Diagnosis of and Early Revision Surgery for Biological Fixation Failure Due to Proximal-Distal Mismatch of Proximally Coated Tapered Cementless Stem.
The diagnosis of and decision-making for early revision surgery to treat failure of biological fixation with a proximally coated cementless stem are challenging. A 73-year-old woman was referred to our hospital with thigh pain 2 years after the initial total hip arthroplasty. Although a plain radiograph showed no signs indicating biological fixation failure, digital tomosynthesis showed a highly radiodense line along the proximal part, and bone scintigraphy showed uptake at the distal part. With the diagnosis of biological fixation failure due to the proximal-distal mismatch, the cementless stem was revised to a cemented stem, and the thigh pain was improved after the revision surgery. Digital tomosynthesis and bone scintigraphy can be helpful for the diagnosis of biological fixation failure due to proximal-distal mismatch.


Prognostic Significance of Nutrition-Associated Markers in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.
The prognostic significance of nutrition indicators in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. This systematic review and meta-analysis aimed to assess the prognostic value of serum albumin (SA), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index (PNI) in patients with HFpEF. Databases of PubMed, Embase, The Cochrane Library, and Web of Science were systematically searched for all studies published up to January 2022. The prognostic significance of SA, GNRI, and PNI for HFpEF was explored. Pooled hazard ratio (HR) and 95% confidence interval (CI) were estimated using the STATA 15.0 software. The Quality of Prognosis Studies tool was used to assess the quality of studies. Nine studies met the inclusion criteria, and 5603 adults with HFpEF were included in the meta-analysis. The analyses showed that a decreased SA or GNRI was significantly related to high all-cause mortality (HR: 1.98; 95% CI: 1.282-3.057; p = 0.002; and HR: 1.812;95% CI: 1.064-3.086; p = 0.029, respectively). Furthermore, a lower SA indicates a bad composite outcome of all-cause mortality and HF rehospitalization (HR: 1.768; 95% CI: 1.483-2.108; p = 0.000), and a lower GNRI was significantly associated with high cardiovascular mortality (HR: 1.922; 95% CI: 1.504-2.457;p = 0.000). However, a lower PNI did not correlate with all-cause mortality (HR: 1.176; 95% CI: 0.858-1.612, p=0.314). Our meta-analysis indicates that SA and GNRI may be useful indicators to predict the prognosis of patients with HFpEF.


The effect of prosthetic alignment on hip and knee joint kinetics in individuals with transfemoral amputation.
Prosthetic alignment directly affects the biomechanical loading in individuals with lower-limb amputation, and improper alignment may be contribute to the high incidence of hip and knee osteoarthritis (OA). The biomechanical changes caused by different alignments should be considered in prosthetic fitting. However, the quantitative effect of alignment on the kinetic features of individuals with transfemoral amputation remains unclear. As important kinetics indexes, how are the hip and knee joint moments affected by prosthetic alignment in individuals with transfemoral amputation? Gait tests of ten individuals with transfemoral amputation and fifteen individuals without amputation (control group) were performed. Several prosthetic alignment conditions were used, including the so-called "initial" alignment and eight malalignments. The hip and knee joint moments of the individuals with amputation under various alignments were analysed and compared with those of the control group. Statistical analyses were performed by one-way ANOVA, repeated measure multivariate ANOVA, and paired t tests. The peaks and impulses of the hip abductor and external rotator moments on the residual side were significantly smaller than those of the control group (P < 0.0056). The peaks of the hip extensor, adductor and external rotator moments on the intact side were significantly larger than those on the residual side (P < 0.05). Alignment significantly affected the intact hip and knee joint moments for each individual with amputation (P < 0.00625), but there was no consistent effect among individuals. The significantly larger hip joint moment on the intact side of individuals with transfemoral amputation may be associated with the higher incidence of hip OA on the intact side. Alignment significantly affects the hip and knee joint moments of each individual with transfemoral amputation, but the individual responses to alignment changes are different. This situation may imply that the method for optimizing alignment should be personalized.


Production of brefeldin-A.
Fermentation conditions are described for the production of the antitumor antibiotic 7-(S)-brefeldin-A (brefeldin-A) in liquid culture by Eupenicillium brefeldianum, (B.Dodge) Stolk and Scott, ATCC 58665. An analytical hplc method was developed which allowed rapid quantitation of the compound during fermentation. A kilogram of brefeldin-A was isolated from a fermentation at the 6800-liter scale.


Dynamics of left ventricular wall and mitral valve mechanics--a model study.
The relation between global left ventricular pumping characteristics and local cardiac muscle fiber mechanics is represented by a mathematical model of left ventricular mechanics in which the mitral valve papillary muscle system is incorporated. The wall of the left ventricle is simulated by a thick-walled cylinder. Transmural differences in fiber orientation are incorporated by changing the direction of material anisotropy across the wall. The cylinder is free to twist. The upper end of the cylinder is covered by a thin, flexible sheet, representing the base of the left ventricle. The mitral valve is incorporated in this sheet. The tips of the mitral leaflets are connected by chordae tendineae to the papillary muscles which are attached to the bottom of the cylinder. Canine cardiac cycles were simulated for various end-diastolic values of left ventricular volume (25-120 ml, control 60 ml), left atrial pressure (0-2.7 kPa, control 0.22 kPa) and aortic pressure (5-11 kPa, control 11 kPa). In this wide range of preload and afterload mechanical loading of the muscle fibers appeared to be distributed quite evenly (SD: +/- 5% of control value) over all muscular structures of the left ventricle, including the papillary muscles.


Ultrastructural immunocytochemistry for the central region of keratin associated-beta-proteins (beta-keratins) shows the epitope is constantly expressed in reptilian epidermis.
The presence of beta-proteins containing a core-box region in specific regions of reptilian epidermis has been studied by immunological methods. Alpha-keratins are detected by the antibody AK2 that recognizes a sequence toward the C-terminal of acidic alpha-keratins of 48-52kDa. Beta-proteins are recognized by an antibody directed to the core-box region specific for these proteins of 18-37kDa. The AK2 antibody labels with variable intensity alpha-keratin bundles in basal and suprabasal keratinocytes in the epidermis of representative species of reptiles but immunolabeling decreases or disappears in pre-corneous and corneous cells. As opposite, the core-box antibody only labels with variable intensity the dense beta-corneous material formed in pre-corneous and corneous layers of crocodilian and turtle epidermis. In lepidosaurian epidermis the core-box antibody labels the beta-layer while the mesos and alpha-layers are poorly or not labeled. The immunological evidence indicates that beta-proteins are synthesized in the upper spinosus and pre-corneous layers of the epidermis and replace or mask the initial alpha-keratin framework present in keratinocytes as they differentiate into cells of the beta-layer. In the specialized pad lamellae of gecko and anoline lizards charged beta-proteins accumulate in the adhesive setae and may affect the mechanism of adhesion that allows these lizards to walk vertical surfaces. The addition of beta-proteins to the alpha-keratins in upper cell layers of the epidermis recalls the process of cornification of mammalian epidermis where specific keratin-associated proteins (involucrin, loricrin and filaggrin) associate with the keratin framework in terminally differentiating keratinocytes of the stratum corneum.


Effect of ketamine combined with lidocaine in pediatric anesthesia.
We conducted a randomized clinical trial to determine whether adjunctive lidocaine diminishes the incidence of adverse effects in pediatric patients sedated with ketamine. This case-control study involved 586 consecutive pediatric patients necessitating anesthesia. Then systolic blood pressure, heart rate, respiratory rate, and blood oxygen saturation were observed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), and creatinine (Cr) levels were tested. General dose of ketamine, the time of onset and duration of anesthesia and postoperative recovery, anesthesia effect, and adverse reaction were subsequently compared. High-performance liquid chromatography was employed to detect ketamine concentration at different time points after administration, and the postoperative cognition function was further evaluated. Intra- and post-operation, the rising degree of ALT, AST, BUN, and Cr in patients treated with ketamine was higher than those in patients treated with the ketamine-lidocaine complex. General dose of ketamine, the time of onset and duration of anesthesia, postoperative recovery time, and the incidence rate of adverse reaction in patients treated with ketamine-lidocaine complex were lower, but the concentration of ketamine was higher compared to the patients treated with ketamine. In patients treated with the ketamine-lidocaine complex, elimination half-life of ketamine was prolonged, the area under curve was increased, and the plasma clearance rate was decreased relative to those with ketamine alone. Ketamine combined with lidocaine may be beneficial in shortening the onset of anesthesia, promoting postoperative awake, prolonging elimination half-life, increasing area under curve, and decreasing plasma clearance rate and incidence of adverse reactions.


T-Lymphocyte Subset Absolute Counts in the Peripheral Blood of Mediterranean Spotted Fever Patients: Relations to Disease Severity.
Mediterranean spotted fever (MSF) in Bulgaria is caused by Rickettsia conorii conorii. This study aims at investigating the absolute counts of T-lymphocyte subsets in the peripheral blood of patients with MSF in order to establish relationships with disease severity. The absolute counts of T-lymphocyte subsets were tested in the blood of 62 patients in the acute stage of MSF. They were assigned into three age and sex matched groups, based on the severity of disease - with mild, moderate or severe forms. Controls were 32 age and sex matched healthy individuals. The diagnosis was confirmed by an immunofluorescence assay. Immunophenotyping was performed using Epics XL-MCL Coulter, USA flow-cytometer. The absolute counts of immune competent (CD3+) cells, as well as the counts of helper/inducer (CD3+ CD4+) and suppressor/ cytotoxic (CD3+ CD8+) T-cell subsets decreased in parallel with disease severity. Naïve (CD4+ CD45RA+) and activated memory (CD4+ CD45RO+) T-cell subsets were reduced, particularly in severe MSF. Taken as a whole, the counts of activated (CD3+ HLA-DR+) and that of presenting accessory (CD28+) or stimulatory (CD38+) molecules Т-cell subsets was increased, but in the first two subsets the trend from mild to severe forms of the disease was descending. Reduced T-lymphocyte subset counts are likely related to trans-migration into perivascular inflammatory foci. The increased number of T-lymphocytes bearing activation molecules reflects a mobilization of the cell-mediated immune response. An important issue of this study is the possible prognostic value of T-cell subsets counting, predicting the evolution of a clinical condition to clinical forms, according to the disease severity.


Ontogeny of the GVH-R inducing capacity, in conventional and germ-free chickens.
Three strains of MHC homozygous chickens were used to study the ontogeny of the GVH-R. It was found that this function of the immune system was acquired with a delay in animals raised in germ-free conditions. In our previous work, we had shown that, contrary to expectation, bursal cells were capable of mounting a GVH-R against embryos, and actually were particularly efficient in this regard when compared to spleen cells. The present experiments have disclosed that splenomegaly induction may be dissociated from the toxic effect that bursal cells also exert on recipient embryos.


Transvaginal removal of gallbladders with large stones after laparoscopic cholecystectomy.
Very large gallstones sometimes render laparoscopic cholecystectomy time consuming and difficult. In addition, several advantages of laparoscopy, namely decreased postoperative pain and minimal abdominal scarring, could be compromised by the need to enlarge the umbilical incision. Besides the solution of the mechanical or electrohydraulic fragmentation of such large gallstones, as described by several authors, we propose a posterior colpotomy as a simple technique for removing very large gallbladders in women.


Revisiting the function of PSA-NCAM in the nervous system.
Since its first description the polysialylated form of NCAM (PSA-NCAM) is thought to be a major regulator of cell-cell interactions in the nervous system. Over the past few years many crucial questions have been answered concerning PSA biosynthesis and function. Among these are the identification and cloning of the key enzymes that are responsible for its synthesis and the fact that expression of PSA is not restricted to developmental stages but maintained in the adult nervous system. In the adult, PSA has been shown to be not only a marker of structural plasticity but seems to be a major player in these processes. Originally suggested to be a purely anti-adhesive factor, modulating cell-cell interactions in general and by this allowing plasticity, there is now increasing evidence that this might not be the whole story. Instead, it appears possible that PSA-NCAM interacts with secreted signaling molecules and by this fulfills a more instructive function in brain plasticity.


Determination of the functionally important heme peripheral vinyl group orientation in paramagnetic hemoprotein by 2D NMR.
2D NMR spectroscopies have been successfully used to characterize the heme peripheral vinyl groups in paramagnetic hemoprotein in spite of the difficulties from the rapid paramagnetic relaxation and the low digital resolution of the 2D NMR map. The scalar coupling network system among the vinyl protons is clearly identified in the COSY spectra from its characteristic cross-peak pattern and the dipolar coupling connectivities of the vinyl proton resonances with other heme side-chain proton resonances not only provide the specific assignment of vinyl beta-proton resonances but also allow the determination of the vinyl group orientation with respect to the heme plane.


Corn chip laceration of the esophagus and evaluation of suspected esophageal perforation.
Two patients presented to the emergency department within three months with a laceration of the esophagus due to corn chip ingestion. Both complained of odynophagia, and each was evaluated for suspected perforation with confirming esophagrams. Both patients were treated nonoperatively with full recovery.


Biological and proteomic characterization of the venom from Peruvian Andes rattlesnake Crotalus durissus.
The Peruvian rattlesnake Crotalus durissus is a venomous species that is restricted to the Peruvian Departments of Puno and Madre de Dios. Although clinically meaningful in this region, Crotalus durissus venom composition remains largely elusive. In this sense, this work aimed to provide a primary description of Peruvian C. durissus venom (PCdV). The enzymatic activities (SVMP, SVSP, LAAO, Hyaluronidase and PLA2) of PCdV were analyzed and compared to Brazilian Crotalus durissus terrificus venom (BCdtV). PCdV showed higher PLA2 activity when compared to the Brazilian venom. PCdV also showed cytotoxicity in VERO cells. For proteomic analysis, PCdV proteins were separated by HPLC, followed by SDS-PAGE. Gel bands were excised and tryptic digested for MALDI-TOF/TOF identification. Approximately 21 proteins were identified, belonging to 7 families. Phospholipases A2 (PLA2, 66.63%) were the most abundant proteins of the venom, followed by snake venom serine proteinases (SVSPs, 13.37%), C-type lectins (Snaclec, 8.98%) and snake venom metalloproteinases (SVMPs, 7.13%), crotamine (2.98%) and phosphodiesterase (PDE, 0.87%). Moreover, antivenom recognition assays indicated that both Brazilian and Peruvian antivenoms recognize PCdV, indicating the presence of antigenically related proteins in crotalic venoms. The results reported here, may impact in the venom selection for the production of effective Pan-American crotalic antivenom.


K+ current stimulation by Cl- in the midgut epithelium of tobacco hornworm (Manduca sexta). I. Kinetics and effect of Cl(-)-site-specific agents.
Goblet cells in the midgut epithelium of the tobacco hornworm (Manduca sexta larva, 5th instar) actively secrete K+. This can be measured as short-circuit current (Isc) when the tissue is mounted in an Ussing chamber and bathed in K(+)-rich standard saline containing 32 mmol K+.l-1. Isc depends strictly on basolateral (i.e. haemolymph side) K+ and is therefore termed K+ current, IK. Basolateral, but not apical, chloride, bromide and iodide stimulate IK when compared to the baseline current recorded with gluconate-, nitrate- or thiocyanate-containing salines. So-called "Cl(-)-specific" transport inhibitors (frusemide, 9-anthracene carboxylic acid, diphenylamine carboxylic acid and 4,4'-diisothiocyana-to-stilbene-2,2'-disulphonic acid) reduce IK when added to the basolateral bath, whether Cl- or gluconate is the principal ambient anion. Cl- stimulates IK according to saturation kinetics. The Michaelis-Menten-type, K+ concentration-dependent, saturation of IK is altered in a highly specific manner when gluconate is replaced by Cl-: maximal K+ current, as well as the apparent Michaelis constant, are increased by a factor of 4. Since IK develops in these conditions exclusively via basolateral, Ba(2+)-blockable K+ channels, these results can be understood if it is assumed that haemolymph Cl- interferes with the K+ channel by simultaneously lowering the binding affinity for K+ ions and increasing their subsequent transfer rate across the basolateral goblet cell membrane.


Imaging features of portal biliopathy: frequency of involvement patterns with emphasis on MRCP.
To investigate the imaging features of portal biliopathy with emphasis on MR cholangiopancreatography (MRCP). The ancillary vascular findings of portal biliopathy were also evaluated by accompanying MR portography, dynamic contrast-enhanced (CE) CT, and dynamic CE MRI studies. Sixteen patients with portal cavernoma were included in the study. Patients had undergone MRCP (n=16) studies accompanied by MR portography (n=13), dynamic CE CT (n=3) or dynamic CE MRI (n=2) of the liver. Two patients had undergone both dynamic CE CT and dynamic CE MRI. Two radiologists evaluated all the examinations together, retrospectively. MRCP images were analyzed for the presence of biliary stenosis, upstream (prestenotic) dilatation, wavy appearance of the bile ducts, angulation of the common bile duct (CBD), and choledocholithiasis. MR portography, dynamic CE CT and dynamic CE MRI studies were evaluated for the existence of portal cavernomas, and the presence of gall bladder/choledochal varices. All patients had signs of portal biliopathy on MRCP. Frequencies of the biliary findings on MRCP were as follows: biliary stenosis, 93.7%; upstream dilatation, 68.7%; wavy appearance of the biliary tree, 87.5%; angulation of the CBD, 75%. None of the patients had choledocholithiasis. Frequencies of the ancillary vascular findings detected on CE studies were as follows: gall bladder varices, 100%, choledochal varices, 93.7%. MRCP features of portal biliopathy in order to their frequencies were as follows: biliary stenosis, wavy appearance of the bile ducts, angulation of the CBD, and upstream dilatation of the bile ducts.


Acid detergent lignin, lodging resistance index, and expression of the caffeic acid O-methyltransferase gene in brown midrib-12 sudangrass.
Understanding the relationship between acid detergent lignin (ADL) and lodging resistance index (LRI) is essential for breeding new varieties of brown midrib (bmr) sudangrass (Sorghum sudanense (Piper) Stapf.). In this study, bmr-12 near isogenic lines and their wild-types obtained by back cross breeding were used to compare relevant forage yield and quality traits, and to analyze expression of the caffeic acid O-methyltransferase (COMT) gene using quantitative real time-PCR. The research showed that the mean ADL content of bmr-12 mutants (20.94 g kg(-1)) was significantly (P < 0.05) lower than measured in N-12 lines (43.45 g kg(-1)), whereas the LRI of bmr-12 mutants (0.29) was significantly (P < 0.05) higher than in N-12 lines (0.22). There was no significant correlation between the two indexes in bmr-12 materials (r = -0.44, P > 0.05). Sequence comparison of the COMT gene revealed two point mutations present in bmr-12 but not in the wild-type, the second mutation changed amino acid 129 of the protein from Gln (CAG) to a stop codon (UAG). The relative expression level of COMT gene was significantly reduced, which likely led to the decreased ADL content observed in the bmr-12 mutant.


Ig knock-in mice producing anti-carbohydrate antibodies: breakthrough of B cells producing low affinity anti-self antibodies.
Natural Abs specific for the carbohydrate Ag Galalpha1-3Galbeta1-4GlcNAc-R (alphaGal) play an important role in providing protective host immunity to various pathogens; yet little is known about how production of these or other anti-carbohydrate natural Abs is regulated. In this study, we describe the generation of Ig knock-in mice carrying functionally rearranged H chain and L chain variable region genes isolated from a B cell hybridoma producing alphaGal-specific IgM Ab that make it possible to examine the development of B cells producing anti-carbohydrate natural Abs in the presence or absence of alphaGal as a self-Ag. Knock-in mice on a alphaGal-deficient background spontaneously developed alphaGal-specific IgM Abs of a sufficiently high titer to mediate rejection of alphaGal expressing cardiac transplants. In the spleen of these mice, B cells expressing alphaGal-specific IgM are located in the marginal zone. In knock-in mice that express alphaGal, B cells expressing the knocked in BCR undergo negative selection via receptor editing. Interestingly, production of low affinity alphaGal-specific Ab was observed in mice that express alphaGal that carry two copies of the knocked in H chain. We suggest that in these mice, receptor editing functioned to lower the affinity for self-Ag below a threshold that would result in overt pathology, while allowing development of low affinity anti-self Abs.


[Recurrent meningitis in familial deficiency of the 8th component of the complement system].
An 18-year-old man suffered from recurrent bacterial meningitis. Investigation of the complement system revealed deficiency of the 8th complement component (C8) in the patient and his sister. Genetic defects of the terminal complement components C5 to C8 predispose to Neisseria infections, probably due to a lack in bacteriolytic activity. It is to be noted that 1 year ago the patient had been hospitalized for a culture-proved pneumococcal meningitis.


Autonomic changes with seizures correlate with postictal EEG suppression.
Sudden unexpected death in epilepsy (SUDEP) poses a poorly understood but considerable risk to people with uncontrolled epilepsy. There is controversy regarding the significance of postictal generalized EEG suppression as a biomarker for SUDEP risk, and it remains unknown whether postictal EEG suppression has a neurologic correlate. Here, we examined the profile of autonomic alterations accompanying seizures with a wrist-worn biosensor and explored the relationship between autonomic dysregulation and postictal EEG suppression. We used custom-built wrist-worn sensors to continuously record the sympathetically mediated electrodermal activity (EDA) of patients with refractory epilepsy admitted to the long-term video-EEG monitoring unit. Parasympathetic-modulated high-frequency (HF) power of heart rate variability was measured from concurrent EKG recordings. A total of 34 seizures comprising 22 complex partial and 12 tonic-clonic seizures from 11 patients were analyzed. The postictal period was characterized by a surge in EDA and heightened heart rate coinciding with persistent suppression of HF power. An increase in the EDA response amplitude correlated with an increase in the duration of EEG suppression (r = 0.81, p = 0.003). Decreased HF power correlated with an increase in the duration of EEG suppression (r = -0.87, p = 0.002). The magnitude of both sympathetic activation and parasympathetic suppression increases with duration of EEG suppression after tonic-clonic seizures. These results provide autonomic correlates of postictal EEG suppression and highlight a critical window of postictal autonomic dysregulation that may be relevant in the pathogenesis of SUDEP.


The natural polyamines spermidine and spermine prevent bone loss through preferential disruption of osteoclastic activation in ovariectomized mice.
Although naturally occurring polyamines are indispensable for a variety of cellular events in eukaryotic cells, little attention has been paid to their physiological and pathological significance in bone remodelling to date. In this study, we evaluated the pharmacological properties of several natural polyamines on the functionality and integrity of bone in both in vitro and in vivo experiments. Mice were subjected to ovariectomy (OVX) and subsequent oral supplementation with either spermidine or spermine for determination of the bone volume together with different parameters regarding bone formation and resorption by histomorphometric analyses in vivo. Pre-osteoclasts were cultured with receptor activator of NF-κB ligand (RANKL), with or without spermidine and spermine to determine cellular maturation by tartrate-resistant acid phosphatase (TRAP) staining and cellular viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide reduction in vitro. Spermidine or spermine, given in drinking water for 28 days, significantly prevented the increased osteoclast surface/bone surface ratio and the reduced bone volume following OVX in mice. Either spermidine or spermine significantly inhibited the increased number of multinucleated TRAP-positive cells in osteoclasts cultured with RANKL in a concentration-dependent manner without affecting cell survival. The natural polyamines spermidine and spermine prevented OVX-induced bone loss through the disruption of differentiation and maturation of osteoclasts, rather than affecting osteoblasts. The supplementation with these natural polyamines could be beneficial for the prophylaxis as well as therapy of metabolic bone diseases such as post-menopausal osteoporosis.


Differential expression patterns of AIP, UCKL1, and PKN1 genes in breast cancer of different molecular subtypes.
Classification of breast cancer (BC) in the molecular subtypes had the enormous impact on the development of the individualized therapy. Nevertheless, there is a need for additional biomarkers that would help to refine molecular subtypes of BC and propose the therapeutic approach for each patient. To study differential expression patterns of AIP, UCKL1, and PKN1 genes in blood sera and tumor tissue of patients with BC of different molecular subtypes. The total extracellular RNA was isolated from serum of 26 BC patients. cDNAs was synthesized and quantitative polymerase chain reaction was performed. Also, immunohistochemical studies of UCKL, AIP and PKN1 were performed on deparaffined tissue sections. The study was supplemented by a bioinformatic analysis of the publicly available databases. AIP and UCKL-1 extracellular mRNA levels were 100-1000-fold increased in blood sera of all BC patients, compared to the healthy donors. The highest levels were detected in the luminal A and HER2 (ERRB2) BC subtypes. The highest levels of PKN1 were detected blood sera of the patients with luminal B and basal subtypes; its expression levels were just 10-100-fold higher in BC samples compared to healthy donors. The UCKL1, AIP, PKN1 genes are overexpressed at the mRNA level in blood sera of BC patients compared to the sera of healthy individuals. Among three genes under study, only for the AIP gene, the pattern of extracellular mRNA expression in sera paralleled to protein expression in BC tissues of each specified molecular subtype.


Potassium-induced release of neuronotoxic activity by astrocytes.
Medium conditioned by newborn rat cerebral cortex microexplants contains neuronotoxic activity for cerebellar granule cells and hippocampal neurons. The neuronotoxic activity is associated with low-molecular weight molecule(s) (less than 1000 Da) and resists to heating and to freezing and thawing. Using nearly homogenous cultures of neurons or astrocytes, we show that the neuronotoxic activity is released by the latter cell type. This release is enhanced by increasing extracellular K+-concentration. Astrocytes also secrete neuronotrophic activity whose release is not affected by external K+. Neurons can be desensitized against the neuronotoxic activity.


Oxygen Evolution at Manganite Perovskite Ruddlesden-Popper Type Particles: Trends of Activity on Structure, Valence and Covalence.
An improved understanding of the correlation between the electronic properties of Mn-O bonds, activity and stability of electro-catalysts for the oxygen evolution reaction (OER) is of great importance for an improved catalyst design. Here, an in-depth study of the relation between lattice structure, electronic properties and catalyst performance of the perovskite Ca1-xPrxMnO₃ and the first-order RP-system Ca2-xPrxMnO₄ at doping levels of x = 0, 0.25 and 0.5 is presented. Lattice structure is determined by X-ray powder diffraction and Rietveld refinement. X-ray absorption spectroscopy of Mn-L and O-K edges gives access to Mn valence and covalency of the Mn-O bond. Oxygen evolution activity and stability is measured by rotating ring disc electrode studies. We demonstrate that the highest activity and stability coincidences for systems with a Mn-valence state of +3.7, though also requiring that the covalency of the Mn-O bond has a relative minimum. This observation points to an oxygen evolution mechanism with high redox activity of Mn. Covalency should be large enough for facile electron transfer from adsorbed oxygen species to the MnO₆ network; however, it should not be hampered by oxidation of the lattice oxygen, which might cause a crossover to material degradation. Since valence and covalency changes are not entirely independent, the introduction of the energy position of the eg↑ pre-edge peak in the O-K spectra as a new descriptor for oxygen evolution is suggested, leading to a volcano-like representation of the OER activity.


A review of the innovative gas separation membrane bioreactor with mechanisms for integrated production and purification of biohydrogen.
This review article focuses on an assessment of the innovative Gas Separation Membrane Bioreactor (GS-MBR), which is an emerging technology because of its potential for in-situ biohydrogen production and separation. The GS-MBR, as a special membrane bioreactor, enriches CO2 directly from the headspace of the anaerobic H2 fermentation process. CO2 can be fed as a substrate to auxiliary photo-bioreactors to grow microalgae as a promising raw material for biocatalyzed, dark fermentative H2-evolution. Overall, these features make the GS-MBR worthy of study. To the best of the authors' knowledge, the GS-MBR has not been studied in detail to date; hence, a comprehensive review of this topic will be useful to the scientific community.


The Impact of COVID-19 on Medical Dosimetry Education: Students' Perception on the Effectiveness of Program's Immediate Response.
In early 2020, many medical dosimetry programs began to offer lectures and clinical rotations remotely in response to COVID-19. Faculty instituted an IRB-approved study to investigate the effectiveness of medical dosimetry educational programs' immediate response to COVID-19 and modifications to teaching practices during the pandemic. The Program Response to COVID-19 Effectiveness Questionnaire (PRCEQ) survey was developed to measure students' perceptions of their learning experience during COVID-19. The subject of the study was the medical dosimetry current and former student population who received modified education delivery during the COVID-19 pandemic. This study suggests that generally students are satisfied with the quality of their virtual didactic and clinical education as well as communication between faculty and students and students to students. Programs should develop strategies to engage students during the virtual classes to motivate them to learn; utilize a variety of formats for the evaluation of students' learning, incorporate activities to help students make connections with real-world clinical situations, and schedule clinical visits for students to learn tasks that require their physical presence in clinic.


Axonal Development: RhoA Restrains but Does Not Specify.
Neurons develop polarity by the formation of specialized dendritic and axonal structural compartments. A new report now provides evidence that reveals how neurons regulate the initiation and further maintenance of axonal growth, challenging our currently held view of RhoA function in axogenesis.


Pancreatitis complicated with dilated choledochal remnant after congenital choledochal cyst excision.
We describe here three cases of pancreatitis after congenital choledochal cyst excision. In these three cases, the choledochal remnant in the pancreas head was markedly dilated, probably because of an incomplete resection of the cyst at the primary operation, and an increase in intraluminal pressure of the pancreatic duct caused by a dynamic obstruction by a protein plug or a pancreatic calculus. Complete cyst excision, including the choledochal wall in the pancreas, is therefore strongly recommended.


Practical Report on Long-term Disaster Mental Health Services Following the Great East Japan Earthquake: Psychological and Social Background of Evacuees in Sendai City in the Mid- to Long-term Post-disaster Period.
The Great East Japan Earthquake, which occurred on March 11, 2011, caused unprecedented damage. To address evacuees' psychosocial issues, our disaster mental health team provided psychosocial support in the form of careful listening and providing information for reconstruction. To summarize evacuees' psychosocial issues, we reviewed records of our daily activities and analyzed factors related to continuation or termination of support. Terminated support was defined as the resolution or improvement of psychological issues relative to the time of initial support. Based on logistic regression analysis, living in prefabricated temporary housing (odds ratio [OR]: 0.37; 95% confidence interval [CI]: 0.19-0.72), a high number of improved stress symptoms (0.81; 95% CI: 0.67-0.99), and higher support frequency (0.84; 95% CI: 0.78-0.90) were significantly associated with a lower likelihood of continuing support. Conversely, economic and resettlement issues (2.75; 95% CI: 1.63-4.64) and high numbers of stress symptoms (1.24; 95% CI: 1.06-1.45) were strongly and significantly associated with continuing support, particularly in the mid- to long-term phase following the earthquake (ie, after August 1, 2011). No significant association was found between support status and alcohol problems or disaster-related experiences (eg, loss of family or housing). Our findings highlight the need to be aware of evacuees' social issues such as resettlement in the mid- to long-term post-disaster phase. (Disaster Med Public Health Preparedness. 2017;11:439-450).


Outcome of protease inhibitor substitution with nevirapine in HIV-1 infected children.
Protease inhibitors (PIs) have been associated with metabolic complications. There is a trend to switch to simpler therapy to improve these disturbances. We report a case-series describing the effects in metabolic abnormalities in seven HIV-infected children, previously treated with protease inhibitor (PI) after switching to nevirapine. Seven children with stable PI-containing regimen and a long lasting HIV-1 RNA < 50 copies/ml were switched to nevirapine. All patients were naïve to non nucleoside reverse transcriptase inhibitor. PIs were switched to nevirapine. Preentry nucleoside reverse transcriptase inhibitors were maintained. The substitution of PIs with nevirapine was made when the patient showed hyperlipidemia or lipodystrophy or the physician and/or the patient's willingness to simplify. Clinical, laboratory data and anthropometric parameters were assessed every 3 months. Dual-energy X-Ray absorptiometry scans (DXA) was performed at baseline and at 12 months. Seven HIV-infected children were enrolled. Median age: 130 months (99,177). Median baseline CD4%: 32%. All had HIV-1 RNA < 50 copies/ml. Median length of preentry PI-therapy was 47 months (28, 91). Median age at the beginning of nevirapine was 120 months (99,177). Median decrease in cholesterol in 7.2 mmol/L was observed (P = 0.09), from baseline to 12 months. HDL-cholesterol increased in 5.1 mmol/L (P = 0.03) throughout the study period. No significant changes were observed in DXA with regard to body fat, but changes in total body bone mineral content and lean body content were significant. CD4% remained stable. All patients but one maintained viral load < 50 copies/ml at 12 months. The patient with virologic failure referred bad adherence. Children referred to take medication more easily. PI substitution with nevirapine improved lipid profile in our patients, although this strategy did not show significant changes in body fat or lipodystrophy.


Trigeminal neuralgia and persistent trigeminal artery.
We report a case of trigeminal neuralgia caused by persistent trigeminal artery (PTA) associated with asymptomatic left temporal cavernoma. Our patient presented unstable blood hypertension and the pain of typical trigeminal neuralgia over the second and third divisions of the nerve in the right side of the face. The attacks were often precipitated during physical exertion. MRI and Angio-MRI revealed the persistent carotid basilar anastomosis and occasionally left parietal cavernoma. After drug treatment of blood hypertension, spontaneous recovery of neuralgia was observed and we planned surgical treatment of left temporal cavernoma.


An examination of productivity and resource utilization associated with epoetin alfa treatment in employees with predialysis chronic kidney disease.
This study assessed the employer cost burden of predialysis CKD-related anemia for a major US manufacturer, by examining indirect and direct costs before and after initiation of epoetin alfa (EPO). Hemoglobin (Hb) levels, direct costs, and indirect costs for employees with CKD-related anemia were collected for 15 months (9 months pre-EPO and 6 months concurrent/post-EPO treatment). Indirect costs (absenteeism and presenteeism) and direct costs (medical and pharmacy) were compared for the pre- and post-EPO treatment periods. Treating CKD-related anemia with EPO increased Hb levels from 9.4 (1 to 3 months pre-EPO)to 12.2 g/dL (4 to 6 months post-EPO), decreased absenteeism by 52.3 days per patient per year (PPPY), increased productivity by 91.5% PPPY, and reduced health care costs by approximately $4417 PPPY. Among employees with predialysis CKD-related anemia, EPO treatment was associated with increased Hb levels, improved productivity, and decreased direct employer costs.


Flow injection on-line ultrasound-assisted extraction of iron in meat samples coupled to a flame atomic absorption spectrometric system.
Iron was extracted on-line from solid meat samples by a simple and rapid continuous ultrasound-assisted extraction system (CUES). The CUES is connected to a flow injection manifold, which allows the on-line flame atomic absorption spectrometric determination of iron. A Plakett-Burman design was used for the optimisation of the CUES. The method achieved a total sampling frequency of 11 samples per hour with a relative standard deviation for the complete procedure of 0.4%. The detection limit was 0.6 microg g(-1) (dry mass) for a sample amount of 30 mg. Accurate results were obtained by measuring the certified reference materials BCR-186 (pig kidney) and BCR-184 (bovine muscle). The analytical procedure was applied to different real meat samples with satisfactory results.


A prognostic score for postherpetic neuralgia in ambulatory patients.
The main objective was to develop a scoring system for easy use by the physician in daily clinical practice in deciding the appropriate treatment for his herpes zoster patient. Data from 635 patients who did not receive antiviral therapy were included in this analysis. Of these, 131 developed postherpetic neuralgia (PHN). Of the 29 variables tested univariately in this study, 15 showed a significant correlation with the incidence of PHN, but only six proved to contribute to the overall predictive power in the multivariate approach. Using two independent approaches, the model showed a very satisfactory performance in the validation sample. Patients without acute pain rarely developed PHN. In those with acute pain, being female, being over 50 years of age, having more than 50 lesions, having lesions of a hemorrhagic nature, having cranial or sacral localisation of the rash or having pain in the prodromal phase proved to be significant, multivariate factors. An easy-to-use scoring system used in a risk graph is proposed. These data should be useful in the individual treatment decision as well as in the design and analysis of therapeutic trials in herpes zoster.


Carols in the wind.
To compare mood and emotional responses to music played on pipe organs and pipeless (digital) organs. A two-organ (pipe v. digital) crossover study. St Theodore's Anglican Church, Adelaide. 43 non-musician volunteers. Changes in mood and emotions measured by the Profile of Mood States. Both instruments produced significant reductions in the emotions commonly experienced during the Christmas season: tension-anxiety, depression-rejection, anger-hostility and fatigue. There were no significant changes for vigour or confusion-bewilderment, and no significant differences between the mood-altering effects of the two instruments. Pipeless organs are as effective as pipe organs in inducing beneficial mood changes.


Lewis acid activation of molybdenum nitrides for alkyne metathesis.
The substantial kinetic barrier to molybdenum nitride-alkyne metathesis is facilitated by precomplexation of the borane Lewis acid B(C(6)F(5))(3), providing convenient access to metathesis-active molybdenum alkylidynes. Spectroscopic and X-ray structural analysis suggest Mo≡N bond weakening upon borane complexation.


[Clinical phenotype and genetic analysis of a fetus with recombinant chromosome 8 syndrome].
To explore the clinical characteristics and molecular genetic mechanism of a fetus with recombinant chromosome 8 (Rec8) syndrome. A fetus who was diagnosed with Rec8 syndrome at the Provincial Hospital Affiliated to Shandong First Medical University on July 20, 2021 due to high risk for sex chromosomal aneuploidy indicated by non-invasive prenatal testing (NIPT) (at 21st gestational week) was selected as the study subject. Clinical data of the fetus was collected. G-banded karyotyping and chromosomal microarray analysis (CMA) were carried out on the amniotic fluid sample. Peripheral blood samples of the couple were also subjected to G banded karyotyping analysis. Prenatal ultrasonography at 23rd gestational week revealed hypertelorism, thick lips, renal pelvis separation, intrahepatic echogenic foci, and ventricular septal defect. The karyotype of amniotic fluid was 46,XX,rec(8)(qter→q22.3::p23.1→qter), and CMA was arr[GRCh37]8p23.3p23.1(158049_6793322)×1, 8q22.3q24.3(101712402_146295771)×3. The karyotype of the pregnant woman was 46,XX,inv(8)(p23.1q22.3), whilst that of her husband was normal. The Rec8 syndrome in the fetus may be attributed to the pericentric inversion of chromosome 8 in its mother. Molecular testing revealed that the breakpoints of this Rec8 have differed from previously reported ones.


Acute perfusion changes after spontaneous SAH: a perfusion CT study.
Perfusion computed tomography (CT) is a rapid technique that allows the measurement of acute disturbances in local and global cerebral blood flow in patients suffering stroke and spontaneous subarachnoid haemorrhage (SAH). The purpose of this study was to establish the relationship between different measures of brain perfusion made on dynamic-contrast CT reconstructions performed as soon as SAH has been diagnosed and the severity of the bleeding determined by the clinical grade, the extent of the bleeding and the outcome of the patients. After the diagnosis of SAH by conventional CT, a perfusion CT was performed before CT angiography. All imaging studies were performed on a six-slice spiral CT scanner. All images were analysed using perfusion software developed by Philips, which produces perfusion CT quantitative data based on temporal changes in signal intensity during the first pass of a bolus of an iodinated contrast agent. Measurements of mean transient time (MTT), time to peak (TTP), cerebral blood volume (CBV) and cerebral blood flow (CBF) in volumes of interest corresponding to territories perfused by the major cerebral arteries were performed. Different data regarding severity of the bleeding-such as level of consciousness, amount of bleeding in conventional CT-were collected. All poor-grade patients received a ventriculostomy catheter so that ICP recordings were obtained. Also, the occurrence of delayed cerebral ischaemia (DCI) was recorded. Outcome was assessed by the Glasgow Outcome Scale 6 months after the bleeding. For statistical analysis, non-parametric correlations between variables were performed. Thirty-nine patients have been included in the study since January 2007. In SAH patients there are increasing perfusion abnormalities as the severity of the bleeding increases. The most affected perfusion parameters are TTP and MTT, as they significantly increase with the clinical severity of the bleeding and the total volume of bleeding (P < 0.01, Spearman's Rho). When average MTT time is increased over 5.9 s there is a 20-fold (95% CI = 2.1-182) risk of poor outcome. All patients presenting this MTT time suffered from DCI. This value has a positive predictive value of 100% for DCI and 90% for a poor outcome. SAH causes cerebral blood flow abnormalities even in the acute phase of the illness, consisting mainly of an increase in circulation times (TTP and MTT), which are correlated with the severity of the bleeding.


Sazetidine-A Activates and Desensitizes Native α7 Nicotinic Acetylcholine Receptors.
The aim of this study was to investigate the ability of sazetidine-A, a novel partial agonist at α4β2 nicotinic acetylcholine receptors (nAChRs), to affect the function of native α7 nAChRs in SH-SY5Y cells and primary cortical cultures. The α7-selective positive allosteric modulator PNU-120596 was used to reveal receptor activation, measured as an increase in intracellular calcium using fluorescent indicators. In the absence of PNU-120596, sazetidine-A elicited mecamylamine-sensitive increases in fluorescence in SH-SY5Y cells (EC50 4.2 µM) but no responses from primary cortical neurons. In the presence on PNU-120596, an additional response to sazetidine-A was observed in SH-SY5Y cells (EC50 0.4 µM) and robust responses were recorded in 14 % of cortical neurons. These PNU-120596-dependent responses were blocked by methyllycaconitine, consistent with the activation of α7 nAChRs. Preincubtion with sazetidine-A concentration-dependently attenuated subsequent responses to the α7-selective agonist PNU-282987 in SH-SY5Y cells (IC50 476 nM) and cortical cultures. These findings support the ability of sazetidine-A to interact with α7 nAChRs, which may contribute to sazetidine-A's actions in complex physiological systems.


Genome-wide analysis of cervical secretions obtained during embryo transfer reveals the association between deoxyribonucleic acid methylation and pregnancy outcomes.
To study whether the methylation status of cervical secretions can reflect the ability of the endometrium to allow embryo implantation. Case-control study. In vitro fertilization centers. Women undergoing embryo transfer cycles, in which at least 1 good-quality embryo was transferred. Collection of cervical secretions during the procedure of embryo transfer. Methylation profiles of cervical secretions in relation to pregnancy outcomes. Genome-wide methylation profiles differ between cervical secretions from pregnancy and nonpregnancy cycles. Clustering analysis on the basis of the top 2,000 differentially methylated probes of cervical secretions from 28 pregnancy and 29 nonpregnancy cycles correctly categorized 86.0% of the samples in terms of conceptional status, which was verified in selected genes by quantitative methylation-specific polymerase chain reaction and validated in another independent sample set. The combination of selected genes was estimated to predict pregnancy outcomes with a maximal area under the receiver operating characteristic curve of 0.83. The methylation profiles of cervical secretions were associated with pregnancy outcomes in embryo transfer cycles. Although not clinically useful at present, deoxyribonucleic acid methylation in cervical secretions may shed new light on the less invasive assessment of endometrial receptivity.


Some properties of the speciation model for food-web structure-mechanisms for degree distributions and intervality.
We present a mathematical analysis of the speciation model for food-web structure, which had in previous work been shown to yield a good description of empirical data of food-web topology. The degree distributions of the network are derived. Properties of the speciation model are compared to those of other models that successfully describe empirical data. It is argued that the speciation model unifies the underlying ideas of previous theories. In particular, it offers a mechanistic explanation for the success of the niche model of Williams and Martinez and the frequent observation of intervality in empirical food webs.


Spontaneous pneumothorax rates following video-assisted thoracoscopic talc pleurodesis with or without resection of macroscopic bullous disease.
Recurrent primary spontaneous pneumothorax (PSP) is routinely treated by video-assisted thoracoscopic (VATS) talc pleurodesis (with or without localized resection of macroscopic bullous disease). There is a paucity of published data regarding durability of the procedure and the rate of recurrent pneumothorax after such surgery, and this has significant implications from a prognostic and employment limitation perspective. Patients who underwent a VATS talc pleurodesis (with or without localized resection of macroscopic bullous disease) for the treatment of their second or subsequent PSP or a PSP were followed for recurrent ipsilateral pneumothorax and new contralateral PSP. Follow up was by way of telephone interview and medical record verification out to 48 months. New contralateral pneumothorax occurred in 7 patients (11.1%) in the talc pleurodesis plus wedge resection group and 2 (1.8%) in the talc pleurodesis only group. There was one case of recurrent ipsilateral pneumothorax in a patient who had no inflammatory response to talc insufflation. Video-assisted thoracoscopic (VATS) talc pleurodesis (and lung resection for macroscopic bullous disease) is a durable treatment for recurrent PSP. Patients with macroscopic disease have a significant risk of subsequent contralateral PSP.


Anatomic, motor, and clinical assessment of vertical banded gastroplasty.
The aim of this study was to assess gastric anatomy, motility, and emptying after vertical banded gastroplasty and to correlate the anatomic and physiologic results with clinical outcome. Eleven patients were studied at least 7 mo after operation, by which time they had lost 31% +/- 4% (mean +/- SEM) of their excess body weight. Stomal diameter, volume, and distensibility of the proximal gastric pouch were determined by a balloon distention technique. Gastric emptying was monitored scintigraphically both with and without distention of the proximal pouch. Stomal diameters ranged from 10 to 15 mm (mean +/- SEM = 11 +/- 1 mm), and pouch capacity ranged from 20 to 150 ml (76 +/- 9 ml). Mean intrapouch pressure was 13 mmHg before distention, increased to 22 mmHg with distention to half-maximal capacity, and then changed little with further distention to maximum capacity. Near maximal pouch distention during gastric emptying of a 300-ml test meal decreased antral contractile activity and speeded the initial rate of emptying (t25 with distention = 14 +/- 3 min vs. 24 +/- 3 min without distention, p less than 0.03), but did not alter the later rate of emptying. No clear-cut relationship was present between weight loss and stomal diameter, pouch volume, or gastric emptying. The conclusion was that distention of the proximal gastric pouch created by vertical banded gastroplasty inhibited antral contractions and increased the initial rate of gastric emptying, but no clear-cut correlation was found in this cohort between weight loss after the operation and stomal diameter, pouch size, and gastric emptying.


Dispersive liquid-liquid microextraction method based on solidification of floating organic drop combined with gas chromatography with electron-capture or mass spectrometry detection.
A simple dispersive liquid-liquid microextraction (DLLME) method based on solidification of a floating organic drop (DLLME-SFO) technique combined with gas chromatography/electron-capture detection (GC/ECD) or gas chromatography/mass spectrometry (GC/MS) has been developed. The proposed method is simple, low in cost, and of high precision. It overcomes the most important problem in DLLME, the high-toxic solvent used. Halogenated organic compounds (HOCs) in water samples were determined as the model compounds. The parameters optimized for the DLLME-SFO technique were as follows: A mixture of 0.5 mL acetone, containing 10 microL 2-dodecanol (2-DD-OH), was rapidly injected by syringe into the 5 mL water sample. After centrifugation, the fine 2-DD-OH droplets (8+/-0.5 microL) were floated at the top of the screwcap test tube. The test tube was then cooled in an ice bath. After 5 min the 2-DD-OH solvent had solidified and was then transferred into a conical vial; it melted quickly at room temperature and 3 microL (for GC/ECD) or 2 microL (for GC/MS) of it was injected into a gas chromatograph for analysis. The limit of detection (LOD) for this technique was 0.005-0.05microgL(-1) for GC/ECD and was 0.005-0.047 microgL(-1) for GC/MS, respectively. The linear range of the calibration curve of DLLME-SFO was from 0.01 to 500 microgL(-1) with a coefficient of estimation (r2)>0.996 for GC/ECD and was from 0.02 to 500 microgL(-1) with a coefficient of estimation (r2)>0.996 for GC/MS.


Evaluation of the cutaneous-irritation potential of 56 compounds.
The primary cutaneous irritation of 56 chemicals was tested in the rabbit using three different procedures. The three protocols selected for the tests were the method published by the French authorities for the testing of cosmetics and toiletries (Journal Officiel 21 April 1973, p. 3862; ibid 5 June 1973, p. 3953) and the methods proposed for the testing of chemicals by the Association Française de Normalisation (AFNOR) and, in 1979, by the Organisation for Economic Co-operation and Development. The results of the three sets of tests were compared and the effects of differences in procedure and numbers of animals were studied, together with the possible relation between irritancy and the pH of the test material. It was concluded that the AFNOR protocol best met the requirements for such tests and that gloves should be worn for the handling of all substances classified as moderately or severely irritant on that scale.


Femorodistal bypass grafting: quality of life and socioeconomic aspects.
To investigate the socioeconomic aspects and the outcome of femorodistal bypass grafting operations in terms of general health state. Prospective open clinical study. 168 operations in 153 patients. A structured questionnaire was used to assess quality of life, and each patient was classified into a health state group defined by levels of disability and distress. Before operation 23 patients were actively employed, 96 were old age pensioners, 29 received invalidity pension, and five were long term sick. 80% were living in their own home without any help. Only 19 patients were actively employed at follow up, 12 of these had been working before the operation, and seven other patients had taken up paid work. About three-quarters of the patients could manage daily life without help after the operation, and 82% had no or only mild distress. There were significant changes with respect to physical mobility in all groups and emotional status in one group. In all other cases a significant change could not be shown. The median Quality of Life score at follow up was 0.986 (n = 102, variance 0.022). The immediate costs were 1.5 million pounds. The classification into disability and distress groups was informative, but the methods for assessment of the results of vascular surgery on quality of life, evaluation of patient satisfaction and of patients' expectations must be further developed.


Simultaneous recording of hippocampal oxygen and glucose in real time using constant potential amperometry in the freely-moving rat.
Amperometric sensors for oxygen and glucose allow for real time recording from the brain in freely-moving animals. These sensors have been used to detect activity- and drug-induced changes in metabolism in a number of brain regions but little attention has been given over to the hippocampus despite its importance in cognition and disease. Sensors for oxygen and glucose were co-implanted into the hippocampus and allowed to record for several days. Baseline recordings show that basal concentrations of hippocampal oxygen and glucose are 100.26±5.76 μM and 0.60±0.06 mM respectively. Furthermore, stress-induced changes in neural activity have been shown to significantly alter concentrations of both analytes in the hippocampus. Administration of O2 gas to the animals' snouts results in significant increases in hippocampal oxygen and glucose and administration of N2 gas results in a significant decrease in hippocampal oxygen. Chloral hydrate-induced anaesthesia causes a significant increase in hippocampal oxygen whereas treatment with the carbonic anhydrase inhibitor acetazolamide significantly increases hippocampal oxygen and glucose. These findings provide real time electrochemical data for the hippocampus which has been previously impossible with traditional methods such as microdialysis or ex vivo analysis. As such, these sensors provide a window into hippocampal function which can be used in conjunction with behavioural and pharmacological interventions to further elucidate the functions and mechanisms of action of the hippocampus in normal and disease states.


Optimal selection of a battery of tests: a multiobjective optimization methodology.
The general problem of selecting a battery of tests for diagnostic purposes is discussed and multiobjective optimization methodology is applied to solve it, with battery selection being based on performance indices such as sensitivity, specificity, and the cost of testing. For a battery of tests, the extended majority rule is developed and used to interpret the compound test results. The major advantage of the model developed in this paper is that it can generate a set of noninferior batteries without requiring the calculation of all possible combinations of tests. An example in which the method is applied to a real problem--the selection of short-term tests to detect the carcinogenicity of chemicals--is discussed.


Serological profile of potential solid organ donors in Santa Catarina, Brazil.
Serological tests are essential for the donation process. We performed a study to identify the seroprevalence of cytomegalovirus (CMV), toxoplasmosis, HIV, Chagas disease, HTLV, hepatitis B virus (HBV), hepatitis C virus (HCV) and Lues among our potential donors. Among sera of 233 potential donors tested between January 2006 and April 2007, only 97 resulted in effective donation. The seroprevalence of CMV immunoglobulin G (IgG) was 89.3%. Anti-HBc was positive in 63 samples (27%) and just three people were HBsAg antigen-positive. HIV, HCV, HTLV, and Chagas disease showed low prevalence among the potential donors. Toxoplasmosis IgG antibody had a high prevalence in the tested group. CMV and toxoplasmosis were prevalent in the whole sample.


Test-retest Reproducibility of the Assessment of Motor and Process Skills in Children with Unilateral Cerebral Palsy.
To examine test-retest reproducibility of the Assessment of Motor and Process Skills (AMPS) in children aged 8-16 years with unilateral cerebral palsy (UCP). Thirty children with mild to moderate UCP (mean age = 11y 7m, SD 2y 4m; males = 18; Manual Ability Classification System level I = 10, II = 20; Gross Motor Function Classification System level I = 9, II = 21) enrolled in a large randomized controlled trial were recruited via consecutive series sampling. Children carried out two AMPS tasks over two consecutive days according to standardized AMPS administration procedures. The standard error of measurement (SEM), smallest detectable change (SDC), 95% limits of agreement using the Bland-Altman method, and intraclass correlation coefficients (ICC; 2,1) were calculated. The SDC was 0.23 logits for the AMPS motor scale and 0.30 logits for the AMPS process scale. Test-retest reliability was excellent for both the AMPS motor scale (ICC = 0.93) and the AMPS process scale (ICC = 0.86). Intra-rater reliability (n = 10) was excellent for AMPS motor scale (ICC = 0.96) and AMPS process scale (ICC = 0.98). The AMPS can be used by therapists with 8- to 16-year-old children with UCP as an outcome measure with changes in scores reflecting real changes in performance or capacity.


Airway IgG counteracts specific and bystander allergen-triggered pulmonary inflammation by a mechanism dependent on Fc gamma R and IFN-gamma.
Besides IgE, the Ab isotype that gives rise to sensitization and allergic asthma, the immune response to common inhalant allergens also includes IgG. Increased serum titers of allergen-specific IgG, induced spontaneously or by allergen vaccination, have been implicated in protection against asthma. To verify the interference of topical IgG with the allergen-triggered eosinophilic airway inflammation that underlies asthma, sensitized mice were treated by intranasal instillation of specific IgG, followed by allergen challenge. This treatment strongly reduced eosinophilic inflammation and goblet cell metaplasia, and increased Th1 reactivity and IFN-gamma levels in bronchoalveolar lavage fluid. In contrast, inflammatory responses were unaffected in IFN-gamma-deficient mice or when applying F(ab')(2). Although dependent on specific allergen-IgG interaction, inflammation triggered by bystander allergens was similarly repressed. Perseverance of inflammation repression, apparent after secondary allergen challenge, and increased allergen capture by alveolar macrophages further characterized the consequences of topical IgG application. These results assign a novel protective function to anti-allergen IgG namely at the local level interference with the inflammatory cascade, resulting in repression of allergic inflammation through an FcgammaR- and IFN-gamma-dependent mechanism. Furthermore, these results provide a basis for topical immunotherapy of asthma by direct delivery of anti-allergen IgG to the airways.


Pattern of cleft lip and palate in hospital-based population in Saudi Arabia: retrospective study.
To report the patterns of cleft lip and/or cleft palate in Saudi Arabia from data collected at a tertiary care hospital. King Faisal Specialist Hospital and Research Center, Riyadh. All the cleft lip and/or cleft palate patients registered in the Cleft Lip/Palate and Craniofacial Anomalies Registry from June 1999 to December 2005. Retrospectively, 807 cases of cleft lip and/or palate were registered. There were 451 boys and 356 girls. Cleft lip and palate was more common (387) than isolated cleft palate (294) and isolated cleft lip (122). Boys predominated in cleft lip and palate and cleft lip; whereas, girls predominated in isolated cleft palate, with boy to girl ratios of 1.6:1, 1.2:1, and 0.9:1 for cleft lip and/or palate, isolated cleft lip, and isolated cleft palate, respectively. The Riyadh region had more cases (32.0%) than the Asir (15.6%) and Eastern (14.6%) regions. Parents of 439 individuals had consanguineous marriages. A positive family history of cleft was seen in 224 cases. Of 238 cases with associated anomalies, 91 had congenital heart disease. Of the children with isolated cleft palate, 40.5% had associated anomalies, whereas only 23.0% of the children with isolated cleft lip or cleft lip and palate had associated malformations. The pattern of cleft observed in this study does not differ significantly from those reported in the literature for Arab populations.


Chronic urticaria: a disease at a crossroad between autoimmunity and coagulation.
Chronic urticaria (CU), defined as recurrence of wheals with or without angioedema for more than 6 weeks, is a quite common disease that may severely worsen the quality of life. Studies carried out during the last 2 decades have demonstrated an autoimmune pathogenesis mediated by functionally active autoantibodies to the high affinity IgE receptor (FcepsilonRI) or to IgE which are able to induce histamine release from basophils and mast cells. However, such mechanism can be detected in less than 50% of patients only. The present article reviews recent findings showing an additional pathogenic mechanisms in CU patients: activation of the coagulation cascade resulting in thrombin production. Thrombin is a serine protease which may play a key role in urticaria, being able to induce edema through an increase in vascular permeability, mast cell activation and degranulation, and to induce the production of the anaphylotoxin C5a. Such mechanism seems to be active in the majority of CU patients, however their relationship with anti-FcepsilonRI or anti-IgE autoantibodies is still matter of research.


Brain-computer interface: trend, challenges, and threats.
Brain-computer interface (BCI), an emerging technology that facilitates communication between brain and computer, has attracted a great deal of research in recent years. Researchers provide experimental results demonstrating that BCI can restore the capabilities of physically challenged people, hence improving the quality of their lives. BCI has revolutionized and positively impacted several industries, including entertainment and gaming, automation and control, education, neuromarketing, and neuroergonomics. Notwithstanding its broad range of applications, the global trend of BCI remains lightly discussed in the literature. Understanding the trend may inform researchers and practitioners on the direction of the field, and on where they should invest their efforts more. Noting this significance, we have analyzed 25,336 metadata of BCI publications from Scopus to determine advancement of the field. The analysis shows an exponential growth of BCI publications in China from 2019 onwards, exceeding those from the United States that started to decline during the same period. Implications and reasons for this trend are discussed. Furthermore, we have extensively discussed challenges and threats limiting exploitation of BCI capabilities. A typical BCI architecture is hypothesized to address two prominent BCI threats, privacy and security, as an attempt to make the technology commercially viable to the society.


Artificial Intelligence in Surgical Documentation: A Critical Review of the Role of Large Language Models.
This article provides a critical analysis of the application of the advanced language model, GPT-4, in generating surgical operative notes, with a focus on its use in ophthalmology as presented by Waisberg et al. The discussion underscores the inherent complexity and specificity of operative notes, the issue of accountability, and the potential data protection issues associated with the use of AI in healthcare. The letter emphasizes the need for a more comprehensive understanding of the complexities involved in applying AI in healthcare and calls for a more nuanced and responsible approach to the integration of AI in surgical documentation.


Biaryl acids: novel non-nucleoside inhibitors of HIV reverse transcriptase types 1 and 2.
A series of biaryl acids has been found to show micromolar inhibition of the HIV reverse transcriptase (RT) from types 1 and 2 with IC50S in the micromolar range. The series was discovered by consideration of the polymerase active site and sub-structure searching of the company compound collection. Synthesis of analogues to investigate the SAR is described. Two of these compounds have shown inhibition of HIV-2 RT only.


Nationwide Laboratory Adherence to Myocardial Perfusion Imaging Radiation Dose Reduction Practices: A Report From the Intersocietal Accreditation Commission Data Repository.
This study sought to examine current laboratory practices for radiation effective doses for myocardial perfusion imaging (MPI) and laboratory adherence to guideline-directed radiation reduction practices. A recent focus on radiation dose reduction for cardiovascular imaging has led to several published guidelines and consensus statements detailing performance metrics for laboratory practices. We sought to examine laboratory adherence to optimized radiation dose protocol recommendations among 5,216 submitted cases from 1,074 MPI laboratories evaluated for Intersocietal Accreditation Commission accreditation. Eligible imaging centers included MPI laboratories enrolled in the Intersocietal Accreditation Commission data repository of accreditation applications from 2012 to 2013. Accreditation requires submission of 3 to 5 cases for evaluation of a range of representative cases. Based on standard dosimetry for rest and stress MPI, an effective dose (in millisieverts) was calculated. Model simulations were performed to estimate guideline-directed effective doses. The average effective dose was 14.9 ± 5.8 mSv (range 1.4 to 42.4 mSv). A 1-day technetium Tc 99m protocol was used in 82.9% of cases, whereas a 2-day technetium Tc 99m and dual isotope protocol was used in 7.5% of submitted cases. Only 1.5% of participating imaging centers met current guidelines for an average laboratory radiation exposure ≤9 mSv, whereas 10.1% of patient effective doses were >20.0 mSv. A model simulation replacing the radiation exposure of dual isotope MPI with that of a 1-day technetium Tc 99m protocol reduced the proportion of patients receiving an effective dose >20 mSv to only 2.7% of cases (p < 0.0001). Mandatory laboratory accreditation for MPI allows for examination of current radiation dosimetry practices. Current guidelines for reduced patient-specific radiation exposure are rarely implemented, with few laboratories meeting recommendations of ≤9 mSv for 50% of patients. Increased educational efforts and the development of performance measures for laboratory accreditation may be required to meet current radiation dose-reduction standards.


Optimizing the accuracy of detecting a functional corpus luteum in dairy cows.
The objectives were to evaluate the accuracy of detecting a functional CL by transrectal palpation and ultrasonography, and to optimize the accuracy of detecting a functional CL by ultrasonography in Holstein cows. In Experiment 1, four veterinarians performed transrectal palpation in 1250 cows at 37 d in milk (DIM), two veterinarians repeated transrectal palpation in 823 cows at 58 DIM, and one veterinarian performed 206 ultrasonographic examinations at 37 DIM. In Experiment 2, 987 and 983 ultrasonographic examinations were performed at 21 and 24 d after AI by one veterinarian for detection and measurement of CL. Cows with a blood progesterone concentration > or =1ng/mL were assumed to have a functional CL. Sensitivity and specificity were optimized using receiver operating characteristic analysis. In Experiment 1, sensitivity of transrectal palpation for diagnosing a functional CL ranged from 33.3 to 59.9% at 37 DIM and from 48.3 to 68.4% at 58 DIM, whereas specificity ranged from 76.7 to 93.2% at 37 DIM and from 73.3 to 86.7% at 58 DIM. Sensitivity and specificity for ultrasonography were 89.4 and 45.7%, respectively. In Experiment 2, the sensitivity and specificity of ultrasonography were 97.3 and 38.1% at 21 d after AI, and were 97.9 and 51.0% at 24 d after AI. Sensitivity and specificity were optimized using a cutoff diameter of 23mm at 21 d and 22mm at 24 d, which resulted in sensitivity and specificity of 87.2 and 83.0% at 21 d, and 89.5 and 89.4% at 24 d after AI, respectively. Sensitivity was low and specificity was high for transrectal palpation, whereas ultrasonography resulted in high sensitivity and low specificity. Using a cutoff diameter during ultrasonography improved accuracy of detection of a functional CL compared with either ultrasonography without cutoff or transrectal palpation.


Hematomyelia Presenting with Neurogenic Stunned Myocardium.
Various neurological disorders and emotional stress may cause left ventricular dysfunction, known as a neurogenic stunned myocardium. A previously healthy 71-year-old woman collapsed immediately after experiencing left arm numbness and pain. Thereafter, the patient complained of anterior chest pain and became comatose. An electrocardiogram showed ST-segment elevation of I, aVL, and V2-3 and depression of II, III, and aVF. Echocardiography revealed anteroseptal hypokinesis of the left ventricle. Emergency coronary angiography revealed no significant stenosis in the coronary arteries; however, left ventriculography revealed obvious anteroseptal hypokinesis. When the patient regained consciousness the following day, tetraplegia was observed. Spinal computed tomography and magnetic resonance imaging revealed an intramedullary spinal cord hemorrhage from the medulla to the conus. The cardiac function recovered, but the patient remained tetraplegic with poor spontaneous respiration. Although its incidence is extremely rare, hematomyelia should be recognized as a potential cause of neurogenic stunned myocardium.


Visibility of vascular phenylalanine in dynamic uptake studies in humans using magnetic resonance spectroscopy.
In general, vascular contributions to the in vivo magnetic resonance (MR) brain spectrum are too small to be relevant. In cerebral uptake studies, however, vascular contributions may constitute a major confounder. MR visibility of vascular Phe was investigated by recording localized spectra from fully oxygenated and well-mixed whole blood. Blood Phe levels determined by MR spectroscopy (MRS) and ion-exchange chromatography showed excellent correlation. In addition, effects of blood flow were shown to have a small effect on signal amplitude with the MRS methodology used. Hence, blood Phe is almost completely MR visible at 1.5 T, even though it is severely broadened at higher fields. Without appropriate correction, cerebral Phe influx in studies of brain Phe uptake in phenylketonuria patients or healthy subjects would appear to be faster and lead to higher levels. Similar effects are envisaged for studies of ethanol or glucose uptake across the blood-brain barrier.


Role of non-coding RNA in immune microenvironment and anticancer therapy of gastric cancer.
Gastric cancer remains one of the cancers with the highest mortality in the world; therefore, it is very important to investigate its pathogenesis to improve the prognosis of gastric cancer patients. Recently, noncoding RNAs have become a research hotspot in the field of oncology. These RNA molecules play complex roles in the regulation of tumor cells, immune cells, and the tumor microenvironment. Therefore, studying their ability to regulate the gastric cancer immune microenvironment will provide us with a better perspective to understand their potential role in anticancer therapy. In this review, we discuss the regulatory effects of several common noncoding RNAs on the immune microenvironment of gastric cancer and their prospects in anticancer therapy to provide some novel insight into the identification of valuable diagnostic markers and improving the prognosis of gastric cancer patients.


Effect of Fluprostenol Isopropyl Ester and 15-Keto Fluprostenol on Eyelash Growth: A Clinical and Pharmacologic Study.
15-Keto fluprostenol isopropyl ester and 15-keto fluprostenol have demonstrated a stimulatory effect on the growth and thickening of the eyelashes without the disadvantages of the prostaglandin derivatives of the PGF2α group, which have a hydroxyl group at position 15 in their structure. The two 15-ketoderivatives have the same efficacy as the 15-hydroxyl derivatives in allowing the regrowth, lengthening, darkening, or thickening of the eyelashes, but without darkening the edge of the eyelid or coloring the iris, even temporarily.


Chemotaxis-selective colonization of mangrove rhizosphere microbes on nine different microplastics.
Microplastics pollution poses a new threat to the environment of intertidal zone. The sea forest, mangrove, has been polluted by a large number of plastic debris worldwide. To fill the gaps in knowledge of mangrove rhizosphere microbes connected with the 'plasticsphere', a semi-controlled in situ exposure experiment for nine different types of microplastics were conducted in mangrove ecosystem. A sign of biodegrading was observed on polyethylene, polyamide 6 and polyvinyl chloride microplastics surface after 3 months exposure. We discovered that the metabolic activities of the dominant bacteria on certain microplastics were related to the specific groups on polymers molecule. The selective colonization may be driven by the chemotaxis of bacteria. Specially, microplastics biofilms of polyethylene, polyamide 6, polyvinyl chloride and expanded polystyrene possess distinctive dominant bacteria assemblages which have great significance in ecosystem processes involving carbon cycle or sulfur cycle. Community of mangrove soil microorganism and microplastic biofilm varies as the seasons changes. As a new niche, microplastics has higher inclusivity to bacteria than surrounding soil. Additionally, pathogens for human beings (Vibrio parahaemolyticus and Escherichia-Shigella) were detected both in microplastics and soil. We stress that the interaction between microplastics and rhizosphere microorganisms may affect the growth and health of mangrove plants. Besides, we point out that mangrove rhizosphere microorganism can be an ideal candidate for plastics-degradation.


Hospitalization as a life crisis for the preschool child: a critical review.
Review of the literature on the psychological effects of hospitalization on children reveals that it has not increased substantially in quality or quantity since Vernon and his associates published their extensive review a decade ago. More recent research supports the earlier contentions that children between the ages of 6 months and 4 years are especially vulnerable to upset but are also more amenable to change and growth than other age groups. Maternal separation appears to be the primary stressor, but the presence of emotional disturbance prior to hospitalization and the child's level of cognitive development at the time may also be significant factors. Attempts to prepare children for hospitalization and surgery have met with some success, but not for preschool children. The need for some comprehensive theoretical perspective on which to base research is evident. Studies to date appear to have been based either on the concept of "anticipatory worry" or on some form of modeling theory. The author suggests that hospitalization can be considered as a life crisis for a child, a crisis that may result in blocks or distortions in his development if not mastered properly. Crisis theory provides a meaningful and useful model for understanding the experience of hospitalization for young children and for providing a basis for intervention. The psychopathology present in some children and their families is made apparent during such a crisis as hospitalization; this may present the only time when they are accesible to mental health professionals.


Generation of stable heading representations in diverse visual scenes.
Many animals rely on an internal heading representation when navigating in varied environments1-10. How this representation is linked to the sensory cues that define different surroundings is unclear. In the fly brain, heading is represented by 'compass' neurons that innervate a ring-shaped structure known as the ellipsoid body3,11,12. Each compass neuron receives inputs from 'ring' neurons that are selective for particular visual features13-16; this combination provides an ideal substrate for the extraction of directional information from a visual scene. Here we combine two-photon calcium imaging and optogenetics in tethered flying flies with circuit modelling, and show how the correlated activity of compass and visual neurons drives plasticity17-22, which flexibly transforms two-dimensional visual cues into a stable heading representation. We also describe how this plasticity enables the fly to convert a partial heading representation, established from orienting within part of a novel setting, into a complete heading representation. Our results provide mechanistic insight into the memory-related computations that are essential for flexible navigation in varied surroundings.


Evaluation of eye movement variables of Chinese and American readers. Information abstraction by Chinese and American readers.
Eye movements were recorded while competent readers of English and Chinese read in their respective languages. There were no important differences in oculometric patterns of fixation pause durations for Chinese and American readers, suggesting that cognitive aspects of reading are more important than perceptual ones in determining eye movement patterns and fixation pauses of competent readers. An analysis of undershoot saccades associated with return of the eyes from the end of one line to the beginning of the next line suggests that these occur more frequently during reading than during the performance of similar eye movements that are more perceptually determined, however, the amount of undershoot does not discriminate between readers of alphabetic and logographic texts.


Validating the poly-cyclodextrins based local drug delivery system on plasma-sprayed hydroxyapatite coated orthopedic implant with toluidine blue O.
Local antibiotics delivery is an efficient solution to reduce the risk of infections associated with orthopedic implant. This study aims to functionalize plasma-sprayed hydroxyapatite coated titanium (Ti-HA) hip joint implant material with cyclodextrins-polymer (polyCD)-based local drug delivery system for loading therapeutic molecules (e.g. antibiotics), to offer a sustainable drug delivery. The process of polyCD coating on Ti-HA material was optimized with the help of model guest molecule - toluidine blue O (TBO) for evaluating the efficacy of polyCD system. The obtained results clearly showed that polyCD's treatment can firmly coat on the Ti-HA material under the optimized processing parameters concerning the type of CD, thermal treatment temperature and duration. PolyCD system has been proven to have a high capacity of TBO adsorption and long release duration. In vitro study also showed non-cytotoxicity of polyCD functionalized samples to osteoblastic cells. Trial study with gentamicin revealed very promising potential of polyCD system for sustained delivery of antibiotics. To conclude, the study substantiates the prospective flexibility of drug choice when applying polyCD treated implants including antibiotics, antimitotic agents or other therapeutical molecules. One or more drugs can be loaded, thus synergism and multi-factorial effects are feasible.


An intelligent classifier for prognosis of cardiac resynchronization therapy based on speckle-tracking echocardiograms.
Predicting response after cardiac resynchronization therapy (CRT) has been a challenge of cardiologists. About 30% of selected patients based on the standard selection criteria for CRT do not show response after receiving the treatment. This study is aimed to build an intelligent classifier to assist in identifying potential CRT responders by speckle-tracking radial strain based on echocardiograms. The echocardiograms analyzed were acquired before CRT from 26 patients who have received CRT. Sequential forward selection was performed on the parameters obtained by peak-strain timing and phase space reconstruction on speckle-tracking radial strain to find an optimal set of features for creating intelligent classifiers. Support vector machine (SVM) with a linear, quadratic, and polynominal kernel were tested to build classifiers to identify potential responders and non-responders for CRT by selected features. Based on random sub-sampling validation, the best classification performance is correct rate about 95% with 96-97% sensitivity and 93-94% specificity achieved by applying SVM with a quadratic kernel on a set of 3 parameters. The selected 3 parameters contain both indexes extracted by peak-strain timing and phase space reconstruction. An intelligent classifier with an averaged correct rate, sensitivity and specificity above 90% for assisting in identifying CRT responders is built by speckle-tracking radial strain. The classifier can be applied to provide objective suggestion for patient selection of CRT.


Diabetes mellitus and vascular lesions.
Cardiovascular complications represent by far the most severe manifestations of diabetes mellitus. Treatment aimed at stopping progression of vascular lesions may fall short if initiated when the disease becomes clinically evident. Therefore, identification of the earliest vascular disfunctions may offer the best opportunity to interfere with pathogenic mechanisms and avoid progression of diabetic vasculopathy. In this report, we present a few mechanisms that alter hemodynamic and metabolic homeostasis in the course of diabetes mellitus. Endothelial function with special emphasis on nitric oxide and oxidative stress, advanced glycation end products, and the renin angiotensin system are briefly discussed. New pharmacological agents that may favorably influence these parameters are presently undergoing clinical trials. However, tight control of plasma glucose and cardiovascular risk factors represent the cornerstone of the treatment in diabetes to slow progression of vascular disease.


Acromioclavicular dislocations treated by coracoacromial ligament transfer.
Forty-seven patients with acute Allman type-III acromioclavicular dislocations were treated with open reduction and coracoacromial ligament transfer. At follow-up 1.6-10 years (mean 6) post-operatively 44 patients (94%) had excellent or good functional results. Two of the three patients with unsatisfactory results had degenerative joint changes. No late dislocation was found but there were three subluxations (3-5 mm). Two of the three patients with subluxation in the acromioclavicular joint at follow-up had unsatisfactory results. Complications were infrequent and cosmetic results satisfactory.


Growth of mouse neuroblastoma cell line in a defined medium.
The mouse neuroblastoma tumor line Cl300, clone Neuro-2a, can proliferate in a serum-free synthetic medium supplemented with insulin, transferring, progesterone, selenium and putrescine (N2 medium), with a marked increase in cell number as compared to the optimal 10% serum containing medium. More extensive and elaborate neurite formation with contacts is seen in N2 that in serum supplemented medium. However, electron microscopic studies of the cells grown in N2 lack the formation of synapses, in contrast to the cells grown in serum supplemented medium where at least primitive stages of synaptogenesis are common.


A computational fluid dynamic analysis of peri-bracket salivary flow influencing the microbial and periodontal parameters.
Fixed vestibular appliances decrease the "self-cleansing" action of saliva and promote aggregation of dental plaque by disturbing the salivary flow field on tooth surfaces, leading to a higher prevalence of enamel demineralization and periodontal diseases. In the current study, we investigated the salivary dynamic characteristics of plaque retention and periodontal status around appliances during orthodontic treatment. By reconstructing lower central incisors and orthodontic appliances, we simulated saliva flow on the tooth surface and then characterized and quantified the salivary flow pattern surrounding the bracket and archwire. In parallel, we tested the total peri-bracket bacterial counts and periodontal status to assess interrelations. Our results demonstrate that orthodontic appliances disturb the salivary flow field on tooth surfaces and can lead to a decrease in salivary velocity and an increase in bacterial numbers. Local vortexes forming in the areas gingival to the bracket, together with the narrow space limitation, contributed to the periodontal inflammatory response. This study confirms that changes in salivary flow are an obvious predisposing factor for bacterial accumulation, and advances the ability to replicate, in vitro, the salivary characteristics of plaque retention and periodontal status around appliances during orthodontic treatment.


Preparation of magnetic hyper-crosslinked polymer for high efficient preconcentration of four aflatoxins in rice and sorghum samples.
Aflatoxins have carcinogenic effect on human health, developing effective adsorbents for their enrichment and detection is particularly required. A magnetic hyper-crosslinked polymer (MHCP-TPE) was prepared and used as a magnetic sorbent to adsorb and isolate aflatoxins from rice and sorghum samples prior to high performance liquid chromatography-fluorescence detection. MHCP-TPE exhibited good magnetic separation ability and reusability, with fast adsorption kinetics and quite good adsorption efficiency for the aflatoxins. At optimized conditions, a sensitive and reliable method was established for the determination of four aflatoxins (B1, B2, G1 and G2) in rice and sorghum samples. The limits of detection were 0.003-0.075 ng g-1 and 0.01-0.25 ng g-1 for rice and sorghum, respectively. Good method recoveries ranging from 83.0 % to 117 % were obtained, with relative standard deviations less than 8.0 %. This method offered a superior alternative to determine trace level of aflatoxins in cereal foods. MHCP-TPE holds great potential in separation science.


Degenerative changes, DNA synthesis and mitotic activity in rat liver following single and repeated exposure to fenarimol.
Degenerative changes were observed in liver of rats treated with single and repeated doses of fenarimol (250 mg/kg body weight x day). Regenerative changes i.e. increase in: DNA synthesis, hepatic DNA, mitotic activity and number of binuclear hepatocytes, were also noted.


Severe pulmonary hypertension in aging female apolipoprotein E-deficient mice is rescued by estrogen replacement therapy.
Apolipoprotein E (ApoE) is a multifunctional protein, and its deficiency leads to the development of atherosclerosis in mice. Patients with pulmonary hypertension (PH) have reduced expression of ApoE in lung tissue. ApoE is known to inhibit endothelial and smooth muscle cell proliferation and has anti-inflammatory and anti-platelet aggregation properties. Young ApoE-deficient mice have been shown to develop PH on high fat diet. The combined role of female sex and aging in the development of PH has not been investigated before. Here, we investigated the development of PH in young and middle-aged (MA) female ApoE-deficient mice and explored the role of exogenous estrogen (E2) replacement therapy for the aging females. Wild type (WT) and ApoE-deficient female mice (Young and MA) were injected with a single intraperitoneal dose of monocrotaline (MCT, 60 mg/kg). Some ApoE-deficient MA female mice that received MCT were also treated with subcutaneous E2 pellets (0.03 mg/kg/day) from day 21 to 30 after MCT injection. Direct cardiac catheterization was performed terminally to record right ventricular systolic pressure (RVSP). Right ventricular (RV), left ventricular (LV), and interventricular septum (IVS) were dissected and weighed. Lung sections were examined using trichrome and immunofluorescence staining. Western blot analyses of lung and RV lysates were performed. In WT female mice, the severity of PH was similar between young and MA mice as RVSP was not significantly different (RVSP = 38.2 ± 1.2 in young vs. 40.5 ± 8.3 mmHg in MA, p < 0.05). In ApoE-deficient mice, MA females developed significantly severe PH (RVSP = 63 ± 10 mmHg) compared to young females (RVSP; 36 ± 3 mmHg, p < 0.05 vs. MA female). ApoE-deficient MA females also developed more severe RV hypertrophy compared to young females (RV hypertrophy index (RV/[LV + IVS]) = 0.53 ± 0.06 vs. 0.33 ± 0.01, p < 0.05). ApoE-deficient MA female mice manifested increased peripheral pulmonary artery muscularization and pulmonary fibrosis. E2 treatment of MA female ApoE-deficient mice resulted in a significant decrease in RVSP, reversal of pulmonary vascular remodeling, and RV hypertrophy. In MA female ApoE-deficient mice with PH, only the expression of ERβ in the lungs, but not in RV, was significantly downregulated, and it was restored by E2 treatment. The expression of ERα was not affected in either lungs or RV by PH. GPR30 was only detected in the RV, and it was not affected by PH in MA female ApoE-deficient mice. Our results suggest that only aging female ApoE-deficient but not WT mice develop severe PH compared to younger females. Exogenous estrogen therapy rescued PH and RV hypertrophy in aging female ApoE-deficient mice possibly through restoration of lung ERβ.


Tumor necrosis factor receptor superfamily 10B (TNFRSF10B): an insight from structure modeling to virtual screening for designing drug against head and neck cancer.
Head and neck cancer (HNC) belongs to a group of heterogeneous disease with distinct patterns of behavior and presentation. TNFRSF10B, a tumor suppressor gene mapped on chromosome 8. Mutation in candidate gene is responsible for the loss of chromosome p arm which is frequently observed in head and neck tumors. TNFRSF10B inhibits tumor formation through apoptosis but deregulation encourages metastasis, migration and invasion of tumor cell tissues. Structural modeling was performed by employing MODELLER (9v10). A suitable template [2ZB9] was retrieved from protein databank with query coverage and sequence identity of 84% and 30% respectively. Predicted Model evaluation form Rampage revealed 93.2% residues in favoured region, 5.7% in allowed region while only 1 residue is in outlier region. ERRAT and ProSA demonstrated 51.85% overall quality with a -1.08 Z-score of predicted model. Molecular Evolutionary Genetics Analysis (MEGA 5) tool was executed to infer an evolutionary history of TNFRSF10B candidate gene. Orthologs and paralogs [TNFRSF10A & TNFRSF10D] protein sequences of TNFRSF10B gene were retrieved for developed ancestral relationship. Topology of tree presenting TNFRSF10A gene considered as outgroup. Human and gorilla shared more than 90% similarities with conserved amino acid sequence. Virtual screening approach was appliedfor identification of novel inhibitors. Library (Mcule) was screened for novel inhibitors and utilized the scrutinized lead compounds for protein ligand docking. Screened lead compounds were further investigated for molecular docking studies. STRING server was employed to explore protein-protein interactions of TNFRSF10B target protein. TNFSF10 protein showed highest 0.999 confidence score and selected protein-protein docking by utilizing GRAMM-X server. In-silico docking results revealed I-58, S-90 and A-62 as most active interacting residues of TNFRSF10B receptor protein with R-130, S-156 and R-130 of TNFSF10B ligand protein. Current research may provide a backbone for understanding structural and functional insights of TNFRSF10B protein. The designed novel inhibitors and predicted interactions might serve to inhibit the disease. Effective in-vitro potent ligands are required which will be helpful in future to design a drug to against Head and neck cancer disease. There is an urgent need for affective drug designing of head and neck cancer and computational tools for examining candidate genes more efficiently and accurately are required.


Qualitative and Quantitative Characterization of Protein-Carbohydrate Interactions by NMR Spectroscopy.
Solution-state nuclear magnetic resonance (NMR) spectroscopy can be used to monitor protein-carbohydrate interactions. Two-dimensional 1H-15N heteronuclear single quantum coherence (HSQC)-based techniques described in this chapter can be used quickly and effectively to screen a set of possible carbohydrate-binding partners, to quantify the dissociation constant (Kd) of any identified interactions, and to the map the carbohydrate-binding site on the structure of a protein. Here, we describe the titration of a family 32 carbohydrate-binding module from Clostridium perfringens (CpCBM32) with the monosaccharide N-acetylgalactosamine (GalNAc), in which we calculate the apparent dissociation of the interaction and map the GalNAc binding site onto the structure of CpCBM32. This approach can be applied to other CBM- and protein-ligand systems.