[Surgical treatment of intra-articular calcaneus fractures].
The instable fractures of os calcis are usually treated by conservative methods with early functional mobilization. In a few cases we think that in the Tongue Type and especially in the Joint Depression Type of Essex-Lopresti a surgical treatment may be useful to reestablish the congruence and the geometry of the joint surface.


Attenuation of fibroblast growth factor signaling by poly-N-acetyllactosamine type glycans.
Fibroblast growth factors (FGFs) and their receptors are expressed in a variety of mammalian tissues, playing a role in development and cell proliferation. While analyzing human sperm motility, we found that sperm treated with endo-β-galactosidase (EBG), which specifically hydrolyzes poly-N-acetyllactosamine type glycans (polyLacs), enhanced motility. Mass spectrometry analysis revealed that sperm-associated polyLacs are heavily fucosylated, consistent with Lewis Y antigen. Immunohistochemistry of epididymis using an anti-Lewis Y antibody before and after EBG treatment suggested that polyLacs carrying the Lewis Y epitope are synthesized in epididymal epithelia and secreted to seminal fluid. EBG-treated sperm elevated cAMP levels and calcium influx, indicating activation of fibroblast growth factor signaling. Seminal fluid polyLacs bound to FGFs in vitro, and impaired FGF-mediated signaling in HEK293T cells.


Perioperative Considerations in a Patient with Kleine-Levin Syndrome Undergoing a Neurosurgical Procedure under General Anesthesia.
Kleine-Levin syndrome (KLS) is a rare central disorder of daytime hypersomnolence and is often characterized by a relapsing and remitting course, recurrent episodes of excessive sleep lasting from 12 to 20 hours a day, and symptoms including hyperphagia, hallucinations, derealization, disorientation, and hypersexuality. There are numerous perioperative considerations in dealing with KLS that include challenges during induction of anesthesia, delayed emergence, postoperative sleep disorders, and delirium. However, due to its rare occurrence, the anesthetic considerations of KLS remain poorly described. This case report outlines the anesthetic considerations and management of a young female patient with KLS who underwent transnasal excision of a trigeminal schwannoma under general anesthesia.


Importance of identification and typing of Brucellae from West African cattle: a review.
Bovine brucellosis is an endemic infectious disease which can impact cattle productivity and welfare negatively, as well as human health. Sufficient knowledge on its epidemiology, particularly on species and biotypes of Brucella at national and/or regional scale are important to set up and implement efficient control measures against brucellosis in a "One health" perspective. The main objective of this review was to investigate available literature on strains of Brucella in order to provide a state of art-knowledge on species and biovars reported in cattle from West Africa. A literature search was conducted to identify relevant data on species and biovars of Brucella in cattle from Western African countries. This search included studies presenting bacteriological and/or molecular results of identification and typing, relied on international classification methods with no time limit and no language restrictions. Studies reporting results of identification at genus level only were not considered for this review. This review revealed that Brucella abortus was the most prevalent species in cattle from West Africa, in line with host preference for Brucellae. So far, biovars 1, 2, 3, 4, 6 and intermediate biovar 3/6 of B. abortus were reported in cattle in the region. Among these strains, biovars 3, recently identified in The Gambia and Ivory Coast, was the most commonly isolated. Brucella melitensis and/or B. suis have not been mentioned yet in cattle in this part of Africa. The public health significance of prevailing strains is discussed and a regional collaborative control program of brucellosis is suggested.


A blow to the fly - Lucilia cuprina draft genome and transcriptome to support advances in biology and biotechnology.
The blow fly, Lucilia cuprina (Wiedemann, 1830) is a parasitic insect of major global economic importance. Maggots of this fly parasitize the skin of animal hosts, feed on excretions and tissues, and cause severe disease (flystrike or myiasis). Although there has been considerable research on L. cuprina over the years, little is understood about the molecular biology, biochemistry and genetics of this parasitic fly, as well as its relationship with its hosts and the disease that it causes. This situation might change with the recent report of the draft genome and transcriptome of this blow fly, which has given new and global insights into its biology, interactions with the host animal and aspects of insecticide resistance at the molecular level. This genomic resource will likely enable many fundamental and applied research areas in the future. The present article gives a background on L. cuprina and myiasis, a brief account of past and current treatment, prevention and control approaches, and provides a perspective on the impact that the L. cuprina genome should have on future research of this and related parasitic flies, and the design of new and improved interventions for myiasis.


Anti-inflammatory effects of Z23 on LPS-induced inflammatory responses in RAW264.7 macrophages.
Fissistigma oldhamii (Hemsl.) Merr, a traditional Chinese herb medicine, is used for treating rheumatoid arthritis in China. In our previous study, an effective compound, 7'-(3',4'-dihydroxyphenyl)-N-[(4-methoxyphenyl) ethyl] propenamide (Z23), from this herb has showed potent immunosuppressive effects both in vitro and in vivo. However, its anti-inflammatory effect and mechanism is still need to explore. We examined the in vitro effects of Z23 on the production of nitric oxide (NO), prostaglandin E2 (PGE2) and cytokines by lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Z23 significantly decreased the production of PGE2, NO, tumour necrosis factor alpha (TNFalpha) and IL6 production. Inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX2) gene expression were also significantly reduced. These results demonstrated that Z23 exerted an anti-inflammatory effect through modulating the synthesis of several mediators and cytokines involved in the inflammatory process. This study provided evidence to understand the therapeutic effects of Fissistigma oldhamii (Hemsl.) Merr and indicated that Z23 has the potential for treatment of various inflammatory diseases where the overproduction of NO, PGE2 and inflammatory cytokines has been shown to play a role, e.g. rheumatoid arthritis.


A true hermaphrodite dispermic chimera with 46,XX and 46,XY karyotypes.
A 16-year-old male with hypospadias and gynaecomastia had a rudimentary uterus with a right Fallopian tube and ovary; the left gonad was a functioning testis. Cytogenetic studies showed cells with 46,XX and 46,XY sex chromosomes in cultured blood, skin and gonadal tissues. Cells with the 46,XX constitution predominated in all tissues. Extensive investigations failed to demonstrate blood cell and serum chimerism, but there was little genetic variation of these characters between family members. Cytogenetic studies demonstrated that the father had contributed different marker chromosomes to the 46,XY and 46,XX cell lines of the propositus, whereas the mother had contributed the same two informative markers to both cell lines. The patient was a chimera with two diploid cell lines of different sex that had developed from the products of two separate acts of syngamy. Dispermy was demonstrated, and, whereas there was no evidence of different maternal contributions to the chimeric cell lines, uncertainty remains that these were identical.


COV-BT Ire study: safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with brain tumors.
The BNT162b2 vaccine conferred 95% protection against COVID-19 in people aged 16 years or older. The aim of this observational study was to evaluate safety and efficacy of vaccine in patients affected by primary brain tumor (PBT). We proposed COVID-19 vaccine to all patients affected by PBT followed by Neuroncology Unit of National Cancer Institute Regina Elena. 102 patients received the first dose, 100 the second, and 73 patients received the booster dose. After first dose, we observed one patient with fever and severe fatigue, while after the second one, we recorded adverse events in ten patients. No correlation was observed between adverse events and comorbidities. The COVID-19 vaccine is safe and well tolerated in PBT patients.


Association of Illicit Fentanyl Use with Injection Risk Practices Among People who Inject Drugs.
We investigated the association between fentanyl injection frequency and sharing of injection equipment among people who inject drugs. We surveyed 249 people who inject drugs in Toronto in 2019. We estimated predicted probabilities of associations between fentanyl injection frequency and injection risk practices. In prior 6 months, 117 (47.0%) of participants injected fentanyl daily, 49 (19.7%) less than daily, and 78 (31.3%) did not inject fentanyl. Participants who injected fentanyl daily shared syringes more often than those not injecting fentanyl (25.0% vs. 4.9%; χ2 = 11.54, p = 0.0007). Participants who injected fentanyl daily (42.4% vs. 11.3%; χ2 = 18.05, p < 0.0001) and less than daily (37.2% vs. 11.3%; χ2 = 5.88 p = 0.02) shared cookers more often than those not injecting fentanyl. Participants who injected fentanyl daily (30.2% vs. 9.7%; χ2 = 9.05, p = 0.003) and less than daily (30.3% vs. 9.7%; χ2 = 4.11, p = 0.04) shared filters more often than those not injecting fentanyl. No differences in probabilities of sharing equipment were detected between participants who injected fentanyl daily and less than daily. People using fentanyl reported injection practices that increased risk for infectious disease transmission.


From Scope to Screen: The Evolution of Histology Education.
Histology, the branch of anatomy also known as microscopic anatomy, is the study of the structure and function of the body's tissues. To gain an understanding of the tissues of the body is to learn the foundational underpinnings of anatomy and achieve a deeper, more intimate insight into how the body is constructed, functions, and undergoes pathological change. Histology, therefore, is an integral element of basic science education within today's medical curricula. Its development as a discipline is inextricably linked to the evolution of the technology that allows us to visualize it. This chapter takes us on the journey through the past, present, and future of histology and its education; from technologies grounded in ancient understanding and control of the properties of light, to the ingenuity of crafting glass lenses that led to the construction of the first microscopes; traversing the second revolution in histology through the development of modern histological techniques and methods of digital and virtual microscopy, which allows learners to visualize histology anywhere, at any time; to the future of histology that allows flexible self-directed learning through social media, live-streaming, and virtual reality as a result of the powerful smart technologies we all carry around in our pockets. But, is our continuous pursuit of technological advancement projecting us towards a dystopian world where machines with artificial intelligence learn how to read histological slides and diagnose the diseases in the very humans that built them?


Rabies in a pronghorn antelope, Antilocapra americana.
A ten week old antelope died from rabies 35 days after being bitten on the left hock by a skunk. The result of the direct fluorescent antibody test for rabies was positive.


Distinct domains in Ndc1 mediate its interaction with the Nup84 complex and the nuclear membrane.
Nuclear pore complexes (NPCs) are embedded in the nuclear envelope and built from ∼30 different nucleoporins (Nups) in multiple copies, few are integral membrane proteins. One of these transmembrane nucleoporins, Ndc1, is thought to function in NPC assembly at the fused inner and outer nuclear membranes. Here, we show a direct interaction of Ndc1's transmembrane domain with Nup120 and Nup133, members of the pore membrane coating Y-complex. We identify an amphipathic helix in Ndc1's C-terminal domain binding highly curved liposomes. Upon overexpression, this amphipathic motif is toxic and dramatically alters the intracellular membrane organization in yeast. Ndc1's amphipathic motif functionally interacts with related motifs in the C-terminus of the nucleoporins Nup53 and Nup59, important for pore membrane binding and interconnecting NPC modules. The essential function of Ndc1 can be suppressed by deleting the amphipathic helix from Nup53. Our data indicate that nuclear membrane and presumably NPC biogenesis depends on a balanced ratio between amphipathic motifs in diverse nucleoporins.


Osmotic Demyelination Syndrome following Correction of Hyponatremia by ≤10 mEq/L per Day.
Overly rapid correction of chronic hyponatremia may lead to osmotic demyelination syndrome. European guidelines recommend a correction to ≤10 mEq/L in 24 hours to prevent this complication. However, osmotic demyelination syndrome may occur despite adherence to these guidelines. We searched the literature for reports of osmotic demyelination syndrome with rates of correction of hyponatremia ≤10 mEq/L in 24 hours. The reports were reviewed to identify specific risk factors for this complication. We identified 19 publications with a total of 21 patients that were included in our analysis. The mean age was 52 years, of which 67% were male. All of the patients had community-acquired chronic hyponatremia. Twelve patients had an initial serum sodium <115 mEq/L, of which seven had an initial serum sodium ≤105 mEq/L. Other risk factors identified included alcohol use disorder (n=11), hypokalemia (n=5), liver disease (n=6), and malnutrition (n=11). The maximum rate of correction in patients with serum sodium <115 mEq/L was at least 8 mEq/L in all but one patient. In contrast, correction was <8 mEq/L in all but two patients with serum sodium ≥115 mEq/L. Among the latter group, osmotic demyelination syndrome developed before hospital admission or was unrelated to hyponatremia overcorrection. Four patients died (19%), five had full recovery (24%), and nine (42%) had varying degrees of residual neurologic deficits. Osmotic demyelination syndrome can occur in patients with chronic hyponatremia with a serum sodium <115 mEq/L, despite rates of serum sodium correction ≤10 mEq/L in 24 hours. In patients with severe hyponatremia and high-risk features, especially those with serum sodium <115 mEq/L, we recommend limiting serum sodium correction to <8 mEq/L. Thiamine supplementation is advisable for any patient with hyponatremia whose dietary intake has been poor.


Pattern of expanding consciousness in midlife women: creative movement and the narrative as modes of expression.
This study is based on Newman's theory of expanding consciousness; it expands Newman's method to include creative movement as a mode of expression. The researcher engaged in two in-depth interviews and one creative movement group experience with each of 17 midlife women. Results demonstrate expanding consciousness at midlife, with patterns of meaning identified in relationships with others, self, and spirit as well as challenges of loss, illness, and threats to relationships. Activities of consciousness were choosing, balancing, accepting, and letting go. Concepts of flow, turbulence, and a movement dialectic were identified in study findings. Creative movement supported self-awareness.


Six autoantibodies as potential serum biomarkers of hepatocellular carcinoma: A prospective multicenter study.
Serum autoantibodies have been reported to react with tumor-associated antigen (TAA) in various cancers. This multicenter study evaluated the diagnostic and prognostic value of six autoantibodies against a panel of six hepatocellular carcinoma (HCC)-associated antigens, including Sui1, p62, RalA, p53, NY-ESO-1 and c-myc. A total of 160 patients with HCC and 74 healthy controls were prospectively enrolled from six institutions. Serum antibody titers were determined by enzyme-linked immunosorbent assays. The sensitivities were 19% for Sui1, 18% for p62, 17% for RalA, 11% for p53, 10% for NY-ESO-1 and 9% for c-myc. Overall sensitivity of the TAA panel (56%) was higher than that of α-fetoprotein (41%, P < .05). The combined sensitivity of the TAA panel and α-fetoprotein was significantly higher than that of α-fetoprotein alone (P < .001). The difference in overall survival of TAA panel-positive and panel-negative patients was significant when the Stage I/II patients were combined (P = .023). Overall survival was worse in NY-ESO-1 antibody-positive than in NY-ESO-1 antibody-negative patients (P = .002). Multivariate analysis found that positivity for the TAA panel was independently associated with poor prognosis (P = .030). This TAA panel may have diagnostic and prognostic value in the patients with HCC.


[Pemetrexed salvage chemotherapy for NSCLC: implementation study].
Registration trials demonstrated the activity of pemetrexed in non small cell lung carcinoma (NSCLC) either in combination with first-line agents or in monotherapy for salvage treatment. The aim of our implementation study was to verify, in an unselected population, the results obtained with pemetrexed salvage chemotherapy in clinical practice. The charts of all patients diagnosed with NSCLC, receiving pemetrexed for progressive disease after at least one previous course of chemotherapy, were retrospectively reviewed in two academic institutions. Response was assessed according to WHO and toxicity using the CTCAE and WHO criteria. Between November 2004 and September 2009, 84 patients were given pemetrexed as second, third or greater than third line therapy (n=18/14/52). Intent-to-treat response rate was 11.9% (95% CI, 5%-18.8%). Median progression-free survival was 2.2 months and median survival time was 6.4 months. The most frequent grade 3-5 toxicity was neutropenia (23.9%). Salvage chemotherapy with pemetrexed for progressing NSCLC confirmed, in an unselected population, who had been extensively treated previously, the level of activity observed in registration trials although a significant toxicity was noted.


Magnesium Fluoride Forms Unique Protein Corona for Efficient Delivery of Doxorubicin into Breast Cancer Cells.
The efficacy of chemotherapy is undermined by adverse side effects and chemoresistance of target tissues. Developing a drug delivery system can reduce off-target side effects and increase the efficacy of drugs by increasing their accumulation in target tissues. Inorganic salts have several advantages over other drug delivery vectors in that they are non-carcinogenic and less immunogenic than viral vectors and have a higher loading capacity and better controlled release than lipid and polymer vectors. MgF₂ crystals were fabricated by mixing 20 mM MgCl₂ and 10 mM NaF and incubating for 30 min at 37 °C. The crystals were characterized by absorbance, dynamic light scattering, microscopic observance, pH sensitivity test, SEM, EDX and FTIR. The binding efficacy to doxorubicin was assessed by measuring fluorescence intensity. pH-dependent doxorubicin release profile was used to assess the controlled release capability of the particle-drug complex. Cellular uptake was assessed by fluorescence microscopy. Cytotoxicity of the particles and the drug-particle complex were assessed using MTT assay to measure cell viability of MCF-7 cells. Particle size on average was estimated to be <200 nm. The crystals were cubic in shape. The particles were pH-sensitive and capable of releasing doxorubicin in increasing acidic conditions. MgF₂ nanocrystals were safe in lower concentrations, and when bound to doxorubicin, enhanced its uptake. The protein corona formed around MgF₂ nanoparticles lacks typical opsonins but contains some dysopsonins. A drug delivery vector in the form of MgF₂ nanocrystals has been developed to transport doxorubicin into breast cancer cells. It is pH-sensitive (allowing for controlled release), size-modifiable, simple and cheap to produce.


Alteration in biogenic amine levels in the snail Lymnaea acuminata by the latex of Euphorbia royleana.
The latex of Euphorbia royleana which has high molluscicidal and anti-cholinesterase activity against Lymnaea acuminata reduced the levels of 5-hydroxytryptamine (5HT) and dopamine (DA) in the nervous tissue of L. acuminata. There was, however, no significant change in the level of 5-hydroxyindole acetic acid (5HIAA). The changes were found to be dependent on concentration of the latex extract. Similar changes were produced by both water and organic solvent extracts of the latex. The latex of E. royleana thus affects all the known neurotransmission mechanisms in the snail either separately or through a complex interaction between the different neurotransmitters. This may account for its high toxicity to snails.


Effect of ibuprofen on bilirubin-albumin binding.
Ibuprofen is used for closing the ductus arteriosus in premature newborn infants. Ibuprofen interferes with bilirubin-albumin binding and increases the unbound bilirubin in pooled newborn plasma to levels similar to those produced by sulfisoxazole, a drug that causes kernicterus in premature newborn infants.


LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers.
Among the various risk factors involved in the development and progression of carotid atherosclerosis, the oxidation of LDL has been proposed to play a relevant role. LDL oxidation has been investigated in 94 patients with severe carotid atherosclerosis undergoing elective carotid artery endarterectomy and in 42 matched control subjects. LDL oxidation was evaluated in all patients as (1) the susceptibility to in vitro oxidation, (2) vitamin E concentration and its efficiency in LDL, and (3) the presence of autoantibodies against oxidatively modified lipoprotein to monitor the occurrence of the oxidative processes taking place in vivo. No difference was detected between control subjects and patients concerning vitamin E concentration and the kinetics of conjugated diene formation in isolated LDL exposed to CuSO4. However, vitamin E efficiency was lower (9.6 +/- 4.2 versus 30.2 +/- 7.6 min/nmol vitamin E) and the duration of the vitamin E-independent lag phase was longer (105.5 +/- 16.5 versus 58 +/- 11.8 minutes) in the patient group. Autoantibodies against oxidatively modified lipoproteins were measured with an ELISA method using native LDL, Cu(2+)-oxidized LDL (oxLDL), or malondialdehyde-derivatized LDL (MDA-LDL) as antigens. To monitor cross-reactivity of the antibodies detected with other oxidatively modified proteins, human serum albumin (HSA) and MDA-derivatized HSA (MDA-HSA) were also employed. The antibody titer was calculated as the ratio of antibodies against modified versus native proteins.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of cocktails of labeled monoclonal antibodies on the localization of antibodies in human tumor xenografts.
In order to evaluate the usefulness of cocktails of labeled monoclonal antibodies (MoAbs) recognizing different antigen molecules to localize human cancer xenografts, we have compared the potential of three MoAbs recognizing representative cancer-associated CA 19-9, 17-1A and CEA antigens when administered alone or in combination. Specific binding of radioiodinated F(ab')2 fragments of these three MoAbs was observed to human colorectal cancer cell lines SW1116, LS180 and Co-3. The percentage of in vitro cell binding of a cocktail of any two MoAbs to cancer cells was equal to the average of those obtained with the two MoAbs alone. The three MoAbs were preferentially localized in tumor tissues xenografted in nude mice. When cocktails of any two MoAbs were used, the obtained tumor-to-normal tissue ratios and percent of injected dose per gram of tumor were between the levels obtained for each MoAb when administered alone, in all three tumors transplanted in nude mice. These data suggest that, although cocktails of labeled MoAbs recognizing different antigens may extend the spectrum of tumor specificities, their use does not improve the tumor localization ability of MoAb-conjugates.


Selected ventriculoplasty for idiopathic dilated cardiomyopathy with advanced congestive heart failure: midterm results and risk analysis.
To treat advanced heart failure due to idiopathic dilated cardiomyopathy, surgical ventricular restoration with mitral reconstruction was conducted and evaluated. In 95 patients (81 men, mean age: 54 years), New York Heart Association class III/IV was 44/51, and 33 patients (36%) were inotropic dependent preoperatively. Mitral regurgitation (>or=2+) was noted in all patients. All patients underwent left ventriculoplasty (septal anterior ventricular exclusion in 38, partial left ventriculectomy in 57) and mitral reconstruction (repair 53, replacement 42). Fifty-two patients (55%) had concomitant tricuspid repair. Intra-aortic balloon pumping and left ventricular assist device was used in 24 patients and two patients, respectively. Hospital mortality was 11.6% (11 of 95), with 6.6% (5 of 76) in elective and 31.6% (6 of 19) in emergency operations. The ejection fraction and cardiac index increased from 22.3+/-6.3% to 27.2+/-8.0% and from 2.3+/-0.5 ml/m2/min to 2.8+/-0.5 ml/m2/min, respectively (p<0.001). The endodiastolic volume index, endosystolic volume index and diastolic dimension decreased from 232.9+/-56.1 ml/m2 to 160.0+/-49.8 ml/m2, from 178.9+/-46.7 ml/m2 to 113.8+/-44.7 ml/m2 and from 82.0+/-9.0 mm to 68.9+/-11.6 mm, respectively (p<0.001). Late death occurred in 27 patients with 22 cardiac deaths. The mean NYHA class was 1.7 among the survivors. One-, 3- and 5-year survival rates were 72.8%, 61.4% and 50.5%, respectively. In the 62 patients who were non-inotropic dependent preoperatively, 1-, 3-, and 5-year survival rates (81.8%, 73.7% and 62.9%) were significantly better than the inotropic-dependent group (55.3%, 37.3% and 28.0%). Patients with mitral annuloplasty showed a significantly higher 5-year survival rate than patients with mitral valve replacement (59.6% vs 43.6%) in univariate analysis. By application of the exclusion site selection method, the two different ventriculoplasty procedures did not show significant difference in survival rates. Multivariate analysis showed that preoperative inotropes and old age were significant predictors for postoperative mortality. The selected ventriculoplasty in combination with mitral annuloplasty is a useful option for patients with an extremely dilated left ventricle in idiopathic dilated cardiomyopathy. Surgery should be considered before inotropic dependency occurs when prior medical treatment has failed.


Lung Ultrasound for Detecting Tracheal and Mainstem Intubation: A Systematic Review and Meta-Analysis.
Precise positioning of the left or right main bronchus is a prerequisite for effective lung isolation in thoracic surgeries. This study aimed to clarify the ability of lung ultrasound to detect tracheal and mainstem intubation. Studies that investigated the ability of lung ultrasound to detect tracheal and mainstem intubation were searched from PubMed and ScienceDirect databases from their inception to March 2021. The pooled accuracy of this method and its sensitivity and specificity were computed with a fixed-effects model using Stata 14.0. Nine eligible articles that involved a total of 617 participants were included in this systematic review and meta-analysis. Overall, the accuracy of lung ultrasound in detecting tracheal and mainstem intubation was 86.7%, with a sensitivity of 93.0% and a specificity of 75.0%. Subgroup analysis revealed that the accuracy remained high regardless of patient age, ultrasonic method, sample size, study design or ultrasonic skills training. Sensitivity analysis indicated that the results were stable. Deeks' test showed no publication bias. These findings imply that lung ultrasound is an effective method for detecting tracheal and mainstem intubation.


The transfer of NIR calibrations for undried grass silage from the laboratory to on-site instruments: comparison of two approaches.
As a first step in a project whose aim is to implement near infrared (NIR) analysis of animal feed on the farm, the present work has examined the possibility of transferring undried grass silage calibrations for dry matter, crude protein, and neutral detergent fiber from a dispersive laboratory NIR instrument (Foss NIRSystem 6500) to a diode array on-site NIR instrument (Zeiss Corona 45 visNIR 1.7). Because the samples are complex and heterogeneous and have high humidity levels it is not easy to establish good calibrations, and it is even more of a challenge to transfer them. By cutting the spectral range to 1100-1650 nm and treating with first or second derivative followed by standard normal variate (SNV) scatter correction, it was possible to obtain very similar spectra from the two instruments. To make the transfer, two approaches were tried. Simply correcting the Corona spectra by subtracting the mean difference spectrum from a transfer set met with only limited success. Making a calibration on the Foss using a calibration set of 503 samples with spectra orthogonalized to the all the difference spectra in the transfer set of 10 samples resulted in a successful transfer for all three calibrations, as judged by performance on two prediction sets of size 22 and 29. Measuring 5 replicate subsamples with the Corona allows it to see a similar surface area to that of 3 replicates in the Foss transport cell, and it is suggested that this is an appropriate level of replication for the Corona.


Muscle-specific programmed cell death 5 deletion attenuates cardiac aging.
Programmed cell death 5 (PDCD5) is a tumor suppressor gene that regulates the cell cycle, apoptosis and immune responses. However, the physiological function of Pdcd5 in cardiac aging remains unknown. We find that Pdcd5 mRNA and protein levels were significantly increased in the heart of mice with age. Therefore, we hypothesize that Pdcd5 regulates cardiac aging. To test the hypothesis, we generated muscle-specific Pdcd5-deficient mice. Mature adult Pdcd5-deficient mice had normal cardiac morphology and function. In naturally aged mice, Pdcd5 deficiency alleviated age-related cardiac phenotypes including reduced fibrosis and suppressed cardiomyocyte hypertrophy. Moreover, muscle-specific Pdcd5 deficiency attenuated cellular senescence in the heart as demonstrated by decreased number of senescence-associated β-galactosidase-positive cells, diminished p53, p21 and p16 expression, and reduced the senescence-associated secretory phenotype. Apoptotic cell death was reduced by Pdcd5 deficiency in the heart as revealed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay, which was coincident with diminished Bcl-2-associated X protein, and enhanced B-cell lymphoma 2 and X-linked inhibitor of apoptosis protein expression. Mitochondrial quality in cardiomyocytes was improved by Pdcd5 deficiency through increased Parkin-mediated mitophagy. In addition, Pdcd5 deficiency alleviated doxorubicin-induced premature cellular senescence and cardiac aging. Furthermore, Pdcd5 protein abundance was significantly correlated with p53 protein abundance, and Pdcd5 interacted with p53 in the heart. Taken together, our results reveal that Pdcd5 deficiency attenuates cardiac aging by reducing cellular senescence and apoptosis, and increasing Parkin-mediated mitophagy, likely through p53. Pdcd5 is a novel regulator of cardiac aging and a potential therapeutic target.


Combined transnasal/transoral endoscopic odontoid resection in pediatric patients: Otolaryngologic considerations to airway management, endoscopic exposure, and complication management.
Anterior brainstem compression from odontoid pathology can occur in patients with craniocervical disorders. Occasionally, odontoid resection is required. In adults, odontoid resection has evolved toward transnasal-only endoscopic techniques. Pediatric patients, however, pose special challenges due to abnormal anatomy and smaller working spaces. A combined transnasal/transoral endoscopic odontoid resection (TN/TO EOR) can overcome this limitation. We present a case series with emphasis on otolaryngologic considerations to airway management, endoscopic approach, and management of complications. A single center, retrospective review of patients aged ≤18 undergoing combined transnasal/transoral endoscopic odontoid resection between 2011 and 2022 is presented. Clinical and surgical variables consisting of diagnosis, intubation approach, other airway procedures performed, symptoms, complications, blood loss, and time to extubation, return to oral feeding, and discharge were recorded. 19 patients aged 10.7 ± 4.3 (range: 3-18) were included. Diagnoses included congenital syndrome (n = 6), complex Chiari malformation (n = 11), and congenital syndrome with Chiari (n = 2). Patients commonly required indirect videolaryngoscopy for intubation, with or without fiberoptic endoscopic assistance. Seven underwent adenoidectomy, two underwent adenotonsillectomy, and one required adenoidectomy with midline palatal split and inferior turbinate outfracture. Four patients had undergone prior adenotonsillectomy. Presenting symptoms included extremity weakness (n = 9), dysphagia (n = 8), velopharyngeal insufficiency (n = 4), sleep disturbance (n = 5), and headaches (n = 8). Four patients had complications, including one re-operation for residual odontoid, one flap dehiscence, one cerebrospinal fluid (CSF) leak repaired primarily, and one complicated course including temporary spinal cord injury. Blood loss was 50 ± 43 cc (median 30). Time to extubation was 1.1 ± 2.1 days (median 0; one patient underwent tracheotomy for respiratory failure), time to oral intake was 2.9 ± 3.7 days (median 1), and time to discharge was 7.1 ± 7.5 days (median 4). A combined transnasal/transoral approach can be successfully used in pediatric patients to overcome difficult endoscopic access. Although complications exist, early extubation and return to oral intake occurs in the vast majority of cases. For pediatric TN/TO EOR, the otolaryngologist plays a key role in preoperative assessment, airway management, endoscopic exposure, and complication management.


Increased FDG uptake in breast cancer is associated with prognostic factors.
To evaluate the relationship between FDG uptake and prognostic factors of breast cancer such as hormone receptors (estrogen and progesterone), expression of c-erbB-2, axillary lymph node status, tumor histology, grade and size. Between May 2009 and February 2011; 79 patients (mean age ± SD: 52.9 ± 13.9 years) with biopsy proven breast cancer underwent F-18 FDG PET/CT scanning for staging. Patients with excisional biopsy or neoadjuvant chemotherapy were excluded from the study. Histological types included were invasive ductal carcinoma (n = 68), invasive lobular carcinoma (n = 2), and invasive ductal plus lobular mixed carcinoma (n = 9). Maximum standardized uptake values (SUVmax) were compared with estrogen (ER) and progesterone receptors (PR), expression of c-erbB-2, as well as tumor grade and tumor size. For the evaluation of relationship between tumor SUVmax values and prognosticators such as hormone receptors, tumor histologic grade, and tumor size, statistical analyses were performed using Student t test, Mann-Whitney U Test and Pearson correlation coefficient and p values of less than 0.05 were considered to indicate statistically significant differences. All primary breast neoplasms were detected by PET/CT scanner. The mean SUVmax values and breast cancer tumor sizes ranged from 2.09 to 39.0 and 0.7 to 10 cm, respectively. Tumors with negative ER [(n = 19); SUVmax median (min-max): 15 (2.09-39.0)] were associated with higher SUVmax values (p = 0.01). Tumors with overexpression of C-erbB-2 [(n = 28); SUVmax median (min-max): 16.0 (5.0-39.0)]; tumor grade 3 [(n = 25); SUVmax median (min-max): 15 (6.43-39)]; axillary lymph node involvement [(n = 60); SUVmax median (min-max): 13.61 (4.0-39.0)]; tumor histopathology and increased tumor size were associated with higher maximum standardized uptake values. However, PR did not show any relationship with SUVmax values. In the present report, strong relationships were detected between the negativity of ER, overexpression of c-erbB-2, tumor grade, tumor size, histopathology, axillary lymph node involvement and SUVmax values. Accordingly, we believe that SUVmax values obtained with (18)F-FDG PET/CT may provide some information about tumor biology of breast cancer.


Nutritional status, growth and development in children undergoing intensive treatment for cystic fibrosis.
Dietary intakes were measured over a period of 5 days in 36 malnourished and 36 well-nourished patients with cystic fibrosis. Both energy and protein intakes were significantly less in the malnourished patients for the two age groups studied: 4-9.99 years (p less than 0.01 for both parameters), and 10-16 years (p less than 0.05 and p less than 0.01, respectively). In both age groups and both patient groups, average protein intakes were well in excess of the recommended daily intake, but energy intake in the malnourished patients was below the recommended daily intake. Nutritional supplementation of 10 malnourished patients with a polymeric formula, infused overnight via a gastrostomy tube, resulted in a seven-fold increase in weight gain (p less than 0.001) and a doubling of linear growth velocity (p less than 0.01) over a period of 18 months, compared to the 18 months prior to gastrostomy feeding. Measurements of total body nitrogen in eight of these patients demonstrated a 38% increase in body nitrogen content over 12 months, indicating a replenishment of the protein deficit.


Effects of cadmium and arsenic on growth and metal accumulation of Cd-hyperaccumulator Solanum nigrum L.
Remediation of heavy metal contaminated sites using hyperaccumulators presents a promising alternative to current environmental methodologies. In the pot-culture experiment, the effects of Cd, and Cd-As on the growth and its accumulation in the Cd-hyperaccumulator (Solanum nigrum L.) were determined. No reduction in plant height and shoot dry biomass was noted when the plants were grown at Cd concentration of <or= 25 mg/kg. The contents of Cd in the stems increased from 122 to 387 mg/kg with increasing Cd, with the Cd transfer factor and bioaccumulation factor being >1.0. The plant can be classified as a Cd-hyperaccumulator. Growing in the presence of 10 mg/kg Cd and 50 mg/kg As, the plant height and shoot dry matter yields did not decrease significantly (p>0.05) compared to that at 10 mg/kg Cd, however the stem Cd content increased by 28%. It was also observed that S. nigrum used exclusion strategy to reduce As uptake in the roots and restricted translocation into the shoots, resulting in As contents of the plant being root>leaf>stem>seed. The Cd accumulation capacity coupled with its relatively high As tolerance ability could make it useful for phytoremediation of sites co-contaminated by Cd and As.


Genome-wide aberrations in pancreatic adenocarcinoma.
Chromosomal instability, manifesting as copy number alterations (CNAs), is characteristic of pancreatic adenocarcinoma. We used bacterial artificial chromosome (BAC) array-based comparative genomic hybridization (aCGH) to examine the pancreatic adenocarcinoma genome for submicroscopic amplifications and deletions. Profiles of 33 samples (17 first-passage xenografts and 16 cell lines) identified numerous chromosomal regions with CNAs, including losses at 1p36.33 approximately p34.3, 1p13.3 approximately p13.2, 3p26, 3p25.2 approximately p22.3, 3p22.1 approximately p14.1, 4q28.3, 4q31, 4q35.1, 5q14.3, 6p, 6q, 8p23.3 approximately p12, 9p, 9q22.32 approximately q31.1, 13q33.2, 15q11.2, 16p13.3, 17p, 18q11.21 approximately q23 , 19p13.3 approximately p13.12, 19q13.2, 21p, 21q, and 22p, 22q and gains at 7p21.1 approximately p11.2, 7q31.32, 7q33, 8q11.1 approximately q24, 11p13, 14q22.2, 20p12.2, and 20q11.23 approximately q13.33. Novel regions containing CNAs were identified and refined by combining the increased resolution of our BAC CGH array with a statistical algorithm developed for assigning significance values to altered BACs across samples. A subset of array-based CNAs was validated using polymerase chain reaction-based techniques, immunohistochemistry and fluorescence in situ hybridization. BAC aCGH proved to be a powerful genome-wide strategy to identify molecular alterations in pancreatic cancer and to distinguish differences between cell line and xenograft aberration profiles. These findings should greatly facilitate further research in understanding the pathogenesis of this lethal disease, and could lead to the identification of novel therapeutic targets and biomarkers for early detection.


Prevalence and severity of cornea guttata in the graft following Descemet Membrane Endothelial Keratoplasty (DMEK).
The aim of this study was to determine the prevalence and severity of cornea guttata (CG) in grafts after Descemet membrane endothelial keratoplasty (DMEK) and to investigate its impact on various clinical parameters during follow-up. This retrospective study included 664 operations (DMEK and triple-DMEK) on 466 patients. The prevalence and progression of CG after the operation were examined using endothelial specular microscopy images. The severity grade of CG was classified into four grades: G0 without CG, G1 - G3 with increasing severity of CG. Clinical parameters such as central corneal thickness (CCT), visual acuity (VA), endothelial cell density (ECD), pleomorphism and polymegalism were examined during a postoperative follow-up time of 19.6 ± 15.8 months. Cornea guttata (CG) appeared postoperatively in 124 (18.7%) eyes. 112 (16.9%) could be classified as G1, 9 (1.4%) as G2 and only 3 (0.5%) as G3. The examination of clinical parameters showed significant differences between healthy and low-grade CG (G0/G1) and high-grade CG (G2/G3). A significant deterioration was found in the corrected distance visual acuity (CDVA) (p = 0.02). CCT showed an increase between G0 (534 ± 58 μm) and G2 (549 ± 71 μm)/G3 (558 ± 56 μm) with a p-value of 0.02. Additionally, a significant increase in pleomorphism (p = 0.003) and polymegalism (p = 0.04) was detected. Cornea guttata (CG) prevalence after DMEK and triple-DMEK was found to be 18.7%, although most of these cases were classified as low-grade CG and showed no clinical significance. Around 1.9% were classified as high-grade CG and significantly affected several clinical parameters during the follow-up.


Survival differences in nasopharyngeal carcinoma among racial and ethnic minority groups in the United States: A retrospective cohort study.
The literature on nasopharyngeal carcinoma survival in the United States has focused mostly on Whites or Asians and not much is known about survivorship in other minority racial and ethnic groups. We aimed to determine the disease-specific survival rate and prognostic factors for nasopharyngeal carcinoma survival across the minority United States population. A retrospective cohort study. The Surveillance, Epidemiology and End Results (SEER) 13 database from 1992 to 2014 was queried for adult cases of nasopharyngeal carcinoma (n = 2549). Eligible cases were Blacks, Hispanics, Asians/Pacific Islanders, American Indians/Alaska Natives; White patients were excluded. A multivariable competing risk survival analysis yielded hazard ratios (HR) for competing mortality and was used to identify independent prognostic factors for survival. Non-Hispanic American Indians/Alaska Natives consistently had the worst cause-specific survival of any group and that non-Hispanic Asians/Pacific Islanders consistently had the best survival (P < 0.001). Even after adjusting for other poor prognostic factors in the study, including older age, keratinising histology, and lack of radiation treatment, non-Hispanic American Indians/Alaska Natives had more than double hazards of death from nasopharyngeal cancer compared with non-Hispanic Asians/Pacific Islanders (aHR = 2.63, 95% CI 1.67, 4.13). There are disparities in nasopharyngeal carcinoma survival among racial and ethnic minority groups in the United States, with American Indians/Alaskan Natives faring worst. It is critical that future research focuses on nasopharyngeal carcinoma among this population to improve survivorship and mitigate cancer-related health disparities.


Development of inhibitors targeting glycogen synthase kinase-3β for human diseases: Strategies to improve selectivity.
Glycogen synthase kinase-3β (GSK-3β) is a conserved serine/threonine kinase that participates in the transmission of multiple signaling pathways and plays an important role in the occurrence and development of human diseases, such as metabolic diseases, neurological diseases and cancer, making it to be a potential and promising drug target. To date, copious GSK-3β inhibitors have been synthesized, but only few have entered clinical trials. Most of them exerts poor selectivity, concomitant off-target effects and side effects. This review summarizes the structural characteristics, biological functions and relationship with diseases of GSK-3β, as well as the selectivity profile and therapeutic potential of different categories of GSK-3β inhibitors. Strategies for increasing selectivity and reducing adverse effects are proposed for the future design of GSK-3β inhibitors.


Study on the influence of the B4C layer thickness on the neutron flux and energy distribution shape in multi-electrode ionisation chamber.
A model of a multi-electrode ionisation chamber, with polypropylene electrodes coated with a thin layer of B4C was created within Monte Carlo N-Particle Transport Code (MCNPX) and Fluktuierende Kaskade (FLUKA) codes. The influence of the layer thickness on neutron absorption in B4C and on the neutron spectra in the consecutive intra-electrode gas volumes has been studied using the MCNPX and FLUKA codes. The results will be used for designing the new type of the ionisation chamber.


Adjuvant postoperative radiation therapy following radical hysterectomy in stage IB CA of the cervix--analysis of treatment failure.
Among 240 patients treated by radiation therapy for clinical Stage IB cancer of the cervix between 1969 and 1980, 38 patients received postoperative pelvic radiation therapy after radical hysterectomy because of positive pelvic lymph nodes and/or close surgical margins. The overall recurrence was 45% (17 of 38), and the major complication rate was 15% in minimum 5-year follow-up. In patients with positive pelvic lymph nodes, the pelvic recurrence was 13% (3 of 23). However, distant metastases alone was 26% (6 of 23), which was the most common treatment failure. In 11 patients with close surgical margins, eight patients had paracervical margins and three had vaginal margins. All five patients with paracervical margins treated with vaginal ovoid irradiation only had pelvic recurrence. No local failure occurred in the other three patients treated with whole pelvic irradiation. All patients with vaginal margin alone treated with vaginal ovoid or whole pelvic irradiation had no recurrence of cancer in the pelvis. On the basis of our data, whole pelvic irradiation with or without vaginal ovoid irradiation is necessary in those with a close paracervical margin. In patients with close vaginal margin, whole pelvic irradiation with or without vaginal ovoid irradiation is recommended. The vaginal ovoid irradiation alone should be limited to very selected cases.


Chemometric assisted natural DES based VA-DLLME-LC-MS/MS method for the quantitative determination of Garcinol in biofluids/tissues: A practical application to pharmacokinetics and biodistribution studies.
Garcinol (GAR) is a polyisoprenylated benzophenone obtained from Garcinia indica used as anti-oxidant and anti-inflammatory in traditional medicine and due to these activities, it possesses anticancer properties. It is considered to be a next generation epigenetic drug. A green solvent based analytical method which is efficient, sophisticated, and highly enriched has been developed for the quantitative analysis of GAR in biological samples (plasma, liver, kidney and spleen) with the use of deep eutectic solvent (DES) for its extraction. A series of 23 DESs were synthesized and out of which, Thymol (Th)-Terpeniol (T), 2:1 molar ratio with a more hydrophobic environment and high interaction efficiency between GAR and DES was identified for the better extraction from mice plasma and tissue samples. The Design of Experiment approaches like placket-burmann design and central composite design were used to optimize the method conditions. The method validation characteristics, such as limit of detection (0.193-0.237 ng/mL), limit of quantification (0.644-0.697 ng/mL), lower limit of quantification (0.5 ng/mL), broad range of linearity with R2 (0.9994-0.9997) with a percent recovery not less than 87% was observed, which are well within the acceptance criteria for a bioanalytical method. The enrichment factor is upto 53-60 folds, with high extraction efficiency (89-97%). The measurement uncertainty was estimated with an expanded uncertainty ranged between 10.9%-19.0%. The method developed and validated was effectively applied to examine the pharmacokinetic and biodistribution patterns for GAR in mice.


Clonal chromosome changes in non-neoplastic ureters.
Cytogenetic analysis was performed on 23 samples from non-neoplastic ureters. Clonal chromosome abnormalities were found in eight. They were: loss of Y chromosome, as a single abnormality (five cases) or associated with trisomy 10 and 20 (one case) or with trisomy 2 (one case); and duplication of Y chromosome (one case). Different numerical and structural sporadic abnormalities were found in nine cases. Immunohistochemical analysis and direct observation using the inverted microscope showed that the cells were mainly of the fibroblastic type. FISH analysis with chromosome 7 alpha-satellite probes failed to detect the presence of trisomy 7 in three epithelial cases tested.


The B-cell antigen receptor integrates adaptive and innate immune signals.
B cells respond to antigens by engagement of their B-cell antigen receptor (BCR) and of coreceptors through which signals from helper T cells or pathogen-associated molecular patterns are delivered. We show that the proliferative response of B cells to the latter stimuli is controlled by BCR-dependent activation of phosphoinositidyl 3-kinase (PI-3K) signaling. Glycogen synthase kinase 3β and Foxo1 are two PI-3K-regulated targets that play important roles, but to different extents, depending on the specific mitogen. These results suggest a model for integrating signals from the innate and the adaptive immune systems in the control of the B-cell immune response.


Regional centromeres in the yeast Candida lusitaniae lack pericentromeric heterochromatin.
Point centromeres are specified by a short consensus sequence that seeds kinetochore formation, whereas regional centromeres lack a conserved sequence and instead are epigenetically inherited. Regional centromeres are generally flanked by heterochromatin that ensures high levels of cohesin and promotes faithful chromosome segregation. However, it is not known whether regional centromeres require pericentromeric heterochromatin. In the yeast Candida lusitaniae, we identified a distinct type of regional centromere that lacks pericentromeric heterochromatin. Centromere locations were determined by ChIP-sequencing of two key centromere proteins, Cse4 and Mif2, and are consistent with bioinformatic predictions. The centromeric DNA sequence was unique for each chromosome and spanned 4-4.5 kbp, consistent with regional epigenetically inherited centromeres. However, unlike other regional centromeres, there was no evidence of pericentromeric heterochromatin in C. lusitaniae. In particular, flanking genes were expressed at a similar level to the rest of the genome, and a URA3 reporter inserted adjacent to a centromere was not repressed. In addition, regions flanking the centromeric core were not associated with hypoacetylated histones or a sirtuin deacetylase that generates heterochromatin in other yeast. Interestingly, the centromeric chromatin had a distinct pattern of histone modifications, being enriched for methylated H3K79 and H3R2 but lacking methylation of H3K4, which is found at other regional centromeres. Thus, not all regional centromeres require flanking heterochromatin.


Characterization of a human NK1 tachykinin receptor in the astrocytoma cell line U 373 MG.
The human NK1 tachykinin receptor in the astrocytoma cell line U 373 MG was characterized using selective agonists and antagonists described for this receptor in the rat. Specific [3H]substance P binding sites were present on cell homogenates, whereas [3H]neurokinin A or [3H]-senktide binding sites were absent. The binding was saturable and reversible. The binding of [3H]substance P was inhibited by very low concentrations of [L-Pro9]substance P and [Sar9,Met(O2)11]substance P; septide was approximately 1,000-fold less potent. The most potent peptide antagonist was trans-4-hydroxy-1-(1H-indol-3-ylcarbonyl)-L-prolyl-N-methyl-N-(phe nylmethyl)-L- tyrosineamide. The rank order of potency for the nonpeptide antagonists was (S,S)-CP 96,345 > (+/-)-CP 96,345 > (+/-)-2-chlorobenzylquinuclidinone > (R,R)-CP 96,345 > RP 67580 > RP 68651. In [3H]-inositol-labeled cells, substance P stimulated phosphatidylinositol turnover. A good correlation was found when the abilities of NK1 receptor agonists for stimulating inositol phosphate production and for inhibiting [3H]substance P binding were compared. Similarly, the binding and functional assays were well correlated for the antagonists. As a result of its high sensitivity and selectivity, the U 373 MG cell line thus appears an excellent tool for investigating the pharmacology of the human NK1 receptor.


A simple and general method for determining the protein and nucleic acid content of viruses by UV absorbance.
UV spectra of viruses are complicated by overlapping protein and RNA absorbance and light scattering. We describe and validate methodology for estimating RNA and protein concentration from such spectra. Importantly, we found that encapsidation did not substantially affect RNA absorbance. Combining absorbance data with a known T number, we confirmed that brome mosaic virus packages about 3100 nucleotides/capsid, consistent with its genome. E. coli-expressed hepatitis B virus (HBV) packages host RNA based on capsid charge and volume. We examined HBV capsid protein (Cp183, +15 charge) and a less basic mutant (Cp183-EEE, +12 charge) that mimics a phosphorylated state. Cp183-EEE packaged ~3450 nucleotides per T=4 capsid and Cp183 packaged ~4800 nucleotides, correlating to the size of HBV's RNA pre-genome and mature DNA genome, respectively. The RNA:protein charge ratio (about 1.4 phosphates per positive charge) was consistent with that of other ssRNA viruses. This spectroscopic method is generalizable to any virus-like particle.


Polyphemin: a teichoic acid-binding lectin from the horseshoe crab, Limulus Polyphemus.
A Staphylococcus aureus-agglutinating lectin, capable of binding to N-acetyl-D-glucosamine, was isolated from the serum of Limulus polyphemus. The monosaccharide alone was incapable of inhibiting bacterial agglutination by this lectin. Quantitative precipitation studies with purified cell wall-derived teichoic acids, either devoid of or containing N-acetyl-D-glucosamine, confirmed the carbohydrate-binding specificity of the lectin and suggested that secondary, non-specific interactions contribute to binding biomolecules containing this sugar. The agglutination pattern with various S. aureus strains having N-acetyl-D-glucosamine-associated teichoic acid, teichoic acid without this sugar, and no teichoic acid indicated that this cell wall component is not the sole binding site for the lectin on intact S. aureus cells. Affinity gel chromatography, using N-acetyl-D-glucosamine-associated teichoic acid as the specific absorbent, has been used to isolate this lectin from Limulus serum.


Pseudoaneurysm of cystic artery after laparoscopic cholecystectomy.
The formation of a pseudoaneurysm of the cystic artery is a rare occurrence after laparoscopic cholecystectomy. Seven weeks after laparoscopic cholecystectomy, a 31-year-old woman presented with a picture of obstructive jaundice. The diagnosis of cystic artery aneurysm was verified by arteriography, CT and MRCP. At laparotomy the pseudoaneurysm was found to be compressing the common bile duct. It was successfully managed by ligation of the right hepatic artery. Although this complication is rare, the surgeon must have a high index of suspicion to make the diagnosis.


Selenium homeostasis and antioxidant selenoproteins in brain: implications for disorders in the central nervous system.
The essential trace element selenium, as selenocysteine, is incorporated into antioxidant selenoproteins such as glutathione peroxidases (GPx), thioredoxin reductases (TrxR) and selenoprotein P (Sepp1). Although comparatively low in selenium content, the brain exhibits high priority for selenium supply and retention under conditions of dietary selenium deficiency. Liver-derived Sepp1 is the major transport protein in plasma to supply the brain with selenium, serving as a "survival factor" for neurons in culture. Sepp1 expression has also been detected within the brain. Presumably, astrocytes secrete Sepp1, which is subsequently taken up by neurons via the apolipoprotein E receptor 2 (ApoER2). Knock-out of Sepp1 or ApoER2 as well as neuron-specific ablation of selenoprotein biosynthesis results in neurological dysfunction in mice. Astrocytes, generally less vulnerable to oxidative stress than neurons, are capable of up-regulating the expression of antioxidant selenoproteins upon brain injury. Occurrence of neurological disorders has been reported occasionally in patients with inadequate nutritional selenium supply or a mutation in the gene encoding selenocysteine synthase, one of the enzymes involved in selenoprotein biosynthesis. In three large trials carried out among elderly persons, a low selenium status was associated with faster decline in cognitive functions and poor performance in tests assessing coordination and motor speed. Future research is required to better understand the role of selenium and selenoproteins in brain diseases including hepatic encephalopathy.


Electrofocusing the compost organic matter obtained by coupling SEC-PAGE.
Humic acids (HA)-like extracted from compost at the beginning (t(0)) and after 130 days of composting (t(130)) were fractionated by coupling size exclusion chromatography to polyacrylamide gel electrophoresis (SEC-PAGE). HA-like fractions with the same molecular size (MS) and electrophoretic mobility were pooled and further characterised by analytical polyacrylamide gel electrofocusing (EF) and compared with HA separated from a Typic Chernozem soil. During the composting process all fractions were subjected to quantitative and qualitative modifications: the high MS fraction was degraded, the mid MS fractions were qualitatively changed, the content of low MS fractions increased and changed qualitatively. The main changes in EF pattern of the non fractionated HA-like t(130) were associated to low MS fractions. Such data seem to be reliable for explanation what mechanisms and monitoring of the evolution of the compost organic matter for their agricultural uses.


Associations between polysomnography measurements and postoperative adverse respiratory events in children with neuromuscular disease.
To determine if polysomnographic cardiorespiratory outcomes are associated with and could have the potential to predict the presence of postoperative adverse respiratory events in children with neuromuscular disease undergoing any surgical procedure. A retrospective cohort study was conducted at a tertiary pediatric institution. The study population included individuals with neuromuscular disease admitted for a surgical intervention under general anesthetic who had undergone a polysomnogram within 1 year before surgical intervention. Polysomnographic indices and postoperative adverse respiratory events were collected through chart review. Multivariable logistic regression was used to model postoperative adverse respiratory events, where PSG results were considered primary predictors. Postoperative adverse respiratory events occurred in 25/61 (41%) of individuals and consisted mainly of desaturations requiring intervention 33 (73%), airway obstruction 15 (33%), and atelectasis (22%). Results from the unadjusted and adjusted logistic regression models indicated that saturation nadir and bulbar dysfunction individually were independent risk factors for postoperative adverse respiratory events with the highest areas under the receiver operating characteristic curve. A multivariable prediction model using these 2 risk factors provided an area under the receiver operating characteristic curve of 0.74 (95% confidence interval, 0.65-0.83). Knowing that nocturnal oxygen saturation nadir and the presence of bulbar dysfunction are potential predictors of postoperative adverse respiratory events is useful for future counseling of families and surgical planning, in an effort to improve perioperative management and reduce adverse events.


Photomodulation of the electrode potential of a photochromic spiropyran-modified Au electrode in the presence of Zn2+: a new molecular switch based on the electronic transduction of the optical signals.
The electrode potential of a photochromic spiropyran-modified Au electrode could be reversibly modulated by UV/visible light irradiation in the presence of Zn2+, and a new molecular switch and an "AND" logic gate based on this electronic transduction of the optical signals were established.


The Abc of Phosphonate Breakdown: A Mechanism for Bacterial Survival.
Bacteria have evolved advanced strategies for surviving during nutritional stress, including expression of specialized enzyme systems that allow them to grow on unusual nutrient sources. Inorganic phosphate (Pi ) is limiting in most ecosystems, hence organisms have developed a sophisticated, enzymatic machinery known as carbon-phosphorus (C-P) lyase, allowing them to extract phosphate from a wide range of phosphonate compounds. These are characterized by a stable covalent bond between carbon and phosphorus making them very hard to break down. Despite the challenges involved in both synthesizing and catabolizing phosphonates, they are widespread in nature. The enzymes required for the bacterial C-P lyase pathway have been identified and for the most part structurally characterized. Nevertheless, the mechanistic principles governing breakdown of phosphonate compounds remain enigmatic. In this review, an overview of the C-P lyase pathway is provided and structural aspects of the involved enzyme complexes are discussed with a special emphasis on the role of ATP-binding cassette (ABC) proteins.


Treatment of residual pockets using an oscillating chitosan device versus regular curettes alone-A randomized, feasibility parallel-arm clinical trial.
A brush made of chitosan has shown to be an effective and harmless device for non-surgical treatment of mild to moderate peri-implantitis. To date, no study has evaluated the use of a chitosan brush in the non-surgical treatment of residual pockets in periodontal treatment. Seventy-eight patients with periodontitis were included in this multicenter, randomized, examiner-blind clinical trial of 6 months duration. Patients with residual probing pocket depth (PPD) of ≥5 mm and ≤7 mm following previous active periodontal treatment were included. Patients were assigned either subgingival treatment with curettes (control) or an oscillating chitosan brush (test). Changes in bleeding on probing (BoP) and PPD between baseline and terminal evaluation at 6 months were evaluated. A significant reduction in both PPD and BoP was seen within both groups. There was no significant difference in BoP between test and control groups after 6 months, but the reduction in PPD was significantly improved in the test group (P ≤ 0.01). The combined outcome of no BOP and PPD ≤4 mm was significantly better in the test group (P ≤ 0.01). No adverse reactions were seen. Treatment of residual periodontal pockets (PPD = 5 to 7 mm) with a chitosan brush disclosed equal or better clinical results as compared to regular curettes. This study supports that a chitosan brush can be used for subgingival biofilm removal and soft tissue curretage in the treatment of periodontitis.


Dysmorphic features, simplified gyral pattern and 7q11.23 duplication reciprocal to the Williams-Beuren deletion.
We report a patient with mild pachygyria, ascertained during a screening of subjects with abnormal neuronal migration and/or epilepsy, having a 7q11.23 duplication reciprocal to the Williams-Beuren critical region (WBCR) deletion. He exhibited speech delay and mental retardation together to type II trigonocephaly and other abnormalities. The proband's mother carried the same imbalance, though her phenotype was milder and no abnormal conformation of the cranium was reported. She had suffered a few seizures in infancy, as already described in other duplicated subjects. This genomic imbalance, now described in 17 subjects, including one parent for each of the four probands, is associated with a variable phenotype. Speech impairment is present in most cases; no distinctive facial gestalt is recognizable; seizures have been reported in four subjects and brain magnetic resonance, performed in eight cases, resulted abnormal in six, while detected abnormal neuronal migration in two. Although the clinical description of additional cases is needed to delineate a definite phenotypic core for WBCR duplications, trigonocephaly, also reported in another dup(7)(q11.23) patient, is possibly a trait that, together with speech impairment, may call for clinically oriented specific screening. Abnormal development of the cerebral cortex, reported also in the Williams-Beuren deletion, suggests that at least one gene is present in the critical region whose deletion/duplication impairs neuronal migration.


Arsenic adsorption from aqueous solutions by activated red mud.
Heat treatment and acid treatment methods have been tested on red mud to increase its arsenic adsorption capability. The results indicate that the adsorptive capacity of red mud can be increased by acid treatment. This treatment causes sodalite compounds to leach out. As(III) and As(V) adsorption characteristics of activated red mud have similar tendencies with raw red mud. Batch adsorption studies have shown that activated red mud in dosages ranging from 20 to 100 g l(-1) can be used effectively to remove arsenic from aqueous solutions. The process is pH dependent, the optimum range being 5.8-7.5 for As(III) and 1.8-3.5 for As(V). The maximum removals are 96.52% for As(V) and 87.54% for As(III) for solutions with a final pH of 7.25 and 3.50, respectively, for the initial arsenic concentration of 133.5 micromol l(-1) (10 mg l(-1)), activated red mud dosage of 20 g l(-1), contact time of 60 min and temperature of 25 degrees C. The adsorption data obtained follow a first-order rate expression and fit the Langmuir isotherm well. Isotherms have been used to obtain the thermodynamic parameters. It was found that the adsorption of As(III) was exothermic, whereas As(V) adsorption was endothermic.


A pro-inflammatory glycoprotein biomarker is associated with lower bilirubin in metabolic syndrome.
Bilirubin exerts anti-oxidative and anti-inflammatory properties which may beneficially influence the development of cardio-metabolic disorders. A nuclear magnetic resonance (NMR) spectroscopy-based glycoprotein biomarker, designated GlycA, whose signal originates from several glycosylated acute-phase proteins, has been recently developed. We tested whether plasma GlycA is associated with bilirubin in subjects with and without MetS. GlycA (NMR spectroscopy), high sensitivity C-reactive protein (hs-CRP) and bilirubin were measured in 58 fasting subjects with MetS and in 63 subjects without MetS (including 65 subjects with type 2 diabetes mellitus). GlycA and hs-CRP were higher, coinciding with lower bilirubin in MetS (p<0.01 for each). In all subjects combined, GlycA was strongly correlated with hs-CRP (r=0.631, p<0.001). Age-, sex- and diabetes status-adjusted multivariable linear regression analysis demonstrated that GlycA and hs-CRP were both associated positively with the presence of MetS (β=0.256, p=0.014 and β=0.259, p=0.012, respectively). GlycA and hs-CRP were negatively related to bilirubin (β=-0.258, p=0.007 and β=-0.305, p<0.001, respectively), independent of MetS (p>0.05 for each) and diabetes status (p>0.50 for each). GlycA is elevated in MetS, and may represent a quantitative measure of a pro-inflammatory state. Increased levels of glycosylated acute-phase proteins are associated with lower bilirubin in MetS.


Actin dynamics in the growth cone: a key player in axon regeneration.
Neuronal development, maintenance and function depends on the tight regulation of cytoskeleton organization and dynamics. Following injury, adult central nervous system neurons have a limited ability to regenerate and to recapitulate their robust developmental axon growth. This decreased regenerative capacity is set by their inability to establish regeneration-competent growth cones. Growth cones are actin-enriched structures that regulate axon extension rate and direction. During neuronal development, increasing actin dynamics in the growth cone through the regulation of the activity of specific actin-binding proteins leads to increased axon elongation. Here, we will focus on recent findings showing that enhanced axon regeneration in the adult nervous system can be achieved by promoting actin dynamics, or by decreasing actomyosin contraction in the growth cone. These discoveries underscore the importance of actin organization in the growth cone as a key factor to promote axon (re)growth that should be further explored in the future.


Germ cell-specific gene 1 targets testis-specific poly(A) polymerase to the endoplasmic reticulum through protein-protein interactions.
Testis-specific poly(A) polymerase (TPAP) is a cytoplasmic poly(A) polymerase that is highly expressed in round spermatids. We identified germ cell-specific gene 1 (GSG1) as a TPAP interaction partner protein using yeast two-hybrid and coimmunoprecipitation assays. Subcellular fractionation analysis showed that GSG1 is exclusively localized in the endoplasmic reticulum (ER) of mouse testis where TPAP is also present. In NIH3T3 cells cotransfected with TPAP and GSG1, both proteins colocalize in the ER. Moreover, expression of GSG1 stimulates TPAP targeting to the ER, suggesting that interactions between the two proteins lead to the redistribution of TPAP from the cytosol to the ER.


Co-transduction of p27Kip1 strongly augments Fas ligand- and caspase-8-mediated apoptosis in U-373MG glioma cells.
p27Kip1 is a potential tumor suppressor gene. As malignant gliomas express Fas at high levels, the relationship between Fas-mediated apoptosis and p27Kip1 expression may improve therapeutic approaches for treating gliomas. In this study, we transduced U-373MG glioma cells with the Fas ligand or caspase-8 genes using adenovirus vectors after transduction of the p27Kip1 gene to induce cell cycle arrest in U-373MG cells, and evaluated the degree of apoptosis. The results demonstrate that expression of p27Kip1 enhanced Fas ligand- or caspase-8-mediated apoptosis in U-373MG cells. Expression of apoptosis-related genes such as Bax, Bcl-X(L), Bcl-2 or caspase-8 were reduced by p27Kip1 transduction compared with that of beta-actin, whereas p27Kip1 transduction did not affect the expression level of Fas or the Fas ligand. Combined transduction of p27Kip1 with Fas ligand or caspase-8 would overide the resistance mechanism to apoptosis in malignant gliomas.


A longitudinal analysis of chronic MRSA and Pseudomonas aeruginosa co-infection in cystic fibrosis: A single-center study.
Few studies have examined the association between chronic methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) co-infection and health outcomes despite evidence that these pathogens alone contribute to higher morbidity and mortality in cystic fibrosis (CF). This study examines outcomes among CF patients with chronic MRSA and PA co-infection compared with patients with either or neither of these organisms. CF patients attending the care center in Atlanta, GA from 2007-2013 comprised the study cohort. Chronic co-infection was defined as >50% PA+ cultures and >50% MRSA+ cultures and modeled as time-varying. The rate of decline in lung function (FEV1) and the rate of IV treatments were the main outcomes. Among all patients (N=354), chronic co-infection was associated with a significantly more rapid rate of FEV1 decline compared with patients with chronic PA alone [adjusted difference: -0.60% predicted/year (-1.13, -0.08)] and chronic MRSA alone [adjusted difference: -0.89% predicted/year (-1.56, -0.22)]. Rate of IV treatments was significantly higher among patients with chronic co-infection compared with patients with chronic PA alone [adjusted IRR: 1.24 (1.01, 1.52)] and chronic MRSA alone [adjusted IRR: 1.34 (1.03, 1.74)]. Data from the Atlanta Care Center suggest that chronic MRSA and PA co-infection may be associated with increased rate of lung function decline and rate of intravenous antibiotics compared with patients with either pathogen alone.


Transient left homonymous hemianopsia and encephalopathy following treatment of testicular carcinoma with cisplatinum, vinblastine, and bleomycin.
A 36-year-old man being treated with cisplatinum, vinblastine, and bleomycin for testicular carcinoma developed a dense left homonymous hemianopsia, encephalopathy, and a partial nondominant parietal lobe syndrome. He subsequently had a resolution of all signs and symptoms, suggesting that these alarming events were a toxic but reversible side effect of the chemotherapy.


Fibroblast growth factor-2 up-regulates the expression of nestin through the Ras-Raf-ERK-Sp1 signaling axis in C6 glioma cells.
Nestin is a 240-kDa intermediate filament protein expressed mainly in neural and myogenic stem cells. Although a substantial number of studies have focused on the expression of nestin during development of the central nervous system, little is known about the factors that induce and regulate its expression. Fibroblast growth factor-2 (FGF-2) is an effective mitogen and stimulates the proliferation and differentiation of a subset of nestin-expressing cells, including neural progenitor cells, glial precursor cells, and smooth muscle cells. To assess whether FGF-2 is a potent factor that induces the expression of nestin, C6 glioma cells were used. The results showed that nestin expression was up-regulated by FGF-2 via de novo RNA and protein synthesis. Our RT-PCR results showed that C6 glioma cells express FGFR1/3, and FGFRs is required for FGF-2-induced nestin expression. Further signaling analysis also revealed that FGF-2-induced nestin expression is mediated through FGFR-MAPK-ERK signaling axis and the transcriptional factor Sp1. These findings provide new insight into the regulation of nestin in glial system and enable the further studies on the function of nestin in glial cells.


Diagnosis and Management of Hematuria.
Microscopic and gross hematuria present unique and difficult diagnostic and management challenges in the already complex general surgery patient. This article provides the general surgeon with relevant knowledge in the pathophysiology, anatomy, etiologies, workup, and treatments of hematuria. In addition common causes of hematuria that may be encountered by the general surgeon (including trauma, urinary tract infection, urolithiasis, and malignancy), the difficult to manage clinical situation of clot urinary retention is presented. This article provides a urologic framework of thinking for the clinician to best manage a general surgery patient who has hematuria.


First evidence for continuous circulation of hepatitis A virus subgenotype IIA in Central Africa.
Although a high seroprevalence of antibodies against hepatitis A virus (HAV) has been estimated in Central Africa, the current status of both HAV infections and seroprevalence of anti-HAV antibodies remains unclear due to a paucity of surveillance data available. We conducted a serological survey during 2015-2017 in Gabon, Central Africa, and confirmed a high seroprevalence of anti-HAV antibodies in all age groups. To identify the currently circulating HAV strains and to reveal the epidemiological and genetic characteristics of the virus, we conducted molecular surveillance in a total of 1007 patients presenting febrile illness. Through HAV detection and sequencing, we identified subgenotype IIA (HAV-IIA) infections in the country throughout the year. A significant prevalence trend emerged in the young child population, presenting several infection peaks which appeared to be unrelated to dry or rainy seasons. Whole-genome sequencing and phylogenetic analyses revealed local HAV-IIA evolutionary events in Central Africa, indicating the circulation of HAV-IIA strains of a region-specific lineage. Recombination analysis of complete genome sequences revealed potential recombination events in Gabonese HAV strains. Interestingly, Gabonese HAV-IIA possibly acquired the 5'-untranslated region (5'-UTR) of the rare subgenotype HAV-IIB in recent years, suggesting the present existence of HAV-IIB in Central Africa. These findings indicate a currently stable HAV-IIA circulation in Gabon, with a high risk of infections in children aged under 5 years. Our findings will enhance the understanding of the current status of HAV infections in Central Africa and provide new insight into the molecular epidemiology and evolution of HAV genotype II.


Characterization of the primate TRIM gene family reveals the recent evolution in primates.
The tripartite motif (TRIM) gene family encodes diverse distinct proteins that play important roles in many biological processes. However, the molecular evolution and phylogenetic relationships of TRIM genes in primates are still elusive. We performed a genomic approach to identify and characterize TRIM genes in human and other six primate genomes. In total, 537 putative functional TRIM genes were identified and TRIM members varied among primates. A neighbor joining (NJ) tree based on the protein sequences of 82 human TRIM genes indicates seven TRIM groups, which is consistent with the results based on the architectural motifs. Many TRIM gene duplication events were identified, indicating a recent expansion of TRIM family in primate lineages. Interestingly, the chimpanzee genome shows the greatest TRIM gene expansion among the primates; however, its congeneric species, bonobo, has the least number of TRIM genes and no duplication event. Moreover, we identified a ~ 200 kb deletion on chromosome 11 of bonobos that results in a loss of cluster3 TRIM genes. The loss of TRIM genes might have occurred within the last 2 mys. Analysis of positive selection recovered 9 previously reported and 21 newly identified positively selected TRIM genes. In particular, most positive selected sites are located in the B30.2 domains. Our results have provided new insight into the evolution of primate TRIM genes and will broaden our understanding on the functions of the TRIM family.


Caregiving for mental health service users: A study exploring the perceptions of mental health service users and their caregivers in Cape Town, South Africa.
Our study explores perceptions of the caregiver support for mental health service users (MHSUs) in a low- to middle-income country setting. We conducted in-depth individual interviews with 16 MHSUs and their treatment partners/caregivers from a treatment partner and text-message intervention study. Treatment partners/caregivers felt obligated to care for MHSUs, but had a limited understanding of mental illness. They found supporting adherence to treatment difficult due to a number of factors including violence, food insecurity and substance abuse. Socioeconomic and environmental factors affecting the lives of MHSUs have impact on caregiver relationships with MHSUs in their care.


Immunoreactivity for cyclin D3 is frequently detectable in high-grade primary gastric lymphomas in the absence of the t(6;14)(p21.1;q32.3) chromosomal translocation.
Cyclin D3 plays a pivotal role in controlling the physiological progression from the G1 to the S phase of the cell cycle. Recent data suggest that cyclin D3 may be deregulated in extranodal non-Hodgkin's lymphomas (NHLs) as a consequence of the t(6;14)(p21.1;q32.3) translocation. The present study investigated for the first time by dual-colour fluorescence in situ hybridization (FISH) on interphase nuclei and immunohistochemistry the prevalence of the t(6;14) translocation and cyclin D3 immunoreactivity (IR) in a series of 29 stage I-IIE primary gastric NHLs (PGLs). No case showed the t(6;14) translocation. However, in five (17.2%) cases (two extranodal marginal zone lymphomas of MALT type, LGM; one diffuse large-cell lymphoma with a MALT component, DLCLM; and two diffuse large-cell lymphomas without a MALT component, DLCL), three to four cyclin D3 signals were detected by FISH. Co-hybridization with probes specific for the centromeric region and long arm of chromosome 6 indicated trisomy in one case (DLCL), whereas in the remaining four cases the pattern was highly suggestive of the presence of an isochromosome 6p. One (12.5%) case of LGM, six (75%) cases of DLCLM, and seven (53.8%) cases of DLCL (p = 0.0378) were immunoreactive for cyclin D3. Cyclin D3 IR was detected in two (40%) of the five cases with extra cyclin D3 signals and in 12 of the remaining 24 cases (50%, p = 1.000). These results suggest that the t(6;14) may represent a rare event in the pathogenesis of PGL and that cyclin D3 deregulation is most likely the result of epigenetic mechanisms.


Urgent endovascular aorta repair for a rupture of a traumatic infrarenal aortic dissection: Case report and review of literature.
Traumatic aortic injury is a life-threatening condition usually followed by blunt trauma with damage at the thoracic aorta. Abdominal aortic injuries are rare and usually seen with seatbelt trauma. Timing and approach of treatment are associated with significant morbidity and mortality. This case concerns a 66-year-old man with a high impact trauma after a fall from height. Upon presentation in our level two trauma center, he was conscious but hemodynamically unstable. Computer Tomography scan revealed multiple rib, spine and pelvic fractures with bilateral lung contusions warranting a transfer to a level one trauma center. However, an infrarenal aortic dissection with a retroperitoneal rupture and active bleeding necessitated acute surgical intervention. He was treated endovascularly with an off-the-shelf aortic stent graft which is meant for aortic aneurysm repair. Surgery was performed percutaneously under local anesthetic. Other fractures were treated conservatively. Postoperatively, the patient made a swift recovery without any complications in follow-up. As this case demonstrates, urgent endovascular repair of a traumatic infrarenal aortic injury can be done quickly with a minimally invasive approach with conventional stent graft systems thereby reducing the high morbidity and mortality rates associated with this life-threatening condition.


The delusive benefit of the doubt.
Science promises benefits, some true and some illusory. Consider a scientific agnostic who thinks that to reap the true benefits of a scientific theory he does not have to believe in its theoretical posits. Instead, it is enough if he believes that the theory successfully predicts the behavior of the observables, as ultimately only such predictions matter. Say, however, that given the results of her thorough research, a psychologist proposes a theory describing a psychological mechanism underlying a certain class of normative judgments. Moreover, the mechanism seems unfit for the task-once you see the details of the mechanism, you will realize that this is not the way they should be produced. Therefore, if the psychologist is right, it seems that these normative judgments should not inform one's normative theorizing or one's actions (Greene, 2008; Greene, 2014; Kelly, 2014). And say that the agnostic accepts the psychologist's theory, trusting that it makes correct predictions about, for example, fMRI images and subjects' reaction times, as they are observable. He also thinks that if the psychologist's description of the mechanism is correct, the judgments should not be trusted. Yet, since the mechanism posited by the theory is not observable, the agnostic is agnostic about it. He thus cannot be convinced that these judgments are produced in a flawed way and, consequently, has no reason to distrust them. Scientific agnosticism comes, therefore, at the cost of dismissing normative arguments that invoke unobservable posits of psychological models. The ability to make such arguments is a true (rather than illusory) benefit of science, despite the agnostic's promise that his philosophical theory leaves intact benefits that genuinely matter.


Biodegradation of anthelmintics in soils: does prior exposure of soils to anthelmintics accelerate their dissipation?
Anthelmintics (AHs) control animal infections with gastrointestinal nematodes. They reach soil through animal faeces deposited on soils or through manuring. Although soil constitutes a major AH sink, we know little about the mechanisms controlling their soil dissipation. We employed studies with fumigated and non-fumigated soils collected from 12 sheep farms with a variable record of albendazole (ABZ), ivermectin (IVM) and eprinomectin (EPM) use. From each farm, we collected soils from inside small ruminant barn facilities (series A, high exposure) and the associated grazing pastures (series B, low exposure). We asked the following questions: (a) What is the role of soil microorganisms in AH dissipation? (b) Does repeated exposure of soils to AHs lead to their accelerated biodegradation? (c) Which soil physicochemical properties control AH dissipation? Soil fumigation significantly retarded ABZ (DT50 1.9 and 4.33 days), IVM (34.5 and 108.7 days) and EPM dissipation (30 and 121 days) suggesting a key role of soil microorganisms in AH dissipation. No significant acceleration in AH dissipation was evident in soils from units with a record of the administration of AHs or in soil series A vs series B, suggesting that the level of prior exposure was not adequate to induce their enhanced biodegradation. Significant positive and negative correlations of soil total organic carbon (TOC) and ABZ and IVM dissipation, respectively, were observed. Soil adsorption of AHs increased in the order IVM > ABZ > EPM. TOC controlled soil adsorption of IVM and EPM, but not of ABZ, in support of the contrasting effect of TOC on IVM and ABZ dissipation.


Accumulation of physical activity: blood pressure reduction between 10-min walking sessions.
The accumulation of intermittent bouts of physical activity (PA) has been found to reduce blood pressure (BP) in prehypertension and hypertension. Yet, the BP response among several short sessions within the accumulation of PA in a single day has not been examined. The purpose of the study was (1) to investigate the BP reduction during the rest periods following three successive 10-min walking sessions accumulated over a 3-h period in prehypertensive adults and (2) to observe the role of autonomic modulation during the rest periods following each short PA session. Adults with prehypertension (131.9+/-4.7/82.5+/-6.4 mm Hg) participated in the study. BP using ambulatory monitoring and autonomic modulation through heart rate variability (HRV) using Holter monitoring were measured at baseline and during the rest periods following three short sessions (three 10-min treadmill walks at 50% of peak oxygen uptake (VO2peak); at least 50 min apart) over a 3-h period. Variables of BP and autonomic modulation were averaged for the baseline and for the rest periods following each 10-min walk. One-way analysis of variance with repeated measures was used to test the differences over time in BP and HRV (P<0.05). A significant main effect was found in systolic BP (P=0.039), whereas none was found in diastolic BP (P=0.630). Systolic BP was decreased following the third short session (-4.0+/-7.4 mm Hg) compared to baseline. No significance was found in any of the autonomic modulation variables. In conclusion, accumulating intermittent bouts of PA, as short as 10 min, total 30-min walk sessions may reduce systolic BP in prehypertension.


Beclin 1 expression is an independent prognostic factor for gastric carcinomas.
Beclin 1, an important autophagy-related protein in human cells, is involved in autophagy, differentiation, anti-apoptosis, and cancer progression, which is increased during periods of cell stress and extinguished during the cell cycle. In order to clarify the role of Beclin 1 in gastric carcinogenesis and subsequent progression, its expression was examined by immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing gastric carcinomas, adjacent non-neoplastic mucosa, and metastatic lymph node. Gastric carcinoma tissue and cell lines were studied for Beclin 1 expression by Western blot or RT-PCR, respectively. The results demonstrated that Beclin 1 was distinctively expressed in GES-1, AGS, BGC-823, GT-3 TKB, HGC-27, KATO-III, MGC-803, MKN28, MKN45, SCH, SGC-7901, or STKM-2 at both mRNA and protein levels. However, Beclin 1 mRNA was highly expressed in gastric carcinoma than matched mucosa by real-time PCR and ISH (P < 0.05). Beclin 1 expression was negatively related to distant metastasis and poor prognosis of gastric carcinoma (P < 0.05). Beclin 1 was highly expressed in male than female patients with gastric carcinoma (P < 0.05). The 65-year-elder patients with gastric carcinoma had higher Beclin 1 expression than the younger ones (P < 0.05). The diffuse-type carcinomas showed less Beclin 1 expression than intestinal- and mixed-type ones (P < 0.05). In intestinal-type gastric carcinoma, Beclin 1 expression was inversely associated with venous invasion, lymph node metastasis, and tumor-node-metastasis (TNM) staging (P < 0.05). Kaplan-Meier analysis indicated that Beclin 1 expression was positively linked to favorable prognosis of the patients with overall and intestinal-type carcinoma (P < 0.05). Cox's proportional hazard model indicated that venous invasion, lymph node metastasis, distant metastasis, TNM staging, and Beclin 1 expression were independent prognostic factors for gastric carcinomas (P < 0.05). It was suggested that aberrant Beclin 1 expression is closely linked to pathogenesis, metastasis, and differentiation of gastric carcinoma. Beclin 1 expression might be employed to indicate the favorable prognosis of gastric carcinomas as an independent factor.


Synthesis and antiviral activity evaluation of novel 2-phenyl-4-(D-arabino-4'-cycloaminobutyl)triazoles: acyclonucleosides containing unnatural bases.
Five 2-phenyl-4-(D-arabino-4'-cycloamino-3'-hydroxy-O-1',2'-isopropylidene-butyl)-2H-1,2,3-triazoles, acyclonucleosides containing unnatural bases have been synthesised by opening of the epoxide ring of 2-phenyl-4-(D-arabino-3',4'-epoxy-O-1',2'-isopropylidenebutyl)-2H-1,2,3-triazole with the corresponding cyclic amines in 70-85% yields. The starting arabino-epoxytriazole was prepared in five steps starting from D-glucose in an overall yield of 15%. All the five triazolylacyclonucleosides were unambiguously identified on the basis of their spectral data. The structure of one of the intermediates, that is 2-phenyl-4-(D-arabino-1',2',3',4'-tetrahydroxybutyl)-2H-1,2,3-triazole was confirmed by its X-ray crystallographic studies. These acyclonucleosides were subjected to antiviral activity evaluation in CEM-SS cell-based anti HIV assay with the lymphocytropic virus strains HIV-1(IIIB) and HIV-1(RF).


Aberrant Neuronal Activity in a Model of Work-Related Upper Limb Pain and Dysfunction.
Work-related musculoskeletal disorders associated with intense repetitive tasks are highly prevalent. Painful symptoms associated with such disorders can be attributed to neuropathy. In this study, we characterized the neuronal discharge from the median nerve in rats trained to perform an operant repetitive task. After 3-weeks of the task, rats developed pain behaviors and a decline in grip strength. Ongoing activity developed in 17.7% of slowly conducting neurons at 3-weeks, similar to neuritis. At 12-weeks, an irregular high frequency neuronal discharge was prevalent in >88.4% of slow and fast conducting neurons. At this time point, 8.3% of slow and 21.2% of fast conducting neurons developed a bursting discharge, which, combined with a reduction in fast-conducting neurons with receptive fields (38.4%), is consistent with marked neuropathology. Taken together, we have shown that an operant repetitive task leads to an active and progressive neuropathy that is characterized by marked neuropathology following 12-weeks task that mainly affects fast conducting neurons. Such aberrant neuronal activity may underlie painful symptoms in patients with work-related musculoskeletal disorders. PERSPECTIVE: Aberrant neuronal activity, similar to that reported in this study, may contribute to upper limb pain and dysfunction in patients with work-related musculoskeletal disorders. In addition, profiles of instantaneous frequencies may provide an effective way of stratifying patients with painful neuropathies.


Evolution of DFT studies in view of a scientometric perspective.
This bibliometric study aims to analyze the publications in which density functional theory (DFT) plays a major role. The bibliometric analysis is performed on the full publication volume of 114,138 publications as well as sub-sets defined in terms of six different types of compounds and nine different research topics. Also, a compound analysis is presented that shows how many compounds with specific elements are known to be calculated with DFT. This analysis is done for each element from hydrogen to nobelium. We find that hydrogen, carbon, nitrogen, and oxygen occur most often in compounds calculated with DFT in terms of absolute numbers, but a relative perspective shows that DFT calculations were performed rather often in comparison with experiments for rare gas elements, many actinides, some transition metals, and polonium. The annual publication volume of DFT literature continues to grow steadily. The number of publications doubles approximately every 5-6 years while a doubling of publication volume every 11 years is observed for the CAplus database (14 years if patents are excluded). Calculations of the structure and energy of compounds dominate the DFT literature.


[Phalengeal actinomycosis: a rare disease].
Bone involvement in actinomycosis is rare. We report a case of a 38 year-old woman with foot bone actinomycosis. The clinical symptoms were non-specific and the diagnosis was difficult. An X-ray revealed an osteolysis and a sclerosis of the proximal phalanx of the big toe. A phalengiectomy was carried out after the failure of antistaphylococcic antibiotherapy. The diagnosis of actinomycosis was substantiated by a histological examination. The clinical outcome was good after six-month treatment by penicillin G substitutes for cotrimoxazol. The patient completely recovered and was feeling well. The mean follow up was fifteen months. Clinical and therapeutic aspects of this rare localization are reviewed.


Where am I and how will I get there from here? A role for posterior parietal cortex in the integration of spatial information and route planning.
The ability of an organism to accurately navigate from one place to another requires integration of multiple spatial constructs, including the determination of one's position and direction in space relative to allocentric landmarks, movement velocity, and the perceived location of the goal of the movement. In this review, we propose that while limbic areas are important for the sense of spatial orientation, the posterior parietal cortex is responsible for relating this sense with the location of a navigational goal and in formulating a plan to attain it. Hence, the posterior parietal cortex is important for the computation of the correct trajectory or route to be followed while navigating. Prefrontal and motor areas are subsequently responsible for executing the planned movement. Using this theory, we are able to bridge the gap between the rodent and primate literatures by suggesting that the allocentric role of the rodent PPC is largely analogous to the egocentric role typically emphasized in primates, that is, the integration of spatial orientation with potential goals in the planning of goal-directed movements.