Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in Canada during 2000.
A total of 2,245 clinical isolates of Streptococcus pneumoniae were collected from 63 microbiology laboratories from across Canada during 2000 and characterized at a central laboratory. Of these isolates, 12.4% were not susceptible to penicillin (penicillin MIC, >or=0.12 microg/ml) and 5.8% were resistant (MIC, >or=2 microg/ml). Resistance rates among non-beta-lactam agents were the following: macrolides, 11.1%; clindamycin, 5.7%; chloramphenicol, 2.2%; levofloxacin, 0.9%; gatifloxacin, 0.8%; moxifloxacin, 0.4%; and trimethoprim-sulfamethoxazole, 11.3%. The MICs at which 90% of the isolates were inhibited (MIC90s) of the fluoroquinolones were the following: gemifloxacin, 0.03 microg/ml; BMS-284756, 0.06 microg/ml; moxifloxacin, 0.12 microg/ml; gatifloxacin, 0.25 microg/ml; levofloxacin, 1 microg/ml; and ciprofloxacin, 1 microg/ml. Of 578 isolates from the lower respiratory tract, 21 (3.6%) were inhibited at ciprofloxacin MICs of >or=4 microg/ml. None of the 768 isolates from children were inhibited at ciprofloxacin MICs of >or=4 microg/ml, compared to 3 of 731 (0.6%) from those ages 15 to 64 (all of these >60 years old), and 27 of 707 (3.8%) from those over 65. The MIC90s for ABT-773 and telithromycin were 0.015 microg/ml for macrolide-susceptible isolates and 0.12 and 0.5 microg/ml, respectively, for macrolide-resistant isolates. The MIC of linezolid was <or=2 microg/ml for all isolates. Many of the new antimicrobial agents tested in this study appear to have potential for the treatment of multidrug-resistant strains of pneumococci.


Multivariable control of the bifurcation and harmonic perturbations to improve the performance of air-handling units.
In this research, nonlinear dynamics of an air-ehandling unit (AHU) is studied for tracking objectives, in the presence of harmonic perturbations. Three arbitrary realistic set-paths are considered for the indoor temperature and relative humidity. Two controllers based on feedback linearization (FBL) and pole placement approaches are designed to preserve the dynamic system around the desired tracking paths. It is shown that FBL controller works efficiently in bifurcation control and transforms the quasi-periodic limit cycles into the periodic ones (and consequently comfortable indoor conditions). In addition, FBL controller guarantees suppression of larger periodic limit cycles into the smaller ones, while it requires the lower air and cold water flow rates with less oscillatory behavior (in comparison with the pole-placement controller). However, it is observed that FBL controller fails in bifurcation control when the disturbance frequency increases. Re-tuning the dynamic gains of FBL controller is essential under such conditions.


A liposomal hydrogel for the prevention of bacterial adhesion to catheters.
The adhesion of bacteria to medical implants and the subsequent development of a biofilm frequently results in the infection of surrounding tissue and may require removal of the device. We have developed a liposomal hydrogel system that significantly reduces bacterial adhesion to silicone catheter material. The system consists of a poly (ethylene glycol)-gelatin hydrogel in which liposomes containing the antibiotic ciprofloxacin are sequestered. A poly (ethylene glycol)-gelatin-liposome mixture was applied to a silicone surface that had been pre-treated with phenylazido-modified gelatin. Hydrogel cross-linking and attachment to surface-immobilized gelatin was accomplished through the formation of urethane bonds between gelatin and nitrophenyl carbonate-activated poly (ethylene glycol). Liposomal hydrogel-coated catheters were shown to have an initial ciprofloxacin content of 185+/-16 microg cm(-2). Ciprofloxacin was released over seven days with an average release rate of 1.9+/-0.2 microg cm(-2) h(-1) for the first 94 h. In vitro assays using a clinical isolate of Pseudomonas aeruginosa established the antimicrobial efficacy of the liposomal hydrogel. A modified Kirby-Bauer assay produced growth-inhibition zone diameters of 39+/-1 mm, while bacterial adhesion was completely inhibited on catheter surfaces throughout a seven-day in vitro adhesion assay. This new antimicrobial coating shows promise as a prophylactic and/or treatment for catheter-related infection.


[Intracardiac myxoma complicated by acute aortic occlusion (case report)].
We report the case for a 44-year-old patient without medical history, admitted in our department for bilateral acute limb ischemia (H6). The patient was hemodynamically stable and the physical examination shows limb sever ischemia (no femoral arterial pulses, coldness, cyanosis and paralysis). Abdominal CT angiography showed a complete occlusion of the infra renal abdominal aorta compatible with embolus. An embolectomy with Fogarty catheters was performed. Echocardiography showed a mass in the left atrium. Pathological examination of the material embolic confirmed the diagnosis of the cardiac myxoma. The clinical course was marked by the development of a sever syndrome of revascularization, death occurred the third day of hospitalization. Cardiac myxomas are the most common primary cardiac tumor. The mobility of the tumor and its gelatinous and crumbly consistency generates peripheral emboli.


Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma.
In response to IFN-gamma, the latent cytoplasmic protein signal transducers and activators of transcription 1 (Stat1) becomes phosphorylated on Y701, dimerizes, and accumulates in the nucleus to activate transcription of IFN-gamma-responsive genes. For maximal gene activation, S727 in the transcription activation domain of Stat1 also is inducibly phosphorylated by IFN-gamma. We previously purified a group of nuclear proteins that interact specifically with the Stat1 transcription activation domain. In this report, we identified one of them as the multifunctional Ca(2+)/calmodulin-dependent kinase (CaMK) II. We demonstrate that IFN-gamma mobilizes a Ca(2+) flux in cells and activates CaMKII. CaMKII can interact directly with Stat1 and phosphorylate Stat1 on S727 in vitro. Inhibition of Ca(2+) flux or CaMKII results in a lack of S727 phosphorylation and Stat1-dependent gene activation, suggesting in vivo phosphorylation of Stat1 S727 by CaMKII. Thus two different cellular signaling events, IFN-gamma receptor occupation and Ca(2+) flux, are required for Stat1 to achieve maximal transcriptional activation through regulation of phosphorylation.


Parkinsonism in the presence of intracranial extracerebral haematomas.
Bilateral Parkinsonism has been observed in a 60-year-old female with a chronic subdural intracranial haematoma. Scattered, poorly marginated, hypodense areas within the ipsilateral pallidus and putamen were evident on the preoperative CT scans. The rapid neurological improvement following the surgical drainage of the subdural clot and the evolution of the densitometric features of the nuclear lesions, which became clear-cut, though smaller, in the following months, suggest a cause-and-effect relation between the haematoma and the clinical symptomatology. To the best of our knowledge this is the first case in which anatomical lesions within the basal ganglia could be detected neuroradiologically.


Foot and Ankle Injuries in Professional Soccer Players: Diagnosis, Treatment, and Expectations.
Soccer is one of the most popular sports in the world. It has undergone many changes in recent years, mainly because of increased physical demands, and this has led to an increased injury risk. Direct contact accounts for half of all injuries in both indoor and outdoor soccer and ankle sprains are the most common foot and ankle injury. There is a spectrum of foot and ankle injuries and their treatment should be individualized in these high-demand patients. An injury prevention program is also important and should the players, the trainer, responsible physician, and physical therapists.


Molecular and biological properties of an abrin A chain immunotoxin designed for therapy of human small cell lung cancer.
An immunotoxin (IT) comprising abrin A chain attached to the mouse monoclonal antibody SWA11, recognising a cell surface antigen highly associated with human small cell lung cancer (SCLC), was synthesised using a hindered disulphide crosslinker, N-succinimidyl 3-(2-pyridyldithio) butyrate (SPDB), and purified by Blue Sepharose CL-6B affinity chromatography. The IT preparation contained monomeric conjugate, composed of one abrin A chain molecule linked to one SWA11 molecule, and was free from unconjugated A chain or antibody. The IT fully retained the cell-binding capacity of the antibody component and the ribosome-inactivating activity of the A chain. In cytotoxicity assays using the SW2 SCLC cell line in tissue culture, SWA11-SPDB-abrin A chain inhibited the incorporation of 3H-leucine by 50% at a concentration of 10 pM and by 99% at a concentration of 1 nM. The anti-tumour efficacy of the IT was tested in nude mice bearing established s.c. solid SW2 tumour xenografts. A single i.v. injection of SWA11-SPDB-abrin A chain at a non-toxic dose induced a significant 7 to 10 day growth delay that could not be matched by administration of equivalent doses of either unconjugated SWA11 or abrin A chain alone. The results of this study indicate that the antigen recognised by SWA11 is an effective target for therapy of SCLC with A chain ITs in vivo.


Modulation of the anti-Candida activity of apo-lactoferrin by dietary sucrose and tunicamycin in vitro.
The sensitivity to apo-lactoferrin (apo-LF) of two oral isolates each of Candida albicans and C. krusei preincubated in either sucrose- or tunicamycin-supplemented media was investigated. Known apo-LF-sensitive isolates of both C. albicans and C. krusei demonstrated significantly increased resistance to apo-LF when preincubated in sucrose-supplemented media, but such preincubation had no effect on an apo-LF-resistant isolate of C. albicans, irrespective of the sugar concentration in the medium. Surprisingly, an apo-LF-resistant isolate of C. krusei demonstrated increased susceptibility to apo-LF when preincubated in sucrose. Further, when preincubated with tunicamycin, a chemical that interferes with candidal cell-wall formation, the susceptibility to apo-LF of the resistant isolates increased significantly. These results, when extrapolated in vivo, imply that dietary sucrose may diminish the anticandidal potency of salivary lactoferrin. However, the aberrant behaviour of a single isolate of C. krusei under these circumstances is possibly due to the different cell-wall structure of this yeast and needs to be further investigated.


Renal allograft rupture: surgical treatment by renal corsetage with lyophilized human dura.
We report 5 cases of renal allograft rupture in which diagnosis was established early through clinical data, laboratory tests and echography. Immediate surgery confirmed the suspicion in all cases. Acute rejection was present in 4 patients and in 1 the previous surgical puncture from the perirenal collection demonstrated serohematic fluid with a biological character similar to that of lymph. This latter case seemed to confirm the suspicion that any process associated with edema in a kidney with obstructed lymphatic tracts (meticulous lymphatic ligatures during donor extraction) is capable of causing a rupture. Conventional surgical treatment is dangerous and insecure on an edematous and friable kidney, resulting in a nephrectomy rate of 55.7 per cent and a postoperative death rate of 8 per cent. Hematoma evacuation, hemostasis by local compression and tridimensional containment of the ruptured areas should be the principles of this operation. By means of renal corsetage with lyophilized human dura these principles can be achieved. This surgical technique, which is simple and secure, its variations and future possibilities are described. In 3 of our 5 patients corsetage with lyophilized human dura was applied. All 5 grafts have taken. Renal function is good in 3 cases and acceptable in 2 at followup between 2 and 15 months.


Microarray transfection analysis of conserved genomic sequences from three immediate early genes.
In an effort to define novel transcriptional regulatory elements, microarray cotransfection was used to functionally characterize conserved non-coding sequences (CNSs) of three immediate early genes: c-fos, JunB and EGR-1. Cotransfection of fluorescent CNS reporter constructs and expression vectors for constitutively active signaling proteins demonstrated that many of the CNSs alter both the basal and regulated expressions of reporter constructs, but the effects of these CNSs were usually specific for their homologous promoter. One CNS located in the first intron of the c-fos gene conferred regulation by cAMP-dependent protein kinase (PKA), cGMP-dependent protein kinase (PKG) and Raf. Mutagenesis and cotransfection experiments showed that PKA regulation of this c-fos intronic element was mediated by two adjacent CRE-like sequences and the transcription factor CREB. In the context of a reporter containing previously characterized regulatory elements, the novel intronic sequence contributed 50% of the transcriptional response to PKA. These studies suggest that microarray transfection studies may be useful in functional characterization of conserved genomic sequences on a larger scale.


Reaction of O6-alkylguanine-DNA alkyltransferase with O6-methylguanine analogues: evidence that the oxygen of O6-methylguanine is protonated by the protein to effect methyl transfer.
The DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) repairs the promutagenic O6-methylguanine lesion by transferring the methyl group to a cysteine residue on the protein. A mechanism in which AGT activates the guanyl moiety as a leaving group by protonation of a heteroatom on guanine was probed by reacting AGT with analogues of O6-methylguanine in which the heteroatoms were changed. The initial rates of reaction were measured at various substrate concentrations in 50 mM Hepes, 1 mM EDTA, 1 mM DTT, and 10% glycerol, pH 7.8 at 37 degrees C. The kinact (h-1) and Kin (mM) were determined for O6-methylguanine (1.66 +/- 0.19, 1.51 +/- 0.32), 6-methoxypurine (1.07 +/- 0.25, 10.6 +/- 4.2), S6-methyl-6-thioguanine (0.63 +/- 0.04, 1.17 +/- 0.18), 6-methylthiopurine (no reaction), Se6-methyl-6-selenoguanine (1.76 +/- 0.28, 10.6 +/- 5.0), 6-methylselenopurine (2.51 +/- 0.62, 15.7 +/- 6.3), O6-methyl-1-deazaguanine (1.71 +/- 0.34, 14.8 +/- 4.4), O6-methyl-3-deazaguanine (1.90 +/- 0.24, 2.54 +/- 0.59), and O6-methyl-7-deazaguanine (1.97 +/- 0.26, 2.56 +/- 0.72). These results indicate that replacement of the nitrogens does not affect the kinact parameter but the Kin is increased upon removal of the exocyclic amino group and the nitrogen at the 1-position. Replacement of the oxygen with sulfur decreases the kinact, and replacement with selenium increases the Kin. The results are consistent with a mechanism in which O6-methylguanine binds to the active site of AGT with hydrogen bonds to the oxygen, the exocyclic amino group, and the nitrogen at the 1-position of the substrate.(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of cesarean delivery at Assiut University Hospital using the Ten Group Classification System.
To evaluate the feasibility of using the Robson Ten Group Classification System (TGCS) for cesarean delivery (CD) indications at institutional level. Prospective clinical audits of women delivering by CD at Women's Health Hospital, Assiut, Egypt, were conducted in 2008 and 2011. The CD rates overall and in each Robson group were calculated, as was the contribution of each group to the overall CD rate. In addition, the CD indications in each group were analyzed. The CD rate was 32% (443/1357) in 2008 and 38% (626/1628) in 2011. The most common CD indication at both time intervals was a previous CD. Multiparas without uterine scar, a single cephalic term pregnancy, and spontaneous labor (Robson Group 3) comprised the largest group of women undergoing CD, followed by nulliparas with a single cephalic term pregnancy and spontaneous labor (Group 1), and multiparas with a scarred uterus and a single cephalic term pregnancy (Group 5). Group 5 was the largest contributor (30%) to the overall CD rate, followed by Groups 1 and 4 (10% each). The TGCS can be applied at institutional level. It helps in planning strategies for specific subgroups of women to reduce CD rates and improve outcomes.


[Delirium after a fractured hip in more than one-third of the patients].
Inventarisation and evaluation of the incidence, risk factors, and prognosis of postoperative delirium in patients with a fractured hip admitted to a surgical ward. Descriptive study of patient records. All patients with a fractured hip admitted to the surgical ward of the Jeroen Bosch Hospital, Den Bosch, the Netherlands, in 2004 were included and evaluated. Active multidisciplinary interventions for the recognition and treatment of delirium by non-pharmacological and pharmacological means take place in this surgical ward. The records of all patients from the surgical and geriatric wards were evaluated and the data were analysed statistically by means of univariate and multivariate logistic 'step-forward' regression analysis. 114 patients were included. The incidence of postoperative delirium was 37%. Older age was a significant risk factor for the development of delirium in both the univariate and the multivariate analysis after correcting for overestimation (p < 0.01). Several other factors, including sex, type of surgery, and medical history, had no effect on the risk of delirium. Delirium after a hip fracture is not rare; the most important risk factor is older age.


Liver Explants of Biliary Atresia Patients Transplanted in Adulthood Show Features of Obliterative Portal Venopathy: Case Series and Guidelines for Pathologic Reporting of Adult Explants.
Biliary atresia (BA) patients can have portal vein (PV) abnormalities. To investigate the explant pathology of BA patients transplanted in adulthood with a focus on portal venous abnormalities. Adult BA liver explants were reviewed, along with prior biopsies, Kasai portoenterostomy (KP), and relevant medical records. Three explants were identified; all patients were female, with age at diagnosis, KP, and liver transplantation (LT) as follows: (1) less than 1 week, 8 days, and 25 years; (2) 15 weeks, 16 weeks, and 32 years; and (3) 7 weeks, 8 weeks, and 33 years, respectively, with normalization of conjugated bilirubin within 6 months of KP and development of portal hypertension (PHTN) within 3 years of KP for all 3. The first 2 had recurrent cholangitis. Duration of pre-LT PHTN was 22, 29, and 30 years, and that of pre-LT cholangitis was 9, 3, and 0 years, respectively. All 3 explants showed hilar and extrahepatic fibromyxoid intimal hyperplasia of the PV with parenchymal hepatoportal sclerosis. Cholestasis was limited to those with a history of cholangitis. Patient 3, without cholangitis, showed delicate septal fibrosis with peripheral accentuation without biliary cirrhosis. In the context of a functioning KP, cholestasis and biliary cirrhosis are likely related to recurrent cholangitis, which may or may not occur after KP. In the absence of biliary cirrhosis, PHTN may be secondary to obliterative venopathy. Adult BA explants should be sampled thoroughly, with a focus on hilar/perihilar connective tissue to include PV branches. Explants may not show biliary cirrhosis and should be reported with appropriate clinicopathologic correlation.


Impact of invasive fungal infections in men from a state in southern Brazil: A geospatial analysis.
To analyse the records of male hospitalisation for fungal infections, including their spatial distribution and the main invasive epidemiological and sociodemographic characteristics in the State of Paraná, Brazil. Spatial analysis based on data from male admission records for invasive fungal infections (IFIs) in the State of Paraná, from 2015 to 2019. Data were taken from the hospital records obtained in the Hospital Information System of the Unified Health System, being collected, georeferenced and analysed to infer the existence of autocorrelation with the hospitalisation rates in the state. From 2015 to 2019, there were 385 cases of IFIs in men, being more prevalent in white individuals aged 61-70 years. We observed that the metropolitan, southeast, central-eastern, north-central, northwestern and western regions formed high-high clusters, with regions with a high number of registered cases. In the regression, there was an association with socioeconomic and demographic factors that showed a correlation with the rates of hospitalisation for IFIs. The study draws attention to Paraná as an endemic region for paracoccidioidomycosis, in addition to presenting high rates of nosocomial fungal infections. We also emphasise the importance of compulsory notification in the state and in the country to gain greater control over the incidence and prevalence of cases and to incentivise the creation of public policies for the prevention of IFIs.


Telmisartan treatment decreases visceral fat accumulation and improves serum levels of adiponectin and vascular inflammation markers in Japanese hypertensive patients.
Hypertension contributes to the occurrence and progression of cardiovascular diseases. The angiotensin II type 1 receptor blocker telmisartan is reported to activate the peroxisome proliferator-activated receptor gamma and improve insulin sensitivity. We investigated the effects of telmisartan treatment on visceral fat, serum adiponectin and vascular inflammation markers in Japanese hypertensive patients. This was an open-label, non-controlled study. Twenty-eight essential hypertensive patients (22 men and 6 women; age 60.6+/-1.9 years; body mass index [BMI] 25.5+/-0.6 kg/m(2)) participated. Fat area was assessed with computerized tomography. All the subjects were started on telmisartan 40 mg/day, which was increased to 80 mg/day to achieve the blood pressure target of less than 130/80 mmHg. We assessed the visceral and subcutaneous fat areas, serum adiponectin levels, and vascular inflammation markers at baseline and 24 weeks of telmisartan treatment. There were significant reductions in visceral fat area (from 103.1+/-7.9 to 93.3+/-8.4 cm(2), p<0.01) and pulse wave velocity (from 1,706+/-52 to 1,587+/-51 cm/s, p<0.01) at 24 weeks. In contrast, significant increases in serum high-density lipoprotein cholesterol (from 5.06+/-0.15 to 5.32+/-0.13 mmol/L, p<0.05) and adiponectin levels (from 8.27+/-0.76 to 9.13+/-0.81 microg/mL, p<0.05) were observed. Also, there were reductions in the interleukin-6 level (from 2.26+/-0.27 to 1.60+/-0.14 pg/mL, p<0.01). We also conducted these investigations in male subjects alone and similar findings were obtained for all of these parameters. In conclusion, telmisartan treatment was associated with an improvement of vascular inflammation, reductions in visceral fat and increases in serum adiponectin.


Dry to wet weight biomass conversion constant for Tetrahymena elliotti (Ciliophora, Protozoa).
The wet and dry weights of both axenic and monoxenic cultures of the ciliate Tetrahymena were determined directly. These estimates are dependent upon the method of volume determination. Assuming a prolate spheroidal shape for the ciliate, we calculate a mean wet weight of 0.4157±0.0713 pg μm-3 and a mean dry weight of 0.2793±0.0652 pg μm-3. Using electronic cell sizing, our estimates are 0.7869±0.1659 pg μm-3 and 0.5239±0.1101 pg μm-3, respectively. Independent of the method of volume determination, we estimate a mean biomass conversion ratio (dry weight/wet weight) of 0.59±0.08.


Tourette syndrome: recent advances.
In spite of new information relevant to the clinical and biological features of Tourette syndrome, areas of controversy still exist. A genetic substrate is present in at least some affected families; there also is clearly a genetic relationship between Tourette syndrome and chronic motor tic disorder. Patients with Tourette syndrome have an increased incidence of behavior problems, attention deficit disorder, and obsessive-compulsive symptoms. Treatment of the attention deficit disorder with psychostimulant drugs will exacerbate tics in some patients. Haloperidol remains the most consistently useful therapeutic agent. Pimozide and clonidine also may be useful, but further work is required before standard treatment protocols can be developed. The disorder most likely results from dysfunction of dopaminergic systems.


Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and risk of depression among older people with hypertension.
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), commonly used antihypertensive drugs, may have a protective effect against depression in older individuals, but evidence in humans is limited. We evaluated the risk of depression, among older individuals with hypertension, comparing ACE or ARB initiators to thiazide(-like) diuretic initiators. Thiazide(-like) diuretics were used as control because these drugs are not associated with mood disorders. We used a propensity score-matched new user cohort design with routinely collected data from general practices in England from the Clinical Practice Research Datalink database. We matched 12,938 pairs of new users of ACEIs/ARBs and thiazide(-like) diuretics with hypertension (mean age 67.6 years; 54.7% women). Follow-up time started on the date of drug initiation and ended on the date of treatment discontinuation plus 30 days, or switch to a comparator, occurrence of a study event, death, date of patient's transfer out of practice, or end of the study period. The primary outcome was a composite endpoint of treated depression and nonfatal and fatal self-harm. Compared to the thiazide(-like) diuretic group, ACEIs/ARBs use was not associated with a lower risk of the primary outcome (hazard ratio 0.96 (95% confidence interval: 0.79; 1.15)). Results did not differ according to lipophilicity, duration of use, and average daily dose, or class (ACEIs or ARBs). New use of ACEIs or ARBs is not associated with a lower risk of depression among individuals with hypertension.


Use of In Vitro Kernel Culture to Study Maize Nitrogen and Carbohydrate Metabolism.
Grain yield in maize is the result of a genotype's response to environmental conditions and agronomic management. However, whether in a field, greenhouse, or growth chamber, plant-to-plant variation exists within the same genotype, necessitating large amounts of plants and growth area to determine a metabolic response to a change in growth conditions or fertilizer supply. Additionally, because of whole-plant interactions in the supply of nutrients to kernels, it is difficult to study assimilate or temperature effects on the growth of kernels. The in vitro growth of kernels is one way to circumvent this problem because it allows for kernel growth under defined conditions of nutrient supply, while minimizing environmental and maternal influences. The in vitro kernel culturing method can be used to identify source: sink relationships, assimilate transport, metabolism, plant growth regulators, and other physiological responses by altering the source supply to individual kernels within an ear, thereby reducing or controlling environmental effects, while maintaining kernel-cob and organ-wide interactions. A single control-pollinated immature maize ear can be divided and quickly subjected to various growth conditions using liquid media to more precisely generate physiological and metabolic changes in the earshoot than in planta.


Cerebral Ischemia/Reperfusion Injury and Pharmacologic Preconditioning as a Means to Reduce Stroke-induced Inflammation and Damage.
Stroke is one of the leading causes of death and long-term serious disability. Current therapeutic strategy is limited to thrombolytic agents, consequently, boosting endogenous neuroprotective mechanisms of the brain to protect itself against harmful stimuli and restore from damages are widely studied. Preconditioned brain to tolerate cerebral ischemia/reperfusion injury could be initiated by several different pharmacological and mechanical strategies, such as ischemic preconditioning, ethanol pharmacological preconditioning and other pre- and post-conditions, such as remote ischemic preconditioning and exercise preconditioning. In this article, we will discuss the major mechanism of ischemia/reperfusion injury and provide an overview of preconditioning in all its various forms, describe the underlying mechanisms and review the recent clinical application of this emerging neuroprotective strategy.


Environmental and Intestinal Phylum Firmicutes Bacteria Metabolize the Plant Sugar Sulfoquinovose via a 6-Deoxy-6-sulfofructose Transaldolase Pathway.
Bacterial degradation of the sugar sulfoquinovose (SQ, 6-deoxy-6-sulfoglucose) produced by plants, algae, and cyanobacteria, is an important component of the biogeochemical carbon and sulfur cycles. Here, we reveal a third biochemical pathway for primary SQ degradation in an aerobic Bacillus aryabhattai strain. An isomerase converts SQ to 6-deoxy-6-sulfofructose (SF). A novel transaldolase enzyme cleaves the SF to 3-sulfolactaldehyde (SLA), while the non-sulfonated C3-(glycerone)-moiety is transferred to an acceptor molecule, glyceraldehyde phosphate (GAP), yielding fructose-6-phosphate (F6P). Intestinal anaerobic bacteria such as Enterococcus gilvus, Clostridium symbiosum, and Eubacterium rectale strains also express transaldolase pathway gene clusters during fermentative growth with SQ. The now three known biochemical strategies for SQ catabolism reflect adaptations to the aerobic or anaerobic lifestyle of the different bacteria. The occurrence of these pathways in intestinal (family) Enterobacteriaceae and (phylum) Firmicutes strains further highlights a potential importance of metabolism of green-diet SQ by gut microbial communities to, ultimately, hydrogen sulfide.


Role of polymorphonuclear neutrophils on infectious complications stemming from Enterococcus faecalis oral infection in thermally injured mice.
Thermally injured mice are susceptible to Enterococcus faecalis translocation. In this study, the role of polymorphonuclear neutrophils (PMN) on the development of sepsis stemming from E. faecalis translocation was studied in SCID-beige (SCIDbg) mice depleted of PMN (SCIDbgN mice) or macrophages (Mphi) and PMN (SCIDbgMN mice). Sepsis was not developed in SCIDbgN mice orally infected with E. faecalis, while the orally infected pathogen spread systemically in the same mice inoculated with PMN from thermally injured mice (TI-PMN). SCIDbgMN mice were shown to be greatly susceptible to sepsis caused by E. faecalis translocation, while orally infected E. faecalis did not spread into sepsis in the same mice that were previously inoculated with Mphi from unburned SCIDbg mice (resident Mphi). In contrast, orally infected E. faecalis spread systemically in SCIDbgMN mice inoculated with resident Mphi and TI-PMN, while all SCIDbgMN mice inoculated in combination with resident Mphi and PMN from unburned SCIDbg mice survived after the infection. After cultivation with TI-PMN in a dual-chamber transwell, resident Mphi converted to alternatively activated Mphi, which are inhibitory on the generation of classically activated Mphi (typical effector cells in host antibacterial innate immunities). TI-PMN were characterized as immunosuppressive PMN (PMN-II) with abilities to produce cc-chemokine ligand-2 and IL-10. These results indicate that PMN-II appearing in response to burn injury impair host antibacterial resistance against sepsis stemming from E. faecalis translocation through the conversion of resident Mphi to alternatively activated Mphi.


Chordoma.
Optimal therapy of chordoma is a combined approach of surgical resection followed by proton beam irradiation for residual disease. The goals of surgery are to establish a definitive diagnosis, obtain total or maximal resection, and "shape" any residual disease so that it is favorable for radiation. Given the difficult locations and large sizes of these tumors, potential morbidity from these surgeries is high. Chordomas respond best to high doses of radiation, but nearby neurologic structures limit doses that can be delivered. Proton beam radiation appears to have a distinct advantage over conventional external beam radiation in this disease because of the rapid fall-off of radiation beyond the target. Unfortunately, the data on efficacy and safety of treatments for chordoma is limited because of the rarity of disease. Current reports in the literature are exclusively case series and reports, limiting the strength of the conclusions that can be drawn.


Effect of Copper Ion Concentration on Bacteria and Cells.
In the oral cavity, dental implants-most often made of commercially pure titanium-come in contact with bacteria, and antibacterial management has been researched extensively to improve patient care. With antibiotic resistance becoming increasingly prevalent, this has resulted in copper being investigated as an antibacterial element in alloys. In this study, the objective was to investigate the copper ion concentrations at which cyto-toxicity is avoided while bacterial inhibition is ensured, by comparing Cu ion effects on selected eukaryotes and prokaryotes. To determine relevant copper ion concentrations, ion release rates from copper and a 10 wt. % Cu Ti-alloy were investigated. Survival studies were performed on MC3T3 cells and Staphylococcus epidermidis bacteria, after exposure to Cu ions concentrations ranging from 9 × 10-3 to 9 × 10-12 g/mL. Cell survival increased from <10% to >90% after 24 h of exposure, by reducing Cu concentrations from 9 × 10-5 to 9 × 10-6 g/mL. Survival of bacteria also increased in the same range of Cu concentrations. The maximum bacteria growth was found at 9 × 10-7 g/mL, probably due to stress response. In conclusion, the minimum inhibitory concentrations of Cu ions for these prokaryotes and eukaryotes were found in the range from 9 × 10-5 to 9 × 10-6 g/mL. Interestingly, the Cu ion concentration correlating to the release rate of the 10 wt. % Cu alloy (9 × 10-8 g/mL) did not kill the bacteria, although this alloy has previously been found to be antibacterial. Further studies should investigate in depth the bacteria-killing mechanism of copper.


Selenium supplementation improves mood in a double-blind crossover trial.
The possibility that a sub-clinical deficiency of the trace element selenium might exist in a sample of the British population was examined by giving a selenium supplemented for 5 weeks. Using a double-blind crossover design 50 subjects received either a placebo or 100 micrograms selenium on a daily basis. On three occasions they filled in the Profile of Moods state. Mood did not change when taking the placebo, whereas when taking the selenium the subjects reported a substantial improvement after both 2.5 and 5 weeks.


Effect of butylated hydroxyanisole added in vitro or administered to rats on N,N-dibutylnitrosamine and N-butyl-N-(4-hydroxybutyl)nitrosamine metabolism by post-mitochondrial supernatant of liver homogenates.
The effect of butylated hydroxyanisole (BHA) on P-450-dependent omega-hydroxylation of N,N-dibutylnitrosamine (NDBA) to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), and the further oxidation of BBN to N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN) by the alcohol/aldehyde dehydrogenase system was investigated using the post-mitochondrial supernatant of liver homogenates (S9) from acutely and chronically BHA pretreated animals or S9 fractions from untreated rats with BHA added. Acute oral BHA (50 and 250 mg.kg-1) did not change NDBA omega-oxidation, which was reduced by 35% only when the compound was administered 0.5% in the diet for 3 weeks. BCPN formation from BBN was unaffected by acute and chronic BHA pretreatment. In order to verify whether BHA or its metabolite(s) had a direct effect on NDBA and BBN oxidation, the compound was added to S9 fractions from untreated rats at various concentrations. Only when BHA concentrations were equimolar or in a 10-fold molar excess to the substrate concentration, we observed 30-50% inhibition of BBN formation and a reduced BCPN formation (60-80% of control values), from BBN. Thus, only at very high BHA concentrations could we confirm the inhibition of P-450-dependent mixed function oxidase and alcohol dehydrogenase activities involved in the metabolism of NDBA and BBN.


Prevalence of orthohantavirus in rodents: A systematic review and meta-analysis.
Orthohantaviruses are zoonotic diseases transmitted mainly by rodents, particularly mice and rats, associated with multiple outbreaks in different continents. Despite its epidemiological relevance, there is a lack of systematic reviews and meta-analyses. To determine the combined global prevalence of Orthohantavirus infection in rodents. A systematic literature review was carried out in six databases (Web of Sciences, Scopus, PubMed, SciELO, Lilacs, Google Scholar) to evaluate the proportion of rodents infected with Orthohantavirus, defined by molecular and immunological techniques. The meta-analysis used a random effects model for the pooled prevalence and 95% confidence intervals (95%CI). Heterogeneity measures, Cochrane's Q, the I2 index and the tau-squared test were estimated. A total of 35,706 rodents (229 studies) were evaluated for ELISA, in which 3360 were found positive, for seroprevalence of 4.9% (95%CI 4.3-5.4%) (τ2 = 0.001; Q = 4027.708; I2 = 94.339%, p < 0.001). For PCR (N = 8812, 91 studies) it was 3.2% (95%CI 2.5-3.9%) (τ2 = 0.001; Q = 397.483; I2 = 77.358%; p < 0.001). For IFA (N = 555, 7 studies) it was 18.8% (95%CI 9.4-28.2%) (τ2 = 0.011; Q = 51.239; I2 = 88.29%, p < 0.001). At the genus level, the studies evaluated Oligoryzomys (8.98%), Reithrodontomys (8.98%), Peromyscus (8.20%), Rattus (8.20%), and Akodon (6.64%). The global prevalence of Orthohantavirus is worrisome, with an increase in its report in certain regions, including Latin America. In this context, rodents have a role as reservoirs. The data of the present meta-analysis showed considerable seroprevalences with great variations by years, countries and Orthohantavirus species.


miR-34a/BCL-2 signaling axis contributes to apoptosis in MPP+ -induced SH-SY5Y cells.
Parkinson's disease (PD) is a neurodegenerative disorder which mainly affects the elderly population of various societies. The main hallmark of this disease is the loss of dopaminergic (DA) neurons. So far, numerous studies have implied the role of microRNAs in fine-tuning cellular processes including apoptosis. Studies have also shown that miR-34a is mainly involved in age-related disorders including Alzheimer's disease, and its expression is usually higher in the brain sample patients. Furthermore, the key role of miR-34a in the expression of BCL-2, and thus, in vitro and in vivo apoptosis has been revealed. miR-34a/BCL-2 axis is therefore of critical importance in inducing or inhibiting apoptosis. In this study, human SH-SY5Y cells were treated with MPP+ and the expression of miR-34a and BCL2 was assessed. Our results also showed that treating human SH-SY5Y neuronal cells using MPP+ to induce oxidative stress and apoptosis led to the upregulation of miR-34a, as compared to the nontreated control group. Moreover, evaluating the expression level of BCL-2 in these cells indicated a contradictory pattern, as compared with miR-34a. It was also revealed that the expression of BCL-2 was significantly decreased in MPP+ -treated cells, thereby confirming previous studies regarding a new concept. In this study, we show that miR-34a/BCL-2 axis is directly correlated with oxidative stress and apoptosis in SH-SY5Y cells as a model of DA neurons. miR-34a and its target gene, BCL-2, play a possible role in the induction of apoptosis in DA neurons, and therefore, they have a potential role in the pathogenesis of PD. Consequently, the therapeutic potential of miR-34a could be considered in order to inhibit the progression of PD.


The medicinal plants of Gunung Leuser National Park, Indonesia.
This paper describes an ethnopharmacological study of two remote settlements in Indonesia. Interviews with practitioners of traditional medicine (dukuns) were carried out to determine the vernacular names of plants used for medicinal purposes. Parts used, methods of preparation and the medicinal uses of 158 species are presented in an inventory. Samples from several species are currently undergoing chemical analysis.


Low systemic exposure after repeated topical application of Pimecrolimus (Elidel), SD Z ASM 981) in patients with atopic dermatitis.
Pimecrolimus is a cell-selective inhibitor of inflammatory cytokine release developed specifically for the treatment of inflammatory skin diseases. The objective of this study was to evaluate blood concentrations and tolerability of pimecrolimus during topical treatment. Twelve adult patients with extensive atopic dermatitis were enrolled in an open-label, noncontrolled, pharmacokinetic study. The patients were treated twice daily for 3 weeks with pimecrolimus cream 1% on all lesions. Pimecrolimus blood concentrations were measured at regular time points, and the safety and tolerability were monitored throughout the study. In 78% of the 444 blood samples evaluated, pimecrolimus concentrations remained below the limit of quantitation (0.5 ng/ml). The highest concentration measured was 1.4 ng/ml. There was no indication of drug accumulation. Pimecrolimus was well tolerated locally and systemically. The 3-week twice daily treatment with pimecrolimus cream 1% results in consistently low pimecrolimus blood concentrations with no accumulation. Pimecrolimus cream appears suitable for the long-term management of atopic dermatitis.


Synthesis, biological evaluation, and modeling studies of inhibitors aimed at the malarial proteases plasmepsins I and II.
The increasing resistance of the malarial parasite to antimalarial drugs is a major contributor to the reemergence of the disease and increases the need for new drug targets. The two aspartic proteases, plasmepsins I and II, from Plasmodium falciparum have recently emerged as potential targets. In an effort to inhibit these hemoglobinases, a series of inhibitors encompassing a basic hydroxyethylamine transition state isostere as a central fragment were prepared. The synthesized compounds were varied in the P1' position and exhibited biological activities in the range of 31 to >2000 nM. To try to rationalize the results, molecular docking and 3D-QSAR analysis were used.


[Pneumoblastoma].
Pneumoblastoma is a rare malignant pulmonary tumor. A new case is reported in a 2 years 5 month-old girl. Because the lack of locoregional extension an isolated surgical excision was performed. However, 6 months later, a local relapse occurred, with inframediastinal extension and cerebral metastases. On the occasion of this case, the authors review the problems set by the histogenesis of this tumor, its therapeutic indications, poorly codified due to its rarity and, overall, its often unfavourable outcome.


Gastrointestinal nematode infection and performance of weaned stocker calves in response to anthelmintic control strategies.
Gastrointestinal nematode (GIN) parasite control recommendations are in a state of flux because of the increase in anthelmintic resistant cattle parasites, such as Cooperia spp. In addition, Cooperia spp. infection is typically high in warm-season grass pastures and can affect growth performance of grazing stocker calves in the Gulf Coast Region. This study evaluated the effects of moxidectin pour-on, oxfendazole oral suspension, or a combination of the two given at separate times on infection and performance of weaned beef calves grazing summer forages. Steers (n=42) and heifers (n=31) were stratified by sex, d-11 fecal egg count (FEC), and d-1 shrunk body weight (BW) to one of 10 pastures with four anthelmintic treatments and one control. Treatments included: (1) oxfendazole given on d 0 and moxidectin on d 73 (O+M), (2) moxidectin given on d 0 and oxfendazole on d 73 (M+O), (3) moxidectin given on d 0 (M), (4) oxfendazole given on d 0 (O) and (5) no anthelmintic given (CON). Calves grazed for d-110 beginning May 27th. Response variables were FEC (collected on d-11, 14, 31, 45, 59, 73, 87 and 108), coprocultures (evaluated for d 87 and 108), final shrunk BW, shrunk BW gain, average daily gain (ADG), and full BW gain (collected on d 31, 59, 73, 87, and 108). Calves treated with either oxfendazole (O+M and O) or moxidectin (M+O and M) on d 0 had significantly lower (P<0.001) FEC than the CON calves on d 14, 31 and 45. However, the M+O treated calves had significantly higher (P<0.001) FEC than both oxfendazole treated groups. In addition, calves treated with a second dewormer on d 73 (O+M and M+O) had significantly lower (P<0.001) FEC by d 87 than the CON or M treated calves. Shrunk BW gain and ADG were significantly greater (P=0.005) for the O+M compared to the M treated and CON calves, but comparable with the M+O and O treated calves, respectively. Coprocultures sampled on d 87 and 108 for calves not receiving a second dewormer were predominantly Cooperia spp. and Ostertagia spp. On d 87, no larvae were recovered from the M+O treated calves, whereas the O+M treated calves had 94% Cooperia spp. and 3% Ostertagia spp. recovered. Providing a benzimidazole with a macrocyclic lactone given at two different periods may provide better GIN parasite control and improve animal gains for stocker calves grazing warm-season grass pastures.


Effects of class I heparin binding growth factor and fibronectin on platelet adhesion and aggregation.
Fibronectin and heparin binding growth factor-type 1 have been affixed to vascular graft surfaces to enhance the attachment and the proliferation of transplanted endothelial cells, respectively. The current study examines the effect of fibronectin and heparin binding growth factor-type 1 on platelet adhesion and activation in vivo and on platelet aggregation in vitro. Expanded polytetrafluoroethylene prostheses (5 cm x 4 mm internal diameter) were treated either with fibronectin (n = 9), fibronectin/heparin/heparin binding growth factor-type 1/heparin (n = 12), or neither (n = 13) and were interposed into canine aortoiliac systems bilaterally. Autogenous radiolabeled (Indium 111 oxine, 650 microCi) platelets were injected intravenously before reestablishment of circulation. Perfusion was maintained for 30 minutes, and prostheses were removed with segments of native aorta and distal iliac arteries bilaterally. Specimens were examined for thrombus-free surface area, by gamma well counting for adherent radiolabeled platelets, and by light microscopy and transmission and scanning electron microscopic techniques. Results showed that both the fibronectin and fibronectin/heparin/heparin binding growth factor-type 1/heparin pretreated prostheses contained significantly greater numbers of platelets and adherent radioactivity than did control graft segments when normalized to their ipsilateral iliac arteries. Fibronectin/heparin/heparin binding growth factor-type 1/heparin pretreated prostheses contained 27 +/- 16 times more radioactivity per square millimeter than ipsilateral iliac arteries, fibronectin pretreated prostheses had 13 +/- 8 times more radioactivity per square millimeter than ipsilateral iliac arteries, and untreated expanded polytetrafluoroethylene had 4 +/- 3 times more radioactivity per square millimeter than ipsilateral iliac arteries. Fibronectin/heparin/heparin binding growth factor-type 1/heparin was more radioactive than fibronectin alone (p = 0.056). Histologic evaluation and thrombus-free surface area determinations corroborated the gamma well counting data. Platelet aggregation in vitro was not activated by either fibronectin (1 to 100 micrograms/100 microliters) or heparin binding growth factor-type 1 (25 to 2500 ng/100 microliters). These data suggest that fibronectin and heparin binding growth factor-type 1 promote platelet adhesion not aggregation.


Can negative life events and coping style help explain socioeconomic differences in perceived stress among adolescents? A cross-sectional study based on the West Jutland cohort study.
Previous research suggests that perceived stress in adolescence is socially patterned, but that this relationship may depend on the measure of socioeconomic status (SES) used. This study examines if social gradients in perceived stress, negative life events, and coping exist amongst Danish adolescents, and, if life events and coping strategies can partly account for an association between SES and perceived stress. These relationships are studied separately for two different measures of SES. Questionnaire data were collected from 3054 14-15 year old youths (83% response rate) during baseline measurement in the West Jutland birth cohort study. Parents were identified via the Central Office of Civil Registration in which the respondents are linked to their parents or guardians via their CPR-number, a personal identification number given to everyone in Denmark. The study employs data from two independent sources, adolescent self-report data (stress, life events and coping) and national registers (parental educational level, household income and confounder variables). Ordinary Least Squares regression estimated the effects of parental SES, negative life events and coping on perceived stress. Analyses were stratified by gender. Girls reported more perceived stress than boys. SES accounted for a small but significant amount of the variance in perceived stress. Lower parental education and lower household income were associated with higher stress levels irrespective of gender, but the social gradient was strongest amongst girls when parents' education was used to measure SES, and strongest for boys when income was used. Life events and coping were also found to be associated with SES and both mediated part of the SES-perceived stress relationship. In general, the social gradient in perceived stress was accounted for by the study variables to a higher degree among girls than among boys. Lower parental education and household income are associated with higher levels of perceived stress amongst Danish adolescents. Furthermore, both life events and coping appear to mediate this relation. Gender differences in the ways SES and stress are related may exist.


Endogenous RD-114 virus of cats: absence of antibodies to RD-114 envelope antigens in cats naturally exposed to feline leukemia virus.
Healthy cats, including those exposed to feline leukemia virus in leukemia cluster households, lack evidence of humoral immunity to virion surface antigens of the endogenous RD-114 virus.


Saliva composition and functions: a comprehensive review.
The aim of this study was to perform a literature review about the composition and functions of saliva as well as describe the factors that influence salivary flow (SF) and its biochemical composition. Saliva represents an increasingly useful auxiliary means of diagnosis. Sialometry and sialochemistry are used to diagnose systemic illnesses, monitoring general health, and as an indicator of risk for diseases creating a close relation between oral and systemic health. This review provides fundamental information about the salivary system in terms of normal values for SF and composition and a comprehensive review of the factors that affect this important system. Since several factors can influence salivary secretion and composition, a strictly standardized collection must be made so the above-mentioned exams are able to reflect the real functioning of the salivary glands and serve as efficient means for monitoring health. Since many oral and systemic conditions manifest themselves as changes in the flow and composition of saliva the dental practitioner is advised to remain up-to-date with the current literature on the subject.


A one-year follow-up of cystoid macular edema following intraocular lens implantation.
Retrospective and prospective techniques were used to analyze a consecutive series of 406 eyes to identify factors contributing to cystoid macular edema following lens implantation. Vitreous loss and rupture of the posterior capsule were highly significant in the production and persistence of this complication.


Comparison of templates for homology model of ρ1 GABAC receptors: More insights to the orthosteric binding site's structure and functionality.
Five sets of ρ1 GABAC homology models were generated based on X-ray crystal structures of the acetylcholine binding protein (AChBP), the ion channel from Caenorhabditis elegans (GLIC), the ion channel from Erwinia chrysanthemi (ELIC), the homomeric GABAA β3 ion channel, and the homomeric α-subunit of glutamate-gated homopentameric chloride channel (GluCl). The GluCl based model was found to the represent the structure of ρ1 GABAC receptors. The GABA pose docked in the selected best model was confirmed by QM-polarized ligand docking and induced fit docking protocol, and used to study molecular interactions in the ρ1 GABA binding site. The potential interactions of identified residues are discussed. This study identified several residues with potential ligand interactions located on loops F and G with their side chain oriented toward the binding site such as Ser215 and Gln83. The partial agonists muscimol and imidazole-4-acetic acid (I4AA) were docked into the binding site of the most reliable 'GABA bound' homology model. The potency and efficacy of these partial agonists in activating recombinant ρ1 receptors were correlated with their docking results. The model predicts that muscimol resembles GABA in the docking pose with similar interactions. However, I4AA has a very different docking pose to GABA and was predicted by the model to form π-π stacking with aromatic residues in the orthosteric binding site. A set of TPMPA bound ρ1 homology models based on the GluClα 'apo state' template was built in order to study a competitive antagonist in the ρ1 orthosteric binding site. The results demonstrated the ability of our model to explain most experimental findings and predict potential roles of residues within the orthosteric binding site.


Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Alzheimer's disease (AD) causes unrelenting, progressive cognitive impairments, but its course is heterogeneous, with a broad range of rates of cognitive decline1. The spread of tau aggregates (neurofibrillary tangles) across the cerebral cortex parallels symptom severity2,3. We hypothesized that the kinetics of tau spread may vary if the properties of the propagating tau proteins vary across individuals. We carried out biochemical, biophysical, MS and both cell- and animal-based-bioactivity assays to characterize tau in 32 patients with AD. We found striking patient-to-patient heterogeneity in the hyperphosphorylated species of soluble, oligomeric, seed-competent tau. Tau seeding activity correlates with the aggressiveness of the clinical disease, and some post-translational modification (PTM) sites appear to be associated with both enhanced seeding activity and worse clinical outcomes, whereas others are not. These data suggest that different individuals with 'typical' AD may have distinct biochemical features of tau. These data are consistent with the possibility that individuals with AD, much like people with cancer, may have multiple molecular drivers of an otherwise common phenotype, and emphasize the potential for personalized therapeutic approaches for slowing clinical progression of AD.


Liberation of 14CO2 from [14C]adipic acid and [14C]octanoic acid by adult rats during riboflavin deficiency and its reversal.
The purpose of the present study was to test the hypothesis that the already well-established mitochondrial lesion in fatty acid oxidation in riboflavin-deficient experimental animals, might be accompanied by an alteration in vivo in the kinetics of oxidation of labelled adipic acid. This dicarboxylic acid was chosen for testing as a metabolic probe because a block in its oxidation was already apparent from urine analysis of riboflavin-deficient animals, whereas the oxidation of medium- or long-chain monocarboxylic acids seemed to be little affected by deficiency in vivo. Female adult Norwegian hooded rats fed on purified diets containing either 15 mg riboflavin/kg diet (controls) or about 0.4 mg/kg (riboflavin-deficient) received an intragastric dose of either [1,6-14C]adipic acid or [1-14C]octanoic acid. Expired carbon dioxide was then collected in an alkaline trap over 3 h, for determination of radioactivity. This test was repeated at intervals for up to 2 weeks following riboflavin repletion of the deficient animals, and in riboflavin-dosed controls. Whereas the rate and extent of [14C]octanoic acid oxidation was not significantly affected by the deficiency or repletion, the extent of [14C]adipic acid oxidation was markedly and significantly increased during repletion of the deficient animals. The time-course indicated a temporary overshoot, followed by a slow return to the control values over 1-2 weeks. Adipate oxidation was also much less affected by a preceding period of overnight starvation, than was octanoate oxidation. Thus, adipic acid (or a related metabolic probe) may have appropriate properties for the design of a functional test of fatty acid oxidation efficiency, during riboflavin deficiency or allied metabolic conditions in human subjects.


EST-derived single nucleotide polymorphism markers for assembling genetic and physical maps of the barley genome.
In a panel of seven genotypes, 437 expressed sequence tag (EST)-derived DNA fragments were sequenced. Single nucleotide polymorphisms (SNPs) that were polymorphic between the parents of three mapping populations were mapped by heteroduplex analysis and a genome-wide consensus map comprising 216 EST-derived SNPs and 4 InDel (insertion/deletion) markers was constructed. The average frequency of SNPs amounted to 1/130 bp and 1/107.8 bp for a set of randomly selected and a set of mapped ESTs, respectively. The calculated nucleotide diversities (pi) ranged from 0 to 40.0 x 10(-3) (average 3.1 x 10(-3)) and 0.52 x 10(-3) to 39.51 x 10(-3) (average 4.37 x 10(-3)) for random and mapped ESTs, respectively. The polymorphism information content value for mapped SNPs ranged from 0.24 to 0.50 with an average of 0.34. As expected, combination of SNPs present in an amplicon (haplotype) exhibited a higher information content ranging from 0.24 to 0.85 with an average of 0.50. Cleaved amplified polymorphic sequence assays (including InDels) were designed for a total of 87 (39.5%) SNP markers. The high abundance of SNPs in the barley genome provides avenues for the systematic development of saturated genetic maps and their integration with physical maps.


Lipid composition and microviscosity of subcellular fractions from rabbit thymocytes. Differences in the microviscosity of plasma membranes from subclasses of thymocytes.
There are indications from freeze-fracture experiments that subclasses of rabbit thymocytes show different mobilities of plasma membrane components. Consequently, one would expect differences in the fluidity of the plasma membrane. For this reason, rabbit thymocytes were separated on a Ficoll/Metrizoate gradient yielding three subclasses representing various levels of cell differentiation. These thymocyte subclasses did not show any significant differences in the degree of fluorescence polarization using the probe 1,6-diphenyl-1,3,5-hexatriene. The fluorescence polarization of the plasma membrane may be overshadowed by the contribution of all cellular lipids due to penetration of the fluorescent probe into the cell. Therefore, plasma membranes were isolated from rabbit thymocytes using a cell-disrupting pump, differential centrifugation, and sucrose density gradient centrifugation. As shown by biochemical and electron microscopical analyses, plasma membranes with a high degree of purity were obtained. As expected the plasma membrane fractions showed a higher microviscosity than the other subcellular fractions. This was attributed to a higher cholesterol to phospholipid molar ratio and a higher degree of saturation of phospholipid fatty acid chains. Subsequently, the microviscosity was measured of plasma membrane preparations obtained from two main subclasses of thymocytes representing mature and immature lymphocytes. The immature thymocytes yielded two plasma membrane fractions with higher microviscosity than the mature cells. These finding is in line with earlier observed differences in the glycerol-induced clustering of intramembranous particles. Furthermore, the results of this study support the view that the fluorescence polarization technique applied to whole cells does not exclusively monitor the plasma membrane.


Recipient ureterocalycostomy in a renal allograft: case report of a transplant salvage.
The use of a recipient ureter ureterocalycostomy in the management of ureteral obstruction in a renal transplant recipient is presented. This technique can be used when primary modes of reconstruction are unavailable and nephrectomy is the only alternative.


Enhancement of lectin-induced cap formation in human neutrophils by cyclosporin A.
Cyclosporin A, a potent immunosuppressive agent, has been extensively studied for its immunomodulatory effects on T-cells. Recently Cyclosporin A has been shown to cause renal damage, which correlates with increased glomerular neutrophil migration. The precise role of Cyclosporin A on neutrophil function has not been established. In this study we investigated the role of Cyclosporin A in the regulation of cap formation in human neutrophils. Our results show an increased concanavalin A-induced cap formation in human neutrophils pretreated with Cyclosporin A, implicating a possible role of Cyclosporin A in human neutrophil activation. The correlation between enhanced capping, renal nephrotoxicity and neutrophil migration remains to be studied.


Ocular Perfusion Pressure and the Risk of Open-Angle Glaucoma: Systematic Review and Meta-analysis.
Low ocular perfusion pressure (OPP) has been proposed as an important risk factor for glaucoma development and progression, but controversy still exists between studies. Therefore, we conducted a systematic review and meta-analysis to analyze the association between OPP and open-angle glaucoma (OAG). Studies were identified by searching PubMed and EMBASE databases. The pooled absolute and standardised mean difference in OPP between OAG patients and controls were evaluated using the random-effects model. Meta-regression analysis was conducted to investigate the factors associated with OPP difference between OAG patients and controls. A total of 43 studies were identified including 3,009 OAG patients, 369 patients with ocular hypertension, and 29,502 controls. The pooled absolute mean difference in OPP between OAG patients and controls was -2.52 mmHg (95% CI -4.06 to -0.98), meaning significantly lower OPP in OAG patients (P = 0.001). Subgroup analyses showed that OAG patients with baseline IOP > 21 mmHg (P = 0.019) and ocular hypertension patients also had significantly lower OPP than controls (P < 0.001), but such difference in OPP was not significant between OAG patients with baseline IOP of ≤21 mmHg and controls (P = 0.996). In conclusion, although no causal relationship was proven in the present study, our findings suggest that in patients with high baseline IOP, who already have a higher risk of glaucoma, low OPP might be another risk factor.


Effects of heavy-metal-contaminated soil on growth, phenology and biomass turnover of Hieracium piloselloides.
The effects of low levels of heavy metals on plant growth, biomass turnover and reproduction were investigated for Hieracium pilosella. Plants were grown for 12 weeks on substrates with different concentrations of heavy metals obtained by diluting contaminated soils with silica sand. To minimize effects of other soil factors, the substrates were limed, fertilized, and well watered. The more metal-contaminated soil the substrate contained, the lower the leaf production rate and the plant mass were, and the more the phenological development was delayed. Flowering phenology was very sensitive to metals. Leaf life span was reduced at the highest and the lowest metal levels, the latter being a result of advanced seed ripening. Even if the effect of low metal levels on plant growth may be small, the delayed and reduced reproduction may have large effects at population, community and ecosystem level, and contribute to rapid evolution of metal tolerance.


Three-dimensional culture using human plasma-medium gel with fragmin/protamine microparticles for proliferation of various human cells.
Fragmin/protamine microparticles (F/P MPs) have been used as carriers for the preservation and activation of cytokines in human plasma (HP)-Dulbecco's modified Eagle's medium (DMEM) gels. This study investigated a three-dimensional (3D) culture system using an HP-DMEM gel with 0.1 mg/mL F/P MPs and 5 ng/mL FGF-2 for the proliferation of human dermal fibroblast cells (DFCs), human microvascular endothelial cells (MVECs) and human coronary smooth muscle cells (SMCs), or 5 ng/mL interleukin (IL)-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) for a human hematopoietic cell line (TF-1 cells). DFCs, MVECs, SMCs and TF-1 cells grew rapidly under 3D culture conditions using a low-concentration HP (2 %)-DMEM gel with F/P MPs and FGF-2 (for DFCs, MVECs and SMCs) or IL-3/GM-CSF (for TF-1 cells) at doubling times of 22, 23, 25 and 18 h, respectively, without the use of animal serum, compared to under 2D culture conditions using low-concentration human serum (2 %)-DMEM with 5 ng/mL FGF-2 or IL-3/GM-CSF on F/P MP-coated plates at doubling times of approximately 26, 25, 40 and 20 h, respectively.


The relative importance of kinetic mechanisms and variable enzyme abundances for the regulation of hepatic glucose metabolism--insights from mathematical modeling.
Adaptation of the cellular metabolism to varying external conditions is brought about by regulated changes in the activity of enzymes and transporters. Hormone-dependent reversible enzyme phosphorylation and concentration changes of reactants and allosteric effectors are the major types of rapid kinetic enzyme regulation, whereas on longer time scales changes in protein abundance may also become operative. Here, we used a comprehensive mathematical model of the hepatic glucose metabolism of rat hepatocytes to decipher the relative importance of different regulatory modes and their mutual interdependencies in the hepatic control of plasma glucose homeostasis. Model simulations reveal significant differences in the capability of liver metabolism to counteract variations of plasma glucose in different physiological settings (starvation, ad libitum nutrient supply, diabetes). Changes in enzyme abundances adjust the metabolic output to the anticipated physiological demand but may turn into a regulatory disadvantage if sudden unexpected changes of the external conditions occur. Allosteric and hormonal control of enzyme activities allow the liver to assume a broad range of metabolic states and may even fully reverse flux changes resulting from changes of enzyme abundances alone. Metabolic control analysis reveals that control of the hepatic glucose metabolism is mainly exerted by enzymes alone, which are differently controlled by alterations in enzyme abundance, reversible phosphorylation, and allosteric effects. In hepatic glucose metabolism, regulation of enzyme activities by changes of reactants, allosteric effects, and reversible phosphorylation is equally important as changes in protein abundance of key regulatory enzymes.


Functional and pharmacodynamic evaluation of metronomic cyclophosphamide and docetaxel regimen in castration-resistant prostate cancer.
The aim of our study was to investigate the association of docetaxel and metronomic cyclophosphamide (CYC) in castration-resistant prostate cancer (CRPC). CRPC xenografts were established with PC3 cells. Mice were treated with a combination of CYC (50 mg/kg/day) and docetaxel (10-30 mg/kg/week) or with docetaxel alone. Docetaxel plasma levels were analyzed in patients receiving the drug alone or combined with CYC. Metronomic CYC is an effective adjuvant in blocking tumor growth in vivo, with comparable efficacy and less toxic effects compared with docetaxel treatment. CYC acts by downregulating cell proliferation and inducing apoptosis thorough upregulation of p21 and inhibition of angiogenesis. Finally, CYC increases docetaxel plasma levels in patients. Metronomic CYC exerts anti-tumoral effects in an in vivo model of prostate cancer and in patients with CRPC, and also increases the bioavailability of docetaxel. These results explain the favorable toxicity and activity profiles observed in patients treated with this regimen.


Dual resistance to lambda-cyhalothrin and dicrotophos in Hippodamia convergens (Coleoptera: Coccinellidae).
Insecticide resistance is usually associated with pests, but may also evolve in natural enemies. In this study, adult beetles of three distinct North American populations of Hippodamia convergens Guérin-Méneville, and the progeny of reciprocal crosses between the resistant and most susceptible population, were treated topically with varying concentrations of lambda-cyhalothrin and dicrotophos. In addition, the LD50s of both insecticides were applied in combination to resistant individuals. The developmental and reproductive performance of each population was assessed in the absence of insecticide exposure to compare baseline fitness. California and Kansas populations were susceptible to both materials, whereas Georgia (GA) beetles exhibited a resistance ratio (RR50) of 158 to lambda-cyhalothrin and 530 to dicrotophos. Inheritance of lambda-cyhalothrin resistance was X-linked, whereas inheritance of dicrotophos resistance was autosomal. Mortality of resistant beetles treated with a mixture of LD50s of both materials was twice that of those treated with lambda-cyhalothrin alone, but not significantly different from those receiving dicrotophos alone. Life history parameters were largely similar among populations, except that Georgia beetles had higher egg fertility relative to susceptible populations. We conclude that the high levels of resistance to lambda-cyhalothrin and dicrotophos in Georgia beetles reflect heavy loads of these insecticides in local environments, most likely the large acreage under intensive cotton cultivation.


The noradrenergic innervation of the vasa nervorum in old rats: a fluorescence histochemical study.
The effect of ageing on the density and pattern of noradrenergic nerves in the perivascular nerve plexus supplying the vasa nervorum of the rat sciatic nerve was studied using combined catecholamine histofluorescence and quantitative image analysis techniques. The density of noradrenergic fibres around arteries and arterioles of the rat sciatic nerve vasa nervorum increased in the old animals. In contrast, no changes in perivascular nerve fibres supplying the veins and venules were found in the vasa nervorum of old rats. The increase in old age of noradrenergic innervation of arteries and arterioles of the vasa nervorum may be related to the pathogenesis of some peripheral nerve diseases.


Bach Mai Procedure for complete mesocolic excision, central vascular ligation, and D3 lymphadenectomy in total laparoscopic right hemicolectomy: a prospective study.
Total laparoscopic right hemicolectomy with complete mesocolic excision (CME), central vascular ligation (CVL), and D3 lymphadenectomy is still the most challenging colon procedures for gastrointestinal surgeons. We herein report the technical details and our preliminary experience of Bach Mai Procedure - a novel-combining (cranial, medial to lateral, and caudal) approach with early resection of the terminal ileum. The dissection stage was central vascular isolation and ligation by a combined multiple approaches in the following four steps: cranial approach, dissecting along the inferior aspect of pancreatic isthmus to reveal the middle colic vessels and the anterior aspect of the superior mesentery vein and then exposed the right gastroepiploic vein and the trunk of Henle; medial-to-lateral approach, exposing the surgical axis - the superior mesenteric vascular axis and then early resection of the terminal ileum to open the dissection from the bottom up; and caudal approach, radical ligation of the ileocecal artery and right colic artery (central vascular ligation), lymph node dissection (D3 lymphadenectomy), and resecting the Toldt fascia of the colon to release the entire right colon from the abdominal wall. In 12 months, there were 32 cases of primary right-sided colon malignancies that have undergone tLRHD3, CME/CVL based on the Bach Mai Procedure. In 3 cases (9.4%), the tumor site was hepatic flexure. The median of lymph node number (LNN) was 38, with the maximum number which was 101. No serious postoperative complications (grade 3 or higher) neither inhospital mortality was detected. This Bach Mai procedure, a novel-combining approach with early resection of the terminal ileum, is technically feasible and safe for tLRHD3, CME/CVL. Further investigations and follow-up must be proceeded to evaluate the long-term outcomes of our technique.


Structural and spectroscopic characterization of 2-mesityl-1H-benzo[d]imidazol-3-ium chloride: a combined experimental and theoretical analysis.
The title molecular salt, 2-mesityl-1H-benzo[d]imidazol-3-ium chloride (C(16)H(17)N(2)(+)·Cl-), was synthesized unexpectedly from the reaction of N-[(1E)-mesitylmethylene]benzene-1,2-diamine and CoCl(2)·6H(2)O, and characterized by elemental analysis, (1)H NMR and FT-IR spectroscopies, and single-crystal X-ray diffraction technique. In addition, quantum chemical calculations employing density functional theory (DFT) method with the 6-311++G(d,p) basis set were performed to study the molecular, spectroscopic and some electronic structure properties of the title compound, and the results were compared with the experimental findings. The computational result shows that the optimized geometry can well reproduce the crystal structural parameters. The intermolecular proton transfer process between the ionic (C(16)H(17)N(2)(+)·Cl-) and nonionic forms (C(16)H(16)N(2)·HCl) of the title salt is investigated and found to be almost barierless with an energy value of 0.20 kcal mol(-1). The NLO properties of the compound are bigger than those of urea.


Choledochal cysts in children: Intrahepatic ductal dilatation does not indicate true intrahepatic biliary duct disease.
Choledochal cysts (CCs) are rare abnormalities of the biliary tract. Presenting our clinical experience with CCs herein, we aimed to identify if intrahepatic ductal dilatation indicates true intrahepatic biliary duct disease. We retrospectively reviewed all cases of CCs in children diagnosed at a single center (Başkent University Fac-ulty of Medicine, Department of Pediatric Surgery) institution from 2005 to 2015. Of 18 patients with CCs, 7 were males (39%). The age range was 3 months to 17 years (mean age, 6.2±3.8 years). Intrahepatic bile duct dilatation was detected in 13 (72%) patients by preoperative scanning. Type I, II, III, and IVA cysts were diagnosed in 13, 1, 1, and 3 patients, respectively. In all patients, total cyst excision and Roux-en-Y hepaticoenterostomy were performed. In this study, most intrahepatic ductal dilatations seen on preoperative imaging were thought to be caused by a distal obstruction, not true intrahepatic biliary duct disease. This study supports the hypothesis that preoperatively distinguishing between type I and type IVA CCs is not necessary; it does not affect the initial treatment. We consider that complete cyst excision with Roux-en-Y hepaticojejunostomy is safe and should be performed soon after diagnosis, irrespective of symptom severity to avoid future complications.


Does interhemispheric communication relate to the bilateral function of muscles? A study of scapulothoracic muscles using transcranial magnetic stimulation.
Interhemispheric connections have been demonstrated between the motor cortex controlling muscle pairs. However, these investigations have tended to concentrate upon hand muscles. We have extended these investigations to proximal muscles that control the scapula upon the trunk and help to move and stabilise the shoulder. Using a paired pulse transcranial magnetic stimulation protocol, the interhemispheric interactions between different shoulder girdle muscle pairs, serratus anterior, upper trapezius and lower trapezius were investigated. Test motor evoked potentials were conditioned using conditioning pulse intensities of 80% and 120% of active motor threshold at three different condition-test intervals, during three different tasks. Interhemispheric inhibition was observed in upper trapezius using a conditioning intensity of 120% and condition-test interval of 8 ms (17 ± 18%, p < 0.007). A trend towards inhibition was observed in lower trapezius and serratus anterior using a conditioning intensity of 120% and a condition-test interval of 8 ms (13 ± 22%; p < 0.07 and 10 ± 19% respectively; p < 0.07). No interhemispheric facilitation was evoked. The study demonstrates that a low level of interhemispheric inhibition rather than interhemispheric facilitation could be evoked between these muscle pairs.


The radiology of urinary tract abnormalities associated with hysterectomy.
A review of urinary tract complications following hysterectomy shows that these are more likely to occur after radical hysterectomy than after hysterectomy for benign conditions. The role of associated radiotherapy has also been considered and the use of preoperative and postoperative radiological investigations of the urinary tract discussed. Ureteric complications include transient hydroureter and hydronephrosis, ureteric stricture, ureteric fistulae and ureteric severance. The bladder complications which may occur are vesicovaginal fistula, impingement from postoperative haematoma and abscess, the development of bladder calculi, urinary retention and prolaspe of the bladder base. Ureteric complications are often serious especially when there has been fistula or stricture formation, but other abnormalities may be transient. Serious bladder complications such as fistula formation are rare, but urinary retention and prolapse of the bladder base are not uncommon. The purpose and means of radiological investigation have been discussed, as well as some diagnostic pitfalls.


Sensitivity of fluvial sediment source apportionment to mixing model assumptions: A Bayesian model comparison.
Mixing models have become increasingly common tools for apportioning fluvial sediment load to various sediment sources across catchments using a wide variety of Bayesian and frequentist modeling approaches. In this study, we demonstrate how different model setups can impact upon resulting source apportionment estimates in a Bayesian framework via a one-factor-at-a-time (OFAT) sensitivity analysis. We formulate 13 versions of a mixing model, each with different error assumptions and model structural choices, and apply them to sediment geochemistry data from the River Blackwater, Norfolk, UK, to apportion suspended particulate matter (SPM) contributions from three sources (arable topsoils, road verges, and subsurface material) under base flow conditions between August 2012 and August 2013. Whilst all 13 models estimate subsurface sources to be the largest contributor of SPM (median ∼76%), comparison of apportionment estimates reveal varying degrees of sensitivity to changing priors, inclusion of covariance terms, incorporation of time-variant distributions, and methods of proportion characterization. We also demonstrate differences in apportionment results between a full and an empirical Bayesian setup, and between a Bayesian and a frequentist optimization approach. This OFAT sensitivity analysis reveals that mixing model structural choices and error assumptions can significantly impact upon sediment source apportionment results, with estimated median contributions in this study varying by up to 21% between model versions. Users of mixing models are therefore strongly advised to carefully consider and justify their choice of model structure prior to conducting sediment source apportionment investigations. An OFAT sensitivity analysis of sediment fingerprinting mixing models is conductedBayesian models display high sensitivity to error assumptions and structural choicesSource apportionment results differ between Bayesian and frequentist approaches.


Pharmacokinetic Drug Interaction Study of Sorafenib and Morphine in Rats.
A combination of the tyrosine kinase inhibitor-sorafenib-and the opioid analgesic-morphine-can be found in the treatment of cancer patients. Since both are substrates of P-glycoprotein (P-gp), and sorafenib is also an inhibitor of P-gp, their co-administration may affect their pharmacokinetics, and thus the safety and efficacy of cancer therapy. Therefore, the aim of this study was to evaluate the potential pharmacokinetic drug-drug interactions between sorafenib and morphine using an animal model. The rats were divided into three groups that Received: sorafenib and morphine (ISOR+MF), sorafenib (IISOR), and morphine (IIIMF). Morphine caused a significant increase in maximum plasma concentrations (Cmax) and the area under the plasma concentration-time curves (AUC0-t, and AUC0-∞) of sorafenib by 108.3 (p = 0.003), 55.9 (p = 0.0115), and 62.7% (p = 0.0115), respectively. Also, the Cmax and AUC0-t of its active metabolite-sorafenib N-oxide-was significantly increased in the presence of morphine (p = 0.0022 and p = 0.0268, respectively). Sorafenib, in turn, caused a significant increase in the Cmax of morphine (by 0.5-fold, p = 0.0018). Moreover, in the presence of sorafenib the Cmax, AUC0-t, and AUC0-∞ of the morphine metabolite M3G increased by 112.62 (p < 0.0001), 46.82 (p = 0.0124), and 46.78% (p = 0.0121), respectively. Observed changes in sorafenib and morphine may be of clinical significance. The increased exposure to both drugs may improve the response to therapy in cancer patients, but on the other hand, increase the risk of adverse effects.


Cetaceans playing with single-use plastics (SUPs): A widespread interaction with likely severe impacts.
Play is a common behaviour in wild cetaceans that includes the manipulation of natural, as well as artificial objects such as marine debris. Yet, very little is known about these interactions despite the potential impacts on cetacean health. We combined a detailed review of the scientific literature and social media with 12 years of observations to examine cetacean interactions with plastic litter. A total of 11 odontocete species (Tursiops truncatus, Stenella longirostris, Delphinus delphis, Grampus griseus, Steno bredanensis, Stenella frontalis, Sotalia guianensis, Pseudorca crassidens, Orcinus orca, Globicephala melas and Physeter macrocephalus) were documented in 59 events carrying or throwing plastic litter with their head and/or flippers suggesting a form of play. Interactions occurred in the Atlantic, Pacific, Indian Ocean, Mediterranean, and Red Sea, with single-use plastics composing the main typology registered. While these interactions appeared harmless to the observers, they can pose a significant risk through subsequent entanglement or ingestion.


[Sudden deafness: apropos of 19 cases. Results of treatment with pentoxifylline. Value of erythrocyte filtration time].
Between March 85 and November 86, 20 patients underwent treatment for sudden deafness [19] or bilateral tinnitus [1] by Pentoxifylline (1 200 mg/24 Hrs, including 400 mg IV over 24 Hrs) and Carbogen sessions (2 or 3/24 Hrs), during six days on an in-patient basis, followed by 1 200 mg/24 Hrs orally during another eight days. The results, assessed by clinical examination, audiometry, and erythrocyte filtration time (using the Reid and Dormandy method) on the first, sixth, and fourtheenth days, were: -- good or very good a little more than 75%, -- moderate: 5%, -- poor: a little fewer than 20%. Filtration times in a group of asymptomatic patients, determined by the same method, were used as a reference.


Emergency Department Screening for Hepatitis C Virus: Geographic Reach and Spatial Clustering in Central Alabama.
Hepatitis C virus (HCV) infection is a growing problem, disproportionately affecting those born between 1945 and 1965. Here, we demonstrate the wide geographic reach and surveillance potential of emergency department-based screening and identify areas of elevated HCV infection in central Alabama that were socioeconomically disadvantaged compared with surrounding communities.


The Effect of Patient's Choice of Cognitive Behavioural or Psychodynamic Therapy on Outcomes for Panic Disorder: A Doubly Randomised Controlled Preference Trial.
It remains unclear whether offering psychiatric patients their preferred treatment influences outcomes at the symptom level. To assess whether offering patients with panic disorder with/without agoraphobia (PD/A) a choice between 2 psychotherapies yields superior outcomes to random assignment. In a doubly randomised, controlled preference trial (DRCPT), 221 adults with PD/A were randomly assigned to: choosing panic-focused psychodynamic therapy (PFPP) or panic control treatment (PCT; a form of cognitive behavioural therapy); random assignment to PFPP or PCT; or waiting list control. Primary outcomes were PD/A severity, work status and work absences at post-treatment assessment. Outcomes at post-treatment assessment, 6-, 12-, and 24-month follow-ups were assessed using segmented multilevel linear growth models. At post-treatment assessment, the choice and random conditions were superior to the control for panic severity but not work status/absences. The choice and random conditions did not differ during treatment or follow-up for the primary outcomes. For panic severity, PCT was superior to PFPP during treatment (standardised mean difference, SMD, -0.64; 95% confidence interval, CI, -1.02 to -0.25); PFPP was superior to PCT during follow-up (SMD 0.62; 95% CI 0.27-0.98). There was no allocation by treatment type interaction (SMD -0.57; 95% CI -1.31 to 0.17). Previous studies have found that offering patients their preferred treatment yields small to moderate effects but have not employed designs that could rigorously test preference effects. In this first DRCPT of 2 evidence-based psychotherapies, allowing patients with PD/A to choose their preferred treatment was not associated with improved outcomes. Further DRCPTs are needed.


Corrigendum for "How can social workers be meaningfully involved in palliative care? A scoping review on the prerequisites and how they can be realised in practice".
[This corrects the article DOI: 10.1177/26323524211058895.].


Evaluation of effect of empirical attack-preventive immunotherapies in neuromyelitis optica spectrum disorders: An update systematic review and meta -analysis.
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system, which mainly involves the optic nerve and spinal cord. Frequent relapse can accumulate the degree of disability. At present, the main treatment options are immunosuppressants and blood purification. The first-line immunosuppressants for NMOSD are mainly rituximab (RTX), mycophenolate mofetil (MMF) and azathioprine (AZA). Therefore, we designed this systematic review and meta-analysis to evaluate the safety and effect of the above three drugs in the treatment of NMOSD patients. The following Medical Subject Heading (MeSH) and related entry terms are used to search English literature in PubMed, MEDLINE and CENTRAL databases, respectively. MeSH include: Neuromyelitis optic and Rituximab or Azathioprine or Mycophenolate Mofetil; entry terms include: NMO Spectrum Disorder, NMO Spectrum Disorders, Neuromyelitis Optica (NMO) Spectrum Disorder, Neuromyelitis Optica Spectrum Disorders, Devic Neuromyelitis Optica, Neuromyelitis Optica, Devic, Devic's Disease, Devic Syndrome, Devic's Neuromyelitis Optica, Neuromyelitis Optica (NMO) Spectrum Disorders, CD20 Antibody, Rituximab CD20 Antibody, Mabthera, IDEC-C2B8 Antibody, GP2013, Rituxan, Mycophenolate Mofetil, Mofetil, Mycophenolate, Mycophenolic Acid, Morpholinoethyl Ester, Cellcept, Mycophenolate Sodium, Myfortic, Mycophenolate Mofetil Hydrochloride, Mofetil Hydrochloride, Mycophenolate, RS 61443, RS-61443, RS61443, azathioprine sodium, azathioprine sulfate (note: literature retrieval operators "AND" "OR" "NOT" are used to link MeSH with Entry Terms.) The literature search found a total of 3058 articles about rituximab, mycophenolate mofetil and azathioprine in the treatment of NMOSD, 63 of which were included in this study after a series of screening. 930,933,732 patients with NMOSD were enrolled, who had been treated with MMF, AZA and RTX, respectively. The pooled standardized mean difference (SMD) of EDSS before and after RTX treated was -0.58 (95%CI: -0.72, -0.44) (I2 = 0%, p = 0.477), before and after MMF treated was -0.47 (95%CI: -0.73, -0.21) (I2 = 85.6%, p<0.001), before and after AZA treated was -0.41 (95%CI: -0.60, -0.23) (I2 = 65.4%, p<0.001). there was no significant difference in the effect of the three drugs on reducing EDSS scores (RTX vs MMF, p = 0.522; RTX vs AZA, p = 0.214; MMF vs AZA, p = 0.732). The pooled standardized mean difference (SMD) of ARR before and after RTX treated was -1.45 (95%CI: -1.72, -1.18) (I2 = 72.4%, p<0.001), before and after MMF treated was -1.14 (95%CI: -1.31, -0.97) (I2 = 54.5%, p<0.001), before and after AZA treated was -1.11 (95%CI: -1.39, -0.83) (I2 = 83.4%, p<0.001). RTX significantly reduced ARR compared with the other two drugs (RTX vs MMF, p = 0.039; RTX vs AZA, p = 0.049; MMF vs AZA, p = 0.436). The results of this systematic review and meta-analysis showed that the treatment of NMOSD patients with RTX, MMF and AZA is associated with decreased number of relapses and disability improvement as well, and there was no significant difference in the effect of the three drugs on reducing EDSS scores, but RTX significantly reduced ARR compared with the other two drugs.


Non-random organization of the Biomphalaria glabrata genome in interphase Bge cells and the spatial repositioning of activated genes in cells co-cultured with Schistosoma mansoni.
Biomphalaria glabrata is a major intermediate host for the parasitic trematode Schistosoma mansoni, a causative agent of human schistosomiasis. To decipher the molecular basis of this host-parasite interaction, the Bge embryonic cell line provides a unique in vitro model system to assess whether interactions between the snail and parasite affect the cell and genome biology in either organism. The organization of the B. glabrata genome in Bge cells was studied using image analysis through positioning territories of differently sized chromosomes within cell nuclei. The snail chromosome territories are similar in morphology as well as in non-random radial positioning as those found in other derived protostome and deuterostome organisms. Specific monitoring of four gene loci, piwi, BgPrx, actin and ferritin, revealed non-random radial positioning of the genome. This indicates that specific parts of the snail genome reside in reproducible nuclear addresses. To determine whether exposure to parasite is reflected in genome organization, the interphase spatial positioning of genes was assessed after co-culturing Bge cells with either normal or irradiation attenuated miracidia for 30 min to 24 h. The loci of actin and ferritin, genes that are up-regulated in the snail when subjected to infection, were visualized by fluorescence in situ hybridisation (FISH) and their radial nuclear positions i.e. their position in the interphase nucleus with respect to the nuclear edge/envelope, mapped. Interestingly, large scale gene repositioning correlated to temporal kinetics of gene expression levels in Bge cells co-cultured with normal miracidia while irradiated parasites failed to elicit similar gene expression or gene loci repositioning as demonstrated using the ferritin gene. This indicates that normal but not attenuated schistosomes provide stimuli that evoke host responses that are reflected in the host's nuclear architecture. We believe that this is not only the first time that gene-repositioning studies have been attempted in a mollusc but also demonstrates a parasite influencing the interphase genome organization of its host.


Recurrent chondromyxoid fibroma of the distal femur treated with percutaneous cryoablation.
Chondromyxoid fibroma is a rare, benign tumor of the bone with excellent prognosis but a high rate of recurrence. We report a patient presenting with pain and a history of chondromyxoid fibroma of the distal left femur previously treated with multiple prior curettage and bone graft procedures. Magnetic resonance imaging and histopathology indicated a recurrence of tumor. Due to the small size of the tumor recurrence and challenges associated with prior open surgery, the patient underwent cryoablation of the lesion with computed tomography guidance. Follow-up 18 months later indicated a resolution of pain and improvement on magnetic resonance imaging, and no concerns after 20 months. To our knowledge, this is the first reported case of chondromyxoid fibroma treated with cryoablation. This case suggests cryoablation could be considered in the setting of recurrent chondromyxoid fibroma for local tumor control.


Untangling the confounded relationship between perceiver sex and walker sex on the bistable perception of emotion displaying point-light walkers.
Point-light displays of walking gait carries an assortment of information about the individual and this information is often perceivable to others. Some of these bits of information are entangled, with some facilitating and others inhibiting each other. We sought to untangle the perception of basic threat emotions from sex of the walker and the perceiver, as expressed through the bistable perception of anticipated approaching or withdrawing point-light walkers. Stationary point-light walkers displaying anger or fear were shown to 164 psychology student perceivers, who were told that the walkers would be either walking towards them or walking away from them. Perceivers were asked to identify the displayed emotion for each walker stimulus. Expected walker direction showed no influence on the perception of either emotion, across either sex of the perceivers or walkers. Anger was identified better on male walkers and fear was identified better on female walkers. Female perceivers were able to identify both emotions better than male perceivers, but only when displayed by female walkers. The sex of both the perceiver and the walker interact to influence the perception of basic threat emotions displayed through point-light walking gait, with implications for the development of inter-sexual and intra-sexual group cohesion programs.


Diabetes Distress Is Associated With Future Risk of Progression of Diabetic Nephropathy in Adults With Type 2 Diabetes: A Prospective Cohort Study (Diabetes Distress and Care Registry at Tenri [DDCRT23]).
Our aim in this study was to investigate the prospective association between diabetes distress assessed with Problem Areas in Diabetes (PAID) survey scores at baseline and the subsequent risk of development or progression of diabetic nephropathy in people with type 2 diabetes. Longitudinal data were acquired from 2,845 individuals with type 2 diabetes registered in a Japanese diabetes registry. A Cox proportional hazards model was used to adjust for possible confounders to examine the prospective association between baseline diabetes distress (PAID score ≥40) and the development or progression of albuminuria. Mean patient age, body mass index, and glycated hemoglobin level were 64.8 years, 24.5 kg/m2, and 57.4 mmol/mol (7.5%), respectively. We did not observe a significant association between diabetes distress and the subsequent risk of diabetic nephropathy development from normoalbuminuria to microalbuminuria/macroalbuminuria (multivariable-adjusted hazard ratio [HR]=0.95 over 4.2 years, 95% confidence interval [CI] 0.77 to 1.17, p=0.640); however, we identified a significant association for progression from microalbuminuria to macroalbuminuria (multivariable-adjusted HR=1.34 over 7.0 years, 95% CI 1.01 to 1.80, p=0.045). Stratification by sex revealed a significant association between diabetes distress and the subsequent risk of progressing diabetic nephropathy (HR=1.45, 95% CI 1.06 to 1.98, p=0.019) in males, but not females (HR=1.42, 95% CI 0.95 to 2.14, p=0.087). Diabetes distress at baseline, assessed using the PAID survey, was associated with a subsequent risk of progressing diabetic nephropathy independent of possible confounders in males, but not females, with type 2 diabetes.


[Tuberculous ulcer of the palate. Apropos of a case].
We present a case of orificial tuberculosis in a male of 51, consisting on an ulcer in the pallatum. This diagnosis lead us into finding an advanced active pulmonary tuberculosis which the patient ignored. We want also to emphasize the importance of a correct differential diagnosis regarding oral cavity ulcers, among which we must always keep in mind that tuberculosis is still quite common in our environment, as well as squamous cell carcinoma, reticulum cell sarcoma, eosinophilic granuloma, stomatitis ulceromembranous.