegans.
Uropathogenic Escherichia coli (UPEC) is a major bacterial pathogen that causes urinary tract infections (UTIs). The mouse is an available UTI model for studying the pathogenicity; however, Caenorhabditis elegans represents as an alternative surrogate host with the capacity for high-throughput analysis. Then, we established a simple assay for a UPEC infection model with C. elegans for large-scale screening. A total of 133 clinically isolated E. coli strains, which included UTI-associated and fecal isolates, were applied to demonstrate the simple pathogenicity assay. From the screening, several virulence factors (VFs) involved with iron acquisition (chuA, fyuA, and irp2) were significantly associated with high pathogenicity. We then evaluated whether the VFs in UPEC were involved in the pathogenicity. Mutants of E. coli UTI89 with defective iron acquisition systems were applied to a solid killing assay with C. elegans. As a result, the survival rate of C. elegans fed with the mutants significantly increased compared to when fed with the parent strain. The results demonstrated, the simple assay with C. elegans was useful as a UPEC infectious model. To our knowledge, this is the first report of the involvement of iron acquisition in the pathogenicity of UPEC in a C. elegans model.


X-ray Diffraction to 302 Gigapascals: High-Pressure Crystal Structure of Cesium Iodide.
X-ray diffraction measurements have been carried out on cesium iodide (CsI) to 302 gigapascals with a platinum pressure standard. The results indicate that above 200 gigapascals CsI at 300 K has a hexagonal close-packed crystal structure with the ideal c/a ratio of 1.63 +/- 0.01. The crystal structure and pressure-volume relations converge at high pressure with those of solid xenon, which is isoelectronic with CsI. The results indicate a significant loss of ionic bonding in the hexagonal close-packed metallic phase of CsI at ultrahigh pressure.


Exercise in therapy and prevention of type II diabetes. Implications for blacks.
The rationale for the use of exercise in the treatment of type II (non-insulin-dependent) diabetes and its special implications for Blacks are reviewed herein. When performed on a regular basis, exercise may improve glycemic control and improve several risk factors for coronary heart disease including hypertriglyceridemia, hypertension, and hyperinsulinemia. In addition, it may be a useful adjunct to diet in producing weight loss. The metabolic benefits of exercise in part appear to be related to its ability to enhance insulin sensitivity. Benefits are short lived after discontinuing exercise. Because of problems with compliance and concurrent medical problems, many patients with type II diabetes are not good candidates for an exercise-diet program. For this reason, the optimum target population may be people at risk for type II diabetes and premature atherosclerosis. Such a population might include the offspring of patients with these disorders and individuals with impaired glucose tolerance, hyperinsulinemia, gestational diabetes, and/or an android pattern of fat distribution. Type II diabetes is more common in Blacks than in the general population. In most instances, it is associated with cardiovascular risk factors benefited by exercise. Despite this, there are no available studies regarding the effects of regular exercise in Blacks with type II diabetes or those at risk for it.


The role of postoperative patient posture in the recurrence of traumatic chronic subdural hematoma after burr-hole surgery.
Chronic subdural hematoma (CSDH) is one of the most common types of intracranial hemorrhage, especially in the elderly, with a significant recurrence rate ranging from 9.2 to 26.5%. The role of postoperative patient posture in the recurrence of CSDH has not been studied sufficiently. A total of 84 consecutive patients with unilateral traumatic CSDH without known risk factors of CSDH recurrence were prospectively enrolled in this study. All patients underwent burr-hole surgery with closed system drainage and were then allocated randomly to either of two groups: Group A (n = 42) patients were kept in a supine position for 3 days after the operation, whereas Group B (n = 42) patients assumed a sitting position in bed, with the head of the bed elevated to 30 to 40 degrees, for the same duration as Group A. After 3 days, there was no restriction in patients' activities in both groups. All patients were followed-up for at least 3 months after surgery. The groups were not significantly different in age, sex, presence of brain atrophy or hydrocephalus, preoperative hematoma width, and postsurgery subdural space width. The recurrence rate in Groups A and B were 2.3 and 19.0% (necessitating repeat surgery in one patient), respectively (P = 0.02). Other complications in Groups A and B, respectively, were atelectasis (10 versus seven; P = 0.41), pneumonia (five versus four; P = 0.72), decubitus ulcer (three versus two; P = 0.64), and deep vein thrombosis (zero versus one; P = 0.31). Assuming an upright posture soon after burr-hole surgery was associated with a significantly increased incidence of CSDH recurrence but not with a significant change in other position-related postsurgical complications. According to this result, it is not recommended that elderly patients assume an upright posture soon after burr-hole surgery to prevent postoperative atelectasis and dementia, as these might significantly increase the risk of CSDH recurrence.


Complications and device failures associated with urolift: Findings from the MAUDE database.
Urolift is an established intervention for symptoms of bladder outflow obstruction caused by benign prostate enlargement. Reported advantages include its minimally invasive profile, short learning curve and feasibility as a day case procedure. Our aim was to use a national registry as a means to evaluate the nature of complications and device failures that have been documented to occur. Retrospective review was performed of the US Manufacturer and User Facility Device Experience (MAUDE) database, a prospective register, which contains voluntarily submitted adverse events associated with surgical devices. Information collected include event timing, underlying cause, procedural completion, complications and mortality status. Between 2016 and 2023, 103 device failures, 5 intra-operative complications and 165 post-operative complications (early: 151, late: 14) were registered. The commonest device problem (56%, n = 58) was failure of the implant to deploy with subsequent requirement for complete replacement. There were 50 cases of documented urosepsis. 62 patients with post operative haematuria were registered including 12 that underwent emergency embolisation. Other complications included stroke (n = 5), pulmonary embolism (n = 3) and necrotising fasciitis (n = 1). Twelve ITU admissions were registered. In the reports, 22 cases were filed that recorded a hospital stay of 7 days or more. Eleven deaths were captured in the database over the study period. While urolift is recognised as less invasive intervention compared to alternatives such as transurethral resection of the prostate, serious adverse events have been reported to occur including death. Our findings can provide learning points for surgeons and allow for improved patient counselling and treatment planning accordingly.


Detection of iron-labeled single cells by MR imaging based on intermolecular double quantum coherences at 14 T.
To evaluate the efficiency and feasibility of intermolecular multiple quantum coherence (iMQC) magnetic resonance (MR) imaging for single cell detection, we obtained intermolecular double quantum coherence (iDQC) and conventional gradient echo (GE) images of macrophage cells labeled by contrast agents in gel. The iDQC images obtained with echo-planar readout visualized the labeled cells effectively and with a higher contrast than seen in conventional GE images, especially at low planar resolutions and with thick slices. This implies that iDQC imaging with contrast agents could be a good alternative to conventional MR imaging for detecting labeled single cells or cell tracking under favorable conditions.


Changes in the mode of travel to work and the severity of depressive symptoms: a longitudinal analysis of UK Biobank.
Although commuting provides an opportunity for incorporating physical activity into daily routines, little is known about the effect of active commuting upon depressive symptoms. This study aimed to determine whether changes in commute mode are associated with differences in the severity of depressive symptoms in working adults. Commuters were selected from the UK Biobank cohort if they completed ≥2 assessment centre visits between 2006 and 2016. Modes of travel to work were self-reported at each visit. Participants were categorised as 'inactive' (car only) or 'active' commuters (any other mode(s), including walking, cycling and public transport). Transitions between categories were defined between pairs of visits. The severity of depressive symptoms was defined using the two-item Patient Health Questionnaire (PHQ-2). Scores were derived between zero and six. Higher values indicate more severe symptoms. Separate analyses were conducted in commuters who were asymptomatic (zero score) and symptomatic (non-zero score) at baseline. The analytical sample comprised 5474 participants aged 40-75 at baseline with a mean follow-up of 4.65 years. Asymptomatic commuters who transitioned from inactive to active commuting reported less severe symptoms at follow-up than those who remained inactive (β -0.10, 95% CI [-0.20, 0.00]; N = 3145). A similar but non-significant relationship is evident among commuters with pre-existing symptoms (β -0.60, 95% CI [-1.27, 0.08]; N = 1078). After adjusting for transition category, longer commutes at baseline were associated with worse depressive symptoms at follow-up among symptomatic participants. Shifting from exclusive car use towards more active commuting may help prevent and attenuate depressive symptoms in working adults.