Melatonin, lipid peroxidation, and age in heterophils from the ring dove (Streptopelia risoria).
Numerous recent studies have shown the ability of physiological as well as all pharmacological concentrations of melatonin to prevent oxidative stress. We have found that incubating avian heterophils from young birds with a pharmacological concentration of 100 microM (23x10(6) pg/ml) melatonin reduced superoxide anion levels by modulating the activity of superoxide dismutase while also enhancing phagocytosis. There was also a decline in lipid peroxidation levels with both physiological and pharmacological concentrations of this indolamine. In the present work, we evaluated malonaldehyde (MDA) levels as an indicator of lipid peroxidation (both basal and antigen-induced) in young and old animals (ring doves) at different times of day (16:00 and 00:00) and with two incubation times (15 and 60 min). The lipid peroxidation was also measured in heterophils from old animals, incubated with the physiological concentrations of melatonin measured in young animals (50 and 300 pg/ml, diurnal and nocturnal, respectively). The results, expressed as nmol MDA/mg protein, show that MDA levels were higher in heterophils of old animals than in the young birds in all the experimental groups studied at both 16:00 and 00:00 (00:00 is the time at which the lowest peroxidation levels were obtained). Incubation with melatonin was found to reduce MDA levels, with the maximum reduction being after the 60?min incubation time and the nocturnal melatonin concentration. At both concentrations (diurnal and nocturnal), melatonin also counteracted the enhancement of MDA levels caused by latex beads, with the effect being greater at the longer incubation time. In conclusion, the results are further evidence of the antioxidant effect of melatonin even at physiological concentrations, and suggest its utility as a therapeutic agent in some pathological processes associated with age.


The binding characteristics of the interaction between 3-(2-cyanoethyl) cytosine and human serum albumin.
The binding characteristics of the interaction between 3-(2-cyanoethyl) cytosine (CECT) and human serum albumin (HSA) were investigated using fluorescence, UV absorption spectroscopic and molecular modeling techniques under simulative physiological conditions. The intrinsic fluorescence intensity of HSA was decreased with the addition of CECT. The fluorescence data handled by Stern-Volmer equation proved that the quenching mechanism of the interaction between CECT and HSA was a static quenching procedure. The binding constants evaluated utilizing the Lineweaver-Burk equation at 17, 27 and 37 °C, were 2.340 × 10(4), 2.093 × 10(4) and 1.899 × 10(4) L mol(-1), respectively. The thermodynamic parameters were calculated according to van't Hoff equations. Negative enthalpy (ΔH) and positive entropy (ΔS) values indicated that both hydrogen bond and hydrophobic force played a major role in the binding process of CECT to HSA, which was consistent with the results of the molecular modeling study. In addition, the effect of other ions on the binding constant of CECT-HSA was examined.


Korean nurses' attitudes towards older people with dementia in acute care settings.
To identify and describe Korean nurses' attitudes towards older people with dementia in acute care settings and to examine the effect of selected socio-demographics and nursing work characteristics on attitudes. In Korea, older people receive health care services in acute care settings because long-term care settings are not the norm. Culturally, it is considered shameful to place parents or relatives in a long-term care facility. A descriptive survey design. Attitudes towards older people with dementia were measured in Korean registered nurses (n = 100) working in acute care settings of two hospitals in southern Korea in 2009. The Attitudes toward the Elderly with Dementia (AED) and the Approaches to Dementia Questionnaire (ADQ) were administered to participants. Moderately positive attitudes towards older people with dementia in the acute care setting were found. Two-thirds of the nurse participants (n = 65, 65.7%) working in medical wards demonstrated significantly more positive attitudes than those working in surgical wards (n = 34, 34.3%). Demographics including years of experience in the current unit and in the service, and nurses' position did not correlate significantly with their attitudes. The environment, work routine and technology may influence the likelihood of negative attitude towards people with dementia. IMPLICATIONS FOR PRACTICE. There may be conflict between nurses' cultural values and care practices in acute care settings. Therefore, there is a need for ongoing education of nurses in dementia care that may reduce the potential of such conflicts.


Sensory Function and Chronic Pain in Multiple Sclerosis.
To examine whether hypoesthesia and chronic pain are related in patients with MS. Sixty-seven MS patients with pain and 80 persons without MS were included. Sensory functioning was tested by bedside neurological examination. Touch, joint position (dorsal column-medial lemniscus pathway), temperature sense, and pain (spinothalamic tract) were tested. Pain intensity was measured by the Colored Analogue Scale (CAS Intensity) and the Faces Pain Scale (FPS); pain affect was also measured by CAS Affect and Number of Words Chosen-Affective (NWC-A). Mood was assessed with the SCL-90 anxiety and depression subscales and the Beck Depression Inventory (BDI). A significant negative relationship was found between pain intensity and the function of the dorsal column-medial lemniscal pathway, but not with the spinothalamic tract. In addition to the already known relation between hyperesthesia and pain, hypoesthesia for touch and joint position also seems to be related to chronic pain in MS patients.


Duane's retraction syndrome associated with cerebral arteriovenous malformation.
We have described a case of Duane's retraction syndrome in association with well documented cerebral arteriovenous malformation. This syndrome has been previously reported in association with anomalies of other parts of the body, but perusal of pertinent literature did not disclose reports of such a combination as seen in our patient.


Contribution of polymorphisms in UDP-glucuronosyltransferase and CYP2D6 to the individual variation in disposition of carvedilol.
It has been reported that carvedilol, which has beta-adrenergic blocking and vasodilating activities, is mainly metabolized by UDP-glucuronosyltransferase (UGT) 1A1, UGT2B4, UGT2B7 and CYP2D6. The aim of this study was to determine whether the activity of glucuronidation has an influence on the area under the curve (AUC) of carvedilol and whether polymorphisms in UGTs and CYP2D6 contribute to individual variation in disposition of carvedilol in Japanese. Plasma concentrations of carvedilol and its glucuronide were determined by reversed-phase high-performance liquid chromatography (HPLC). Genotyping of UGT1A1, UGT2B4 and UGT2B7 genes was carried out by the direct sequence method. CYP2D6 genotyping was carried out using an amplification refractory mutation system (ARMS) assay and PCR-restriction fragment length polymorphism (RFLP). The level of carvedilol glucuronidation ability in the high-level AUC group was significantly lower than that in the low-level group. The frequencies of UGT1A1*6, UGT2B7*3 and CYP2D6*10 in the low level ability of glucuronidation group were significantly higher than those in the high level group, and the same tendency was found in the frequency of CYP2D6*5, though there was no significant difference. Polymorphisms of UGT1A1, UGT2B7 and CYP2D6 strongly affect the pharmacokinetics and disposition of carvedilol in Japanese.


[Magnetic resonance tomography in sinus tarsi syndrome].
The sinus tarsi is a cone-shaped anatomical space in the hind foot that is bounded by the talus and calcaneus, the talonavicular and posterior sub-talar joint, and is continuous with the tarsal canal medially. The space courses from posteromedial to anterolateral, with the larger portion of the cone laterally situated. The sinus tarsi consists of fatty tissue, arterial anastomoses, joint recesses posteriorly, nerve endings, and five ligaments. These include the lateral, intermediate, medial roots of the inferior extensor retinaculum, the cervical ligament, and the interosseous ligament. The sinus syndrome is characterized by lateral foot pain, focal pain to palpation over the tarsal sinus, and hind foot instability. This chronic disease is related to a history of inversion trauma in the majority of patients. Magnetic resonance imaging (MRI) may be used in the evaluation of abnormalities associated with the sinus tarsi syndrome.


TL-350, an ergoline derivative with dopamine receptor agonist properties.
Intravenous and intraduodenal injection of a new ergoline derivative, TL-350, produced dose-dependent inhibition of heart rate increase produced by cardioaccelerator nerve stimulation in anesthetized cats. ID50 values of TL-350 were 0.019 and 0.047 mumol/kg after i.v. and intraduodenal injection, respectively. This inhibition was reversed by either sulpiride (0.15 mumol/kg i.v.) or haloperidol (0.13 mumol/kg i.v.) but not by yohimbine (0.14 mumol/kg i.v.). TL-350 did not change isoproterenol-induced tachycardia and hypotensive responses. TL-350 caused dose-dependent decrease of arterial blood pressure and heart rate in anesthetized cats. Haloperidol (0.13 mumol/kg i.v.) prevented the hypotensive and bradycardic effects of the compound. TL-350 also produced concentration-dependent inhibition of heart rate responses to transmural stimulation of isolated cat right atria. IC50 value was 0.026 microM. Dopaminergic antagonists, haloperidol and sulpiride, antagonized the inhibitory effect of TL-350 in in vitro experiments. TL-350 did not stimulate presynaptic alpha-2 adrenergic receptors in rat vas deferens and guinea-pig ileum. TL-350 induced rotation for 3 hr in rats with unilateral denervated caudate nucleus. The compound was 0.5 as potent as apomorphine. In [3H]dopamine binding assays using rat caudate tissue, TL-350 had approximately the same activity as apomorphine in displacing the radioligand. It was concluded that TL-350 is a selective dopamine receptor agonist without possessing alpha and beta adrenergic receptor stimulating activity.


The outcome of transanal advancement flap repair of rectovaginal fistulas is not improved by an additional labial fat flap transposition.
Transanal advancement flap repair (TAFR) has been advocated as the treatment of choice for patients with low rectovaginal fistulas. Recently, several studies have reported a significantly lower healing rate. We also encountered low healing rates after TAFR. In an attempt to improve our results, we added labial fat flap transposition (LFFT) to the TAFR of rectovaginal fistulas. The aim of the present study was to evaluate the outcome after TAFR and to investigate the impact of an additional LFFT. Between 1991 and 1997, 21 consecutive patients of median age 33 years underwent TAFR. The etiology of the fistulas was: obstetric injury (n=9), cryptoglandular abscess (n=8) and wound infection after anterior anal repair (n=4). The first 9 patients underwent TAFT with (n=3) or without (n=6) anterior anal repair. In the following 12 patients, LFFT was added to the advancement flap. In 4 of these a concomitant anterior anal repair was performed. The median follow-up was 15 months. The overall healing rate was 48%. In the first 9 patients, in whom no additional LFFT was performed, the rectovaginal fistula healed in 4 cases (44%). In the following 12 patients in whom an additional LFFT was performed, a similar healing rate was observed (50%). In conclusion, the outcome of transanal advancement flap repair of rectovaginal fistulas is poor. Addition of a labial fat flap transposition does not improve this outcome.


Surgical shunts compared with endoscopic sclerotherapy for the treatment of variceal bleeding in adults with portal hypertension: a systematic review and meta-analysis.
Portal hypertension is a common complication of chronic liver disease and can cause variceal bleeding which is associated with high mortality. Choices for the treatment of variceal bleeding include surgical shunts and endoscopic sclerotherapy. The aim of this study was to compare the efficacy of surgical shunts and endoscopic sclerotherapy in treating variceal bleeding due to portal hypertension. Systematic review and meta-analysis. Medline, PubMed, Cochrane and Google Scholar databases were searched until 12 February 2015, for relevant randomised control trials. Twenty studies with a total of 1540 participants were included. Patients with variceal bleeding due to portal hypertension. Surgical shunts compared to endoscopic sclerotherapy. Rates of rebleeding, survival and hepatoencephalopathy, and length of hospital stay. Pooled data for 17 studies showed that the rate of rebleeding was significantly more frequent with sclerotherapy compared with surgical shunt therapy (OR 3.99, 95% CI 2.98 to 5.33, p<0.001). The sclerotherapy patient group compared with the shunt group was less likely to develop hepatoencephalopathy (15 studies: pooled OR 0.53, 95% CI 0.31 to 0.91, p=0.021) and had shorter hospital stays (pooled mean difference-4.32, 95% CI- 7.97 to -0.66, p=0.021). No significant difference in the survival rate was observed between the two groups (seven studies: OR 1.01, 95% CI 0.63 to 1.62, p=0.964). This analysis indicated that the two types of treatment have similar mortality rates but differed with respect to rebleeding rate, incidence of hepatoencephalopathy and length of hospital stay.


Construction of a recombinant adenovirus containing the denV gene from bacteriophage T4 which can partially restore the DNA repair deficiency in xeroderma pigmentosum fibroblasts.
The denV gene from bacteriophage T4 encodes a pyrimidine dimer-specific endonuclease that has the capacity to initiate excision repair of DNA. Cells from excision repair-deficient xeroderma pigmentosum (XP) patients are able to carry out excision repair initiated by the denV gene product and introduction of the denV gene into XP cells results in the partial restoration of colony-forming ability after irradiation with UV light. In this work we have constructed a helper-independent recombinant human adenovirus, Ad5denV, which contains the denV gene. A 1.9 kb cartridge consisting of the denV gene flanked by the long terminal repeat (LTR) promoter from Rous sarcoma virus (RSV) and the simian virus 40 (SV40) polyadenylation (poly A) splice signals, was inserted into the E3 region of an E3 deletion mutant (Ad5d1E3) of adenovirus type 5. Infection of human fibroblasts and other permissive human cells with Ad5denV resulted in lytic infection and expression of the denV gene was confirmed by primer extension of infected cell RNA. The ability of the denV gene to restore the DNA repair deficiency in XP fibroblasts was examined using host cell reactivation of viral structural antigen formation for UV-irradiated adenovirus. The control virus, Ad5VSV, was also a recombinant which contained the gene for vesicular stomatitis virus glycoprotein G inserted into the E3 region of Ad5d1E3. UV survival of Ad5denV was similar to that of Ad5VSV following infection of two normal fibroblast strains and a Cockayne syndrome fibroblast strain, CS7SE, from complementation group B. In contrast, UV survival of Ad5denV was significantly greater than that for Ad5VSV after infection of three unrelated XP fibroblast strains from complementation groups A, C and E. However, UV survival of Ad5denV in the XP fibroblasts did not reach levels obtained in normal fibroblasts, indicating that restoration of the XP defect was partial.


Nutrition and prevention of chronic diseases: a unifying eco-nutritional strategy.
Increasing efforts are being made to address, in public health policy (PHP), both the persistence of nutritional deprivation in economically disadvantaged communities, and the increase in so-called "chronic disease" (abdominal obesity, diabetes, cardiovascular disease, certain cancers, osteoporosis, arthritides, and inflammatory disease) in communities at all stages of economic development. The problems in the "chronic disease" descriptor are that its origins may be as early as conception, rather than during the postnatal lifespan, or even in previous generations; it may appear abruptly or slowly; and it may be amenable to environmental and behavioural intervention well into its course and in older age groups. It is also not necessarily "non-communicable", a qualifier often used for "chronic disease" (chronic non-communicable disease or CNCD) and often has inflammatory features, for example the inflammatory marker C-reactive protein is a predictor of macrovascular disease and ischaemic events can, in part, be prevented in the affected by influenzal vaccination. The nexus between immunodeficiency, inflammatory processes and nutritional status which is characteristic of "infective" and food-borne illness, is also more and more evident in "chronic disease". It may be more helpful to consider "chronic disease" as "eco-disease" with its environmental and behavioural contributors, and to regard that which is clearly nutritionally dependent as "eco-nutritional disease".


Einstein oscillators in thallium filled antimony skutterudites.
Inelastic neutron scattering measurements on several Tl filled skutterudites (Tl0.5Co3.5Fe0.5Sb12, Tl0.8Co3FeSb12, and Tl0.8Co4Sb11Sn) all show a sharp peak in the vibrational density of states at 57+/-2 K, which is absent in the unfilled skutterudite CoSb3. Heat capacity measurements on Tl0.8Co4Sb11Sn as compared to CoSb3 are consistent with the presence of a localized vibrational mode associated with the "rattling" thallium atoms in this filled skutterudite compound. Both results are well described by a localized Einstein mode model with an Einstein temperature Theta(E) of 53+/-1 K. These data provide perhaps the clearest example of local mode behavior in a concentrated metallic system.


Macroeconomic changes and educational inequalities in traffic fatalities in the Baltic countries and Finland in 2000-2015: a register-based study.
This study examined trends and inequalities in road traffic accident (RTA) mortality in the Baltic countries (Estonia, Latvia, Lithuania) and Finland in relation to large-scale macroeconomic changes in the 2000s. Educational inequalities in RTA mortality in 2000-2003, 2004-2007, 2008-2011 and 2012-2015 among 30-74 year olds were examined using census-linked longitudinal mortality data and by estimating the relative and slope index of inequality. Overall RTA mortality decreased substantially between 2000-2003 and 2012-2015. From 2004-2007 to 2008-2011, the RTA mortality decline accelerated but was larger in the Baltic countries. Among men the RTA mortality decline was mostly driven by a larger fall among the high and middle educated. Among women, the changes in RTA mortality by educational level had no clear pattern. From 2000-2003 to 2012-2015 relative educational inequalities in RTA mortality increased among men, although more in the Baltic countries. Among women the pattern was mixed across countries. Absolute inequalities fell in all countries among both sexes. Educational inequalities in male RTA mortality may be growing because of increasingly less access to safer cars and a more hazardous driving culture among the lower educated.


Efficient delivery of the lncRNA LEF1-AS1 through the antibody LAIR-1 (CD305)-modified Zn-Adenine targets articular inflammation to enhance the treatment of rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia. Maintaining a balance between the proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs) is crucial for preventing the erosion of bone and cartilage and, ultimately, mitigating the progression of RA. We found that the lncRNA LEF1-AS1 was expressed at low levels in the RASFs and inhibited their abnormal proliferation by targeting PIK3R2 protein and regulating the PI3K/AKT signal pathway through its interaction with miR-30-5p. In this study, we fabricated a nano-drug delivery system for LEF1-AS1 using Zn-Adenine nanoparticles (NPs) as a novel therapeutic strategy against RA. The expression levels of LEF1-AS1, miR-30-5p, PIK3R2, p-PI3K, and p-AKT were detected in the primary RASFs and a human fibroblast-like synovial cell line (HFLS). Zn-Adenine nanoparticles (NPs) were functionalized with anti-CD305 antibody to construct (Zn-Adenine)@Ab. These NPs were then loaded with LEF1-AS1 to form (Zn-Adenine)@Ab@lncRNA LEF1-AS1. Finally, the (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs were locally injected into a rat model with collagen-induced arthritis (CIA). The arthritic injuries in each group were evaluated by HE staining and other methods. LEF1-AS1 was expressed at low levels in the primary RASFs. High expression levels of LEF1-AS1 were detected in the HFLS cells, which corresponded to a significant downregulation of miR-30-5p. In addition, the expression level of PIK3R2 was significantly increased, and that of p-PI3K and p-AKT were significantly downregulated in these cells. The (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly inhibited the proliferation of RASFs and decreased the production of inflammatory cytokines (IL-1β, IL-6, TNF-α). Intra-articular injection (IAI) of (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly alleviated cartilage destruction and joint injury in the CIA-modeled rats. LEF1-AS1 interacts with miR-30-5p to inhibit the abnormal proliferation of RASFs by regulating the PI3K/AKT signal pathway. The (Zn-Adenine)@Ab NPs achieved targeted delivery of the loaded LEF1-AS1 into the RASFs, which improved the cellular internalization rate and therapeutic effects. Thus, LEF1-AS1 is a potential target for the treatment of RA.


Rapid steroid discontinuation for pediatric renal transplantation: a single center experience.
To determine the outcomes of pediatric renal transplant recipients who received immunosuppression consisting of early withdrawal of corticosteroids at a single Northern California center. Protocols using minimal steroid exposure have been recently reported in adult transplant recipients with successful results. We examined the outcomes of pediatric renal transplant recipients who were managed at our center using a protocol with very early discontinuation of steroids after renal transplantation. We retrospectively studied the medical records of all renal transplant recipients followed at the Children's Hospital at the University of California, Davis Medical Center from 01/2004 to 12/2005. All patients were less than 18 yr of age at the time of transplantation. The immunosuppressive protocol included three tapering daily doses of methylprednisolone, together with five doses of thymoglobulin followed by maintenance therapy with tacrolimus and MMF. Eight patients with equal numbers of males and females were transplanted during this time period. There were equal numbers of Caucasians, African-Americans, Hispanics, and Asians. A total of 37.5% (3/8) of the subjects received preemptive transplantation, 25% (2/8) received peritoneal, and 37.5% (3/8) received hemodialysis before transplantation. The median (range) age at transplantation was 12.3 (3.1-16.0) year with a follow-up of 1.7 (0.9-2.8) year. At one yr post-transplantation, 57% (4/7) of patients still required anti-hypertensives. Three children required erythropoietin supplementation after transplantation. The mean delta height standard deviation score at 12 months was 0.20 +/- 0.56. There were no episodes of clinical acute rejection. One patient switched from tacrolimus to sirolimus due to biopsy-proven CAN. No patient became diabetic or required hypoglycemic agents. Surveillance biopsies showed no subclinical acute rejection in any patient. Steroid-free immunosuppression is safe in children after renal transplantation. Larger number of patients and longer follow-up are required to further confirm the effectiveness and safety of immunosuppression with rapid steroid discontinuation.


Is parotid saliva sterile on entry to the oral cavity?
The present study indicates that parotid saliva is sterile on entry to the oral cavity. The objective was to investigate if parotid saliva is sterile on entry to the oral cavity and, thus, prior to contamination by oral bacteria. Forty healthy volunteers were included in sterile parotid saliva collection. Parotid saliva was collected using a sterile Lashley cup, placed over the papilla of the Stensen´s duct, as well as sterile tubes and syringes for collection. All collections were followed by collection of a positive control sample where some of the sterile obtained parotid saliva had been exposed to the contralateral mucosal membranes. All samples parotid saliva, as well as the positive controls, were cultivated, and 10 randomly selected parotid saliva samples underwent polymerase chain reaction (PCR) analyses. In 33 of 40 parotid saliva samples there were no cultivable bacteria, whereas bacteria were cultivated in all positive control samples. In eight of 10 PCR samples no bacterial DNA was detected. The most frequent bacteria in the remaining non-sterile parotid saliva samples and positive control samples were non-haemolytical streptococci and the coagulase negative staphylococci.


Validation of an apicoplast genome target for the detection of Plasmodium species using polymerase chain reaction and loop mediated isothermal amplification.
The genome of the Plasmodium apicoplast, which has a higher copy number compared with current targets for molecular diagnosis of malaria, appears to be a suitable target for detection of submicroscopic infections that are capable of sustaining transmission. Novel primers targeting a conserved segment of the apicoplast (PFC10_AP|0010:rRNA) were designed and used in a number of different high throughput platforms such as single-step PCR (ssPCR), nested PCR (nPCR) and loop-mediated isothermal amplification (LAMP) for parasite detection. Replicates of ten-fold serial dilutions of Plasmodium falciparum 3D7 DNA, with equivalent parasite density ranges of 200,000 to 0.2 parasites/μL, were used to determine the limit of detection and repeatability of each assay. A panel of 184 archived DNA samples extracted from either EDTA whole blood or dried blood spots, from across West Africa and South East Asia was used to determine the diagnostic performance of the assays. All assays amplified the 2 parasites/μL dilution except the ssPCR, which amplified two of the three replicates. Using an 18S rRNA PCR as reference, the sensitivity was 98% (95% CI 93-100%) for the LAMP assay, 87% (95% CI 79-93%) for ssPCR and 100% (95% CI 97-100%) for nPCR. Specificity was 91% (95% CI 83-96%) for LAMP, 82% (95% CI 72-90%) for ssPCR and 66% (95% CI 54-76%) for nPCR. The apicoplast genome-based nPCR detected more positive samples overall than the reference method. Discrepant samples were confirmed as true positives using a probe-based real-time quantitative PCR assay. The results show that the apicoplast genome is a suitable target for molecular diagnosis of malaria.


Vanadate-dependent NADH oxidation in microsomal membranes of sugar beet.
Microsomal membranes isolated from sugar beet (Beta vulgaris L. var. GWD-2) storage tissue were found to contain a Na3VO4-dependent system for the oxidation of NADH. The system was demonstrated to be enzymatic in nature and specific for Na3VO4. Maximal Na3VO4-dependent NADH oxidation was observed at pH 6.5, when Na3VO4 was present at 200 microM and when NADH was present at 100 microM. The oxidation activity was insensitive to rotenone and antimycin A but was inhibited by NaN3, NaCN, and quinacrine. Sodium vanadate-dependent NADH oxidation occurred with a concomitant uptake of O2 from the assay solution. Both NADH oxidation and O2 consumption were dependent upon the presence of Na3VO4, inhibited by manganese, and preferred NADH to NADPH. Catalase prevented Na3VO4-dependent O2 consumption but accelerated NADH oxidation. The effects of manganese and catalase suggest that superoxide anion and hydrogen peroxide may be involved in this process. While it is unclear as to the physiological significance of Na3VO4-dependent NADH oxidation in plant cells, the presence of this system indicates that caution must be exercised when coupled ATPase assays depending upon NADH oxidation are used with plant membranes in the presence of Na3VO4.


Preoperative patient preparation: psychological and educational aspects.
Effective preoperative preparation can be a major investment in the determination of positive patient outcomes. Psychological preparation and patient education are important aspects of the patient's surgical experience. The trend toward ambulatory surgery decreases the time nurses spend with preoperative patients and challenges the perioperative nurse to provide effective comprehensive support in a limited amount of time.


HOXA4 protein levels and localization in the aorta and in human abdominal aortic aneurysms.
This report presents evidence for the specificities of select commercially available HOXA4 antibodies in regards to concerns about the specificity of the HOXA4 antibody used by Lillvis et al. (Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms. BMC Physiol 2011, 11:9). Using an antibody characterized extensively by us, Lillvis et al. report detecting HOXA4 at a size of 33 kDa despite our previous reports that HOXA4 is detected at ~37-39 kDa and that the ~30-33 kDa band is non-specific. Using small interfering RNA targeting HOXA4, forced expression of full-length HOXA4 and HOXA4-positive and -negative ovarian cancer cell lines, we confirm our previous findings that the ~30-33 kDa band is non-specific and that HOXA4 is detected at ~37-39 kDa. Moreover, we demonstrate that HOXA4 small interfering RNA reduces the ~37-39 kDa HOXA4 band, but not the ~30-33 kDa non-specific band, in a human acute monocytic leukemia cell line used by Lillvis et al. Western blot analysis performed with two additional commercially available HOXA4 antibodies also detected HOXA4 at ~37-39 kDa. Lastly, immunofluorescent staining of a HOXA4-negative ovarian cancer cell line with the antibody used by Lillvis et al. yields strong perinuclear staining, similar to that observed by Lillvis et al., which cannot be attributed to HOXA4. Our results highlight and briefly discuss the importance of careful antibody validation and selection for use in various applications.


The consequences of diarrhea occurring during chemotherapy for colorectal cancer: a retrospective study.
Diarrhea is one of the dose-limiting toxicities associated with chemotherapy agents in treatment regimens for colorectal cancer. The objectives of this study were to analyze the impact of all grades of diarrhea on clinical decisions for patients receiving treatment for colorectal cancer by characterizing the diarrhea that occurred, quantifying changes in chemotherapy treatment, identifying methods to treat diarrhea, and determining the economic impact. Patients and Methods. We retrospectively reviewed the treatment of 100 consecutive patients with colorectal cancer who experienced diarrhea during the course of chemotherapy. The diarrhea was documented in the progress notes and graded according to National Cancer Institute Common Toxicity Criteria. Changes in chemotherapy treatment and resource utilization associated with diarrhea were recorded. The 100 patients received 673 chemotherapy cycles, of which 45% +/- 2% were associated with diarrhea. Approximately 52% of patients experienced diarrhea of grades 3 or 4, and 56 patients underwent 66 modifications in their chemotherapy treatment, such as dose reductions (22), delays in therapy (8), discontinuations of therapy (15), or multiple changes (11). Thirty-seven patients consumed resources beyond oral antidiarrheals to control diarrhea: 14 patients received emergency outpatient treatment, 23 patients were hospitalized, 21 patients received intravenous fluids, and one death due to dehydration was reported. Discussion and Conclusion. Diarrhea was a significant consequence of colorectal chemotherapy, with the majority of patients experiencing grades 3 or 4 diarrhea and 56% of all patients also modifying their chemotherapy treatment. Even mild diarrhea of grades 1 and 2 was associated with changes in treatment in 11% of patients; thus, diarrhea of all grades should be recognized and treated appropriately to maintain full-dose chemotherapy.


Thin axons relative to myelin spiral length in hereditary motor and sensory neuropathy, type I.
The relationship of axonal to myelin area in semithin transverse sections of myelinated fibers obtained from sural nerves at the ankle level was morphometrically assessed using computer imaging. Ten patients with hereditary motor and sensory neuropathy, type I and 41 control subjects were examined. In large- and intermediate-diameter myelinated fibers of diseased nerves, axons were significantly attenuated relative to the amount of myelin. Using electron micrographs, a similar finding was obtained when axon area was regressed on myelin spiral length. The altered relationship was found to be greater with more severe fiber loss. These data, plus other evidence, indicate that in this disorder there is a progressive atrophy of axons, usually most severe in distal aspects of lumbosacral neurons and associated with secondary segmental demyelination and remyelination and hypertrophic neuropathy, preceding distal axonal loss. Because the process may begin in utero or in infancy, not only atrophy but also maldevelopment of axons may be involved.


Factors affecting safe and healthy diet in older adults in Italy: results of a preliminary study performed in a community-dwelling sample.
To investigate, through a questionnaire, older adults' demographic and socio-economic characteristics, knowledge, attitudes and practices in terms of food safety and healthy diet; and to develop dietary and hygiene indices able to represent participants' nutritional and food safety behaviour, exploring their association with demographic and socio-economic factors. One-year cross-sectional study. Gemelli Teaching Hospital (Rome, Italy). People aged ≥65 years, Italian speaking, accessing the Centre of Ageing Medicine. Mean age of the sample was 74 (sd 7·7) years. Subjective perception of a safe diet was high: 64·2 % of respondents believed they have a balanced diet. Interviewees got informed about proper nutrition mainly from television, magazines, newspapers, Internet (29·9 %) and from health professionals (34·8 %) such as dietitians, whereas 15·4 % from general practitioners. Regarding food safety, 33·8 % of participants reported to consume expired food, even more than once per month; between 80 and 90 % of participants reported to follow food safety practices during preparation and cooking, even though 49·3 % defrosted food at room temperature. Calculated dietary and hygiene indices showed that the elderly participants were far from having optimal nutritional and food safety behaviours. These results suggest it is necessary to increase the awareness of older adults in the matter of healthy diet and food safety. Specific and targeted educational interventions for the elderly and their caregivers could improve the adoption of recommended food safety practices and safe nutritional behaviours among older adults.


Effect of Nerve Growth Factor on Innervation of Perivascular Nerves in Neovasculatures of Mouse Cornea.
Angiogenesis, which is the generation of new vascular networks from existing blood vessels, occurs under normal and pathophysiological conditions. Perivascular nerves, which innervate mature vasculatures, maintain vascular tone and regulate tissue blood flow. However, little is known whether perivascular nerves innervate newborn blood vessels. Therefore, the aim of this study was to investigate the distribution and characterization of perivascular nerves in neovasculatures, which were generated by the mouse corneal micropocket method. Under anesthesia, a pellet containing basic fibroblast growth factor (bFGF) (100 ng/pellet) was implanted into a mouse cornea in one side of the eyeball. Nerve growth factor (NGF) was locally (2 or 20 ng) applied with the pellet, or subcutaneously (40 ng/h for 7 d) administered with an osmotic mini-pump. After the implantation, vascular endothelial cells, smooth muscle cells, and perivascular nerves in the cornea were immunohistochemically studied. Neovessels generated from existing limbal vessels were observed in pellet-implanted cornea. Immunostaining of neovasculatures showed the presence of CD31-like immunoreactive (LI) endothelial cells and α-smooth muscle actin-LI vascular smooth muscles. Perivascular nerves immunostained by protein gene product (PGP) 9.5, an axonal marker, were found in the existing limbal vessels, but they were not observed in neovasculatures. Local and subcutaneous treatment of NGF inhibits bFGF-derived angiogenesis and resulted in loop-shaped vessels that had many anastomoses, and produced innervation of PGP 9.5-LI perivascular nerves around bFGF-derived neovessels. These findings suggest that neovasculatures have no innervation of perivascular nerves, and that NGF facilitates innervations of perivascular nerves to regulate the blood flow in neovessels.


Analysis of cyclin D1 (CCND1) allelic imbalance and overexpression in sporadic human pituitary tumors.
Cyclin D1 plays an important role in the regulation of cell progression through G1 of the cell cycle and has been demonstrated to have oncogenic properties. Using RFLP-PCR, an A/G polymorphism within the cyclin D1 (CCND1) gene was analyzed in 151 sporadic human pituitary tumors, of which 60 were informative at this locus. Further analysis showed that in 15 of 60 (25%) tumors, there was evidence of allelic imbalance, which is indicative of gene amplification. Allelic imbalance was observed more frequently in invasive tumors (11 of 29 tumors; 38%) than in their noninvasive counterparts (4 of 31 tumors; 13%; P = 0.02). Forty-six of the tumors informative for the polymorphism were available for immunohistochemical analysis. Cyclin D1 expression (nuclear and/or cytoplasmic) was detected in 25 of 46 (54%) tumors. Of these cases, expression of nuclear cyclin D1 was detected in 9 of 46 (20%) tumors, whereas 16 of 46 (35%) tumors showed cyclin D1 staining exclusively confined to the cytoplasm. Neither nuclear staining nor cytoplasmic staining was observed in any of the normal pituitaries or in the negative control. Expression of cyclin D1 was observed in significantly more nonfunctional tumors (18 of 27 tumors; 67%) than in somatotrophinomas (7 of 19 tumors; 37%; P = 0.046). Nuclear cyclin D1 expression was observed more frequently in nonfunctional tumors (8 of 27 tumors; 30%) than in somatotrophinomas (1 of 19 tumors; 5%; P = 0.04). There was no correlation between cyclin D1 expression and tumor grade or between allelic imbalance of CCND1 and cyclin D1 expression. We conclude that amplification of CCND1 occurs in pituitary tumors and that the overexpression of cyclin D1 may be an early event in tumorigenesis. Cyclin D1 overexpression occurring in the absence of CCND1 allelic imbalance suggests that additional mechanisms responsible for deregulated cyclin D1 expression are involved in human pituitary tumorigenesis.


The outcomes of pathway database computations depend on pathway ontology.
Different biological notions of pathways are used in different pathway databases. Those pathway ontologies significantly impact pathway computations. Computational users of pathway databases will obtain different results depending on the pathway ontology used by the databases they employ, and different pathway ontologies are preferable for different end uses. We explore differences in pathway ontologies by comparing the BioCyc and KEGG ontologies. The BioCyc ontology defines a pathway as a conserved, atomic module of the metabolic network of a single organism, i.e. often regulated as a unit, whose boundaries are defined at high-connectivity stable metabolites. KEGG pathways are on average 4.2 times larger than BioCyc pathways, and combine multiple biological processes from different organisms to produce a substrate-centered reaction mosaic. We compared KEGG and BioCyc pathways using genome context methods, which determine the functional relatedness of pairs of genes. For each method we employed, a pair of genes randomly selected from a BioCyc pathway is more likely to be related by that method than is a pair of genes randomly selected from a KEGG pathway, supporting the conclusion that the BioCyc pathway conceptualization is closer to a single conserved biological process than is that of KEGG.


Dynamic changes in concentrations of auxin, cytokinin, ABA and selected metabolites in multiple genotypes of Douglas-fir (Pseudotsuga menziesii) during a growing season.
Changes in concentrations of several endogenous phytohormones and metabolites were analyzed in the long shoots of nine genotypes of coastal Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco var. menziesii) at five developmental stages: (1) closed buds, (2) flushing buds, (3) rapidly elongating shoots, (4) growing shoots and (5) near full-length shoots during one growing season. When averaged across genotypes, indole-3-acetic acid (IAA) concentration was high at stages 1 and 3. The only pattern that correlated with cone productivity was the one that was unique to IAA, in which high concentrations at stages 3 and 4 were found in all genotypes with high female cone productivity. Concentrations of isopentenyl adenosine (iPA) decreased and zeatin riboside (ZR) concentrations increased as the buds initiated and differentiated; ZR was 30 and 28 ng g(-1) dry weight (DW) at stages 1 and 4, respectively, before increasing to 166 ng g(-1) DW at stage 5. Isopentenyl adenosine peaked at 92 ng g(-1) DW at stage 2 and declined to low concentrations at stages 4 and 5. Zeatin-O-glucoside was 30 ng g(-1) DW at stage 1, declined at stages 2 and 3 and increased at stages 4 and 5. High abscisic acid (ABA) concentrations were positively correlated with rapid shoot elongation (stages 1 and 2), but as growth slowed and terminated, ABA concentrations decreased. Abscisic acid was 7 microg g(-1) DW at stage 1, increased to 13 microg g(-1) DW at stage 2 and then declined. The glucosyl ester (GE) of ABA decreased rapidly in early summer, and increased inversely with an increase in ABA. Between stages 1 and 2, ABA-GE decreased from 10 to 0.2 microg g(-1) DW and then increased. Of the ABA catabolites studied, 7'-hydroxy-ABA was about 2 microg g(-1) DW at stage 1, declined at stages 2 and 3 and increased at stages 4 and 5; phaseic acid concentrations were low at all stages, whereas dihydrophaseic acid was detected only at stages 4 and 5.


Wolbachia in butterflies and moths: geographic structure in infection frequency.
Butterflies and moths (Lepidoptera) constitute one of the most diverse insect orders, and play an important role in ecosystem function. However, little is known in terms of their bacterial communities. Wolbachia, perhaps the most common and widespread intracellular bacterium on Earth, can manipulate the physiology and reproduction of its hosts, and is transmitted vertically from mother to offspring, or sometimes horizontally between species. While its role in some hosts has been studied extensively, its incidence across Lepidoptera is poorly understood. A recent analysis using a beta-binomial model to infer the between-species distribution of prevalence estimated that approximately 40 % of arthropod species are infected with Wolbachia, but particular taxonomic groups and ecological niches seem to display substantially higher or lower incidences. In this study, we took an initial step and applied a similar, maximum likelihood approach to 300 species of Lepidoptera (7604 individuals from 660 populations) belonging to 17 families and 10 superfamilies, and sampled from 36 countries, representing all continents excluding Antarctica. Approximately a quarter to a third of individuals appear to be infected with Wolbachia, and around 80 % of Lepidoptera species are infected at a non-negligible frequency. This incidence estimate is very high compared to arthropods in general. Wolbachia infection in Lepidoptera is shown to vary between families, but there is no evidence for closely related groups to show similar infection levels. True butterflies (Papilionoidea) are overrepresented in our data, however, our estimates show this group can be taken as a representative for the other major lepidopteran superfamilies. We also show substantial variation in infection level according to geography - closer locations tend to show similar infection levels. We further show that variation in geography is due to a latitudinal gradient in Wolbachia infection, with lower frequencies towards higher latitudes. Our comprehensive survey of Wolbachia infection in Lepidoptera suggests that infection incidence is very high, and provides evidence that climate and geography are strong predictors of infection frequency.


Adherence to antiretroviral therapy in HIV-infected adults in Soweto, South Africa.
Little is known about achievable levels of antiretroviral treatment (ART) adherence in resource-limited settings. We conducted a cross-sectional study of adherence among patients at Chris Hani Baragwanath Hospital's Adult HIV Clinic in Soweto, South Africa. Adherence was assessed using a 1-month, self-report questionnaire and was calculated as a ratio of doses taken to doses prescribed. The 66 patients studied had a mean age of 36.1 years, a median duration of ART use of 18 months, and an overall baseline median CD4(+) cell count of 200/mm(3) (IQR: 114-364). The adherence reported by these patients for the previous month was >95% for 58 patients (88%), 90-95% for 6 (9%) and, < 90% for 2 (3%). The main reasons given for missing doses were being away from home (30%), difficulty with the dosing schedules (23%), and running out of pills (12%). Adherence decreased considerably with fear of being stigmatized by the sexual partner (OR = 0.13 95%, CI 0.02-0.70). Plasma HIV RNA levels were <400 copies/ml in the majority of patients (73% of those with adherence >95% and 88% of patients with < or =95% adherence) and the overall median CD4(+) cell count rose to 324/mm(3) (IQR: 193-510). High adherence and viral suppression are achievable for a significant proportion of HIV-infected patients taking ART in a resource-limited area such as Soweto, South Africa. Strategies to maximize adherence in this setting should emphasize ready access to affordable and simple ART regimens, as well as HIV education programs to help increase awareness and decrease disease stigmatization.


Laboratory and radiological investigations in general practice. I-Type requested and rate of use.
The use that 30 general practitioners in four group practices made of open access laboratory and radiological facilities was studied for one year. We were particularly interested in whether general practitioners hoped to exclude rather than confirm abnormality when requesting investigations. All but two of the general practitioners studied used investigations to exclude abnormality to a greater extent than to confirm it. The rate at which the practices investigated patients and the number of investigations requested were appreciably different and were different for individual general practitioners, part time general practitioners requesting more investigations than trainees and full time general practitioners. Haematological investigations accounted for over 30% of requests for investigations in all but one practice, biochemical investigations being requested as often as bacteriological investigations in two of the four practices. The ratio of expected to unexpected results varied among general practitioners; no general practitioner had more unexpected results and the range of ratios was similar for full time and part time general practitioners and for trainees. The proportion of patients with abnormalities uncovered by each practice increased disproportionately as the use of investigations increased, supporting a higher rather than lower rate of investigation among general practitioners. Compared with the results of other studies the use of the radiological facilities available was low. X ray examinations of the skeleton were requested more than chest and contrast media examinations by three of the four practices. Most x ray examinations were used to exclude rather than confirm abnormality by all the practices, with over 85% of results confirming the general practitioner's initial diagnosis.


PRMT8 demonstrates variant-specific expression in cancer cells and correlates with patient survival in breast, ovarian and gastric cancer.
Recent emphasis has been placed on the role of epigenetic regulators and epigenetic marks as biomarkers for cancer diagnosis and prognosis, and as therapeutic targets for treatment. One such class of regulators is the protein arginine methyltransferase (PRMT) family. The present study examined available curated data regarding the expression and alteration of one of the least studied PRMT family members, PRMT8, in various types of cancer and cancer cell lines. Publicly available cancer data on PRMT8 expression were examined using the Human Protein Atlas and the Kaplan-Meier Plotter, and reverse transcription-polymerase chain reaction was used to screen a selection of human cell lines for variant-specific PRMT8 expression. High levels of PRMT8 expression in breast, ovarian and cervical cancer was observed. Additionally, in patients with breast and ovarian cancer, high PRMT8 expression was correlated with increased patient survival, whereas in gastric cancer, high PRMT8 expression was correlated with decreased patient survival. The present study also investigated the expression of PRMT8 variant 2, a novel transcript variant recently identified in our laboratory, in various cancer cell lines. Variant-specific expression of PRMT8 in numerous distinct cancer cell lines derived from different tissues, including the expression of the novel PRMT8 variant 2 in U87MG glioblastoma cells was demonstrated. The present study proposes the possibility of PRMT8 as a cancer biomarker, based on the high level of PRMT8 expression in various types of cancer, particularly in tissues that would not normally be expected to express PRMT8, and on the correlation of PRMT8 and patient lifespan in several cancer types. Variant-specific expression of PRMT8 in diverse cancer cell lines suggests the possibility of alternate PRMT8 isoforms to have diverse effects on cancer cell phenotypes.


[Leptospirosis and kidneys: a clinical case].
We describe here the case of a young patient, employed in agriculture, who entered the emergency room with fever, headache, hematuria and a worsening of renal function; we diagnosed leptospirosis with renal involvement. As the patient lamented very generic symptoms, the anamnesis was fundamental in leading us to suspect an infection, execute the right laboratory analysis, and correctly diagnose a pathology which is currently very rare in Italy.


A C-type lectin receptor pathway is responsible for the pathogenesis of acute cyclophosphamide-induced cystitis in mice.
Hemorrhagic cystitis often arises after cyclophosphamide (CYP) administration. As yet, however, the mechanism involved in its pathogenesis is unknown. In this study, it was found that the Fc receptor γ chain (FcRγ)- caspase recruitment domain-containing protein 9 (CARD9)-dependent pathway rather than the myeloid differentiation primary response gene 88 (MyD88)-dependent pathway is involved in the pathogenesis of acute CYP-induced cystitis in mice. Rapid and transient production of interleukin (IL)-6 and IL-1β was detected in the bladder at 4 hr, preceding IL-23 and IL-17A production and an influx of neutrophils, which reached a peak at 24 hr after injection. As assessed by weight, edema and neutrophil infiltration, cystitis was significantly attenuated in CARD9 knockout (KO) and FcRγKO mice, this attenuation being accompanied by impaired production of IL-1β, IL-6, IL-23 and IL-17A. The major source of IL-17A is the vesical γδ T cell population: IL-17AKO, CδKO and Tyk2KO mice showed little IL-17A production and reduced neutrophil infiltration in the bladder after CYP injection. These results suggest that FcRγ-CARD9-dependent production of proinflammatory cytokines such as IL-1β, IL-6, and IL-23 and the subsequent activation of IL-17A-producing γδ T cells are at least partly involved in the pathogenesis of acute CYP-induced cystitis in mice.


Feasibility of interactive magnetic resonance imaging of moving anatomy for clinical practice.
Real-time magnetic resonance imaging (MRI) imaging with real-time reconstruction has been available for some time. The technique acquires and presents the MRI images to the operator the instant they are acquired. However, besides guiding purposes, like catheter tracking and placement of electrodes during neurosurgery, the diagnostic value of this method is relatively unexplored. To test an interactive slice-positioning system with respect to real-time MRI reconstruction for imaging of moving anatomical structures on two different scanner brands by using inexpensive computer hardware. The MRI data were sampled using two acquisition schemes: a Cartesian sampling scheme and a radial sampling scheme based on the golden ratio. Four anatomical targets, which exhibit non-periodic movement, were identified and imaged: movement of the gastric ventricle emptying, movement of the small bowels, the articulators of a professional singer and of a 20-week old fetus. Informative anatomical images were obtained in different settings of moving targets. The implemented real-time system acquired, reconstructed and displayed MRI images in real time with a high frame rate using inexpensive computer hardware on two standard 1.5 T clinical MRI scanners. Our approach verified that when imaging selected moving anatomical targets, with no a priori knowledge of the movement, interactive slice positioning using real-time reconstruction may be a feasible approach for finding the optimal slice position in cases in which a standard 3D volumetric scan is impeded by movement. Future studies are needed to explore its full potential.


The Na+/Ca2+ exchange inhibitor 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate (KB-R7943) also blocks ryanodine receptors type 1 (RyR1) and type 2 (RyR2) channels.
Na(+)/Ca(2+) exchanger (NCX) is a plasma membrane transporter that moves Ca(2+) in or out of the cell, depending on membrane potential and transmembrane ion gradients. NCX is the main pathway for Ca(2+) extrusion from excitable cells. NCX inhibitors can ameliorate cardiac ischemia-reperfusion injury and promote high-frequency fatigue of skeletal muscle, purportedly by inhibiting the Ca(2+) inward mode of NCX. Here we tested two known NCX inhibitors, 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)-isothiourea methanesulfonate (KB-R7943) and the structurally related 2-[[4-[(4-Nitrophenyl)methoxy]phenyl]methyl]-4-thiazoli dinecarboxylic acid ethyl ester (SN-6), for their influence on electrically or caffeine-evoked Ca(2+) transients in adult dissociated flexor digitorum brevis (FDB) skeletal muscle fibers and human embryonic kidney (HEK) 293 cells that have stable expression of type 1 ryanodine receptor (RyR1). KB-R7943 (< or = 10 microM) reversibly attenuates electrically evoked Ca(2+) transients in FDB and caffeine-induced Ca(2+) release in HEK 293, whereas the structurally related NCX inhibitor SN-6 does not, suggesting that KB-R7943 directly inhibits RyR1. In support of this interpretation, KB-R7943 inhibits high-affinity binding of [(3)H]ryanodine to RyR1 (IC(50) = 5.1 +/- 0.9 microM) and the cardiac isoform RyR2 (IC(50) = 13.4 +/- 1.8 microM). KB-R7943 interfered with the gating of reconstituted RyR1 and RyR2 channels, reducing open probability (P(o)), shortening mean open time, and prolonging mean closed time. KB-R7943 was more effective at blocking RyR1 with cytoplasmic conditions favoring high P(o) compared with those favoring low P(o). SN-6 has negligible activity toward altering [(3)H]ryanodine binding of RyR1 and RyR2. Our results identify that KB-R7943 is a reversible, activity-dependent blocker of the two most broadly expressed RyR channel isoforms and contributes to its pharmacological and therapeutic activities.


Asymmetry in above- and belowground productivity responses to N addition in a semi-arid temperate steppe.
Nitrogen (N) enrichment often increases aboveground net primary productivity (ANPP) of the ecosystem, but it is unclear if belowground net primary productivity (BNPP) track responses of ANPP. Moreover, the frequency of N inputs may affect primary productivity but is rarely studied. To assess the response patterns of above- and belowground productivity to rates of N addition under different addition frequencies, we manipulated the rate (0-50 g N m-2 year-1 ) and frequency (twice vs. monthly additions per year) of NH4 NO3 inputs for six consecutive years in a temperate grassland in northern China and measured ANPP and BNPP from 2012 to 2014. In the low range of N addition rates, BNPP showed the greatest negative response and ANPP showed the greatest positive responses with increases in N addition (<10 g N m-2 year-1 ). As N addition increased beyond 10 g N m-2 year-1 , increases in ANPP dampened and decreases in BNPP ceased altogether. The response pattern of net primary productivity (combined above- and belowground; NPP) corresponded more closely to ANPP than to BNPP. The N effects on BNPP and BNPP/NPP (fBNPP ) were not dependent on N addition frequency in the range of N additions typically associated with N deposition. BNPP was more sensitive to N addition frequency than ANPP, especially at low rates of N addition. Our findings provide new insights into how plants regulate carbon allocation to different organs with increasing N rates and changing addition frequencies. These root response patterns, if incorporated into Earth system models, may improve the predictive power of C dynamics in dryland ecosystems in the face of global atmospheric N deposition.


7Alpha-methyl-19-nortestosterone maintains sexual behavior and mood in hypogonadal men.
The synthetic steroid 7alpha-methyl-19-nortestosterone (MENT) is a potent androgen that is resistant to 5alpha-reductase. It thus has decreased activity at the prostate and may have advantages over testosterone-based regimens in long term treatment or as part of a male contraceptive. Administration to eugonadal men results in suppression of gonadotropins, but its ability to support androgen-dependent behavior has not been investigated. For sustained release administration, MENT acetate was used, because its diffusion characteristics were more suitable for use in implants. However, upon release the acetate is rapidly hydrolyzed, and MENT is the biologically active moiety in circulation. We studied the effects of MENT on sexual interest and activity, spontaneous erection, and mood states in comparison with testosterone enanthate (TE) in 20 Caucasian and Chinese hypogonadal men recruited in Edinburgh and Hong Kong (n = 10 in each center). Outcomes were measured using a combination of daily diaries, semistructured interviews, and questionnaires. Nocturnal penile tumescence (NPT) was also recorded in the Edinburgh group. After withdrawal of androgen replacement treatment (wash-out phase) for a minimum of 6 weeks, subjects were randomized to two groups in a cross-over design. Drug treatment regimens were of 6-week duration and consisted of two implants, each containing 115 mg MENT acetate, inserted s.c. into the upper arm and removed after 6 weeks and two injections of TE (200 mg, i.m.) 3 weeks apart. MENT treatment resulted in stable plasma MENT concentrations of 1.4 +/- 0.1 nmol/L after 3 weeks and 1.3 +/- 0.1 nmol/L after 6 weeks (mean +/- SEM; all men). Nadir testosterone concentrations were 3.6 +/- 0.6 nmol/L at the end of the wash-out phase and 9.4 +/- 0.6 nmol/L 3 weeks after each injection. There were no differences in hormone concentrations between centers. There were no adverse toxicological effects. There were only minor differences between the two treatments. Both MENT and TE treatment resulted in significant increases in sexual interest and activity, spontaneous erection (both by self-report and NPT measurement), and increases in positive moods, with decreases in negative moods in the Edinburgh group. In the Hong Kong group, both treatments increased waking erection, with a trend toward increased sexual interest and activity. Mood states appeared to be less affected during the wash-out phase than in Edinburgh men and showed no significant response to either treatment. These results demonstrate that MENT has similar effects on sexual activity and mood states as testosterone in hypogonadal men. As NPT is a physiological androgen-dependant outcome, these data provide further evidence for the androgenicity of MENT. The lack of detected effect of either androgen in Hong Kong men other than on waking erection illustrates the importance of the cultural context of symptomatology and its measurement. The appropriate dose of MENT remains to be determined, but these results support its development as a potential androgen replacement therapy.


Menopausal symptoms among four major ethnic groups in the United States.
The purpose of the study was to explore ethnic differences in symptoms experienced during the menopausal transition among four major ethnic groups in the United States. This study was done via a cross-sectional Internet survey among 512 midlife women recruited using a convenience sampling. The instruments included questions on background characteristics, ethnicity-related factors, health, and menopausal status and the Midlife Women's Symptom Index. The data were analyzed using descriptive and inferential statistics. Significant ethnic differences were found in the total number and severity of the symptoms. The most frequently reported symptoms and predictors of the total number and severity of the symptoms differed by ethnic identity. More in-depth cultural studies are needed to understand the reasons for the ethnic differences in menopausal symptom experience.


[Angiodysplasias of the head and neck: present-day principles of treatment using elements of plastic surgery].
The authors assessed the outcomes of treatment of fifty-one patients presenting with angiodysplasias of the head and neck. Of these, 24 patients suffered from the venous form and 27 had the arteriovenous form. The 51 patients accounted for 23.5% of the total number of patients with congenital vascular malformations over a five-year period. The topicity and angioarchitectonics of the lesion were specified by means of the standard diagnostic complex (i. e., duplex scanning of the vessels, ultrasonographic study of the soft tissues and osseous structures, computed and magnetic resonance tomography, echocardiography, and angiography). Radical excision of the angiomatous tissues was performed in 15 patients and palliative one - in 36 cases. Eight patients were subjected to stagewise resection interventions, ten patients underwent stagewise sessions of laser coagulation, and seven patients endured stagewise roentgenoendovascular embolisations of the afferent arteries. Two patients with the venous form were postoperatively subjected to sessions of sclerotherapy of the residual venous caverns. Two patients in the remote period (7-10 days) underwent autodermoplasty with a free perforated cutaneous flap. This technique was used while closing the wound surface after removing the angiomatous tissues of the parotid region and hairy portion of the head. In five patients the wound surface was closed with a mobilized cervical fat-cutaneous flap. Taking into consideration the importance of the cosmetic outcome after excising the angiomatous tissues on the face and neck, it is necessary to seek for wide application of plastic methods of closing the wound. These methods simultaneously allow of making operative interventions for angiodysplasias more radical.


The relationship between nursing students' environmental literacy and awareness of Global Climate Change.
This study aims to examine the correlation between environmental literacy and levels of awareness of global climate change in nursing students. The cross-sectional and correlational design. 476 undergraduate nursing students METHODS: Data were collected with The Personal Information Form, the Awareness Scale of University Students about Global Climate Change, and Environmental Literacy Scale for Adults in March 2023. Descriptive statistics, correlation, and linear regression analysis (stepwise method) were used to analyze the data. The mean scores of the Environmental Literacy Scale and the Awareness Scale of University Students about Global Climate Change Scale were 87.31 ± 8.61 and 75.60 ± 14.86, respectively. A positive correlation was found between the awareness of global climate change and environmental literacy (p < 0.05). As participation in meetings on environmental problems, environmental concerns and awareness increased, awareness of global climate change increased. Nursing students had high levels of awareness of global climate change and environmental literacy. The awareness of nursing students on climate change and their environmental literacy levels are highly important in protecting public health against the adverse effects of climate change and reducing climate change through effective resource management in health services in the future. It is recommended that integrate courses related to environment health to curriculum of nursing school and in-service training during healthcare. The study draws attention to the Sustainable Development Goals related to climate change.


Brief communication: oxygen isotopes as a biomarker for sickle-cell disease? Results from transgenic mice expressing human hemoglobin S genes.
The origins of sickle-cell disease (SCD) are well understood, as are its evolutionary pressures on humans and pathological presentation. However, because it has not been possible to identify SCD in archaeological contexts, its biocultural effects on past populations are unknown. Previous research investigating oxygen isotope fractionation during respiration among anemics suggests that oxygen isotopes in bone apatite may provide a biological marker for SCD in skeletal remains. This pilot study reports δ(18) O ratios in bone apatite of transgenic laboratory mice expressing human SCD globins and compares them to healthy control mice. The δ(18) O ratios of sick mice are significantly lower than those of healthy mice (-5.6‰ vs. -4.5‰; P = 0.002), and the sickest mice exhibit the lowest ratios of all (mean δ(18) O = -5.8‰). These preliminary results suggest that this method may be usefully applied to skeletal materials of past human populations whose diets and water sources do not differ substantially.


Septum orbitale: high-resolution MR in orbital anatomy.
The purpose of this study was to ascertain whether MR imaging, with the use of a surface coil, can accurately show small intraorbital structures; in particular, the septum orbitale. Examinations of 26 patients who underwent unilateral orbital high-resolution MR imaging for different indications were evaluated to differentiate the septum orbitale from related structures, such as the aponeurosis of the levator palpebrae, the superior tarsal (Müller's) muscle, and the superior orbital (Whitnall's) ligament. A subtle differentiation of the septum orbitale was obtained in 23 patients (88%) and of the levator aponeurosis and Müller's muscle in 24 patients (92%). The orbicularis oculi muscle and the submuscular fibroadipose tissue were reliably identified in all patients. High-resolution MR imaging is suitable for differentiating small intraorbital structures. Nevertheless, an exact depiction of the septum orbitale remains very much dependent on the cooperation of the patient. The site of orbital disease can be determined precisely and in a noninvasive manner in relation to the septum orbitale.


Compression-induced changes on physical structures and calcification of the aromatic polyether polyurethane composite.
It is generally accepted that stress causes calcification in both bio-prosthetic and polyurethane heart valves. However, simple uni-axially- and bi-axially-stretched samples did not yield a feasible model for the elaboration of the stress-induced calcification. In this study, heat compaction combined with the incorporation of polyethylene has been explored. Specimens of polyurethane were solution cast onto a porous bi-axially-drawn ultra-high-molecular-weight polyethylene film and then heat compacted under a pressure of 18 MPa at a chosen temperature for 1.5 h. The heat-compaction-induced calcification and physical changes of the polyurethane composite were evaluated using a 28-day in vitro calcification model and Attenuated Total Reflection-Fourier Transform-Infrared (ATR-FT-IR) spectroscopy. The calcification results indicated that heat-compaction-induced calcification was double that achieved without heat compaction. Heat-compacted polyurethane composite showed higher affinity to calcium ions than the non-heat compacted sample. The ATR-FT-IR results showed that the heat-compaction-induced physical changes include distortions of polymeric molecules and permanent changes of microstructures. The distortions of polymeric molecules could be deteriorated in contact with different media. The relaxation of the stressed structures of the polyether moiety might serve as a calcium trap and a heterogeneous nucleation site for calcification. The permanent changes of microstructures resulted from high distortions also served as affinity sites attracting calcification.


The impact of aging on gray matter structural covariance networks.
Previous anatomical volumetric studies have shown that healthy aging is associated with gray matter tissue loss in specific cerebral regions. However, these studies may have potentially missed critical elements of age-related brain changes, which largely exist within interrelationships among brain regions. This magnetic resonance imaging research aims to assess the effects of aging on the organization of gray matter structural covariance networks. Here, we used voxel-based morphometry on high-definition brain scans to compare the patterns of gray matter structural covariance networks that sustain different sensorimotor and high-order cognitive functions among young (n=88, mean age=23.5±3.1 years, female/male=55/33) and older (n=88, mean age=67.3±5.9 years, female/male=55/33) participants. This approach relies on the assumption that functionally correlated brain regions show correlations in gray matter volume as a result of mutually trophic influences or common experience-related plasticity. We found reduced structural association in older adults compared with younger adults, specifically in high-order cognitive networks. Major differences were observed in the structural covariance networks that subserve the following: a) the language-related semantic network, b) the executive control network, and c) the default-mode network. Moreover, these cognitive functions are typically altered in the older population. Our results indicate that healthy aging alters the structural organization of cognitive networks, shifting from a more distributed (in young adulthood) to a more localized topological organization in older individuals.


Cyproterone acetate for hirsutism.
Hirsutism is a distressing and relatively common endocrine problem in women which may prove difficult to manage. Cyproterone acetate, an anti-androgen, is frequently used to treat hirsutism, usually in combination with ethinyl estradiol. The objective of this review was to investigate the effectiveness of cyproterone acetate alone, or in combination with ethinyl estradiol, in reducing hair growth in women with hirsutism secondary to ovarian hyperandrogenism. The Cochrane Menstrual Disorders and Subfertility Group trials register was searched (last search - 4 June 2002). The Cochrane Menstrual Disorders and Subfertility Group register is based on regular searches of MEDLINE (1966 to 2002), EMBASE (1980 to 2002), CINAHL (1982 to 2002), PsycINFO (1987 to 2002) and CENTRAL (Issue 2, 2002 of the Cochrane Library) the handsearching of several journals and conference proceedings, and searches of several key grey literature sources. All publications of randomised controlled trials of cyproterone acetate with or without estrogen versus placebo or other drug therapies for hirsutism were identified. All randomised controlled studies comparing:- cyproterone acetate to placebo- cyproterone acetate with ethinyl estradiol to placebo- cyproterone acetate with ethinyl estradiol to cyproterone acetate alone- cyproterone acetate (with or without estradiol) to other medical therapies for treatment of hirsutism. Eleven studies were identified which fulfilled the inclusion criteria. Nine randomised studies were included in the review, and two were excluded because of insufficient information. Only one study had more than 100 women included in the analysis. The major outcomes included: subjective improvement in hirsutism, changes in Ferriman Gallwey scores, changes in linear hair growth and hair shaft diameter, alterations in endocrine parameters, side effects to treatment, withdrawals during therapy There were no clinical trials comparing cyproterone acetate alone with placebo. There was one small study comparing cyproterone acetate in combination with ethinyl estradiol to placebo. In this study there was a significant subjective reduction in hair growth with cyproterone acetate therapy, although the confidence limits were large. There were no studies comparing cyproterone acetate alone with cyproterone acetate in combination with ethinyl estradiol to treat hirsutism. In studies where cyproterone acetate was compared to other drug modalities (ketoconazole, spironolactone, flutamide, finasteride, GnRH analogues) no difference in clinical outcome was noted. There were, however, endocrinological differences in androgen and estrogen levels between different drug therapies. There were insufficient data to assess differences in side effects between women treated with cyproterone acetate and other medical therapy. Cyproterone acetate combined with estradiol results in a subjective improvement in hirsutism compared to placebo. Clinical differences in outcome between cyproterone acetate and other medical therapies were not demonstrated in the studies included in this review. This may be because of the small size of the studies, lack of standardized assessment and lack of objective determinants of improvement in hirsutism. The endocrinological effects of the different drug therapies reflect the mode of action. Larger carefully designed studies are needed to compare efficacy and safety profiles between drug therapies for hirsutism.


Interactions between CYP3A4 and Dietary Polyphenols.
The human cytochrome P450 enzymes (P450s) catalyze oxidative reactions of a broad spectrum of substrates and play a critical role in the metabolism of xenobiotics, such as drugs and dietary compounds. CYP3A4 is known to be the main enzyme involved in the metabolism of drugs and most other xenobiotics. Dietary compounds, of which polyphenolics are the most studied, have been shown to interact with CYP3A4 and alter its expression and activity. Traditionally, the liver was considered the prime site of CYP3A-mediated first-pass metabolic extraction, but in vitro and in vivo studies now suggest that the small intestine can be of equal or even greater importance for the metabolism of polyphenolics and drugs. Recent studies have pointed to the role of gut microbiota in the metabolic fate of polyphenolics in human, suggesting their involvement in the complex interactions between dietary polyphenols and CYP3A4. Last but not least, all the above suggests that coadministration of drugs and foods that are rich in polyphenols is expected to stimulate undesirable clinical consequences. This review focuses on interactions between dietary polyphenols and CYP3A4 as they relate to structural considerations, food-drug interactions, and potential negative consequences of interactions between CYP3A4 and polyphenols.


Hepatitis C virus (HCV) employs multiple strategies to subvert the host innate antiviral response.
Hepatitis C virus (HCV) is a serious global health problem which accounts for approximately 40% of chronic liver diseases worldwide. HCV frequently establishes a persistent infection, although it is recognized and targeted by innate immunity as well as cellular and humoral immune mechanisms. This suggests that HCV has developed powerful strategies to escape elimination by innate and adaptive immunity. HCV-induced liver injury is thought to be mainly immune-mediated rather than due to direct cytopathic effects of the virus. Hence, therapeutic strategies should target those mechanisms favoring viral persistence since unspecific enhancement of host antiviral immunity may theoretically also promote liver injury. The present review summarizes our current understanding of how the hepatitis C virus interferes with the innate antiviral host-response to establish persistent infection.


In vivo engineering of mobilized stem cell grafts with the immunomodulatory drug FTY720 for allogeneic transplantation.
The immunological attributes of stem cell grafts play an important role in the outcome of allogeneic stem cell transplants. Currently, ex vivo manipulation techniques such as bulk T-cell depletion or positive selection of CD34(+) cells are utilized to improve the immunological attributes of grafts and minimize the potential for graft-versus-host disease (GvHD). Here, we demonstrate a novel graft engineering technique, which utilizes the immunomodulatory drug FTY720 for in vivo depletion of naïve T (TN ) cells from donor G-CSF-mobilized grafts without ex vivo manipulation. We show that treatment of donor mice with FTY720 during mobilization depletes grafts of TN cells and prevents lethal GvHD following transplantation in a major mismatch setting. Importantly, both stem cells and NK cells are retained in the FTY720-treated grafts. FTY720 treatment does not negatively affect the engraftment potential of stem cells as demonstrated in our congenic transplants or the functionality of NK cells. In addition, potentially useful memory T cells may be retained in the graft. These findings suggest that FTY720 may be used to optimize the immunological attributes of G-CSF-mobilized grafts by removing potentially deleterious TN cells which can contribute to GvHD, and by retaining useful cells which can promote immunity in the recipient.


Inflammation in the vascular bed: importance of vitamin C.
Despite decreases in atherosclerotic coronary vascular disease over the last several decades, atherosclerosis remains a major cause of mortality in developed nations. One possible contributor to this residual risk is oxidant stress, which is generated by the inflammatory response of atherosclerosis. Although there is a wealth of in vitro, cellular, and animal data supporting a protective role for antioxidant vitamins and nutrients in the atherosclerotic process, the best clinical trials have been negative. This may be due to the fact that antioxidant therapies are applied "too little and too late." This review considers the role of vitamin C, or ascorbic acid in preventing the earliest inflammatory changes in atherosclerosis. It focuses on the three major vascular cell types involved in atherosclerosis: endothelial cells, vascular smooth muscle cells, and macrophages. Ascorbate chemistry, recycling, and function are described for these cell types, with emphasis on whether and how the vitamin might affect the inflammatory process. For endothelial cells, ascorbate helps to prevent endothelial dysfunction, stimulates type IV collagen synthesis, and enhances cell proliferation. For vascular smooth muscle cells, ascorbate inhibits dedifferentiation, recruitment, and proliferation in areas of vascular damage. For macrophages, ascorbate decreases oxidant stress related to their activation, decreases uptake and degradation of oxidized LDL in some studies, and enhances several aspects of their function. Although further studies of ascorbate function in these cell types and in novel animal models are needed, available evidence generally supports a salutary role for this vitamin in ameliorating the earliest stages of atherosclerosis.


Comparative Pathogenicity of United Kingdom Isolates of the Emerging Pathogen Candida auris and Other Key Pathogenic Candida Species.
Candida auris, first described in 2009, has since emerged as an important, multidrug-resistant, nosocomial agent of candidemia, with large outbreaks reported worldwide and high mortality rates associated with therapeutic failure. The current study employed C. auris isolates from a variety of centers in the United Kingdom to evaluate the pathogenicity of this emerging pathogen compared to that of other common pathogenic yeast species in the invertebrate Galleria mellonella infection model. We showed that C. auris isolates differ in their growth characteristics in vitro, with a proportion of isolates failing to release daughter cells after budding, resulting in the formation of large aggregates of cells that cannot be physically disrupted. Our results also demonstrate strain-specific differences in the behavior of C. auris in G. mellonella, with the aggregate-forming isolates exhibiting significantly less pathogenicity than their nonaggregating counterparts. Importantly, the nonaggregating isolates exhibited pathogenicity comparable to that of C. albicans, which is currently accepted as the most pathogenic member of the genus, despite the fact that C. auris isolates do not produce hyphae and produce only rudimentary pseudohyphae either in vitro or in G. mellonella. IMPORTANCE The incidence of invasive candidiasis, which includes candidemia and deep tissue infections, continues to rise and is associated with considerable mortality rates. Candida albicans remains the most common cause of invasive candidiasis, although the prevalence of non-albicans species has increased over recent years. Since its first description in 2009, Candida auris has emerged as a serious nosocomial health risk, with widespread outbreaks in numerous hospitals worldwide. However, despite receiving considerable attention, little is known concerning the pathogenicity of this emerging fungal pathogen. Here, using the Galleria mellonella insect systemic infection model, we show strain-specific differences in the virulence of C. auris, with the most virulent isolates exhibiting pathogenicity comparable to that of C. albicans, which is currently accepted as the most pathogenic member of the genus.


α2-Macroglobulin-like protein 1 can conjugate and inhibit proteases through their hydroxyl groups, because of an enhanced reactivity of its thiol ester.
Proteins in the α-macroglobulin (αM) superfamily use thiol esters to form covalent conjugation products upon their proteolytic activation. αM protease inhibitors use theirs to conjugate proteases and preferentially react with primary amines (e.g. on lysine side chains), whereas those of αM complement components C3 and C4B have an increased hydroxyl reactivity that is conveyed by a conserved histidine residue and allows conjugation to cell surface glycans. Human α2-macroglobulin-like protein 1 (A2ML1) is a monomeric protease inhibitor but has the hydroxyl reactivity-conveying histidine residue. Here, we have investigated the role of hydroxyl reactivity in a protease inhibitor by comparing recombinant WT A2ML1 and the A2ML1 H1084N mutant in which this histidine is removed. Both of A2ML1s' thiol esters were reactive toward the amine substrate glycine, but only WT A2ML1 reacted with the hydroxyl substrate glycerol, demonstrating that His-1084 increases the hydroxyl reactivity of A2ML1's thiol ester. Although both A2ML1s conjugated and inhibited thermolysin, His-1084 was required for the conjugation and inhibition of acetylated thermolysin, which lacks primary amines. Using MS, we identified an ester bond formed between a thermolysin serine residue and the A2ML1 thiol ester. These results demonstrate that a histidine-enhanced hydroxyl reactivity can contribute to protease inhibition by an αM protein. His-1084 did not improve A2ML1's protease inhibition at pH 5, indicating that A2ML1's hydroxyl reactivity is not an adaption to its acidic epidermal environment.


Differences in sialic acid density in pathogenic and non-pathogenic Aspergillus species.
ASPERGILLUS: fumigatus is a ubiquitous soil fungus that causes invasive lung disease in the immunocompromised host. The structure of the conidial wall has not been well characterized although it is thought that adhesins present on the surface are involved in attachment of the conidia to host lung cells and proteins, which is a prerequisite for the establishment of infection. Negatively charged carbohydrates on the conidial surface have been previously identified as the molecules responsible for attachment of conidia to extracellular matrix proteins. The aim of this research was to identify carbohydrates on the conidial surface that contribute to its negative charge. Direct chemical analysis and indirect binding assays have demonstrated that A. fumigatus possesses sialic acids on the conidial surface. Pre-treatment of A. fumigatus conidia with sialidase decreased binding of a sialic acid-specific lectin, Limax flavus agglutinin (LFA), to the conidial surface and decreased adhesion of conidia to the positively charged polymer poly L-lysine. Two other sialic acid-specific lectins, Maackia amurensis agglutinin and Sambucus nigra agglutinin, exhibited negligible binding to A. fumigatus conidia indicating that 2,3-alpha- and 2,6-alpha-linked sialic acids are not the major structures found on the conidial surface. Mild acid hydrolysis and purification of conidial wall carbohydrates yielded a product that had the same R(F) as the Neu5Ac standard when analysed by high-performance thin-layer chromatography. A density of 6.7 x 10(5) sialic acid residues per conidium was estimated using a colorimetric assay. Conidia grown on a minimal medium lacking sialic acid also reacted with LFA, indicating that sialic acid biosynthesis occurs de novo. Sialic acid biosynthesis was shown to be regulated by nutrient composition: the density of sialic acids on the surface of conidia grown in minimal media was lower than that observed when conidia were grown on rich, complex media. It has previously been shown that pathogenic Aspergillus species adhere to basal lamina proteins to a greater extent than non-pathogenic Aspergillus species. To determine whether the expression of sialic acid on the conidial surface was correlated with adhesion to basal lamina, conidia from other non-pathogenic Aspergillus species were tested for their reactivity towards LFA. Flow cytometric analysis demonstrated that A. fumigatus had a significantly greater sialic acid density than three non-pathogenic Aspergillus species. Sialic acids on the conidial wall may be involved in adhesion to fibronectin, a component of the basal lamina, as binding of A. fumigatus conidia to fibronectin was strongly inhibited in the presence of a sialylated glycoprotein.


[Women with hereditary risk of breast cancer: consensus of surgical representatives of study groups for hereditary tumors regarding intensive monitoring, diagnosis and preventive resection].
Women in whom a hereditary increased risk of breast cancer is established are often moved by anxiety to ask a surgeon for intensive periodical checking of the breasts or prophylactic resection breast tissue. This article contains a consensus on the relevant policy reached by surgeons from the two cancer centres and eight university hospitals in the Netherlands. Intensive follow-up is indicated only when the risk of breast cancer is twice as high as in women from the population in general. The age from which check-up examinations are carried out is from 25 years or from 5 years before the age at which the youngest relative developed breast cancer. For female gene carries from families with hereditary breast cancer, whether or not identified, the risk of death from breast cancer in spite of intensive follow-up is 7-20%. Preventive bilateral mastectomy is recommended only in case of a demonstrated gene mutation or a life-long risk of breast cancer in excess of 50%. Even after preventive surgical treatment, women should report annually for examination, because frequently a little mammary tissue remains behind.


The forgotten protection factor: A nationwide score-based assessment of motorcycle eye protection legislation.
Motorcycle accidents cause millions of deaths and injuries globally. It is estimated that billions of dollars would be saved in the United States alone if safety equipment, such as helmets and eye protection, was ubiquitously worn. Legislation concerning eye protection specifically is understudied and poorly characterized. We reviewed all motorcycle-related safety equipment laws in all 50 states of the United States for information regarding eye protection. We graded the rigor of each statute using our six-category Eye Safety Metric and performed a comparative analysis of statutes across all jurisdictions. Fourteen states did not have any statutes regarding eye protection. Among states that did, 23 states had weak statutes (0-2 points), 20 states had moderately stringent statutes (3-4 points), and 7 states had strong statutes (5-6 points). States in western United States tended to have less strict eye protection laws. Twenty-six states had eye protection exemptions for windshields, which are a poor form of eye protection. Six states that had universal helmet laws had no laws requiring eye protection. We characterized eye protection legislation across the country and found great diversity in the stringency of laws across all jurisdictions. Despite only two states lacking helmet laws, we found that 14 states lacked eye protection laws. These findings from our Eye Safety Metric can be used as a springboard for future research, which can be used to determine the need for and significance of eye safety legislation for motorcyclists and to inform legislative decision-making. With this research, we hope to further the understanding of legislation regarding eye protection for motorcyclists and help policymakers identify states that need improved eye safety standards.


Bimodal transmission of cerebral malaria and severe malarial anemia and reciprocal co-existence of sexual and asexual parasitemia in an area of seasonal malaria transmission.
The parasite dynamics in severe malaria (SM) varies with malaria endemicity. This study was conducted in eastern Sudan, an area of seasonal and unstable malaria transmission. From the beginning of October to the end of December (malaria season) in the years 2000, 2001, and 2003, 99 patients with severe malarial anemia (SMA) and 54 patients with cerebral malaria (CM) were identified. There was marked variation in the incidence of SMA and CM (up to six folds) and in the CM/SMA incidence ratio, over 3 years. In the heavy season of 2003, CM peaked at the beginning of the season and declined within a month at a time that the SMA reached the peak. At diagnosis, the rate of gametocytemia had inclined from approximately 10% to 100% from the beginning to the end of the season. During follow-up, gametocytemia was more associated with SMA than with CM. Paradoxically, the late occurring SMA was associated with early gametocytemia (day 7) and the opposite was true in CM. In conclusion, within the season the transmission of CM and SMA was bimodal, the prevalence of the asexual and sexual parasitemia was reciprocal, and the peaks of transmission and gametocytemia were paradoxical.


Splenectomy in chronic myeloid leukaemia. A case report and review.
We report the case of a man with chronic myeloid leukaemia, whose disease had undergone transformation and whose life was threatened. Splenectomy was performed, and two years later he is alive and well, taking no anti-leukaemic therapy. Since splenectomy he has had one severe attack of malaria, and one episode of jaundice thought to be due to viral hepatitis. He discontinued his malaria prophylaxis one year ago and has not been ill since. Splenectomy as a last resort will benefit some patients with chronic myeloid leukaemia after transformation, and elective splenectomy should be considered in the management of patients with this disease. However, final unequivocal proof of the value of elective splenectomy is still awaited.


Strategic adjustments in sperm production within and between two island populations of house mice.
Sperm production is physiologically costly. Consequently, males are expected to be prudent in their sperm production, and tailor their expenditure according to prevailing social conditions. Differences in sperm production have been found across island populations of house mice that differ in the level of selection from sperm competition. Here, we determined the extent to which these differences represent phenotypic plasticity and/or population divergence in sperm production. We sourced individuals from two populations at the extreme levels of sperm competition, and raised them under common-garden conditions while manipulating the social experience of developing males. Males from the high-sperm competition population produced more sperm and better quality sperm than did males from the low-sperm competition population. In addition, males reared under a perceived "risk" of sperm competition produced greater numbers of sperm than males reared with "no risk." However, our analyses revealed that phenotypic plasticity in sperm production was greater for individuals from the high-sperm competition population. Our results are thus consistent with both population divergence and phenotypic plasticity in sperm production, and suggest that population level of sperm competition might affect the degree of adaptive plasticity in sperm production in response to sperm competition risk.


Immunological persistence of a seasonal influenza vaccine in people more than 3 years old.
To evaluate antibody persistence of Aleph inactivated split influenza vaccine, 3308 healthy Chinese people more than 3 years old were enrolled in a hemagglutination inhibition (HI) assay before vaccination, 641 were screened by HI assay negative, 437 of which received one dose of Aleph inactivated split influenza vaccine and 204 of which received one dose of control vaccine (recombinant hepatitis B). After vaccination, the receivers were collected blood at 1st month, 3rd month, 6th month and 12th month for Aleh influenza vaccine antibody persistence assess. The antibody test were determined by hemagglutination inhibition (HI) assay. There were significant difference in antibody geometric mean titer between experimental group and control at 1st month and 3rd month after vaccination. Influenza antibody could persist at least up to 3rd month. Because of the local spring influenza epidemic, we could not analyze the results of 6th and 12th month. Aleph influenza vaccines showed good immune persistence in healthy volunteers at least in the 3 months after vaccination. Influenza viruses are important human respiratory pathogens. Immunization is widely acknowledged to currently be the most effective method of minimizing the impact of pandemic influenza. Through we have checked many references about Influenza vaccine, the duration of protective antibody for influenza vaccines are still not available. Based on this situation and our previous work, (11) Influenza vaccine antibody duration analyze are necessary. This manuscript presents data on the persistence of Hemagglutination Inhibition (HI) immune response against the A/California/7/2009(H1N1), A/Peth/16/2009(H3N2) strain and B/Brisbane/60/2008. 641 were screened from 3302 volunteers by HI test of influenza A and confirmed enrollment based on the antibodies titer less than 1:10. After administered with one dose of Aleph influenza vaccine, blood samples were collected. 437 subjects (3-10 y: 131; 11-17 y: 110; 18-54 y: 69; ≥ 55 y: 127) were vaccinated influenza vaccine as test group. 204 subjects (3-10 y: 70; 11-17 y: 47; 18-54 y: 28; ≥ 55 y: 59) were vaccinated recombinant hepatitis B vaccine as control group. Immunogenicity end points were based on the European licensure criteria for pandemic influenza vaccines. The persistence of HI immune response against the vaccine strain was assessed through GMT. The immunogenicity of the Aleph influenza vaccine induced all reached the standards at 1st month and GMTs peak could persist at least up to 3rd month. (This study has been registered at clinicaltrials.gov under registration no. NCT01758185.). Because of the local spring influenza epidemic we could not analyze the results of 6th and 12th month. Aleph influenza vaccines showed good immune persistence in healthy volunteers at least in the 3 months after vaccination.


[A Patient with Small Cell Lung Cancer Presenting with Paralysis and Intramedullary Metastasis Successfully Treated with Chemotherapy].
A 77-year-old man was diagnosed with small cell lung cancer (SCLC: cT3N3M1b, Stage ⅣA)with bone metastases 1 year and 9 months ago. Although partial response was obtained after 6 courses of chemotherapy with carboplatin(CBDCA)and etoposide(VP-16), multiple brain metastases were observed 5 months after the completion of chemotherapy. The multiple brain metastases completely disappeared after whole brain irradiation. However, the patient experienced lower extremity weakness, predominantly in the left side, 5 months after irradiation. Contrast-enhanced magnetic resonance imaging(MRI) revealed an abnormal nodular lesion at the Th10 level, indicative of intramedullary spinal cord metastasis originating from the SCLC. After the patient was admitted to our hospital, his neurological symptoms progressed rapidly and he began to experience difficulty in standing, along with bowel and bladder dysfunction. Chemotherapy with CBDCA plus VP-16 improved the neurological symptoms, and MRI after 1 course of chemotherapy revealed a decrease in the size of the metastatic lesion in the spinal cord. Although neurological symptoms are common in patients with lung cancer, intramedullary metastases often promote irreversible neurological dysfunction. Herein, we report a patient with SCLC who developed intramedullary spinal cord metastasis and whose neurological symptoms dramatically improved after systemic chemotherapy.