Existence of tenascin-C isoforms in rat that contain the alternatively spliced AD1 domain are developmentally regulated during hippocampal development.
Tenascin-C (TN-C) is a multimodular glycoprotein of the extracellular matrix which is important for the development of the nervous system and has a range of different functions which are mediated by the different protein domains present. TN-C contains eight constitutive fibronectin type III (FNIII) domains and a region of alternatively spliced FNIII domains. In the mouse and chick, six of these domains have been described and characterized, whereas in human there are nine of them. In this report, we show that seven alternatively spliced FNIII domains exist in rat and describe the differential expression pattern of the additional domain AD1 during embryonic and postnatal rat brain development. The AD1 domain of rat is homologous to the ones described in human and chick proteins but does not exist in mouse. Its expression can be located to the developing rat hippocampus and the lining of the lateral ventricle, regions where the TN-C protein may affect the behavior of stem and progenitor cells. During hippocampal development AD1 and the other alternatively spliced domains are differentially expressed as shown by RT-PCRs, immunocytochemistry and in situ hybridizations.


"Guttmann Cognitest"®, preliminary validation of a digital solution to test cognitive performance.
Thanks to technological advances, the administration of cognitive assessments via digital solutions continues to increase, both in research and clinical practice. "Guttmann Cognitest"°ledR is a digital solution for cognitive assessment which includes seven computerized tasks designed to assess main cognitive functions requiring approximately 20 min to be completed. The purpose of the present study was to validate it against standard and more extensive in-person neuropsychological assessments in the context of the Barcelona Brain Health Initiative (BBHI) cohort study. We studied 274 participants of the BBHI (126 women, mean age = 56.14, age range 44-69), who underwent an extensive in-person assessment, including a classical paper-and-pencil neuropsychological assessment and a cognitive assessment via the "Guttmann Cognitest"°ledR. Principal component analysis indicated that "Guttmann Cognitest"°ledR measures four main cognitive domains and convergent validity analysis demonstrated that cognitive performance was associated with gold standard paper and pencil tests. Results also showed an expected negative correlation with age, a relation with educational level as well as a gender effect. Regression-based norming equations for the sample tested are also reported. Performing a cognitive assessment with this digital solution is feasible and potentially useful to gather information about cognitive functioning in large samples and experimental settings.


Dynamics of temperature dependent modifications of blood in the near-infrared.
Laser irradiation induces blood coagulation by heating of blood components. It is a complex phenomenon which encompasses a variety of processes, such as cell shape modification, cell membrane rupture, protein denaturation, aggregation, and finally blood gelation. An in vitro study was performed to investigate heating temperatures leading to transformation of blood and to have a better understanding of the dynamics of temperature dependent modifications of blood in the near-infrared. Slow heating of whole blood and hemolized blood was performed using a specific optical chamber. Eight hundred and five and 940 nm light transmission of blood was measured as a function of time during heating at various temperatures (60-75 degrees C). During heating of whole blood, three phases were clearly identified. For hemolized blood, only phase 3 was present. For whole blood, the duration of each phase was correlated to blood temperature. A temporary increase of transmission was observed during heating with a maximum at 65 degrees C. The analysis of the dynamics of temperature dependent modifications of blood are consistent with cell shape modification, denaturation, and aggregation of blood, resulting in the formation of an aqueous gel-matrix. "Slow" vessel heating which is now proposed as the optimal mechanism for permanent vessel closure should be reconsidered in terms of our results. In that particular case, the optical coefficients of blood could be different from those expected. In case of a large blood vessel, this could be an advantage since a "temporary" higher transmission of light could lead to a more homogeneous heating of the blood vessel. In case of a small blood vessel, this phenomenon could lead to a collateral damage of the skin.


Accidental pneumatic rupture of the esophagus.
A case of accidental pneumatic rupture of the thoracic esophagus in a 6-year-old boy is reported. Early operation with transthoracic esophageal repair resulted in survival of the patient, and follow-up at 18 months has demonstrated normal esophageal function and anatomy. A search of the literature has yielded 11 similar cases.


Nutrient dynamics in small mesotrophic fens surrounded by cultivated land : I. Productivity and nutrient uptake by the vegetation in relation to the flow of eutrophicated ground water.
In a typical Dutch polder landscape the effects of nutrient transport from cultivated grassland to mesotrophic fen communities were studied. In a comparative approach, biomass production and nutrient (N, P and K) uptake were determined monthly in four fens and a hayfield differeing in productivity and species composition. The interstitial ground water was sampled every two weeks for determinations of inorganic nutrient concentrations.The differences in productivity between the fens were clearly reflected in the amount of N, P and K taken up in the above-ground vegetation. N and P proved to be limiting plant growth in the fens, whereas K was the main limiting factor in the hayfield. The ground water welling up from the sandy bottom into the fens proved to be rich in ammonia (3-5 ppm). There are strong indications that this continual seepage leads to a considerable input of N into the fens but not to a higher productivity, as the ammonia is absorbed by the lowermost peat layers covering the sand.At this moment, the differences in productivity between the fens must be caused by differences in the rates of mineralization of the superficial peat layer. The degree of fixation of the floating vegetation mat, determining whether or not low water levels lead to an aerated soil top layer, is important in this respect. Within a period of decades, however, the continuous inflow of ammonia may eventually cause an increase in the productivity and a change in the species composition of the fens.


Ischemic heart disease. A major obstacle to becoming old.
Four classes of etiologic agents that cause human illness have been discovered. Sometimes members of two or more classes of agents cooperate to cause illness. Knowledge of etiology is necessary if a disease is to be eradicated. The leading causes of death in the United States have changed dramatically in the last century. Infection has been replaced by chronic illnesses of obscure etiology. Ischemic heart disease is the leading cause of death in middle age and is the major obstacle to becoming old. There are numerous similarities between animals deficient in copper and people with ischemic heart disease. The most important of these similarities are glucose intolerance, hypercholesterolemia, abnormal electrocardiogram, hyperuricemia, and hypertension, as these characteristics are predictive of risk of ischemic heart disease. No other nutritional insult has produced these characteristics in experiments with animals; men fed diets low in copper have been found to have increased cholesterol, decreased glucose tolerance, and abnormal electrocardiograms. The process that results in ischemic heart disease is remarkably similar to that of copper deficiency. Links have been found between copper metabolism and several hypotheses on the origin of ischemic heart disease. Several aspects of the lipid hypothesis can be interpreted in terms of copper metabolism. More features of the etiology, pathogenesis, and pathophysiology of ischemic heart disease can be explained in terms of copper deficiency than can be explained by any other environmental insult.


Spindle-shaped appendages of IIIab-pyramids filled with lipofuscin: a striking pathological change of the senescent human isocortex.
Brains from 30 mentally normal men, ranging in age from 18--90 years, were studied to assess the occurrence and development of lipofuscin-filled spindle-shaped appendages of pyramidal cells of the isocortex; these can generally be encountered in the senescent brain within layer IIIab. The number of pigmented spindles was determined in a circumscribed part of prefrontal area revealing a close association of this conspicuous pathological alteration with growing age.


Antibody status to HHV-6 in children with leukaemia.
Forty children with acute lymphoblastic (33) or myeloid leukaemia (seven) were studied for IgG and IgM antibodies and IgG avidity against human herpesvirus 6 (HHV-6) at the time of diagnosis, and compared with age-, sex- and season-matched children with various neurological diseases of suspected viral origin. Of the children with leukaemia, 97.5% had IgG antibodies and 40% IgM antibodies to HHV-6 compared with 92.3% and 7.7% of reference subjects (P = 0.005). A seronegative child with leukaemia seroconverted 3 weeks after the diagnosis. The avidity of IgG antibodies (based on the resistance to urea treatment) was high in all children with leukaemia. One reference child had HHV-6-specific IgG antibodies with low avidity, which together with his positive IgM indicated an acute infection. The presence of specific IgM antibodies in 40% of children with leukaemia and the high avidity of IgG suggest a reactivation or an inaproppriate primary response to HHV-6 infection. The results support the conclusion of the role of the HHV-6 infection at the onset of childhood leukaemia.


Recent advances in STED and RESOLFT super-resolution imaging techniques.
Stimulated emission depletion (STED) and reversible saturable optical fluorescence transition (RESOLFT) microscopy are the super-resolution imaging techniques that can acquire nanoscale spatial resolution. The spatial resolution of the other far-field optical microscopic techniques is bound by diffraction limit, however, STED/RESOLFT techniques eliminate the diffraction barrier. These microscopic techniques have taken the limits of optical image resolution down to the nanometer scale and opened new paths for biomedical and nanophosphor research. In this paper, we review the recent advancements of these techniques in the field of nanoscopy using continuous wave (CW) laser sources. Further, we discuss the main limitation of the STED microscopy in terms of essential requirements of higher depletion beam power and photobleaching issues. The RESOLFT microscopic technique can be considered as an alternate technique to overcome limitations of existing STED microscopy. Moreover, the Bessel and Gaussian-Bessel beam STED microscopic techniques are also reviewed to produce deep images with faster scanning of the samples. The organic molecules as well as the fluorescent doped nanoparticles like ZnSe:Mn having characteristics of excited state absorption can be investigated using RESOLFT microscopy.


Dispersity of des-L X Val7-D X Val8-Gramicidin A single channel conductances argues for different side chain orientations as basis.
Planar bilayer studies are reported on the channel activity of des-L X Val7-D X Val8-Gramicidin A. This analog is designed to provide more long-lived side chain distributions involving the Trp residues than occur with Gramicidin A. The carbonyls of these residues coordinate the permeant cation and the energetics of the coordination, which is proposed to depend on side chain orientation, determines the free energies of the rate limiting entrance-exit barriers and the binding sites. The finding of an increased dispersity of single channel conductance for the analog supports the perspective that dispersity derives from different side chain distributions on the same backbone conformation. Channel mechanism is not understood until dispersity is explained.


Efficiency of transcriptional terminators in Bacillus subtilis.
To promote more efficient synthesis of heterologous gene products in a Bacillus subtilis host, we have developed a system for rapidly testing the effect of a putative terminator on in vivo gene expression. Terminator structures from the Bacillus amyloliquefaciens amyE gene, the Bacillus licheniformis penP gene, the B. subtilis bglS gene, and the Bacillus thuringiensis cry gene were subcloned and inserted into a vector in such a way as to disrupt expression of the cat-86 gene. Comparisons are made between gene expression levels and the stabilities of the respective stem-loop structures.


Comparative Proteomic Profiling of Leishmania tropica: Investigation of a Case Infected with Simultaneous Cutaneous and Viscerotropic Leishmaniasis by 2-Dimentional Electrophoresis and Mass Spectrometry.
Viscerotropic leishmaniasis caused by Leishmania tropica poses a significant problem in the diagnosis and treatment management. Since differential gene expression is more important in outcome of the infection, we employed proteomic approach to identify potential proteins involved in visceralization of L. tropica. The proteomes profiling of L. tropica isolated from cutaneous and visceral tissues of one host were compared by 2-DE/MS proteomics study. Moreover, the transcript level of some identified proteins was confirmed using real-time RT-PCR. Of the 700 protein spots that were detected reproducibly on each gel, 135 were found to be differentially expressed (P≤ 0.05). Most of responsive proteins in visceral isolate changed in less abundant compared to cutaneous isolate. Among differentially expressed proteins, 56 proteins were confidently identified and classified according to the biological process. The largest groups consist of proteins involved in carbohydrate metabolism and protein synthesis. Most of the identified proteins, which implicated in energy metabolism, cell signaling and virulence were down-regulated, whereas some proteins that have a role in protein folding, antioxidant defense and proteolysis were up-regulated in visceral form. Moreover, the transcript level of some identified proteins such as co-chaperon was confirmed using real-time RT-PCR. L. tropica probably uses different mechanisms for survival and multiplication in viscera to establish viscerotropic leishmaniasis. The current study provides some clues into the mechanisms underlying the dissemination of L. tropica .


Slit-lamp beamsplitter for two stereoscopic views.
A double binocular beamsplitter, compatible with Zeiss optics, splits the light from each optical train of a slip-lamp microscope to provide an observer the exact stereoscopic view of the examiner. It has advantages in teaching slit-lamp examination techniques. Further, in surgery at the slit lamp, it allows the observer to function as an assistant and the surgeon to have both hands free.


Lumbar epidurography and epidural analgesia in cancer patients.
In an attempt to clarify the correlation between the spread of a local anesthetic and a radiographic contrast medium in the epidural space, a lumbar epidural catheter was inserted in 21 cancer patients. In group I, 10 patients, a single dose of bupivacaine 0.5%, 8 ml, was injected. The epidural block was evaluated by assessing loss of pin-prick sensation. The following day a contrast medium, iohexol 180 mg I/ml, 1.2 ml, was injected and the position of the catheter determined. A second dose of iohexol 180 mg I/ml, 8 ml, was injected and epidurograms were taken. The vertebral spread was measured in cephalad and caudad directions from the catheter tip. Group II, 11 patients, underwent the same procedures as group I with the exception of the volumes injected. On the first day they were given bupivacaine 0.5%, 16 ml, and on the second day iohexol 180 mg I/ml, 1.2 ml by 16 ml. In both groups the position of the patients was supine and the speed of injection standardized. In group I there was no statistically significant correlation between the spread of contrast medium and the extension of the epidural block either in the cephalad or in the caudad direction. In group II there was a statistically significant correlation in both the cephalad and caudad direction. It is concluded that epidurography can provide an estimate of the epidural block, but cannot predict the exact segmental distribution of the block.


Interatrial conduction times in paroxysmal atrial fibrillation patients with normal atrial volume and their correlation with areas of local prolonged bipolar electrograms.
Recent evidence has shown that the presence of abnormal substrate can be demonstrated also among patients with "lone" AF. Interatrial conduction slowing is likely to characterize patients with paroxysmal atrial fibrillation (AF) and it could be correlated to the left atrium area of prolonged local bipolar endocardial electrograms. P-wave duration (PWD), amplified PWD and endocavitary interatrial conduction time (IACT), were analyzed in 60 patients; 30 undergoing de novo ablation for paroxysmal AF with normal atrial volumes and without any other cardiac disease and 30 of similar age undergoing electrophysiological study for atrioventricular nodal reentrant tachycardia or atrioventricular re- entrant tachycardia. In patients with AF, voltage maps and local bipolar electrograms (LBE) duration map were evaluated. Although PWD was <120 ms in 28 patients with AF and in 29 controls, patients with AF exhibited longer PWD, amplified-PWD and IACT. Although low-voltage areas (<0.5 mV) were not found in the study population, 28 of them demonstrated areas with LBE longer than 60 ms. These LBE were found mainly in the roof of the left atrium and their extension was correlated to IACT (R = 0.51, p = 0.004). IACT >135.5 ms identified the subjects who experienced AF with 90% sensitivity and 97% specificity. A subclinical interatrial conduction disturbance is demonstrable in subjects with paroxysmal AF and normal left atrial volume. IACT has a good correlation to the areas of abnormal LBE in the left atrium. IACT >135 ms identified subjects who have experienced AF.


Sedentary behavior: Different types of operationalization influence outcome measures.
Sedentary behavior (SB) influences health status independently of physical activity. The formal definition of SB is: "any waking behavior characterized by an energy expenditure ≤1.5 METs while in a sitting or reclining posture". However, measuring SB mostly does not include both the intensity and postural component. The aim of this study was to quantify the effect of type of operationalization of SB on total sedentary time and the pattern of SB. 53 healthy subjects were measured 24h with a multi-sensor activity monitor that provides a valid one-second detection of body postures and movements and a calculated intensity measure. The SB outcome measures were: total sedentary time; number of sedentary bouts; mean bout length; fragmentation; and W-index. All outcomes were calculated for three types of operationalization of SB: 1) waking time in lying and sitting posture and below the sedentary intensity threshold (<0.016g comparable with Actigraph <150 counts, COMBI); 2) waking time in lying and sitting posture (POST); 3) waking time below the sedentary intensity threshold (<0.016g, INT). Outcome measures based on these three operationalizations were compared with repeated measures ANOVA. Total sedentary time was significantly different (p<0.001) between all three conditions: 505.8 (113.85)min (COMBI), 593.2 (112.09)min (POST), and 565.5 (108.54)min (INT). Significant differences were also found for other outcome measures. Our study shows that type of operationalization significantly affects SB outcome measures. Therefore, if SB is defined according to the formal definition, measurements must include both the intensity and postural component.


Decidual NK Cells Transfer Granulysin to Selectively Kill Bacteria in Trophoblasts.
Maternal decidual NK (dNK) cells promote placentation, but how they protect against placental infection while maintaining fetal tolerance is unclear. Here we show that human dNK cells highly express the antimicrobial peptide granulysin (GNLY) and selectively transfer it via nanotubes to extravillous trophoblasts to kill intracellular Listeria monocytogenes (Lm) without killing the trophoblast. Transfer of GNLY, but not other cell death-inducing cytotoxic granule proteins, strongly inhibits Lm in human placental cultures and in mouse and human trophoblast cell lines. Placental and fetal Lm loads are lower and pregnancy success is greatly improved in pregnant Lm-infected GNLY-transgenic mice than in wild-type mice that lack GNLY. This immune defense is not restricted to pregnancy; peripheral NK (pNK) cells also transfer GNLY to kill bacteria in macrophages and dendritic cells without killing the host cell. Nanotube transfer of GNLY allows dNK to protect against infection while leaving the maternal-fetal barrier intact.


Molecular analysis of intraspousal transmission of hepatitis C virus.
Although intraspousal transmission of hepatitis C virus (HCV) has been speculated, there is no direct evidence. To investigate whether transmission of HCV occurs by this route, 295 spouses of persons diagnosed with HCV were studied. Of these, 25 (8.8%) tested positive for anti-HCV. Next, the HCV genotype was determined by polymerase chain reaction using a mixed primer set, and cDNA was obtained in 17 of the 25 couples for comparison of the genotypes. Of these 17, 14 (82.4%) spouses were shown to be infected with HCV of the same genotype. Analysis of the nucleotide sequences of putative E1 gene of eight couples having the same HCV genotype revealed that five couples had remarkably high nucleotide sequence homologies (> 97%), whereas samples obtained from the remaining three couples showed relatively low homology (91-92%). Nucleotide sequence homologies were significantly higher between spouses than between non-spouse pairs of isolates. Phylogenetic analysis using the neighbor-joining method suggests that infection in these five couples probably occurred after marriage. Furthermore, none of the five couples had shared other possible transmission routes such as intravenous drug use, dental treatment or acupuncture. These data strongly suggest the occurrence of intraspousal transmission of HCV.


Cellulase-Hemicellulase Activities and Bacterial Community Composition of Different Soils from Algerian Ecosystems.
Soil microorganisms are important mediators of carbon cycling in nature. Although cellulose- and hemicellulose-degrading bacteria have been isolated from Algerian ecosystems, the information on the composition of soil bacterial communities and thus the potential of their members to decompose plant residues is still limited. The objective of the present study was to describe and compare the bacterial community composition in Algerian soils (crop, forest, garden, and desert) and the activity of cellulose- and hemicellulose-degrading enzymes. Bacterial communities were characterized by high-throughput 16S amplicon sequencing followed by the in silico prediction of their functional potential. The highest lignocellulolytic activity was recorded in forest and garden soils whereas activities in the agricultural and desert soils were typically low. The bacterial phyla Proteobacteria (in particular classes α-proteobacteria, δ-proteobacteria, and γ-proteobacteria), Firmicutes, and Actinobacteria dominated in all soils. Forest and garden soils exhibited higher diversity than agricultural and desert soils. Endocellulase activity was elevated in forest and garden soils. In silico analysis predicted higher share of genes assigned to general metabolism in forest and garden soils compared with agricultural and arid soils, particularly in carbohydrate metabolism. The highest potential of lignocellulose decomposition was predicted for forest soils, which is in agreement with the highest activity of corresponding enzymes.


Hemoconcentration is a good prognostic predictor for clinical outcomes in acute heart failure: data from the Korean Heart Failure (KorHF) Registry.
Hemoconcentration is a surrogate marker of effective decongestion and diuresis therapy. Recently, hemoconcentration has been associated with decreased mortality and rehospitalization in heart failure (HF) patients. However, the prognostic power of hemoconcentration in a large sample-sized HF cohort was limited until now. We analyzed data from hospitalized patients with acute heart failure (AHF) that were enrolled in the Korean Heart Failure Registry(n=2,357). The primary end point was a composite of all-cause mortality and HF rehospitalization during the follow-up period (median=347, interquartile range=78-744 days).Hemoconcentration, defined as an increased hemoglobin level between admission and discharge, was presented in 1,016 AHF patients (43.1%). In multivariable logistic regression, hemoglobin, total cholesterol, and serum glucose levels at admission, and ischemic HF, were significant determinants for hemoconcentration occurrence. The Kaplan-Meier curve showed that event-free survival was significantly higher in the hemoconcentration group compared to the non-hemoconcentration group (65.1% vs. 58.1%, log rank p<0.001). In multiple Cox proportional hazard analysis, hemoconcentration was an independent predictor of the primary end point after adjusting for other HF risk factors (hazard ratio=0.671, 95% confidence interval=0.564-0.798, p<0.001). Hemoconcentration during hospitalization was a prognostic marker of fewer clinical events in the AHF cohort. Therefore, this novel surrogate marker will help in the risk stratification of AHF patients.


Intravenous regional analgesia.
Despite its introduction in 1908, the technique of intravenous regional analgesia did not achieve popularity until it was reintroduced by Holmes in 1963. This simple technique has proved its usefulness in most operative and manipulative procedures on the extremities, including suture of lacerations, tendon repair, abscess incision and fracture work. It is more often used in the upper limb, as the arm requires a lesser total dose of the local anaesthetic agent, and does not have the same potential for precipitation of vascular pathology.


The effect of sex and protein supplementation on bone metabolism during a 36-h military field exercise in energy deficit.
This study investigated sex differences in, and the effect of protein supplementation on, bone metabolism during a 36-h military field exercise. Forty-four British Army Officer cadets (14 women) completed a 36-h field exercise. Participants consumed either their habitual diet [n = 14 women (Women) and n = 15 men (Men Controls)] or the habitual diet with an additional 46.6 g·day-1 of protein for men [n = 15 men (Men Protein)]. Women and Men Protein were compared with Men Controls to examine the effect of sex and protein supplementation. Circulating markers of bone metabolism were measured before, 24 h after (postexercise), and 96 h after (recovery) the field exercise. Beta C-telopeptide cross links of type 1 collagen and cortisol were not different between time points or Women and Men Controls (P ≥ 0.094). Procollagen type I N-terminal propeptide decreased from baseline to postexercise (P < 0.001) and recovery (P < 0.001) in Women and Men Controls. Parathyroid hormone (PTH) increased from baseline to post-exercise (P = 0.006) and decreased from postexercise to recovery (P = 0.047) in Women and Men Controls. Total 25(OH)D increased from baseline to postexercise (P = 0.038) and recovery (P < 0.001) in Women and Men Controls. Testosterone decreased from baseline to post-exercise (P < 0.001) and recovery (P = 0.007) in Men Controls, but did not change for Women (all P = 1.000). Protein supplementation in men had no effect on any marker. Men and women experience similar changes to bone metabolism-decreased bone formation and increased PTH-following a short-field exercise. Protein had no protective effect likely because of the energy deficit.NEW & NOTEWORTHY Energy deficits are common in arduous military training and can cause disturbances to bone metabolism. This study provides first evidence that short periods of severe energy deficit and arduous exercise-in the form of a 36-h military field exercise-can suppress bone formation for at least 96 h, and the suppression in bone formation was not different between men and women. Protein feeding does not offset decreases in bone formation during severe energy deficits.


Signal transmission and transduction in excitation-contraction coupling.
For the better understanding of the molecular mechanism of E-C coupling, two key questions remain to be resolved: (a) how the excitation signal elicited in the T-tubule membrane is transmitted to the ryanodine receptor, RyR (signal transmission), and (b) how the signal transmitted from the T-tubule to the RyR is translated into the action of opening the sarcoplasmic reticulum Ca2+ channel to induce Ca2+ release and muscle contraction (signal transduction). Our recent studies on E-C coupling with the use of the isolated triads and synthetic peptides have provided several pieces of new information. It appears that the signal transmission is mediated by the voltage-controlled binding of the Thr671-Leu690 region (Trigger) of the cytoplasmic II-III loop of the dihydropyridine receptor alpha 1 a subunit to the putative activator site on the RyR. The transmitted signal is translated to the action of channel opening by mediation of rapid conformational changes occurring in the RyR. Upon T-tubule polarization the Glu724-Pro760 region of the loop (Blocker) replaces the RyR-bound Trigger. This reprimes the RyR to the original conformational state.


TSPO acts as an immune resistance gene involved in the T cell mediated immune control of glioblastoma.
Glioblastoma (GB) IDH-wildtype is the most malignant primary brain tumor. It is particularly resistant to current immunotherapies. Translocator protein 18 kDa (TSPO) is upregulated in GB and correlates with malignancy and poor prognosis, but also with increased immune infiltration. Here, we studied the role of TSPO in the regulation of immune resistance of human GB cells. The role of TSPO in tumor immune resistance was experimentally determined in primary brain tumor initiating cells (BTICs) and cell lines through genetic manipulation of TSPO expression and subsequent cocultures with antigen specific cytotoxic T cells and autologous tumor-infiltrating T cells. Death inducing intrinsic and extrinsic apoptotic pathways affected by TSPO were investigated. TSPO-regulated genes mediating apoptosis resistance in BTICs were identified through gene expression analysis and subsequent functional analyses. TSPO transcription in primary GB cells correlated with CD8+ T cell infiltration, cytotoxic activity of T cell infiltrate, expression of TNFR and IFNGR and with the activity of their downstream signalling pathways, as well as with the expression of TRAIL receptors. Coculture of BTICs with tumor reactive cytotoxic T cells or with T cell-derived factors induced TSPO up-regulation through T cell derived TNFα and IFNγ. Silencing of TSPO sensitized BTICs against T cell-mediated cytotoxicity. TSPO selectively protected BTICs against TRAIL-induced apoptosis by regulating apoptosis pathways. TSPO also regulated the expression of multiple genes associated with resistance against apoptosis. We conclude that TSPO expression in GB is induced through T cell-derived cytokines TNFα and IFNγ and that TSPO expression protects GB cells against cytotoxic T cell attack through TRAIL. Our data thereby provide an indication that therapeutic targeting of TSPO may be a suitable approach to sensitize GB to immune cell-mediated cytotoxicity by circumventing tumor intrinsic TRAIL resistance.


proTRH gene expression by fetal pancreatic islets in culture.
The hypothalamic tripeptide, thyrotropin-releasing hormone (TRH), has been detected in neonatal pancreatic tissue and localized by immunocytochemistry in the islets of Langerhans. To determine whether the TRH gene is expressed in islets, we have extracted RNA from cultured rat islets and probed for proTRH mRNA using a [32P]-labeled antisense RNA. Islet proTRH mRNA comigrated with the 1.6 kilobase proTRH mRNA present in the rat hypothalamus. Normalized to total RNA, islets cultured for 7 days contained at least 10 times more proTRH mRNA than day 1 whole pancreas. We conclude that pancreatic TRH is synthesized in situ in the islets of Langerhans. This is the first attempt to characterize and quantify proTRH mRNA using neoformed foetal islets. We propose that quantitative analysis of proTRH mRNA concentrations in this culture system will enable study of the direct regulation of TRH biosynthesis in the pancreas.


Kawasaki disease: monitoring of circulating immune complexes.
We followed the levels of circulating immune complexes (CIC) in 27 patients with Kawasaki disease (KD) from the acute stage of the disease through convalescence, using the test for platelet-reactive IgG-IC, and C1q-binding and conglutinin-binding enzyme immunoassays. CIC were detected by one or more techniques in all but one patient. Positive results were obtained most often with the test for platelet-reactive IgG-IC. Measurement of complement components C3 and C4 in 14 patients revealed an increase in C3 levels during the first few weeks of the disease and normal levels of C4. The blood platelet count correlated directly with the level of platelet-reactive IgG-IC. The highest levels of CIC were found during weeks 3 through 7 after the onset of disease. Measurement of CIC is, however, not applicable to the clinical follow-up of patients with KD.


Effect of cyclosporin A on hepatocyte proliferation after partial hepatectomy in rats: comparison with standard immunosuppressive agents.
The effects of cyclosporin A on the regenerating liver were studied in rats after partial hepatectomy and were compared with those of conventional immunosuppressants such as methylprednisolone and azathioprine. In Group I, a standard hepatectomy removing two thirds of the organ was performed. In Group II, an oral dose of 10 mg/kg of cyclosporin A was given 1 day before and immediately, 24 hours, and 48 hours after the same hepatectomy. In Groups III and IV, azathioprine and methylprednisolone were administered in 8 mg/kg doses by way of the tail vein by the same protocol as in Group II. The mortality rate, liver weight restoration, and histologic and mitotic characteristics of the liver remnants, as well as serum levels of animotransferase, total bilirubin, and creatinine were examined from 24 hours to 10 days after the operation. Azathioprine and methylprednisolone substantially suppressed hepatocyte mitosis when compared with the control group; however, cyclosporin A treatment did not inhibit, but may, in fact, have stimulated liver cell proliferation. Changes in other parameters coincided with this phenomenon. The noninhibitory effect of cyclosporin A on liver regeneration has also been discussed.


Oxa-TriQuinoline: A New Entry to Aza-Oxa-Crown Architectures.
A new 15-membered-macrocyclic molecular entity, oxa-TriQuinoline (o-TQ), was designed and synthesized. In o-TQ, three oxygen atoms were joined onto three quinoline units at the 2- and 8-positions in a head-to-tail fashion by three-fold SN Ar reactions, giving rise to the characteristic N3 O3 aza-oxa-crown architecture. o-TQ can serve as a new tridentate nitrogen ligand to capture a CuI cation and adopt a bowl shape, before supramolecular complexation with corannulene and [12]cycloparaphenylene (CPP) occurs through π-π and CH-π interactions. In the presence of the CuI cation, the non-emissive o-TQ becomes a highly emissive material in the solid state, whereby the emission wavelengths depend on the ancillary ligand on the CuI cation. The o-TQ/CuI complex is able to promote carbene catalysis to provide a range of enamines with a gem-difluorinated terminus.


Biochemical evidence of platelet activation in patients with persistent unstable angina.
Thromboxane released from activated platelets and prostacyclin of the vessel wall may act as potent antagonistic modulators of platelet aggregability and coronary vascular tone. Therefore, urinary excretion of their major metabolites, 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1 alpha, was studied in 16 patients presenting with prolonged angina at rest. The 10 patients whose condition did not improve under vigorous antianginal treatment within 48 hours exhibited higher thromboxane metabolite excretion than did the 6 patients who responded to therapy (2,208 +/- 1,542 versus 609 +/- 312 ng/g creatinine; p less than 0.001). Elevated values were also found in four of eight patients with sustained postinfarction angina. Enhanced thromboxane metabolite excretion was frequently associated with angiographic evidence of thrombus formation. When nine patients were restudied in a stable phase after 11 +/- 5 months, thromboxane metabolite excretion was consistently normal or high normal. Excretion of prostacyclin metabolites was not depressed in any patient but correlated weakly with thromboxane (r = 0.41). Thus, enhanced thromboxane production as an index of platelet activation may identify patients with active thrombus formation who could benefit most from platelet inhibitory treatment.


Impact of carbon, oxygen and sulfur content of microscale zerovalent iron particles on its reactivity towards chlorinated aliphatic hydrocarbons.
Zerovalent iron (ZVI) abiotically degrades several chlorinated aliphatic hydrocarbons (CAHs) via reductive dechlorination, which offers perspectives for in situ groundwater remediation applications. The difference in reactivity between ZVI particles is often linked with their specific surface area. However, other parameters may influence the reactivity as well. Earlier, we reported for a set of microscale zerovalent iron (mZVI) particles the disappearance kinetic of different CAHs which were collected under consistent experimental conditions. In the present study, these kinetic data were correlated with the carbon, oxygen and sulfur content of mZVI particles. It was confirmed that not only the specific surface area affects the disappearance kinetic of CAHs, but also the chemical composition of the mZVI particles. The chemical composition, in addition, influences CAHs removal mechanism inducing sorption onto mZVI particles instead of dechlorination. Generally, high disappearance kinetic of CAHs was observed for particles containing less oxygen. A high carbon content, on the other hand, induced nonreactive sorption of the contaminants on the mZVI particles. To obtain efficient remediation of CAHs by mZVI particles, this study suggested that the carbon and oxygen content should not exceed 0.5% and 1% respectively. Finally, the efficiency of the mZVI particles may be improved to some extent by enriching them with sulfur. However, the impact of sulfur content on the reactivity of mZVI particles is less pronounced than that of the carbon and oxygen content.


Efficacy of Laser Acupuncture for Children With Autism Spectrum Disorder: Clinical, Molecular, and Biochemical Study.
Low-level laser acupuncture (LLLA) biostimulation could contribute to improving the symptoms and communication of children manifesting autism spectrum disorder (ASD). Photobiomodulation might influence the level of brain-derived neurotrophic factor (BDNF) and miR-320 expression. The aim was to investigate the influence of LLLA biostimulation on the severity, language abilities, BDNF levels, and miR-320 in a sample of children with ASD. The participants with ASD (N = 30) were randomly divided equally into groups: Group I received LLLA therapy twice a week for 12 sessions and Group II did not receive it. Assessments of the severity, language abilities, BDNF level by enzyme-linked immunosorbent assay, and miR-320 expression by reverse transcriptase quantitative polymerase chain reaction were performed before and after the intervention. A comparison between ASD cases (N = 30) before starting the therapy and neurotypical children (N = 15) regarding miR-320 expression was performed. Following the intervention, the severity of ASD was reduced and language performance was elevated in both groups. The improvement in Group I was higher with (P = 0.002; 0.03). The plasma BDNF level was reduced only in Group I (P < 0.001). The expression level of miR-320 in Group I did not show a change (P = 0.641). A significant difference in miR-320 expression between children with ASD and the neurotypical group (P = 0.000) was observed. This study introduces LLLA therapy as a safe and promising therapeutic procedure for improving the core manifestations and communication abilities and for modulating BDNF levels in children with ASD. The reduced expression of miR-320 showed a good diagnostic value in children with ASD.


Raman spectra of gas hydrates--differences and analogies to ice 1h and (gas saturated) water.
It is generally accepted that Raman spectroscopic investigations of gas hydrates provide vital information regarding the structure of the hydrate, hydrate composition and cage occupancies, but most research is focused on the vibrational spectra of the guest molecules. We show that the shape and position of the Raman signals of the host molecules (H(2)O) also contain useful additional information. In this study, Raman spectra (200-4000 cm(-1)) of (mixed) gas hydrates with variable compositions and different structures are presented. The bands in the OH stretching region (3000-3800 cm(-1)), the O-H bending region (1600-1700 cm(-1)) and the O-O hydrogen bonded stretching region (100-400 cm(-1)) are compared with the corresponding bands in Raman spectra of ice Ih and liquid water. The interpretation of the differences and similarities with respect to the crystal structure and possible interactions between guest and host molecules are presented.


Predicting the packing parameter for lipids in monolayers with the use of molecular dynamics.
Lipid molecules form the backbone of biological membranes. Due to their amphiphilic structure, they can self-organize in a plethora of different structures when in contact with water. The type of self-assembled structure and its curvature depend on so-called shape factor or critical packing parameter, CPP, that can be derived knowing the molecular volume of a lipid (V), optimal surface area (a0) and critical chain length (lc) (see Intermolecular and Surface Forces by Jacob N. Israelachvili, Third Edition, 2011). The value of CPP allows not only to predict the type of self-assembled structure but also is a key factor for molecular interactions, which play a great role both in physiological and pathological conditions. The greatest difficulties arise when calculating the a0 parameter, and although for some typical membrane lipids these values have been determined, there are a number of derivatives for which this parameter, and thus CPP, are unknown. The value of CPP allows not only to predict the type of self-assembled structure but also is a key factor for molecular interactions, which play a great role both in physiological and pathological conditions. So far, the determination of the packing parameter required the use of theoretical models with assumptions deviating from the physical conditions. Here we report a method based on molecular dynamics, which was applied to simulate lipid membranes consisting of cholesterol, oxysterols, sphingolipids, phosphatidylcholines, and phosphatidylethanolamines. For lipid molecules for which CPPs have already been determined, high compliance has been demonstrated. This proves that the method presented herein can be successfully used to determine packing parameters for other membrane lipids and amphiphilic molecules.


Enzymhistochemical evaluation of ulnar nerve grafts in brachial plexus lesions.
Our concept for the reconstruction of brachial plexus injuries includes an intercostal nerve transfer to the vascularized ulnar nerve graft. A free neurovascular latissimus dorsi is then transferred in a second stage operation. For optimization of the regeneration result, the operative planning of the second step includes nerve biopsies and enzymhistochemical evaluation for the distribution of motor axons. The staining method according to Scabolcz et al. is described and clinical cases are presented.


The calcium channel Orai1 is required for osteoblast development: Studies in a chimeric mouse with variable in vivo Runx-cre deletion of Orai-1.
The calcium-selective ion channel Orai1 has a complex role in bone homeostasis, with defects in both bone production and resorption detected in Orai1 germline knock-out mice. To determine whether Orai1 has a direct, cell-intrinsic role in osteoblast differentiation and function, we bred Orai1 flox/flox (Orai1fl/fl) mice with Runx2-cre mice to eliminate its expression in osteoprogenitor cells. Interestingly, Orai1 was expressed in a mosaic pattern in Orai1fl/fl-Runx2-cre bone. Specifically, antibody labeling for Orai1 in vertebral sections was uniform in wild type animals, but patchy regions in Orai1fl/fl-Runx2-cre bone revealed Orai1 loss while in other areas expression persisted. Nevertheless, by micro-CT, bones from Orai1fl/fl-Runx2-cre mice showed reduced bone mass overall, with impaired bone formation identified by dynamic histomorphometry. Cortical surfaces of Orai1fl/fl-Runx2-cre vertebrae however exhibited patchy defects. In cell culture, Orai1-negative osteoblasts showed profound reductions in store-operated Ca2+ entry, exhibited greatly decreased alkaline phosphatase activity, and had markedly impaired substrate mineralization. We conclude that defective bone formation observed in the absence of Orai1 reflects an intrinsic role for Orai1 in differentiating osteoblasts.


Quantum-mechanical characteristics of apigenin: Antiradical, metal chelation and inhibitory properties in physiologically relevant media.
Density functional theory was used to examine the antioxidant activity of apigenin. All protonated species that are present in a non-negligible population at physiological pH were considered in the study. The ability to scavenge the hydroperoxide radical was evaluated in lipid and aqueous environments. The capacity to halt the Fenton reaction by chelating Fe(III) and Cu(II) ions was also investigated, as was the ability to inhibit xanthine oxidase. The results indicate that these activities may be particularly important in describing the beneficial effects of apigenin, especially because of its lower anti-•OOH potential than Trolox or vitamin C. The findings underscore the significant role of dianion in the antiradical and chelating properties, despite its presence in much lower molar fractions than other ions.


Gene expression profile changes in Eisenia fetida chronically exposed to PFOA.
Eisenia fetida is a terrestrial organism, which can be used to diagnose sub-lethal concentrations of PFOA by using molecular biomarkers. In order to identify potential molecular biomarkers, we have exposed E. fetida to 10 mg/kg of PFOA in soil for 8 months. The mRNA isolation, sequencing, transcriptome assembly followed by differential gene expression studies have revealed that genes that are involved in apoptotic process, reproduction, calcium signalling, neuronal development and lipid metabolism are predominantly affected. Highly specific genes that are altered by PFOA can be further validated and used as biomarker to detect sub-lethal concentrations of PFOA in the soil.


Copper(II)/phenanthroline-mediated CD-enhancement and chiral memory effect on a meta-ethynylpyridine oligomer.
meta-Ethynylpyridine 18-mer associates with octyl β-D-glucopyranoside to show an induced circular dichroism (CD) band at around 337 nm in CH(2)Cl(2). The addition of copper(II) triflate and o-phenanthroline enhanced the CD band. Even when an equimolar amount of β-L-glucopyranoside was added to make the system racemic, the CD was memorized and remained for several weeks.


[Eco-physiological studies on desert plants : VI. Germination and growth inhibitors in the fruits of Zilla spinosa Prantl].
1. The germination of Lepidium sativum seeds is inhibited by the water extract from pericarps of Zilla spinosa. This inhibitory effect is reversible. Irradiation of the extract with UV showed no influence on the inhibitory effects of the extract. On the other hand, boiling the extract (of high concentration) reduces the inhibitory effect to a great extent. The inhibition was found not to be due to the osmotic influence of the extract. 2. Similar inhibitory effects of the extract were obtained with the seeds of Zilla spinosa. 3. Using organic solvents it is possible to distinguish between promotors and inhibitors of germination and growth. The substances promoting the linear growth, specially of the root, and the dry matter production are separated by organic solvents. 4. Pericarp extracts of old fruits shed from the mother plant a long time ago have less inhibitory effect on germination. However, these extracts promote the linear growth of the seedlings. In other words, the growth promoting substance (or substances) are not affected by aging whereas the germination inhibitors are partly destroyed or removed. 5. The ecological importance of the presence of germination and growth inhibitors and promoters is discussed.


Enhanced ability of skeletal muscle containing cyclocreatine phosphate to sustain ATP levels during ischemia following beta-adrenergic stimulation.
Breast muscle of young chicks fed chow diets containing the creatine analog 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine) accumulated up to 40 mumol/g wet weight of the synthetic phosphagen 1-carboxymethyl-2-imino-3-phosphonoimidazolidine (cyclocreatine-P2-). ATP levels were sustained at high values substantially longer in breast muscle of cyclocreatine-fed chicks, compared to control-fed chicks, during total ischemia initiated 2 h after injection of both groups with the beta-adrenergic agonist isoproterenol (5 mg/kg subcutaneous). For example, in chicks fed 0.5% cyclocreatine for 10-19 days ATP levels in isoproterenol-stimulated breast muscles after 1 h of ischemia at 37 degrees C were 6.1 mumol/g, compared to 1.9 mumol/g for the control-fed group, and after 2 h of ischemia were 3.5 mumol/g compared to 0.6 mumol/g for controls. Creatine-P reserves in isoproterenol-stimulated breast muscles of all dietary groups were essentially exhausted within the first hour of ischemia. In contrast, breast muscle of chicks fed either 1 or 0.5% cyclocreatine still contained 28 and 19 mumol/g of cyclocreatine-P, respectively, after 1 h of ischemia; after 2 h of ischemia, the respective cyclocreatine-P values were 20 and 13 mumol/g. Isoproterenol-stimulated chick breast muscle provides the first skeletal muscle model system for studying the molecular mechanisms by which dietary cyclocreatine helps sustain ATP levels during ischemia. Although adaptive factors are also involved, it is suggested that a significant portion of the ATP-sustaining activity of dietary cyclocreatine in ischemic breast muscle can be attributed to the unique thermodynamic properties of the accumulated cyclocreatine-P. These properties enable cyclocreatine-P to continue to thermodynamically buffer the adenylate system and transport high energy phosphate throughout the long muscle fibers at cytosolic pH values and phosphorylation potentials well below the range where the creatine-P system can function effectively. Synergism between glycolysis and this long-acting synthetic phosphagen might well help delay depletion of ATP levels in skeletal muscles during ischemia. Cyclocreatine feeding provides a unique experimental tool for quantitative evaluation of the proposed protective role of ATP against irreversible cellular damage in skeletal and cardiac muscles during ischemic episodes.


Validity of the Postoperative Morbidity Survey after abdominal aortic aneurysm repair-a prospective observational study.
Currently, there is no standardised tool used to capture morbidity following abdominal aortic aneurysm (AAA) repair. The aim of this prospective observational study was to validate the Postoperative Morbidity Survey (POMS) according to its two guiding principles: to only capture morbidity substantial enough to delay discharge from hospital and to be a rapid, simple screening tool. A total of 64 adult patients undergoing elective infrarenal AAA repair participated in the study. Following surgery, the POMS was recorded daily, by trained research staff with the clinical teams blinded, until hospital discharge or death. We modelled the data using Cox regression, accounting for the competing risk of death, with POMS as a binary time-dependent (repeated measures) internal covariate. For each day for each patient, 'discharged' (yes/no) was the event, with the elapsed number of days post-surgery as the time variable. We derived the hazard ratio for any POMS morbidity (score 1-9) vs. no morbidity (zero), adjusted for type of repair (endovascular versus open), age and aneurysm size. The hazard ratio for alive discharge with any POMS-recorded morbidity versus no morbidity was 0.130 (95 % confidence interval 0.070 to 0.243). The median time-to-discharge was 13 days after recording any POMS morbidity vs. 2 days after scoring zero for POMS morbidity. Compliance with POMS completion was 99.5 %. The POMS is a valid tool for capturing short-term postoperative morbidity following elective infrarenal AAA repair that is substantial enough to delay discharge from hospital. Daily POMS measurement is recommended to fully capture morbidity and allow robust analysis. The survey could be a valuable outcome measure for use in quality improvement programmes and future research.


Acetylcholine receptor antibody in myasthenia gravis: purification and characterization.
Acetylcholine receptor antibody was measured in serum and IgG fractions from patients with myasthenia gravis using different analyses for antibody interfering with the toxin binding site and for antibody directed against other sites. No correlation was found between the concentration of receptor antibody as measured with the two assays. The different antibody activities also showed different isoelectric spectra. Receptor antibody was purified about 1000 times from IgG by affinity chromatography on a partially purified human skeletal muscle receptor preparation. The purified antibody was homogeneous in SDS-gel electrophroesis and showed a polyclonal pattern in agarose gel electrophoresis and isoelectric focusing. Both kinds of light chains were demonstrated. The results imply that the acetylcholine receptor antibody found in myasthenia gravis is heterogeneous and of multiclonal origin.


Nomograms for Predicting Overall and Recurrence-free Survival From Pathologic Stage IA and IB Lung Cancer After Lobectomy.
Stage I non-small-cell lung cancer (NSCLC) is potentially curable with surgical resection. Significant proportions of patients may still experience recurrence and death despite undergoing curative surgery. This study describes predictive nomograms for recurrence-free (RFS) and overall survival (OS) after lobectomy. A total of 301 patients with the American Joint Committee on Cancer pathologic stage IA and IB NSCLC who underwent open, thoracoscopic, or robotic lobectomy from January 2011 to April 2017 were analyzed. Multivariate Cox proportional hazards regression models were used to create nomograms for OS and RFS. Kaplan-Meier survival curves were calculated for OS and RFS comparing high-risk and low-risk cohorts based on nomogram scores. Histology (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.10-0.56; P = .002), lymphovascular invasion (HR, 0.46; 95% CI, 0.29-0.74; P = .001), smoking status (HR, 3.46; 95% CI, 1.25-9.55: P = .02), and total lymph nodes removed (HR, 1.05; 95% CI, 1.01-1.10; P = .021) were significant predictors for OS in a multivariate model. Lymphovascular invasion (HR, 0.55; 95% CI, 0.36-0.83; P = .0040), smoking status (HR, 2.56; 95% CI, 1.16-5.62; P = .02), total lymph nodes removed (HR, 1.04; 95% CI, 1.00-1.08; P = .029), and tumor size (HR, 1.30; 95% CI, 1.30-1.68; P = .047) were significant predictors of RFS in a multivariate model. Nomograms can predict OS and RFS for pathologic stage IA and IB NSCLC after lobectomy regardless of operative approach. The risk for death and recurrence after stratification by the nomogram scores may provide guidance regarding adjuvant therapy and surveillance.


Ubiquitin biology: an old dog learns an old trick.
Regulated protein degradation in eukaryotes occurs principally through covalent tagging of substrates with ubiquitin, thereby targeting them for destruction by 26S proteasomes. Classical allostery has now been added to the repertoire of mechanisms that can modulate ubiquitin tagging, allowing feed-forward regulation to be achieved through targeted protein destruction.


Measuring the perceived content of auditory objects using a matching paradigm.
Two previous studies manipulated spatial cues to alter the perceptual organization of a sound mixture containing an ambiguous sound element (a pure tone; the "target") that could belong to two competing auditory objects (a sequential tone stream and a simultaneous harmonic complex). In both studies, the sum of the contributions of the target to the two objects was less than the physical target level in the mixture. However, many listeners had difficulties making consistent judgments about the perceptual contribution of the target to the harmonic complex. The current study used stimuli similar to those used in the previous study, but with a target made up of five tones rather than a single pure tone. In addition, listeners performed a direct matching task to indicate the perceptual contribution of the target to the competing objects rather than relying on an indirect mapping procedure. The matching task proved to be efficient and reliable. However, the complex-tone target was perceptually stronger in the harmonic complex and weaker in the sequential tone stream than in past studies. As a result, the sum of the target contributions to the two objects roughly equaled the physical target level for all tested spatial configurations, unlike in the previous studies.


Influence of bias electric field on elastic waves propagation in piezoelectric layered structures.
Theoretical and computer investigations of acoustic wave propagation in piezoelectric layered structures, subjected to the dc electric field influence have been fulfilled. Analysis of the dispersive parameters of elastic waves propagation in the BGO/fused silica and fused silica/LiNbO3 piezoelectric layered structures for a number of variants of dc electric field application has been executed. Transformation of bulk acoustic wave into SAW type mode under the dc electric field influence has been found. Possibility to control the permission or prohibition of the wave propagation by the dc electric field application and the appropriate choice of the layer and substrate materials has been discussed.


Reflexions about imaging technique and examination protocol 1. Computed tomography.
Computed tomography as imaging technique is established since decades, especially in examinations of the orbit. New technical development of multi-slice helical CT requires new attention, concerning radiation burden. Always asked is the use of contrast material in orbital examination. Indications and contraindications are discussed.


An in situ hybridization technique for the study of B19 human parvovirus replication in bone marrow cell cultures.
An in situ hybridization technique using digoxigenin labelling was developed to study B19 infection. By using appropriate DNA probes, transcription of structural and non-structural genes was detected in bone marrow cell cultures. Such a simple system is useful to the study of B19-cell interactions in non-permissive cell lines.


Congenital cataract facial dysmorphism neuropathy syndrome: a clinically recognizable entity.
Congenital cataracts facial dysmorphism neuropathy syndrome is a recently delineated autosomal recessive condition exclusively found in the Gypsy population. Congenital cataracts facial dysmorphism neuropathy syndrome is caused by a homozygous mutation in the CTDP1 gene, leading to disruption of the ribonucleic acid transcription machinery. This report presents a young Gypsy female affected by this rare disorder. Electromyography and sural nerve histology were in accordance with a hypomyelinating neuropathy. After clinical recognition of congenital cataracts facial dysmorphism neuropathy syndrome some years ago, we recently demonstrated the presence of the homozygous IVS6+389C-->T mutation in the CTDP1 gene in this family.


Effectiveness of low-level gallium aluminium arsenide laser therapy for temporomandibular disorder with myofascial pain: A systemic review and meta-analysis.
Temporomandibular disorder (TMD) causes masticatory muscle pain and mouth opening limitations and affects patients' ability to eat, practice oral health and perform other activities of daily living. Although the benefits of low-energy lasers in treating TMD have been reported, the results vary greatly depending on the equipment used and the energy output. This study systematically evaluated the efficacy of a low-level gallium aluminium arsenide (GaAlAs) laser treatment for TMD with myofascial pain and maxillary pain. We searched the PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov databases for randomized controlled trials (RCTs) published since database inception to April 5, 2020, that compared low-level laser treatment to sham/placebo treatment or no intervention in patients suffering from TMD with myofascial pain. Three reviewers independently screened the literature, extracted data, and assessed the quality of the included studies according to the risk-of-bias tool recommended by the Cochrane Handbook V.5.1.0 (Cochrane Collaboration, London, UK). Then, a meta-analysis was performed using RevMan 5.3 and Stata 15.1 software. The data from 8 randomized controlled trials including 181 patients were analyzed. The severity of myofascial TMD pain (measured on a visual analogue scale, VAS) at the end of treatment was significantly different between the control laser therapy and the low-level GaAlAs laser therapy (weighted mean difference [WMD] = -0.76, 95% confidence interval [CI] -1.51 to 0.01, P = .046); at 3 to 4 weeks after treatment, there was no significant difference (WMD = 1.24, 95% CI -0.04 to 2.51, P = .057). In addition, there was no significant improvement in maximum mouth opening (MMO) at the end of treatment (WMD = -0.03, 95% CI -4.13 to 4.06, P = .987) or at 3 to 4 weeks after treatment (WMD = 1.22, 95% CI -2.94 to 5.39, P = .565). The results of this study suggest that there is insufficient evidence to indicate an efficacy of low-level GaAlAs laser therapy in improving TMD pain and maximal oral opening. These results suggest that clinicians should make appropriate recommendations to inform patient decision-making.


Elimination of inappropriate axonal branches of regenerating cockroach motor neurons as detected by the retrograde transport of horseradish peroxidase conjugated wheat germ agglutinin.
A procedure is described for identifying the motor neurons innervating individual cockroach muscles by use of the retrograde transport of extracellularly injected horseradish peroxidase and the staining of cells in whole mount preparations. A modification of this procedure using wheat germ agglutinin covalently conjugated to horseradish peroxidase is required in order to identify regenerating motor neurons that have an axonal process that had regrown into a particular leg muscle at various times after axotomy. At early stages of regeneration 23 out of 31 axotomized motor neurons with axons leaving the metathoracic ganglion through nerve root 5 send an axonal process into muscle 178. In intact animals this muscle receives innervation from only one motor neuron, Df. At later stages of regeneration these inappropriate axonal branches become eliminated until this muscle is again innervated only by Df. These results indicate that the specificity required for the reformation of the original innervation pattern of the leg muscles does not come from factors which are components of paths along the nerve root or which are being released from denervated muscles which could selectively control the direction of growth of axons of particular motor neurons.


The Elbmarsch leukemia cluster: are there conceptual limitations in controlling immission from nuclear establishments in Germany?
The childhood leukemia cluster in the proximity of the German nuclear establishments of Geesthacht is unique in its spatial and temporal concentration. After a steep increase in cases in 1990, the cluster continues to show a significant increase up to the present. Early investigations of blood samples from a casual sample of local residents showed an increase in dicentric chromosomes in lymphocytes, indicating exposure exceeding dose limits. Analyses of the immission data revealed several unexpected deliveries of fission and activation products in the environment but provided no explanation of the source. Because of the observed overdispersion of dicentric chromosomes in cells, the idea of a contribution by densely ionizing emitters was compelling. The routine programs, however, do not include alpha emitters. These were measured in specific studies that proved contamination by transuranic nuclides. As shown in the present investigation, routine environmental surveillance programs support the occurrence of an accidental event near Geesthacht in September 1986. Until now, neither the cause nor the complete scenario of the activity release could be established. The ongoing discussion highlights limitations in the immission-control concept, which is predominantly based on gamma-radiation monitoring.


LCPT once-daily extended-release tacrolimus tablets versus twice-daily capsules: a pooled analysis of two phase 3 trials in important de novo and stable kidney transplant recipient subgroups.
African-American and elderly kidney transplant recipients (KTR) have increased risk for poor clinical outcomes post-transplant. Management of immunosuppression may be challenging in these patients and contribute to worse outcomes. A novel once-daily formulation of tacrolimus (LCPT) has demonstrated noninferiority, similar safety, improved bioavailability, a consistent concentration time profile, and less peak and peak-trough fluctuations vs. tacrolimus twice-daily (Tac BID). This pooled analysis of two phase 3 randomized, controlled trials, including 861 (LCPT N = 428; Tac BID N = 433; 38% of patients were stable KTR, and 62% were de novo KTR) patients, examined the efficacy of LCPT in KTR subgroups (blacks, females, and age ≥65). Overall, treatment failure [death, graft failure, centrally read biopsy-proven acute rejection (BPAR), or lost to follow-up] at 12 months was as follows: LCPT: 11.9%, BID Tac: 13.4% [-1.48% (-5.95%, 2.99%)]. BPAR rates were as follows: LCPT: 8.2%, Tac BID: 9.5% [-1.29% (-5.14%, 2.55%)]. Numerically, fewer treatment failure events with LCPT were found in the majority of subgroups, with significantly less treatment failure associated with LCPT among black KTR [-13.82% (-27.22%, -0.31%)] and KTR ≥65 [-13.46% (-25.27%, -0.78%)]. This pooled analysis suggests numerically lower efficacy failure rates associated with LCPT among high-risk subgroups, in particular black KTR and KTR ≥65 years old.


Vasovagal syncope related to emotional stress predicts coronary events in later life.
The aim of the study was to assess whether history of vasovagal syncope (VVS) mediated by emotional (emotional VVS) or orthostatic stress (orthostatic VVS) is associated with an increased risk of cardiovascular (CV) events in later life. Retrospective analysis based on medical records of the consecutive 3,288 cardiologic outpatients (mean age, 61 ± 12 years; 43% men). A total of 254 patients (7.7%) reported emotional VVS, whereas 294 (9.0%) had history of orthostatic VVS. First-ever syncopal episode was reported at a median age of 16 years (interquartile range [IQR], 12 years to 28 years), and the median total number of episodes was two (IQR, 1 to 5). There were 779 patients (23.7%) with at least one CV event, and the median age for the first CV event was 59 years (IQR, 52 years to 67 years). In the fully adjusted model, history of emotional VVS was predictive of CV event (hazard ratio [95% confidence interval]: 1.63, [1.27-2.09]; P < 0.001), myocardial infarction (1.99, [1.49-2.66]; P < 0.001), and percutaneous coronary intervention (1.84, [1.31-2.60]; P = 0.001). There was one significant interaction (P = 0.07) between history of emotional VVS and gender. Emotional VVS was predictive of CV event in men (1.89 [1.41-2.53]; P < 0.001) but not in women (1.24 [0.79-1.94]; P = 0.35). History of emotional but not orthostatic VVS is independently associated with increased risk of coronary events in later life. The relationship between predisposition to emotional VVS in adolescence and development of cardiovascular disease requires further studies.


From courtroom to couch. Working with repressed memory and avoiding lawsuits.
Hundreds of lawsuits have been filed during the last decade against therapists who work with patient having repressed memories. These lawsuits claim that therapists are engaged in "repressed memory" therapy, which does not retrieve memories, but instead actually imparts false beliefs, which serve as "pseudo-memories". This article explores the issues of repressed, false, and implanted memories. Advice is given concerning good therapeutic practice and the avoidance of legal liability.


The effects of prenatal and postnatal environmental interaction: prenatal environmental adaptation hypothesis.
Adverse antenatal maternal environments during pregnancy influence fetal development that consequently increases risks of mental health problems including psychiatric disorders in offspring. Therefore, behavioral and brain alterations caused by adverse prenatal environmental conditions are generally considered as deficits. In this article, we propose a novel hypothesis, along with summarizing a body of literatures supporting it, that fetal neurodevelopmental alterations, particularly synaptic network changes occurring in the prefrontal cortex, associated with adverse prenatal environmental conditions may be adaptation to cope with expected severe postnatal environments, and therefore, psychiatric disorders may be able to be understood as adaptive strategies against severe environmental conditions through evolution. It is hoped that the hypothesis presented in this article stimulates and opens a new venue on research toward understanding of biological mechanisms and therapeutic treatments of psychiatric disorders.


Prevalence and clinical characteristics of sleep-disordered breathing in patients with heart failure of different left ventricular ejection fractions.
The prevalence of sleep-disordered breathing (SDB) is high in patients with heart failure (HF), while the prevalence of SDB in HF with different left ventricular ejection fractions (LVEF) has rarely been reported. We aimed to explore the prevalence and clinical characteristics of SDB in patients with HF having different LVEF. Patients with stable HF were consecutively enrolled. All patients underwent portable overnight cardiorespiratory polygraphy and echocardiography. According to their LVEF, the patients were divided into the HFrEF (HF with reduced EF, EF < 40%), HFmrEF (HF with mid-range EF, 40 ≤ EF < 50), and HFpEF groups (HF with preserved EF, EF ≥ 50%). The prevalence and clinical data of SDB among the 3 groups were then compared. A total of 252 patients, including 134 men, were enrolled in the study. The prevalence of SDB in patients with HF was 70%. Obstructive sleep apnea (OSA) was diagnosed in 48% and central sleep apnea (CSA) in 22%. The prevalence of SDB in the HFrEE, HFmrEF, and HFpEF groups was 86%, 86%, and 62%, respectively (P = 0.001). The prevalence of OSA among the 3 groups was 42%, 47%, and 49%, respectively (P = 0.708), while the prevalence of CSA among the 3 groups was 44%, 40%, and 13% (P < 0.001). Logistic regression analysis revealed that age and BMI were independent risk factors for OSA in patients with HF, while LVEF and smoking were independent risk factors for CSA in patients with HF. Correlational analyses revealed that LVEF was negatively correlated with apnea-hypopnea index (AHI) (r = -0.309, P < 0.001) and central apnea index (CAI) ( r = -0.558, P < 0.001), while there was no significant correlation with obstructive apnea index (OAI). The ROC curve revealed that LVEF could predict the occurrence of CSA and SDB, with AUC = 0.683 (95%CI 0.600-0.767, P < 0.001) and AUC = 0.630 (95%CI 0.559-0.702, P = 0.001), but not of OSA. SDB was highly common in HF, and the prevalence of SDB was different in HF with different LVEF, mainly due to the difference in cardiac functions. The prevalence and severity of SDB in HFrEF and HFmrEF were significantly higher than those in HFpEF, which was mainly related to the increase in CSA. When HFmrEF was similar to HFrEF in cardiac functions, the prevalence, type, and severity of SDB were similar between the two groups. Changes in LVEF had a significant impact on CAI, but not on OAI. LVEF can predict the occurrence of CSA and SDB to a certain extent.


Hypopigmented macules in acantholytic disorders.
Widespread hypopigmented macules are rarely seen in heavily pigmented patients with Darier's disease. Previous hypotheses concerning the cause of decreased pigmentation suggest it is a postinflammatory phenomenon or that the hypomelanosis is evidence of subclinical acantholysis. This report presents 2 patients: a new case of disseminated guttate leukoderma in a black patient with Darier's disease and the first such case in a patient with transient acantholytic dermatosis (Grover's disease). Direct immunofluorescence and electron-microscopic studies were carried out on lesional biopsies. Numerous small hypopigmented macules were observed in two black patients followed for acantholytic disorders. Three biopsies of the hypopigmented macules revealed acantholysis, while one showed only decreased melanin. Direct immunofluorescence studies were negative. Electron-microscopic studies of the leukodermic macules showed sparse melanocytes and melanosomes that were mostly pigmented stage IV melanosomes. Disseminated guttate leukoderma can occur in transient acantholytic dermatosis, as well as in Darier's disease. It is readily apparent on darkly pigmented skin because of contrast. The etiology of this phenomenon is still unknown.


Uranium distribution and radon exhalation from Brazilian dimension stones.
This paper provides evaluations of the radiometric behavior and exhalation patterns of radon gas in decorative and dimension stones explored in the Brazilian states of Minas Gerais and Espírito Santo, given the importance of determining radon gas concentrations in human-inhabited environments. A total of 10 silicate rock types were studied, featuring different petrographic/petrophysical characteristics given by seven magmatic rocks (three of which are granitic pegmatites) and three metamorphic rocks. The study, comprising radiometric data of U and monitoring of (222)Rn gas exhalation, shows a strong correlation between petrographic parameters and the physical properties of rocks. U levels ranged between 2.9 and 37 ppm, revealing a good coherence between the presence and the absence of radioactive element-bearing accessory minerals for each rock type. The rate of radon exhalation from the stones is related to the petrographic/petrophysical features of each material. By comparing the (222)Rn level generated by a rock to the amount effectively emanated by it, the rate of emanated gas proves to be insignificant; also, a rock that produces more Rn will not always emanate more. Simulations performed to estimate the radon levels inside residences or any given indoor environment showed that nine samples attained values below the 4 pCi/L EPA limit, whereas one was above that limit.


Enhancing image analytic tools by fusing quantitative physiological values with image features.
Computer-aided diagnosis systems (CADs) can quantify the severity of diseases by analyzing a set of images and employing prior statistical models. In general, CADs have proven to be effective at providing quantitative measurements of the extent of a particular disease, thus helping physicians to better monitor the progression of cancer, infectious diseases, and other health conditions. Electronic Health Records frequently include a large amount of clinical data and medical history that can provide critical information about the underlying condition of a patient. We hypothesize that the fusion of image and clinical-physiological features can be used to enhance the accuracy of automatic image classification models. In particular, this paper shows how image analytic tools can move beyond classical image interpretation models to broader systems where image and physiological measurements are fused and used to create more generic detection models. To test our hypothesis, a CAD system capable of quantifying the severity of patients with pulmonary fibrosis has been developed. Results show that CAD systems augmented with multimodal physiological values are more robust and accurate at determining the severity of the disease.


Non-Suspensionplasty by Abductor Pollicis Longus Tendon for First Carpometacarpal Osteoarthritis of the Thumb.
Many surgical procedures have been described for treating painful osteoarthritis at the carpometacarpal joint of the thumb. We describe the new nonsuspension abductor pollicis longus (APL) arthroplasty of base of the thumb after excision of trapezium. APL arthroplasty formed neojoint scapho-metacarpo-trapezoid joint. This technique is effective, technically straightforward, and appears to be robust.


Some critical comments on the paper titled "Some critical considerations in applying the construct of psychopathy to research and classification of childhood disruptive behavior disorders".
Frick (2022) presented a narrative review of some literature and made several critical comments regarding the extension of the full psychopathy construct to research and classification of childhood disruptive behavior disorders (DBDs). His arguments cautioned against the use of the multicomponent concept of psychopathy for specification of DBDs for several reasons including definitional issues, symptom sequencing, specifier versus risk factor considerations, potential overlap with other disorders and criteria (e.g., ADHD), and concerns regarding harm. While I agree with Frick (2022) that we need to be cautious when extending personality constructs to the DBDs, the remaining arguments in his paper fall short of calling for the exclusion of psychopathy components in the examination of DBDs. Rather, the counterpoints in this paper further convince that the multidimensional model of psychopathy, when applied to the DBDs, could better facilitate understanding of the etiology and mechanisms for Conduct Disorder (CD), and, it may help us to predict the prognosis and treatment outcomes of children with various forms of DBDs such as CD and Oppositional Defiant Disorder (ODD). To have the most informative designs, future research should examine the broad construct to glean a better understanding of psychopathy and the DBDs. Further, research should continue to examine sequencing and external correlates at the component level and to test the incremental value of the multicomponent model of psychopathy to help us better comprehend how each component may facilitate our understanding of the types and severity of conduct problems exhibited by youth with DBDs (i.e., CD, ODD).


Heat shock protein 90 inhibition by 17-DMAG lessens disease in the MRL/lpr mouse model of systemic lupus erythematosus.
Elevated expression of heat shock protein 90 (HSP90) has been found in kidneys and serum of systemic lupus erythematosus (SLE) patients and MRL/Mp-Fas(lpr)/Fas(lpr) (MRL/lpr) autoimmune mice. We investigated if inhibition of HSP90 would reduce disease in MRL/lpr mice. In vitro, pretreatment of mesangial cells with HSP90 inhibitor Geldanamycin prior to immune-stimulation showed reduced expression of IL-6, IL-12 and NO. In vivo, we found HSP90 expression was elevated in MRL/lpr kidneys when compared to C57BL/6 mice and MRL/lpr mice treated with HSP90 inhibitor 17-DMAG. MRL/lpr mice treated with 17-DMAG showed decreased proteinuria and reduced serum anti-dsDNA antibody production. Glomerulonephritis and glomerular IgG and C3 were not significantly affected by administration of 17-DMAG in MRL/lpr. 17-DMAG increased CD8(+) T cells, reduced double-negative T cells, decreased the CD4/CD8 ratio and reduced follicular B cells. These studies suggest that HSP90 may play a role in regulating T-cell differentiation and activation and that HSP90 inhibition may reduce inflammation in lupus.


Enhanced inulinase production by Streptomyces sp. in solid state fermentation through statistical designs.
In this work, inulinase was produced by solid state fermentation by Streptomyces sp. using copra waste as carbon source. The nutrients were screened by Plackett-Burman design. From the pareto chart it was found that the nutrients, namely, soya bean cake, MgSO4·7H2O and (NH4)2SO4 were found to be most significant nutrient components. Hence, these three components were selected for further optimization using central composite design (CCD) in response surface methodology (RSM). The optimum conditions were soya bean cake: 0.05711 g/gds, MgSO4·7H2O: 0.00063 g/gds and (NH4)2SO4: 0.00772 g/gds. Under these optimized conditions, the production of inulinase was found to be 131 U/gds. The constants in the Michaelis-Menten equation were evaluated and high R2 value implies the fitness of the model.


Downbeating nystagmus and muscle spasms in a patient with glutamic-acid decarboxylase antibodies.
To report the ophthalmic findings and response to treatment in a patient with glutamic-acid decarboxylase antibodies. Case report. A 55-year-old woman developed progressive, painful, low back muscle spasms, vertical diplopia, downbeating nystagmus, and asymmetric appendicular ataxia. Downbeating nystagmus was present in primary gaze with an alternating skew deviation in lateral gaze. Serum and cerebrospinal fluid GAD antibodies were detected. Treatment with diazepam led to resolution of spasticity, whereas repeated courses of intravenous immunoglobulin improved cerebellar function, including appendicular ataxia and downbeating nystagmus. Patients with GAD antibodies may have elements of both Stiff-person syndrome (muscle rigidity and spasms) and prominent cerebellar dysfunction. Treatment with diazepam rapidly improved Stiff-person symptoms, whereas IVIg was partially effective at the early stage of cerebellar dysfunction.


Methylene blue-mediated antimicrobial photodynamic therapy for canine dermatophytosis caused by Microsporum canis: A successful case report with 6 months follow-up.
Dermatophytosis is a superficial skin infection that widely effects companion animals. Miscrosporum canis is one of the most prevalent species isolated from dogs and cats, and because of the serious zoonotic potential, short-term treatment regimens are preferred to prevent the spread of disease either by direct contact or through contamination of the environment. Antimicrobial photodynamic therapy (APDT) has emerged as a promising strategy able to kill effectively a wide range of pathogens in a short period with minimal morbidity . In this case report, a 7-year-old male dog was diagnosed with dermatophytosis caused by M. canis. Methylene blue-mediated antimicrobial photodynamic therapy (MB-APDT) was applied over the lesions in two sessions with an interval of 7 days. The dog successfully healed, achieving a complete clinical cure after 21 days, without reports of recurrence after a follow-up period of 6 months. Therefore, MB-APDT could be a potential ally of small animal clinicians to treat superficial fungal diseases and should be further explored in Veterinary Medicine.


Isotachophoretic determination of amines from workroom air.
Eight different isotachophoretic systems for the analysis of 27 aliphatic amines are described. Complete methods including sampling and analysis procedures for the determination of eight amines in workroom air are also given. Different systems for the generation of gaseous amine standards in air are discussed, as well as sampling with washing bottles, adsorption tubes and liquid dosimeters. The methods were used in industrial environments. The isotachophoretic method is compared with gas and high-performance liquid chromatography.


Attracting and retaining nurses in HIV care.
Attracting and retaining nurses in HIV care is essential to treatment success, preventing the spread of HIV, slowing its progression, and improving the quality of life of people living with HIV. Despite the wealth of studies examining HIV care, few have focused on the factors that influenced nurses' choices to specialize in HIV care. We examined the factors that attracted and retained eight nurses currently working in HIV care in two large Canadian cities. Participants were primarily women between the ages of 20 and 60 years. Interviews were conducted between November 2010 and September 2011 using interpretive description, a qualitative design. Factors that influenced participants to focus their careers in HIV care included both attracting factors and retaining factors. Although more research is needed, this exploration of attracting and retaining factors may motivate others to specialize in HIV nursing, and thus help to promote adequate support for individuals suffering from the disease.


Magnitude of serosal changes predicts peritoneal recurrence of gastric cancer.
Peritoneal dissemination is the most frequent mode of recurrence in patients with gastric cancer. We tried to identify factors that predict peritoneal recurrence with high sensitivity. Clinical and pathologic data from 587 consecutive patients with gastric cancer were reviewed retrospectively. The stepwise Cox proportional hazards regression model was used to assess the prognostic significance of the magnitude of serosal changes. Multiple stepwise logistic regression analysis was used to determine factors associated with peritoneal recurrence in 375 patients who underwent curative resection. The 5-year survival rate of patients with S2 disease (greatest dimension of macroscopic serosal changes >/= 2.5 cm) was 18%, which was worse than S0 (no serosal changes) and S1 disease (macroscopic serosal changes < 2.5 cm)(p < 0.001). Patients with S0 tumors who underwent curative resection had the best 5-year survival rate. Multivariate analyses indicated that the magnitude of serosal changes was an independent prognostic factor for survival both overall and after curative resection. Logistic regression analysis showed that peritoneal recurrence was more than four times as likely with S2 than with S0 or S1 tumors. The sensitivity for predicting peritoneal recurrence was 79%; the sensitivity of cytologic examination was 38%. Magnitude of serosal changes is easy to measure intraoperatively and predicts peritoneal recurrence of gastric cancer with greater sensitivity than conventional peritoneal lavage cytology.


Staged total hip arthroplasty in a patient with hip dysplasia and a large pertrochanteric bone cyst.
Hip arthroplasty in young patients requires thoughtful preoperative planning. Patients with proximal femoral bone loss complicate this planning and may require a staged procedure to optimize implant insertion. We report on a case of a 26-year-old woman with secondary hip arthritis from developmental dysplasia of the hip and a large pertrochanteric bone cyst that was treated with staged total hip arthroplasty. The cyst was decompressed and filled with an osteoconductive and osteoinductive bone graft substitute called EquivaBone. One year later, the patient underwent a successful primary total hip arthroplasty. Fifteen-month follow-up after her hip replacement revealed resolution of postoperative pain and significant functional improvement.


Basophil Activation Test Shows Poor Sensitivity in Immediate Amoxicillin Allergy.
In light of the pandemic of spurious penicillin allergy, correct diagnosis of amoxicillin (AX) allergy is of great importance. The diagnosis of immediate hypersensitivity reactions relies on skin tests and specific IgE, and although reliable, these are not absolutely predictive. Therefore, drug challenges are needed in some cases, which contain the risk of severe reactions. Safe in vitro diagnostics as an alternative for the drug challenge in the diagnostic workup of AX allergy would be more than welcome to fill this gap. In this respect, the basophil activation test (BAT) has shown potential, but its clinical reliability is doubtful. To investigate the reliability of the BAT to AX and determining its exact place in the diagnostic algorithm of AX allergy. BAT for AX was performed in 70 exposed control individuals and 66 patients diagnosed according to the European Academy of Allergy and Clinical Immunology guidelines for AX allergy. Upregulation of both CD63 and CD203c was flow-cytometrically assessed. Analyses revealed that 1370 μmol/L and 685 μmol/L were the most discriminative stimulation concentrations for CD63 and CD203c upregulation, respectively, and a diagnostic threshold of 9% for positivity for both markers was identified. At these concentrations, sensitivity and specificity for CD63 upregulation were 13% and 100%, respectively, and for CD203c upregulation, 23% and 98%. BAT with dual analysis of CD63 and CD203c is of poor performance to document AX allergy. The sensitivity is too low to let it occupy a prominent role in the diagnostic algorithm.


Clozapine treatment of borderline patients: a preliminary study.
Clinicians frequently encounter patients who present with borderline personality disorder (BPD) and prolonged and/or pronounced psychotic symptoms of an atypical nature. Fifteen such patients were treated with clozapine and rerated blind to baseline symptomatology and functional level from 2 to 9 months after beginning treatment (mean = 4.2 +/- 2.1). The overall symptomatology of these patients as rated on the Brief Psychiatric Rating Scale (BPRS) decreased significantly from a mean of 57.0 +/- 10.4 to a mean of 37.8 +/- 7.7 (t = 7.03, df = 14, P = .001). Their positive, negative, and general symptoms as rated by the BPRS also decreased significantly. Additionally, their Global Assessment Scale (GAS) score increased significantly from a mean of 30.8 +/- 4.7 to a mean of 43.1 +/- 8.6 (t = 5.19, df = 14, P = .001). These results suggest that clozapine may be an effective antipsychotic agent for this subset of BPD patients. However, double-blind, placebo-controlled studies are necessary to confirm these preliminary results.


Common and distinct patterns of gray matter alterations in borderline personality disorder and posttraumatic stress disorder: A dual meta-analysis.
Borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) are severe psychiatric disorders and often co-occur, either of the two will seriously threaten to public health. However, we lack ample evidences to understand the potential pathophysiologic mechanisms of gray matter (GM) alterations in the two disorders. We performed a meta-analysis in both BPD (15 datasets including 442 BPD subjects versus 441 healthy controls) and PTSD (11 datasets including 214 PTSD subjects versus 258 healthy controls) applying anisotropic effect-size-based algorithms (AES-SDM) method. Conjunction analysis found relative GM volume reductions in both disorders in the orbitofrontal gyrus and anterior cingulate cortex, contrarily, differences were predominantly observed that GM volume increased in the posterior cingulate gyrus and precuneus in BPD subjects, and GM volume decreased in the amygdala-hippocampal fear circuit, fusiform gyrus in PTSD subjects. Group comparisons and conjunction analyses in BPD and PTSD identified same regions of GM volume reductions in the orbitofrontal gyrus and anterior cingulate cortex, which may provide clues for the neurobiological mechanisms and clinical diagnosis underpinning two disorders.


Beneficial effects of banding on venous intimal-medial hyperplasia in arteriovenous loop grafts.
Local hemodynamics were modified in a canine arteriovenous loop graft model by placing a flow-limiting band on femoral polytetrafluoroethylene (PTFE) grafts. Banded and unbanded grafts were implanted in a paired fashion. Hemodynamic studies included Reynolds number and phonoangiography as measures of turbulence. Intimal-medial thickness was measured 8 weeks after implantation. Reduction of the volumetric flow rate by 50 percent resulted in significant changes in flow velocity, flow pulsatility, pressure, and turbulence at the venous anastomosis. Hyperplastic lesions developed in a reproducible manner at the venous anastomosis of the unbanded but not the banded grafts, as evidenced by combined intimal-medial thickness measurements: unbanded grafts 0.68 +/- 0.13 mm (p less than 0.01 versus control), banded grafts 0.25 +/- 0.03 mm (p greater than 0.05 versus control). Stepwise regression analysis indicated Reynolds number had the best correlation with the development of hyperplasia (r = 0.915, p less than 0.005), this being the first time this correlation has been quantitatively determined. We conclude that flow disturbance or turbulence is a major factor in the development of venous intimal-medial hyperplasia in arteriovenous loop grafts.


Prepro-alpha-factor has a cleavable signal sequence.
MAT alpha Saccharomyces cerevisiae secrete a small peptide mating pheromone termed alpha-factor. Its precursor, prepro-alpha-factor, is translocated into the endoplasmic reticulum and glycosylated at three sites. The glycosylated form is the major product in a yeast in vitro translation/translocation system. However, there is another translocated, nonglycosylated product that contains a previously unidentified modification. Contrary to previous results suggesting that the signal sequence of prepro-alpha-factor is not cleaved, amino-terminal radiosequencing has identified this product as prepro-alpha-factor without its signal sequence, that is, pro-alpha-factor. The translocated, glycosylated proteins are also processed by signal peptidase. Moreover, we have found that both purified eukaryotic and prokaryotic signal peptidase can process prepro-alpha-factor. Experiments using a yeast secretory mutant (sec 18) blocked in transport from the endoplasmic reticulum to the Golgi indicate that the protein is also cleaved in vivo. Finally, characterization of the Asn-linked oligosaccharide present on pro-alpha-factor in the yeast in vitro system by use of specific glucosidase and mannosidase inhibitors indicates that they have had the three terminal glucoses and probably one mannose removed. Therefore they most likely consist of Man8GlcNAc2 structures, identical to those found in the endoplasmic reticulum in vivo.


Management of myocarditis in clinical practice.
Myocarditis is an inflammatory heart muscle disease characterized by heterogeneous clinical presentation and outcome. Clinical heterogeneity of myocarditis, ranging from acute onset chest pain with electrocardiographic changes resembling an acute coronary syndrome, to arrhythmic storm and chronic decompensated heart failure, makes diagnosis challenging. However, a correct diagnosis is fundamental to proper patients' management and should always be seeked. Although a definite diagnosis is only provided by endomyocardial biopsy, the European Society of Cardiology task force on myocardial and pericardial diseases provided specific criteria for the diagnosis of clinically suspected myocarditis, which has been facilitated by the advent of noninvasive imaging tests (i.e. cardiovascular magnetic resonance based myocardial tissue characterization). Due to the heterogeneous presentation and disease course of myocarditis, a tailored treatment would be the best strategy, but a standardized management is still not available. However, over the years, new, promising therapies, such as antiviral and immune-suppressive treatment, have come side by side to the standard pharmacological heart treatment, i.e. antiheart failure medications. In this paper we will review the basic principles of myocarditis management in clinical practice, including diagnostic work-up, conventional and disease-specific therapy and patients' follow-up.


miR-146a modulates TLR1/2 and 4 induced inflammation and links it with proliferation and lipid production via the indirect regulation of GNG7 in human SZ95 sebocytes.
Activation of Toll-like receptors (TLR) 1/2 and 4 are central in inducing inflammation in sebocytes by regulating the expression of protein coding mRNAs, however the microRNA (miRNA) profile in response to TLR activation and thus the possible role of miRNAs in modulating sebocyte functions has not been elucidated. In this work we identified miR-146a to have the highest induction in the TLR1/2 and 4 activated SZ95 sebocytes and found that its increased levels led to the down-regulation of IL-8 secretion, decreased the chemoattractant potential and stimulated the proliferation of sebocytes. Assessing the gene expression profile of SZ95 sebocytes treated with a miR-146a inhibitor, the induction of GNG7 was one of the highest, while when cells were treated with a miR-146a mimic, the expression of GNG7 was down-regulated. These findings correlated with our in situ hybridization results, that compared with control, miR-146a showed an increased, while GNG7 a decreased expression in sebaceous glands of acne samples. Further studies revealed, that when inhibiting the levels of GNG7 in SZ95 sebocytes, cells increased their lipid content and decreased their proliferation. Our findings suggest, that miR-146a could be a potential player in acne pathogenesis by regulating inflammation, inducing proliferation and, through the indirect down-regulation of GNG7, promoting the lipid production of sebocytes.