Starvation increases the number of coliform bacteria in the caecum and induces bacterial adherence to caecal epithelium in rats.
To investigate the impact of starvation for 24 and 48 h on the number of coliform bacteria in the caecal contents, on the mucosal adherence of coliform bacteria, and on bacterial translocation in rats. Open prospective study. University departments of surgery and microbiology, Sweden. 46 adult male Sprague-Dawley rats. 19 rats served as controls, and were fed until samples were taken. Six animals were starved for 24 h and another 15 for 48 h, with free access to water, and then anaesthetised before blood, mesenteric lymph nodes (MLN), caecum, and caecal contents were sampled. To verify bacterial translocation in this strain of rats, another six rats underwent controlled haemorrhage for 60 min to reduce the blood pressure to 55 mm Hg mean arterial pressure (MAP). These rats had free access to food and water before haemorrhage but were allowed only water until samples were taken 24 h after haemorrhage. Presence and number of coliform bacteria in samples taken from caecal contents, caecal epithelium, MLN, and blood. Starvation for 24 h increased the number of coliform bacteria (colony forming units (CFU)/g) in the caecal contents 25-fold (p < 0.05). Starvation for 48 h further increased the number by a factor of 100. The number of coliform bacteria that adhered to the caecal epithelium increased 3,000 times in rats that had been starved for 48 h (p < 0.001). There was no significant difference in translocation (as indicated by cultures from MLN) between rats that had been fed and those that had been starved for 48 h. In 4 of the 6 rats that were bled and then starved for 24 h there were signs of bacterial translocation, which was significantly more than the 1/19 in fed rats (p < 0.05). Starvation increases the number of bacteria in the caecal contents and increases bacterial adherence to the caecal epithelium. These changes may contribute to the previously reported increase in bacterial translocation in starved compared wit fed rats that were subjected to stress. The same changes in the gut were observed in animals subjected to haemorrhagic stress in addition to starvation, and in which bacterial translocation was evident.


An uncommon case of fibrolipoma.
Lipoma is a common benign soft-tissue neoplasm derived from mature adipose tissue neoplasm, but its presence in the oral and pharyngeal region is relatively uncommon. Oral lipoma was first described by Roux in 1848 as "yellow epulis." It has an incidence rate of about 1%-4% of all benign oral lesions, with a prevalence rate of about 0.0002%. Fibrolipoma is an extremely rare subtype of lipoma which accounts for 1.6% of all facial lipomas. Specific anatomic locations of occurrence within the oral and maxillofacial region include the parotid region, buccal mucosa, lips, submandibular region, tongue, floor of mouth, and palate. Here, we present fibrolipoma, a very rare subtype of lipoma involving the left retromolar region in a 50-year-old female patient.


Structural study of the relationship between the rate of membrane fusion and the ability of the fusion peptide of influenza virus to perturb bilayers.
The amino-terminal segment of the HA2 protein of influenza virus (fusion peptide) has been identified as an important region for membrane fusion. The wild type virus can fuse to membranes more rapidly at pH 5 than at pH 7.4. It has been demonstrated that there is a relationship between the ability of the peptide to promote the formation of inverted phases and the fusogenicity of the intact virus. In this work, we use small-angle X-ray diffraction to study the mechanism of the structural effect of the peptide, at different pHs, on lipid systems characterized by each having a different spontaneous radius of curvature. The overall results show that the action of the peptide on the polymorphism of the lipid systems investigated is strongly pH-dependent. In particular, a rapid formation of cubic phases at pH 5.0 is observed in the presence of this fusion peptide. The ability of the fusion peptide to promote cubic phases exhibits the same dependence on the pH as does the fusogenicity of the intact virus. It is proposed that the peptide promotes cubic phases at pH 5.0 by changing the kinetics of the lamellar to inverted phase transitions.


[Psychosocial problems and coping with illness by patients with defective healing after facial paralysis].
Twenty patients with defective healing following idiopathic or infection-induced facial paralysis (group 1) and 14 patients with defective healing after excision of an acoustic neuroma and subsequent hypoglossal-facial nerve anastomosis (group 2) were questioned as to their psychosocial conditions. The principle gueries involved the impact of facial impairment on social activities, behavior in public, professional performance and communication, as well as strategies in coping with disfigurement. One third of the patients (with a majority in group 2) experienced stigmatization and a feeling of embarrassment or anxiety in public. Many patients minimized facial expressions and communication in order to hide their paralyses. In particular, patients in group 2 frequently had to change their employment and had great problems in accepting their conditions. Additional problems had with a clinical diagnosis of "acoustic neuroma" involved greater stress and more pronounced social withdrawal than experienced by the patients with idiopathic pareses.


Does a higher frequency of difficult patient encounters lead to lower quality care?
Difficult patient encounters in the primary care office are frequent and are associated with physician burnout. However, their relationship to patient care outcomes is not known. To determine the effect of difficult encounters on patient health outcomes and the role of physician dissatisfaction and burnout as mediators of this effect. A total of 422 physicians were sorted into 3 clusters based on perceived frequency of difficult patient encounters in their practices. Patient charts were audited to assess the quality of hypertension and diabetes management and preventive care based on national guidelines. Summary measures of quality and errors were compared among the 3 physician clusters. Of the 1384 patients, 359 were cared for by high-cluster physicians (those who had a high frequency of difficult encounters), 871 by medium-cluster physicians, and 154 by low-cluster physicians. Dissatisfaction and burnout were higher among physicians reporting higher frequencies of difficult encounters. However, quality of patient care and management errors were similar across all 3 groups. Physician perception of frequent difficult encounters was not associated with worse patient care quality or more medical errors. Future studies should investigate whether other patient outcomes, including acute care and patient satisfaction, are affected by difficult encounters.


Real-time ultrasound guided placement of temporary internal jugular vein catheters: assessment of technical success and complication rates in nephrology practice.
Internal jugular vein (IJV) catheterization is often required to gain access for haemodialysis. Use of ultrasound guidance has reduced the complication rates of this procedure. We hypothesized that nephrologists may perform IJV cannulation with a high technical success and low immediate complication rates under real-time ultrasound guidance. We prospectively analyzed 323 patients (186 male, 137 female) who underwent IJV cannulation with real-time ultrasound guidance. The number of needle punctures, technical success, the time between injection of local anaesthetic and entry into the IJV, and immediate complications were recorded. Patients with a history of multiple catheter insertions, previous difficulties during catheterization, poor compliance, obesity, impaired consciousness, skeletal deformity, disorder of haemostasis were regarded as high-risk group. Cannulation of IJV was achieved in all patients. Of the 323 catheters, 125 (38.7%) were placed in high-risk patients. Average number of puncture was 1.26 (range, 1-4). IJV was entered on the first attempt in 261 (80.8%) patients. Only ten complications (10/323, 3.2%) developed; five (2.5%) in the normal-risk group, and five (4.0%) in the high-risk group. Cannulation of IJV took a longer time in the high-risk group than in the normal-risk group. The number of needle punctures, percent of successful cannulation on the first attempt, and the frequency of complications were similar between the high- and normal-risk groups. Cannulation of IJV under real-time ultrasound guidance is very safe with high technical success rates. Nephrologists can use this technique with ease and with minimal complications in normal- and high-risk patients.


The HUSH complex cooperates with TRIM28 to repress young retrotransposons and new genes.
Retrotransposons encompass half of the human genome and contribute to the formation of heterochromatin, which provides nuclear structure and regulates gene expression. Here, we asked if the human silencing hub (HUSH) complex is necessary to silence retrotransposons and whether it collaborates with TRIM28 and the chromatin remodeler ATRX at specific genomic loci. We show that the HUSH complex contributes to de novo repression and DNA methylation of an SVA retrotransposon reporter. By using naïve versus primed mouse pluripotent stem cells, we reveal a critical role for the HUSH complex in naïve cells, implicating it in programming epigenetic marks in development. Although the HUSH component FAM208A binds to endogenous retroviruses (ERVs) and long interspersed element-1s (LINE-1s or L1s), it is mainly required to repress evolutionarily young L1s (mouse-specific lineages <5 million years old). TRIM28, in contrast, is necessary to repress both ERVs and young L1s. Genes co-repressed by TRIM28 and FAM208A are evolutionarily young, or exhibit tissue-specific expression, are enriched in young L1s, and display evidence for regulation through LTR promoters. Finally, we demonstrate that the HUSH complex is also required to repress L1 elements in human cells. Overall, these data indicate that the HUSH complex and TRIM28 co-repress young retrotransposons and new genes rewired by retrotransposon noncoding DNA.


The effect of neuropeptide Y and peptide YY on electrogenic ion transport in rat intestinal epithelia.
1. Neuropeptide Y (NPY), peptide YY (PYY) and, to a lesser extent, human pancreatic polypeptide (HPP) reduced short-circuit current (SCC) in a concentration-dependent manner in epithelial preparations of rat jejunum and descending colon. 2. From concentration-response curves in the jejunum EC50 values of 3 nM for PYY and 10 nM for NPY were obtained. HPP was much less potent, the threshold concentration being around 100 nM, and NPY 13-36 was inactive. 3. Repeated exposure of jejunal preparations to either NPY or PYY led to a rapid desensitization. Cross-desensitization to the actions of these two peptides was also observed. Neither tetrodotoxin (TTX) nor phentolamine affected responses to either NPY or PYY on the jejunum. 4. Responses to both peptides were inhibited by the presence of transport inhibitors, particularly diphenylamine-2-carboxylate (DPC, a chloride channel blocker) and piretanide (Na+-K+-2Cl- co-transport inhibitor). These results may indicate that the reduction in SCC caused by the neuropeptides is due to a net increase in chloride movement in the apical to basolateral direction. 5. 36Cl-flux studies identified an inhibition of chloride secretion as the predominant mechanism of action of NPY and PYY, together with a smaller stimulation of chloride absorption. No significant changes in the movement of 22Na were seen in either direction. 6. The cyclo-oxygenase inhibitors piroxicam (5 microM) and indomethacin (5 microM) significantly reduced the responses to both NPY and PYY in rat jejunum. From this and other evidence it was concluded that the peptides depended for their effect on the endogenous formation of eicosanoids, the prevention of which attenuated the SCC reduction due to the peptides.


[Submental intubation: surgical and anesthesiological aspects].
In patients with cranio-maxillofacial trauma and in corrections of cranio-facial anomalies submental intubation may be used during surgery and postoperatively. In the period June 2001-May 2002 submental intubation was performed on five patients with cranio-maxillofacial trauma and on two patients with cranio-facial anomalies (Dubowitz syndrome (LeFort II osteotomy and distraction) in one patient and cheilognathopalatoschisis (Le Fort I osteotomy and distraction) in the other). In accordance with the literature the submental intubation technique was a useful, fast and safe technique which provides a secure airway during surgery. No postoperative intubation-related complications were seen in the group of patients. It provides the surgeon with an excellent view of the operation field and permits optimal intra-operative control of the dental occlusion. Combined procedures by the surgeon and the anaesthetist must be planned beforehand.


Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT).
To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis (PsA). One hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug (DMARD) had failed were recruited into this investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial. During the initial blinded portion of the study, patients received infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and 14. After week 16, patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50, while patients initially randomized to infliximab continued to receive active treatment at the same dose through week 50. The primary efficacy outcome was achievement of the American College of Rheumatology 20% criteria for improvement in rheumatoid arthritis (ACR20) at week 16. Additional predefined clinical efficacy assessments included the Psoriasis Area and Severity Index (PASI) score, the ACR50 and ACR70 criteria, the Disease Activity Score in 28 joints, the Health Assessment Questionnaire, ratings of enthesitis and dactylitis, and the Psoriatic Arthritis Response Criteria score. The proportion of infliximab-treated patients who achieved an ACR20 response at week 16 (65%) was significantly higher than the proportion of placebo-treated patients who achieved this response (10%). In addition, 46% of infliximab-treated patients achieved an ACR50 response, and 29% achieved an ACR70 response; no placebo-treated patient achieved these end points. Among patients who had PASI scores of >/=2.5 at baseline, 68% of infliximab-treated patients achieved improvement of >/=75% in the PASI score at week 16 compared with none of the placebo-treated patients. Continued therapy with infliximab resulted in sustained improvement in articular and dermatologic manifestations of PsA through week 50. The incidence of adverse events was similar between the treatment groups. Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis, psoriasis, dactylitis, and enthesitis in patients with active PsA that had been resistant to DMARD therapy. With continued infliximab treatment, benefits were sustained through 50 weeks. The benefit-to-risk ratio appeared favorable in this study population.


[Chronic viral hepatitis and interferons: preliminary results in 60 patients with chronic hepatitis C and cellular mechanism of action].
Interferons exhibit antiviral and immunomodulatory properties. Antiviral effects appear mainly mediated via 2'5' oligoadenylate synthetase and protein kinase proteins which inhibit viral components synthesis. Interferons also influence the immune system through various mechanism among whom an increased expression of HLA class I antigens on hepatocyte plasma membrane and the promotion of natural killer cell activity leading to the clearance of infected hepatocytes. We report the results of various alpha interferon therapeutic regimens in 60 patients with chronic hepatitis C. In our series, 20 patients (33%) achieved a complete response but 78% of them relapsed after therapy withdrawal. Predictors of good response include young age, low serum ALT levels and mild liver injury. On the contrary, cirrhosis is associated with a poorer response.


PsbR, a missing link in the assembly of the oxygen-evolving complex of plant photosystem II.
The oxygen-evolving complex of eukaryotic photosystem II (PSII) consists of three extrinsic nuclear-encoded subunits, PsbO (33 kDa), PsbP (23 kDa), and PsbQ (17 kDa). Additionally, the 10-kDa PsbR protein has been found in plant PSII and anticipated to play a role in water oxidation, yet the physiological significance of PsbR has remained obscure. Using the Arabidopsis psbR mutant, we showed that the light-saturated rate of oxygen evolution is strongly reduced in the absence of PsbR, particularly in low light-grown plants. Lack of PsbR also induced a reduction in the content of both the PsbP and the PsbQ proteins, and a near depletion of these proteins was observed under steady state low light conditions. This regulation occurred post-transcriptionally and likely involves a proteolytic degradation of the PsbP and PsbQ proteins in the absence of an assembly partner, proposed to be the PsbR protein. Stable assembly of PsbR in the PSII core complex was, in turn, shown to require a chloroplast-encoded intrinsic low molecular mass PSII subunit PsbJ. Our results provided evidence that PsbR is an important link in the PSII core complex for stable assembly of the oxygen-evolving complex protein PsbP, whereas the effects on the assembly of PsbQ are probably indirect. The physiological role of the PsbR, PsbP, and PsbQ proteins is discussed in light of their peculiar expression in response to growth light conditions.


Machine learning based on biomarker profiles identifies distinct subgroups of heart failure with preserved ejection fraction.
The lack of effective therapies for patients with heart failure with preserved ejection fraction (HFpEF) is often ascribed to the heterogeneity of patients with HFpEF. We aimed to identify distinct pathophysiologic clusters of HFpEF based on circulating biomarkers. We performed an unsupervised cluster analysis using 363 biomarkers from 429 patients with HFpEF. Relative differences in expression profiles of the biomarkers between clusters were assessed and used for pathway over-representation analyses. We identified four distinct patient subgroups based on their biomarker profiles: cluster 1 with the highest prevalence of diabetes mellitus and renal disease; cluster 2 with oldest age and frequent age-related comorbidities; cluster 3 with youngest age, largest body size, least symptoms and lowest N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels; and cluster 4 with highest prevalence of ischaemic aetiology, smoking and chronic lung disease, most symptoms, as well as highest NT-proBNP and troponin levels. Over a median follow-up of 21 months, the occurrence of death or heart failure hospitalization was highest in clusters 1 and 4 (62.1% and 62.8%, respectively) and lowest in cluster 3 (25.6%). Pathway over-representation analyses revealed that the biomarker profile of patients in cluster 1 was associated with activation of inflammatory pathways while the biomarker profile of patients in cluster 4 was specifically associated with pathways implicated in cell proliferation regulation and cell survival. Unsupervised cluster analysis based on biomarker profiles identified mutually exclusive subgroups of patients with HFpEF with distinct biomarker profiles, clinical characteristics and outcomes, suggesting different underlying pathophysiological pathways.


Effects of prepartum supplementation of linoleic and mid-oleic sunflower seed on cow performance, cow reproduction, and calf performance from birth through slaughter, and effects on intake and digestion in steers.
Two experiments were conducted to determine the effects of sunflower seed supplements with varying fatty acid profiles on performance, reproduction, intake, and digestion in beef cattle. In Exp. 1, 127 multiparous spring-calving beef cows with free-choice access to bermudagrass hay were individually fed 1 of 3 supplements for an average of 83 d during mid to late gestation. Supplements (DM basis) included 1) 1.23 kg/d of a soybean hull-based supplement (control treatment); 2) 0.68 kg/d of linoleic sunflower seed plus 0.23 kg/d of the control supplement (linoleic treatment); and 3) 0.64 kg/d of mid-oleic sunflower seed plus 0.23 kg/d of the control supplement (oleic treatment). During the first 62 d of supplementation, the BW change was 11, 3, and -3 kg for cows fed the control, linoleic, and oleic supplements, respectively (P < 0.001). No difference in BW change was observed during the subsequent period (-65 kg, P = 0.83) or during the entire 303-d experiment (-31 kg, P = 0.49). During the first 62 d of supplementation, cows fed sunflower supplements tended (P = 0.08) to lose more body condition than cows fed the control diet, but BCS was not different (P > 0.22) for any subsequent measurement. At the beginning of the breeding season, the percentage of cows exhibiting luteal activity was greater for cows fed the control diet (43%; P = 0.02) than for cows fed either linoleic (20%) or oleic (16%) supplementation; however, first-service conception rate (67%; P = 0.22) and pregnancy rate at weaning (92%; P = 0.18) were not different among supplements. No differences were detected in calf birth (P = 0.46) or weaning BW (P = 0.74). In Exp. 2, 8 ruminally cannulated steers were used to determine the effects of sunflower seed supplementation on forage intake and digestion. Treatments (DM basis) included 1) no supplement; 2) a soybean hull-based supplement fed at 0.29% of BW/d; 3) whole linoleic sunflower seed fed at 0.16% of BW/d; and 4) whole high-oleic sunflower seed fed at 0.16% of BW/d. Hay intake was not influenced (P = 0.25) by supplement (1.51% of BW/d); however, DMI was greatest (P < 0.01) for steers fed the soybean hull-based supplement (1.93% of BW/d). Sunflower seed supplementation reduced (P < 0.01) NDF and ADF digestibility while increasing (P < 0.01) apparent CP and apparent lipid digestibility. In conclusion, whole sunflower seed supplementation resulted in reduced cow BW gain during mid to late gestation, but this reduction did not influence subsequent cow BW change, pregnancy rate, or calf performance.


Two-photon cross-correlation analysis of intracellular reactions with variable stoichiometry.
We successfully demonstrate the effectiveness of two-photon fluorescence cross-correlation spectroscopy (TPCCS) to study the complex binding stoichiometry of calmodulin (CaM) and Ca(2+)/CaM-dependent protein kinase II (CaMKII). Practical considerations are made for developing an intracellular cross-correlation assay, including characterization of the fluorescent molecules involved, calibration procedures of the setup, and optimal measurement conditions. Potential pitfalls and artifacts are discussed, and the complex stoichiometry of the molecular system is accounted for by a new experimental and theoretical framework for TPCCS. Our tailored model accommodates up to 12 red-labeled CaMs binding to a single green-labeled dodecameric CaMKII holoenzyme and accounts for the probability distributions of bound ligand as well as the respective changes in fluorescence emission upon binding. The model was experimentally demonstrated both in solution and in living cells by analyzing the binding of Alexa 633(C2)CaM to eGFP-CaMKII under different biochemical conditions known to induce the basal, activated, and autophosphorylated forms of the enzyme. Key binding parameters, such as binding degree, concentrations of reactants, and binding affinities, were determined under varying conditions with certain assumptions. TPCCS thus offers the unique ability to test our biochemical understanding of protein dynamics in the intracellular milieu.


The role of TNC in atherosclerosis and drug development opportunities.
Tenascin C (TNC), a rich glycoprotein of the extracellular matrix, exhibits a pro-atherosclerosis or anti-atherosclerosis effect depending on its location. TNC, especially its C domain/isoform (TNC-C), is strongly overexpressed in atherosclerotic plaque active areas but virtually undetectable in most normal adult tissues, suggesting that TNC is a promising delivery vector target for atherosclerosis-targeted drugs. Many delivery vectors were investigated by recognizing TNC-C, including G11, G11-iRGD, TN11, PL1, and PL3. F16 and FNLM were also investigated by recognizing TNC-A1 and TNC, respectively. Notably, iRGD was undergoing clinical trials. PL1 not only recognizes TNC-C but also the extra domain-B (EDB) of fibronectin (FN), which is also a promising delivery vector for atherosclerosis-targeted drugs, and several conjugate agents are undergoing clinical trials. The F16-conjugate agent F16IL2 is undergoing clinical trials. Therefore, G11-iRGD, PL1, and F16 have great development value. Furthermore, ATN-RNA and IMA950 were investigated in clinical trials as therapeutic drugs and vaccines by targeting TNC, respectively. Therefore, targeting TNC could greatly improve the success rate of atherosclerosis-targeted drugs and/or specific drug development. This review discussed the role of TNC in atherosclerosis, atherosclerosis-targeted drug delivery vectors, and agent development to provide knowledge for drug development targeting TNC.


Role of lysine187 within the second extracellular loop of the type A cholecystokinin receptor in agonist-induced activation. Use of complementary charge-reversal mutagenesis to define a functionally important interdomain interaction.
Activation of guanine nucleotide-binding protein (G protein)-coupled receptors is believed to involve conformational change that exposes a domain for G protein coupling at the cytosolic surface of the helical confluence, although the mechanisms for achieving this are not well understood. This conformational change can be achieved by docking a diverse variety of agonist ligands, known to occur by interacting with different regions of these receptors. In this study, we focus on the importance of a specific basic residue (Lys187) within the second extracellular loop of the receptor for the peptide hormone, cholecystokinin. Alanine-replacement and charge-reversal mutagenesis of this residue showed that it had no effect on the binding of natural peptide and nonpeptidyl ligands of this receptor but markedly interfered with agonist-stimulated signaling. It was demonstrated that this negative effect on biological activity could be eliminated with the truncation of the first 30 residues of the amino-terminal tail of this receptor. Complementary charge-reversal mutagenesis of each of the five conserved acidic residues within this region of the receptor in the presence of the charge-reversed Lys187 revealed that only the Asp5 mutant fully reversed the negative functional impact of the Lys187 charge reversal. Thus, we have demonstrated that a basic residue within the second extracellular loop of the cholecystokinin receptor interacts with a specific acidic residue within the amino terminus of this receptor. This residue-residue interaction is nicely accommodated within a new molecular model of the agonist-occupied cholecystokinin receptor.


Cystic parotomegaly in an HIV-seropositive patient. A case report.
The case of a middle-aged woman with a 1-year history of painless, bilateral parotid gland enlargement is reported. The clinical signs and immunological markers of Sjögren's syndrome were absent. Serology for human immunodeficiency virus (HIV) was positive and radiological findings were characteristic of a well-described, HIV-associated cystic parotomegaly. Attention of clinicians is drawn to this clinical presentation, which may precede classic AIDS stigmata by several years.


Trends in body mass index distribution and prevalence of thinness, overweight and obesity in two cohorts of Surinamese South Asian children in The Netherlands.
Asians have a smaller muscle mass and a larger fat mass at the same body mass index (BMI) than most other ethnic groups. Due to a resulting higher cardiometabolic risk, the BMI cut-offs for overweight and obesity were lowered for adults. For Asian children universal criteria apply. The objectives of this study were to determine the normal BMI distribution and assess the BMI class distribution in a reference cohort of affluent South Asian children born before the obesity epidemic and to assess the influence of the obesity epidemic on the distributions. Historical cohort study with 4350 measurements of height and weight of two cohorts (born 1974-1976 and 1991-1993) of Surinamese South Asian children living in The Netherlands, analysed with WHO Child Growth References and International Obesity Task Force (IOTF) BMI cut-offs. The reference cohort 1974-1976 was significantly lighter (BMI Z-score=-0.63; 95% CI -0.69 to -0.58) and more variable (SD=1.19) than WHO reference. Total thinness prevalence was exceptionally high, both in cohort 1974-1976 (WHO 38.3%; IOTF 36.4%) and 1991-1993 (WHO 23.6%; IOTF 23.9%). Overweight and obesity prevalences were low in the reference cohort (WHO respectively 6.0% and 2.1%; IOTF 5.3%, 0.9%), but much higher in cohort 1991-1993 (WHO 13.6%, 9.1%; IOTF 11.7%, 6.0%). The low mean BMI Z-score and high prevalence of thinness are likely expressions of the characteristic body composition of South Asians. Universal BMI cut-offs should be applied carefully in South Asian populations as thinness prevalence is likely to be overestimated and obesity underestimated. The development of ethnic specific cut-offs is recommended.


A possible physiological basis for ocular dominance.
An experiment is undertaken to investigate the relationship between "sighting" and motor dominance. A review of recent work on the neurophysiology of vision is carried out and an attempt to explain ocular dominance using this is made.


Seizure Duration and Hemodynamic State During Electroconvulsive Therapy: Sodium Thiopental Versus Propofol.
General anesthesia is required for Electroconvulsive Therapy (ECT) and it is usually provided by a hypnotic agent. The seizure duration is important for the treatment, and it is usually accompanied by severe hemodynamic changes. The aim of this study was to compare the effects of sodium thiopental versus Propofol on seizure duration and hemodynamic variables during ECT. A number of 100 patient-sessions of ECT were included in this randomized clinical trial. The initial hemodynamic state of each patient was recorded. Anesthesia was induced by Sodium thiopental in the 1st group and with Propofol in 2nd group. All the patients received the muscle relaxant succinylcholine. The hemodynamic variables after seizure and seizure duration were recorded. The data were analyzed through SPSS 20 and independent t-test. P<0.05 was considered significant. The mean duration of seizure in the sodium thiopental group was significantly longer than the Propofol group (40.3±16.6 sec versus 32±11.3 sec) (P=0.001). There was no statistically significant difference between the mean energy level applied in the two groups (20.5±3.81 joules in the sodium thiopental versus 20.2±3.49 joules in the Propofol group). The mean systolic and diastolic blood pressure at all times after seizure and mean heart rate at 3 and 5 minutes after seizure were significantly lower in Propofol than sodium thiopental groups. Propofol provides a more stable hemodynamic state for the ECT procedures, and its use is highly preferred over sodium thiopental in patients with cardiovascular disease.


A cross-species approach for the identification of Drosophila male sterility genes.
Male reproduction encompasses many essential cellular processes and interactions. As a focal point for these events, sperm offer opportunities for advancing our understanding of sexual reproduction at multiple levels during development. Using male sterility genes identified in human, mouse, and fruit fly databases as a starting point, 103 Drosophila melanogaster genes were screened for their association with male sterility by tissue-specific RNAi knockdown and CRISPR/Cas9-mediated mutagenesis. This list included 56 genes associated with male infertility in the human databases, but not found in the Drosophila database, resulting in the discovery of 63 new genes associated with male fertility in Drosophila. The phenotypes identified were categorized into six distinct classes affecting sperm development. Interestingly, the second largest class (Class VI) caused sterility despite apparently normal testis and sperm morphology suggesting that these proteins may have functions in the mature sperm following spermatogenesis. We focused on one such gene, Rack 1, and found that it plays an important role in two developmental periods, in early germline cells or germline stem cells and in spermatogenic cells or sperm. Taken together, many genes are yet to be identified and their role in male reproduction, especially after ejaculation, remains to be elucidated in Drosophila, where a wealth of data from human and other model organisms would be useful.


Editorial: Climate Change and the Spread of Vector-Borne Diseases, Including Dengue, Malaria, Lyme Disease, and West Nile Virus Infection.
The major health threats from climate change include increasing temperatures, air pollution, extreme weather events, changes in the spread of infectious diseases, antimicrobial resistance, emerging pathogens, and an increase in vector-borne disease. Between October and December 2023, in 200 medical journal, epidemiologists, clinicians, healthcare policymakers, and journal editors published an emergency call to action to health professionals, the United Nations, and political leaders on climate change and its effects on the ecosystem and human health. Also, in December 2023, the Intergovernmental Panel on Climate Change (IPCC) published its sixth Assessment Report (AR6) that summarizes current knowledge, impacts, and health risks from climate change, as well as suggestions for mitigation and adaptation. For over a decade, the IPCC has reported that the prevalence of vector-borne diseases has increased and highlighted the importance of monitoring dengue, malaria, Lyme disease, West Nile virus infection, and other vector-borne diseases. This editorial aims to provide an update on the association between climate change and the spread of vector-borne diseases and highlights the urgent need for public health and disease prevention and treatment strategies to control the rise in vector-borne diseases.


Adequacy of a food composition database to estimate fat and fatty acid intake.
This work examined the adequacy of the only food composition database available in Croatia to estimate fat and fatty acid intake. A 7-day food record with 39 participants was carried out. In addition to Croatian food composition tables (FCT1), the Swedish food tables (FCT2) were used to convert food records into quantities of total fat and saturated, monounsaturated and polyunsaturated fatty acids, respectively. The subjects simultaneously collected duplicates of all consumed food. The chemical analysis of duplicates to determine total fat and fatty acids included extraction of fat, followed by methylation of fatty acids and GC analysis. According to the comparison of methods, FCT2 are a better predictor of fat and fatty acid intake than FCT1 because of their closer agreement with analysed values. The correlation coefficients imply that both food tables estimate most of these nutrients similarly to a reference method. However, food records combined with either of the food tables could not predict intake of polyunsaturated fatty acids by men. In order to improve applicability of FCT1 in dietary surveys concerned with fat and fatty acids, the next issue should include changes in respect to an identified systematic error, as well as a greater choice of food items and their varieties. Accuracy of food records based on FCT1 could further be increased with subjects giving details on recipe ingredients, analysis of missing foods, etc.


Posterior Reversible Encephalopathy Syndrome (PRES).
Emergency medicine residents of all levels. Posterior reversible encephalopathy syndrome (PRES) is a clinically significant cause of seizures, headache, neurologic deficit, and hypertensive emergency that is not uncommon in the emergency department. Posterior reversible encephalopathy syndrome was initially described as a clinical syndrome in 1996.1 It is an important cause of hypertensive emergency that is not often covered in depth in the emergency medicine curriculum since the true incidence and disease process continues to be researched.Populations who are at most risk for PRES include those with chronic hypertension, chronic renal disease, autoimmune disease, and immune suppression.2 Patients with PRES will often present with varied forms of encephalopathy and sometimes even focal neurologic symptoms that would suggest a cerebral vascular accident. These neurologic symptoms can include visual complaints and headache. Seizures are also frequently reported in association with PRES.3Early identification and appropriate management of PRES decreases morbidity and mortality without chronic neurologic sequelae. The pillars of diagnosis and management can be initiated in the emergency department. This includes a diagnosis made by a thorough history and physical exam and cerebral imaging.4 The mainstay of management is parenteral anti-hypertensives with proper blood pressure monitoring.5. By the end of the simulation, the learner will be able to: 1) manage an acute seizure 2) discuss imaging modalities to diagnose PRES 3) discuss medical management of PRES. This simulation exercise is meant to be presented as a traditional medium-to-high-fidelity medical simulation case. With minor adjustments, it could be utilized as a low-fidelity case or an oral exam case. The educational content and general usefulness of this simulation was evaluated by open verbal (qualitative) feedback from a convenience sample of random participants following a completion of the case and debriefing by a participant group (n=30) of emergency medicine residents at a large 3-year residency training program. The overall feedback was positive. Participants felt that it was a good opportunity to practice identifying PRES and managing it in a safe learning environment. They especially appreciated learning more about the pathophysiology of PRES, the high-risk factors for PRES, and management of the condition. Posterior reversible encephalopathy syndrome, an uncommon condition, presents similar to many other benign and common complaints. It is crucial to be able to differentiate PRES from other causes of headache, visual disturbance, and seizures. It is important to keep PRES in mind when considering hypertensive emergencies. Many PGY-1 residents struggled to diagnose and treat PRES because it was often not on their differential, and this case helped broaden their differential. PGY-2 and PGY-3 were more frequently able to appropriately diagnose and treat PRES in this patient but found the case to be helpful in their decision-making and learning more about PRES pathophysiology. This case and associated high-yield debriefing session were effective for learners of all levels. Posterior reversible encephalopathy syndrome (PRES), altered mental status, seizure, headache, hypertensive emergency.


[Early detection of diabetic nephropathy].
Due to the unfavorable prognosis of advanced stages of diabetic nephropathy (DN), the ideal approach is to identify renal involvement as early as possible. It is recommended to measure urinary albumin excretion (UAE) annually, in random urine samples, in order to detect the stages of DN [microalbuminuria (UAE 17-174 mg/l or 30-300 mg albumin/g of creatinine) and macroalbuminuria (> 174 mg/l or > 300 mg/g)]. However, it has been suggested that UAE levels below the threshold of consensus could already signal the risk for DN progression and increased mortality, indicating the need to revise cutoff values. As a substantial amount of UAE (the immunounreactive fraction), is not detected by conventional methods, HPLC would be more sensitive to identify the presence of damage by measuring total UAE (immunoreactive + immunounreactive). Another recent observation is that diminished glomerular filtration rates (GFR) occurs in the presence of normoalbuminuria. Therefore, besides evaluating UAE, it is recommended to estimate GFR with equations employing creatinine; such as the Modification of Diet in Renal Disease (MDRD) study, available at www.mdrd.com. Owing to the known limitations of creatinine, alternative endogenous markers are being studied, and cystatin-C is a promising marker under investigation. Finally, new strategies that could detect DN even earlier, include biomarkers such as proteomics, defining a profile of urinary protein excretion able to identify the subsequent risk of renal disease.


Robust neutralization assay based on SARS-CoV-2 S-protein-bearing vesicular stomatitis virus (VSV) pseudovirus and ACE2-overexpressing BHK21 cells.
The global pandemic of coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable neutralization assay is very important for the development of vaccines and novel drugs. In this study, a G protein-deficient vesicular stomatitis virus (VSVdG) bearing a truncated spike protein (S with C-terminal 18 amino acid truncation) was compared to that bearing the full-length spike protein of SARS-CoV-2 and showed much higher efficiency. A neutralization assay was established based on VSV-SARS-CoV-2-Sdel18 pseudovirus and hACE2-overexpressing BHK21 cells (BHK21-hACE2 cells). The experimental results can be obtained by automatically counting the number of EGFP-positive cells at 12 h after infection, making the assay convenient and high-throughput. The serum neutralizing titer measured by the VSV-SARS-CoV-2-Sdel18 pseudovirus assay has a good correlation with that measured by the wild type SARS-CoV-2 assay. Seven neutralizing monoclonal antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 S protein were obtained. This efficient and reliable pseudovirus assay model could facilitate the development of new drugs and vaccines.


Circulating galectin-3 promotes metastasis by modifying MUC1 localization on cancer cell surface.
Adhesion of circulating tumor cells to the blood vessel endothelium is a critical step in cancer metastasis. We show in this study that galectin-3, the concentration of which is greatly increased in the circulation of cancer patients, increases cancer cell adhesion to macrovascular and microvascular endothelial cells under static and flow conditions, increases transendothelial invasion, and decreases the latency of experimental metastasis in athymic mice. These effects of galectin-3 are shown to be a consequence of its interaction with cancer-associated MUC1, which breaks the "protective shield" of the cell-surface MUC1 by causing MUC1 polarization, leading to exposure of smaller cell-surface adhesion molecules/ligands including CD44 and ligand(s) for E-selectin. Thus, the interaction in the bloodstream of cancer patients between circulating galectin-3 and cancer cells expressing MUC1 bearing the galectin-3 ligand TF (Galbeta1,3GalNAc-) promotes metastasis. This provides insight into the molecular regulation of metastasis and has important implications for the development of novel therapeutic strategies for prevention of metastasis.


Left inferior frontal activations depending on the canonicity determined by the argument structures of ditransitive sentences: an MEG study.
To elucidate the relationships between syntactic and semantic processes, one interesting question is how syntactic structures are constructed by the argument structure of a verb, where each argument corresponds to a semantic role of each noun phrase (NP). Here we examined the effects of possessivity [sentences with or without a possessor] and canonicity [canonical or noncanonical word orders] using Japanese ditransitive sentences. During a syntactic decision task, the syntactic structure of each sentence would be constructed in an incremental manner based on the predicted argument structure of the ditransitive verb in a verb-final construction. Using magnetoencephalography, we found a significant canonicity effect on the current density in the left inferior frontal gyrus (IFG) at 530-550 ms after the verb onset. This effect was selective to canonical sentences, and significant even when the precedent NP was physically identical. We suggest that the predictive effects associated with syntactic processing became larger for canonical sentences, where the NPs and verb were merged with a minimum structural distance, leading to the left IFG activations. For monotransitive and intransitive verbs, in which structural computation of the sentences was simpler than that of ditransitive sentences, we observed a significant effect selective to noncanonical sentences in the temporoparietal regions during 480-670 ms. This effect probably reflects difficulty in semantic processing of noncanonical sentences. These results demonstrate that the left IFG plays a predictive role in syntactic processing, which depends on the canonicity determined by argument structures, whereas other temporoparietal regions would subserve more semantic aspects of sentence processing.


Postcoital bleeding due to cervical endometriosis.
Endometriosis of the uterine cervix is a rare lesion that is generally asymptomatic in gynaecological practice. We present a case with postcoital bleeding due to a cervical mass mimicking cervical polyp or fibroma which was histologically proven as cervical endometriosis later. Cervical endometriosis should be considered in the differential diagnosis of cervical masses with postcoital bleeding.


Population Structure of mtDNA Variation due to Pleistocene Fluctuations in the South American Maned Wolf (Chrysocyon brachyurus, Illiger, 1815): Management Units for Conservation.
The maned wolf (Chrysocyon brachyurus) is one of the largest South American canids, and conservation across this charismatic carnivore's large range is presently hampered by a lack of knowledge about possible natural subdivisions which could influence the population's viability. To elucidate the phylogeographic patterns and demographic history of the species, we used 2 mtDNA markers (D-loop and cytochrome b) from 87 individuals collected throughout their range, in Argentina, Bolivia, Brazil, and Uruguay. We found moderate levels of haplotype and nucleotide diversity, and the 14 D-loop haplotypes were closely related. Genetic structure results revealed 4 groups, and when coupled with model inferences from a coalescent analysis, suggested that maned wolves have undergone demographic fluctuations due to changes in climate and habitat during the Pleistocene glaciation period approximately 24000 years before present (YBP). This genetic signature points to an event that occurred within the timing estimated for the start of the contraction of the Cerrado around 50000 YBP. Our results reveal a genetic signature of population size expansion followed by contraction during Pleistocene interglaciations, which had similar impacts on other South American mammals. The 4 groups should for now be considered management units, within which future monitoring efforts should be conducted independently.


[In vitro activities of levofloxacin and other antibiotics against fresh clinical isolates].
In this study, the in vitro activity of levofloxacin (LVFX) against 1,020 fresh bacterial clinical isolates was compared with the activities of a range of ofloxacin, ciprofloxacin (CPFX), ampicillin (ABPC), cefaclor, cefpodoxime, methicillin and benzylpenicillin. The clinical isolates except Vibrio cholerae were collected in Japan during 1998 from patients with infectious diseases. MICs were determined using the agar dilution method according to the recommendations by the Japan Society of Chemotherapy. Some isolates of methicillin resistant Staphylococcus aureus (MRSA) and coagulase negative Staphylococcus were resistant to fluoroquinolones, but the MIC50 of LVFX against MRSA was 6.25 micrograms/ml. LVFX was the most active against MRSA among the antibiotics tested. Most of Staphylococcus epidermidis strains were susceptible to the fluoroquinolones. LVFX showed greater activity against all streptococci strains compared with fluoroquinolones tested. In particular, all Streptococcus pneumoniae strains including PRSP were susceptible to LVFX at < or = 1.56 micrograms/ml. Among Enterococcus, ABPC showed superior activity against Enterococcus faecalis but many isolates of Enterococcus species were resistant to ABPC. LVFX was more active against to these Enterococcus species compared with other fluoroquinolones. On the other hand, LVFX and CPFX showed similar activity against isolates of Enterobacteriaceae. CPFX had an MIC50/90 of 0.20, 0.39 microgram/ml and LVFX showed an MIC50/90 of 0.78, 1.56 micrograms/ml against Pseudomonas aeruginosa. LVFX (MIC50/90 0.10, 0.20 microgram/ml) was more active against Acinetobacter species than CPFX (MIC50/90 0.10, 0.39 microgram/ml). Haemophilus influenzae, Branhamella (Moraxella) catarrhalis and V. cholerae were inhibited by low concentration of the fluoroquinolones tested. The MIC90 of LVFX and CPFX were < or = 0.10 microgram/ml against above three species. Some isolates of Neisseria gonorrhoeae and Campylobacter species were moderately resistant to the fluoroquinolones tested but the MIC50 of LVFX and CPFX were < or = 0.39 microgram/ml. Among anaerobes, Propionibacterium acnes was more susceptible than Peptostreptococcus species, and the MIC90 of beta-lactams and fluoroquinolones tested were < or = 0.78 microgram/ml. In conclusion, this study, performed on large number of strains, confirmed an excellent and wide spectrum antibacterial activity of LVFX compared with the fluoroquinolones and beta-lactams tested. And our results suggest that LVFX may be useful in the treatment of various bacterial infections.


Presence of specific 11C-meta-Hydroxyephedrine retention in heart, lung, pancreas, and brown adipose tissue.
(11)C-meta-Hydroxyephedrine (HED) is used in cardiac PET as an index of norepinephrine (NE) reuptake transporter (NET) density and synaptic NE levels. Whereas cardiac uptake is well documented, tracer retention in other tissues with rich noradrenergic innervation is unclear. Dysfunctional sympathetic nervous system (SNS) function in extracardiac metabolic storage tissues (i.e., adipose tissue and skeletal muscle) and endocrine organs contributes to several disorders. The aim of this study was to determine the potential of HED as an index of NE function in brown adipose tissue, lung, pancreas, skeletal muscle, and kidney by identifying NET-specific retention and determining the presence of radiolabeled metabolites. Male Sprague-Dawley rats were administered HED and sacrificed at 30 min after tracer injection. Tissues were rapidly excised and counted for radioactivity, and relative tracer retention was quantified. Pretreatment with NET inhibitors established specific HED accumulation. The effect of elevated NE was tested by subcutaneous minipump NE infusion or inhibition of monoamine oxidase. Column-switch high-performance liquid chromatography (HPLC) was used to analyze the presence of radiolabeled metabolites in heart, brown adipose tissue, pancreas, and plasma. NET-specific retention was observed in heart, brown adipose tissue, lung, and pancreas but not in liver, skeletal muscle, or kidney. A dose-dependent response of HED accumulation to treatments elevating NE levels was established in tissues exhibiting specific uptake. At 30 min after tracer administration, HPLC analysis revealed 93%-95% of total radioactivity signal derived from unchanged HED in heart, pancreas, and brown adipose tissue compared with 61% +/- 8% unchanged HED in plasma. In addition to the heart, lung, pancreas, and brown adipose tissue exhibit specific and NE-responsive uptake of HED, supporting the potential for novel PET studies of SNS integrity in these tissues.


Long-term persistence of humoral and cellular immune responses induced by an AS03A-adjuvanted H1N1 2009 influenza vaccine: an open-label, randomized study in adults aged 18-60 years and older.
This manuscript presents data on the persistence of Hemagglutination Inhibition (HI) immune response against the A/California/7/2009 strain, six and 12 mo after adults received one dose (n = 138) or two doses (n = 102; 21 d apart) of a 3.75 µg Hemagglutinin antigen AS03-adjuvanted H1N1 2009 vaccine (NCT00968526). Two hundred forty subjects (18-60 y: 120;>60 y: 120) were vaccinated. Immunogenicity end points were based on the European licensure criteria for pandemic influenza vaccines. Exploratory analyses assessed the cell-mediated immune response (CMI) up to Month 12 and the influence of previous influenza vaccination on persistence of immune response. At Month 6, the CHMP criteria were met in subjects aged 18-60 y who received one or two vaccine doses and in subjects aged>60 y who received two vaccine doses. At Month 12, the CHMP criteria were met only in subjects aged 18-60 y who received two vaccine doses. Persistence of HI immune response against the vaccine strain was higher in subjects without prior influenza vaccination. Exploratory analyses showed that two doses of the H1N1 2009 vaccine induced persistence of H1N1-specific CD4+ T cells up to Month 6 and memory B cells up to Month 12. In conclusion, HI immune responses persisted up to 12 mo after vaccination with one-dose and two-dose regimens of the AS03-adjuvanted 3.75 µg HA H1N1 2009 pandemic influenza vaccine, although not all three CHMP guidance criteria for both groups were met at Month 6 and Month 12. The CD4+ T cell and B cell responses also persisted up to Month 12.


Disseminated tumour cells from the bone marrow of early breast cancer patients: Results from an international pooled analysis.
Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients. In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06-1.43, p = 0.006), 1.30 (95% CI: 1.12-1.52, p < 0.001) and 1.30 (95% CI: 1.08-1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68-2.16; p = 0.512). DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy.


Twitter as a tool for communication and knowledge exchange in academic medicine: A guide for skeptics and novices.
Twitter is a tool for physicians to increase engagement of learners and the public, share scientific information, crowdsource new ideas, conduct, discuss and challenge emerging research, pursue professional development and continuing medical education, expand networks around specialized topics and provide moral support to colleagues. However, new users or skeptics may well be wary of its potential pitfalls. The aims of this commentary are to discuss the potential advantages of the Twitter platform for dialogue among physicians, to explore the barriers to accurate and high-quality healthcare discourse and, finally, to recommend potential safeguards physicians may employ against these threats in order to participate productively.


The PTEN-Akt pathway impacts the integrity and composition of mitotic centrosomes.
Loss of the tumor suppressor PTEN is observed in many human cancers that display increased chromosome instability and aneuploidy. The subcellular fractions of PTEN are associated with different functions that regulate cell growth, invasion and chromosome stability. In this study, we show a novel role for PTEN in regulating mitotic centrosomes. PTEN localization at mitotic centrosomes peaks between prophase and metaphase, paralleling the centrosomal localization of PLK-1 and γ-tubulin and coinciding with the time frame of centrosome maturation. In primary keratinocytes, knockdown of PTEN increased whole-cell levels of γ-tubulin and PLK-1 in an Akt-dependent manner and had little effect on recruitment of either protein to mitotic centrosomes. Conversely, knockdown of PTEN reduced centrosomal levels of pericentrin in an Akt-independent manner. Inhibition of Akt activation with MK2206 reduced the whole-cell and centrosome levels of PLK-1 and γ-tubulin and also prevented the recruitment of PTEN to mitotic centrosomes. This reduction in centrosome-associated proteins upon inhibition of Akt activity may contribute to the increase in defects in centrosome number and separation observed in metaphase cells. Concomitant PTEN knockdown and Akt inhibition reduced the frequency of metaphase cells with centrosome defects when compared with MK2206 treatment alone, indicating that both PTEN and pAkt are required to properly regulate centrosome composition during mitosis. The findings presented in this study demonstrate a novel role for PTEN and Akt in controlling centrosome composition and integrity during mitosis and provide insight into how PTEN functions as a multifaceted tumor suppressor.


Visual-perceptual training with acquisition of the observed motor pattern contributes to greater improvement of visual anticipation.
This experiment investigated the contribution of visual and additive motor experience to improvement of visual anticipation. Club cricket batters were randomized into (a) a visual-perceptual group that received temporal occlusion training (n = 13), (b) a visuomotor group that received temporal occlusion training coupled with motor pattern practice of the observed bowler's action (n = 13), and (c) a no-training control group (n = 13). They completed a fast bowler video-based temporal occlusion prepost anticipation test, as well as a transfer temporal occlusion test that included different fast and slow bowlers. Results indicated visual-perceptual and visuomotor groups equally improved pick up of advance cues across prepost tests. Additive motor pattern practice for the visuomotor group facilitated superior anticipation through earlier pick up of advance information across the transfer tests. No improvement was found for the control group. The findings indicate that visual and combined motor experience facilitates learning, but additive motor experience facilitates superior transfer. Findings have implications for theoretical and applied knowledge to develop anticipation skill. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Heparan sulphate sulphotransferase. Properties of an enzyme from ox lung.
A heparan sulphate sulphotransferase was partially purified from an ox lung homogenate by (NH(4))(2)SO(4) precipitation. Various glycosaminoglycans were assayed as sulphate acceptors with this enzyme. The highest acceptor activity was obtained with desulphated heparin and heparan sulphate, which indicates that sulphate transfer may be to free amino groups of the substrate. Some heparan sulphate was (35)S-labelled by incubation with the enzyme and re-isolated. On treatment of this heparan [(35)S]sulphate with nitrous acid and separation of the degradation products on Sephadex G-15, a major peak of radioactivity was obtained, and identified as [(35)S]sulphate by high-voltage electrophoresis at pH5.3. The [(35)S]sulphate is believed to be derived from N-[(35)S]sulphated groups of heparan [(35)S]-sulphate. That the ox lung preparation contained an N-sulphotransferase was confirmed by the isolation of 2-deoxy-2-[(35)S]sulphoamino-d-glucose as the major product from the flavobacterial degradation of heparan [(35)S]sulphate.


Time-restricted feeding schedules modify temporal variation of gentamicin experimental nephrotoxicity.
The effect of timing of gentamicin dosing relative to food access periods was evaluated in experimental animals. Female Sprague-Dawley rats were treated for 4 and 10 days with gentamicin (40 mg/kg of body weight/day) intraperitoneally at either 0700, 1300, 1900, or 0100 h according to three food presentation schedules: food was available from 0800 to 1600 h in the first group, from 1600 to 0000 h in the second group, and from 0000 to 0800 h in the last group. Animals were thus subjected to a restricted feeding period. Results indicate that time-restricted feeding schedules displace the peak and the trough of gentamicin-induced renal toxicity, as evaluated by changes in the inhibition of sphingomyelinase activity, cellular regeneration (incorporation of [3H]thymidine into DNA of renal cortex), and blood urea nitrogen and serum creatinine levels, as well as histopathological lesions observed after 10 days of treatment. In fact, the toxicity was minimal when gentamicin was injected during the feeding period, while the maximal toxicity was found when gentamicin was administered during the fasting period. It is concluded that the feeding period can modulate aminoglycoside nephrotoxicity. The time of dosing of gentamicin relative to the time of feeding seems to be a more important modulator of gentamicin nephrotoxicity than the light-dark cycle.


Potential effect of revising the CDC surveillance case definition for AIDS.
The Centers for Disease Control (CDC) revised the surveillance case definition for acquired immunodeficiency syndrome (AIDS) in August, 1987. To determine the impact of this revision, information was extracted from the medical charts of the 630 patients receiving comprehensive medical care as of 1980 at 6 haemophilia treatment centres, and who were therefore likely to have been infected with human immunodeficiency virus (HIV). 38 (6%) and 47 (7%) met the 1985 and 1987 case definitions, respectively (22% increase). Of the cases added by use of the 1987 case definition, 3 patients had HIV dementia, 3 had Pneumocystis carinii pneumonia (2 of whom were presumptively diagnosed and 1 who had been receiving steroids and immunosuppressives), and 3 had HIV wasting syndrome. These data suggest that the revision of the AIDS case definition will have a substantial impact on future AIDS surveillance trends in persons with haemophilia and perhaps in other risk groups.


Template-based fabrication of nanowire-nanotube hybrid arrays.
The fabrication and structure characterization of ordered nanowire-nanotube hybrid arrays embedded in porous anodic aluminum oxide (AAO) membranes are reported. Arrays of TiO(2) nanotubes were first deposited into the pores of AAO membranes by a sol-gel technique. Co nanowires were then electrochemically deposited into the TiO(2) nanotubes to form the nanowire-nanotube hybrid arrays. Scanning electron microscopy and transmission electron microscopy measurements showed a high nanowire filling factor and a clean interface between the Co nanowire and the TiO(2) nanotube. Application of these hybrids to the fabrication of ordered nanowire arrays with highly controllable geometric parameters is discussed.


Distinct Contributions of CD18 Integrins for Binding and Phagocytic Internalization of Pseudomonas aeruginosa.
Phagocytosis is the key mechanism for host control of Pseudomonas aeruginosa, a motile Gram-negative, opportunistic bacterial pathogen which frequently undergoes adaptation and selection for traits that are advantageous for survival. One such clinically relevant adaptation is the loss of bacterial motility, observed within chronic infections, that is associated with increased antibiotic tolerance and phagocytic resistance. Previous studies using phagocytes from a leukocyte adhesion deficiency type 1 (LAD-I) patient identified CD18 as a putative cell surface receptor for uptake of live P. aeruginosa However, how bacterial motility alters direct engagement with CD18-containing integrins remains unknown. Here we demonstrate, with the use of motile and isogenic nonmotile deletion mutants of two independent strains of P. aeruginosa and with CRISPR-generated CD18-deficient cell lines in human monocytes and murine neutrophils, that CD18 expression facilitates the uptake of both motile and nonmotile P. aeruginosa However, unexpectedly, mechanistic studies revealed that CD18 expression was dispensable for the initial attachment of the bacteria to the host cells, which was validated with ectopic expression of complement receptor 3 (CR3) by CHO cells. Our data support that surface N-linked glycan chains (N-glycans) likely facilitate the initial interaction of bacteria with monocytes and cooperate with CD18 integrins in trans to promote internalization of bacteria. Moreover, talin-1 and kindlin-3 proteins promote uptake, but not binding, of P. aeruginosa by murine neutrophils, which supports a role for CD18 integrin signaling in this process. These findings provide novel insights into the cellular determinants for phagocytic recognition and uptake of P. aeruginosa.


Efficacy of two Staphylococcus aureus phage cocktails in cheese production.
Staphylococcus aureus is one of the most prevalent pathogenic bacteria contaminating dairy products. In an effort to reduce food safety risks, virulent phages are investigated as antibacterial agents to control foodborne pathogens. The aim of this study was to compare sets of virulent phages, design phage cocktails, and use them in a cocktail to control pathogenic staphylococci in cheese. Six selected phages belonging to the three Caudovirales families (Myoviridae, Siphoviridae, Podoviridae) were strictly lytic, had a broad host range, and did not carry genes coding for virulence traits in their genomes. However, they were sensitive to pasteurization. At MOI levels of 15, 45, and 150, two anti-S. aureus phage cocktails, each containing three phages, one from each of the three phage families, eradicated a 10(6)CFU/g S. aureus population after 14 days of Cheddar cheese curd ripening at 4°C. The use of these phages did not trigger over-production of S. aureus enterotoxin C. The use of phage cocktails and their rotation may prevent the emergence of phage resistant bacterial strains.


Factors influencing local recurrence of cancer after partial mastectomy.
From 1957 to 1975, 291 patients underwent partial mastectomy for carcinoma of the breast. In a follow-up period of 6 to 25 years, 32 patients had local recurrences. These 32 were matched with 32 patients without local recurrence but who had had the same treatment during the same periods of time for the same clinical stage of disease. Comparisons were made for age of the patient, family history, size of tumor, proximity of tumor to line of resection, involvement of lymph nodes, and prophylactic radiation. The average age of the patients with recurrence was 7 years less than those without, and the incidence of nodal involvement was three times as high in those with local recurrence as in those without. These were the only factors that showed any significant difference between the two groups. When axillary dissection is done in patients treated by partial mastectomy, valuable information is obtained about the likelihood of local recurrence.


The non-invasive assessment of stroke volume and cardiac output by impedance cardiography: a review.
Impedance cardiography (IC) is an inexpensive, reliable and noninvasive technique for determining stroke volume (SV) and cardiac output (CO). It relies on the measurement of phasic changes in transthoracic electrical resistivity, related to ejection of blood into the ascending aorta with each heart beat. Because of its non-invasive nature, IC is becoming increasingly used in clinical settings, as well as in many areas of physiological research. This paper discusses IC in terms of its theoretical basis, the components of the impedance signal and how impedance data is mathematically processed. One of the major controversies surrounding IC concerns how well it compares with conventional methods of determining SV and CO, such as thermodilution. A literature review of such comparative studies demonstrated that the controversy is far from settled, but that IC is generally agreed to be capable of accurately monitoring trends in cardiovascular dynamics. The question of accuracy of IC in terms of absolute values of SV and CO remains to be determined. The methodological limitations, accuracy, reliability and reproducibility of IC are examined, as are some of the methods developed to improve these aspects of the technique. The application and utility of IC in aerospace medicine research is also addressed.


Geospatial analysis and participant characteristics associated with colorectal cancer screening participation in Alberta, Canada: a population-based cross-sectional study.
Colorectal cancer (CRC) is a leading cause of death in Canada and early detection can prevent deaths through screening. However, CRC screening in Alberta, Canada remains suboptimal and varies by sociodemographic and health system characteristics, as well as geographic location. This study aimed to further the understanding of these participant and health system characteristics associated with CRC screening in Alberta and identify clusters of regions with higher rates of overdue or unscreened individuals. We included Albertans aged 52 to 74 as of December 31, 2019 (index date) and we used data from administrative health data sources and linked to the Alberta Colorectal Cancer Screening Program database to determine colorectal cancer screening rates. We used multivariable multinomial logistic regression analysis to investigate the relationship between sociodemographic, health system characteristics and participation in CRC screening. We used optimized Getis-Ord Gi* hot-spot analysis to identify hot and cold-spots in overdue for and no record of CRC screening. We included 919,939 Albertans, of which 65% were currently up to date on their CRC screening, 21% were overdue, and 14% had no record of CRC screening. Compared to Albertans who were currently up to date, those who were in older age groups, those without a usual provider of care, those who were health system non-users, and those living in more deprived areas were more likely to have no record of screening. Areas with high number of Albertans with no record of screening were concentrated in the North and Central zones. Our study showed important variation in colorectal cancer screening participation across sociodemographic, health system and geographical characteristics and identified areas with higher proportions of individuals who have no record of screening or are under-screened in Alberta, Canada.


Citalopram (antidepressant) administration causes sexual dysfunction in male mice through RF-amide related peptide in the dorsomedial hypothalamus.
Citalopram is the most potent selective serotonin reuptake inhibitor (SSRI) which is used as an antidepressant but causes sexual dysfunction. Whether citalopram induced sexual dysfunction is a result of gonadotropin-releasing hormone (GnRH), kisspeptin or RF-amide related peptide (RFRP) alteration is unknown. In this study, we tested mice for sexual behavior after vehicle (0.9% NaCl) and citalopram treatment (5 mg/kg) daily for 1 day (acute) and 21 or 28 days (chronic). Effects of acute and chronic treatments on neuronal numbers and mRNA expression of GnRH, kisspeptin and RFRP were measured. In addition, RFRP fiber projections to preoptic (POA)-GnRH neurons were analyzed using double-label immunohistochemistry. The expression of 14 different serotonin receptor types mRNA was examined in immunostained laser dissected single RFRP neurons in the dorsomedial hypothalamus (DMH), however only 11 receptors types were identified. Acute citalopram treatment did not affect sexual behavior, whereas, the total duration of intromission was reduced with chronic treatment. There was no effect in the expression of kisspeptin (neuronal numbers and mRNA) in the anteroventral periventricular nucleus and the arcuate nucleus and expression of GnRH (neuronal numbers and mRNA) in the POA after citalopram treatment. However, RFRP neuronal numbers in the DMH and fiber projections to the POA were significantly increased after chronic citalopram treatment, which suggests citalopram induced inhibition of sexual behavior involves the modulation of RFRP through serotonin receptors in the DMH.


[Suppression of DNA synthesis in lymphocytes by UV-irradiated plasma].
The autologous plasma, isolated upon UV-irradiation of the whole blood, has an inhibitory effect on mitogen-induced, blastogenesis of human lymphocytes. Its addition to the culture medium results in a statistically significant suppression of DNA synthesis in lymphocytes in the presence of phytohemagglutinin and concanavalin A. No such effect was observed with the use of pokeweed mitogen. Our studies show that this phenomenon is associated with photoconversion of the plasma components.


Phthalate esters on urban airborne particles: Levels in PM10 and PM2.5 from Mexico City and theoretical assessment of lung exposure.
Endocrine disrupting chemicals (EDCs) from the environment are associated with reproductive abnormalities (i.e. decreased sperm concentration; increased endometriosis) and alterations of the cardiovascular system (i.e. increased blood pressure and risk of coronary disease). Some phthalates esters have been identified as EDCs, for which inhalation is considered as one of the routes of exposure. However, only little is known regarding inhalational exposure to EDCs via urban airborne particles. In the present study, we report the monthly concentration of 8 phthalate esters measured in PM10 and PM2.5 collected and recovered during 7 months in a highly populated area of Mexico City. Using the levels of PM10 and PM2.5 reported by the automatized network of environmental monitoring of Mexico City for the sampling site, we estimated exposure levels for people of different ages and gender. Two endocrine disrupting compounds, the phthalate esters DEHP and DnBP, were found on the particles in higher concentrations during the warmer months of the year. The highest concentration was reported for DEHP (229.7μg/g of particles) in PM2.5 collected in May 2013. After calculations of the DEHP concentration in the atmosphere, and using the respiratory flow rate, we determined males were potentially exposed to larger quantities of DEHP, reaching up to 18ng/8h in April 2013. Despite the concentrations of phthalates seem to be rather small, a comprehensive characterization of its presence is necessary in order to evaluate the overall exposure to these compounds, providing a clear view of exposure on children, adolescents and pregnant women.


Role of vasopressin in acutely altered baroreflex sensitivity during hemorrhage in rats.
Experiments were performed to examine the potential role of circulating arginine vasopressin (AVP) on baroreflex sensitivity during hypotensive and nonhypotensive hemorrhage in the conscious rat. Animals were chronically instrumented for measurement of cardiac output, blood pressure, and heart rate (HR). Three potential stimuli for release of AVP were utilized: 1) rapid 20% arterial hemorrhage that resulted in hypotension, 2) nonhypovolemic hypotension induced by intravenous infusion of nitroprusside, and 3) nonhypotensive hemorrhage (rapid 10% arterial blood withdrawal). Hypotensive hemorrhage was associated with significant reductions in blood pressure, cardiac output, HR, and calculated total peripheral resistance, an increase in baroreflex (BRR) bradycardia in response to pressor infusions of phenylephrine, and a moderate elevation in circulating AVP. Prior intravenous administration of a specific V1-vasopressinergic antagonist augmented the hypotensive response to hemorrhage; however, neither V1- nor V2-blockade affected hemorrhage-induced augmentation of the BRR. Inducement of hypotension by infusion of nitroprusside did not alter subsequent BRR sensitivity. Finally, nonhypotensive hemorrhage was associated with an increase in resting HR and augmented BRR sensitivity. However, in contrast to hypotensive hemorrhage, either V1- or V2-antagonism attenuated the increase in BRR sensitivity seen with 10% hemorrhage. These data suggest that, although AVP may play a role in blood pressure maintenance via its direct vasoconstrictor actions during hypotensive hemorrhage, the observed augmentation of BRR sensitivity associated with severe blood loss is not attributable to a vasopressinergic mechanism activated by circulating AVP. However, blood-borne AVP may contribute to BRR sensitivity alterations in response to mild blood loss.


Fenofibrate lowers blood pressure in salt-sensitive but not salt-resistant hypertension.
Peroxisome proliferator-activated receptor α agonists reduce blood pressure in rodents, but clinical trials provide conflicting data regarding their effects in humans. We tested the hypothesis that the effect of fenofibrate on blood pressure depends on salt sensitivity. Thirty-one hypertensive volunteers (17 salt-resistant, 14 salt-sensitive) completed a randomized, crossover, double-blind protocol with three dietary phases: low salt diet (10 mmol/day) followed by two consecutive high salt diets (200 mmol/day), each for 6 days. During high salt, volunteers were randomized to fenofibrate 160 mg/day or placebo. Hemodynamic and metabolic parameters were measured on the last morning of each treatment arm. Fenofibrate reduced triglycerides similarly in salt-sensitive and salt-resistant volunteers. Fenofibrate did not affect blood pressure in salt-resistant volunteers. In salt-sensitive volunteers, fenofibrate significantly decreased diastolic (P = 0.02 versus placebo) and mean arterial (P = 0.04 versus placebo) blood pressure during high salt. In all volunteers, the decrease in systolic pressure during fenofibrate correlated inversely with the salt sensitivity of mean arterial pressure as a continuous variable. Fenofibrate significantly decreased heart rate, plasma renin activity, and renal vascular resistance during high salt in salt-sensitive volunteers, but not salt-resistant volunteers. Fenofibrate did not affect sodium excretion or weight gain during high salt. The effect of salt intake and fenofibrate on plasma and urine epoxyeicosatrienoic acid concentrations differed in salt-resistant and salt-sensitive volunteers. Fenofibrate reduces blood pressure, heart rate and renal vasoconstriction in salt-sensitive volunteers, but not in salt-resistant volunteers. These findings have implications for the treatment of hyperlipidemia in hypertensive individuals.


Phylodynamic analysis and molecular diversity of the avian infectious bronchitis virus of chickens in Brazil.
Avian infectious bronchitis virus (IBV) is the etiological agent of a highly contagious disease, which results in severe economic losses to the poultry industry. The spike protein (S1 subunit) is responsible for the molecular diversity of the virus and many sero/genotypes are described around the world. Recently a new standardized classification of the IBV molecular diversity was conducted, based on phylogenetic analysis of the S1 gene sequences sampled worldwide. Brazil is one of the biggest poultry producers in the world and the present study aimed to review the molecular diversity and reconstruct the evolutionary history of IBV in the country. All IBV S1 gene sequences, with local and year of collection information available on GenBank, were retrieved. Phylogenetic analyses were carried out based on a maximum likelihood method for the classification of genotypes occurring in Brazil, according to the new classification. Bayesian phylogenetic analyses were performed with the Brazilian clade and related international sequences to determine the evolutionary history of IBV in Brazil. A total of 143 Brazilian sequences were classified as GI-11 and 46 as GI-1 (Mass). Within the GI-11 clade, we have identified a potential recombinant strain circulating in Brazil. Phylodynamic analysis demonstrated that IBV GI-11 lineage was introduced in Brazil in the 1950s (1951, 1917-1975 95% HPD) and population dynamics was mostly constant throughout the time. Despite the national vaccination protocols, our results show the widespread dissemination and maintenance of the IBV GI-11 lineage in Brazil and highlight the importance of continuous surveillance to evaluate the impact of currently used vaccine strains on the observed viral diversity of the country.


Multi-Electrode Alpha tACS During Varying Background Tasks Fails to Modulate Subsequent Alpha Power.
Transcranial alternating-current stimulation (tACS) for entraining alpha activity holds potential for influencing mental function, both in laboratory and clinical settings. While initial results of alpha entrainment are promising, questions remain regarding its translational potential-namely if tACS alpha entrainment is sufficiently robust to context and to what extent it can be upscaled to multi-electrode arrangements needed to direct currents into precise brain loci. We set out to explore these questions by administering alternating current through a multi-electrode montage (mtACS), while varying background task. A multi-electrode analog of previously employed anterior/posterior stimulation failed to replicate the reported alpha entrainment, suggesting that further work is required to understand the scope of applicability of tACS alpha entrainment.


N-nitrosamines in grass silages.
During the fermentation of silages from nitrate-rich grass, the conditions are suitable for the formation of N-nitrosamines. Earlier investigations had shown that only low concentrations of volatile N-nitrosamines were formed. The first ten days of ensilage were investigated. The formation of nitrite was accompanied by the formation of volatile N-nitrosamines. NDMA and NDEA were detected in concentrations of up to about 2 micrograms/kg. After stabilisation of the silage, these concentrations dropped to about 0.6 microgram/kg. Preliminary results are presented concerning the presence of non-volatile N-nitroso compounds. The method of Walters et al. (1980) indicates that non-volatile N-nitroso compounds were present in amounts equivalent to 85 mg NPIP/kg sample.


Monitoring Analysis of Perfluoroalkyl Substances and F-53B in Bottled Water, Tea and Juice Samples by LC-MS/MS.
Monitoring analysis of 14 per- and polyfluoroalkyl substances (PFAS), 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (F-53B) and dodecafluoro-3H-4,8-dioxanonanoate (ADONA) in bottled drinking water, tea and juice samples was performed using LC coupled with tandem mass spectrometry (LC-MS/MS) and solid-phase extraction (SPE). In the electrospray negative ion mode, the limit of detection and limit of quantification (LOQ) values were 0.1 to 0.8 ng/mL and 0.2 to 1.6 ng/mL, respectively. The calibration curves were linear from LOQ to 50 ng/mL (r2 > 0.999). The SPE procedure (Presep PFC-II) was utilized for sample preparation and recovery rates for three standards (35, 70 and 140 ng/L) were 80.4-118.8% with relative standard deviation (RSD) ≤ 0.6%. Using the developed method, various samples (n = 54) from Japanese markets were investigated for PFAS and F-53B contamination, and values below the LOQ were observed. It is concluded that for monitoring products in the Japanese market, our method represents a significant improvement over complex techniques for the quantification of PFAS and related compounds from various foods.


The pyruvic acid analog 3-bromopyruvate interferes with the tetrazolium reagent MTS in the evaluation of cytotoxicity.
3-Bromopyruvate (3BrPA) is a pyruvate analog known for its alkylating property. Recently, several reports have documented the antiglycolytic and anticancer effects of 3BrPA and its potential for therapeutic applications. 3BrPA-mediated cytotoxicity has been evaluated in vitro by various methods including tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)-based assays such as MTT, MTS, and so on. However, growing body of evidences has shown that tetrazolium reagent may interfere with the test compounds. In this study, we investigated whether the tetrazolium reagent interferes with the assessment of 3BrPA cytotoxicity. The results of the tetrazolium-based MTS assay were compared with 3 distinct cell viability detection methods, that is, Trypan Blue staining, ATP depletion, and Annexin V staining in 2 different cell lines, Vx-2 and HepG2. The MTS assay data showed false positive results by indicating increased cell viability at 1 mM and 2 mM 3BrPA whereas the other cell viability assays demonstrated that both Vx-2 and HepG2 cells are not viable at the same treatment conditions. In order to validate the direct interaction of 3BrPA with MTS reagent, we tested cell-free media incubated with different concentrations of 3BrPA. The results of cell-free media showed an increase in absorbance in a dose-dependent manner confirming the interaction of MTS with 3BrPA. Thus, our data clearly demonstrate that 3BrPA interferes with the accuracy of MTS-based cytotoxicity evaluation. Hence, we suggest that employing multiple methods of biochemical as well as morphological cytotoxicity assays is critical to evaluate 3BrPA-mediated cell death.


Treatment of calculi in the upper ureter with extracorporeal shock wave lithotripsy.
Sixty-six symptomatic primary stones in the upper ureter were treated using extracorporeal shock wave lithotripsy (ESWL). All patients underwent preprocedural cystoscopy for stone manipulation and 27 of the patients had the stones dislodged proximally. The stone-free success rate for this group of dislodged stones was 93 per cent. Of 39 ureteral stones treated in situ (impacted), 33 patients were rendered stone-free at three months. Three stones in this group failed to disintegrate and required surgical treatment. Complications of ESWL were minimal. ESWL of upper ureteral stones is an effective noninvasive, noncontact method of treatment. Successful stone manipulation increased the stone-free rate, yet impacted stones disintegrated and passed in 85 per cent of treatments. Lithotripsy of small renal stones prior to migration and proximal ureteral stones early in the symptomatic course may significantly alter the incidence of distal ureteral calculi requiring hospitalization, cystoscopy or ureteroscopy.


Trends in cancer mortality rates among migrants in Australia: 1981-2007.
Previous studies have shown that migrants have lower cancer mortality rates compared to the Australian-born population, particularly for colorectal and breast cancers, which are associated with an affluent lifestyle. This study seeks to update knowledge in this field by examining mortality from colorectal, stomach, lung, melanoma, breast and bladder cancers, as well as all cancers combined between 1981 and 2007. Data were obtained from the Australian Bureau of Statistics. Average annual age and sex-standardised mortality rates were calculated for each region of birth, period of death registration and cancer site. Generally, mortality rates declined over the study period for most conditions for the majority of migrant groups. Notable exceptions included migrants from South Eastern Europe and Eastern Europe who experienced a significant increase in mortality due to all cancers combined and Australian-born individuals who recorded a significant increase in mortality due to melanoma of the skin. Migrants generally had more favourable cancer mortality outcomes, particularly for colorectal cancer and melanoma. Migrants from Southern Europe, South Eastern Europe, Chinese Asia and Southern Asia had the greatest advantage. However, migrants displayed higher rates of stomach, lung and bladder cancers than the Australian-born population. The migrant advantage can in part be explained by the protective effects of diet, lifestyle and reproductive behaviours. Possible explanations for why some migrants display greater mortality from stomach and bladder cancer include the consumption of abrasive, salted and preserved foods and higher rates of smoking. Greater emphasis should be placed on targeting at-risk migrant groups through screening and education programs at migrant resource centres and community groups. The study calls for further research to explain the observed trends, which has the potential to uncover important risk and protective factors.


Artificial breakwaters as garbage bins: Structural complexity enhances anthropogenic litter accumulation in marine intertidal habitats.
Coastal urban infrastructures are proliferating across the world, but knowledge about their emergent impacts is still limited. Here, we provide evidence that urban artificial reefs have a high potential to accumulate the diverse forms of litter originating from anthropogenic activities around cities. We test the hypothesis that the structural complexity of urban breakwaters, when compared with adjacent natural rocky intertidal habitats, is a driver of anthropogenic litter accumulation. We determined litter abundances at seven sites (cities) and estimated the structural complexity in both urban breakwaters and adjacent natural habitats from northern to central Chile, spanning a latitudinal gradient of ∼15° (18°S to 33°S). Anthropogenic litter density was significantly higher in coastal breakwaters when compared to natural habitats (∼15.1 items m(-2) on artificial reefs versus 7.4 items m(-2) in natural habitats) at all study sites, a pattern that was temporally persistent. Different litter categories were more abundant on the artificial reefs than in natural habitats, with local human population density and breakwater extension contributing to increase the probabilities of litter occurrence by ∼10%. In addition, structural complexity was about two-fold higher on artificial reefs, with anthropogenic litter density being highest at intermediate levels of structural complexity. Therefore, the spatial structure characteristic of artificial reefs seems to enhance anthropogenic litter accumulation, also leading to higher residence time and degradation potential. Our study highlights the interaction between coastal urban habitat modification by establishment of artificial reefs, and pollution. This emergent phenomenon is an important issue to be considered in future management plans and the engineering of coastal ecosystems.


Evaluation of oxidative stress and antioxidant status in diabetic and hypertensive women during labor.
Pregnancy in insulin-dependent diabetes mellitus is associated with a greater incidence of fetal abnormality. Animal studies suggested that increased free-radical production and antioxidant depletion may contribute to this risk. The objective of this work was to evaluate oxidative stress and antioxidant capacity in hypertensive, diabetics, and healthy control women during labor. Simultaneous determination of antioxidant enzymes activities, namely glutathione peroxidase (GSH-Px), glutathione reductase (GSH-red), superoxide dismutase (SOD), total antioxidant, and lipid peroxides measured as thiobarbituric acid-reactive substances (TBARS) levels, were carried out in maternal plasma during labor. Plasma GSH-Px activity was found to be significantly increased as it doubled in hypertensive, and diabetic women when compared with healthy control women (P < 0.05). In contrast, plasma SOD activity was significantly decreased in both groups when compared to the control group (P < 0.05). No significant differences were detected in GSH-Red activity between diabetic, hypertensive and control groups. Alterations in antioxidant enzyme activities were accompanied by a significant increase in the levels of plasma lipid peroxides in hypertensive and diabetic women during labor. Plasma levels of total antioxidants were significantly increased in diabetic women as compared with the control group. Based on our results, it may be concluded that enhanced generation of oxidative stress causes alteration of antioxidant capacity in diabetic and hypertensive women during labor. Alterations in antioxidant and prooxidant components may result in various complications including peroxidation of vital body molecules which may be regarded as an increased risk factor for pregnant women as well as the fetus.


DNase-seq predicts regions of rotational nucleosome stability across diverse human cell types.
DNase-seq is primarily used to identify nucleosome-depleted DNase I hypersensitive (DHS) sites genome-wide that correspond to active regulatory elements. However, ≈ 40 yr ago it was demonstrated that DNase I also digests with a ≈ 10-bp periodicity around nucleosomes matching the exposure of the DNA minor groove as it wraps around histones. Here, we use DNase-seq data from 49 samples representing diverse cell types to reveal this digestion pattern at individual loci and predict genomic locations where nucleosome rotational positioning, the orientation of DNA with respect to the histone surface, is stably maintained. We call these regions DNase I annotated regions of nucleosome stability (DARNS). Compared to MNase-seq experiments, we show DARNS correspond well to annotated nucleosomes. Interestingly, many DARNS are positioned over only one side of annotated nucleosomes, suggesting that the periodic digestion pattern attenuates over the nucleosome dyad. DARNS reproduce the arrangement of nucleosomes around transcription start sites and are depleted at ubiquitous DHS sites. We also generated DARNS from multiple lymphoblast cell line (LCL) samples. We found that LCL DARNS were enriched at DHS sites present in most of the original 49 samples but absent in LCLs, while multi-cell-type DARNS were enriched at LCL-specific DHS sites. This indicates that variably open DHS sites are often occupied by rotationally stable nucleosomes in cell types where the DHS site is closed. DARNS provide additional information about precise DNA orientation within individual nucleosomes not available from other nucleosome positioning assays and contribute to understanding the role of chromatin in gene regulation.


Prescribing for comorbid disease in a palliative population: focus on the use of lipid-lowering medications.
The balance of benefit versus burden of ongoing treatments for comorbid disease in palliative populations as death approaches needs careful consideration given their particular susceptibility to adverse drug effects. To provide descriptive data regarding the medications being prescribed to patients who have a life-limiting illness at the time of referral to a palliative care service in regional Australia, with particular focus on lipid-lowering medications. A prospective case note review of 203 patients reporting the number of medications prescribed and, for lipid-lowering medications, the indication and level of prevention sought (primary, secondary, tertiary). Rates were compared by performance status, disease phase and comorbidity burden. Mean number of regular medications prescribed was 7.2, with higher rates observed in those patients with a non-malignant primary diagnosis (rate ratio 1.28, confidence interval (CI) 1.11-1.50) or poorer performance status (rate ratio 1.37, CI 1.11-1.69) and lower rates for those in the terminal phase of disease (rate ratio 0.48, CI 0.30-0.76). Over one fifth of patients were prescribed a lipid-lowering medication, and two fifths of these prescriptions were for primary prevention of cardiovascular disease. Patients in the highest quartile of Charlson Comorbidity Index score were 4.6 (CI 2.06-10.09) times more likely to be prescribed a lipid-lowering medication than those in the lowest quartile. Polypharmacy is prevalent for this group of patients, placing them at high risk of drug-drug and drug-host interactions. Prescribing may be driven by risk factors and disease guidelines rather than a rational, patient-centred approach.


Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis.
Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the peptidyl-tRNA in the P site and play a critical role in promoting the synthesis of polyproline peptides. Using misacylated Pro-tRNAPhe and Phe-tRNAPro, we show that the imino acid proline and not tRNAPro imposes the primary eIF5A requirement for polyproline synthesis. Though most proline analogs require eIF5A for efficient peptide synthesis, azetidine-2-caboxylic acid, a more flexible four-membered ring derivative of proline, shows relaxed eIF5A dependency, indicating that the structural rigidity of proline might contribute to the requirement for eIF5A. Finally, we examine the interplay between eIF5A and polyamines in promoting translation elongation. We show that eIF5A can obviate the polyamine requirement for general translation elongation, and that this activity is independent of the conserved hypusine modification on eIF5A. Thus, we propose that the body of eIF5A functionally substitutes for polyamines to promote general protein synthesis and that the hypusine modification on eIF5A is critically important for poor substrates like proline.