A von Hámos spectrometer for diamond anvil cell experiments at the High Energy Density Instrument of the European X-ray Free-Electron Laser.
A von Hámos spectrometer has been implemented in the vacuum interaction chamber 1 of the High Energy Density instrument at the European X-ray Free-Electron Laser facility. This setup is dedicated, but not necessarily limited, to X-ray spectroscopy measurements of samples exposed to static compression using a diamond anvil cell. Si and Ge analyser crystals with different orientations are available for this setup, covering the hard X-ray energy regime with a sub-eV energy resolution. The setup was commissioned by measuring various emission spectra of free-standing metal foils and oxide samples in the energy range between 6 and 11 keV as well as low momentum-transfer inelastic X-ray scattering from a diamond sample. Its capabilities to study samples at extreme pressures and temperatures have been demonstrated by measuring the electronic spin-state changes of (Fe0.5Mg0.5)O, contained in a diamond anvil cell and pressurized to 100 GPa, via monitoring the Fe Kβ fluorescence with a set of four Si(531) analyser crystals at close to melting temperatures. The efficiency and signal-to-noise ratio of the spectrometer enables valence-to-core emission signals to be studied and single pulse X-ray emission from samples in a diamond anvil cell to be measured, opening new perspectives for spectroscopy in extreme conditions research.


[New approaches to the secretolytic therapy of chronic bronchitis in dogs].
6 dogs with chronic obstructive pulmonary disease (COPD) are treated with acetylcysteine and get three infusions of isotonic NaCl (7-10% of body weight). Their dyspnea is visibly improved. Their therapeutic benefit is objectified by radiology and blood gas parameters.


Exploring Urological Surgery Wait Times as a Quality Indicator of Care: A Case Study of Different Health Care Systems.
We determined and compared wait times for urological procedures at 2 centers in different health care systems to more fully understand the usefulness of wait times as a quality indicator. A retrospective review of patient wait times for transurethral bladder tumor resection was performed at Albany Medical Center, Albany, New York and Kingston General Hospital, Kingston, Ontario, Canada. The time from the decision for surgery until the completion of surgery (Wait 2) was determined for 495 consecutive patients during calendar years 2011 and 2012. Patient, surgeon and tumor factors that could potentially affect wait times were collected, as were wait times from referral to initial consultation (Wait 1) for new patients. These findings were contrasted with the wait times for 375 patients who underwent transurethral prostate resection. Median Wait 2 time for transurethral bladder tumor resection was statistically but not clinically different at 24 days at Albany Medical Center and at 35 days at Kingston General Hospital. High grade and stage were associated with shorter wait times at Albany Medical Center but not at Kingston General Hospital. Median Wait 1 time was different at Albany Medical Center (13 days) vs Kingston General Hospital (25 days), significantly adding to the total wait. For transurethral prostate resection the Wait 2 times were more disparate at 29 and 58 days at Albany Medical Center and Kingston General Hospital, respectively. The use of wait time as a measure of surgical quality of care is complex. These results suggest that measuring a summary wait time (Wait 2) may not identify the structural and process issues that affect care delivery.


A novel magnetic bead bioassay platform using a microchip-based sensor for infectious disease diagnosis.
New technologies are greatly needed to improve laboratory tests that can be used in point-of-care clinical settings. Here, a biosensor was used to detect micron-scale paramagnetic beads in order to replace the conventional enzymatic label used in ELISAs. This novel biosensor was fabricated through standard complementary metal oxide semiconductor (CMOS) manufacturing and was used to quantify magnetic beads bound to the sensor surface by immunological recognition, analogous to ELISA. CMOS technology can integrate multiple laboratory functions into the sensor chip, potentially enabling inexpensive, compact and sophisticated diagnostic systems for a number of diseases. We present results for two immunological assays: antigen capture of purified mouse IgG and detection of human anti-dengue virus IgG in clinical serum samples. The sensitivity of detecting purified protein with magnetic beads was comparable to ELISA. We found a high correlation between the ELISA optical density and the biosensor output in the clinical assay. We also demonstrate the use of a controlled magnetic field to remove non-specifically bound magnetic beads from the sensor surface, effectively washing the sensor surface. This novel sensor can be mass-produced at low cost and can detect magnetic beads bound to the surface through specific antibody-antigen interactions, making it a potential platform for new simplified and rapid point-of-care diagnostic tests.


Association between esophageal motor disorders and pulmonary involvement in patients affected by systemic sclerosis: a retrospective study.
Systemic sclerosis (SSc) is a rare autoimmune disease of the connective tissue that can affect multiple organs. The esophagus is the most affected gastrointestinal tract, while interstitial lung disease (ILD) is a main feature associated with SSc. The aim of the present study was to evaluate the association and prognostic implication between motor esophageal disorders and pulmonary involvement in SSc patients. We retrospectively assessed patients with SSc who underwent both the HRM with the new Chicago Classification 4.0 and pulmonary evaluation comprehensive of function tests and high-resolution computer tomography (HrCT) with the use of Warrick score. A total score ≥ 7 was considered predictive of ILD, while a score ≥ 10 in a HrCT acquired prospectively from baseline evaluation was considered to establish significant interstitial involvement. Forty-two patients were included. We found a score ≥ 7 in 11 patients with aperistalsis, in 6 subjects with IEM and in 6 patients with a normal manometry. Otherwise, a score < 7 was observed in 3 patients with aperistalsis, and in 2 and 14 patients with IEM and with a normal contractility, respectively. Higher scores were observed in subjects with absent contractility or ineffective esophageal motility than subjects with normal motility, indeed DCI and HrCT score were inversely correlated in linear and logarithmic regression analysis. Prospectively, lower baseline LESP and greater HrCT scores at follow-up evaluation were significantly correlated. This study shows an association between motor esophageal disorder and pulmonary involvement in SSc patients: more severe is the esophageal involvement, more critical is the pulmonary disease.


Oxidation-reduction potentials of human fetal hemoglobin and gamma chains. Effects of blocking sulfhydryl groups.
The oxidation-reduction equilibrium of the gamma chains of human fetal hemoglobin (Hb F) has been studied and compared with that of the alpha and beta chains of human adult hemoglobin (Hb A). The effects of the sulfhydryl (--SH) reagents, iodoacetate, iodoacetamide, and p-mercuribenzoate (PMB), on the three kinds of chains and on Hb F have been compared. The midpoint potentials (E-m) of all three sorts of chains are lower than those of tetrameric hemoglobin A or F. The E-m values of alpha chains are the lowest, E-m = 0.049 volt at 6 degrees, and are unaffected by pH change or by PMB treatment, at least from pH 6 to 8. The E-m values of beta-SH chains are higher; E-m = 0.102 volt at pH 7, decreasing to 0.050 volt at pH 8, both at 6 degrees. These results agree with those of Banerjee and Cassoly ((1969) J. Mol. Biol. 42, 337-349). They reported no effect of PMB on beta chains, but we find that 2 eq of PMB/chain raise E--M to 0.139 volt at pH 7 at 6 degrees, chiefly as the result of reaction at beta-93, not at beta-112. Carboxymethylation at beta-93 has an insignificant effect compared with that of PMB. The oxidation-reduction potential of gamma chains is similar to that of beta chains. E-m = 0.098 volt at pH 7 at 6 degrees, decreasing to 0.064 at pH 8 and 0.010 at pH 9. The effects of --SH reagents, reacting at position gamma-93 (the only --SH group present in gamma chains), are essentially the same as those seen with beta chains. The oxidation-reduction potential of Hb F is almost identical with that of Hb A, except for being 0.008 volt lower at pH 6 at 6 degrees. This agrees with the results reported by Flohe and Uehleke ((1966) Life Sci. 5, 1041-1045). PMB or iodoacetamide treatment lowers E-m by 0.02 to 0.03 volt, depending on the pH, from 6 to 9, in much the same way as previously reported for Hb A(Brunori, M., Taylor, J.F., Antonini, E., Wyman, J., and Rossi-Fanelli, A. (1967) J. Biol. Chem. 242, 2295-2300). The "residual oxidation Bohr effect" noted in Hb F can be attributed to the oxidation Bohr effect of the gamma chains. The apparent pK of the heme-linked water molecule was found at 25 degrees to be, for Hb F, 8.1; for gamma-SH chains, 7.85; for gamma-PMB chains, 8.35; and for gamma chains treated with iodoacetate, 7.80. Sedimentation coefficients, s-20, w, at a protein concentration of 5 mg/ml, were found to be, for fetal hemoglobin 4.09, for iodoacetamide-treated fetal hemoglobin 4.04, for PMB-treated fetal hemoglobin 3.41, for fetal gamma-SH chains 4.25, and for fetal gamma-PMB chains 3.08.


Copper changes the yield and cadmium/zinc accumulation and cellular distribution in the cadmium/zinc hyperaccumulator Sedum plumbizincicola.
Non-accumulated metals in mixed metal contaminated soils may affect hyperaccumulator growth and metal accumulation and thus remediation efficiency. Two hydroponics experiments were conducted to investigate the effects of copper (Cu) on cadmium (Cd) and zinc (Zn) accumulation by the Cd/Zn hyperaccumulator Sedum plumbizincicola, Cu toxicity and plant detoxification using chemical sequential extraction of metals, sub-cellular separation, micro synchrotron radiation based X-ray fluorescence, and transmission electron microscopy. Compared with the control (0.31 μM Cu), 5-50 μM Cu had no significant effect on Cd/Zn accumulation, but Cu at 200 μM induced root cell plasmolysis and disordered chloroplast structure. The plants held Cu in the roots and cell walls and complexed Cu in insoluble forms as their main detoxification mechanisms. Exposure to 200 μM Cu for 4 days inhibited plant Cd uptake and translocation but did not affect Zn concentrations in roots and stems. Moreover, unloading of Cd and Zn from stem to leaf was restrained compared to control plants, perhaps due to Cu accumulation in leaf veins. Copper may thus interfere with root Cd uptake and restrain Cd/Zn unloading to the leaves. Further investigation of how Cu affects plant metal uptake may help elucidate the Cd/Zn hyper-accumulating mechanisms of S. plumbizincicola.


Contrast-enhanced ultrasonography for detecting histological carotid plaque rupture: Quantitative analysis of ulcer.
Few studies have evaluated the distinct ability of contrast-enhanced ultrasonography for detecting carotid plaque rupture versus histological observations. The aim of this study was to quantitatively assess the ability of contrast-enhanced ultrasonography to detect plaque rupture compared to ultrasonographic and histological images in terms of geometric accordance. Carotid plaque morphology was classified as "smooth," "irregular," or "ulcerated" on 45 conventional ultrasonography and contrast-enhanced ultrasonography images from consecutive patients undergoing endarterectomy, and 55 regions of interests were captured on contrast-enhanced ultrasonography. A comparative study with a receiver operating characteristic analysis was performed using histological findings for reference. Contrast-enhanced ultrasonography exhibited a higher percentage of "ulcerated" findings in patients with plaque rupture compared to conventional ultrasonography (P = 0.002) as well as an association with thrombus formation (P = 0.048) and fibrous cap disruption (P < 0.0001). On contrast-enhanced ultrasonography, "ulcerated" were significantly more likely than "smooth" findings when the fibrous cap was disrupted (odds ratio (OR), 41.5). The receiver operating characteristic areas under the curve for the orifice, depth, and width of the concavities on contrast-enhanced ultrasonography were significantly greater than 0.5, while their optimal cut-off values were 1.40 mm, 1.30 mm, and 1.88 mm, respectively. When one of these variables was greater than the optimal cut-off value, the sensitivity, negative hit rate, and odds ratio for detecting fibrous cap disruption were 91.3%, 91.6%, and 23.1, respectively. In our study, contrast-enhanced ultrasonography has high sensitivity for identifying histological plaque rupture, and the measurement of concavity on contrast-enhanced ultrasonography may enable the accurate detection of fibrous cap disruption.


Nonagenarian surgical admissions for the acute abdomen: who benefits?
Patients 90 years and older form an increasing proportion of the general population. Outcomes of their acute surgical admissions are not well documented. Surgical management of 49 consecutive nonagenarian admissions (median age: 92 years) with an acute abdomen was compared with the management and outcome of 50 younger patients (median age: 53.5) admitted with a suspected acute abdomen over the same period. Nonagenarian group consisted of mainly women (71% vs. 50%; p = 0.003). The use of laboratory investigations and imaging was similar for the patients aged over 90 and the younger patients, although proportionately fewer nonagenarians were investigated by abdominal CT scan (8% vs. 24%). Of the 49 nonagenarian patients admitted, only 4% (n = 2) were operated on. In contrast, 38% (n = 19) of patients aged 50-59 (p = 0.0001) underwent a surgical intervention. A much greater proportion of nonagenarians died in hospital than patients in the 50-59 comparator group (16% nonagenarians vs. 4% comparator patients; p = 0.04). The very large majority of survivors in both age groups were discharged back to their preadmission domicile [39 (95%) nonagenarians vs. 46 (96%) comparator 50-59 year group]. In this study, when compared with younger patients, very few nonagenarian patients (2%) with a suspected acute abdomen benefited from surgical admission. Instead, the large majority of nonagenarians either died or were discharged back to their home address without surgery.


Electromyography as a Method for Distinguishing Dystonia in Mice.
Electromyography (EMG) methods allow quantitative analyses of motor function. The techniques include intramuscular recordings that are performed in vivo. However, recording muscle activity in freely moving mice, particularly in models of motor disease, often creates challenges that prevent the acquisition of clean signals. Recording preparations must be stable enough for the experimenter to collect an adequate number of signals for statistical analyses. Instability results in a low signal-to-noise ratio that prohibits proper isolation of EMG signals from the target muscle during the behavior of interest. Such insufficient isolation prevents the analysis of full electrical potential waveforms. In this case, resolving the shape of a waveform to differentiate individual spikes and bursts of muscle activity can be difficult. A common source of instability is an inadequate surgery. Poor surgical techniques cause blood loss, tissue damage, poor healing, encumbered movement, and unstable implantation of the electrodes. Here, we describe an optimized surgical procedure that ensures electrode stability for in vivo muscle recordings. We implement our technique to obtain recordings from agonist and antagonist muscle pairs in the hindlimbs of freely moving adult mice. We validate the stability of our method by holding EMG recordings during dystonic behavior. Our approach is ideal for studying normal and abnormal motor function in actively behaving mice and valuable for recording intramuscular activity when considerable motion is expected.


Recent advances in modification of novel carbon-based composites: Synthesis, properties, and biotechnological/ biomedical applications.
Nowadays, carbon-based materials owing to great interest in biomedical science/biotechnology and applied for effective diagnosis and treatment of disease. To enhance the effectiveness of carbon nanotubes (CNTs)/graphene-based materials for bio-medical science/technology applications, different kinds of surface modification/functionalization were developed for the attachment of metal oxides nanostructures, biomolecules and polymers. The attachment of pharmaceutical agents with CNTs/graphene, make it a favorable candidate in research field of bio-medical science/technology applications. Surface modified/functionalized CNTs and graphene derivatives materials integrated with pharmaceutical agents has been developed for the purpose of cancer therapy, antibacterial action, pathogens bio detection, drug and gene delivery. Surface modification or functionalization of CNT/graphene materials provides good platform for pharmaceutical agents attachment with improved surface Raman scattering, fluorescence and its quenching capability. Graphene-based biosensing and bioimaging technologies are widely applied to identify numerous trace level analytes. These fluorescent and electrochemical sensors are utilized primarily for detecting organic, inorganic, and biomolecules. In this article, we highlights and summarized overview of the current research progress concerned on the CNTs/graphene-based materials as a new generation materials for detection and treatment of diseases.


Persistent trigeminal artery variant associated with ipsilateral hypoplasia of the internal carotid artery.
A persistent trigeminal artery is the most common persistent carotid-vertebrobasilar anastomosis, while persistent trigeminal artery variants involve termination at the cerebellar artery without connecting to the basilar artery. Internal carotid artery hyperplasia is also a rare congenital anomaly. To the best of our knowledge, there are no reports of persistent trigeminal artery variant associated with ipsilateral hypoplasia of the internal carotid artery. Herein, we report a case of a 44 year-old woman who visited a neurosurgical clinic because of chronic headaches. Magnetic resonance angiography showed impaired delineation of the left internal carotid artery, and she was referred to our hospital for catheter angiography. Angiogram revealed left internal carotid artery hypoplasia and a left persistent trigeminal artery variant that terminated at the left anterior inferior cerebellar artery. Computed tomography bone images showed a narrow left carotid canal. We diagnosed congenital hypoplasia of the left internal carotid artery concomitant with ipsilateral persistent trigeminal artery variant. Careful imaging assessment is important for identifying persistent trigeminal artery variant when associated with ipsilateral internal carotid artery hypoplasia.


The impact of acute kidney injury in diabetes mellitus.
Little data exist on outcome of acute kidney injury (AKI) in diabetes. We describe short-term recovery of renal function, patient mortality and progressive renal dysfunction following AKI in diabetic patients. Using the diagnosis of either diabetes or no diabetes as the defining variable, AKI episodes were identified from records of a clinical biochemistry department serving a population of 560 000. Patient co-morbidity and mortality were collated from electronic patient records. Outcomes were compared with a non-diabetic cohort with AKI. Acute kidney injury was identified in 101 diabetic and 392 non-diabetic patients. Patients with diabetes had less severe AKI, compared with the non-diabetic cohort (AKI stage 1 76% vs 55%, P = 0.0006). Overall acute mortality, and mortality adjusted for co-morbidity, was comparable in the diabetic and non-diabetic groups. Recovery to baseline renal function was greater in diabetic patients (87% vs 63% P = 0.001), and the proportion of patients developing progressive chronic kidney disease was lower in the (14%) compared with the non-diabetic cohort (48%, P < 0.00001). Although acute mortality is comparable following an AKI episode in diabetic patients compared with that associated with AKI in a non-diabetic cohort, for those surviving the acute episode, its impact on renal function is significantly less than in a non-diabetic group.


Autism and the preference for imaginary worlds.
Dubourg and Baumard mention a potential role for the human drive to systemise as a factor motivating interest in imaginary worlds. Given that hyperexpression of this trait has been linked with autism (Baron-Cohen, , ), we think this raises interesting implications for how those on the autism spectrum may differ from the neurotypical population in their engagement with imaginary worlds.


Surface modification of intraocular lenses to reduce corneal endothelial damage.
Two methods of surface modification of PMMA, permanent and temporary, were investigated for use on intraocular lenses to reduce corneal endothelial damage due to corneal-IOL touch. Monomer grafting using gamma irradiation was found to produce permanently hydrophilic surfaces. Temporary surface modifications developed and tested were peelable and dissolvable coatings. Test samples were touched to freshly excised rabbit corneas to evaluate the effectiveness of the various surface modifications in reducing endothelial cell damage. This touch testing was performed using static testing in which the test sample was touched to the cornea without movement and dynamic testing in which there was relative movement between the cornea and the test sample. While unmodified PMMA did significant cell damage in both static and dynamic tests perpamently modified (hydrophilic grafted) surfaces were found to perform well in the static, but not in the dynamic tests. Dissolvable coatings performed well in both tests, even with very thin coatings. There was little differentiation between the various water-soluble coatings tested. Due to its characteristics and rate of dissolution, polyvinyl alcohol appears to be an optimum material for coating IOLs. A series of in vitro and in vivo tests performed to assess its safety indicate that PVA is nontoxic and safe in animal eyes.


Effect of BIX-01294 on proliferation, apoptosis and histone methylation of acute T lymphoblastic leukemia cells.
To determine effect of G9a inhibitor BIX-01294 on proliferation, apoptosis and histone methylation of acute T lymphoblastic leukemia cells (MOLT-4 and Jurkat) and to explore the underlying mechanism. Cell proliferation was detected by MTT assay and apoptosis and cell cycle were measured by flow cytometry. Western blot was performed to determine expression of caspase-3, Bcl-2, Bax, P21, P15 and DNMT1 as well as levels of histone H3 acetylation, histone H3K9 mono- di- and tri-methylation. BIX-01294 inhibits expression of Bcl-2, upregulates expression of Bax and caspase-3 and induces cell apoptosis. BIX-01294 upregulates cell cycle inhibitor P21 expression and induces cell cycle arrest in the phase G0/G1. Furthermore, BIX-01294 suppresses expression of DNA demethylase DNMT1 and promotes expression of tumor suppressor protein P15, thereby inhibiting proliferation of MOLT-4 and Jurkat cells. BIX-01294 downregulates histone H3K9 mono- and di-methylation levels and has no effect on H3K9 trimethylation and histone H3 acetylation. Taken together, our results indicate that by regulating H3K9 methylation and cell cycle, BIX-01294 inhibits the proliferation and induces apoptosis of acute T lymphoblastic leukemia cells.


Acinetobacter calcoaceticus infection following a dog bite.
A frequent complication of dog bite wounds is bacterial infection. The choice of antibiotics is based upon the most likely organisms. Failure to achieve wound healing suggests that an uncommon organism(s) is present and should lead the clinician to culture the wound. A case of Acinetobacter calcoaceticus infection following a dog bite is described.


Refining the prognostic significance of DNA ploidy status in colorectal cancer: a prospective flow cytometric study.
A consecutive series of 123 colorectal cancers, prospectively followed for 3 years, was studied to determine if the prognostic significance of DNA ploidy related to: (a) thresholds used to define DNA aneuploidy, or (b) aneuploid sub-groups defined by DNA index (DI) and peak size. Aneuploidy was defined using 3 methods depending on the minimum proportion of nuclei considered to constitute an aneuploid peak; type 1, 5%; type 2, 10%; type 3, 10% if DI is 1.1-1.8, but 15% if DI is 1.9-2.1. DNA aneuploidy rates were type 1, 75%; type 2, 67%; type 3, 58%. The significance of clinical and pathological correlations varied with the use of different methods. All were associated with a significant DNA diploid survival advantage which was strongest for type 3 (p = 0.006). DI was unrelated to survival irrespective of the presence or absence of an associated S/G2; 33% with a DI of 1.1-1.8 and 35% with a DI of 1.9-2.1 survived. Prognosis was inversely proportional to aneuploid peak size, 48% with small peaks (less than 20%), 30% with intermediate peaks (greater than 20% less than 40%), but none with large peaks (greater than 40%) survived (p = 0.03). We conclude that: (a) thresholds used to define DNA aneuploidy affect the prognostic significance of DNA ploidy; (b) survival is independent of the DI of aneuploid peaks; and (c) measurement of aneuploid peak size refines the prognostic value of DNA ploidy.


Processable Rylene Diimide Dyes up to 4 nm in Length: Synthesis and STM Visualization.
Long and planar: Facile syntheses of soluble hexarylene diimides (HDI) and octarylene diimides (ODI) are described. They are stable in both solution and the solid state and exhibit broad and intense NIR absorption. Scanning tunneling microscopy (STM) reveals that HDI, after deposition from solution, forms a unique herringbone bilayer or stable multilayers depending on the concentration.


Effect of androgen and thyroid hormones on renin-1 messenger ribonucleic acid levels in mouse submandibular gland.
The synthesis of renin and other biologically active polypeptides in the granular convoluted tubule cells of the mouse submandibular gland (SMG) is regulated by androgen and thyroid hormones. In this study genetically hypothyroid (hyt/hyt) mice carrying a single renin structural gene (Ren-1) were used to investigate the mechanism of hormonal action in mouse SMG. Treatment of female mice with 5 alpha-dihydrotestosterone (DHT) and/or thyroxine (T4) enhanced renin-1 activity and increased renin-1 mRNA, determined by Northern analysis. Compared to euthyroid (hyt/+) littermates, hyt/hyt mice had lower basal levels of renin-1 mRNA and a blunted response to either hormone alone. DHT and T4 acted synergistically to increase renin-1 activity and renin-1 mRNA in the SMG of hyt/hyt females. Furthermore, levels of renin-1 activity and renin-1 mRNA varied concordantly in the SMG of these animals. These data indicate that androgen and thyroid hormones influence levels of renin-1 in mouse SMG primarily by regulating the amount of renin-1 mRNA available for translation.


Evaluation of the physico-chemical properties of chitosan as a potential carrier for rifampicin, using voltammetric and spectrophotometric techniques.
Rifampicin is an antibiotic which, on a carbon paste electrode, shows an oxidation response of 0.492 V (vs. Ag/AgCl) at pH 7.0, due to the electroactivity of the hydroquinone group. Interaction of rifampicin with chitosan is strongly dependent on pH, species concentrations and contact time between the latter. Compared to the carbon paste electrode, electrodes modified with chitosan showed greater sensitivity, with optimum voltammetric profile obtained at pH 8.0. Spectrophotometric measurements indicate that rifampicin is strongly absorbed by chitosan at pH less than the pKa of the pharmaceutical, such behaviour being favourable for the use of chitosan as a carrier for the controlled release of rifampicin in the intestinal tract.


Sodium valproate does not augment Prpsc in murine neuroblastoma cells.
Sodium valproate (VPA) has been reported to increase the accumulation of the pathologic isoform of prion protein (PrPsc) in scrapie-infected murine neuroblastoma cells. In this study, the effect of VPA on PrPsc accumulation was investigated in murine N2a neuroblastoma cells chronically infected with scrapie strain 22L (N2a-22L). No accumulation of PrPsc was detected after short-term (3 days) or long-term (21 days) treatment of N2a-22L cells with 4.8, 12, 18 or 24 microM VPA. Higher VPA concentrations (240 and 600 microM) also failed to augment PrPsc expression. In conclusion, in our experimental conditions, no deleterious effect was induced by VPA on prions replication.


[Calorimetry of chromatin and DNA from ascitic cells of C3HA mice in the presence of copper ions].
The process of chromatin denaturation in the composition of C3HA line mice ascites cells was investigated by the method of scanning microcalorimetry. It is shown that copper ions injected into ascites tumour are inculcated in DNA double helix and injure it, and this caused disorder of high ordered chromatin structure.


Vasoactive intestinal polypeptide regulates barrier function via mast cells in human intestinal follicle-associated epithelium and during stress in rats.
Vasoactive intestinal polypeptide (VIP) has been implicated as a regulator of intestinal barrier function and inflammation. Our aim was to elucidate the role of VIP in follicle-associated epithelium (FAE) and villus epithelium (VE) permeability following stress in rats and on human intestinal barrier function. Rats were injected intraperitoneally (i.p.) with VIP receptor-antagonists (anti-VPACs), a mast cell stabilizer, doxantrazole (DOX), or NaCl, and submitted to acute water avoidance stress. Ileal segments were mounted in Ussing chambers to assess (51) chromium-edta ((51) Cr-edta) and Escherichia (E.) coli (strain K-12) permeability. Rat ileal and human ileal and colonic segments were exposed to VIP ± anti-VPACs or DOX. An in vitro co-culture model of human FAE was used to study epithelial-VIP effects. VIP/VPACs distribution was assessed by microscopy. Stress increased (51) Cr-edta and E. coli permeability in VE and FAE. The increases were abolished by i.p. injection of DOX or anti-VPACs. Ileal VIP-exposure ex vivo increased bacterial passage and this was reduced by DOX. In human FAE ex vivo, VIP treatment doubled bacterial uptake, which was normalized by DOX or anti-VPACs. No barrier effects were observed in human colonic tissue. VPACs were found in rat and human ileal follicles, with partial mast cell co-localization. The co-culture model confirmed VIP-mast cell-epithelial interactions in the regulation of barrier function. Stress affects the FAE barrier by mechanisms involving VIP and VPACs on mucosal mast cells. We suggest a regulatory role for VIP in the control of ileal permeability that may be relevant to bacterial-epithelial interactions in stress-related intestinal disorders.


Novel strategy to remove the odor in goat milk: Dynamic discovey magnetic field treatment to reduce the loss of phosphatidylcholine in flash vacuum from the proteomics perspective.
In present study, a precisely profile of PC species in goat milk was presented by quantitative lipidomics, and the matrix effect (bovine, goat and breast milk) on the lipase catalysis of PC metabolism patterns was explored via proteomics. The effects of flash vacuum and magnetic field processes to PC profile were investigated. Results showed PC(16:0_18:1) (1365.24 μg/mL) and PC(16:0_20:2) (1354.73 μg/mL) had the most abundant intensity in goat milk. Twelve novel bioactive lipases: LDHB, NSDHL, ALDH3B1, DPYD, ALDH1A1, ALDOC, ENO1, ALDOA, PRDX6, XDH, ENO3 and GAPDH were nuclear-localized in PC biosynthesis. PC in C15:0, C16:0 increased while C6:0, C8:0 decreased and the characterized protein XDH was about 91 times up regulated under 0.085 MPa, 65 °C flash vacuum and 5 mT magnetic field. The findings suggest different bioactive lipases show desirable effects on PC species metabolism, and magnetic field realize a beneficial programming impact on reducing the loss of PC.


Reduction of potential respiratory pathogens by oral hygienic treatment in patients undergoing endotracheal anesthesia.
This study was conducted to evaluate the usefulness of mechanical and chemical prophylactic oral cleansing treatments for reducing potential respiratory pathogens existing in the oral cavity. Thirty-two patients scheduled to undergo oral and maxillofacial surgery that required endotracheal anesthesia were randomly allocated to one of the two groups, the oral cleansing group (n = 16) or the noncleansing group (n = 16). Culture and polymerase chain reaction (PCR) methods were used to detect and enumerate pathogens. Oral cleansing was carried out with an electric toothbrush capable of automatically supplying and aspirating povidone-iodine solution before surgery, followed by rinsing twice a day after surgery. Cephazolin (3 g x day(-1)) was given to all patients for 5 days after surgery. The PCR detection rates of Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Porphyromonas gingivalis in gargle samples before treatment were 87.5%, 68.8%, 53.1%, and 40.6%, respectively. Oral cleansing reduced the detection rates and numbers of methicillin-sensitive Staphylococcus species, S. pneumoniae, and H. influenzae. In contrast, there was no significant reduction of methicillin-resistant Staphylococcus species, S. pneumoniae, H. influenzae, or P. aeruginosa in subjects who underwent systemic cephazolin administration without oral cleansing. The combination of mechanical and chemical oral cleansing resulted in a significant reduction of potential respiratory pathogens in the oral cavity.


The measurement of substance use among adolescents: when is the 'bogus pipeline' method needed?
The use of objective measures to assess cigarette smoking among adolescents has become commonplace in research studies in recent years. This trend is based on evidence that this so called pipeline methodology can increase the disclosure of socially proscribed behaviors in a setting where adolescents might otherwise feel pressure to deny that they smoke. This paper examines the effects of the pipeline methodology alone and in combination with procedures designed to ensure anonymity on the disclosure of tobacco, alcohol, and marijuana use by young adolescents. The data indicate that the pipeline procedures significantly increase disclosure of tobacco and marijuana use when students are promised confidentiality but not anonymity. However, when anonymity was assured, disclosure of cigarette use was just as high without the pipeline; for marijuana use, disclosure was higher without the pipeline. No effects were observed for alcohol disclosure. These data are interpreted for their implications for prospective and cross sectional studies.


Beta tricalcium phosphate ceramics with controlled crystal orientation fabricated by application of external magnetic field during the slip casting process.
Beta tricalcium phosphate (β-TCP) is a resorbable bioceramic that has hitherto been utilized in the medical field. Since it crystallizes in the anisotropic hexagonal system, properties such as chemical and physical ones are expected to depend on its crystal axis direction and/or on its crystal plane (anisotropy). Control of crystal orientation is thus important when used in polycrystalline form. Meanwhile, application of a strong magnetic field has been found to be a promising technique to control crystal orientation of anisotropic shape or structured crystals. In this work, we attempted to fabricate β-TCP ceramics with controlled crystal orientation by applying an external magnetic field during the slip casting process and subsequently sintering them at 1050°C, below the β-α transition temperature. Application of a vertical magnetic field increased intensities of planes perpendicular to c-plane on the top surface, while a horizontal one with simultaneous mechanical mold rotation decreased it. These results indicated that crystal orientation of β-TCP ceramics were successfully controlled by the external magnetic field and together that the magnetic susceptibility of β-TCP is χ(c[perpendicular])>χ(c//).


Transplant Islets Into the Pinna of the Ear: A Mouse Islet Transplant Model.
Islets transplanted under the ear skin would allow easy observation of the graft response and survival in vivo. This research was designed to establish an efficient mouse islet transplant model to probe the dynamic cellular interplay in vivo. Green fluorescent protein transgenic mice and BALB/c mice were used as donors and recipients. All recipients were divided into 6 groups of 6 mice each. First, we treated the transplant recipients, including diabetes induction, autologous epididymal fat pad, and MATRIGEL transplant to the ears. Then, 1. we transplanted isolated islets to the ear/ear with fat/ear with MATRIGEL; and 2. transplanted islets with collagen + basic fibroblast growth factor or islets with collagen + vascular endothelial growth factor. Mice in the control group received a sham transplantation with phosphate buffer saline. All recipients were then observed for 30 days with blood glucose (BG) monitoring. Finally, ears were removed with graft on day 28 for histologic examination. It was suggested that transplant of islets alone could not correct hyperglycemia. Fat, MATRIGEL, collagen, and growth factors have the similar function to form a microenvironment conducive to islet survival. The effect of islet transplantation for correcting hyperglycemia of the fat modification group was better than other groups (P < .05). BG could be normalized, and living islets were detected by anti-insulin immunohistochemistry. Transplant islets into the ear with transplanted autologous fat is the optimal way which can be used to analyze the allograft response in vivo and track cell population and migration using labels by confocal microscopy.


Topoisomerase II alpha as a reliable proliferation marker in meningiomas.
The value of DNA Topoisomerase IIalpha expression as a proliferation marker in meningiomas was investigated. The correlation to MIB-1 expression and tumor grade in 85 meningiomas (60 classical, 19 atypical and 6 anaplastic) was analysed by immunohistochemistry. MIB-1 labeling indices (LI) were 1.1% (+/- 0.85) for classical meningiomas, 1.9% (+/- 1.5) for atypical meningiomas and 5.6% (+/- 4.1) for anaplastic meningiomas, differences statistically significant (p = 0.03, < 0.0001, < 0.0001). Topoisomerase IIalpha LIs were 1.4% (+/- 1.2) for classical, 3.2% (+/- 2.4) for atypical and 9.7% (+/- 6.6) for anaplastic meningiomas, differences statistically significant (p = 0.003, < 0.0001, < 0.0001). Proliferation indices based on cells staining for MIB-1 and Topoisomerase IIalpha correlated highly with one another (r= 0.906, p <0.0001). Topoisomerase IIalpha exhibited a more distinct, less variable nuclear staining pattern compared to MIB-1 expression. DNA Topoisomerase IIalpha LI represents a reliable alternative to MIB-1 as a proliferation marker in human meningiomas, especially for computer assisted assessment, where a distinct uniform staining pattern is required.


L-glutamate decreases glucose utilization by rat cortical astrocytes.
Microenvironmental changes including elevated levels of L-glutamate, ionic homeostasis, acidification, and oxygen level are associated with brain insults. Their effects on energy metabolism were studied in cultured astrocytes. L-glutamate caused a decrease in lactate accumulation through the activation of transporter in astrocytes in a concentration- and time-dependent manner. Decreases in glucose uptake, lactate synthesis and accumulation as well as increases in mitochondrial activity indicated a switch of the astrocytic metabolism from glycolytic to oxidative. Environmental changes co-operated with L-glutamate to regulate the metabolic strategy, e.g. KCl and oxygen deprivation reversed but acidification exacerbated the L-glutamate-mediated decrease in lactate accumulation. Taken together, during chronic exposure, oxidation of non-glucose substrates such as L-glutamate fuels the active transport of L-glutamate into astrocytes.


Adrenal tumors: involvement of the inferior vena cava.
We report 3 cases of adrenal neoplasms with extension of tumor thrombus into the vena cava. Preoperative documentation of the presence and extent of vena caval involvement is mandatory before surgical extirpation of adrenal tumors.


Retracted: Study on the Relationship between AAD and Clinical Features in Emergency Ward Patients and the Application Effect of Probiotics.
[This retracts the article DOI: 10.1155/2022/6164843.].


The lack of nurse-infant transmission of type B hepatitis in a special care nursery.
Twenty-four infants cared for by a nurse who developed acute B hepatitis with HBsAg present in her serum and saliva were examined for serologic evidence of hepatitis B virus transmission. None of the infants had HBsAg by radioimmunoassay or anti-HBc by complement fixation. One infant had anti-HBs whose transient presence was consistent with passive acquisition. Using sensitive serologic tests, no identifiable risk to newborn infants in a special care nursery could be documented as a result of exposure to a nurse who developed acute type B hepatitis during their period of care.


Serum interleukin--4 and tumor necrosis factor alpha concentrations in children with primary acid gastroesophageal reflux and acid gastroesophageal reflux secondary to cow's milk allergy.
The possible role of serum interleukin 4 (IL-4) and tumor necrosis factor alpha (TNF- α) in pathogenesis of the reflux symptoms in children with primary acid gastroesophageal reflux (GER) and acid GER secondary to cow's milk allergy (CMA). Out of 264 children, 76 (28.8%) patients with primary GER and 62 (23.5%) patients with GER secondary to CMA (pH - monitoring) serum IL-4 and TNF- α concentrations were assessed before treatment, 1 and 2 years after the initiation of the periodically administered pharmacotherapy. Children with primary GER had mean IL-4 concentrations 0.17 ± 0.06 pg/ml before treatment, 0.08 ± 0.07 pg/ ml after 1-year and 0.07 ± 0.06 pg/ml after 2-years of treatment. The mean IL-4 concentrations were 1.07 ± 0.24, 0.5 ± 0.22 and 0.44 ± 0.19 pg/ml respectively in children with GER secondary to CMA. The mean serum TNF- α concentrations was 3.62 ± 1.30 pg/ml before treatment , 2.16 ± 1,35 pg/ ml after 1 year and 1.65 ± 1.16 pg/ml after 2 years of treatment in children with primary GER. In group with GER secondary to CMA mean serum TNF- α concentrations were 4.95 ± 1.88, 2.53 ± 0.80 and 2.02 ± 0.78 pg/ml respectively. Statistical analysis of the concentration of both cytokines showed their differentiation between them and in the study groups. The highest mean serum IL-4 and TNF-α concentrations were observed in children with GER secondary to CMA and in children in control group (with cow's milk allergy and/or other food allergy diagnosed - CMA/FA) before the treatment administration.


AβP1-42 incorporation and channel formation in planar lipid membranes: the role of cholesterol and its oxidation products.
Amyloid beta peptide (AβP) is a natural peptide, normally released into the cerebrospinal fluid (CSF), that plays a key role in Alzheimer's disease. The conversion of the peptide from a native soluble form to a non-native and often insoluble form, such as small and large aggregates, protofibrils and fibrils of AβP appears to be implicated in the pathogenesis of AD. Although the molecular mechanisms of AβP neurotoxicity are not fully understood, a large body of data suggests that the primary target of amyloid peptides is the cell membrane of neurons, that may modulate the structural and functional conversion of AβP into assemblies involved in pathological processes. In our study, we provide a systematic investigation of AβP1-42's ability to incorporate and form channel-like events in membranes of different lipid composition and focus on cholesterol and its oxidation products. We propose that cholesterol and its oxidation products can be considered neuroprotective factors because a) by favouring AβP1-42 insertion into membranes, the fibrillation/clearance balance shifts toward clearance; b) by shifting channel selectivity toward anions, the membrane potential is moved far from the threshold of membrane excitability, thus decreasing the influx of calcium into the cell.


LQR approach to robust stabilization of state space systems with matched uncertainties.
This note shows an elegant relationship between the quadratic optimal control and robust stabilization for linear time-invariant (LTI) systems, where the former control can robustly stabilize the latter system, provided that the matched uncertainty is bounded. Through reviewing the relevant literature, some common mistakes in regard to this relationship are found. The correct results are obtained and proved in both frequency and time domains. The results are applicable to both single- and multi-input cases. They are significant as the simple LQR design for the nominal system can be utilized to directly solve-with no further effort-the complex robust stabilization problem for a class of linear uncertain systems.


Impact of totally laparoscopic combined management of colorectal cancer with synchronous hepatic metastases on severity of complications: a propensity-score-based analysis.
Thanks to widespread diffusion of minimally invasive approach in the setting of both colorectal and hepatic surgeries, the interest in combined resections for colorectal cancer and synchronous liver metastases (SCLM) by totally laparoscopic approach (TLA) has increased. Aim of this study was to compare outcome of combined resections for SCLM performed by TLA or by open approach, in a propensity-score-based study. All 25 patients undergoing combined TLA for SCLM at San Raffaele Hospital in Milano were compared in a case-matched analysis with 25 out of 91 patients undergoing totally open approach (TOA group). Groups were matched with 1:2 ratio using propensity scores based on covariates representing disease severity. Main endpoints were postoperative morbidity and long-term outcome. The Modified Accordion Severity Grading System was used to quantify complications. The groups resulted comparable in terms of patients and disease characteristics. The TLA group, as compared to the TOA group, had lower blood loss (350 vs 600 mL), shorter postoperative stay (9 vs 12 days), lower postoperative morbidity index (0.14 vs 0.20) and severity score for complicated patients (0.60 vs 0.85). Colonic anastomosis leakage had the highest fractional complication burden in both groups. In spite of comparable long-term overall survival, the TLA group had better recurrence-free survival. TLA for combined resections is feasible, and its indications can be widened to encompass a larger population of patients, provided its benefits in terms of reduced overall risk and severity of complications, rapid functional recovery and favorable long-term outcomes.


The increasing importance of LNAA supplementation in phenylketonuria at higher plasma phenylalanine concentrations.
Large neutral amino acid (LNAA) treatment has been suggested as alternative to the burdensome severe phenylalanine-restricted diet. While its working mechanisms and optimal composition have recently been further elucidated, the question whether LNAA treatment requires the natural protein-restricted diet, has still remained. Firstly, to determine whether an additional liberalized natural protein-restricted diet could further improve brain amino acid and monoamine concentrations in phenylketonuria mice on LNAA treatment. Secondly, to compare the effect between LNAA treatment (without natural protein) restriction and different levels of a phenylalanine-restricted diet (without LNAA treatment) on brain amino acid and monoamine concentrations in phenylketonuria mice. BTBR Pah-enu2 mice were divided into two experimental groups that received LNAA treatment with either an unrestricted or semi phenylalanine-restricted diet. Control groups included Pah-enu2 mice on the AIN-93 M diet, a severe or semi phenylalanine-restricted diet without LNAA treatment, and wild-type mice receiving the AIN-93 M diet. After ten weeks, brain and plasma samples were collected to measure amino acid profiles and brain monoaminergic neurotransmitter concentrations. Adding a semi phenylalanine-restricted diet to LNAA treatment resulted in lower plasma phenylalanine but comparable brain amino acid and monoamine concentrations as compared to LNAA treatment (without phenylalanine restriction). LNAA treatment (without phenylalanine restriction) resulted in comparable brain monoamine but higher brain phenylalanine concentrations compared to the severe phenylalanine-restricted diet, and significantly higher brain monoamine but comparable phenylalanine concentrations as compared to the semi phenylalanine-restricted diet. Present results in PKU mice suggest that LNAA treatment in PKU patients does not need the phenylalanine-restricted diet. In PKU mice, LNAA treatment (without phenylalanine restriction) was comparable to a severe phenylalanine-restricted diet with respect to brain monoamine concentrations, notwithstanding the higher plasma and brain phenylalanine concentrations, and resulted in comparable brain phenylalanine concentrations as on a semi phenylalanine-restricted diet.


The relative body fat and anthropometric prediction of body density of South Australian females aged 17-35 years.
One hundred and thirty-five females were tested in order to: produce some normative percentage body fat (% BF) data on an Australian sample which represented a cross-section of physical activity patterns, cross-validate existing multiple regression equations which predict body density (BD) from anthropometric measurements, and if necessary develop population specific equations. Measurements were taken of 10 girths, 3 widths and 7 skinfolds. Body density was measured by underwater weighing with the residual volume (RV) being determined by helium dilution. The Siri equation was then used to convert BD to % BF. The % BF scores had an overall mean of 23.4 (range 10.8-49.2). The very active group (n = 45) had a significantly lower (p less than 0.05) relative body fat (X = 20.6% BF) than either the active (n = 45; 23.5% BF) or sedentary groups (n = 45; 26.2% BF). Previously published equations were found to have limited applicability to Australian subjects. A stepwise multiple regression was therefore used to develop the following equation (R = 0.893): BD(g X cm-3) = 1.16957-0.06447 (log10 sigma triceps, subscapular, supraspinale, front thigh, abdominal and calf skinfolds in mm)-0.00081 (gluteal girth in cm) + 0.0017 (forearm girth in cm) + 0.00606 (biepicondylar humerus breadth in cm). Only those predictors which resulted in a statistically significant increase in r (p less than or equal to 0.05) were included. The standard error of estimate of 0.00568 g X cm-3 was equivalent to 2.6% BF at the mean.


Modular assembly of indole alkaloids enabled by multicomponent reaction.
Indole alkaloids are one of the largest alkaloid classes, proving valuable structural moiety in pharmaceuticals. Although methods for the synthesis of indole alkaloids are constantly explored, the direct single-step synthesis of these chemical entities with broad structural diversity remains a formidable challenge. Herein, we report a modular assembly of tetrahydrocarboline type of indole alkaloids from simple building blocks in a single step while showing broad compatibility with medicinally relevant functionality. In this protocol, the 2-alkylated or 3-alkylated indoles, formaldehyde, and amine hydrochlorides could undergo a one-pot reaction to deliver γ-tetrahydrocarbolines or β-tetrahydrocarbolines directly. A wide scope of these readily available starting materials is applicable in this process, and numerous structural divergent tetrahydrocarbolines could be achieved rapidly. The control reaction and deuterium-labelling reaction are conducted to probe the mechanism. And mechanistically, this multicomponent reaction relies on a multiple alkylamination cascade wherein an unusual C(sp3)-C(sp3) connection was involved in this process. This method could render rapid access to pharmaceutically interesting compounds, greatly enlarge the indole alkaloid library and accelerate the lead compound optimization thus facilitating drug discovery.


Ileal epithelial cell migration after 40% small-bowel resection. Autoradiographic studies in the rat.
Adaptation in the small bowel after resection is associated with increases in crypt cell proliferation and villus height. This paper gives the results of an autoradiographic investigation with [3H]thymidine of epithelial cell migration 60 days after 40% small-bowel resection in the rat. The mean number of cell positions between the crypt--villus junction and the leading labeled cell 30 hr after injection was increased by 19.4% in the resected group (P less than 0.02). The mean total number of cells per villus column was increased by 27.8% (P less than 0.002). Migration rate estimated in cell positions per hour was accelerated by 18.9% (P less than 0.001) after resection. The 8.1% lengthened life span of villus cells was not statistically significant. The increased number of cells per villus column and unaltered life span of villus cells would facilitate functional adaptation. The causal relationship between the larger villus cell population and accelerated migration after resection and increased crypt cell proliferation is unknown.


Coronary unroofing does not fits all anomalous aortic origin of coronary arteries.
Anomalous aortic origin of coronary artery (AAOCA) is the second leading cause of sudden cardiac death in children and young adults. Intramural-interarterial course is the most frequent anatomic variation and coronary unroofing is widest adopted for surgical management. Symptoms recurrence is described regardless of the technique used. This study aims to describe how an anatomic patient-centered approach aimed to restore a normal coronary artery take-off is associated with symptoms resolution. From 2008 to 2021, 25 patients were operated on for an AAOCA at a median age of 20 years. Nineteen patients had a right AAOCA and six had left AAOCA. Intramural course was present in 18 patients. Seventy-six percent were symptomatic. No episodes of aborted sudden cardiac death before surgery was described in the population. Surgical technique used were coronary unroofing in 18 patients, coronary neo-ostioplasty in 3, coronary Reimplantation in 3, and main pulmonary artery re-location in 1. No hospital mortality or reoperation was observed in our experience as well as major complications related to surgery. Mean hospital length of stay was 8.5 days. None of patients reported symptoms recurrence at follow-up. Young athletes returned to play competitive sport. Postoperative computed tomography scan evaluation showed a general improvement of the take-off angle. AAOCA requires a patient anatomic-based surgical management. There is not a single surgical technique that can fits all anatomic subtype of AAOCA. Surgical techniques may be selected on the base of the preoperative images and intraoperative findings. In our experience, this policy is associated with no symptoms recurrence.


First-trimester maternal serum alpha-fetoprotein and human chorionic gonadotropin screening for chromosome defects.
The aim of this study was to determine the efficacy of combined maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG) screening in detecting chromosome defects in the first trimester of pregnancy. Sera of 492 women (previously assayed for MSAFP) were analysed for MShCG under code without knowledge of cytogenetic results. Overall, 48 of 492 patients (9.8 per cent) had either an MSAFP multiple of the median less than or equal to 0.5 or an MShCG beta/alpha ratio multiple of the median less than or equal to 0.25, eight of whom had a fetus with a serious chromosome defect. A third of fetuses with Down's syndrome and 83 per cent with trisomy 18 were detected at a potential 'cost' of providing chorionic villus sampling or amniocentesis in 8.6 per cent of women screened.


Interaction effects of visual stimulus speed and contrast on postural sway.
Manipulating the characteristics of visual stimuli that simulate self-motion through the environment can affect the resulting postural sway magnitude. In the present study, we address the question whether varying the contrast and speed of a linear translating dot pattern influences medial-lateral postural sway. In a first experiment, we investigated whether the postural sway magnitude increases with increasing dot speed, as was previously demonstrated for expanding and contracting stimuli. In a second experiment, we also manipulated the contrast of the stimuli. For reasons that high-contrast stimuli can be considered 'perceptually' stronger, we expect that higher-contrast stimuli induce more sway than lower-contrast stimuli. The results of the first experiment show that dot speed indeed influences postural sway, although in an unexpected way. For higher speeds, the sway is in the direction of the stimulus motion, yet for lower speeds the sway is in a direction opposite to the stimulus motion. The results of the second experiment show that dot contrast does affect postural sway, but that this depends on the speed of the moving dots. Interestingly, the direction of postural sway induced by a relatively low dot speed (4°/s) depends on dot contrast. Taken together, our results suggest that interactions between the visual, vestibular and proprioceptive system appear to be influenced by an internal representation of the visual stimulus, rather than being influenced by the external visual stimulus characteristics only.


Modulation of MDM2/p53 and cyclin-activating kinase during the megakaryocyte differentiation of human erythroleukemia cells.
This study was undertaken to address the involvement of CDK activating kinase (CAK), p53, and MDM2 proteins in the mitotic arrest associated with the acquisition of a polyploid DNA content during megakaryocyte differentiation of human erythroleukemia (HEL) cells. To evaluate this mechanism we investigated HEL cells as a model system in which there is a marked increase in DNA content during megakaryocyte differentiation induced by phorbol-diesters. Specific cell-cycle phases were separated by centrifugal elutriation and SDS PAGE and Western analysis were performed to determine the relative abundance of these proteins. Kinase assays were carried out following immunoprecipitation of cellular lysates with the antibodies to the proteins. Polyploid HEL cells show an increase in the abundance of the CAK complex proteins, CDK7 and cyclin H, and a sixfold increase in CAK-specific activity. Increased CAK activity in polyploid HEL cells follows both the downregulation of p53 protein and its decreased association with CAK complex. Consistent with the reduction of p53, polyploid HEL cells undergo a dramatic increase in MDM2 protein abundance that in turn facilitates increased interaction of this protein with p53. These observations demonstrate that deregulated expression of MDM2 and p53 during megakaryocyte differentiation allow a relaxation of the control over genomic stability, allowing further replicative rounds of DNA synthesis.


[Demonstration of the direct projections of ACTH immunoreactive neurons on the complex of the locus coeruleus in cats].
Using a combined retrograde HRP and immunohistochemical technique in the cat, we have demonstrated the existence of direct descending projections of the ACTH immunoreactive neurons in the arcuate nucleus of the hypothalamus to the pontine tegmentum, especially, to the nucleus locus coeruleus alpha.


6-Hydrophobic aromatic substituent pyrimethamine analogues as potential antimalarials for pyrimethamine-resistant Plasmodium falciparum.
The series of des-Cl (unsubstituted) and m-Cl phenyl analogues of PYR with various flexible 6-substituents were synthesized and studied for the binding affinities with highly resistant quadruple mutant (QM) DHFR. The derivatives carrying 4 atoms linker with a terminal carboxyl substituted on the aromatic ring exhibited good inhibition to the QM enzyme and also showed effective antimalarial activities against resistant P. falciparum bearing the mutant enzymes with relatively low cytotoxicity to mammalian cells. The X-ray crystallographic analysis of the enzyme-inhibitor complexes suggested that the hydrophobic substituent at 6-position was accommodated well in the hydrophobic pocket and the optimal length of the flexible linker could effectively promote the binding of the terminal carboxyl group to the key amino acid residues, Arg59 and Arg122.


The application of GO-Fe3O4 nanocomposite for chromium adsorption from tannery industry wastewater.
The discharge of untreated tannery industrial wastewater into the environment has resulted in an adverse effect on the ecosystem and public health. Therefore, this work aimed to remove chromium ions from tannery wastewater through magnetite graphene oxide-nanocomposite (GO-Fe3O4). The experimental design of the study was a full factorial 24 approach using pH, adsorbent dose, contact time, and initial chromium concentrations. The results of FTIR analysis revealed the presence of functional groups such as hydroxyl (3438 cm-1), alcohol (1230 cm-1), aromatic (1467 cm-1), ketone (1629 cm-1), and ether (1120 cm-1). Similarly, GO-Fe3O4 acquired a high surface area of 296.2 m2/g whereas the XRD analysis showed the presence of predominant peaks which are attributed to the magnetite component. Moreover, the SEM image showed many ups and downs on the surface of the adsorbent. These cracks of morphology can create a conducive environment for the interaction of adsorbent and adsorbate. The maximum chromium removal of 95.9% was achieved at the optimum conditions of the initial chromium concentration of 40 mg/L, pH 4, adsorbent dose 1 g/100 mL, and contact time of 120 min whereas the removal of chromium from real tannery wastewater was found to be 90.3%. Based on the adsorption isotherm, the Langmuir model was the best fit for experimental data at R2 0.99, indicating homogeneous and monolayer adsorption. Finally, it can be concluded that GO-Fe3O4 was effective for chromium removal, which is a promising technology to be scaled up at the industrial level for wastewater treatment.


Typical antibiotic exposure and dysglycemia risk in an elderly Chinese population.
Studies examined the connection between antibiotic exposure in urine and dysglycemia risk (including prediabetes and diabetes) in the elderly were limited. Multiple linear regression, binary logistic regression, restricted cubic splines (RCS), and stratified analysis were applied to analyze the relationship between antibiotic exposure and dysglycemia risk. We observed that sulfaclozine exposure 0.07 (95% confidence interval [CI]: 0.01-0.23) significantly increased fasting blood glucose (FBG) level. By mechanism, usage, and antimicrobial action, sulfonamides 0.08 (95% CI: 0.06-0.36), veterinary antibiotics (VA) 0.07 (95% CI: 0.01-0.30), or bacteriostatic antibiotics 0.07 (95% CI: 0.02-0.29) significantly increased FBG level. Additionally, sulfaclozine exposure 1.54 (95% CI: 1.02-2.33) resulted in a higher dysglycemia risk, while doxycycline exposure 0.53 (95% CI: 0.30-0.95) resulted in a lower dysglycemia risk. By mechanism, usage, and antimicrobial action, sulfonamides 1.44 (95% CI: 1.02-2.04), VA 1.68 (95% CI: 1.21-2.35), or bacteriostatic antibiotics 1.40 (95% CI: 1.02-1.93) exposure had a higher dysglycemia risk. Taken together, exposure to sulfonamides, VA, especially sulfaclozine, was correlated with a higher dysglycemia risk in the elderly. Exposure to bacteriostatic antibiotics was associated with a higher dysglycemia risk in the female.


Incidental post-partum isolation of Brucella melitensis in an asymptomatic woman.
A 25-year-old Somali-born female was admitted to the hospital in active labour. Following post-partum hemorrhage, Brucella melitensis grew from a blood culture and the placenta. Identification and relatedness were determined through reverse transcriptase polymerase chain reaction (RT-PCR), single nucleotide polymorphism (SNP), and whole genome sequencing. The patient and her child were completely asymptomatic at their initial assessment.


The function of apolipoproteins L.
The function of the proteins of the apolipoprotein L (apoL) family is largely unknown. These proteins are classically thought to be involved in lipid transport and metabolism, mainly due to the initial discovery that a secreted member of the family, apoL-I, is associated with high-density lipoprotein particles. However, the other members of the family are believed to be intracellular. The recent unravelling of the mechanism by which apoL-I kills African trypanosomes, as well as the increasing evidence for modulation of apoL expression in various pathological processes, provides new insights about the functions of these proteins. ApoLs share structural and functional similarities with proteins of the Bcl-2 family. Based on the activity of apoL-I in trypanosomes and the comparison with Bcl-2 proteins, we propose that apoLs could function as ion channels of intracellular membranes and be involved in mechanisms triggering programmed cell death.


Cognitive deficits and impaired hippocampal long-term potentiation in KATP-induced DEND syndrome.
ATP-sensitive potassium (KATP) gain-of-function (GOF) mutations cause neonatal diabetes, with some individuals exhibiting developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome. Mice expressing KATP-GOF mutations pan-neuronally (nKATP-GOF) demonstrated sensorimotor and cognitive deficits, whereas hippocampus-specific hKATP-GOF mice exhibited mostly learning and memory deficiencies. Both nKATP-GOF and hKATP-GOF mice showed altered neuronal excitability and reduced hippocampal long-term potentiation (LTP). Sulfonylurea therapy, which inhibits KATP, mildly improved sensorimotor but not cognitive deficits in KATP-GOF mice. Mice expressing KATP-GOF mutations in pancreatic β-cells developed severe diabetes but did not show learning and memory deficits, suggesting neuronal KATP-GOF as promoting these features. These findings suggest a possible origin of cognitive dysfunction in DEND and the need for novel drugs to treat neurological features induced by neuronal KATP-GOF.


Detection of Fusarium wilt pathogens of Psidium guajava L. in soil using culture independent PCR (ciPCR).
Traditional culturing methods take a long time for identification of pathogenic isolates. A protocol has been developed for the detection of Fusarium from soil samples in the early stage of infection. Seventeen soil samples from different locations were collected before the onset of rains to find out the presence of Fusarium spp. population present in the soil of guava orchards and to correlate its presence with incidence of wilt. A PCR based method was developed for the molecular characterization of Fusarium using Fusarium spp. specific primer. DNA extracted by this method was free from protein and other contaminations and the yield was sufficient for PCR amplification. The primer developed in this study was amplifying ∼230 bp in all infected samples while not in healthy soil. The specificity and sensitivity of primer were tested on several Fusarium spp. and found that this primer was amplifying 10(-6) dilution of the fungal DNA. The present study facilitates the rapid detection of Fusarium spp. from infected soil samples of guava collected from different agroclimatic regions in India. A rapid detection method for pathogens and a diagnostic assay for disease would facilitate an early detection of pathogen and lead to more effective control strategies.


Effects of danazol on endometrial DNA synthesis in rats.
The suppressive effects of Danazol, an isoxazol derivative of the synthetic steroid 17 alpha-ethinyltestosterone, on endometrial DNA synthesis were investigated in rats by immunohistochemistry with bromodeoxyuridine (BrdU) and DNA-synthesizing enzyme assays. Rats treated with Danazol for 14 days at 17-19 weeks of age showed a decrease of plasma gonadotropins associated with ovarian hypofunction, persistent diestrus, and a smaller number of corpora lutea in ovary, resulting in no BrdU-immunoreactive (S-phase) cells in endometrial epithelium and lower activity of thymidine kinase in the uterus compared with control.


Evidence to date: ranibizumab and its potential in the treatment of retinopathy of prematurity.
Retinopathy of prematurity (ROP) is a leading and preventable cause of childhood blindness worldwide. Although laser photocoagulation remains the gold standard for treatment, the off-label use of anti-vascular endothelial growth factor (anti-VEGF) therapy to treat ROP, particularly posterior zone I disease, is increasing. Although initial studies on anti-VEGF therapy for ROP have focused on bevacizumab, recent studies have proposed that ranibizumab may be a safer and more effective alternative for use in this population. This review updates recent evidence regarding the use of ranibizumab in the management of ROP.


"Reversible gastric banding" in surgical treatment of morbid obesity--results of animal experiments.
The basic principle of "reversible gastric banding" as a new surgical approach to morbid obesity treatment is the creation of a small fundus reservoir using a silicone cuff which is coiled around the stomach close to the cardia. The extent of obstruction corresponds to the amount of liquid in the cuff which can be varied by puncture of a valve implanted in the subcutis. The reversibility of gastric obstruction is the great advantage of this method as compared to vertical banded gastroplasty or gastric bypass. We studied this method in animal experiments using seven "Göttinger Minipigs". In two animals the objectives of the study were reached, the observed complications, mostly caused by the nature of the test animal, are analyzed and discussed. To our knowledge, this is the first report in the literature on animal experiments in bariatric surgery.


[The use of UV irradiated autoblood for the prevention and treatment of pulmonary complications after operations on organs of the abdominal cavity].
The authors have made an analysis of incidence of postoperative pneumonias in 285 patients aged from 60 to 83 after operation on the abdominal organs. The use of reinfusion of the UV irradiated blood in the complex of prophylactic measures for prevention of postoperative pneumonias resulted in 2 times less amount of such complications.


Association study of polymorphisms in the ABO gene and their gene-gene interactions with ischemic stroke in Chinese population.
To investigate the impact of 4 single nucleotide polymorphisms (SNPs) within ABO gene and their gene-gene interactions on ischemic stroke (IS) susceptibility in Chinese Han population. A total of 1993 participants (1375 males, 618 females) were selected, including 991 IS patients and 1002 normal controls. The SNPstats (http://bioinfo.iconcologia.net/SNPstats) was used for Hardy-Weinberg equilibrium (HWE) test. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among 4 SNPs within ABO gene. Logistic regression was performed to calculate the ORs (95%CI) for interaction between SNPs. Both rs579459 and rs505922 within ABO gene were associated with IS risk in additive and dominant models. IS risks were higher in those with minor alleles of rs579459 and rs505922 than those with wild-type homozygotes, OR (95%CI) were 1.62 (1.19-2.10) and 1.69 (1.23-2.18), respectively. We did not find any relation of rs651007 and rs529565 with IS risk in both additive and dominant models. GMDR model indicated a significant two-locus model (P = .0010) involving rs505922 and rs579459, indicating a potential interaction between rs505922 and rs579459, the cross-validation consistency of the two-locus models was 9/10, and the testing accuracy was 60.72%. We also found that participants with rs505922- TC/CC and rs579459- TC/CC genotype have the highest IS risk, compared to participants with rs505922- TT and rs579459- TT genotype, OR (95%CI) was 2.94 (1.28-4.66). We found that rs579459 and rs505922 within ABO gene and their interaction were both associated with increased IS risk in Chinese population.


Calcium-activated neutral proteinase (calpain) activity in C6 cell line: compartmentation of mu and m calpain.
Calcium-activated neutral proteinase (calpain) activity was determined, including in cytosol and membrane fractions, in rat glioma C6 cell line. The mu and m forms of calpain were separated by DEAE and phenylsepharose column chromatography and with removal of the endogenous inhibitor calpastatin. C6 cells contained more mcalpain than the mu isoform. More than 70% of mcalpain activity was membrane-associated and 20% was cytosolic. Isolated plasma membrane also contained 69% of the mcalpain activity. In contrast, approximately 80% of mucalpain activity was cytosolic and 16% was membranous. Half-maximal activity for mu and mcalpain was obtained at 1 microM and 0.2 mM CaCl2, respectively. Trypsin dissociation of cells reduced activity. Triton X-100 stimulated mcalpain activity of the whole homogenate and the membrane pellet but not of the cytosol. Activity of the myelin marker enzyme adenosine 2'3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), was also found in C6 cells. The identification of calpain and CNPase in C6 cells is in keeping with an interpretation that C6 differentiation resembles, at least in part, that of the myelin-forming oligodendroglial cells.


Peripheral Refraction, Peripheral Eye Length, and Retinal Shape in Myopia.
To investigate how peripheral refraction and peripheral eye length are related to retinal shape. Relative peripheral refraction (RPR) and relative peripheral eye length (RPEL) were determined in 36 young adults (M +0.75D to -5.25D) along horizontal and vertical visual field meridians out to ±35° and ±30°, respectively. Retinal shape was determined in terms of vertex radius of curvature Rv, asphericity Q, and equivalent radius of curvature REq using a partial coherence interferometry method involving peripheral eye lengths and model eye raytracing. Second-order polynomial fits were applied to RPR and RPEL as functions of visual field position. Linear regressions were determined for the fits' second order coefficients and for retinal shape estimates as functions of central spherical refraction. Linear regressions investigated relationships of RPR and RPEL with retinal shape estimates. Peripheral refraction, peripheral eye lengths, and retinal shapes were significantly affected by meridian and refraction. More positive (hyperopic) relative peripheral refraction, more negative RPELs, and steeper retinas were found along the horizontal than along the vertical meridian and in myopes than in emmetropes. RPR and RPEL, as represented by their second-order fit coefficients, correlated significantly with retinal shape represented by REq. Effects of meridian and refraction on RPR and RPEL patterns are consistent with effects on retinal shape. Patterns derived from one of these predict the others: more positive (hyperopic) RPR predicts more negative RPEL and steeper retinas, more negative RPEL predicts more positive relative peripheral refraction and steeper retinas, and steeper retinas derived from peripheral eye lengths predict more positive RPR.


Isolation and characterization of a single-stranded RNA virus infecting the marine planktonic diatom Chaetoceros tenuissimus Meunier.
Diatoms are important components of the biological community and food web in the aquatic environment. Here, we report the characteristics of a single-stranded RNA (ssRNA) virus (CtenRNAV01) that infects the marine diatom Chaetoceros tenuissimus Meunier (Bacillariophyceae). The ca. 31-nm virus particle is icosahedral and lacks a tail. CtenRNAV01 forms crystalline arrays occupying most of the infected host's cytoplasm. By growth experiments, the lytic cycle and the burst size were estimated to be <24 h and approximately 1 x 10(4) infectious units per host cell, respectively. Stationary-phase C. tenuissimus cultures were shown to be more sensitive to CtenRNAV01 than logarithmic-phase cultures. The most noticeable feature of this virus is its exceptionally high yields of approximately 10(10) infectious units ml(-1); this is much higher than those of any other algal viruses previously characterized. CtenRNAV01 has two molecules of ssRNA of approximately 8.9 and 4.3 kb and three major proteins (33.5, 31.5, and 30.0 kDa). Sequencing of the total viral genome has produced only one large contig [9,431 bases excluding the poly(A) tail], suggesting considerable overlapping between the two RNA molecules. The monophyly of CtenRNAV01 compared to another diatom-infecting virus, Rhizosolenia setigera RNA virus, was strongly supported in a maximum likelihood phylogenetic tree constructed based on the concatenated amino acid sequences of the RNA-dependent RNA polymerase domains. Although further analysis is required to determine the detailed classification and nomenclature of this virus, these data strongly suggest the existence of a diatom-infecting ssRNA virus group in natural waters.


Lateral differences in lexical access: word length vs. stimulus length.
A. W. Young and A. W. Ellis (1985, Brain and Language, 24, 326-358) have shown that visual length of stimuli is a major determinant of lateral differences in word processing. They suggest that the right hemisphere must first code the words in graphemic form and, therefore, is affected by the word length. They demonstrated that visual length is best defined as the number of letters. The present experiment was conducted with 36 normal subjects to test this definition of the visual length by contrasting the number of letters and the physical length in the visual field. Spaces were inserted in the short words (4-letter) so that they matched the physical length of the long words (7-letter). Our results replicated those of Young and Ellis and confirmed that visual length can be defined by the number of letters. In addition, the imagery value of the words tended to affect this Hemifield x Length effect, a result not obtained by Young and Ellis.


Limited efficacy of omeprazole-based dual and triple therapy for Helicobacter pylori: a randomized trial employing "optimal" dosing.
To evaluate the efficacy and side effects of dual omeprazole/amoxicillin therapy for Helicobacter pylori given in "optimal" fashion (omeprazole twice a 3 g of amoxicillin daily, drugs started concurrently, 2 wk of therapy) and to assess the utility of adding a second antibiotic, tetracyline. Sixty healthy volunteers with H. pylori infection documented by 13C-urea breath test were randomly assigned to receive 2 wk of therapy with either 1) omeprazole 20 mg b.i.d. and amoxicillin 1 g t.i.d. (OA), or 2) OA plus tetracycline 500 mg t.i.d. (OAT). Patients returned after 2 wk for pill count and clinical assessment, and 13C-urea breath test was repeated 4 wk after the end of therapy. H. pylori was eradicated in 15 (50%) of 30 patients receiving OA therapy and in nine (30%) of 30 given OAT (p = 0.19). Side effects occurred in five (17%) patients in the OA group [two (7%) discontinued therapy due to side effects] and eight (27%) of the OAT group [three (10%) stopped therapy due to side effects]. Good compliance (> 80% of prescribed study drugs taken) was seen in 87% of each group, and eradication rates were 54% and 35% among patients with good compliance in the OA and OAT groups (p = 0.26). Dual therapy with omeprazole and amoxicillin, when given in "optimal" fashion, had limited efficacy, with an eradication rate of 50%. The addition of tetracycline to the dual therapy did not improve the rate of cure. Because virtually all of our subjects were from minority groups, with over three-fourths Hispanic, we speculate that differences in H. pylori strains or host factors may explain, at least in part, the discrepancy between our results and those in Northern European populations.


Mothers' dietary diversity and associated factors in megacity Dhaka, Bangladesh.
Mothers in developing countries are nutritionally vulnerable due to an undiversified diet. Dietary diversity and healthy dietary patterns of mothers are necessary for the health and nutrition of both the mother and the child. Keeping these in mind, the study was designed to investigate the determinants of mothers' dietary diversity in the capital city (Dhaka) of Bangladesh. A total 613 mothers who had at least one child aged 6-59 months were surveyed in 2020. Dietary diversity (DD) was measured by 24 h recall period following the established guidelines. To explore the determinants of dietary diversity, a log linear regression model was employed. The findings revealed that the overall DD of mothers was low, with less than 15% of respondents consuming more than 5 of the 9 food groups. The study found that if a mother receives one more year of formal education, her DD, on average, would increase by 0.70%. Receiving antenatal care (ANC) for four or more times during pregnancy increases DD by 5.13% compared to mothers who receive ANC less than four times. The findings also showed that mothers with access to assets have 10.18% higher DD than mothers without access to assets. On the other hand, mothers' employment status was negatively associated with DD. Redistributing the household workload between mother and other household members can play a critical role in increasing mothers' DD. Providing care facilities and counseling to mothers about the nutritional value of consuming different food groups can substantially improve the situation.


Occurrence of 9- and 13-keto-octadecadienoic acid in biological membranes oxygenated by the reticulocyte lipoxygenase.
Membranes of intact rabbit reticulocytes and rat liver mitochondrial membranes oxygenated by the pure reticulocyte lipoxygenase contain 13-keto-9Z,11E-octadecadienoic acid and 9-keto-10E,12Z-octadecadienoic acid. In mitochondrial membranes not treated with lipoxygenase and in rabbit erythrocyte membranes these products were not detected. The chemical structure of the compounds has been identified by cochromatography with authentic standards on various types of HPLC columns, by uv and ir spectroscopy and GC/MS. In the membranes of rabbit reticulocytes up to 2% of the linoleate residues are present as its 9- and 13-keto derivatives. Most of the keto compounds (up to 90%) are esterified in the membrane ester lipids, only about 10% were found in the free fatty acid fraction. It is proposed that the keto dienoic fatty acids are formed via decomposition of hydroperoxy polyenoic fatty acids originating from the oxygenation of the membrane lipids by the reticulocyte lipoxygenase.


Rheological properties of milk-based desserts with the addition of oat gum and κ-carrageenan.
A growing interest in development of milk desserts with good nutritional and rheological properties can be observed. A good and stability rheological as well as nutritional properties of such desserts can be provided by applying suitably composed gum mixtures. In this work, the effect of 0.1% κ-carrageenan addition on the rheological properties of based-milk desserts with different oat gum concentrations (0.1, 0.3 and 0.5%) was investigated. All milk desserts tested in presented study showed a time dependent and shear-thinning flow behavior. The mechanical spectra were characterized by storage module (G') greater than loss module (G"), typical for viscoelastic materials such as gels and dispersions. The incorporation of 0.1% κ-carrageenan into milk dessert with different oat gum concentrations allows to obtain stronger gel structure compared to milk dessert with separate oat gum addition. It can be also observed that desserts systems with the 0.1% κ-carrageenan had more stable viscoelastic properties. Moreover, the use the κ-carrageenan addition caused an increase in consistency coefficient (K) and decreased in n-value for Ostwald de Waele rheological model. Combined addition of oat gum and carrageenan allows to obtain milk dessert with stronger texture. The hardness of milk desserts range from 0.32 to 0.49 N for desserts without κ-carrageenan addition and from 0.513 to 0.557 N for desserts with κ-carrageenan. The high synergistic effect of composed gum mixtures on rheological properties of milk dessert occurs at 0.1% oat gum and 0.1% κ-carrageenan concentration.


Spatial metrology of dopants in silicon with exact lattice site precision.
Scaling of Si-based nanoelectronics has reached the regime where device function is affected not only by the presence of individual dopants, but also by their positions in the crystal. Determination of the precise dopant location is an unsolved problem in applications from channel doping in ultrascaled transistors to quantum information processing. Here, we establish a metrology combining low-temperature scanning tunnelling microscopy (STM) imaging and a comprehensive quantum treatment of the dopant-STM system to pinpoint the exact coordinates of the dopant in the Si crystal. The technique is underpinned by the observation that STM images contain atomic-sized features in ordered patterns that are highly sensitive to the STM tip orbital and the absolute dopant lattice site. The demonstrated ability to determine the locations of P and As dopants to 5 nm depths will provide critical information for the design and optimization of nanoscale devices for classical and quantum computing applications.


The impact of Treosulfan-based conditioning for inborn errors of immunity: Is dose monitoring crucial?
In children with inborn errors of immunity (IEI) who will receive a hematopoietic stem cell transplant (HSCT) treosulfan-based conditioning is currently preferred. The aim of this study was to investigate early and late outcomes in pediatric IEI patients receiving pre-HSCT treosulfan and to examine the effect of treosulfan dose monitoring on outcomes. Seventy-three pediatric patients receiving this management between 2015 and 2022 were included. Overall survival rate was 80%, and event-free survival was 67.8%. A larger treosulfan dose AUC after first application increased the rate of early toxicity (p = .034) and slowed lymphocyte engraftment (r = .290; p = .030). Underlying disease, treosulfan AUC, donor type, stem cell type, number of immunosuppressive agents, the dose of anti-thymocyte globulin, and post-transplantation cyclophosphamide did not to increase risk of acute graft-versus-host disease. The risk of mixed chimerism (MC) in patients with autoimmune lymphoproliferative syndrome and leukocyte adhesion deficiency were higher than those with severe combined immunodeficiency (p = .021 and p = .014, respectively). The risk of MC was lower in those receiving peripheral blood stem cells (SC) compared with bone marrow derived SC (OR = .204, p = .022). The AUC of the treosulfan dose was not associated with poorer late outcomes. Treosulfan is an agent that can be used safely in the IEI patient group, level measurement appears essential to identify early toxicities. Prospective studies with more extended follow-up periods are needed.


On 3-Coloring of ( 2 P 4 , C 5 )-Free Graphs.
The 3-coloring of hereditary graph classes has been a deeply-researched problem in the last decade. A hereditary graph class is characterized by a (possibly infinite) list of minimal forbidden induced subgraphs H 1 , H 2 , … ; the graphs in the class are called ( H 1 , H 2 , … ) -free. The complexity of 3-coloring is far from being understood, even for classes defined by a few small forbidden induced subgraphs. For H-free graphs, the complexity is settled for any H on up to seven vertices. There are only two unsolved cases on eight vertices, namely 2 P 4 and P 8 . For P 8 -free graphs, some partial results are known, but to the best of our knowledge, 2 P 4 -free graphs have not been explored yet. In this paper, we show that the 3-coloring problem is polynomial-time solvable on ( 2 P 4 , C 5 ) -free graphs.


Right ventricular infarction. The evolution of ST-segment elevation and Q wave in right chest leads.
ST-segment elevation in right chest leads V3R-V7R and Q wave in V3R was measured early (1-4 hours) and late (18-24 hours) after the onset of infarction in six patients. The patients died within 9 days of infarction, and autopsy demonstrated more than 50% necrosis of the right ventricle (inclusion criterion). Abnormal ST elevation was recorded in all patients in the early and late electrocardiograms, but mean ST elevation decreased significantly between these recordings. ST elevation greater than or equal to 1 mm was recorded in all patients in the early electrocardiogram but was present in only three (50%) in the second electrocardiogram. The number of leads exhibiting abnormal ST elevation decreased from 27 (90%) to 24 (80%) (NS), and those exhibiting ST elevation greater than or equal to 1 mm decreased from 24 (80%) to 15 (50%), (p less than 0.05). Q wave in V3R was present in both electrocardiograms in three patients. Evolution of Q wave was seen in only one patient, whereas two patients were without Q wave in both electrocardiograms. These results indicate that ST elevation in V3R-V7R may vanish within the initial 24 hours despite large right ventricular infarction. Furthermore, Q wave in V3R may evolve very early after the onset of right ventricular infarction.


Transformation of carbon tetrachloride by bisulfide treated goethite, hematite, magnetite, and kaolinite.
This study investigated the transformation of carbon tetrachloride (CT) by goethite, hematite, magnetite, and kaolinite treated with bisulfide to form coatings of iron monosulfide (FeS) and other Fe(II) species. These coatings contribute to abiotic natural attenuation in anaerobic environments. Batch kinetic experiments were performed under anoxic conditions at pH 8.0. Surface-area-normalized pseudo-first-order rate constants for CT transformation did not differ significantly for the three HS- treated iron oxides, but the rate of CT transformation by bisulfide-treated kaolinite was significantly lower, most likely due to kaolinite's lower iron content. The yield of chloroform (CF) from CT transformation was typically approximately 1%. There was negligible or only slight adsorption of several natural organic matter (NOM) model compounds to the surface of HS- treated goethite, and these compounds had no influence on CT transformation rate constants or CF yields. Juglone, on the other hand, adsorbed to a greater extent, and also significantly influenced the CF yield, increasing it by a factor of approximately 20 for HS- treated hematite. We speculate that juglone or its HS- addition product adsorbed to the mineral surface and acted as a hydrogen atom donor that reacted with the trichloromethyl radical intermediate, increasing the CF yield.


Intravenous Ketorolac Reduces Pain Score and Opioid Requirement in Orbital Surgery.
Intravenous ketorolac (IVK) is an effective agent to reduce postoperative pain without the risks inherent to opioid analgesics. However, many clinicians avoid using this agent due to concerns regarding hemorrhagic complications. This study was performed to assess the efficacy and safety of IVK in the setting of orbital surgery. In a single dose prospective study, patients either received IVK immediately before orbital surgery (n = 50) or acted as controls (n = 50). Postoperative pain was evaluated via a numerical scale (range = 0-10) immediately after surgery, before discharge to home, and on the first postoperative day (POD1). The requirements for opioid analgesic and anti-emetic medications were determined by the nursing staff and recorded. Statistical analyses were performed via a dedicated software package. Fifty patients received IVK (24 males, 26 females, mean age = 54 years, SD = 18 years) and 50 patients acted as controls (26 males, 24 females, mean age = 50 years, SD = 19 years) immediately before orbital surgery. Mean pain scores were lower in patients who received IVK than in controls immediately after surgery (3.08 vs. 5.44, p = 0.0001) and on POD1 (1.04 vs. 2.66, respectively, p = 0.0001). Four patients (8%) who received IVK and 12 patients who did not (24%) required opioid analgesics to control pain (p = 0.03). No patient experienced a hemorrhagic complication or required an emergent return to the operating room. In the setting of orbital surgery, IVK safely and effectively reduces pain and the requirement for opioid analgesics. Within the limits of the study size, increased risks of bleeding-related complications were not identified.


Resolution of atrial-ventricular block secondary to Listeria monocytogenes with antimicrobials.
Listeria endocarditis is a rare, but serious disease with high mortality rate. Currently, little is known regarding the optimal treatment modality of Listeria endocarditis in affected individuals. Here, we present the case of a 66-year-old female with history of mitral and aortic replacement with bioprosthetic valve, and hospital course complicated by Listeria monocytogenes infective endocarditis with atrial-ventricular (AV) block. Listeria monocytogenes infection was eradicated by a 6-week antimicrobials course involving ampicillin and gentamicin, culminating in the resolution of AV block. On further investigation, the patient admitted to frequent consumption of salami and provolone cold-cut sandwiches, which based on previous evidence in literature is hypothesized to be the source of infection. Our findings suggest the development of perivalvular abscesses as the cause of the AV block. To our knowledge, this is the first reported case in literature where AV block secondary to listeriosis resolved with treatment solely by antimicrobials. While further research and larger studies are needed to extend our findings, patients with AV block secondary to listeriosis may benefit from optimized management with antimicrobials.


Effect of exposure to carbon disulfide on tryptophan metabolism and the tissue vitamin B6 contents of rats.
Female Wistar rats were exposed to 100 ppm or 600 ppm carbon disulfide for 6 hours a day, 5 days a week for 12 weeks. During the exposure period, their urinary excretion of 4-pyridoxic acid was determined. The urinary excretions of xanthurenic acid and kynurenic acid after tryptophan loading were also determined. At the end of the exposure period, the rats were sacrificed and the levels of the five major forms of vitamin B6, pyridoxine, pyridoxal, pyridoxamine, pyridoxal phosphate and pyridoxamine phosphate, in the liver, kidneys and brain were determined by HPLC fluorometry. During the exposure the urinary excretions of xanthurenic acid and kynurenic acid after i.p. administration of tryptophan increased significantly in both experimental groups. However, urinary excretion of 4-pyridoxic acid decreased only slightly in the group exposed to carbon disulfide at 600 ppm and did not decrease in the group exposed to 100 ppm carbon disulfide. Furthermore, no significant changes were observed in the contents of vitamins B6 in any tissues examined. These results indicate that carbon disulfide does not cause vitamin B6 deficiency and thus that the disorders of tryptophan metabolism induced by carbon disulfide intoxication are not due to vitamin B6 deficiency.


Long-term outcome of Hemophilus influenzae meningitis related to antiobiotic treatment.
Of 82 patients treated for Hemophilus influenzae meningitis from 1968 to 1975, a total of 22 (26.8%) showed neurologic or psychologic sequelae, or both. Auditory impairment was the most common type of sequelae; it occurred in 15 patients. Complications during acute illness were more frequent in patients who later developed sequelae than in patients who recovered completely. Sequelae were more often found in patients who received both ampicillin and chloramphenicol concomitantly compared with patients who were treated with one of these drugs. A possible antagonistic interaction between ampicillin and chloramphenicol is discussed.


Multipotent mesenchymal stromal cells in otorhinolaryngology.
Multipotent mesenchymal stromal cells (MSCs) are primitive cells capable of restoring damaged mesenchyme and with the ability to differentiate into mature cells of bone, cartilage, muscle, fat, nerve or fibrous tissues. MSCs are therefore good candidates for applications in regenerative medicine and cell based therapy. They regenerate through self-renewal, differentiational capacity, immune modulation and secretion of bioactive molecules. Authors present a review of MSCs applications in otorhinolaryngology. The major interest is focused on phonosurgery, sensorineural deafness and reconstruction of large tissue defects with bone, cartilage or soft tissue replacement. Current evidence of MSCs treatment efficacy in otorhinolaryngology is based on animal models. The true impact on clinical treatment will not be known until clinical studies prove functional outcomes in human medicine.