Planar and SPECT imaging with technetium-99m labeled antigranulocyte antibodies in bone and soft tissue infection.
Scintigraphy with technetium-99m labeled antigranulocyte antibodies including planar and SPECT imaging demonstrated areas of inflammation in bone and soft tissue of the thigh of a 38-year-old man who had a fracture of the femur 20 years earlier. The clinical potential of this imaging modality in the diagnostic assessment of inflammatory diseases is discussed.


Isolation and identification of the phosphorylated species of rhodopsin.
Rhodopsin is phosphorylated in a light-dependent manner by a kinase intrinsic to the rod outer segment. We have used chromatofocusing to separate six phosphorylated species of rhodopsin and have recovered in the pH gradient fractions 60-80% of the initial phosphorylated sample loaded on the column. The isolated species of rhodopsin coincide with the species that are observed in isoelectric focusing gels in the pH range 6.1-4.7. Unphosphorylated rhodopsin focuses at a pI of 6.0. Two species having two phosphates per rhodopsin with isoelectric points of 5.45 and 5.40 have been isolated. The phosphate to rhodopsin ratios for the remaining species are 3.8, 5.0, 6.1, and 8.2 with isoelectric points of 5.16, 4.99, 4.85, and 4.73, respectively. The chromatofocusing profile suggests that there may be multiple forms of rhodopsin with the same number of phosphates among some of the other phosphorylated forms of rhodopsin.


Alemtuzumab in a Large Real-Life Cohort: Interim Baseline Data of the TREAT-MS Study.
The non-interventional long-Term study foR obsErvAtion of Treatment with alemtuzumab in active relapsing-remitting MS (TREAT-MS) study collects the so far largest real-life cohort regarding utilization, long-term effectiveness, and safety of alemtuzumab, a humanized monoclonal antibody directed against the cell surface glycoprotein CD52, in adult patients with active relapsing-remitting multiple sclerosis (RRMS). An interim analysis of baseline parameters at inclusion of a non-interventional real-world study about alemtuzumab in Germany including previous multiple sclerosis (MS) medication utilization, MS activity, severity, and duration, as well as comorbidities was performed. Of the 883 patients, 71.6% were women. Mean age was 35.7 ± 9.2 years, time since first MS symptoms (=disease duration) is 8.0 ± 6.8 years, and Expanded Disability Status Scale (EDSS) is 2.7 ± 1.8 points (range, 0.0-7.5 points). The number of relapses in the 12 and 24 months prior to inclusion were 1.6 ± 1.2 and 2.2 ± 1.8, respectively. Of the patients, 14.4% were treatment naive, while for the majority, a wide spectrum of MS disease-modifying treatments (DMTs) and treatment sequences were documented. Overall, interferon beta (IFN-beta) was reported most frequently (52.4%), followed by fingolimod (35.2%), natalizumab (34.9%), and glatiramer acetate (28.9%). Patients with longer disease duration and higher EDSS had a higher number of previous DMTs. Compared to the pivotal phase 2/3 studies, RRMS patients starting alemtuzumab treatment had a longer disease duration in real-world conditions. There was variety of different treatment sequences before the final switch to alemtuzumab. In the future, linking these treatment sequences or other baseline characteristics with effectiveness and safety outcomes might be useful to support treatment decisions. Registered at Paul-Ehrlich-Institut under NIS 281.


Organic mental disorders--an American perspective.
The new American psychiatric classification (DSM-III) features a radically new approach to organic mental disorders. The concept of organicity has been liberalised to allow inclusion of psychiatric correlates of cerebral disorders which not only fail to involve cognitive impairment but in some cases also resemble affective, paranoid, and schizophrenic disorders. The highlights, and implications of the new approach are discussed.


Reproducibility of techniques using Archimedes' principle in measuring cancellous bone volume.
Researchers have been interested in developing techniques to accurately and reproducibly measure the volume fraction of cancellous bone. Historically bone researchers have used Archimedes' principle with water to measure the volume fraction of cancellous bone. Preliminary results in our lab suggested that the calibrated water technique did not provide reproducible results. Because of this difficulty, it was decided to compare the conventional water method to a water with surfactant and a helium method using a micropycnometer. The water/surfactant and the helium methods were attempts to improve the fluid penetration into the small voids present in the cancellous bone structure. In order to compare the reproducibility of the new methods with the conventional water method, 16 cancellous bone specimens were obtained from femoral condyles of human and greyhound dog femora. The volume fraction measurements on each specimen were repeated three times with all three techniques. The results showed that the helium displacement method was more than an order of magnitudes more reproducible than the two other water methods (p < 0.05). Statistical analysis also showed that the conventional water method produced the lowest reproducibility (p < 0.05). The data from this study indicate that the helium displacement technique is a very useful, rapid and reproducible tool for quantitatively characterizing anisotropic porous tissue structures such as cancellous bone.


Investigation of the interaction between human serum albumin and antitumor palladium(II) complex containing 1,10-phenanthroline and dithiocarbamate ligands.
The interaction between [Pd(But-dtc)(phen)]NO3 (where But-dtc = butyldithiocarbamate and phen = 1,10-phenanthroline) with HSA (Human Serum Albumin) was investigated by applying fluorescence, UV-Vis and circular dichroism techniques under physiological conditions. The results of fluorescence spectra indicated that the Pd(II) complex could effectively quench the fluorescence intensity of HSA molecules via static mechanism. The number of binding sites and binding constant of HSA-Pd(II) complex were calculated. Analysis of absorption titration data on the interaction between Pd(II) complex and HSA revealed the formation of HSA-Pd(II) complex with high-binding affinity. Thermodynamic parameters indicated that hydrophobic forces play a major role in this interaction. Furthermore, CD measurements were taken to explore changes in HSA secondary structure induced by the Pd(II) complex.


[Ten cases of locally advanced rectal cancer that were treated with preoperative chemotherapy with S-1 plus oxaliplatin].
The purpose of this study was to evaluate S-1 plus oxaliplatin( SOX) as neoadjuvant chemotherapy for the treatment of patients with locally advanced rectal cancer. The clinical features and management of 10 patients with this disease seen at the Hirosaki University Hospital between 2011 and 2013 were examined. Of these patients, 30% were treated with bevacizumab, and the mean number of courses was 3.3. There were no adverse events of severity greater than Grade 3, and no patient required treatment interruption because of toxicity. SOX administered every 3 weeks was associated with a partial response rate of 40% and a tumor control rate of 100%; progressive disease was not observed. Curative resection was performed in all patients except in 1 with liver metastasis. With regard to the pathological findings, 2 cases were of Grade 0; 4 cases, of Grade 1a; and 2 cases, of Grade 2. Postoperative complications such as anastomotic leakage were observed in 80% of the patients. Thus, SOX administration without a central venous drug injection port was very useful because most patients could receive SOX treatment on an outpatient basis. However, the frequency of postoperative complications associated with this treatment is increasing, and therefore, it is important to accumulate more evidence.


Concurrent subarachnoid haemorrhage and myocardial injury.
Subarachnoid haemorrhage is frequently associated with myocardial injury and dysfunction. This report describes such a case, reviews the understanding of this phenomenon, and discusses the implications for timing of surgical clipping of intracranial aneurysm in patients with concurrent myocardial damage. A 64-yr-old women presented with syncope and congestive heart failure. A diagnosis of subarachnoid haemorrhage was made three days following the initial diagnosis of myocardial infarction. The patient presented for clipping of an intracranial aneurysm on day 36, after her cardiac status had stabilized. No new myocardial ischaemic events occurred, either intra-operatively or post-operatively. Ultimate neurological recovery was poor. This case report demonstrates four important aspects of the clinical course of patients with concurrent subarachnoid haemorrhage and myocardial damage: 1) On presentation, cardiac features may predominate, and delay diagnosis and treatment of the underlying subarachnoid haemorrhage. 2) Left ventricular dysfunction, although dramatic, is usually transient. 3) There is confusion regarding the appropriate cardiac risk assessment and management in such patients when presenting for surgery. 4) Long-term morbidity is most often related to neurological, not medical, complications.


Pimpinella anisum L. Essential Oil a Valuable Antibacterial and Antifungal Alternative.
Anise (Pimpinella anisum L.) essential oils are intensely investigated worldwide for the beneficial properties, due to the specific bioactive compound's structure. (1) Background: This study characterized the structure of the Pimpinella anisum essential oil and evaluated its antimicrobial properties. (2) Methods: An evaluation of the antibacterial and antifungal activity targeted strains of Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923), Streptococcus pyogenes (ATCC 19615), and levure Candida albicans (ATCC 10231). Gas chromatography coupled with mass spectrometry (GC/MS) was used for structure identification, and the optical density mass loss was applied for the analysis of different dilutions of aniseed essential oils antimicrobial activity. (3) Results: A total of 13 compounds were identified, of which trans-anethole was in the highest proportion (72.49%), followed by limonene (10.01%), anisole (5%), and α-pinene (3.26%). The results obtained and statistically analyzed, utilizing one-way ANOVA with Bonferroni's multiple comparison test, indicated the antimicrobial activity (p < 0.001) of anise essential oil. (4) Conclusion: Anise essential oil is a promising phyto-remedy with important antimicrobial activity against both Gram-positive and Gram-negative pathogens. Inhibition high percentages were found for the p. aeruginosa and S. aureus strains, but also excellent antifungal activity against C. albicans was ascertained.


[Quantitative study of nonsegmented and segmented neutrophilic granulocytes in newborn].
Serial white blood cell counts were studied in 20 healthy full-term babies and 252 newborn babies of different birthweights (61 of them without and 191 with perinatal risks). Nonsegmented (band form) and segmented neutrophils participate in roughly equal quantities in the physiological postnatal neutrophil reaction, which begins 1 hour after birth (8100/mm3 +/- 2600), reaches the peak after 9 hours (15 500/mm3 +/- 4000), and drops to the initial level within 42 hours. During the first 3 days the shift to the left with the relative and absolute increase of the band forms is more significant for a perinatal infection than the rise of total neutrophil count, which can remain within the normal range. However, these changes are not specific for infectious diseases. In the period the white blood count has only a diagnostic value in relation with the age of the newborn in hours and with short term follow-ups. Newborns of low birth weight (under 2500 g) show lower absolute counts and less significant changes than newborns of normal birth weight.


Room temperature C-N bond cleavage of anionic guanidinate ligand in rare-earth metal complexes.
The dissociation of the anionic guanidinate ligand N=C(NMe2)2 promoted by rare-earth metal complexes at room temperature is described. Treatment of CpLnCl2(THF)3 with two equiv. of Li[N=C(NMe2)2] in THF at room temperature affords [Cp2Ln(μ-η(1):η(2)-L2)]2 (Ln = Y; L = N=C(NMe2)N=C(NMe2)2) and CpLn[N=C(NMe2)2](μ-η(1):η(2)-L)2LnCp2 (Ln = Dy) in moderated yields, respectively. YCl3 reacts with three equiv. of Li[N=C(NMe2)2] under the same conditions to give a trinuclear yttrium guanidinate [(Me2N)2C=N]5Y3[μ-N=C(NMe2)2]2(μ-η(1):η(2)-L)2 in 63% yield. These reactions show that rare-earth metals can promote a C-N bond cleavage of the guanidine anion [N=C(NMe2)2](-) at room temperature. All new complexes were characterized by elemental analysis and spectroscopic properties, and their solid-state structures were determined through single-crystal X-ray diffraction analysis.


[Analysis of measurements: arterial blood pressure, pulse rate and oxygen saturation in arterial blood during broncho-fibroscopy and bronchoalveolar lavage in patients with bronchial asthma and chronic bronchitis].
Bronchial asthma and chronic bronchitis in stable period of disease could be an indication for diagnostic bronchofiberoscopy and broncho-alveolar lavage (BAL). 30 patients with bronchial asthma (aged 27.2 +/- 9.3), 30 patients with chronic bronchitis (aged 55.9 +/- 11.0) and subjects of control group (aged 27.0 +/- 9.7) took part in this study. Selected parameters: heart rate (HR), arterial blood pressure (ABP) and arterial O2 saturation (SaO2) monitored by pulsoximetry were measured during the procedure. It was showed that broncho-fibroscopy and BAL could be performed safe in patients with asthma and chronic bronchitis as well. Bronchospasm was observed only in one subject with asthma. The highest decrease of saturation was observed during BAL in every investigated subject. Because of none of recorded parameters allows identification of the patients at risk of poor tolerance of the procedure, we propose close observation of patient, monitoring parameters: HR, ABP and SaO2, and oxygen supplementation during the investigation.


Approach to calculate normal modes by decomposing the dyadic Green's function.
Normal mode is a very fundamental notion in quantum and classical optics. In this paper, we present a method to calculate normal modes by decomposing dyadic Green's function, where the modes are excited by dipoles. The modes obtained by our method can be directly normalized and their degeneracies can be easily removed. This method can be applied to many theoretical descriptions of cavity electrodynamics and is of interest to nanophotonics.


[Selecting and affinity analysis of DNA aptamers to MPT64 protein from Mycobacterium tuberculosis].
To obtain DNA oligonucleotide aptamers which can specifically bind to MPT64 protein from Mycobacterium tuberculosis by SELEX technology. An in vitro synthesized 78 per random DNA library was subjected to 12 rounds of selection by SELEX (Systematic evolution of ligands by exponential enrichment) method against MPT64 protein. Binding of the aptamers to the protein was examined by biotin-streptavidin-horseradish peroxidase system. DNAMAN package was employed to analyze the sequences and the second structures of the aptamers. Moreover, target protein was bound to one aptamer and another aptamer modified with biotin together forming a sandwich-like complex, which was captured in microwell, to be tested in negative group including BCG and reference strains from nontuberculous mycobacteria, and positive group including H37Rv, Mycobacterium bovis reference strain, and clinical strains from Mycobacterium tuberculosis. After 12 rounds of selection, high-affinity aptamers to MPT64 was obtained. The OD value at 450 nm of affinity of aptamers to MPT64 protein was from 0. 492 to 1.243, in which 73.3% was over 1.0. Pocket and stem-loops was the basis of aptamers binding to MPT64 protein by the analysis of structures,with several GC pairs among bridges between pocket and stem-loops. The analysis of the sandwich-like complex system based on two aptamers and protein showed that the positive percentage was 87. 9% in the positive group while the negative percentage was 85.7% in the negative group, with positive H37Rv and Mycobacterium bovis, and negative BCG, when the cut-off value for a positive response was 0.61 OD. A set of aptamers with considerable binding affinity to MPT64 protein were successfully selected from the initial random DNA library.


Application of dexamethasone combined with tranexamic acid in perioperative period of total hip arthroplasty.
To evaluate the efficacy and safety of dexamethasone (DEXA) combined with tranexamic acid (TXA) in the perioperative period of total hip arthroplasty. A total of 100 cases were randomly divided into 2 groups (50 cases per group). All patients were given 15 mg/kg TXA before skin incision and 3 hours later. Patients in the intervention group (TXA + DEXA group) were given 20 mg dexamethasone intravenously after the onset of anesthesia, and the same dose of DEXA was administered again 24 hours later. Patients in the placebo group (TXA group) were only given the same dose of normal saline. Postoperative c-reactive protein and interleukin-6, postoperative nausea and vomiting, fatigue visual analogue scale score, postoperative length of stay, range of motion, and consumption of analgesic and antiemetics were statistically analyzed in the 2 groups. The levels of c-reactive protein and interleukin-6 in the TXA + DEXA group were lower than those in the TXA group at 24, 48, 72 hours post-operatively (P < .001). Walking pain scores in the TXA + DEXA group were also significantly lower than those in the TXA group at 24 and 48 hours (P < .001); rest pain scores were lower at 24 hours (P < .001). Compared with the TXA group, the incidence of nausea VAS, postoperative nausea and vomiting, fatigue, analgesia and antiemetics consumption, postoperative length of stay, and range of motion were lower in the TXA + DEXA group (all P < .05), while there were no significant differences in postoperative hematocrit, total blood loss, and complications (P > .05). The combination of TXA (15 mg/kg; before skin incision and 3 hours later) and DEX (20 mg dexamethasone intravenously after the onset of anesthesia, and again 24 hours later) is an effective and safe strategy for patients undergoing total hip arthroplasty.


COP1 targets C/EBPα for degradation and induces acute myeloid leukemia via Trib1.
The ubiquitin ligase constitutively photomorphogenic 1 (COP1) is involved in many biological responses in mammalian cells, but its role in tumorigenesis remains unclear. Here we show that COP1 is a ubiquitin ligase for the tumor suppressor CCAAT/enhancer-binding protein (C/EBPα) and promotes its degradation in vivo, thereby blocking myeloid differentiation of hematopoietic cells for tumorigenesis. In this process, mammalian homolog of Tribbles, Trib1, which contains a COP1-binding motif, is essential for down-regulation of C/EBPα expression. Murine bone marrow transplantation experiments showed that coexpression of COP1 accelerates development of acute myeloid leukemia induced by Trib1, which pathologically resembles that of p42C/EBPα-deficient mice. Interestingly, coexpression of ligase activity-deficient COP1 mutant abrogated Trib1-induced leukemogenesis. These results indicate that COP1 and Trib1 act as an oncoprotein complex functioning upstream of C/EBPα, and its ligase activity is crucial for leukemogenesis.


Sympathoadrenal, metabolic, and regional blood flow responses to cold in fetal sheep.
Because environmental temperature falls when the fetus is delivered from the uterus, the role of cold in stimulating cardiovascular and sympathoadrenal responses at the time of birth was examined in fetal lambs. In eight fetuses (gestational age 140 +/- 2 d), catheters were inserted into hind-limb and neck arteries and veins, and into an umbilical vein. After returning the fetus to the uterus and administering a muscle relaxant (succinylcholine chloride), blood gases, glucose and lactate concentrations, and plasma catecholamine and atrial natriuretic peptide concentrations were measured. Fetal combined ventricular output and organ blood flows were measured by the radionuclide-labeled microsphere technique. Measurements were repeated after delivering the fetus into a warm water bath (40 degrees C) and at 15 and 30 min after the bath temperature was cooled to 25 degrees C. Fetal cooling stimulated a sympathoadrenal response, which was manifested by an immediate increase in heart rate and arterial blood pressure, a rise in atrial natriuretic peptide, and modest increase in norepinephrine concentration. Contrary to earlier reports that investigated the effect of cold on fetal lambs using an intrauterine cooling coil, we did not find a decrease in fetal arterial oxygen tensions and pH, an increase in plasma glucose and lactate concentrations, or changes in fetal oxygen consumption. Combined ventricular output did not increase with cooling, and blood flow to most organs did not change significantly; however, blood flow to the skin decreased markedly, particularly in the lower body.(ABSTRACT TRUNCATED AT 250 WORDS)


High dose of radioactive iodine per se has no effect on glucose metabolism in thyroidectomized rats.
Thyroid concentrates radioactive iodine by sodium-iodide symporter; this is used for treating hyperthyroidism and thyroid cancer. Pancreas expresses NIS and radioactive iodine uptake may damage pancreatic beta-cells and predispose patients to type 2 diabetes. The aim of this study was to determine whether radioactive iodine is associated with glucose metabolism in thyroidectomized rats. Forty male Wistar rats were divided into four groups (n = 10/each); control, thyroidectomized, thyroidectomized-treated with 131-I (TX+I), and thyroidectomized-treated with 131-I and L-thyroxine (TX+I+T4). At the end of study, serum fasting glucose, insulin, thyroid-stimulating hormone, and free tetraiodothyronine were measured, intraperitoneal glucose tolerance test was performed, and homeostasis model assessment-insulin resistance was calculated. In in vitro experiments, glucose-stimulated insulin secretion from pancreatic islets and sodium-iodide symporter mRNA expression in thyroid and islets were determined. Compared to control group, free tetraiodothyronine was lower by 41 and 77% and thyroid-stimulating hormone was higher by 36 and 126% in thyroidectomized and TX+I groups, respectively. Compared to controls, rats in TX+I group had glucose intolerance as assessed using the area under curve of intraperitoneal glucose tolerance test (12,376 ± 542 vs. 20,769 ± 1070, P < 0.001) and L-thyroxine replacement therapy restored the value (14,286 ± 328.24) to near normal. Fasting insulin and homeostasis model assessment-insulin resistance were comparable in all groups, however fasting glucose was higher in TX+I group. In in vitro experiments, glucose-stimulated insulin secretion from islets did not differ between groups. Radioactive iodine therapy per se had no effect on glucose metabolism, just intensified thyroid hormone deficiency and the alterations on glucose metabolism in thyroidectomized rats. L-thyroxine therapy restored the glucose intolerance observed in radioactive iodine-treated thyroidectomized rats.


Effects of pubertal cannabinoid administration on attentional set-shifting and dopaminergic hyper-responsivity in a developmental disruption model of schizophrenia.
Adolescent exposure to cannabinoids in vulnerable individuals is proposed to be a risk factor for psychiatric conditions later in life, particularly schizophrenia. Evidence from studies in animals has indicated that a combination of repeated pubertal cannabinoid administration with either neonatal prefrontocortical lesion, isolation rearing, or chronic NMDA receptor antagonism administration induces enhanced schizophrenia-like behavioral disruptions. The effects of adolescent exposure to CB1 receptor agonists, however, have not been tested in a developmental disruption model of schizophrenia. This was tested in the methylazoxymethanol (MAM) model, in which repeated treatment with the synthetic cannabinoid agonist WIN 55,212-2 (WIN; 1.2mg/kg) was extended over 25 days throughout puberty (postnatal days 40-65) in control and MAM rats. The rats received 20 injections, which were delivered irregularly to mimic the human condition. Adult rats were tested for attentional set-shifting task and locomotor response to amphetamine, which was compared with in vivo recording from ventral tegmental area (VTA) dopamine (DA) neurons. MAM-treated rats showed impairment in the attentional set-shifting task, augmented locomotor response to amphetamine administration, and an increased number of spontaneously active DA neurons in the VTA. Interestingly, pubertal WIN treatment in normal animals induced similar changes at adulthood as those observed in MAM-treated rats, supporting the notion that adolescence exposure to cannabinoids may represent a risk factor for developing schizophrenia-like signs at adulthood. However, contrary to expectations, pubertal WIN administration did not exacerbate the behavioral and electrophysiological changes in MAM-treated rats beyond that observed in WIN-treated saline rats (Sal). Indeed, WIN treatment actually attenuated the locomotor response to amphetamine in MAM rats without impacting DA neuron activity states. Taken together, the present results indicate that the impact of cannabinoids during puberty/adolescence on schizophrenia models is more complex than may be predicted.


[Depressive Disorder and Gut-brain Interaction].
Depressive disorder is a stress-induced condition, which has been suggested to have bidirectional interactions with the gut microbiota. Probiotics such as Bifidobacterium and Lactobacillus have been suggested to mitigate stress response. Irritable bowel syndrome (IBS) is a typical phenotype of psychological distress manifested in the gastrointestinal system, and often develops in patients with depressive disorder. The altered gut microbiota and resultant inflammation in the gut play an important role in at least a portion of IBS. Animal models of depression have shown abnormalities in the gut such as increased gut permeability, and the probiotics ameliorate their chronic depression-like behaviors and altered stress responses. There have been only a few studies that have directly investigated the gut microbiota in patients with depression. We reported results suggesting that individuals with lower bacterial counts for Bifidobacterium and/or Lactobacillus are more common in patients with major depressive disorder than in healthy controls. the collectively use of gut microbiota in the diagnosis and treatment of depressive disorder seems to be a promising approach.


Multiple myeloma presenting as CEA-producing rectal cancer.
We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas.


Glutamatergic synaptic deficits in the prefrontal cortex of the Ts65Dn mouse model for Down syndrome.
Down syndrome (DS), the most prevalent cause of intellectual disability, stems from a chromosomal anomaly resulting in an entire or partial extra copy of chromosome 21. This leads to intellectual disability and a range of associated symptoms. While there has been considerable research focused on the Ts65Dn mouse model of DS, particularly in the context of the hippocampus, the synaptic underpinnings of prefrontal cortex (PFC) dysfunction in DS, including deficits in working memory, remain largely uncharted territory. In a previous study featuring mBACtgDyrk1a mice, which manifest overexpression of the Dyrk1a gene, a known candidate gene linked to intellectual disability and microcephaly in DS, we documented adverse effects on spine density, alterations in the molecular composition of synapses, and the presence of synaptic plasticity deficits within the PFC. The current study aimed to enrich our understanding of the roles of different genes in DS by studying Ts65Dn mice, which overexpress several genes including Dyrk1a, to compare with our previous work on mBACtgDyrk1a mice. Through ex-vivo electrophysiological experiments, including patch-clamp and extracellular field potential recordings, we identified alterations in the intrinsic properties of PFC layer V/VI pyramidal neurons in Ts65Dn male mice. Additionally, we observed changes in the synaptic plasticity range. Notably, long-term depression was absent in Ts65Dn mice, while synaptic or pharmacological long-term potentiation remained fully expressed in these mice. These findings provide valuable insights into the intricate synaptic mechanisms contributing to PFC dysfunction in DS, shedding light on potential therapeutic avenues for addressing the neurocognitive symptoms associated with this condition.


Association study of the FTO gene polymorphisms with the risk of pulmonary tuberculosis in a sample of Iranian population.
The aim of the present study was to find out the impact of fat mass and obesity-associated (FTO) gene on risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. This case-control study was carried out on a total of 354 subjects including 185 PTB patients and 169 healthy subjects. Genotyping of FTO rs9939609 and rs8050136 variants was done using polymerase chain reaction-restriction fragment length polymorphism method. FTO rs9939609 variant showed no statistically significant difference in allele and genotype frequencies between PTB patients and controls. The rs8050136 polymorphism marginally increased the risk of PTB in dominant (OR = 1.53, 95% CI = 1.00-2.33, p = 0.055, CA+AA vs. CC) inheritance model tested, where rs8050136 A allele significantly increased the risk of PTB (OR = 1.42, 95% CI = 1.02-1.97, p = 0.045) compared with C allele. The finding of the present study showed an association between FTO rs9939609 variant and risk of PTB. Further studies with larger sample sizes and different ethnicities are necessary to confirm the findings.


[The treatment of the tracheobronchial stenosis by extracorporeal circulation].
Six children with tracheobronchial stenosis secondary to cardiovascular ring were operated with extracorporeal surgery. Three of them with pulmonary sling had a tracheobroncoplasty with costal cartilage, one with xiphoides appendix and another with pericardio. One girl 2 years old was operated resecting three tracheal rings and anastomosis end to end. The child that was operated with pericardio died with infection and sepsis three months after the operation. The other five are well five, four and two years after plasty.


Phenotypic and genotypic characterization of tetracycline- and oxytetracycline-resistant Aeromonas hydrophila from cultured channel catfish (Ictalurus punctatus) and their environments.
Oxytetracycline-resistant (OTcr) and tetracycline-resistant (Tcr) Aeromonas hydrophila were isolated commonly from catfish intestinal contents and the water and sediment of catfish culture ponds, but less frequently in market catfish. Isolates demonstrated two resistance phenotypes, Tcr OTcr and Tcs OTcr, when plated directly on to MacConkey agar containing 30 micrograms of tetracycline or oxytetracycline per ml. Tcs OTcr isolates expressed Tcr after induction by 1 h of growth in tryptic soy broth containing 1 microgram of tetracycline per ml. Over 90% of the resistant aeromonads hybridized with DNA probes for class A or class E Tcr determinants; class E was twice as prevalent as class A. The distribution of class A and E Tcr determinants varied with the Tcr phenotypes. Prior to induction, 86% of isolates with class A determinants were Tcr as well as OTcr, while only 16% with class E determinant were Tcr. Three of 5 Tcr aeromonads without class A or class E determinants and 1 of 14 with class E determinants transferred Tcr to Escherichia coli.


Asymmetric Total Syntheses of (+)-Davisinol and (+)-18-Benzoyldavisinol: A HAT-Initiated Transannular Redox Radical Approach.
The first and asymmetric total syntheses of two C11-oxygenated hetisine-type diterpenoid alkaloids, namely, (+)-davisinol and (+)-18-benzoyldavisinol, is described. The concise synthetic approach features a HAT-initiated transannular redox radical cyclization, an ODI-Diels-Alder cycloaddition, and an acylative kinetic resolution. By incorporating an efficient late-stage assembly of the azabicycle, our strategy would streamline the synthetic design of C20-diterpenoid alkaloids and pave the way for their modular syntheses.


Helminth-induced immunoregulation of an allergic response to food.
Work from our laboratory has shown that an enteric helminth infection can act as an adjuvant to prime for a Th2-biased response to a typically tolerogenic form of dietary antigen. Helminth infection did not, however, prime for an allergic response. Using a model in which systemic anaphylactic symptoms and antigen specific IgE are induced in C3H/HeJ mice by repeated intragastric administration of peanut antigen with the mucosal adjuvant cholera toxin we showed that an enteric helminth infection protects against the development of food allergy. Helminth-dependent protection against allergy was abrogated when the helminth-infected, allergen-sensitized mice were treated with neutralizing antibodies to IL-10. Recent work from our laboratory and others has implicated helminth induced immunoregulatory cells in protection against allergy. We will discuss the characteristics of the immunoregulatory cell populations that have been described and the mechanism(s) by which they may function in the suppression of allergy.


Biological roles of ionic zinc.
We tentatively conclude from our work that intracellular calcium acts as a second messenger to affect membrane function through activation of calmodulin. This activation, if too great, leads to pathological erythrocyte adherence and aggregation phenomena. We have shown that calmodulin inhibitors can prevent some of these calcium-induced abnormalities. Since some of this work involves a very specific anticalmodulin antibody, it appears very likely that calmodulin is involved in producing membrane effects. Zinc appears to act upon the membrane in part, at least, through the inhibition of calmodulin action. Our work leads us to believe that zinc regulates copper absorption from the gastrointestinal tract in a somewhat complex manner. That is, direct zinc-copper antagonism within the lumen of the gastrointestinal tract is not adequate to explain the effects of zinc on inhibiting copper absorption in man. It appears from our work that tissues must become loaded with zinc before an effect on copper absorption is observed. This produces a lag effect during which zinc administration does not produce a negative copper balance. However, after this lag effect, zinc has produced a negative to neutral copper balance in 5 of 5 Wilson's disease patients studied. At this time, therefore, we believe that zinc therapy can be offered as an alternative to penicillamine therapy in previously decoppered patients or patients who are not yet symptomatic. However, we recommend that this therapy only be used at this time in accordance with the one zinc therapy regimen we have tested.


The B-type channel is a major route for iron entry into the ferroxidase center and central cavity of bacterioferritin.
Bacterioferritin is a bacterial iron storage and detoxification protein that is capable of forming a ferric oxyhydroxide mineral core within its central cavity. To do this, iron must traverse the bacterioferritin protein shell, which is expected to occur through one or more of the channels through the shell identified by structural studies. The size and negative electrostatic potential of the 24 B-type channels suggest that they could provide a route for iron into bacterioferritin. Residues at the B-type channel (Asn-34, Glu-66, Asp-132, and Asp-139) of E. coli bacterioferritin were substituted to determine if they are important for iron core formation. A significant decrease in the rates of initial oxidation of Fe(II) at the ferroxidase center and subsequent iron mineralization was observed for the D132F variant. The crystal structure of this variant shows that substitution of residue 132 with phenylalanine caused a steric blockage of the B-type channel and no other material structural perturbation. We conclude that the B-type channel is a major route for iron entry into both the ferroxidase center and the iron storage cavity of bacterioferritin.


Radioguided surgery in brain tumors with thallium-201.
Malignant astrocytomas show thallium uptake with a high target-to-background ratio, allowing the use of radioguided surgery. We report on 6 patients (3 men) diagnosed with malignant astrocytoma. All patients signed informed consent documents. Previous thallium-201 SPECT was performed, showing uptake in tumors. In the operating room we injected 37 MBq (1 mCi) of thallium-201 at the same time the craniotomy was performed. With the gamma probe we confirmed the tumor uptake, and a biopsy sample was taken. After conventional tumor resection, we scanned the surgical bed with the gamma probe. All areas of abnormal uptake were evaluated by the surgeon and, if possible, removed. In all patients the biopsy confirmed a high-grade astrocytoma. In all cases we found residual uptake in the surgical bed that was confirmed as residual tumor by pathologic examination. In 3 cases it was not possible to remove all the sites of pathologic uptake because critical areas were involved. In the other 3 patients, only background activity was found after the procedure. Radioguided surgery in brain tumors with thallium-201 is a complex technique and expertise in radioguided surgery and neuroimaging is needed, but we think that it is promising.


Administration of a polyphenol-enriched feed to farmed sea bass (Dicentrarchus labrax L.): Kidney melanomacrophages response.
The reinforcement of the defense mechanism of fish, through the administration of immunostimulants, is considered as a promising alternative to vaccines. Natural immunostimulants such as polyphenols, flavanoids, pigments and essential oils can modulate the innate immune response. In lower vertebrates, melano-macrophage centres, i.e. clusters of pigment-containing cells forming the extracutaneous pigment system, are wide-spread in the stroma of the haemopoietic tissue, mainly in kidney and spleen. In fishes, melano-macrophage centres play an important role in the immune response against antigenic stimulants and pathogens. In the present study, we evaluated the effect of a polyphenol-enriched diet on the health status of European sea bass (Dicentrarchus labrax L.). Farmed sea bass were administered a feed containing a phytocomplex, rich in catechins and epigallocatechins, which was obtained from the seeds of Canosina Nero di Troia Vitis vinifera and mixed with conventional feed at two different concentrations. The effects of such a diet were investigated in juvenile and commercial size samples, i.e. undergoing a short- and long-term period of diet, respectively, focusing on their extracutaneous pigmentary system and, in more detail, on the enzymatic activities leading to melanin biosynthesis. Our results show that prolonged dietary treatments with higher concentration of polyphenols might modulate tyrosinase activity and gene expression in commercial size fishes. An increase of melano-macrophage activity is correlated to a stimulation of cytoprotective functions against antigenic stimulants and pathogens, as an expression of a robust and protective adaptive immune response.


Iris vascular changes in newborns of diabetic mothers.
Routine ophthalmic examinations of 600 full-term neonates, including 54 born to mothers with insulin-dependent diabetes mellitus and 12 whose mothers had developed gestational diabetes, revealed significant tortuosity and dilatation of the iris vessels in over half of the infants born to diabetic mothers. Ninety percent of the newborns in the diabetic group presented hypoplasia of the iris stroma and pupil dynamics were altered in 85%. The vessel changes resolved spontaneously within 2 weeks after birth. These changes, which have also been observed in cocaine-intoxicated newborns, should raise the suspicion of adverse vascular effects in the fetus caused by maternal diabetes.


Synthesis and characterization of methyl 6-O-alpha- and -beta-D-galactopyranosyl-beta-D-galactopyranoside.
Sequential tritylation, acetylation and detritylation of methyl beta-D-galactopyranoside gave crystalline methyl 2,3,4-tri-O-acetyl-beta-D-galactopyranoside (4) and methyl 2,3,6-tri-O-acetyl-beta-D-galactopyranoside, the latter being the minor product resulting from acetyl migration. Reaction of 4 with 2,3,4,6-tetra-O-acetyl-alpha-D-galactosyl bromide in benzene, in the presence of mercuric cyanide and mercuric bromide, gave the alpha- and beta-D-(1----6)-linked disaccharides (7 and 9, respectively) in high yield, and their structure was confirmed by 1H- and 13C-n.m.r. 1d. and 2d. spectroscopy. O-Deacetylation of 7 gave the hitherto unknown, crystalline methyl 6-O-alpha-D-galactopyranosyl-beta-D-galactopyranoside. O-Deacetylation of 9 gave the corresponding, beta-D-linked disaccharide methyl glycoside, the physical constants of which are discussed with respect to controversial data in the literature.


Housewife onycholysis.
The aim of this study was to evaluate the clinical and microbiological aspects of onycholysis in Iraqi housewives. One hundred housewives with onycholysis of the finger nails were evaluated clinically in the Department of Dermatology and Venereology, Baghdad Teaching Hospital, Baghdad, Iraq between October 2002 to March 2003. Swabs were taken from those patients for microbiological evaluation in the Department of Microbiology, College of Medicine, University of Baghdad, Baghdad, Iraq. All cases with skin disorder related systemic diseases like anemia, hypothyroidism and drug intake like minocycline, oral contraceptives were excluded from the study. One hundred housewives with onycholysis were enrolled in the study. Their ages ranged between 17-70 years with a mean of 41.96 +/- 12.57 years. Married females were 89 (89%), while unmarried females were 11 (11%). The site of involvement was mainly the thumb (76%) followed by the ring finger (12%), the index (7%), little (6%) and middle (5%) fingers. The pattern of onycholysis was distal in 47 (47%), lateral in 30 (30%) and both distal and lateral in 23 (23%) of the patients. Onycholysis is a major problem among Iraqi housewives, most probably caused by repetitive mechanical, chemical and physical trauma; therefore, special preventive measures should be undertaken to minimize the incidence of the disease. Housewives should be encouraged to use preventive measures like using gloves and washing machines.


Abdominal CT in the staging of small-cell carcinoma of the lung: incidence of metastases and effect on prognosis.
CT studies of the abdomen performed on 72 patients with small-cell carcinoma of the lung were retrospectively reviewed to assess the role of abdominal CT in staging. Forty-four of the 72 patients had extensive disease, defined as disease extending beyond the confines of one hemithorax, plus or minus mediastinal or ipsilateral supraclavicular disease or ipsilateral pleural effusion. Initial-staging abdominal CT revealed one or more sites of metastatic disease in 26 (59%) of these 44 patients, while 18 patients had normal initial CT examinations. Statistical analysis of patients with extensive disease revealed a significant increase in complete therapeutic response (p = .0054) and in the length of survival (p = .001) among those who had extensive disease without abdominal metastases as compared with those who had abdominal metastases on their initial abdominal CT examination. The development of new or recurrent abdominal metastases in general or in specific organs on follow-up scans obtained in 35 patients did not significantly decrease their survival time as compared with that of patients without such metastases. Our findings suggest that CT of the abdomen is beneficial in the initial staging of patients with small-cell carcinoma of the lung and provides prognostic information concerning response to therapy and length of survival.


[Modern aspects of diagnostics of bacterial endocarditis].
Modern approaches to diagnostics of infective endocarditis (IE) are considered in the article. Possibilities for detection of the disease provided by various diagnostic criteria are analyzed. The authors demonstrate the advantages of improved criteria and present the diagnostic signs of subacute endocarditis in congenital heart diseases, artificial valve IE, and IE in drug addicts. Differential diagnostics issues are covered as well.


Determination of value of bovine respiratory disease control using a remote early disease identification system compared with conventional methods of metaphylaxis and visual observations.
Mitigation of the deleterious effects of bovine respiratory disease (BRD) is an important issue in the cattle industry. Conventional management of calves at high risk for BRD often includes mass treatment with antimicrobials at arrival followed by visual observation for individual clinical cases. These methods have proven effective; however, control program efficacy is influenced by the accuracy of visual observation. A remote early disease identification (REDI) system has been described that monitors cattle behavior to identify potential BRD cases. The objective of this research was to compare health and performance outcomes using either traditional BRD control (visual observation and metaphylaxis) or REDI during a 60-d postarrival phase in high-risk beef calves. The randomized controlled clinical trial was performed in 8 replicates at 3 different facilities over a 19-mo period. In each replicate, a single load of calves was randomly allocated to receive either conventional management (CONV; total = 8) or REDI (total = 8) as the method for BRD control. Cattle were monitored with each diagnostic method for the first 30 d on feed and performance variables were collected until approximately 60 d after arrival. Statistical differences ( < 0.10) were not identified in common performance (ADG) or health (morbidity, first treatment success, and mortality risk) among the treatment groups. Calves in the REDI pens had a lower ( < 0.01) average number of days on feed at first treatment (9.1 ± 1.2 d) compared with CONV pens (15.8 ± 1.2 d). There were no statistical differences ( > 0.10) in risk of BRD treatment and REDI calves were not administered antimicrobials at arrival; therefore, REDI calves had a lower ( < 0.01) average number of doses of antimicrobials/calf (0.75 ± 0.1 doses) compared with CONV calves (1.67 ± 0.1 doses). In this trial, the REDI system was comparable to conventional management with the potential advantages of earlier BRD diagnosis and decreased use of antimicrobials. Further research should be performed to evaluate the longer-term impacts of the 2 systems.


Factors involved in early lenvatinib dose reduction: a retrospective analysis.
Lenvatinib, a multi-tyrosine kinase inhibitor, has been proven to be an effective treatment option for patients with iodine-131-refractory thyroid cancer. Many adverse effects of lenvatinib have been reported; thus, dose reduction is common. However, a few studies have analyzed the causes of lenvatinib dose reduction in daily clinical practice. Here, we investigate the factors involved in early lenvatinib dose reduction to analyze lenvatinib dose modification. We analyzed 20 thyroid cancer patients who began receiving lenvatinib at the Kumamoto University Hospital Cancer Center from July 2015 to November 2016. Patients were classified into the following groups based on the time until first withdrawal or dose reduction in lenvatinib: group A (early, ≤ 10 days) and group B (other, > 10 days). Patients' clinical features and reasons for withdrawal or dose reduction were analyzed. The age range of patients was 54-91 years, and the median observation period was 293 days. There were no significant differences in the administered line of lenvatinib; the presence/absence of primary residual tumors; or the history of hypertension, proteinuria, and diarrhea between the two groups (A, n = 7; B, n = 13). The cause for initial withdrawal or dose reduction was grade 3 hypertension in all group A patients, which was significantly higher than that in group B (p = 0.0001). Our results suggest that early blood pressure control may be effective as a method to maintain the lenvatinib dose intensity.


Smoothness Sensor: Adaptive Smoothness-Transition Graph Convolutions for Attributed Graph Clustering.
Clustering techniques attempt to group objects with similar properties into a cluster. Clustering the nodes of an attributed graph, in which each node is associated with a set of feature attributes, has attracted significant attention. Graph convolutional networks (GCNs) represent an effective approach for integrating the two complementary factors of node attributes and structural information for attributed graph clustering. Smoothness is an indicator for assessing the degree of similarity of feature representations among nearby nodes in a graph. Oversmoothing in GCNs, caused by unnecessarily high orders of graph convolution, produces indistinguishable representations of nodes, such that the nodes in a graph tend to be grouped into fewer clusters, and pose a challenge due to the resulting performance drop. In this study, we propose a smoothness sensor for attributed graph clustering based on adaptive smoothness-transition graph convolutions, which senses the smoothness of a graph and adaptively terminates the current convolution once the smoothness is saturated to prevent oversmoothing. Furthermore, as an alternative to graph-level smoothness, a novel fine-grained nodewise-level assessment of smoothness is proposed, in which smoothness is computed in accordance with the neighborhood conditions of a given node at a certain order of graph convolution. In addition, a self-supervision criterion is designed considering both the tightness within clusters and the separation between clusters to guide the entire neural network training process. The experiments show that the proposed methods significantly outperform 13 other state-of-the-art baselines in terms of different metrics across five benchmark datasets. In addition, an extensive study reveals the reasons for their effectiveness and efficiency.


How valid is dopamine transporter imaging as a surrogate marker in research trials in Parkinson's disease?
To use functional imaging data as indices of disease progression, it is essential that methods are valid. It is not possible for that validation to come from pathology and the methods can only gain validity from the relationship to clinical indices of progression. Validity as a measurement of disease progression depends upon sensitivity to clinical progression, low scan-to-scan error, and resilience to confounding effects. Data from the available dopamine transporter (DAT) positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies are examined for these three key factors. Presently, there are insufficient data to enable the satisfactory design of neuroprotection studies and to enable statements on their relevance to disease progression and neuroprotection. The recently completed CALM-PD neuroimaging study is examined. There is sufficient doubt surrounding the sensitivity, reproducibility, and confounding effects in this study that these data should not be used to formulate a decision on de novo therapy in Parkinson's disease.


[The treatment of the primary intrarenal reflux. Is the surgery always necessary?].
THE AIMS OF THIS STUDY was to evaluate the relationship between intrarenal reflux (I.R.R.) and reflux nephropathy (R.N.) in order to know the results of surgical and non surgical treatment. Fifty one children with 64 kidneys with primary I.R.R. were studied. 53% of them were less than one year of age. Initial examination were: urography, ultrasounds, cystography and DMSA scan; the follow up was done with ultrasounds, DMSA scan and cystography. When no R.N. was present, grade of reflux was < IV, and age < 12 years, a non surgical treatment was indicated. During first examination R.N. was demonstrated in 47% of kidneys; the main difference was the grade of reflux: 16/44 II-III (36%) and 14/20 IV-V (70%). Surgical treatment was performed in 42 (82%) children and non surgical in 9 (18%). Reflux stopped in 98% and 100%, respectively. Only one child, without R.N., developed a new renal scar, and a previous R.N. progressed in two. I.R.R. can be treated successfully without surgery in selected cases.


Ablation of PPARγ in subcutaneous fat exacerbates age-associated obesity and metabolic decline.
It is well established that aging is associated with metabolic dysfunction such as increased adiposity and impaired energy dissipation; however, the transcriptional mechanisms regulating energy balance during late life stages have not yet been fully elucidated. Here, we show that ablation of the nuclear receptor PPARγ specifically in inguinal fat tissue in aging mice is associated with increased fat tissue expansion and insulin resistance. These metabolic effects are accompanied by decreased thermogenesis, reduced levels of brown fat genes, and browning of subcutaneous adipose tissue. Comparative studies of the effects of PPARγ downregulation in young and mid-aged mice demonstrate a preferential regulation of brown fat gene programs in inguinal fat in an age-dependent manner. In conclusion, our study uncovers an essential role for PPARγ in maintaining energy expenditure during the aging process and suggests the possibility of targeting PPARγ to counteract age-associated metabolic dysfunction.


Infants' sex affects neural responses to affective touch in early infancy.
Social touch is closely related to the establishment and maintenance of social bonds in humans, and the sensory brain circuit for gentle brushing is already active soon after birth. Brain development is known to be sexually dimorphic, but the potential effect of sex on brain activation to gentle touch remains unknown. Here, we examined brain activation to gentle skin stroking, a tactile stimulation that resembles affective or social touch, in term-born neonates. Eighteen infants aged 11-36 days, recruited from the FinnBrain Birth Cohort Study, were included in the study. During natural sleep, soft brush strokes were applied to the skin of the right leg during functional magnetic resonance imaging (fMRI) at 3 cm/s velocity. We examined potential differences in brain activation between males (n = 10) and females (n = 8) and found that females had larger blood oxygenation level dependent (BOLD) responses (brushing vs. rest) in bilateral orbitofrontal cortex (OFC), right ventral striatum and bilateral inferior striatum, pons, and cerebellum compared to males. Moreover, the psychophysiological interactions (PPI) analysis, setting the left and right OFC as seed regions, revealed significant differences between males and females. Females exhibited stronger PPI connectivity between the left OFC and posterior cingulate or cuneus. Our work suggests that social touch neural responses are different in male and female neonates, which may have major ramifications for later brain, cognitive, and social development. Finally, many of the sexually dimorphic brain responses were subcortical, not captured by surface-based neuroimaging, indicating that fMRI will be a relevant technique for future studies.


[The importance of the bacterial overgrowth syndrome in the development of disorders metabolic functions of the liver in non-alcoholic fatty liver disease].
To study the basic metabolic functions of the liver in patients with non-alcoholic fatty liver disease and to assess the relationship of these disorders with the bacterial overgrowth syndrome. 50 patients with non-alcoholic fatty liver disease at the stage of steatosis were examined. In the verification of the diagnosis, hepatobiliary system ultrasound and FibroMax test data were used. A study was conducted of indicators of lipid, carbohydrate, protein, pigment, mineral metabolism and the exchange of enzymes in the blood. The bacterial overgrowth syndrome was studied by the results of a hydrogen breath test with lactulose using a LactofаH2 analyzer. Patients with non-alcoholic fatty liver disease showed a significant increase in total cholesterol (median 5.9 mmol/l vs 5.0 mmol/l, p=0.000013), triglycerides (1.35 g/l vs 0.9 g/l, p=0.014), glucose (5.65 mmol/l against 5.1 mmol/l, p=0.000001) of blood serum compared with the control group. An increase in total protein and a tendency to decrease in albumin, an increase in serum sodium and calcium were detected. In patients with non-alcoholic fatty liver disease there is a significant increase in the markers of cytolysis and cholestasis compared with the control group. The bacterial overgrowth syndrome was detected in 72% of cases, with ileocecal valve function impaired in 50% of patients, gastrointestinal motility slowed down, or colon dysbiosis occurred. A correlation analysis revealed positive relationships between the bacterial overgrowth syndrome on the one hand and glucose (r=0.83, p0.05), total protein (r=0.35, p0.05), calcium (r=0.5, p0.05) on the other hand; negative relationship between the bacterial overgrowth syndrome and albumin (r=-0.8, p0.05). In this case, a positive relationship between the bacterial overgrowth syndrome and the increase in glycemia after glucose loading, that is, absorption in the small intestine, was revealed. The established violations of the metabolic functions of the liver with non-alcoholic fatty liver disease are closely related to the bacterial overgrowth syndrome.


Noninflammatory entities and the differential diagnosis of positive three phase bone imaging.
The greater sensitivity of skeletal imaging over radiography (93% vs. 50%) for the detection of early osteomyelitis is well known. The introduction of the three phase protocol has improved the specificity of skeletal imaging by eliminating various noninfectious entities; however, the occurrence of false-positive studies is not unusual. Four such cases have been observed by the authors in a group of 34 patients suspected of having osteomyelitis and who had positive three phase skeletal imaging. These includes a patient with giant cell tumor, synovial cell sarcoma, gouty arthritis, and Reiter's syndrome. A description of these cases and a brief review of several other entities associated with positive three phase bone imaging is the subject of this atlas article, which should serve as an aid in the differential diagnosis of this commonly performed scintigraphic procedure.


When Patient Rudeness Impacts Care: A Review of Incivility in Healthcare.
Healthcare workers increasingly face incivility and rude behaviors from patients, families, and visitors. Although these are less severe than other types of mistreatment, studies have documented that they may still impact healthcare worker well-being and patient care. Defining and measuring incivility can be challenging because current research relies on the perceptions of the targets. Furthermore, there is often overlap among different types of mistreatment, and much of it goes unreported by those who experience it. Nevertheless, multiple studies have documented that incivility is common in healthcare and has been associated with burnout and intent to leave. In clinical settings, multiple consequences for patient care have been documented, including adverse consequences in the diagnostic and intervention performance of teams, as well as team processes. One theory is that incivility incidents divert cognitive resources away from the intervention and that these experiences may interfere with higher-order reasoning. Although limited research has been performed in the areas of prevention, response to incidents of incivility, and best practices for ameliorating the effects of incivility, some promising interventions have been reported in the literature.


[Congenital mitral valve malformations. Anatomical lesions and surgical treatment in paediatric age (author's transl)].
Congenital mitral valve malformations are diverse. When they present clinically in infancy medical treatment is often ineffective. Mitral valve replacement with prosthesis in children carries an high operative and postoperative risk. For these reasons the Authors have undertaken in 1972 a cooperative study which includes: 1) a surgical classification of the congenital mitral valve lesions; 2) a systematic attempt to repair the mitral valve. Over 43 observed cases, 18 have been operated upon. Eleven cases (61%) presented associated cardiac lesions. Hospital mortality was 16% (3 cases). There have been either mortality nor morbidity in the follow-up period. Eight cases have been recatheterized two years after the operation. The pulmonary artery pressure has significantly decreased and the mitral insufficiency disappeared almost completely. The classification, suggested by the Authors, is explained in details.


Vasoreactivity in pre- and postmenopausal women: evaluation by pharmacodynamic modeling.
Postmenopausal women experience an increase in cardiovascular mortality and morbidity compared with their premenopausal counterparts. This study was undertaken to develop a pharmacodynamic model to determine whether vascular reactivity in postmenopausal women differed from that in premenopausal women. Eleven subjects in each group were recruited. Graded doses of norepinephrine and insulin were infused via the dorsal hand vein. Venous diameter was measured by ultrasound. Dosage and venous diameter were fit to a Hill-type pharmacodynamic model in which norepinephrine acts as a vasoconstrictor and insulin counteracts varying fractions of norepinephrine constriction. Fitted pharmacodynamic parameters for norepinephrine did not differ uniformly between groups, but at norepinephrine infusion rates between 14 and 46 ng/mL, postmenopausal women demonstrated increased norepinephrine-induced vasoconstriction. Also, the modeled maximal response to insulin (Emaxi) was greater in premenopausal women. By stepwise linear regression, maximal response to insulin was found to be related to menopausal status and diastolic blood pressure. Postmenopausal women showed differences in vasoreactivity that may have important implications in the pathogenesis of hypertension.


Src family kinases are involved in EphA receptor-mediated retinal axon guidance.
EphA receptor tyrosine kinases and their ephrin ligands play important roles in wiring of the developing nervous system. We have investigated here the function of Src family kinases (SFKs) in the retinotectal projection to dissect the signaling pathways by which EphA receptors control actin/microtubule rearrangements that underlie growth cone guidance and collapse. Both EphAs and SFKs are expressed broadly in retinal growth cones, and SFKs are recruited to EphA receptors after ephrinA stimulation. In the stripe and growth cone collapse assays we observe an abolition of EphA-mediated repulsion after inhibiting SFKs, either pharmacologically or enzymatically via electroporation-mediated overexpression of the SFK inhibitor Csk. In addition, we identify cortactin and the RhoGEF ephexin, which interact with EphA receptors in retinal axons, as targets of SFK-dependent tyrosine phosphorylation. In sum, our data suggest an important role of SFKs as downstream signaling molecules in EphA receptor-mediated repulsive axon guidance.


On numerical classification of solution adsorption isotherms.
To numerically classify solution adsorption isotherms, a difference or deviation measure, DS(mc) (the relative difference between two sums of the adsorption maximum's characteristics of selectivity isotherms x 100), is derived. The measure is applicable to completely miscible binary solutions on solids. This quantity evaluates the difference between an adsorption system and the ideal adsorption system (ideal adsorbed and bulk phases, homogeneous surface, and equal molar area solution components) at the point of maximum adsorption. For model systems, DS(mc)s are calculated at several levels of surface heterogeneity (Gaussian distribution of surface energy) and for different signs of phase nonideality (regular solution phases) on a homogeneous surface and on a simple two-site-type heterogeneous surface. All heterogeneous surfaces have negative DS(mc) values, but nonideal phases have DS(mc)s with signs opposite to the sign of deviation from Raoult's law. DS(mc)s from both U- and S-shape isotherms are reported for 16 experimental systems consisting of hydrocarbon mixtures and both alcohol + hydrocarbon and alcohol + water solutions or acetone + carbon tetrachloride on several silica gels and a variety of carbons.


Female professional divers. Similarities and differences between male and female professional divers.
The aim of the present study was to explore the potential differences between female and male professional divers with regards to demographics, diving certificates, areas of diving, diving activity and health effects. The Norwegian Labour Inspection Authority's Diving certificate register contains data on all professional inshore divers who have held a certificate at any time since 1980. Forty nine per cent of these divers responded to the "Norwegian diver 2011" questionnaire. Of these divers 64 female and 1327 male divers completed the questionnaire about their professional diving career, certificate, year of onset and the year they stopped diving professionally if they were not still active in the diving industry. The level of general education was higher among female divers. More males than females were fully certified in diving. The mean age was lower among female than male fully certified divers. Fully certified female divers reported a lower total number of dives, shallower dives and diving for a shorter period of time than the male divers. They also had a lower percentage of work within the quay/construction sector and more often worked as teachers/instructors. A lower percentage of fully certified females than males had experienced decompression sickness (16.7% vs. 26.9%). Life-threatening events and psychologically challenging events were less common among females, as were adverse health effects. No such gender differences were seen for divers with a restricted certificate. The fully certified, female professional divers in our study had a very short diving career, reported fewer and shallower dives, and chose less physically demanding jobs than their male counterparts. They also had a higher level of education, reported less health problems and a better quality of life. The health effects seem to be related to the type of work rather than to gender.


Compliance in hemodialysis patients: a multivariate regression analysis.
Successful treatment of patients with end-stage renal failure requires, in addition to dialysis, strict control of dietary, fluid and medication intake. In the present study we measured, in 50 chronic hemodialysis patients, serum potassium (K), serum phosphate (PO4) and interdialytic weight gain as indices of diet, medication and fluid compliance, respectively. Dietary compliance did not correlate with fluid or medication compliance, whereas fluid intake and medication compliance were related (p = 0.01). Age, time on dialysis, place of birth and whether the patient came accompanied or not to the dialysis unit were the main variables affecting serum K levels. Sex, ethnic origin and education significantly affected serum PO4. Sex, place of birth, marital status, number of children and years of education affected fluid intake. The compliance of the hemodialysis patient with different aspects of his regimen is thus multifactorial. Attempts to improve compliance and thus reduce morbidity and mortality should be aimed at identifying the population with low compliance and exposing them to educational programs.


Shape and composition control of Bi19S27(Br3-x ,I x ) alloyed nanowires: the role of metal ions.
We present the first colloidal synthesis of highly uniform single-crystalline Bi19S27Br3 nanowires (NWs) with a mean diameter of ∼9 nm and tunable lengths in the range of 0.15-2 μm in the presence of foreign metal ions (Al3+). The Al3+ ions not only control the growth of NWs, but also achieve species transformation, i.e., from Bi2S3 to Bi19S27Br3, and are not present in the resulting NWs. This colloidal chemistry approach can be expanded to prepare a family of single-crystalline Bi19S27(Br3-x ,I x ) alloyed NWs with controlled compositions (0 ≤ x ≤ 3). Interestingly, these alloyed NWs show an unusual composition-independent band gap of ∼0.82 eV, and theoretical calculations indicate that this phenomenon comes from the very minor contributions of the halogens to the valence band maximum and conduction band minimum. The photodetectors made of Bi19S27(Br3-x ,I x ) alloyed NWs show a pronounced photoresponse with high stability and reproducibility, which makes the NWs potentially useful candidates in optoelectronic devices.


Serial ERG monitoring of response to therapy in vitamin A deficiency related night blindness.
Two male patients with known systemic disorders who presented with complaints of nyctalopia underwent a complete ophthalmic examination including electrophysiological evaluation and serum vitamin A (retinol) levels. A significant vitamin A deficiency was detected, supplementation started and repeat electroretinogram (ERG) testing was carried out to monitor the timeline of recovery. Restoration of rod and generalised cone function was rapid within the first week of receiving treatment and near normal recovery was seen after 1 month of supplementation. Serial monitoring of ERG changes in vitamin A deficiency (VAD) associated night blindness plays an important role to demonstrate functional recovery post-treatment. The different effects of VAD on rod and cone function, and their rate of recovery, may reflect differences in the visual cycle between the two photoreceptors. We report the serial ERG changes in VAD related night blindness secondary to intestinal lipofuscinosis and liver cirrhosis in two patients.


[Surgery of the parathyroid gland].
The introduction of various techniques for minimally invasive parathyroidectomy (MIP) has changed both the conceptual and surgical approach to parathyroid disease. The perceived advantages of minimally invasive surgery among both clinicians and patients have been a major factor in the development of new surgical techniques, as well as refinement of preoperative localization techniques such as high-sensitive ultrasound and technetium sestamibi scanning. MIP for primary hyperparathyroidism has become an accepted part of endocrine surgical practice worldwide. In recent years, medical management of hyperparathyroidism has been made possible with the use of therapeutics specifically aimed at the calcium-sensing receptor, a cell-surface protein widely viewed as the primary regulator of parathyroid hormone secretion. The calcimimetic agent cinacalcet is approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis and for the treatment of hypercalcemia in patients with parathyroid carcinoma. Cinacalcet is also expected to be useful in the treatment of intractable hypercalcemia in patients with primary hyperparathyroidism for whom parathyroidectomy is indicated but surgery is clinically inappropriate or contraindicated.


Rituximab: an emerging treatment for recurrent diffuse alveolar hemorrhage in systemic lupus erythematosus.
Diffuse alveolar hemorrhage (DAH) is a rare manifestation of systemic lupus erythematosus (SLE) and is associated with high mortality rates. Treatment typically consists of aggressive immunosuppression with pulse-dose steroids, cyclophosphamide, and plasma exchange therapy. Mortality rates remain high despite use of multiple medical therapies. We present a case of recurrent DAH in a 52-year-old female with SLE after a deceased donor renal transplant who was successfully treated with rituximab. Our report highlights the pathophysiologic importance of B-cell-mediated immunosuppression in SLE-associated DAH and suggests that rituximab may represent a viable alternative to cyclophosphamide in the treatment of this disease. We also review eight other reported cases of rituximab use in SLE-associated DAH.


Bone marrow transplantation for CVID-like humoral immune deficiency associated with red cell aplasia.
Patients with common variable immunodeficiency (CVID) have a higher incidence of autoimmune disease, which may mark the disease onset; however, anemia secondary to pure red cell aplasia is an uncommon presenting feature. Here, we describe a case of CVID-like humoral immune deficiency in a child who initially presented with red cell aplasia and ultimately developed progressive bone marrow failure. Although bone marrow transplantation (BMT) has been associated with high mortality in CVID, our patient was successfully treated with a matched sibling BMT and engrafted with >98% donor chimerism and the development of normal antibody titers to diphtheria and tetanus toxoids.


Observation by fluorescence microscopy of transcription on single combed DNA.
Molecular combing is a powerful procedure for aligning a large array of DNA molecules onto a surface. This technique usually leads to an overstretching of about 150% of the molecules' contour length. By changing the magnitude of capillary forces during the combing process, we were able to reduce the relative extension of the DNA molecules. Thus we achieved combing of T7 DNA with an extension close to its molecule contour length. We checked the ability of combed DNA to interact with DNA binding proteins. Using the T7 bacteriophage transcription system, we investigated the transcription activity of RNA polymerase on combed DNA by direct visualization of newly synthesized fluorescent RNAs. Our experiments show that no transcription activity occurs on overstretched DNA molecules, whereas we observe a transcription activity for nonoverstretched molecules. This activity is observed both in multiple initiation experiments and for one immobilized T7 RNA polymerase per promoter. These results open possibilities for the study of single enzyme actions on combed DNA by optical methods.


Differentiation of Aspartic and Isoaspartic Acid Using 193 nm Ultraviolet Photodissociation Mass Spectrometry.
Spontaneous conversion of aspartic acid (Asp) to isoaspartic acid (isoAsp) is a ubiquitous modification that influences the structure and function of proteins. This modification of Asp impacts the stability of biotherapeutics and has been linked to the development of neurodegenerative diseases. We explored the use of 193 nm ultraviolet photodissociation (UVPD) to distinguish Asp and isoAsp in the protonated and deprotonated peptides. The differences in the relative abundances of several fragment ions uniquely generated by UVPD were used to differentiate isomeric peptide standards containing Asp or isoAsp. These fragment ions result from the cleavage of bonds N-terminal to Asp/isoAsp residues in addition to the side-chain losses from Asp/isoAsp or the losses of COOH, CO2, CO, or H2O from y-ions. Fragmentation of Asp-containing tryptic peptides using UVPD resulted in more enhanced w/w + 1/y - 1/x ions, while isoAsp-containing peptides yielded more enhanced y - 18/y - 45/y - 46 ions. UVPD was also used to identify an isomerized peptide from a tryptic digest of a monoclonal antibody. Moreover, UVPD of a protonated nontryptic peptide resulted in more enhanced y ions N- and C-terminal to isoAsp and differences in b/y ion ratios that were used to identify the isoAsp peptide.


Oxidative Cross-Coupling of sp(3)- and sp(2)-Hybridized C-H Bonds: Vanadium-Catalyzed Aminomethylation of Imidazo[1,2-a]pyridines.
The vanadium-catalyzed oxidative coupling of substituted 2-arylimidiazo[1,2-a]pyridines to N-methylmorpholine oxide, which acts as both a coupling partner and an oxidant, has been achieved. This reaction was applied to various substituted imidiazo[1,2-a]pyridine and indole substrates, resulting in yields as high as 90%. Mechanistic investigations indicate that the reaction may proceed via a Mannich-type process. This work demonstrates how oxidative aminomethylation can be used as a useful method to introduce tertiary amines into heterocycles, thus providing an alternative method for conventional Mannich-type reactions.


Strengths and limitations of genetic mouse models of Parkinson's disease.
Genetic mouse models based on alpha-synuclein overexpression are particularly compelling because abnormal accumulation of alpha-synuclein occurs in sporadic Parkinson's disease (PD). Our laboratory has characterized a mouse overexpressing wild-type human alpha-synuclein under the Thy1 promoter, which confers broad expression of the transgene in neurons. These mice show progressive sensorimotor anomalies starting at 2 months of age, as well as olfactory and digestive deficits similar to those observed in patients at early stages of PD. Patterns of gene expression examined in nigrostriatal neurons isolated by single-cell laser capture microdissection in these mice at 6 months of age show an upregulation of defence mechanisms including increased levels of genes involved in proteasome and mitochondrial function, as well as cholesterol biosynthesis. At the same time, numerous alterations in genes encoding ion channels suggest that changes in the cellular function of these neurons occur independently of cell death. These data provide information on the early effects--in a mammalian brain--of a mutation known to cause PD, and they identify a number of useful end points for evaluating potential neuroprotective therapies that could interfere with the pathophysiological mechanisms of PD upstream of neuronal cell death.


Biomechanics of the optic nerve head and sclera in canine glaucoma: A brief review.
Glaucoma is a leading cause of irreversible blindness, a progressive optic neuropathy with retinal ganglion cell (RGC) death beginning in the optic nerve head (ONH). A primary risk factor for developing glaucoma is elevated intraocular pressure (IOP). Reducing IOP is the only treatment proven to be effective at delaying disease progression. Nevertheless, even when patients have their IOP reduced, the majority of them continue to lose vision. There are, in both humans and dogs, significant interindividual variabilities in susceptibilities to IOP-induced optic nerve damage. Vision loss progresses much more slowly in Beagles with open-angle glaucoma (OAG) caused by ADAMTS10 mutation. This can be attributed to the mutation-related altered ocular biomechanical properties. The principal site of optic nerve (ON) damage in glaucoma is the ONH. It is suggested that the biomechanical properties of the ONH and the surrounding peripapillary sclera (PPS) contribute to glaucoma development and progression. As far as the beneficial biomechanical properties of the ONH and PPS for a decreased susceptibility and slow progression of glaucoma, data are inconsistent and conflicting. Recent biomechanical studies on beagles with ADAMTS10 mutation demonstrated that the mutant dogs have mechanically weak posterior sclera. This weakness was associated with a reduced collagen density and a lower proportion of insoluble collagen. These changes, observed before glaucoma development, were considered intrinsic characteristics caused by the mutation rather than a secondary effect of IOP elevation. Further studies of ADAMTS10-OAG may elucidate the effects of altered biomechanical properties of ONH and PPS in determining the glaucoma progression.


X-linked ichthyosis and X-linked placental sulfatase deficiency: a disease entity. Histochemical observations.
The combined occurrence of X-linked steroid sulfatase deficiency of the placenta and X-linked ichthyosis is reported in 6 unrelated boys. Placental steroid sulfatase deficiency was diagnosed on the basis of a very low total estrogen excretion (6 cases), verified prenatally by the dehydroepiandrosterone sulfate (DHEAS) loading test in 4 cases and postnatally by clinical investigations (6 cases) and by biochemical investigations (5 cases). In addition, microsomal arylsulfatase C (MAS) could not be detected in the placental homogenate of the five cases investigated. Lysosomal arylsulfatases were within the normal range. All boys developed well except for X-linked ichthyosis. In the 5 cases investigated the skin biopsy showed the same MAS deficiency histochemically in the granular layer of the epidermis as in the trophoblast cells. The same holds true for the skin of carriers. Steroid sulfatase activity of cultured skin fibroblasts from the boys was almost nil (3 cases). The histochemical technique offers a practical approach in the scientific investigation of keratotic conditions.


[Qualitative and quantitative determination of bacterial populations in aquatic habitats. 6. Germ regrowth and drinking water].
Regrowth of bacteria in the sphere of drinking water is dependent on time (stagnation of the water in the distribution system) and on the absence or inefficiency of disinfectants e.g. chlorine and chlorinedioxid. Traceable amounts of assimilable organic carbon are not a presupposition for the multiplication of the bacteria. Even in bidistilled water growth of bacteria could be observed. Under laboratory conditions it was shown that the number of bacteria increased to 10(4) per ml after a 4-days-incubation at 20 degrees C. In particular the multiplication is concerned with the autochton bacterial flora of the water e.g. pseudomonas species. As a result of the identification of the bacteria it was observed that the increase number of bacteria was accompanied by a decrease of individual species. After 6-days'-incubation of the water samples pseudomonas-species like P. fluorescens and P. cepacia were the predominating bacterial forms. The number of Gram-positive bacteria decreased significantly during incubation.


Multiplex detection of enzymatic activity with responsive lanthanide-based luminescent probes.
Multiplex analyte detection in complex dynamic systems is desirable for the investigation of cellular communication networks as well as in medical diagnostics. A family of lanthanide-based responsive luminescent probes for multiplex detection is reported. The high modularity of the probe design enabled the rapid assembly of both green and red emitters for a large variety of analytes by the simple exchange of the lanthanide or an analyte-cleavable caging group, respectively. The real-time three-color detection of up to three analytes was demonstrated, thus setting the stage for the non-invasive investigation of interconnected biological processes.


Beta-adrenoceptor blocker toxicity: clinical features and therapy.
Therapy for severe beta-blocker poisoning should be based upon careful supportive therapy. In most cases of poisoning, elimination techniques cannot be expected to remove significant amounts of the drug. Inotropic drugs such as isoproterenol, prenalterol and glucagon in adequate (i.e. large) doses may be necessary to counteract cardiac failure.


Vasopressin phosphorylates HSP27 in aortic smooth muscle cells.
Administration of arginine vasopressin (AVP) time-dependently induced the phosphorylation of heat shock protein 27 (HSP27) at Ser-15 and Ser-85 in smooth muscle of aorta in vivo. The AVP-induced phosphorylation of HSP27 at Ser-15 and Ser-85 was inhibited by a V1a receptor antagonist but not by a V2 receptor antagonist. In cultured aortic smooth muscle A10 cells, AVP markedly stimulated the phosphorylation of HSP27 at Ser-15 and Ser-85. The AVP-induced phosphorylation of HSP27 was attenuated by SB203580 and PD169316, inhibitors of p38 mitogen-activated protein (MAP) kinase, but not by PD98059, a MEK inhibitor. These results strongly suggest that AVP phosphorylates HSP27 via p38 MAP kinase in aortic smooth muscle cells.


Beta-2-microglobulin expression in the liver after liver transplantation.
The distribution of major histocompatibility complex (MHC) class 1 antigens was studied in the liver after transplantation by immunoperoxidase staining for beta-2-microglobulin (beta 2m), a subunit of the class 1 antigen system. Paraffin wax sections were examined from 25 "time zero" biopsy specimens, taken immediately after insertion of the graft, and 87 biopsy specimens taken after transplantation in seven diagnostic categories: acute cellular rejection (n = 22); resolving acute rejection (n = 8); chronic rejection (n = 22); pure cholestasis (n = 14); ischaemia/infarction (n = 5); biliary obstruction (n = 8); massive haemorrhagic necrosis (n = 8). Staining was graded semiquantitatively on a scale of 0-3+ in bile ducts, hepatocytes, sinusoidal lining cells and vascular endothelium. Using the "time zero" biopsy specimens as a baseline for comparison, increased expression of beta 2m was seen in bile ducts, hepatocytes, and endothelial cells after transplantation. These changes were most pronounced in cases of rejection but also occurred in other graft conditions. The degree of hepatocyte and endothelial staining was significantly higher in cases of rejection and massive haemorrhagic necrosis than in the other categories. These findings may have implications for the pathogenesis and diagnosis of rejection of the transplanted liver.


The fifth plot of the Carcinogenic Potency Database: results of animal bioassays published in the general literature through 1988 and by the National Toxicology Program through 1989.
This paper is the fifth plot of the Carcinogenic Potency Database (CPDB) that first appeared in this journal in 1984 (1-5). We report here results of carcinogenesis bioassays published in the general literature between January 1987 and December 1988, and in technical reports of the National Toxicology Program between July 1987 and December 1989. This supplement includes results of 412 long-term, chronic experiments of 147 test compounds and reports the same information about each experiment in the same plot format as the earlier papers: the species and strain of test animal, the route and duration of compound administration, dose level and other aspects of experimental protocol, histopathology and tumor incidence, TD50 (carcinogenic potency) and its statistical significance, dose response, author's opinion about carcinogenicity, and literature citation. We refer the reader to the 1984 publications (1,5,6) for a guide to the plot of the database, a complete description of the numerical index of carcinogenic potency, and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. The five plots of the database are to be used together, as results of individual experiments that were published earlier are not repeated. In all, the five plots include results of 4487 experiments on 1136 chemicals. Several analyses based on the CPDB that were published earlier are described briefly, and updated results based on all five plots are given for the following earlier analyses: the most potent TD50 value by species, reproducibility of bioassay results, positivity rates, and prediction between species.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular systematics of the Sordariales: the order and the family Lasiosphaeriaceae redefined.
The Sordariales is a taxonomically diverse group that has contained from seven to 14 families in recent years. The largest family is the Lasiosphaer-iaceae, which has contained between 33 and 53 genera, depending on the chosen classification. To determine the affinities and taxonomic placement of the Lasiosphaeriaceae and other families in the Sordariales, taxa representing every family in the Sordariales and most of the genera in the Lasiosphaeriaceae were targeted for phylogenetic analysis using partial sequences of the large-subunit (LSU) nrDNA. Based on molecular data, only genera within the families Chaetomiaceae, Lasiosphaeriaceae and Sordariaceae are retained within the redefined Sordariales. The order is a coherent group with morphologies that vary along well-defined lines, including large ascomata with large-celled membraneous or coriaceous walls and ascospores that show variation on a distinctive developmental theme, often with appendages or sheaths. The paraphyletic chaetomiaceous complex and the strongly supported Sordariaceae are nested among taxa traditionally placed in the Lasiosphaeriaceae. Analyses also indicate that 11 genera belong in the paraphyletic lasiosphaeriaceous complex. These taxa share a similar developmental pattern in their ascospore morphology that extends to the Sordariales as a whole. Based on these similarities in morphology, 13 additional genera are retained within the lasiosphaeriaceous complex and more than 35 genera have relationships in the order overall. Based on LSU data, 17 genera that have been assigned to the Lasiosphaeriaceae sensu lato are transferred to other families outside the Sordariales and 22 additional genera with differing morphologies subsequently are transferred out of the order. Two new orders, Coniochaetales and Chaetosphaeriales, are recognized for the families Coniochaetaceae and Chaetosphaeriaceae respectively. The Boliniaceae is accepted in the Boliniales, and the Nitschkiaceae is accepted in the Coronophorales. Annulatascaceae and Cephalothecaceae are placed in Sordariomycetidae inc. sed., and Batistiaceae is placed in the Euascomycetes inc. sed.


Identification of two ryanodine receptor transcripts in neonatal, slow-, and fast-twitch rabbit skeletal muscles.
Analysis of the primary structure of the rabbit skeletal muscle ryanodine receptor led to the identification of two molecules of 5032 and 5037 residues, respectively. Such a sequence discrepancy is likely to be due to the alternative splicing of a 15 bp exon (1) encoding a 5 amino acid insertion (Ala-Gly-Asp-Ala-Gln) after residue 3479. By using PCR on first strand cDNA, we searched for the 15 base pair insertion in the ryanodine receptor mRNA from adult slow- and fast-twitch skeletal muscle, as well as from fast-muscles, at various stages of post-natal development. All rabbit skeletal muscle mRNAs, regardless of their developmental stage and twitch properties, contain two RYR transcripts, suggesting the coexistence of two RYR isoforms in mammalian skeletal muscle.


Protein Kinase CK2, a Potential Therapeutic Target in Carcinoma Management
The Protein kinase CK2 (formerly known as casein kinase 2) is a highly conserved serine/ threonine kinase overexpressed in various human carcinomas and its high expression often correlates with poor prognosis. CK2 protein is localized in the nucleus of many tumor cells and correlates with clinical features in many cases. Increased expression of CK2 in mice results in the development of various types of carcinomas (both solids and blood related tumors, such as (breast carcinoma, lymphoma, etc), which reveals its carcinogenic properties. CK2 plays essential roles in many key biological processes related to carcinoma, including cell apoptosis, DNA damage responses and cell cycle regulation. CK2 has become a potential anti-carcinoma target. Various CK2 inhibitors have been developed with anti-neoplastic properties against a variety of carcinomas. Some CK2 inhibitors have showed good results in in vitro and pre-clinical models, and have even entered in clinical trials. This article will review effects of CK2 and its inhibitors on common carcinomas in in vitro and pre-clinical studies.


On the process of cellular division in Escherichia coli. VI. Use of a methocel-autoradiographic method for the study of cellular division in Escherichia coli.
A technique allowing chain formation by Escherichia coli for the analysis of the segregation of certain cellular components by autoradiographic methods has been developed. Deoxyribonucleic acid labeled with (3)H-thymidine does not appear to segregate preferentially with one or another of the bacteria. Membrane lipids labeled with either (3)H-oleate or (3)H-glycerol are evenly distributed among all progeny cells. A similar pattern of distribution of cell wall material is observed when (3)H-diaminopimelate is used as the marker.


Comparison of two therapeutic regimens using the same topical corticoid for stable psoriasis.
In a masked, randomized, concurrently controlled clinical trial we compared the therapeutic response of two regimens in which the same topical corticoid was used to treat 52 men who had stable psoriasis. One regimen, called reduced dose, consisted of once-a-day application of a representative potent fluorinated topical steroid ointment, fluocinonide (Lidex), combined with three-times-a-day application of its vehicle. The other regimen, called traditional dose, consisted of four-times-a-day topical application of the same steroid. Patients were assigned to one of the two regimens and observed for six weeks. Confidence intervals for the difference in true mean response under these two regimens provide good evidence that for these patients the traditional dose was not clinically superior to the reduced dose.


Development and application of an arabinose-inducible expression system by facilitating inducer uptake in Corynebacterium glutamicum.
Corynebacterium glutamicum is currently used for the industrial production of a variety of biological materials. Many available inducible expression systems in this species use lac-derived promoters from Escherichia coli that exhibit much lower levels of inducible expression and leaky basal expression. We developed an arabinose-inducible expression system that contains the L-arabinose regulator AraC, the P(BAD) promoter from the araBAD operon, and the L-arabinose transporter AraE, all of which are derived from E. coli. The level of inducible P(BAD)-based expression could be modulated over a wide concentration range from 0.001 to 0.4% L-arabinose. This system tightly controlled the expression of the uracil phosphoribosyltransferase without leaky expression. When the gene encoding green fluorescent protein (GFP) was under the control of P(BAD) promoter, flow cytometry analysis showed that GFP was expressed in a highly homogeneous profile throughout the cell population. In contrast to the case in E. coli, P(BAD) induction was not significantly affected in the presence of different carbon sources in C. glutamicum, which makes it useful in fermentation applications. We used this system to regulate the expression of the odhI gene from C. glutamicum, which encodes an inhibitor of α-oxoglutarate dehydrogenase, resulting in high levels of glutamate production (up to 13.7 mM) under biotin nonlimiting conditions. This system provides an efficient tool available for molecular biology and metabolic engineering of C. glutamicum.


Estimating alcohol-attributable injury deaths: A comparison of epidemiological methods.
Injuries often involve alcohol, but determining the proportion caused by alcohol is difficult. Several approaches have been used to determine the causal role of alcohol, but these methods have not been compared directly with one another. Such a comparison would be useful for understanding the strengths and comparability of different approaches. This study compared estimates of average annual alcohol-attributable deaths in the United States from injuries during 2015-19 using a blood alcohol concentration (BAC) method compared with a population attributable fraction (PAF) approach. For the BAC method, we used a direct method involving the proportion of decedents with a high blood alcohol concentration (BAC; e.g. ≥ 0.10%). For the PAF approach, we compared the use of unadjusted survey data with average consumption data adjusted using alcohol sales data to account for underreporting and also accounting for the underreporting of binge drinking. Survey data were from the Behavioral Risk Factor Surveillance System and mortality data were from the National Vital Statistics System. The number of alcohol-attributable injury deaths using the direct method (48 516 deaths annually) was similar to that using PAF methods (47 879 deaths annually), but only when alcohol use measures were adjusted using alcohol sales data. Furthermore, estimates were similar for cause-specific categories of deaths, including non-motor vehicle unintentional injuries and motor vehicle crashes. Among PAF methods, excessive drinking accounted for 38.3% of injury deaths using unadjusted survey data, but 64.8% of injury deaths using adjusted data. Estimates of alcohol-attributable injury deaths from a direct method and from a population attributable fraction method that adjusts for alcohol use based on alcohol sales data appear to be comparable.


Anti-NGF autoantibodies and NGF in sera of Alzheimer patients and in normal subjects in relation to age.
It has been suggested that inflammation may be a possible cause of Alzheimer's disease (AD). Increased anti-NGF autoantibody levels and increased NGF frequency in serum have previously been associated with inflammatory responses. In this study no changes in anti-NGF autoantibody titers or in NGF frequency were detected in sera of AD patients, suggesting that they are not involved in the neuroimmunological mechanisms underlying AD. There were neither age-associated changes in NGF frequency in sera of four groups of normal subjects between 18-91 years of age. In contrast, anti-NGF autoantibodies were significantly increased in sera of the 31-45 yr age group.