How do we forecast tomorrow's transfusion: Infectious safety?
Continuous improvement has led to a very high degree of microbial safety of transfusion. Four issues are likely to impact the future of this safety. There will be further advances in the efficacy and efficiency of donation testing and pathogen reduction, increasing safety and hopefully eliminating unnecessary procedures. While system failures have been essentially eliminated, there will be ongoing, unpredictable issues that are inevitable. Emerging infections are likely the greatest concern and will continue, although advances in science and technology will permit increasingly rapid responses to outbreaks. Finally, the practice of transfusion may eventually impact safety as usage of blood is reduced and perhaps as alternatives to conventional blood components are developed.


Racial differences in low natriuretic peptide levels: Implications for heart failure clinical trials.
Some patients with heart failure (HF) have low natriuretic peptide (NP) levels. It is unclear whether specific populations are disproportionately excluded from participation in randomized clinical trials (RCT) with inclusion requirements for elevated NPs. We investigated factors associated with unexpectedly low NP levels in a cohort of patients hospitalized with HF, and the implications on racial diversity in a prototype HF RCT. We created a retrospective cohort of 31,704 patients (age 72 ± 16 years, 49% female, 52% Black) hospitalized with HF from 2010 to 2020 with B-type natriuretic peptide (BNP) measurements. Factors associated with unexpectedly low BNP levels (<50 pg/mL) were identified using multivariable logistic regression models. We simulated patient eligibility for a prototype HF trial using specific inclusion and exclusion criteria, and varying BNP cut-offs. Unexpectedly low BNP levels were observed in 8.9% of the cohort. Factors associated with unexpectedly low BNP levels included HFpEF (aOR 3.76, 95% CI: 3.36, 4.20), obesity (aOR 1.96, 95% CI: 1.73, 2.21), self-identification as Black (aOR 1.53, 95% CI: 1.36, 1.71), and male gender (aOR 1.45, 95% CI: 1.31, 1.60). Applying limited clinical inclusion and exclusion criteria from PARAGLIDE-HF disproportionately excluded Black patients, with impairment in renal function having the greatest impact. Adding thresholds for BNP of ≥35, ≥50, ≥67, ≥100, and ≥150 pg/mL demonstrated the risk of exclusion was higher for Black compared to non-Black patients (RR = 2.03 [95% CI: 1.73, 2.39], 1.90 [95% CI: 1.68, 2.15], 1.63 [95% CI: 1.48, 1.81], 1.38 [95% CI: 1.28, 1.50], and 1.23 [95% CI: 1.15, 1.31], respectively). Nearly 10% of patients hospitalized with HF have unexpectedly low BNP levels. Simulating inclusion into a prototype HFpEF RCT demonstrated that requiring increasingly elevated NP levels disproportionately excludes Black patients.


Isolation and characterization of Pseudomonas brassicacearum J12 as an antagonist against Ralstonia solanacearum and identification of its antimicrobial components.
A bacterial strain, J12, isolated from the rhizosphere soil of tomato plants strongly inhibited the growth of phytopathogenic bacteria Ralstonia solanacearum. Strain J12 was identified as Pseudomonas brassicacearum based on its 16S rRNA gene sequence. J12 could produce 2,4-diacetylphloroglucinol (2,4-DAPG), hydrogen cyanide (HCN), siderophore(s) and protease. The maximum growth and antagonistic activity were recorded at 30°C and pH 8. Glucose and tryptone were used as the most suitable carbon and nitrogen sources, respectively. Strain J12 significantly suppressed tomato bacteria wilt by 45.5% in the greenhouse experiment. The main antimicrobial compound of J12 was identified as 2,4-diacetylphloroglucinol (2,4-DAPG) by HPLC-ESI-MS analysis. The gene cluster phlACBD, which is responsible for 2,4-DAPG production, was identified and expressed in the bacterial strain Escherichia coli DH5α.


Development of immunodiagnostic tools for in situ investigation of Ovis aries papillomavirus 3 (OaPV3).
Cutaneous squamous cell carcinoma (cSCC) is a malignant lesion characterized by proliferation and transformation of keratinocytes in the epidermis and infiltrating derma. cSCC is reported in domestic and wild animal species, worldwide. The occurrence and development of cSCC rely on synergic multifactorial conditions, most importantly sunlight exposure and Papillomavirus (PV) infection. In sheep, the development of such lesions represents a threat both to animal welfare and milk production. Ovis aries papillomavirus 3 (OaPV3) is the main cSCC viral determinant and oncogenic properties of viral E6 and E7 proteins were preliminarily investigated. However, E6 and E7 role and mechanisms resulting in cSCC have not been fully clarified, mainly due to the lack specific immunological tools, such as antibodies for in situ detection of ovine papillomavirus. This paper reports the development of specific serological tools for the investigation of OaPV3 pathogenicity, and their preliminary use to screen 4 ovine cSSC formalin-fixed paraffin embedded tissues. Relevance of immunological tools to investigation of viral biological properties and diagnosis are also discussed.


Effect of laboratory procedures and thermocycling on the shear bond strength of resin-metal bonding systems.
During fabrication or repair of removable partial dentures, resin-to-metal or resin-to-denture tooth bonds may be stressed by laboratory procedures. The purpose of this in vitro study was to evaluate the effect of steam cleaning, boiling, ultrasonic cleaning (laboratory procedures), and thermocycling on shear bond strength of resin bonds to metal and denture teeth. Resin-metal bonding systems and their specific veneer resins (Rocatec, Sinfony; Rocatec, Visio-Gem, HLC-BOND, Zeta LC and Ducera experimental veneer resin) were tested on a Co-Cr alloy (Wirobond C). The veneer resins were bonded to resin denture teeth. The experimental groups (n=7) were subjected to the following conditions: 24-hour storage of the specimens in air (group I, control group), storage in air and treated with simulated laboratory procedures (2 minutes steam cleaning, 15 minutes ultrasonic cleaning at room temperature, 1 hour boiling in water, group II), storage in air with thermocycling (5000 cycles, 5 degrees to 55 degrees C, group III), storage in air with laboratory procedures followed by thermocycling (group IV), and storage in air with thermocycling followed by laboratory procedures (group V). Shear strength tests (MPa) were performed with a universal testing machine until fracture. After shear bond testing, the failure mode of the resin-metal and resin-denture tooth bonds was assessed. Statistical analysis of the results was carried out with one-way analysis of variance and Bonferroni-Dunn's multiple comparisons post hoc analysis for test groups (alpha=0.05). Except for Ducera/denture tooth specimens (groups III to V: 8.7 +/- 3.4-9.1 +/- 1.7; 10.8 +/- 1.9 MPa control group), the Wirobond C and denture tooth specimens (groups III, IV and V: 1.4 +/- 0.9-11.9 +/- 2.3 MPa), showed significantly lower shear bond strengths than the corresponding control groups (7.5 +/- 2.9-21.0 +/- 3.4 MPa, P<.05). The shear bond strengths of group II of Sinfony/Wirobond C (11.6 +/- 3.3 MPa, P<.0001), Visio-Gem/Wirobond C (7.4 +/- 1.9 MPa, P<0.0001), Ducera/Wirobond C (11.8 +/- 2.9 MPa, P<.0001) and of Zeta/denture tooth (3.9 +/- 1.6 MPa, P=.0005) were significantly decreased by steam, boiling, and ultrasonic procedures compared with the corresponding control groups (21.0 +/- 3.4 MPa; 14.7 +/- 4.0 MPa; 19.1 +/- 2.3 MPa; 7.5 +/- 2.9 MPa, respectively). No significant differences were noted among groups III, IV, and V. Co-Cr specimens subjected to the Rocatec system and bonded with Sinfony and HLC BOND/Zeta specimens showed cohesive failure. Adhesive failure was observed for the experimental veneer resin on the Co-Cr specimens and for all veneer resins on the denture teeth. Simulation of laboratory procedures and thermocycling caused a significant drop in shear bond strength of metal-resin and denture tooth-resin bonds for most of the tested veneer resins. Thermocycling before shear testing had the same effect on veneer resin bond strength as the simulated laboratory procedures.


A defined in vitro system for DNA packaging by the bacteriophage SPP1: insights into the headful packaging mechanism.
Tailed icosahedral bacteriophages and other viruses package their double-stranded DNA inside a preformed procapsid. In a large number of phages packaging is initiated by recognition and cleavage by a viral packaging ATPase (terminase) of the specific pac sequence (pac cleavage), which generates the first DNA end to be encapsidated. A sequence-independent cleavage (headful cleavage) terminates packaging, generating a new starting point for another round of packaging. The molecular mechanisms underlying headful packaging and its processivity remain poorly understood. A defined in vitro DNA packaging system for the headful double-stranded DNA bacteriophage SPP1 is reported. The in vitro system consists of DNA packaging reactions with highly purified terminase and SPP1 procapsids, coupled to a DNase protection assay. The high yield obtained enabled us to quantify directly the efficiency of DNA entry into the procapsids. We show that in vitro DNA packaging requires the presence of both terminase subunits. The SPP1 in vitro system is able to efficiently package mature SPP1 DNA as well as linear plasmid DNAs. In contrast, no DNA packaging could be detected with circular DNA, signifying that in vitro packaging requires free DNA extremities. Finally, we demonstrate that SPP1 in vitro DNA packaging is independent of the pac signal. These findings suggest that the formation of free DNA ends that are generated by pac cleavage in vivo is the rate-limiting step in processive headful DNA packaging.


Cyanide toxicity following nitroprusside induced hypotension.
Several recently reported deaths following the use of sodium nitroprusside have been attributed to the accumulation of the nitroprusside metabolite, cyanide. In this study, brief nitroprusside infusions (mean = 36 minutes) were administered in currently recommended doses during intracranial surgery. The peak blood cyanide following the infusions was 65.2 +/- 17.5 microgram per cent (mean +/- SE) (n = 13). It occurred within 45 minutes after infusion. The highest cyanide level detected was 205 microgram per cent, which is within the range of reported lethal blood cyanide levels. Metabolic acidosis developed in the four patients with the highest blood cyanide levels (range 90-205 microgram per cent). This occurred between 45 and 180 minutes following the cyanide peak. Blood ATP levels were depressed in the same patients. These findings are indicative of disturbed aerobic metabolism. We conclude that there is evidence of cyanide toxicity when nitroprusside is infused into patients using currently recommended doses. We recommend that for short infusions the dose of sodium nitroprusside should not exceed 0.5 mg/kg.


Detection of endotoxin in plasma and ascitic fluid of patients with cirrhosis: its clinical significance.
Endotoxin was measured by the Limulus assay in plasma and ascites in 46 patients with cirrhosis having demonstrable esophageal varices, of whom 29 had ascites and 17 did not. It was positive in ascitic fluid in 23 (79.3%) of the former group. In plasma, a positive test was obtained in 22 (75.9%) in the group with ascites and only 4 (23.5%) without ascites, the difference being significant (P less than 0.01). Of the 23 positive ascites specimens, 17 showed high titers (greater than or equal to 10(-3) microgram per ml). Hepatic uptake of 198Au colloid was markedly reduced in 11 of the 17 patients with endotoxemia who were studied by scanning. Death occurred within 6 months in 47.8% of the patients with a positive endotoxin test, whereas only 16.7% of those with a negative test died in the same period (P less than 0.05). No hypotension was noted in patients with toxemia and only 2 ran a fever above 37.5 degrees C. Development of tolerance to endotoxin is suspected. A follow-up study has demonstrated sustained endotoxemia in some of these patients.


Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice.
In hepatic fibrogenesis, stellate cells are activated leading to production and deposition of extracellular matrix. To clarify the role of PDGF-B in liver fibrogenesis, we overexpressed PDGF-B in the liver of transgenic mice. Transgenic mice for the conditional overexpression of PDGF-B in the liver under control of an albumin promoter were generated utilising the Cre/loxP system. Constitutive PDGF-B expression was achieved after breeding with mice expressing Cre-recombinase under actin promoter control. Tamoxifen inducible expression was achieved after breeding with mice expressing Cre under transthyretin receptor promoter control. Levels of fibrosis were assessed and the expression of regulators of matrix remodelling was measured. PDGF-B expression caused hepatic stellate cell and myofibroblast activation marked by alpha-smooth muscle actin and PDGFR-beta expression. Liver fibrosis was verified macroscopically, histologically and by collagen I mRNA quantification in 4-6 week-old animals. MMP-2, MMP-9 and TIMP-1 were upregulated whereas TGF-beta expression was unchanged. We identified PDGF-B as a proliferative and profibrogenic stimulus and potential inducer of stellate cell transdifferentiation in vivo. PDGF-B overexpression causes liver fibrosis without significantly upregulating TGF-beta1, suggesting a TGF-beta-independent mechanism. The established model provides a tool for testing anti-PDGF-B therapeutic strategies in liver fibrosis in vivo.


Long-term incidence of sensory disturbance in the forehead after fronto-orbital advancement in isolated nonsyndromic craniosynostosis.
In the majority of the craniofacial literature, preservation of the supraorbital nerve during fronto-orbital advancement (FOA) is recommended. However, only a few studies have evaluated the incidence of sensory disturbance in the forehead after FOA during long-term follow-up. 57 children who underwent FOA in their first year of life because of isolated nonsyndromic craniosynostosis including trigonocephaly, anterior plagiocephaly or oxycephaly, were evaluated for sensory disturbance in the frontal region with a minimum follow-up of 27 months. An objective and repeatable measurement using the Semmes-Weinstein test was possible in 36 children older than 5 years at last follow-up. We revealed no sensory deficits in all patients, even in 3 patients, where one of the supraorbital nerves was transected during FOA. As previous reports have suggested a full recovery of sensation after transection of the supraorbital nerve during FOA I seen, the need to preserve the nerve has to be evaluated. However, as release of the nerve from the supraorbital rim is possible, we generally recommend preserving this structure, to minimize the risk of sensory deficits in the forehead region.


Metabolism of isobutylnaphthyl acetic acid in rats: determination of the chemical structures of metabolites.
After oral and intravenous administration of radiolabelled isobutylnaphthyl acetic acid (INAA) to rats two metabolites were isolated from urine and plasma by HPLC. Field desorption, high resolution electron impact mass spectrometry as well as GC-MS after derivatization were used for structure elucidation and identification of the metabolites. The main biotransformation product in rat urine was found to be 5-(2'-hydroxy-2'-methyl-propyl)-1-naphthyl acetic acid (M1). The main metabolite in plasma was derived and was found to be 5-(2'-carboxypropyl)-1-naphthyl acetic acid (M2).


An Evaluation of Pre-Operative Nutritional Assessment Methods in Patients with Chronic Limb Threatening Ischaemia Having Distal Bypass.
The purpose of this study was to evaluate the influence of pre-operative nutritional status on long term outcomes of patients with chronic limb threatening ischaemia (CLTI) after distal bypass. Patients who underwent distal bypass for CLTI from 2011 to 2020 at a single centre were reviewed retrospectively in Japan. Comparisons were made between patients with malnutrition and normal nutrition, as diagnosed by four nutritional assessments: Controlling Nutritional Status (CONUT), Geriatric Nutritional Risk Index (GNRI), Glasgow Prognostic Score (GPS), and Prognostic Nutritional Index (PNI). The primary endpoint was survival, and the secondary endpoints were graft patency, limb salvage, and wound healing. A total of 314 distal bypasses were performed in 249 patients (169 males; median age, 76 years; diabetes mellitus, 70%; and end stage renal disease with haemodialysis, 40%). Malnutrition was observed in 103 patients (41%) evaluated by CONUT, 129 (52%) by GNRI, 76 (31%) by GPS, and 114 (46%) by PNI. The survival rates in the study cohort were 81% at one year, 55% at three years, and 47% at five years. Malnutrition in all assessments was statistically significantly associated with reduced survival rate (CONUT, p < .001; GNRI, p = .002; GPS, p < .001; PNI, p < .001). In multivariable analysis, CONUT was the best predictor of mortality (p = .014). Malnutrition did not affect graft patency and limb salvage, but malnutrition based on CONUT, GNRI, and GPS was statistically significantly associated with reduced wound healing (CONUT, p = .002; GNRI, p = .006; GPS, p = .011). In multivariable analysis, CONUT tended to be the best predictor of wound healing (p = .061). Malnutrition in patients with CLTI with distal bypass was associated with overall mortality and incomplete wound healing. CONUT assessment was most effective for prediction of survival and wound healing. Distal bypass for CLTI patients with malnutrition may be suboptimal, and endovascular treatment may be recommended as an initial revascularisation method.


Penicillin V acylase from Pectobacterium atrosepticum exhibits high specific activity and unique kinetics.
Penicillin V acylases (PVAs, E.C.3.5.11) belong to the Ntn hydrolase super family of enzymes that catalyze the deacylation of the side chain from phenoxymethyl penicillin (penicillin V). Penicillin acylases find use in the pharmaceutical industry for the production of semi-synthetic antibiotics. PVAs employ the N-terminal cysteine residue as catalytic nucleophile and are structurally and evolutionarily related to bile salt hydrolases (BSHs). Here, we report the cloning and characterization of a PVA enzyme from the Gram-negative plant pathogen, Pectobacterium atrosepticum (PaPVA). The enzyme was cloned and expressed in Escherichia coli attaining a very high yield (250 mg/l) and a comparatively high specific activity (430 IU/mg). The enzyme showed marginally better pH and thermo-stability over PVAs characterized from Gram-positive bacteria. The enzyme also showed enhanced activity in presence of organic solvents and detergents. The enzyme kinetics turned out to be significantly different from that of previously reported PVAs, displaying positive cooperativity and substrate inhibition. The presence of bile salts had a modulating effect on PaPVA activity. Sequence analysis and characterization reveal the distinctive nature of these enzymes and underscore the need to study PVAs from Gram-negative bacteria.


Cavitary lung lesions in a neonate: Potential manifestation of COVID-19 related multisystem inflammatory syndrome.
The hyperinflammatory state of multisystem inflammatory syndrome in children (MIS-C) predisposes to thromboembolic complications. We report a neonate with multiple cavitary lesions in lung, which we suspect could be a manifestation of multisystem inflammatory syndrome in neonate (MIS-N) following maternal COVID-19 infection during pregnancy. Eight-day-old neonate was referred with fever and fast breathing. Mother was positive for COVID-19 in 29th week. COVID-19 reverse-transcription polymerase chain reaction was negative, however, antibodies were positive. He had increased leucocyte count, and elevated levels of C-reactive protein (CRP), procalcitonin, ferritin, lactate dehydrogenase, and d-dimer along with bilateral reticulonodular opacities on chest radiograph and multiple nodules with evidence of cavitation in both lungs on chest tomography. All cultures were negative. A possible diagnosis of MIS was made. Infant was treated with intravenous immunoglobulin (IVIG) which he responded to with resolution of symptoms. Neonates exposed to COVID-19 should be evaluated for thromboembolic complications and IVIG can be one of the treatment modalities.


Critical evaluation of a novel DualMesh repair for large hiatal hernias.
The use of mesh for laparoscopic repair of large hiatal hernias may reduce recurrence rates in comparison to primary suture repair. However, there is a potential risk of mesh-related oesophageal complications due to prosthesis erosion. The aim of this study was to critically evaluate a novel mesh (DualMesh) repair of hiatal hernias with particular reference to intraluminal erosion. Medical records of 19 patients who underwent laparoscopic hiatal hernia repair with DualMesh reinforcement of the crural closure were reviewed from a prospectively collected database. Quality of life and symptom analysis was performed using quality of life in reflux and dyspepsia (QOLRAD) questionnaires pre- and postoperatively after 6 weeks, 6 months, 1 year and 2 years. Barium studies were performed on patients pre-operatively and two years postoperatively to assess hernia recurrence. After 2 years, oesophagogastric endoscopy was performed to assess signs of erosion. Mean patient age was 70.5 years (range 49-85 years). Two years after hiatal hernia repair, there was significant improvement in quality-of-life scores (QOLRAD: p < 0.001). Follow-up barium studies performed at 31.3 months (range 29-40 months) after surgery showed moderate recurrent hernias (>4 cm) in 1/14 patients (7%). Endoscopies performed at 34.4 months (range 28-41 months) after surgery did not show any signs of prosthetic erosion. Laparoscopic reinforcement of primary hiatal closure with DualMesh leads to a durable repair in patients with large hiatal hernias. Long-term endoscopic follow-up did not show any signs of mesh erosion after prosthetic reinforcement of the crural repair.


Diabetes in Ghana: a community based prevalence study in Greater Accra.
Data on the prevalence of diabetes in Ghana is scanty and unreliable. In the present study we have ascertained the prevalence of diabetes, impaired fasting glycaemia (IFG) and impaired glucose tolerance (IGT) in a random cluster sample of Ghanaians aged 25 years and above from the Greater Accra area of Ghana. Diabetes, IFG and IGT were defined by criteria of the American Diabetes Association and World Health Organization. The mean age of the 4733 subjects involved in the study was 44.3+/-14.7 years, and participation rate was 75%. The crude prevalence of diabetes was 6.3%. Out of 300 subjects with diabetes, 209 (69.7%) had no prior history of the disease. Diabetes, IGT and combined IFG and IGT increased with age. The oldest age group (64+ years) had the highest diabetes prevalence (13.6%). The age-adjusted prevalence of diabetes, IFG and IGT, were 6.4, 6.0 and 10.7%, respectively. Diabetes was more common in males than females (7.7 vs. 5.5%) [P<0.05]. Worsening glycaemic status tended to be associated with increase in age, body mass index, systolic and diastolic blood pressures. Ascertainment of predictors for diabetes in Ghanaians and the significance of the relatively high rates of and IFG and IGT however, remain to be determined.


Insertion site pattern: global approach by linear amplification-mediated PCR and mass sequencing.
In gene therapy, viral or nonviral integrating vectors are used to deliver a corrected gene to replace the corresponding defective cellular gene. As vector delivery is (yet) commonly not targeted to a specific site in the host genome, and vector integration may lead to unwanted cellular gene deregulation, the comprehensive analysis of vector locations is a crucial approach to assess vector biosafety and to follow the fate of the gene corrected cells in vivo. The retrieved vector integration sites are unique for each transduced cell clone, thereby serving as a molecular marker and allowing to track distinct cell clones in various samples. Today, several PCR-based methods are available for the identification and characterization of unknown flanking DNA sequences (Mueller and Wold Science 246:780-786, 1989; Paruzynski et al. Nat Protoc 5:1379-1395, 2010; Schmidt et al. Nat Methods 4:1051-1057, 2007; Silver and Keerikatte J Virol 63:1924-1928, 1989). Thereof, the linear amplification-mediated PCR (LAM-PCR) proved to exhibit the highest sensitivity, allowing the detection of miscellaneous vector integration sites in one sample. The broad application spectrum and robustness of LAM-PCR has been approved by its application as a tool for the molecular follow up of gene-modified cells in preclinical and clinical gene therapy trials (Li et al. Science 296:497, 2002; Cartier et al. Science 326:818-823, 2009; Ott et al. Nat Med 12:401-409, 2006; Deichmann et al. J Clin Invest 117:2225-2232, 2007). The combination of LAM-PCR and next-generation sequencing (NGS) platforms offers the opportunity to study the clonal inventory and pharmacokinetics in clinical gene therapy studies.


[Chromosome analysis in baboons born following the use of potential, postovulatory, fertility-inhibiting steroids].
The chromosomal aberrations of the offsprings of four mothers of pavians which received the steroid substances STS 456 and J 628 postcoitally were investigated. The aberration rate was within the norm. Malformation of the offsprings did not occur.


A review of the effects of therapy on growth and bone mineralization in children with congenital adrenal hyperplasia.
The medical management of children with congenital adrenal hyperplasia (CAH) can be challenging with regard to optimizing final height. Insufficient glucocorticoid suppression of adrenal hormone production will result in acceleration of bone maturation and premature epiphyseal fusion, while appropriate or excessive glucocorticoid therapy can be accompanied by suppression of the growth axis. The extent of the growth suppression appears to be affected by the type and dose of glucocorticoid. Some studies suggest that such growth suppression can be ameliorated through concomitant use of growth hormone (GH) therapy. Available data published over the last 10 years on height outcomes in CAH patients treated with glucocorticoids will be reviewed.


Behavioral changes of metritic primiparous cows treated with chitosan microparticles or ceftiofur.
The main objective was to characterize behavioral changes in metritic primiparous cows treated with chitosan microparticles (CM) or ceftiofur (CEF). A secondary objective was to compare behavioral patterns of metritic cows with nonmetritic (NMET) cows. Nulliparous Holstein cows (n = 311) were fitted with a neck-mounted automated health-monitoring device (AHMD) from -21 to 60 d relative to calving. Cows diagnosed with metritis (d 0), characterized by watery, fetid, red-brownish uterine discharge within 21 d in milk were assigned randomly to CM (n = 45), intrauterine infusion of 24 g of CM dissolved in 40 mL of sterile distilled water on d 0, 2, and 4; CEF (n = 47), subcutaneous injection of 6.6 mg/kg ceftiofur crystalline-free acid on d 0 and 3; and control (CON; n = 39), no treatment. For comparison, NMET cows (n = 180) were matched with metritic cows according to age at calving and calving date. Postdiagnosis, there was an effect of treatment and an interaction between treatment and time on rumination and activity. The interaction showed that CM had lesser rumination than CEF from d 1 to 11, d 18, and d 20; CM had lesser rumination than CON from d 2 to 8; and CEF was not different from CON. The interaction showed that CM had lesser activity than CON on d 2, from d 6 to 11, and d 13 to 14; CM was not different from CEF; and CEF had lesser activity than CON on d 8, 9, 13, and 14. Prediagnosis, cows in CM, CEF, and CON had lesser rumination and activity than cows in NMET. Postdiagnosis, cows in CM, CEF, and CON had lesser rumination than NMET from d 0 to 2 and had lesser activity than NMET from d 0 to 5. In summary, CM decreased rumination and activity compared with CON, which indicates a negative systemic effect of CM. This may be associated with exacerbated inflammation in the uterus. Additionally, metritic cows had decreased rumination and activity prediagnosis, which may allow for the use of AHMD for metritis diagnosis.


Forgery: 'fingerprinting' documents and packaging.
We have found that almost all paper documents, plastic cards and product packaging contain a unique physical identity code formed from microscopic imperfections in the surface. This covert 'fingerprint' is intrinsic and virtually impossible to modify controllably. It can be rapidly read using a low-cost portable laser scanner. Most forms of document and branded-product fraud could be rendered obsolete by use of this code.


Kaposi's sarcoma of the intestinal tract: roentgen manifestations.
Five cases of generalized Kaposi's sarcoma are reported with roentgen evidence of involvement of the intestinal tract. In three instances, there was extensive involvement of the small bowel with multiple intramural nodules. The fourth patient demonstrated multiple polypoid lesions of the colon, and in the fifth a constricting lesion of the ileum was present. Two patients with small bowel involvement had significant malabsorption. This latter complication of diffuse Kaposi's sarcoma of the small bowel has not been previously reported. The diagnosis of the nature of the roentgen intestinal abnormality can usually be made, because intestinal involvement generally occurs late in the disease, when both extensive cutaneous nodules and edema of the extremities are apparent.


Renal colic due to spontaneous perirenal haematoma secondary to antiplatelet medication: two case reports.
We present two cases of spontaneous unilateral perirenal haematoma, following the administration of antiplatelet medication. Both patients reported no history of trauma. One patient was managed conservatively whereas the second patient needed an urgent nephrectomy. A spontaneous haematoma is a rare diagnosis that is easy to be missed. It is important to have a high index of suspicion as a prompt diagnosis can improve the morbidity and mortality of patients. The causes of spontaneous perirenal haematoma are quite varied and a bleeding diathesis can only be accepted as a cause only when all other causes have been excluded.


Tissue Doppler imaging to assess left ventricular dyssynchrony and resynchronization therapy.
We describe the use of tissue Doppler imaging to assess left ventricular dyssynchrony and subsequent resynchronization in a patient with end-stage heart failure undergoing cardiac resynchronization therapy.


Assumptions governing approaches to diagnosis and treatment.
The article analyses two representative medical textbooks, one about regular or 'orthodox' medicine and the other about alternative or complementary medicine. The following dimensions of the disease-concept are discussed: definition, epidemiology, causation, natural history, pathology, clinical features, diagnostic procedures, treatment, effects, complications, rehabilitation, prognosis, prevention, doctor-patient relations, position of the patient, costs and burdens. Although the analysis is not yet complete, some general inferences may be drawn, i.e. the leading model of thinking in regular medicine may be termed 'classical' as opposed to that of complementary medicine, being more 'perspectivistic' in nature. Definitions of disease, as well as diagnostic procedures and therapeutic interventions are organ-specific in regular medicine, and whole-person oriented in complementary medicine. Complementary medicine pays more attention to developmental aspects in disease, the partnership of the patient, the long-term restoration of health, the avoidance of harmful side effects. Also, organisation of the care system is quite different for these types of medicine: being hospital-directed and highly differentiated in regular medicine, while the organisational model of complementary medicine is essentially of a home-centred, integrated type.


A stochastic Farris transform for genetic data under the multispecies coalescent with applications to data requirements.
Species tree estimation faces many significant hurdles. Chief among them is that the trees describing the ancestral lineages of each individual gene-the gene trees-often differ from the species tree. The multispecies coalescent is commonly used to model this gene tree discordance, at least when it is believed to arise from incomplete lineage sorting, a population-genetic effect. Another significant challenge in this area is that molecular sequences associated to each gene typically provide limited information about the gene trees themselves. While the modeling of sequence evolution by single-site substitutions is well-studied, few species tree reconstruction methods with theoretical guarantees actually address this latter issue. Instead, a standard-but unsatisfactory-assumption is that gene trees are perfectly reconstructed before being fed into a so-called summary method. Hence much remains to be done in the development of inference methodologies that rigorously account for gene tree estimation error-or completely avoid gene tree estimation in the first place. In previous work, a data requirement trade-off was derived between the number of loci m needed for an accurate reconstruction and the length of the locus sequences k. It was shown that to reconstruct an internal branch of length f, one needs m to be of the order of [Formula: see text]. That previous result was obtained under the restrictive assumption that mutation rates as well as population sizes are constant across the species phylogeny. Here we further generalize this result beyond this assumption. Our main contribution is a novel reduction to the molecular clock case under the multispecies coalescent, which we refer to as a stochastic Farris transform. As a corollary, we also obtain a new identifiability result of independent interest: for any species tree with [Formula: see text] species, the rooted topology of the species tree can be identified from the distribution of its unrooted weighted gene trees even in the absence of a molecular clock.


Separation of hydrocarbons from activated carbon as a porous substance in a glycol regeneration process using supercritical carbon dioxide.
Activated carbons are used in industrial applications; their cost is a major barrier to their more widespread application. Regeneration of activated carbons is indispensable to minimize operational costs and product wastage. Supercritical carbon dioxide (SC-CO2) as green technology was used to regenerate activated carbons. In this work, response surface methodology was employed to optimize the supercritical regeneration process and to evaluate the effect of the operational parameters including pressure (100-300 bar), temperature (313-333 K), flow rate (2-6 g/min), and dynamic time (30-150 min) on the regeneration yield. The maximum regeneration yield (93.71%) was achieved at 285 bar, 333 K, 4 g/min, and 147 min. Mathematical modeling was done using two one-parameter kinetics models, which agree well with the experimental data. The fitting parameter of the model was obtained by using a differential evolution algorithm. The chemical composition of the substances extracted from the activated carbon was identified by gas chromatography. The results showed that the regeneration of activated carbon by SC-CO2 can be an alternative method to conventional methods.


Electron tomography of the supramolecular structure of virus-infected cells.
Visualizing the viral life cycle in the host challenges us to extend our understanding of the viral infection mechanism. Three-dimensional images obtained by advanced electron tomographic imaging techniques, if resolved to molecular resolution, are helpful for bridging the atomic structural information of proteins to cellular events. Characteristic large structures appear in virus-infected host cells through the life cycle of various viruses. These structures are likely to provide clues to understanding viral infection mechanisms, such as how viruses move in host cells, how they are assembled, how they egress and how they spread cell-to-cell. Here we review recent advances in the studies of the molecular architecture of virus machinery involved in the mechanism of virus infection using comprehensive electron tomographic imaging techniques.


Initial complications and late results in dismembered pyeloplasty.
A total of 109 dismembered pyeloplasties has been reviewed and examples of initial complications and their management are discussed. These early complications do not preclude excellent long-term results. Over-all followup studies show resolution of pain, hematuria and infection in the vast majority of patients. X-ray results have since, in general, improved or stabilized. No nephrectomies have been done subsequent to the repair of the hydronephrosis.


Psychoactive substance consumption in eating disorders.
Research investigating the comorbidity between eating disorders and substance-use disorders have reported positive but contrasting results. The aim of this study was to further explore this association by studying patterns of consumption of the entire range of psychoactive substances (alcohol, specific drugs, prescribed psychotropics) in a large sample (N=271) of eating-disorder DSM-IV subtypes. Results show that subjects suffering from anorexia of the restrictive type show significantly less drug-consumption behaviors and alcohol abuse and/or dependence disorders than purging anorexic and bulimic subjects. No difference was found in the total consumption of psychotropics among the four groups of eating disorders. However, more than half of eating-disorder subjects are regular consumers of psychotropics. Among these regular consumers, bulimics self-prescribe and increase their doses of psychotropics significantly more than anorexics. Features of impulsivity that are associated with purging and bulimic behaviors could play a specific role in these patterns of comorbidity and account for such differences.


Protective effect of dapsone against bleomycin-induced lung fibrosis in rat.
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial disease of the lung tissue that causes symptoms such as coughing and asthma. It is caused by inflammatory factors and oxidative stress. In vivo model of IPF is induced by bleomycin (BLM,) a chemotherapeutic agent. We have investigated the effect of dapsone on bleomycin-induced IPF in adult male Wistar rats due to its anti-inflammatory and anti-oxidative stress effects. The animals were randomly divided into 5 groups (Control, BLM, BLM + dapsone 1, BLM + Dapsone 3, BLM + Dapsone 10). The control group received normal water and food. In the fibrosis group, bleomycin (BLM) (5 mg/kg) was used to induce pulmonary fibrosis by intratracheal administration. Three groups of animals were treated daily with single doses of 1, 3, and 10 mg dapsone by intraperitoneal injection 1 h after receiving BLM for 2 weeks. The activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and oxidative stress markers such as myeloperoxidase (MPO), malondialdehyde (MDA), protein carbonyl (PC) and nitrite were measured to evaluate bleomycin and therapeutic effect of dapsone. The histological assays of lung tissues were done by Hematoxylin-eosin (H & E) and Masson's trichrome staining. BLM reduced the activity of oxidative enzymes and increased the oxidative stress markers, while treatment with dapsone has reversed the results. In addition, the total number of cells as inflammatory cells such as neutrophils and eosinophils were examined. It has been indicated BLM increased these cells, and dapsone decreased them. The results of H & E and Masson's trichrome staining showed that dapsone reduced inflammation and alveolar wall thickness and BLM-induced pulmonary fibrosis. According to the findings of this study, dapsone seems to have therapeutic effects on pulmonary fibrosis through its anti-inflammatory and anti-oxidative stress properties and reduction of the toxic effects of bleomycin.


Synthesis, in vitro evaluation, and computational simulations studies of 1,2,3-triazole analogues as DPP-4 inhibitors.
Novel 1,2,3-triazole analogues (S7 ~ S10) were synthesized and evaluated for their inhibitory activity against hDPP-4. All the 1,2,3-triazole analogues exhibited moderate in vitro hDPP-4 inhibitory activities (265 ~ 780 nM). These results are somewhat less potent compared to those of known 1,2,3-triazole analogues (S1 ~ S6, 14 ~ 254 nM). S2 and S3 manifested excellent potency against hDPP-4 with IC50s of 28 and 14 nM, respectively. The role of the 1,2,3-triazole moiety in binding the molecule to the target was investigated using combined 10 1,2,3-triazole analogues (S1 ~ S10). Molecular dynamics (MD) simulations following the aforementioned docking phase were performed to elucidate potential binding modes of sitagliptin's 1,2,3-triazole analogues in hDPP-4, with the use of a cocrystal structure of hDPP-4 with sitagliptin (PDB ID: 1X70). Docking and MD simulations of the complexes of hDPP-4 with sitagliptin, S2 and S3 suggest that Glu205, Glu206, Tyr662, and Tyr666 would be the key amino acid residues for the binding of the molecules with the receptor. Especially, S2 and S3 showed additional strong π-π interaction between Phe357 and 1,2,3-triazole. Same strong π-π interaction is also observed between Phe357 and the 1,2,4-triazole ring of sitagliptin. Furthermore, additional interactions with Tyr547, Cys551, and especially Arg358 would enhance the binding affinity of the compounds for the pocket of the enzyme. In overall, in vitro hDPP-4 inhibitory activities of synthetic 1,2,3-triazole analogues were well matched with results of computational simulations studies.


Dechlorination of hexachlorobenzene using ultrafine Ca-Fe composite oxides.
Ca-Fe composite oxides with different Ca/Fe atomic ratios were synthesized by co-precipitation method and characterized by X-ray diffraction (XRD), scanning electron microscopy with elemental X-ray analysis (SEM-EDX) and inductively coupled plasma optical emission spectrometer (ICP-OES). Their dechlorination activities were evaluated using hexachlorobenzene (HCB) as a model compound. The results indicate that the dechlorination activity is related to the composition of metal oxides. Different compositions lead to the formation of different phases of Ca-Fe composite oxides. When Ca/Fe atomic ratio was 3.4, the dechlorination activity reached 97%, which was the highest in the dechlorination of HCB at 300 degrees C for 0.5 h. This may be related to the formation of Ca(2)Fe(2)O(5) phase and small agglomerate size of oxide crystal of about 1 microm. The effect of reaction time on HCB dechlorination and the pathway of dechlorination were investigated using the Ca-Fe composite oxide with the highest activity. It was found that hydrodechlorination took place in the destruction of HCB, the dechlorination efficiency is almost 100% after 2 h reaction. After reaction, quantitative measurement of chloride ion and qualitative analysis of CaCO(3) indicate besides hydrodechlorination, other degradation routes may be present. The mechanism of synergic dechlorination using Ca-Fe composite oxides was discussed.


Anisakis simplex: dangerous--dead and alive?
The risk of infection with Anisakis simplex and related parasites of fish has been recognized for some time, but it is now emerging that ingestion of material from dead parasites in food is also potentially dangerous. The resulting allergic reactions range from rapid onset and potentially lethal anaphylactic reactions to chronic, debilitating conditions. This review discusses the problems and clinical implications associated with A. simplex, other related conditions, and the way in which disease manifestations vary from person to person.


Local skin reactions and the onset of influenza-like signs and symptoms induced by imiquimod.
Since the introduction of imiquimod cream, patients have reported treatment-emergent symptoms that mimic influenza. However, clear relationships between the onset of symptoms from topical imiquimod and various variables (eg, patient's age) remain unclear. To evaluate potential relationships between the onset of visceral symptoms that mimic influenza and variables including patient age, the severity of local cutaneous reactions, the amount of surface area, areas of the body being treated, and serum levels of inflammatory cytokines present during 2 cycles of 14-day treatment of imiquimod 3.75% cream. In this single-center, open-label, investigator-initiated trial, 22 patients with 5-20 actinic keratosis were stratified into 1 of 2 age groups: ages 30-59 and ages 60-89. Although the occurrence of systemic symptoms was infrequent during the treatment period, the majority of patients who reported local skin reactions preceding systemic symptoms developed them within 7-11 days of the treatment cycle. Levels of circulating cytokines had no predictive value. This study was limited by its small sample size as well as the small number of cytokines evaluated. Chemokines and cytokines beyond those evaluated may contribute to influenza symptoms and/or systemic responses to imiquimod. The onset of local skin reactions may serve as a predictor for the potential onset of systemic symptoms that mimic those of influenza and could be used as a talking point for patients, though further research is needed.


Loss of p53 accelerates neointimal lesions of vein bypass grafts in mice.
The transcription factor p53 is essentially involved in regulation of cell death and proliferation. Recently, we have established a mouse model for vein graft arteriosclerosis by grafting autologous jugular veins or vena cava to carotid arteries. Using this model, we studied the role of p53 in the development of vein graft arteriosclerosis in p53(-/-) mice. Four weeks after grafting, neointimal hyperplasia of vein grafts in p53(-/-) mice was increased 2-fold compared with that of wild-type controls. Cell component analysis revealed that neointimal lesions in p53(-/-) mice consisted mainly of alpha-actin positive smooth muscle cells (SMCs), whereas the majority of cells in wild-type mice were MAC-1 (CD11b/18)-positive at 4 weeks. Importantly, SMC apoptosis as determined by TUNEL assay was significantly reduced in p53(-/-) vein grafts. TUNEL positive cells in wild-type vein grafts markedly increased from 0.5% to 6.4% of total cells 4 weeks postoperatively, but remained virtually unchanged in p53(-/-) grafts (0.8%). Immunofluorescence analysis revealed that increased p53 expression in neointimal SMCs of wild-type, but not p53(-/-), mice coincided with oxidative DNA damage in vein grafts. Interestingly, SMCs of p53(-/-) mice showed increased apoptosis in response to TNFalpha and decreased apoptosis in response to sodium nitroprusside. Additionally, p53-deficient SMCs showed a higher rate of proliferation and migration and expressed higher levels of matrix metalloproteinases. Thus, p53 deficiency accelerates neointima formation by facilitating SMC proliferation as well as abrogating cell apoptosis.


New World arenavirus clade C, but not clade A and B viruses, utilizes alpha-dystroglycan as its major receptor.
Alpha-dystroglycan (alpha-DG) has been identified as a major receptor for lymphocytic choriomeningitis virus (LCMV) and Lassa virus, two Old World arenaviruses. The situation with New World arenaviruses is less clear: previous studies demonstrated that Oliveros virus also exhibited high-affinity binding to alpha-DG but that Guanarito virus did not. To extend these initial studies, several additional Old and New World arenaviruses were screened for entry into mouse embryonic stem cells possessing or lacking alpha-DG. In addition, representative viruses were further analyzed for direct binding to alpha-DG by means of a virus overlay protein blot assay technique. These studies indicate that Old World arenaviruses use alpha-DG as a major receptor, whereas, of the New World arenaviruses, only clade C viruses (i.e., Oliveros and Latino viruses) use alpha-DG as a major receptor. New World clade A and B arenaviruses, which include the highly pathogenic Machupo, Guanarito, Junin, and Sabia viruses, appear to use a different receptor or coreceptor for binding. Previous studies with LCMV have suggested the need for a small aliphatic amino acid at LCMV GP1 glycoprotein amino acid position 260 to allow high-affinity binding to alpha-DG. As reported herein, this requirement appears to be broadly applicable to the arenaviruses as determined by more extensive analysis of alpha-DG receptor usage and GP1 sequences of Old and New World arenaviruses. In addition, GP1 amino acid position 259 also appears to be important, since all arenaviruses showing high-affinity alpha-DG binding possess a bulky aromatic amino acid (tyrosine or phenylalanine) at this position.


Five HLA-D clusters associated with HLA-DR4.
In order to investigate the HLA-D clusters associated with DR4, 54 DR4-positive, Dw4- and Dw10-negative responders, together with selected Dw4- or Dw10-positive responders, were tested with 22 HTCs that define DR4-associated D specificities. The results are consistent with previous data defining four distinct D clusters--Dw4, Dw10, DB3, and DYT--and have identified a new cluster provisionally termed LD40. In addition, the DB3 cluster is complex and appears to give typing response patterns overlapping those of the KT2 cluster originally defined as being associated with DR4 in Japanese populations. Of 116 DR4-positive haplotypes tested, 44% typed as Dw4, 18% were LD40, 16% were Dw10, 9% were DB3, 3% were DYT, and 10% gave no typing response to the HTCs defining any of these clusters. These studies are informative not only in defining the DR4-associated D clusters and in supporting the concept that D and DR cannot be considered identical but also in emphasizing the complexity of the D region.


Chemical cross-linking of xenopericardial biomeshes: A bottom-up study of structural and functional correlations.
Decellularized bovine pericardium (DBP)-based biomeshes are the gold standard in reconstructive surgery. In order to prolong their stability after the transplantation, various chemical cross-linking strategies are employed. However, structural and functional properties of the biomeshes differ in dependence on the cross-linker used. Here, we performed a bottom-up study of structural and functional alterations of DBP-based biomeshes following cross-linking with hexamethylene diisocyanate (HMDC), ethylene glycol diglycidyl ether (EGDE), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and genipin. The in vitro cytotoxicity tests supported their clinical applicability. Their structural differences (eg roughness, fibre thickness, pore morphology) were evaluated using the two-photon confocal laser scanning, atomic force, scanning electron and polarized light microscopies. HMDC and EDC samples appeared to be the roughest. Complex mechanical trials indicated the tendency to reduced Young's Modulus and mechanical anisotropy values of DBP upon cross-linking. The lowest mechanical anisotropy was found in EDC and genipin sample groups. In vitro collagenase susceptibility was the highest for EDC samples and the lowest for EGDE samples. The comparative analysis of the results allowed us to recognize the strengths and weaknesses of each cross-linker in relation to a particular clinical application.


Decontamination of Campylobacter jejuni on chicken drumsticks using chemicals and radiation.
A trial was conducted to compare the efficacy of four disinfectants and radiation to reduce the level of C. jejuni contamination on poultry meat. Two levels of each treatment were applied to chicken drumsticks inoculated with a known concentration of a strain of Campylobacter jejuni, biotype 1, isolated from a human patient with diarrhea. Radiation using a cobalt-60 source at a level of 0.5 KGy effected a 99% surface reduction in C. jejuni. With a mean initial surface contamination level of 1.1 X 10(3) Colony Forming Units/cm2, 1 KGy completely eliminated C. jejuni. Glutaraldehyde at 0.5% concentration for 30 minutes had an efficacy similar to the lower dose of radiation. Chlorine showed a negligible effect on C. jejuni. Succinic acid and Poly (hexamethylenebiguanide hydrochloride) were statistically similar in their effectiveness, ranking between glutaraldehyde and chlorine. These results strongly indicate that, of the alternatives tested, low-dose radiation is the method of choice for reducing Campylobacter contamination of poultry products.


Protective effects of epigallocatechin gallate against ischemia reperfusion injury in rat skeletal muscle via activating Nrf2/HO-1 signaling pathway.
Previous studies have demonstrated that epigallocatechin gallate (EGCG) had certain protective effects on myocardial and renal ischemia reperfusion (I/R) injury. We aimed to research the special effects and underling mechanisms of EGCG on skeletal muscle I/R injury. We established an experimental rat model of I/R skeletal muscle injury and treated with different doses of EGCG. Hematoxylin eosin staining, TUNEL assay, ELISA, qRT-PCR and Western blotting were used to evaluate the effects of EGCG. EGCG significantly improved skeletal muscle function of I/R injury rats. Moreover, EGCG had positive effects on decreasing apoptosis of skeletal muscle tissues, alleviating oxidative stress damage and suppressing the production of inflammatory cytokines. Further, EGCG had positive effects on activating Nrf2/HO-1 signaling pathway. EGCG might be a powerful candidate compound for alleviating I/R injury in rat skeletal muscle.


Co-exposure to molybdenum and cadmium triggers pyroptosis and autophagy by PI3K/AKT axis in duck spleens.
Excessive amounts of molybdenum (Mo) and cadmium (Cd) are toxicant, but their combined immunotoxicity are not clearly understood. To estimate united impacts of Mo and Cd on pyroptosis and autophagy by PI3K/AKT axis in duck spleens, Mo or/and Cd subchronic toxicity models of ducks were established by feeding diets with different dosages of Mo or/and Cd. Data show that Mo or/and Cd cause oxidative stress by increasing MDA concentration, and decreasing T-AOC, CAT, GSH-Px and T-SOD activities, restrain PI3K/AKT axis by decreasing PI3K, AKT, p-AKT expression levels, which evokes pyroptosis and autophagy by elevating IL-1β, IL-18 concentrations and NLRP3, Caspase-1, ASC, GSDME, GSDMA, NEK7, IL-1β, IL-18 expression levels, promoting autophagosomes, LC3 puncta, Atg5, LC3A, LC3B, LC3II/LC3I and Beclin-1 expression levels, and reducing expression levels of P62 and Dynein. Furthermore, the variations of abovementioned indexes are most pronounced in co-treated group. Overall, results reveal that Mo or/and Cd may evoke pyroptosis and autophagy by PI3K/AKT axis in duck spleens. The association of Mo and Cd exacerbates the changes.


Peripheral astral microtubules ensure asymmetric furrow positioning in neural stem cells.
Neuroblast division is characterized by asymmetric positioning of the cleavage furrow, resulting in a large difference in size between the future daughter cells. In animal cells, furrow placement and assembly are governed by centralspindlin that accumulates at the equatorial cell cortex of the future cleavage site and at the spindle midzone. In neuroblasts, these two centralspindlin populations are spatially and temporally separated. A leading pool is located at the basal cleavage site and a second pool accumulates at the midzone before traveling to the cleavage site. The cortical centralspindlin population requires peripheral astral microtubules and the chromosome passenger complex for efficient recruitment. Loss of this pool does not prevent cytokinesis but enhances centralspindlin signaling at the midzone, leading to equatorial furrow repositioning and decreased size asymmetry. These data show that basal furrow positioning in neuroblasts results from a competition between different centralspindlin pools in which the cortical pool is dominant.


Computational identification of Plasmodium falciparum RNA pseudouridylate synthase as a viable drug target, its physicochemical properties, 3D structure prediction and prediction of potential inhibitors.
The increased resistance to the currently effective antimalarial drugs against Plasmodium falciparum has necessitated the development of new drugs for malaria treatment. Many proteins have been predicted using various means as potential drug targets for the treatment of the P. falciparum malaria infection. Meanwhile, only a few studies went on to predict the 3-dimensional (3D) structure of potential target. Therefore, this study aimed to predict potential antimalarial drug targets against the deadliest malaria parasite P. falciparum as well as to determine the 3D structure and possible inhibitors of one of the targets. We employed machine learning approach to predict suitable drug targets in P. falciparum. Five of the predicted protein targets were considered as potential drug targets as they were non-homologous to their human counterparts. Out of these, we determined the physicochemical properties, predicted the 3D structure and carried out docking-based virtual screening of P. falciparum RNA pseudouridylate synthase, putative (PfRPuSP). The PfRPuSP was one of the potential five target proteins. Homology modelling and the ab initio methods were used to predict the 3D structure of PfRPuSP. Then, a compound library of 5621 molecules was constructed from PubChem and ChEMBL databases using 5-fluorouridine as the control inhibitor. Docking-based virtual screening was performed using Autodock 4.2 and Autodock Vina to select compounds with high binding affinity. A total of 11 compounds were selected based on their binding energies from 881 compounds which were manually examined after docking. Seven of the 11 compounds that exhibited remarkable interactions with the residues in the active sites of PfRPuSP were analysed. These compounds performed favourably when compared to the control inhibitor and predicted to bind better than 5-fluorouridine. These seven compounds are suggested as new potential lead structures for antimalarial treatment.


Enhanced expression of hepatocyte growth factor in the healing of experimental acute tympanic membrane perforation.
The present study was performed to investigate the expression of hepatocyte (HGF), epidermal (EGF) and vascular endothelial (VEGF) growth factors in the course of healing of experimental tympanic membrane (TM) perforations in rats. The goal was to explain the role of these growth factors in the healing process of TM and to assess the possibility of their future application as healing promoters. Seventy rats were used, of which 10 served as controls and the others had their TM perforated. The experimental animals were divided into six subgroups on the basis of time points (01, 03, 05, 07, 09, 15 day after injury). Videootoscopy and histology were employed to assess the morphology of the healing process. The expressions of HGF, EGF and VEGF were evaluated using Western blot analysis. Tissue localization of HGF was determined by the immunofluorescence method. HGF was hardly detectable in normal TM; however, a significant increase was noted in its expression starting from the third day after injury throughout the follow-up period, with the highest level on day 05. The analysis of HGF tissue localization with immunofluorescence revealed diffuse staining in the cytoplasm of proliferating epithelial cells. The expression of EGF was elevated on the first day after injury, not reaching statistical significance, and then returned to the level observed in the control TM. No significant differences were noted in the expression of VEGF. High expression of HGF during the healing process of acute TM perforations makes it a promising candidate for further studies oriented towards its possible use in augmentation of TM healing.


Anatomy of right atrial structures by real-time 3D transesophageal echocardiography.
The rapid development of catheter ablation techniques for atrial arrhythmias has triggered a renewed interest in the anatomy of the right atrium. In particular, some atrial arrhythmias such as focal atrial arrhythmias or atrial flutter have been linked to the anatomic architecture of specific structures such as the crista terminalis or cavotricuspid isthmus. Real-time 3-dimensional transesophageal echocardiography (RT 3D TEE) is a recently developed technique that provides 3D images of unprecedented quality. Because the right atrium is very close to the transducer, this technique may provide high-quality images of those atrial structures involved in ablation procedures. This review describes a step-by-step approach for acquisition and processing of RT 3D TEE images of right atrial structures of relevance to electrophysiologists. For anatomical correlations of RT 3D TEE images, selected images of right atrial structures were matched to anatomical specimens.


The influence of fragmentation on the acoustic response from shrinking bubbles.
Bubble disruption is associated with the response of ultrasound contrast agents (UCAs) exposed to high acoustic pressures. This behavior is important for bubble detection techniques as well as flow quantitation and some proposed therapeutic applications. Previous work has measured acoustically the disruption threshold and postdisruption echo from populations of microbubbles. This suggests a model for UCA disruption whereby ultrasound breaks their shell, leaving free gas bubbles. Diffusion of gas causes the bubbles to shrink and, consequently, reduces the measured backscatter echo over time. In this work, similar bubbles containing three different gases were measured and their echo behavior with time compared with a simple simulation based on diffusion of gas out of the bubble. It was found that, in general, the simulations and experiments compared well at low disruption pressures. Incorporating bubble fragmentation in the simulation model brought its results closer to experiment.


Tissue distribution and cDNA cloning of a human fatty acid transport protein (hsFATP4).
Fatty acid uptake is partly controlled by the FATP gene family, of which at least five members are known in mice. Using the mmFATP1 cDNA as hybridization probe, a 1.6 kb partial cDNA clone was isolated from a human heart cDNA library. With 5' and 3' RACE procedures, the complete cDNA was isolated. Sequence comparisons with its mouse homologues identified this clone as hsFATP4.


Our world views (may be) incommensurable: now what?
In focusing their view on Kuhn, Robert Veatch and William Stempsey ignore alternative sources of insight from other voices that could help move us beyond incommensurability. Richard Rorty and Helen Longino, for example, offer another view of science and objectivity with constructive insight for the practice of science and medicine.


The development of a radioimmunoassay for the measurement of human plasma arginine vasopressin.
A radioimmunoassay for AVP capable of measuring human plasma AVP is described. Iodination was performed by the chloramine T method and purified by chromatography on Sephadex G-25. Specific activity of 125I-AVP was 1710 +/- 155 Ci/mmol. Antiserum of high affinity (Keq = 2.7 X 10(11) 1/mol) has been raised in rabbits, which shows slight cross-reactivity with LVP and negligible reactivity with oxytocin. The aqueous assay is capable of detecting 0.4 fmol of AVP/tube and it is highly reproducible. A F lorisil extraction technique is described in detail and gives recovery of 70% of synthetic AVP added to plasma over a wide physiological range. The lowest detectable concentration of plasma AVP is 0.3 pmol/l. The method has been validated by studying changes in plasma AVP concentration following overnight dehydration (plasma AVP =3.46 +/- 1.89 (SD) pmol/l), and water loading (plasma AVP = 1.54 +/- 0.59 pmol/l), P less than 0.005, in normal subjects. A highly significant positive correlation has been found between plasma AVP and plasma osmolality (r =+0.75). Plasma AVP concentration has also been determined in patients with DI and the syndrome of inappropriate ADH secretion. No effect was found on the level of plasma AVP in normally hydrated volunteers undergoing postural change but levels rose following strenuous exercise from basal concentrations of 1.57 +/- 0.59 pmol/l to 4.77 +/- 3.43 pmol/l, P less than 0.01.


Are visual assessments of the single-leg squat valid to be used in clinical practice? A systematic review of measurement properties based on the COSMIN guideline.
Evaluate the discriminative and convergent validity of visual scales for the assessment of movement quality in the single-leg squat. Searches performed in CINAHL, Cochrane, Embase, PubMed, SPORTDiscus and Web of Science databases. Studies evaluating discriminative and convergent validity of movement quality visual assessments in single-leg squats were included. The COSMIN risk of bias checklist was used to assess the risk of bias, and certainty of evidence was assessed by the GRADE modified version. Ten studies evaluating three different methods of visual assessment of the single-leg squat (Crossley scale; Whatman score and Medial knee displacement) were included. Very low certainty evidence suggests that the Crossley scale had sufficient discriminative validity for patient-centred outcomes. Very low to moderate certainty evidence suggests that the three visual methods of assessment of the single-leg squat had insufficient discriminative validity for surrogate outcomes and groups. None of the three methods had the convergent validity assessed. The Crossley scale exhibited sufficient discriminative validity for patient-centred outcomes, although the evidence supporting this conclusion is of very low certainty. Visual scales for the assessment of the single-leg squat movement quality should be used with caution in clinical practice as most methods had insufficient discriminative validity and no reports of convergent validity.


Reconstruction of three right hepatic veins using cadaveric iliac vein in right lobe living donor liver transplantation: case report.
In various right hepatic vein anatomies, reconstruction is a surgically challenging technique in right lobe living donor liver transplantation. The right inferior hepatic vein is the most common hepatic vein abnormality in right lobe living-donor liver transplantation. Three accessory right hepatic veins is a rare right hepatic vein variation. We experienced one case of three right hepatic vein reconstruction among 300 partial liver transplantations using the right lobe in our center over 10 years. The donor right lobe had one main right hepatic vein and three accessory hepatic veins at the lower border of the liver. Restoration of accessory hepatic veins to the inferior vena cava was performed after construction of one conduit from the three accessory hepatic veins using a cadaveric donor iliac vein.


Knowledge of basic life support: a pilot study of the Turkish population by Baskent University in Ankara.
A total of 494 participants who were scheduled to take Baskent University's basic life support (BLS) training programme in 2001-02 were asked to complete a 25-item questionnaire prior to the course. The questionnaire investigated the demographic characteristics of the subjects, their knowledge of the theoretical and practical aspects of BLS, and personal experience and attitudes related to BLS. The 'non-medical group' included 179 laypersons, and the 'medical group' was composed of medical students (n=220), residents (n=69) and clinical nurses (n=26). One-hundred and twenty-six (25.5%) of the participants had an encounter with some form of medical emergency event in their past and 207 (41.9%) had taken a BLS course previously. The most commonly cited anxiety about performing BLS was the fear of further harming the victim (56.9%). Nine of the participants said they would not perform mouth-to-mouth ventilation (1.8%). Compared to the other participants, individuals with previous emergency experience, and those who had previous BLS training answered significantly more of the theoretical questions correctly. However, neither of these groups performed significantly better than the other participants in the practical questions (P>0.05 for both comparisons). Based on our findings, we recommend that BLS training for medical undergraduates, other medical personnel and laypersons be improved and standardized throughout Turkey.


Effect of Intravenous Ondansetron on the QT Interval of Patients' Electrocardiograms.
Ondansetron improves the success of oral rehydration in children with gastroenteritis. In postoperative adults, ondansetron has been shown to prolong the corrected QT (QTc). The aim of the study was to evaluate the effect of ondansetron on the QT at peak effect and at 1-hour postpeak effect in pediatric patients. This was an observational study looking at patients aged 6 months to 18 years receiving intravenous ondansetron for nausea, vomiting, or the inability to take fluids in the emergency department. Patients had electrocardiogram performed at baseline, at ondansetron's peak effect, and 1 hour postpeak effect. A paired samples Student t test compared QTc change at peak effect to zero. Peak effect of intravenous ondansetron is 3 minutes. One hundred patients were included. Fifty-five percent of patients were female with a mean age of 8.3 years. The mean (range) baseline QTc was 435 (388 to 501) milliseconds. The mean (range) change in QTc at peak effect of ondansetron was 3 (-40 to 65) milliseconds (P = 0.072). The change in QTc 1-hour postpeak effect of ondansetron was 3 (-43 to 45) milliseconds (P = 0.082). No change at peak effect or 1-hour postpeak effect was clinically significant. Ondansetron does not affect the QTc of pediatric patients receiving the medication for nausea, vomiting, or inability to take fluids in the emergency department. No changes in the QTc are clinically significant. To date, there have been no studies evaluating the effect of ondansetron in this acutely ill population; therefore, a larger study should be completed to confirm these data.


The Dark Side of Lead-Free Metal Halide Nanocrystals: Substituent-Modulated Photocatalytic Activity in Benzyl Bromide Reduction.
We illustrate here the high photocatalytic activity of sustainable lead-free metal halide nanocrystals (NCs), namely, Cs3Sb2Br9 NCs, in the reduction of p-substituted benzyl bromides in the absence of a cocatalyst. The electronic properties of the benzyl bromide substituents and the substrate affinity to the NC surface determine the selectivity in C-C homocoupling under visible light irradiation. This photocatalyst can be reused for at least three cycles and preserves its good performance with a turnover number of ca. 105,000.


Cyclic GMP-dependent cytoprotection against ethanol-induced damage in rabbit isolated gastric parietal cells.
Prostaglandin E2 stimulates a nitric oxide/cyclic GMP (NO/cGMP) pathway which activates basolateral Cl- channels in rabbit gastric parietal cells. We examined whether the NO/cGMP pathway protects parietal cells from ethanol (EtOH)-induced cytotoxicity, using a parietal cell-rich suspension purified from rabbit gastric mucosa. Cytotoxicity was assayed by measuring the release of a fluorescent dye from the cells. N2,O2-dibutyryl guanosine 3',5'-cyclic monophosphate (DBcGMP) showed a concentration-dependent protective effect against EtOH-induced cytotoxicity. The half-maximal effect of DBcGMP was observed at 24 microM. DBcGMP in a concentration-dependent manner opened the basolateral Cl- channels of parietal cells, the EC50 value being 44 microM. The EtOH-induced cytotoxicity decreased as the Cl- concentration of medium decreased. A 30-s treatment with 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), an inhibitor of the Cl- channel, had a cytotoxic effect which was not prevented by pre-incubation with DBcGMP. The cytotoxic effects of EtOH and NPPB were additive and the NPPB effects did not depend on the medium Cl- concentration. The present study showed that cGMP protects the gastric parietal cell from EtOH-induced cytotoxicity, and this cytoprotection is related to basolateral Cl- channel activity in the plasma membrane via an unknown mechanism(s).


The template RNAs of RNA polymerases can have compact secondary structure, formed by long double helices with partial violations of the complementarity.
A new method of contextual analysis was used to search the long non-random inverted repeats and the complementary palindromes in the genes of E. coli and T7 RNA polymerases. These genes were found to contain from 25% to 50% of all the nucleotides involved in such helices. The 5' -and 3' -ends of mRNA can be protected by neighbouring double helices from the nuclease attack. Some double helices are competing and very similar to the attenuator of E. coli trp-operon.


Biotransformation of Major Ginsenoside Rb1 to Rd by Dekkera anomala YAE-1 from Mongolian Fermented Milk (Airag).
Dekkera anomala YAE-1 strain separated from "airag" (Mongolian fermented mare's milk) produces β-glucosidase, which can convert ginsenoside Rb1 from Panax ginseng. Ginseng-derived bioactive components such as ginsenoside Rb1 have various immunological and anticancer activities. Airag was collected from five different mare milk farms located near Ulaanbaatar, Mongolia. YAE-1 strains were isolated from airag to examine the hydrolytic activities of β-glucosidase on Korean Panax ginseng using an API ZYM kit. Supernatants of selected cultures having β-glucosidase activity were examined for hydrolysis of the major ginsenoside Rb1 at 40°C, pH 5.0. The YAE-1 strain was found to be nearly identical at 99.9% homology with Dekkera anomala DB-7B, and was thus named Dekkera anomala YAE-1. This strain exerted higher β-glucosidase activity than other enzymes. Reaction mixtures from Dekkera anomala YAE-1 showed great capacity for converting ginsenoside Rb1 to ginsenoside Rd. The β-glucosidase produced by Dekkera anomala YAE-1 was able to hydrolyze ginsenoside Rb1 and convert it to Rd during fermentation of the ginseng. The amount of ginsenoside Rd was highly increased from 0 to 1.404 mg/ml in fermented 20% ginseng root at 7 days.


Transcranial direct-current stimulation increases extracellular dopamine levels in the rat striatum.
Transcranial direct-current stimulation (tDCS) is a non-invasive procedure that achieves polarity-dependent modulation of neuronal membrane potentials. It has recently been used as a functional intervention technique for the treatment of psychiatric and neurological diseases; however, its neuronal mechanisms have not been fully investigated in vivo. To investigate whether the application of cathodal or anodal tDCS affects extracellular dopamine and serotonin levels in the rat striatum. Stimulation and in vivo microdialysis were carried out under urethane anesthesia, and microdialysis probes were slowly inserted into the striatum. After the collection of baseline fractions in the rat striatum, cathodal or anodal tDCS was applied continuously for 10 min with a current intensity of 800 μA from an electrode placed on the skin of the scalp. Dialysis samples were collected every 10 min until at least 400 min after the onset of stimulation. Following the application of cathodal, but not anodal, tDCS for 10 min, extracellular dopamine levels increased for more than 400 min in the striatum. There were no significant changes in extracellular serotonin levels. These findings suggest that tDCS has a direct and/or indirect effect on the dopaminergic system in the rat basal ganglia.


Enhanced B-phycoerythrin production by the red microalga Porphyridium marinum: A powerful agent in industrial applications.
The production of B-phycoerythrin (B-PE) from the red microalga Porphyridium marinum was optimized before to purify it and subsequently study its antioxidant activities. NaNO3, K2HPO4 and metal traces concentrations of the culture medium, and luminosity parameters were chosen, according to the Plackett-Burman design, as the most influent factors on the B-PE production by P. marinum. The optimization of these factors according to the Box-Behnken plan gave a maximum of B-PE production equal to 40 mg/g dry weight under the following conditions: NaNO3 = 3.4 g/L; K2HPO4 = 0 g/L; light intensity = 70 μmol photons/m2/s and metal solution = 1.5 mL/L. The B-PE also showed an interesting capacity to chelate Fe3+ (IC50 = 13.91 ± 0.21 μg/mL) and a significant reducing power (OD700nm = 0.485 ± 0.011 at 100 μg/mL). The present study reports the antioxidant potential of purified B-PE from P. marinum that could be potentially used as a source of bioactive protein for a wide range of cosmetic and pharmaceutical applications.


Costs and benefits of cervical screening IV: valuation by women of the cervical screening programme.
To assess the value of the cervical smear test to women, taking account of the positive and negative aspects of the cervical screening service. A postal survey. Tayside Health Board region of Scotland. A sample of 2000 women aged 20-59. Maximum willingness to pay (WTP) for a cervical smear test. Women were prepared to pay 50.20 British pounds per smear on a 3-yearly basis. Willingness to pay was positively related to income, but unrelated to age and whether or not the respondent had previously had a smear. Previous studies have estimated the cost per screen or cost per life year saved by cervical screening. This study used the economic instrument of WTP to take account of other potential (dis)benefits to women. The value women place on having a smear was more than the cost to the National Health Service (NHS) of providing the service. The output of a WTP study is potentially useful at the policy level. Future work should explore both the value of alternative approaches to cervical screening, and the value of competing health care interventions.


What interventions do rural doctors think will increase recruitment in rural areas: a survey of 2778 health workers in Beijing.
A shortage of health professionals in rural areas is a major problem facing China, as more than 60% of the population lives in such areas. Strategies have been developed by the government to improve the recruitment of rural doctors. However, the inequitable distribution of doctors working in China has not improved significantly. The objective of this study was to explore the reasons for the poor recruitment and to propose possible strategies to improve the situation. Between September 2009 and November 2009 data were collected from 2778 rural doctors in Beijing, China. A quantitative survey was used to explore health workers' perceptions as to what factors would have the greatest impact on recruitment and whether access to training had been effective in increasing their confidence, enhancing their interest in practicing medicine and increasing their commitment to recruitment. Rural doctors were generally older than average in China. Of the 2778 participants, only 7.23% had obtained a license as a qualified doctor. For 53% of the rural doctors, the job was part-time work. The survey showed that rural doctors considered the training strategy to be inadequate. In general, the initiatives identified by rural doctors as being of most value in the recruitment of doctors were those targeting retirement pension and income. From the perspective of rural doctors, specific initiatives that promised a secure retirement pension and an increased income were considered most likely to assist in the recruitment of rural doctors in Beijing.


A comparison of preparation-related neuronal activity changes in the prefrontal, premotor, primary motor and posterior parietal areas of the monkey cortex: preliminary results.
Single-unit activity of prefrontal (PF), premotor (PM), primary motor (MI) and posterior parietal (PP) cortical areas was analysed from 3 monkeys trained to perform visually guided arm movements in a between-arms choice reaction time (RT) task. Percentages of preparation-related units, i.e. units whose change in activity during the preparatory period was correlated with RT, were 19% in PF, 31% in MI, 46% in PM and 68% in PP, respectively. These data support the hypothesis that neural pathways connecting PP association areas to MI, via PM, are involved mainly in movement planning.


Accurate measurement of refractive indices.
A simple wedge measurement technique of optical refractive index is described. The procedure is more accurate and convenient than the usual minimum deviation method and is not limited to visible light.


Melatonin suppresses doxorubicin-induced premature senescence of A549 lung cancer cells by ameliorating mitochondrial dysfunction.
Melatonin is an indolamine that is synthesized in the pineal gland and shows a wide range of physiological functions. Although the anti-aging properties of melatonin have been reported in a senescence-accelerated mouse model, whether melatonin modulates cellular senescence has not been determined. In this study, we examined the effect of melatonin on anticancer drug-induced cellular premature senescence. We found that the doxorubicin (DOX)-induced senescence of A549 human lung cancer cells and IMR90 normal lung cells was substantially inhibited by cotreatment with melatonin in a dose-dependent manner. Mechanistically, the DOX-induced G2/M phase cell cycle arrest and the decrease in cyclinB and cdc2 expression were not affected by melatonin. However, the DOX-induced increase in intracellular levels of ROS, which is necessary for premature senescence, was completely abolished upon melatonin cotreatment. In addition, the reduction in mitochondrial membrane potential that occurs upon DOX treatment was inhibited by melatonin. An aberrant increase in mitochondrial respiration was also significantly suppressed by melatonin, indicating that melatonin ameliorates the mitochondrial dysfunction induced by DOX treatment. The treatment of A549 cells with luzindole, a potent inhibitor of melatonin receptors, failed to prevent the effects of melatonin treatment on mitochondrial functions and premature senescence in cells also treated with DOX; this suggests that melatonin suppresses DOX-induced senescence in a melatonin receptor-independent manner. Together, these results reveal that melatonin has an inhibitory effect of melatonin on premature senescence at the cellular level and that melatonin protects A549 cells from DOX-induced senescence. Thus, melatonin might have the therapeutic potential to prevent the side effects of anticancer drug therapy.


Morphological response of injured adult rabbit optic nerve to implants containing media conditioned by growing optic nerves.
Adult rabbit retina can express regeneration-associated characteristics after optic nerve injury, provided it is supplied with appropriate diffusible substances originating from media conditioned by regenerating fish optic nerves or by optic nerves of a newborn rabbit [Hadani et al., Proc. Natl. Acad. Sci. U.S.A., 81 (1984) 7965; Schwartz et al., Science, 228 (1985) 600]. This was shown by applying the active substances to the injured axons in the form of 'wrap-around' implants, consisting of collagen-coated silicone tubes which had been soaked in the conditioned media (CM). The regeneration-associated response was manifested biochemically and by sprouting of nerve fibers in culture. The present work provides morphological evidence that the implantation prolongs survival of ganglion cells and optic nerve fibers and induces new growth. Light microscopic analysis (using horseradish peroxidase (HRP) for labeling the fibers) revealed, 1 week following optic nerve injury, labeled fibers and ganglion cells in both the implanted and control (injured only or injured and implanted with collagen-coated silicone tubes free of CM) nerves. However, from the second week after the injury, distinct differences in the appearance of viable ganglion cells and labeled fibers, were seen between experimental and control preparations. In sections taken through the optic nerve, at the region distal to the site of injury, HRP-labeled fibers were seen in the experimental nerves 1 week, 2 weeks and to a significantly lesser extent 1 month after injury.(ABSTRACT TRUNCATED AT 250 WORDS)


The intracellular tyrosine kinase domain of the epidermal growth factor receptor undergoes a conformational change upon autophosphorylation.
The intracellular portion of the epidermal growth factor receptor consists of a tyrosine kinase domain of approximately 290 amino acids and a COOH-terminal regulatory domain of approximately 230 amino acids that contains five sites of autophosphorylation. The effect of autophosphorylation on the conformation of the intracellular domain has been analyzed using gel filtration. Both phosphorylated and dephosphorylated forms of the intracellular domain exist as monomers and as dimers and appear to have an extended conformation. The Stokes' radii of phosphorylated monomers and dimers were larger than those of the dephosphorylated forms, indicating that the dephosphorylated form is more compact. These results indicate that a significant conformational change occurs in the intracellular portion of the epidermal growth factor receptor upon tyrosine autophosphorylation.


Inhibition of mTOR Alleviates Early Brain Injury After Subarachnoid Hemorrhage Via Relieving Excessive Mitochondrial Fission.
The mammalian target of rapamycin (mTOR) was reported to regulate cell autophagy and outcomes of several neurological diseases. Mitochondria, which serve as critical organelles in neurons. are also involved in the pathology of neurological diseases. However, the role of mTOR in mitochondrial morphology has not been clarified especially in subarachnoid hemorrhage (SAH). In this study, we established SAH models both in vivo and in vitro. Rapamycin and 3-methyl adenine (3-MA) were then administered to alter mTOR activity. Post-SAH assessment included SAH grading, neurological evaluation, blood-brain barrier (BBB) permeability, brain water content, mitochondrial membrane potential (MMP), mitochondrial morphology, ATP content, cell viability, cytotoxicity, and expression of proteins related to apoptosis and mitochondrial fission. The results showed that (1) neurological deficits, BBB permeability, and brain edema were increased after SAH and that cell viability was exacerbated in brain tissue. (2) Excessive mitochondrial fission was evident based on changes in mitochondrial morphology, while MMP and ATP content were decreased in neurons after SAH. (3) Administration of rapamycin improved the excessive mitochondrial fission and restored mitochondrial function, which subsequently reduced apoptosis. (4) 3-MA showed an adverse effect on mitochondria and aggravated excessive mitochondrial fission and dysfunction in SAH. Neurological deficits and neuronal viability were also exacerbated following the administration of 3-MA. Therefore, our study suggests that mTOR inhibition has neuroprotective effects against neuronal injury after SAH via alleviating excessive mitochondrial fission.


Altered depression-related behavior and neurochemical changes in serotonergic neurons in mutant R406W human tau transgenic mice.
Mutant R406W human tau was originally identified in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and causes a hereditary tauopathy that clinically resembles Alzheimer's disease (AD). In the current study, we examined the performance of R406W transgenic (Tg) mice in the forced swimming test, a test with high predictivity of antidepressant efficacy in human depression, and found an enhancement of the immobility time. In contrast, the motor function and anxiety-related emotional response of R406W Tg mice were normal. Furthermore, a selective serotonin reuptake inhibitor (SSRI), fluvoxamine (100 mg/kg, p.o.), significantly reduced this enhancement of the immobility time, whereas a noradrenaline reuptake inhibitor, desipramine, had no effect. In an in vivo microdialysis study, R406W Tg mice exhibited a significantly decreased extracellular 5-hydroxyindoleacetic acid (5-HIAA) level in the frontal cortex and also exhibited a tendency toward a decreased extracellular 5-hydroxytryptamine (5-HT) level. Moreover, fluvoxamine, which reduced the enhancement of the immobility time, significantly increased the extracellular 5-HT level in R406W Tg mice. These results suggest that R406W Tg mice exhibit changes in depression-related behavior involving serotonergic neurons and provide an animal model for investigating AD with depression.


Strategies used throughout the scaling-up process of eConsult - Multiple case study of four Canadian Provinces.
eConsult is a model of asynchronous communication connecting primary care providers to specialists to discuss patient care. This study aims to analyze the scaling-up process and identify strategies used to support scaling-up efforts in four provinces in Canada. We conducted a multiple case study with four cases (ON, QC, MB, NL). Data collection methods included document review (n = 93), meeting observations (n = 65) and semi-structured interviews (n = 40). Each case was analyzed based on Milat's framework. The first scaling-up phase was marked by the rigorous evaluation of eConsult pilot projects and the publication of over 90 scientific papers. In the second phase, provinces implemented provincial multi-stakeholder committees, institutionalized the evaluation, and produced documents detailing the scaling-up plan. During the third phase, efforts were made to lead proofs of concept, obtain the endorsement of national and provincial organizations, and mobilize alternate sources of funding. The last phase was mainly observed in Ontario, where the creation of a provincial governance structure and strategies were put in place to monitor the service and manage changes. Various strategies need to be used throughout the scaling-up process. The process remains challenging and lengthy because health systems lack clear processes to support innovation scaling-up.


Warming and leaf litter functional diversity, not litter quality, drive decomposition in a freshwater ecosystem.
Environment, litter composition and decomposer community are known to be the main drivers of litter decomposition in aquatic ecosystems. However, it remains unclear whether litter quality or functional diversity prevails under warming conditions. Using tank bromeliad ecosystems, we evaluated the combined effects of warming, litter quality and litter functional diversity on the decomposition process. We also assessed the contribution of macroinvertebrates and microorganisms in explaining litter decomposition patterns using litter bags made with different mesh sizes. Our results showed that litter decomposition was driven by litter functional diversity and was increasingly higher under warming, in both mesh sizes. Decomposition was explained by increasing litter dissimilarities in C and N. Our results highlight the importance of considering different aspects of litter characteristics (e.g., quality and functional diversity) in order to predict the decomposition process in freshwater ecosystems. Considering the joint effect of warming and litter traits aspects allow a more refined understanding of the underlying mechanisms of climate change and biodiversity shifts effects on ecosystem functioning.


Attending school after treatment for a brain tumor: Experiences of children and key figures.
Reintegration into school is a milestone for childhood brain tumor survivors, as well as for their parents, teachers, and healthcare providers. We explored their experiences following the school re-entry by conducting semi-structured interviews. Thematic analysis resulted in four main themes: "school performance," "psychosocial well-being," "support and approach," and "communication and collaboration." Children were pleased to return to school despite confrontation with adverse outcomes. Parents, teachers, and healthcare providers identified current and future concerns and challenges, as well as opportunities for academic and personal development. Their experiences highlight the importance of coordinated and systematic follow-up in close collaboration with healthcare providers.


Ulnar nerve compression at Guyon's canal by an anomalous abductor digiti minimi muscle: the role of ultrasound in clinical diagnosis.
Anomalous variations of abductor digiti minimi are commonly found at Guyon's canal but rarely cause ulnar nerve compression. We report such a case with particular emphasis on the effectiveness of ultrasound to detect and delineate anatomical structures in this region.


Primary intrarenal lipoma: a case report.
Fat-containing tumors of the kidneys are not uncommon, but primary intrarenal lipomas are extremely rare, with only 19 documented cases reported to date. In most cases, total nephrectomy is performed. We report on a 71-year-old man with the complaint of epigastralgia. Series image studies revealed a high fat-containing tumor with low vascularity arising from the lower pole of the left kidney. We performed partial nephrectomy, and the subsequent pathology report revealed a pure lipoma.


Effects of weight stigma in news media on physical activity, dietary and weight loss intentions and behaviour.
To investigate the effect of weight stigma in news media on (a) intentions to increase physical activity (PA), improve diet quality and lose weight, and (b) changes in PA, diet quality and body mass index (BMI) over one month, in (i) women of all weight categories and (ii) a subsample of women living with obesity. UK-based women (N=172; subgroup with obesity N=81) were assigned to read an experimental (weight stigma; N=75) or control (smoking stigma; N=97) news article. Questionnaires were administered immediately after, and one month subsequently to collect information on BMI, PA, diet quality, intentions, past stigma, and diet and PA self-efficacy. Logistic and linear regression analyses were used to assess the effect of weight stigma on all outcome variables. In the whole sample, there was no significant effect of weight stigma on any primary or secondary outcome. In women with obesity, there was no significant effect of weight stigma on diet quality (0.26 units, 95% CI: -0.36 to 0.87) or PA (-1.83 units, 95% CI: -11.11 to 7.44) at follow up, but exposure to weight stigma was associated with a significant increase in BMI at 1-month follow-up (1.15kg/m2, 95% CI: 0.38 to 1.92) compared with the control group. In people with obesity, exposure to weight-stigmatising media may contribute to increased BMI over time. Larger trials with longer follow-up are needed to confirm these findings.


Jean Langlais (1907-91): an historical case of a blind organist with stroke-induced aphasia and Braille alexia but without amusia.
The subject of a prior report of a blind organist with aphasia and Braille alexia without amusia, published in French, has been identified as Jean Langlais. His artistic and medical history is presented, the latter via translation of the original 1987 paper.


hTERT protein expression is independent of clinicopathological parameters and c-Myc protein expression in human breast cancer.
Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal length and stability thus leading to cellular immortalisation. The hTERT (human telomerase reverse transcriptase) subunit seems to be the rate-limiting determinant of telomerase and knowledge of factors controlling hTERT transcription may be useful in therapeutic strategies. The hTERT promoter contains binding sites for c-Myc and there is some experimental and in vitro evidence that c-Myc may increase hTERT expression. We previously reported no correlation between c-Myc mRNA expression and hTERT mRNA or telomerase activity in human breast cancer. This study aims to examine the correlation between hTERT expression as determined by immunohistochemistry and c-Myc expression, lymph node status, and tumour size and grade in human breast cancer. The immunohistochemical expression of hTERT and c-Myc was investigated in 38 malignant breast tumours. The expression of hTERT was then correlated with the lymph node status, c-Myc expression and other clinicopathological parameters of the tumours. hTERT expression was positive in 27 (71%) of the 38 tumours. 15 (79%) of 19 node positive tumours were hTERT positive compared with 11 (63%) of 19 node negative tumours. The expression was higher in node positive tumours but this failed to reach statistical significance (p = 0.388). There was no significant association with tumour size, tumour grade or c-Myc expression. However, hTERT expression correlated positively with patients' age (correlation coefficient = 0.415, p = 0.0097). hTERT protein expression is independent of lymph node status, tumour size and grade and c-Myc protein expression in human breast cancer.


Prevalence of hearing loss in children living in low- and middle-income countries over the last 10 years: A systematic review.
To summarize the literature on the prevalence of pediatric hearing loss in low- and middle-income countries (LMICs). A systematic review initially identified 2833 studies, of which 122 met the criteria for inclusion. Eighty-six of those studies included diagnoses and were included in a meta-analysis. The meta-analysis indicated a 1% (95% confidence interval = 0.8-2.0) prevalence of childhood hearing loss across LMICs. There was significant heterogeneity between studies and evidence of publication bias. The prevalence of mild and moderate cases of hearing loss was higher than more severe cases and there were fewer cases of mixed hearing loss compared to conductive or sensorineural hearing loss. No differences were identified between the prevalence of unilateral versus bilateral hearing loss or hearing loss according to sex. The quality of the studies, age of participants, and location of data collection may have influenced the results. High variability in the reporting of etiology made the causes of hearing loss unclear. The literature indicates that 1% of children in LMICs have hearing losses. However, most studies missed children with acquired hearing loss, which may lead to under-reporting of global prevalence. This systematic review is an initial step toward developing and implementing population-appropriate treatment and prevention programs for childhood hearing loss in LMICs. The prevalence of childhood hearing loss in low- and middle-income countries is 1%. Reporting of hearing loss etiology was highly variable.