Cytomegalovirus and rheumatic diseases: cases-based review.
Cytomegalovirus (CMV) infection is a common and typically benign disease in immunocompetent individuals. However, immunocompromised patients are at a greater risk of reactivation, leading to more severe outcomes. Patients with rheumatic diseases have a particularly high risk of opportunistic infections due to both the inherent immunosuppressive state conveyed by the disease itself and the use of potent immunosuppressant drugs, such as glucocorticoids, cyclophosphamide, and rituximab. Limited data are available regarding prophylactic or preemptive treatment of CMV infection in patients with rheumatic diseases. In this article the authors present two cases of rheumatic conditions complicated by CMV infection. The first case describes a patient with eosinophilic granulomatosis with polyangiitis, previously treated with glucocorticoids and cyclophosphamide, who developed CMV colitis with bowel perforation. The second case involves a woman with systemic lupus erythematosus who was diagnosed with CMV meningitis. Both cases reinforce the importance of establishing guidelines for surveillance and prophylaxis of CMV infection in these patients.


Clinical Efficacy of Yiqi Yangyin Decoction Combined with Docetaxel on Advanced Ovarian Cancer and the Effect on the Levels of Serum Markers VEGF, HE4, and CA125.
The study is designed to investigate the therapeutic effect of Yiqi Yangyin Decoction combined with docetaxel on advanced ovarian cancer (OC) patients and the effects on serum markers VEGF, HE4, and CA125. 92 patients with advanced OC were grouped into the study group and control group. The control group was given the treatment of basic chemotherapy combined with docetaxel. The study group was added the treatment of Yiqi Yangyin Decoction on the basis of the control group. The short-term efficacy, adverse reactions, tumor markers, quality of life, 3-year survival, and T cell subsets of the two groups were observed. Compared to the control group, the study group's incidence of adverse reactions was lower. VEGF, HE4, and CA125 in the study group were decreased more obviously. The levels of CD3+, CD4+, and CD4+/CD8+ were sharply higher in the study group, while CD8+ was notably reduced. After treatment, the scores of physical health, social function, and mental health in the study group were notably higher than those in the control group. Compared with the control group, the 3-year survival rate of the study group was notably higher, and the therapeutic effect of the study group was obviously better. The combination of Yiqi Yangyin Decoction and docetaxel can improve the body immunity and the therapeutic effect of advanced OC, decrease the incidence of adverse reactions, and prolong the survival time, with good safety and effectiveness.


A fatal neuromuscular disease in an adult patient after poliomyelitis in early childhood: consideration of the pathology of post-polio syndrome.
Post-polio syndrome (PPS) characterized by new neuromuscular problems can appear many years after acute poliomyelitis in polio survivors. We report a 77-year-old man with antecedent poliomyelitis who newly developed neuromuscular disease with a clinical course of 27 years, the final 10 years of which were characterized by apparent progression, thus raising doubt as to the clinical diagnosis of amyotrophic lateral sclerosis (ALS) following PPS. Pathologically, plaque-like, old poliomyelitis lesions were found almost exclusively in the lumbosacral cord, showing complete neuronal loss and glial scars in the anterior horns. Although less severe, neuronal loss and gliosis were also evident outside the old lesions, including the intermediate zone. Moreover, symmetrical degeneration of the corticospinal tracts, as evidenced by CD68 immunostaining, was a feature of the white matter of the lower spinal cord. In the motor cortex, loss of Betz cells was also confirmed. Synaptophysin immunostaining of the lumbosacral cord also revealed decreased expression outside the old lesions, excluding the posterior horn. Interestingly, decreased expression of synaptophysin was also evident in the cervical anterior horns, where no old lesions were observed. No Bunina bodies, TDP-43 inclusions, or Golgi fragmentation were found. Neurogenic atrophy was evident in the iliopsoas and scalenus muscles, and inclusion body myositis-like changes were also observed in these muscles and the tongue. Was it possible to have diagnosed this patient as having ALS? We consider that the features in this case may have represented the pathology of long-standing and/or fatal PPS itself, and not ALS.


A prospective, randomized evaluation of the effect of silver impregnated subcutaneous cuffs for preventing tunneled chronic venous access catheter infections in cancer patients.
This study was performed to evaluate the effect of a silver-impregnated cuff on the incidence of catheter-related bacteremia/fungemia or tunnel tract infection in cancer patients with chronic dual-lumen tunneled venous access catheters. Infection is a frequent and potentially life-threatening complication of tunneled chronic cuffed silastic central venous access catheters in cancer patients. Recent experience with antimicrobial silver-impregnated cuffs placed on nontunneled percutaneously inserted central venous catheters suggests that such a cuff may render the catheter less prone to infection. The authors prospectively randomized 200 cancer patients to receive either a dual-lumen 10 French tunneled cuffed silastic central venous access catheter or the same catheter with a second more proximal subcutaneous silver-impregnated cuff. All patients then were followed prospectively for infectious morbidity until the device was removed or the patient died. The hazard rate for infection/day (95% confidence limits) was 0.0022 (0.0015 to 0.0030) for standard catheters compared with 0.0027 (0.0019 to 0.0037) for catheters with silver-impregnated cuffs (p = not significant). Regression analysis of infection-free interval of both catheter types shows no difference over the lifetime of catheter as well as the over the first 48 days after insertion. The study indicated no effect of a silver-impregnated cuff in decreasing the incidence of catheter-related bacteremias/fungemias, tunnel infections, or the spectrum of causative microorganisms involved in cancer patients with tunneled chronic venous access catheters.


Onco-suppressor genes and their involvement in cancer (review).
Onco-suppressor genes are a heterogeneous set of genes that inhibit the cancer-related phenotype of cells. Because they are difficult to identify, only a few have been described. Evidence for their existence has mainly been indirect and comes from the following types of study. 1. Recessive cancer genes in higher and lower eukaryotes have been detected. If both alleles of these genes are deleted or inactivated, cancer develops. 2. Studies on cell hybrids have implicated genes which suppress various stages in the malignant conversion of normal cells e.g. immortalisation, morphological conversion and metastasis. 3. The isolation from virally induced transformants of flat, non-tumorigenic revertants in which expression of the transforming gene is not down-regulated suggests the presence of genes which suppress the effects of transformation. 4. Blocks to differentiation can be bypassed by inducing compounds or differentiation factors. 5. Studies on tumor inhibitory factors such as tumour necrosis factor and beta-TGF show that they have different effects on different types of cell-acting to promote growth in some cases and inhibit it in others. 6. The discovery of cis-acting negatice regulatory elements suggests that interaction of such elements with proteins may be important for control of gene expression particularly of infecting oncogenic viruses. 7. Suppression of the transformed phenotype of malignant cells by contact with normal cells that controls growth of neighboring cells. 8. The inhibition of proliferation of transformed cells by transfection with DNA from normal cells may be a useful method for cloning onco-suppressor genes. We discuss what is known and what is not known about this important class of gene.


Assessment of Hepatic Lesions After non-Thermal Tumor Ablation by Irreversible Electroporation in a Pig Model.
Irreversible electroporation (IRE) is a non-thermal and minimal invasive modality to ablate pathologic lesions such as hepatic tumors. Histological analysis of the initial lesions after IRE can help predict ablation efficacy. We aimed to investigate the histological characteristics of early hepatic lesions after IRE application using animal models. IRE (1500 V/cm, a pulse length of 100 μs, 60 or 90 pulses) was applied to the liver of miniature pigs. H&E and TUNEL staining were performed and analyzed. Ablated zones of pig liver were discolored and separated from the normal zone after IRE. Histologic characteristics of ablation zones included preserved hepatic lobular architecture with a unique hexagonal-like structure. Apoptotic cells were detected, and sinusoidal dilatation and blood congestion were observed, but hepatic arteries and bile ducts were intact around the ablation zones. The early lesions obtained by delivering monophasic square wave pulses through needle electrodes reflected typical histological changes induced by IRE. Therefore, it was found that the histological assessment of the early hepatic lesion after IRE can be utilized to predict the IRE ablation effect.


International Survey of ALS Experts about Critical Questions for Assessing Patients with ALS.
To define an applicable dataset for ALS patient registries we weighted specific clinical items as scored by worldwide ALS experts. Sixty participants were invited based on relevant clinical work, publications and personal acquaintance. They rated 160 clinical items consensually agreed by the members of our project, incorporating specialists from five European Centres. Scoring scheme was defined as: 1 - essential; 2 - important; 3 - not very important. A mixed effect model was applied to rank items and to find possible correlations with geographical region (Europe vs. outside Europe). We received 40 responses, 20 from Europe and 20 from outside; 42/160 data were scored as essential by >50% of the respondents, including: date of birth, gender, date of disease onset, date of diagnosis, ethnicity, region of onset, predominant upper neuron (UMN) or lower motor neuron (LMN) impairment, proximal versus distal weakness, respiratory symptoms, dysarthria, weight loss, signs of LMN/UMN involvement, emotional incontinence, cognitive changes, respiratory signs, neck weakness, body mass index, ALSFRS-R at entry, ALSFRS-R subscores at entry, timing and pattern of spreading and staging, electromyography, spirometry, MRI, CK level, riluzole intake, genetic background, history of physical exercise and previous and current main occupation. Four components were scored as non-relevant, including place of birth, blood pressure and pain at onset. There was no significant difference between regions (European vs. non-European countries). Our study identified a consensual set of clinical data with 42 specific items that can be used as a minimal data set for patient registers and for clinical trials.


Sexual differentiation of the human hypothalamus: Relationship to gender identity and sexual orientation.
Gender identity (an individual's perception of being male or female) and sexual orientation (heterosexuality, homosexuality, or bisexuality) are programmed into our brain during early development. During the intrauterine period in the second half of pregnancy, a testosterone surge masculinizes the fetal male brain. If such a testosterone surge does not occur, this will result in a feminine brain. As sexual differentiation of the brain takes place at a much later stage in development than sexual differentiation of the genitals, these two processes can be influenced independently of each other and can result in gender dysphoria. Nature produces a great variability for all aspects of sexual differentiation of the brain. Mechanisms involved in sexual differentiation of the brain include hormones, genetics, epigenetics, endocrine disruptors, immune response, and self-organization. Furthermore, structural and functional differences in the hypothalamus relating to gender dysphoria and sexual orientation are described in this review. All the genetic, postmortem, and in vivo scanning observations support the neurobiological theory about the origin of gender dysphoria, i.e., it is the sizes of brain structures, the neuron numbers, the molecular composition, functions, and connectivity of brain structures that determine our gender identity or sexual orientation. There is no evidence that one's postnatal social environment plays a crucial role in the development of gender identity or sexual orientation.


Sensitivity of Electron Transfer Mediated Decay to Ion Pairing.
Ion pairing in electrolyte solutions remains a topic of discussion despite a long history of research. Very recently, nearest-neighbor mediated electronic de-excitation processes of core hole vacancies (electron transfer mediated decay, ETMD) were proposed to carry a spectral fingerprint of local solvation structure and in particular of contact ion pairs. Here, for the first time, we apply electron-electron coincidence detection to a liquid microjet, and record ETMD spectra of Li 1s vacancies in aqueous solutions of lithium chloride (LiCl) in direct comparison to lithium acetate (LiOAc). A change in the ETMD spectrum dependent on the electrolyte anion identity is observed for 4.5 M salt concentration. We discuss these findings within the framework of the formation and presence of contact ion pairs and the unique sensitivity of ETMD spectroscopy to ion pairing.


Partial ileal bypass in type II familial hypercholesterolemia. Eleven-year experience at the Montreal Heart institute.
The National Heart, Lung, and Blood Institute is currently sponsoring a multicenter clinical trial to evaluate the long-term efficacy of partial ileal bypass in the prevention of recurrent myocardial infarction in hypercholesterolemia patients. Thus we felt that a report of our clinical results with this intervention at the Montreal Heart Institute during the last 11 years would be of interest. Twenty patients with type II hyperlipoproteinemia and a mean age of 38 (range 25-54) years underwent partial ileal bypass between March 1971 and April 1978. This intervention was associated with aortocoronary bypass surgery in 11 patients. All patients were followed at regular intervals. The mean survival time was 70.7 (range 1-123) months. Two deaths were observed during follow-up, one from an acute myocardial infarction and the other from ventricular fibrillation, respectively, 1 month and 1 and one-half years after partial ileal bypass. The ileal bypass was undone twice because of gastrointestinal problems including a malabsorption syndrome and repeated episodes of subocclusion. A progressive decrease of the effects of the operation on serum cholesterol was noted, from a 33 per cent reduction at 3 months to 43 per cent at 2 years and 16 per cent at 6 years. Two patients presented an acute myocardial infarction respectively 3 and 4 years after the operation, respectively, and one patient suffered a right-sided hemiplegia at age 30, 12 months after the operation. Of 14 patients with angina pectoris preoperatively (class III in 10), eight remained symptomatic postoperatively (class I and II angina in five).(ABSTRACT TRUNCATED AT 250 WORDS)


Aggregation-Induced Near-Infrared Emission and Electrochemiluminescence of an Iridium(III) Complex for Ampicillin Sodium Sensing.
A new iridium(III) complex was synthesized and characterized. Its photophysical properties and aggregation-induced emission and electrochemiluminescence in the near-infrared range were studied. The large conjugated cyclometallic ligand 1,2-phenylbenzoquinoline (pbq) was selected to form the Ir-C bond with the metal iridium(III) center and provide near-infrared emission of the complex. The auxiliary ligand 4,4'-diamino-2,2'-bipyridine (dabpy) can form hydrogen bonds, which was beneficial for the generation of aggregation-induced emission. The complex was aggregated into small spherical nanoparticles in 80% water and fascinating nanorings in 90% water. The sensing of ampicillin sodium (AMP) antibiotic by the iridium(III) complex were also investigated by photoluminescent and electrochemiluminescent methods. The complex showed a good selectivity toward AMP antibiotic compared to sodium phenylacetate and other eight antibiotics. The detection limits for AMP antibiotic was 0.76 μg/mL. This work provided a new strategy for the design of iridium(III) complex-based aggregation-induced emission and electrochemiluminescence probes for the sensing application.


RUNX1-ETO: Attacking the Epigenome for Genomic Instable Leukemia.
Oncogenic fusion protein RUNX1-ETO is the product of the t(8;21) translocation, responsible for the most common cytogenetic subtype of acute myeloid leukemia. RUNX1, a critical transcription factor in hematopoietic development, is fused with almost the entire ETO sequence with the ability to recruit a wide range of repressors. Past efforts in providing a comprehensive picture of the genome-wide localization and the target genes of RUNX1-ETO have been inconclusive in understanding the underlying mechanism by which it deregulates native RUNX1. In this review; we dissect the current data on the epigenetic impact of RUNX1 and RUNX1-ETO. Both share similarities however, in recent years, research focused on epigenetic factors to explain their differences. RUNX1-ETO impairs DNA repair mechanisms which compromises genomic stability and favors a mutator phenotype. Among an increasing pool of mutated factors, regulators of DNA methylation are frequently found in t(8;21) AML. Together with the alteration of both, histone markers and distal enhancer regulation, RUNX1-ETO might specifically disrupt normal chromatin structure. Epigenetic studies on the fusion protein uncovered new mechanisms contributing to leukemogenesis and hopefully will translate into clinical applications.


Scientific Knowledge Graph of Acupuncture for Migraine: A Bibliometric Analysis from 2000 to 2019.
This study aims to explore the trend and knowledge mapping of acupuncture for migraine through bibliometrics. It retrieved the literature on acupuncture for migraine in the Web of Science database from 2000 to 2019, and then resorted to CiteSpace to conduct bibliometric analysis to attain the knowledge mapping. The total number of publications each year has increased year by year, and the average annual growth rate from 2000 to 2009 was 15.57%, while from 2010 to 2019 was 6.35%, with a faster growth rate from 2000 to 2009. According to the cluster analysis of institutions, authors, cited references, and keywords, 10, 7, 12, and 10 categories were gained from 2000 to 2019. The most productive countries, institutions, and authors are the USA and China, Technical University of Munich and Beijing University of Chinese Medicine, Linde K and Liang FR from 2000 to 2019, whose frequency is 119/103, 28/24, and 28/24, respectively. However, the most important of them are Canada, Sichuan University, and Witt CM. Owing to their highest centrality, they are 0.86, 0.54, and 0.27 separately. Moreover, cited references that contributed to the most co-citations are Linde K (2005), yet, the most vital cited reference is Karst M (2001). Keywords such as migraine, acupuncture, headache, pain, and randomized controlled trial are the most frequently used. However, needle acupuncture is the crucial keyword. In the cluster analysis of institutions, authors, cited references, and keywords from 2000 to 2019, the largest cluster categories are #0 migraine prophylaxis, #1 randomized controlled trial, #0 episodic migraine, and #0 topiramate treatment. Then, randomized controlled trials of acupuncture prevention and treatment of migraine are the most important research content in this field. Through the bibliometric analysis of the research on acupuncture for migraine in the Web of Science database in the past 20 years, the trends and the Knowledge Graph of the country, institution, author, cited reference, and the keyword are acquired, which have an important guiding significance for quickly and accurately positioning the key information in the field.


Waterborne and Surface-Associated Carbohydrates as Settlement Cues for Larvae of the Specialist Marine Herbivore Alderia modesta.
Larvae of the specialist marine herbivore Alderia modesta (Opisthobranchia: Ascoglossa) metamorphose in response to a chemical settlement cue from the alga Vaucheria longicaulis, the obligate adult prey. Bioactivity coeluted with both high and low molecular weight carbohydrates in solution, and with insoluble high molecular weight carbohydrates associated with the algal cell wall. Larvae metamorphosed in response to water conditioned by V. longicaulis, as well as to frozen and homogenized algal tissue. The inducer was efficiently extracted from the algae with boiling water, but after all soluble activity was extracted, residual tissue still induced larval settlement. Ethanol precipitation of a boiled-water extract followed by gel filtration chromatography showed that the precipitate contained carbohydrates of >100,000 Da molecular weight, while the supernatant contained only low molecular weight carbohydrates (<2,000 Da); in both cases all activity was associated with the carbohydrate peak. An aqueous-insoluble 4% NaOH extract was chromatographed in 7 M urea to yield a bioactive high molecular weight carbohydrate peak. Activity was not affected by proteinase K or mild acid hydrolysis, but was significantly decreased by periodate treatment. The results indicate that larvae of A. modesta metamorphose in response to both water-soluble and surface-associated carbohydrates of V. longicaulis, and that the soluble cue exists as both high and low molecular weight isoforms.


Carbon clusters on the Ni(111) surface: a density functional theory study.
To understand the nucleation of carbon atoms to form carbon clusters on transition metal substrates during chemical vapor deposition (CVD) synthesis, the structure, energetics, and mobility of carbon intermediates up to 6 atoms on the Ni(111) surface were investigated using Density Functional Theory (DFT). Carbon clusters were found to be more thermodynamically stable than adsorbed atomic carbon, with linear carbon structures being more stable than branched and ring structures. Carbon chains were also found to have higher mobility than branched configurations. The interaction energy between carbon clusters and the Ni surface shows that branched carbon clusters have stronger interaction with the Ni substrate when compared with the carbon chains, supporting that carbon chains generally have higher mobility than branched clusters. The transition states and energy barriers for the formation of different carbon clusters were also studied. The results show that the formation of the branched configurations is kinetically favored as it presents lower energy barriers than those obtained for carbon chains.


Identification of purine deoxyribonucleoside kinases from human leukemia cells: substrate activation by purine and pyrimidine deoxyribonucleosides.
Cell extracts from human leukemic T lymphoblasts and myeloblasts were chromatographed on DEAE-cellulose columns to separate purine deoxyribonucleoside, deoxyadenosine (dAdo) and deoxyguanosine (dGuo), phosphorylating activities. Three distinct purine deoxyribonucleoside kinases, a deoxycytidine (dCyd) kinase, an adenosine (Ado) kinase, and a deoxyguanosine (dGuo) kinase (the latter appears to be localized in mitochondria), were resolved. dCyd kinase contained the major phosphorylating activity for dAdo, dGuo, and 9-beta-D-arabinofuranosyladenine (ara-A). Ado kinase represented a second kinase for dAdo and ara-A while a third kinase for dAdo was found in mitochondria. dCyd kinase was purified about 2000-fold with ion-exchange, affinity, and hydrophobic chromatographies. On gel electrophoresis, both dCyd and dAdo phosphorylating activities comigrated, indicating that the activities are associated with the same protein. The enzyme showed a broad pH optimum ranging from pH 6.5 to pH 9.5. Divalent cations Mg2+, Mn2+, and Ca2+ stimulated dCyd kinase activity; Mg2+ produced the maximal activity. dCyd kinase from either lymphoid or myeloid cells showed broad substrate specificity. The enzyme used several nucleoside triphosphates, but ATP, GTP, and dTTP were the best phosphate donors. dCyd was the best nucleoside substrate, since dCyd kinase had an apparent Km of 0.3, 85, 90, and 1400 microM for dCyd, dAdo, dGuo, and ara-A, respectively. The enzyme exhibited substrate activation with both pyrimidine and purine deoxyribonucleosides, suggesting that there is more than one substrate binding site on the kinase. These studies show that, in lymphoblasts and myeloblasts, purine deoxyribonucleosides and their analogues are phosphorylated by dCyd kinase, Ado kinase, and dGuo kinase.


[Sleep apnea in pregnancy].
Snoring, chronic rhinitis and fragmentation of sleep are common symptoms in pregnancy, especially in the third trimester. The prevalence of obstructive sleep apnea is also increased in pregnant women and can be associated with pregnancy induced hypertension, preeclampsia and diabetes mellitus. The fetus is as well exposed to a higher risk of prematurity and intra-uterine growth restriction. Given the lack of adequate screening tool, the diagnosis of obstructive sleep apnea is a challenge for the physician and a high degree of clinical suspicion is necessary in order to identify the patients at risk and propose an appropriate management.


Treatment of stress urinary incontinence with duloxetine hydrochloride.
Currently, there are no approved medications for the treatment of stress urinary incontinence (SUI) in the United States. The effectiveness of duloxetine in the treatment of SUI is linked to its inhibition of presynaptic neuronal reuptake of serotonin and norepinephrine in the central nervous system, resulting in elevated levels of serotonin and norepinephrine in the synaptic cleft. In animal studies, this agent leads to an increase in nerve stimulation to the urethral striated sphincter muscle. A similar mechanism in women is believed to result in stronger urethral contractions, with improved sphincter tone during urine storage and physical stress. In 3 randomized, placebo-controlled clinical trials, patients receiving duloxetine had a statistically significant and clinically relevant reduction in the number of incontinence episodes and a corresponding improvement in quality of life. If this use of duloxetine is approved by the U.S. Food and Drug Administration, as it has been by the European regulatory agencies, it will be the first drug indicated for the treatment of SUI. This pharmacologic therapy is an additional option for women and is likely to become an integral component of patient management.


Scaling of adult body weight to height across sex and race/ethnic groups: relevance to BMI.
Body mass index (BMI) is formulated on the assumption that body weight (BW) scales to height with a power of 2 (BW∝height(2)), independent of sex and race-ethnicity. Powers differing from 2 are observed in studies of selected samples, thus raising the question if BMI is a generalizable metric that makes BW independent of height across populations. The objectives were to test the hypothesis that adult BW scales to height with a power of 2 independent of sex and race-ethnicity and to advance an understanding of BMI as a measure of shape by extending allometric analyses to waist circumference (WC). We conducted cross-sectional subject evaluations, including body composition, from the NHANES and the Korean NHANES (KNHANES). Variations of the allometric model (Y = αX(β)) were used to establish height scaling powers (β ± SE) across non-Hispanic white and black, Mexican American, and Korean men and women. Exploratory analyses in population samples established age and adiposity as important independent determinants of height scaling powers (i.e., β). After age and adiposity in the next series of analyses were controlled for, BW scaling powers were nonsignificantly different between race/ethnic groups within each sex group; WC findings were similar in women, whereas small but significant between-race differences were observed in the men. Sex differences in β values were nonsignificant except for BW in non-Hispanic blacks and WC in Koreans (P < 0.05). Nationally representative powers for BW were (NHANES/KNHANES) 2.12 ± 0.05/2.11 ± 0.06 for men and 2.02 ± 0.04/1.99 ± 0.06 for women and for WC were 0.66 ± 0.03/0.67 ± 0.05 for men and 0.61 ± 0.04/0.56 ± 0.05 for women. Adult BW scales to height with a power of ∼2 across the 8 sex and race/ethnic groups, an observation that makes BMI a generalizable height-independent measure of shape across most populations. WC also follows generalizable scaling rules, a finding that has implications for defining body shape in populations who differ in stature.


Mycobacterium tuberculosis triggers autoimmunity?
Mycobacterial infections are known to induce the development of autoantibodies. This study was therefore carried out in endemic areas to look for the prevalence of autoantibodies in pulmonary and extra pulmonary tuberculosis, with and without rheumatological symptoms suggesting a possible role of mycobacterial infection triggering autoimmunity. The results reveal that there is a need for further studies to be carried out in relation to possible autoimmune phenomenon linked with Mycobacterium tuberculosis infections. Tuberculosis patients should ideally be screened for the presence of various autoantibodies, particularly for a detailed study on anti-nuclear antibody (ANA) specificities. Their significance has to be deciphered to understand the role of these background autoantibodies produced. It is important to screen all tuberculosis patients for autoantibody profile and should be followed up after the treatment for any flaring up of autoimmune related symptoms.


Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group.
Conventional chemotherapy has failed to substantially prolong survival for patients with advanced follicular lymphoma. To improve outcomes, the German Low-Grade Lymphoma Study Group (GLSG) initiated a randomized trial to compare the effect of potentially curative myeloablative radiochemotherapy followed by autologous stem cell transplantation (ASCT) with interferon-alpha (IFN-alpha) maintenance therapy in first remission. Three hundred seven patients (younger than 60 years) with follicular lymphoma were recruited into the trial from 130 institutions. After 2 cycles of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) or mitoxantrone-chlorambucil-prednisone (MCP) induction chemotherapy, patients were randomly assigned to either the ASCT or the IFN-alpha group. The respective therapy was started when patients achieved complete or partial remission after induction chemotherapy. Two hundred forty patients with follicular lymphoma are evaluable for the comparison of ASCT and IFN-alpha. In patients who underwent ASCT, the 5-year progression-free survival (PFS) rate was 64.7%, and in the IFN-alpha arm it was 33.3% (P < .0001). As expected, acute toxicity was higher in the ASCT group, but early mortality was below 2.5% in both study arms. In this randomized, multicenter trial, high-dose radiochemotherapy followed by ASCT significantly improved PFS compared with IFN-alpha in patients with follicular lymphoma when applied as consolidation in first remission. Longer follow-up is necessary to determine the effect of ASCT on overall survival.


Synthesis of a novel class of polyhydroxyalkanoates in Arabidopsis peroxisomes, and their use in monitoring short-chain-length intermediates of beta-oxidation.
The poly[(R)-3-hydroxyalkanoate] (PHA) synthase gene (phaC(Ac)) of Aeromonas caviae FA440 was modified by adding a peroxisome targeting signal encoding the last 10 amino acids at the carboxyl-terminal of spinach glycolate oxidase. The modified gene was introduced into Arabidopsis thaliana plants by Agrobacterium-mediated transformation. The transgenic Arabidopsis plant expressed the introduced gene and its protein, and it accumulated PHA in its tissues. Gas chromatography-mass spectrometry analysis demonstrated the accumulation of a novel type of PHA, poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate). This strongly suggests that short-chain-length (R)-3-hydroxyacyl-CoAs were generated from intermediates of peroxisomal beta-oxidation. It was revealed by using this transgenic plant that Tween-20 can activate peroxisomal beta-oxidation of short-chain-length fatty acids.


BamE directly interacts with BamA and BamD coordinating their functions.
The β-barrel assembly machinery (Bam) complex facilitates the assembly of outer membrane proteins (OMPs) in gram-negative bacteria. The Bam complex is conserved and essential for bacterial viability and consists of five subunits, BamA-E. BamA is the transmembrane component, and its β-barrel domain opens laterally to allow folding and insertion of incoming OMPs. The remaining components are regulatory, among which only BamD is essential. Previous studies suggested that BamB regulates BamA directly, while BamE and BamC serve as BamD regulators. However, specific molecular details of their functions remain unknown. Our previous research demonstrated that BamE plays a specialized role in assembling the complex between the lipoprotein RcsF and its OMP partners, required for the Regulator of Capsule Synthesis (Rcs) stress response. Here, we used RcsF/OmpA as a model substrate to investigate BamE function. Our results challenge the current view that BamE only serves as a BamD regulator. We show that BamE also directly interacts with BamA. BamE interaction with both BamA and BamD is important for function. Our genetic and biochemical analysis shows that BamE stabilizes the Bam complex and promotes bidirectional signaling interaction between BamA and BamD. This BamE function becomes essential when direct BamA/BamD communication is impeded.


Exposure to 2.45 GHz electromagnetic fields induces hsp70 at a high SAR of more than 20 W/kg but not at 5W/kg in human glioma MO54 cells.
To determine potential hazards from exposure to a high-frequency electromagnetic field (HFEMF) at 2.45 GHz by studies of the expression of heat-shock protein 70 (hsp70) in MO54 cells. MO54 cells were exposed to a HFEMF at average specific absorption rates (SAR) of 5, 20, 50 and 100 W/kg, using input powers of 0.8, 3.2, 7.8 and 13 W, at a temperature of up to 39 degrees C. An annular culture dish provided three levels of exposure for a given input power, designated inner, middle and outer rings. Two control groups were used: the first was subjected to sham exposure and the second was a temperature control, used to determine the effect of high temperature using incubation in a conventional incubator at 39 degrees C. Cell survival was determined in intervals up to 24 h. Protein was extracted from MO54 cells in both groups after 2, 4, 8 and 16 h exposure times. Changes in the hsp70 protein levels were analysed by Western blots. Little or no cell death was observed in the sham-exposed cells, nor for incubation at 39 degrees C for up to 16 h. Cell survival decreased to about 30% after exposure to HFEMF for 24 h at an average SAR of 100 W/kg. A slight increase in hsp70 was observed in cells in both the inner and outer rings of the plate after exposure at SAR levels of 25 and 78 W/kg, respectively, for 2 h. With increasing exposure time, hsp70 expression increased except for an SAR of 5 W/kg. In the raised temperature control at 39 degrees C, hsp70 expression also increased as the incubation time increased. However, the expression level of hsp70 for the HFEMF exposure was greater than that for the raised temperature control. HFEMF can produce an increased level of hsp70 expression in MO54 cells at SAR levels above 20 W/kg, even when the effect of raised temperature is taken into account.


[Association between WAGR syndrome and diaphragmatic hernia].
Anomalies in WT-1 (Wilms' tumor gene), mapped to 11p13, cause Denys-Drash, Frasier and WAGR syndromes. WAGR syndrome is characterized by Wilms' tumor (W), aniridia (A), genitourinary anomalies (G) and mental retardation (R). In the early human fetus, WT-1 is expressed in the pleural and abdominal mesothelium, and consequently this gene may play a role in diaphragm development. The first report of an association between WAGR syndrome and congenital diaphragmatic hernia has recently been published. We present another infant with aniridia, left cryptorchidism with testicular dysgenesis, right-sided posterolateral diaphragmatic hernia and moderate psychomotor retardation, in whom genetic study showed a deletion of 11p13 and PAX-6, confirming the diagnosis of WAGR syndrome.


Characterisation and dissolution of depleted uranium aerosols produced during impacts of kinetic energy penetrators against a tank.
Aerosols produced during impacts of depleted uranium (DU) penetrators against the glacis (sloping armour) and the turret of a tank were sampled. The concentration and size distribution were determined. Activity median aerodynamic diameters were 1 microm (geometric standard deviation, sigma(g) = 3.7) and 2 microm (sigma(g) = 2.5), respectively, for glacis and turret. The mean air concentration was 120 Bq m(-3), i.e. 8.5 mg m(-3) of DU. Filters analysed by scanning electron microscopy (SEM) and X ray diffraction showed two types of particles (fine particles and large molten particles) composed mainly of a mixture of uranium and aluminium. The uranium oxides were mostly U3O8, UO2.25 and probably UO3.01 and a mixed compound of U and Al. The kinetics of dissolution in three media (HCO3-, HCl and Gamble's solution) were determined using in-vitro tests. The slow dissolution rates were respectively slow, and intermediate between slow and moderate, and the rapid dissolution fractions were mostly intermediate between moderate and fast. According to the in-vitro results for Gamble's solution, and based on a hypothetical single acute inhalation of 90 Bq, effective doses integrated up to 1 y after incorporation were 0.54 and 0.56 mSv, respectively, for aerosols from glacis and turret. In comparison, the ICRP limits are 20 mSv y(-1) for workers and 1 mSv y(-1) for members of the public. A kidney concentration of approximately 0.1 microg U g(-1) was predicted and should not, in this case, lead to kidney damage.


New species of Leleja (Orthoptera: Gryllinae; Gryllini) with first female description for the genus.
Following the recent discovery of a new genus from Thailand, a new species of Leleja Gorochov 2016 was discovered from Sakaerat Environmental Research Station in the same province: Leleja khao sp. n. Despite their close proximity between their known distributions, Leleja khao sp. n. differs from the type species by the male genitalia and also their natural habitat. The female for the genus is also described here for the first time.


Auditory dysfunction in patients with cerebrovascular disease.
Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD) is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked.


Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia.
The Institute of Medicine (IOM) recently developed clinical criteria for chronic fatigue syndrome (CFS). There might be additional criteria that could select a more homogenous and impaired group of patients, particularly those with pain. The current study focused on criteria which involved meeting the four IOM criteria, excluding medical and psychiatric co-morbidities, along with having fibromyalgia (FM). Findings indicated that those meeting the IOM clinical criteria plus FM were more impaired on a wide variety of symptoms and functional areas than those meeting on the IOM criteria or those with just 6 months of fatigue. The implications of using such research criteria are discussed.


Accumulation of nerve growth factor protein at both rostral and caudal stumps in the transected rat spinal cord.
Changes in the nerve growth factor (NGF) content in the rat spinal cord during development or after traumatic spinal cord injury were examined by using a two-site enzyme immunoassay (EIA) system and an immunohistochemical technique. From embryonic day (E) 14 to postnatal day (P) 70, the spinal cord contained 200-300 pg NGF/g of wet tissue evenly in all regions tested. After complete spinal cord transection of P49 rats, the NGF level started to increase in the rostral and caudal stumps nearest to the injury site at 2 and 4 days, respectively. The NGF level of the caudal side returned to the original level by 2 weeks, but that of the rostral side remained high even 3 weeks, after the injury. At 4 days after the injury, NGF-like immunoreactivity in both stumps was predominantly localized in the axon-like structures of the white matter and in cells morphologically resembling immune cells. These observations suggest that the NGF was transported within the spinal tracts, and that NGF secreted from immune cells that had invaded into the injured spinal cord had accumulated around the transection site. Increased NGF at the injury site may be advantageous for injured neurons and involved in mechanisms directing to axonal regeneration of the injured spinal cord.


Overload From Anxiety: A Non-Motor Cause for Gait Impairments in Parkinson's Disease.
Threatening situations lead to observable gait deficits in individuals with Parkinson's disease (PD) who suffer from high trait anxiety levels. The specific characteristics of gait that are affected appear to be similar to behaviors observed while walking during a dual-task (DT) condition. Yet, it remains unclear whether anxiety is similar to a cognitive load. If it were, then those with PD who have high trait anxiety might be expected to be more susceptible to DT interference during walking. Thus, the overall aim of this study was to evaluate whether trait anxiety influences gait during single-task (ST) and DT walking. Seventy participants (high-anxiety PD [HA-PD], N=26; low-anxiety PD [LA-PD], N=26; healthy control [HC], N=18) completed three ST and three DT walking trials on a data-collecting carpet. The secondary task consisted of digit monitoring while walking. Results showed that during both ST and DT gait, the HA-PD group demonstrated significant reductions in walking speed and step length, as well as increased step length variability and step time variability compared with healthy controls and the LA-PD group. Notably, ST walking in the HA-PD group resembled (i.e., it was not significantly different from) the gait behaviors seen during a DT in the LA-PD and HC groups. These results suggest that trait anxiety may consume processing resources and limit the ability to compensate for gait impairments in PD.


[Protective effect of resveratrol on intestinal mucosal barrier in rats with severe acute pancreatitis].
To test the effect of resvertrol on protecting the intestinal mucosal barrier in rats with severe acute pancreatitis. Twenty four SD rats were randomly divided into three groups: severe acute pancreatitis without treatments (SAP group), severe acute pancreatitis with sham-operations (SO group), and severe acute pancreatitis treated with resveratrol (RES group). Specimen were obtained 6 hours after the severe acute pancreatitis was induced. The endotoxin level in the blood taken from portal vein was measured with turbidimetry. Apoptosis of mucosal cells was detected by TUNEL methods. The expressions of Bax and Bcl-2 mRNA in intestinal mucosal cells were determined by semi-quantitative RT-PCR. Mitochondrial membranous electric potential of intestinal mucosal cells was measured by confocal microscopy. The RES group had less serum endotoxin in portal vein than the SAP group (P < 0.01). The SAP group had higher apoptotic index of mucosal cells than the RES group (P < 0.01). The SAP group had higher expression of Bax mRNA in intestinal mucosal cells and lower expression of Bcl-2 mRNA than the RES group (P < 0.01). The SAP group had lower mitochondrial membranous electric potential of intestinal mucosal cells than the REA group (P < 0.01). Resvertrol inhibits the apoptosis of intestinal mucosa cells and protects the intestinal barrier function, which might prevent the translocation of bacteria and endotoxin in patients with severe acute pancreatitis.


A signature index for third order topological insulators.
In this work, we develop an index signature characterising the third order topological phases in 3D systems. This index is an alternating sum of monomial signatures of Higgs triplet values at 3D corners. We extend our method to N-dimensional systems with open boundaries, and demonstrate that the topological invariant can be efficiently generalised to any space dimension including the second order topological insulators. Known results on lower dimensional systems are recovered and an interpretation in the Higgs space parameters is given.


Impact of CD44 gene single nucleotide polymorphism (rs 13347) in mobilization of autologous HSCT.
MOBILIZATION: of stem cells into peripheral blood is a crucial step in the procedure of autologous stem cell transplantation. Mobilization can be affected by many variables;underlying diseases, prior treatment and age. Many genetic polymorphisms mainly in adhesion molecules are thought to affect mobilization success. The CD44 is a cell adhesion molecule which is highly heterogeneous structurally. Polymorphisms in this molecule may impair HSC lodgment in the bone marrow. was to assess the impact of CD44 single nucleotide polymorphism (rs13347) on the efficacy of mobilization of CD34+ hematopoietic progenitor cells in a cohort of Egyptian patients treated for lymphoma and multiple myeloma and scheduled for autologous stem cell transplantation. the study was conducted on 92 patients scheduled for autologous HSC mobilization and transplantation. SNP genotyping was done by 5 ꞌ nuclease assay on rotor gene. A statistical significant difference was detected between the patients with genotypes (CT + CC) and patients with (TT) genotype regarding the number of apheresis sessions required to gather the target CD34 count (p = 0.006).T allele is implicated in poorer mobilization. CD44 SNPs analysis may be helpful for predicting the poor mobilizers. These patients may benefit from newer modalities like adhesion molecules inhibitors.


IgG antibody patterns in aqueous humor of patients with primary open angle glaucoma and pseudoexfoliation glaucoma.
There has been growing body of evidence indicating an immunological component in the pathogenesis of glaucoma. Several studies found specific antibodies in sera of glaucoma patients. Recently, we detected antibody profiles in aqueous humor of patients with normal tension glaucoma that showed significant differences when compared to control subjects. The aim of this study was to compare the IgG antibody patterns against retinal antigens in aqueous humor of patients with primary open angle glaucoma, pseudoexfoliation glaucoma, and control subjects then to identify some of the important biomarkers of this study. Aqueous humor of 44 patients was analyzed: 15 patients with primary open angle glaucoma (POAG), 14 patients with pseudoexfoliation glaucoma (PEX), and 15 control subjects (CO). The aqueous was tested against western blots of bovine retinal antigens. The IgG antibody patterns were analyzed by multivariate statistical techniques. Some of the important biomarkers were identified via mass spectrometry (Maldi-TOFTOF). All patients showed complex patterns of IgG antibodies against retinal antigens. The discriminant analysis revealed a statistically significant difference between the antibody profiles of the POAG and the CO group (p=0.00018). There was also a statistically significant difference between the antibody profiles of the PEX and the CO group (p=0.0013). Not only were up-regulations in the glaucoma groups observed, compared to controls, but also down-regulations. There was no significant difference between the antibody patterns of the POAG and PEX group. The identified biomarkers included heat shock protein 27, alpha-enolase, actin, and GAPDH. We could show significant differences between the IgG antibody profiles of the glaucoma groups (PEX and POAG) and controls. The analysis of intraocular antibodies could provide further hints for autoimmune involvement in glaucoma.


Factors associated with vitamin D deficiency in European adolescents: the HELENA study.
Evidence indicates low 25-hydroxyvitamin D [(25(OH)D] concentrations in European adolescents. Identification of potential determinants is therefore essential to guide public health initiatives aiming at optimizing vitamin D status across Europe. The aim of the study was to identify potential influencing factors of 25(OH)D concentrations in European adolescents aged 12.5 to 17.5 y, participating in the multi-centre cross-sectional Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study. A subset of 1,006 participants (46.8% males) was drawn from the main study. Measures of body composition, biochemical markers, socioeconomic status, dietary intake, physical activity, fitness, sleep time and vitamin D genetic polymorphism (rs1544410) were assessed. Stepwise multivariate linear regression analysis was conducted stratified by gender. In males, linear regression of 25(OH)D, suggested that (1) winter season (β=-0.364; p<0.01), (2) higher latitudes (β=-0.246; p<0.01), (3) BMI z-score (β=-0.198; p<0.05) and (4) retinol concentration (β=0.171; p<0.05) independently influenced 25(OH)D concentrations. In females, (1) winter season (β=-0.370; p<0.01), (2) sleep time (β=-0.231; p<0.01), (3) supplement intake (β=0.221; p<0.05), (4) flexibility (β=0.184; p<0.05), (5) body fat % (β=0.201; p<0.05) (6), BMI z-score (β=-0.272; p<0.05), (7) higher latitudes (β=-0.219; p<0.01) and (8) handgrip strength (β=0.206; p<0.05) independently influenced 25(OH)D concentrations. Season, latitude, fitness, adiposity, sleep time and micronutrient supplementation were highly related to 25(OH)D concentrations found in European adolescents.


Direct effects of catecholamines and tyramine on sinoatrial conduction in isolated and blood-perfused dog atria.
We have investigated the effects of catecholamines (dopamine, norepinephrine, epinephrine and isoproterenol) and tyramine on sinoatrial conduction time (SACT), sinus cycle length (SCL) and developed tension (DT) in isolated atrial muscle, using an isolated and blood-perfused dog atrial preparation, perfused with heparinized blood from the carotid artery of the anesthetized donor dog. Each substance was continuously administered intraarterially into the cannulated sinus node artery. They had dose-dependent positive chronotropic and inotropic effects. Each produced not only a shortening but a prolongation of SACT. In experiments in which only a shortening occurred, the order of the potency for inducing the shortening of the SACT was isoproterenol greater than norepinephrine = epinephrine greater than dopamine greater than tyramine. The ratio of doses required to produce roughly a 15-25% shortening of the SACT was 1: 10: 10: 100: 300, respectively. The isoproterenol-induced shortening of the SACT was inhibited by treatment with propranolol. Tyramine-induced shortening was inhibited by imipramine. From these results, it is suggested that sympathomimetic amines induce a shortening of SACT through adrenergic beta-receptors and also readily induce a pacemaker shift in the SA nodal area.


[Recent progress in endocrine therapy of patients with breast cancer].
Endocrine therapy of breast cancer was reviewed historically, and growth or regression of the tumor in relation to estrogen level in pheripheral blood was elucidated. Discovery of anti-estrogens has brought big revolution in the therapy of breast cancer. Recent developments of GnRH analogue and inhibitor of steroidgenesis are expected to give us more useful tools for the treatment of the disease. Combinations of such hormonal drugs with different action mechanisms will be resulted in better prognosis of breast cancer patients.


Influence of counting statistics on borderline detection of hepatitis B antigen by a solid-phase radioimmunoassay.
The detection of hepatitis B antigen by a solid-phase radioimmunoassay technique is by now well established, particularly where transfusions are concerned. However, it would appear that the use of systematic procedures leading to positive detection, such as the "cutoff" method (mean counts per minute of the negative controls multiplied by a coefficient of 2.1), are open to criticism if elementary precautions concerning the time span and the statistical accuracy of radioactivity counting are not taken. The method may even prove inaccurate in a certain number of borderline cases studies in relation to plasma and different sera, especially if subjected to a single screening process over a large number of samples analyzed by computer. These deficiencies can be avoided by correcting the positive coefficient in relation to the mean counts per minute of negative controls, the statistical accuracy (relative standard deviation) and the distribution of counting times.


Genomic and physiological studies of early cryptochrome 1 action demonstrate roles for auxin and gibberellin in the control of hypocotyl growth by blue light.
Blue light inhibits elongation of etiolated Arabidopsis thaliana hypocotyls during the first 30 min of irradiation by a mechanism that depends on the phototropin 1 (phot1) photoreceptor. The cryptochrome 1 (cry1) photoreceptor begins to exert control after 30 min. To identify genes responsible for the cry1 phase of growth inhibition, mRNA expression profiles of cry1 and wild-type seedlings were compared using DNA microarrays. Of the roughly 420 genes found to be differentially expressed at the point of cry1 response incipience, approximately half were expressed higher and half lower in cry1 relative to the wild type. Many of the cry1-dependent genes encoded kinases, transcription factors, cell cycle regulators, cell wall metabolism enzymes, gibberellic acid (GA) biosynthesis enzymes, and auxin response factors. High-resolution growth studies supported the hypothesis that genes in the last two categories were indeed relevant to cry1-mediated growth control. Inhibiting GA4 biosynthesis with a 3beta-hydroxylase inhibitor (Ca-prohexadione) restored wild-type response kinetics in cry1 and completely suppressed its long-hypocotyl phenotype in blue light. Co-treatment of cry1 seedlings with Ca-prohexadione plus GA4 completely reversed the effects of the inhibitor, restoring the long-hypocotyl phenotype typical of the mutant. Treatment of wild-type seedlings with GA4 was not sufficient to phenocopy cry1 seedlings, but co-treatment with IAA plus GA4 produced cry1-like growth kinetics for a period of approximately 5 h. The genomic and physiological data together indicate that blue light acting through cry1 quickly affects the expression of many genes, a subset of which suppresses stem growth by repressing GA and auxin levels and/or sensitivity.


[Ultrasonic evaluation of the upper abdomen in cystic fibrosis].
Abdominal sonography should compulsory be used in patients with cystic fibrosis (CF). It is not difficult to detect early morphologic changes at liver, gall-bladder, pancreas, spleen, and vessels by ultrasound. As a non-invasive method sonography is a very useful tool for a comprehensive special care of outpatients with CF.


[Therapeutic principles in angioma of the mandible: applications in relation to a clinical observation (author's transl)].
When confronted with a case of angioma of the mandible, treatment should be directed towards two main areas:--to stop blood loss. Ligature of the external carotid can be life-saving, but it does not prevent the formation of nearby anastomotic vessels which refill, more or less rapidly, the external carotid axis. Ligature make embolization impossible by femoral way. A by-pass operation to improve permeability is also dangerous if not impossible. Ligature should be reserved only for those cases in which there is an immediate threat to life. On the contrary, embolization is necessary before surgery. --to treat the angioma. As radiotherapy is not effective or is dangerous, surgical treatment is necessary; either by a conservative operation or by radical resection. All these facts are illustrated dramatically by the case reported.


Sentinel nodes in lung cancer: review of our 10-year experience.
Sentinel node (SN) identification in patients with lung cancer is useful not only to minimize lymph node dissection, but also to target the best lymph nodes for intraoperative frozen section during segmentectomy. Since 2000, we have identified the SN in lung cancer patients using radioisotope (RI). This review presents our data on SN identification, describing the following: the procedure, using a radioisotope tracer; the flow of Tc-99 tin colloid after the injection; the characteristics of patients whose SNs could not be identified; ex vivo SN identification; reliability of in vivo SN identification; the algorithm for reducing mediastinal lymph node dissection; the differences in SN identification between large and small radioisotope particles; SNs at segmental lymph nodes; SN navigation segmentectomy for clinical stage IA non-small cell lung cancer; and small metastasis in the SN.


A functional MRI study of altered spontaneous brain activity pattern in patients with congenital comitant strabismus using amplitude of low-frequency fluctuation.
The aim of this study was to use amplitude of low-frequency fluctuation (ALFF) to investigate local features of spontaneous brain activity in patients with congenital comitant strabismus and clarify their relationship with emotional and psychosocial problems. A total of 20 patients with congenital comitant strabismus (ten males and ten females), and 20 healthy controls (ten males and ten females) closely matched in age, sex, and education underwent resting-state functional magnetic resonance imaging scans. The ALFF method was used to assess local features of spontaneous brain activity. Congenital comitant strabismus patients were distinguished from healthy controls by receiver operating characteristic curve. Correlation analysis was performed to explore the relationships between the observed mean ALFF signal values of the different areas and the Chinese version of the Hospital Anxiety and Depression Scale. Compared with healthy controls, patients with congenital comitant strabismus had significantly lower ALFF in the bilateral medialfrontal gyrus and higher values in the bilateral cerebellum posterior lobe and left angular gyrus. In the congenital comitant strabismus group, the Hospital Anxiety and Depression Scale-depression score showed a negative correlation with the ALFF signal values of the bilateral medial frontal gyrus (r=-0.550, P=0.012) and a negative correlation was noted between the mean ALFF signal values of the left angular gyrus and strabismus duration (r=-0.515, P=0.020). Congenital comitant strabismus mainly involves dysfunction in the bilateral medial frontal gyrus, bilateral cerebellum posterior lobe, and left angular gyrus, which may reflect the underlying pathologic mechanism of congenital strabismus.


Inactivation of human immunodeficiency virus type 1 in tissue culture fluid and in genital secretions by the spermicide benzalkonium chloride.
We have shown that the spermicidal agent benzalkonium chloride can exert a direct inhibitory effect on the viral reverse transcriptase activity of human immunodeficiency virus type 1 (HIV-1) when utilized at concentrations of 0.05% and higher. Exposure of HIV-1 to this disinfectant at concentrations of more than 0.05% was able to completely destroy viral infectivity, as assessed on susceptible target cells. We have further shown that HIV-1, which is present in both seminal and genital secretions, can be inactivated in such fluids by direct exposure to benzalkonium chloride.


One cell, multiple roles: contribution of mesenchymal stem cells to tumor development in tumor microenvironment.
The discovery of tissue reparative and immunosuppressive abilities of mesenchymal stem cells (MSCs) has drawn more attention to tumor microenvironment and its role in providing the soil for the tumor cell growth. MSCs are recruited to tumor which is referred as the never healing wound and altered by the inflammation environment, thereby helping to construct the tumor microenvironment. The environment orchestrated by MSCs and other factors can be associated with angiogenesis, immunosuppression, inhibition of apoptosis, epithelial-mesenchymal transition (EMT), survival of cancer stem cells, which all contribute to tumor growth and progression. In this review, we will discuss how MSCs are recruited to the tumor microenvironment and what effects they have on tumor progression.


The Palestinian-Israeli conflict: a disease for which root causes must be acknowledged and treated.
Fourth of June 2017 marks a half century of the Six Day War, three decades post the first Intifada, seven decades post the Palestinian Nakba (catastrophe), the 70th anniversary of Israeli Independence, and one century post the Balfour Declaration. Both Palestinians and Israelis remain occupied. Five million Palestinians remain sick with hopelessness and despair rendered by years of subjugation. Israelis are stuck, occupied by their historical narrative and transcendental fears. Over two decades have passed since the Oslo accords, which both Israelis and Palestinians hoped might be a historic turning point. This was supposed to put an end to the chronic disease of protracted conflict, allowing Palestinians to enjoy freedom in an independent state side by side to Israel and Israelis to live within peaceful, secure borders with the respect of the international community. Palestinians were ready to give up 78% of their land. Free Palestine would be in the remaining 22%, with East Jerusalem as the capital and a satisfactory solution to the Right of Return. The patient's diagnosis and seeking therapy has been delayed by greed, ignorance, ideology, violence and fear. Accurate diagnosis is needed to successfully heal the wounds and cure this chronic disease.


CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy.
The benefits of CAR-T therapy could be expanded to the treatment of solid tumors through the use of derived autologous αβ T cell, but clinical trials of CAR-T therapy for patients with solid tumors have so far been disappointing. CAR-T therapy also faces hurdles due to the time and cost intensive preparation of CAR-T cell products derived from patients as such CAR-T cells are often poor in quality and low in quantity. These inadequacies may be mitigated through the use of third-party donor derived CAR-T cell products which have a potent anti-tumor function but a constrained GVHD property. Vγ9Vδ2 TCR have been shown to exhibit potent antitumor activity but not alloreactivity. Therefore, in this study, CAR-T cells were prepared from Vγ9Vδ2 T (CAR-γδ T) cells which were expanded by using a novel prodrug PTA. CAR-γδ T cells suppressed tumor growth in an antigen specific manner but only during a limited time window. Provision of GITR co-stimulation enhanced anti-tumor function of CAR-γδ T cells. Our present results indicate that, while further optimization of CAR-γδ T cells is necessary, the present results demonstrate that Vγ9Vδ2 T cells are potential source of 'off-the-shelf' CAR-T cell products for successful allogeneic adoptive immunotherapy.


TRANSMERIDIAN JET LAG AND ITS PHARMACOLOGICAL CORRECTION.
The article deals with the development and correction of acute jet lag in a flight across several time zones. The investigation had the purpose to study dynamics of subjective and objective psychophysiological parameters and demonstrate methods of prophylaxis and correction of acute jet lag due to transmerdian flights. Subjects were 8 normal volunteers (experimental group) at the age of 26-55 years flying eastward over 7 times zones. The investigation included 3 stages: baseline, preparatory (21-d course of Euricoma longifolia extraction) and main (intake of donormil, cirkadin and artificial sleep during the flight). Functional diagnostics was performed on the baseline stage, on completion of the preparatory stage and on the next day after the flight (21-22 days from the beginning of the preparatory stage). Objective and subjective methods were used to evaluate the autonomic and cardiovascular systems and mental performance. In the control group (n = 4) functional diagnostics was performed on the same days. The investigations showed the benefit of preparation for transmeridian air travel and experimentally demonstrated positive effects of the proposed pharmacological correction of acute transmeridian jet lag.


Huntington's Disease in Arab Countries.
Huntington's disease (HD) is an inherited neurodegenerative disorder. Involuntary choreaform movements are the main symptom. The prevalence of HD in Arab countries is not fully understood, as there are only a few reports indicating disease incidence. Therefore, there is an urgent need for an investigation to determine the frequency of HD in the Middle East, especially within Arab countries, and at the same time enhance people's awareness of the disease.


Total Synthesis of Carbazomycins A and B.
Total syntheses of carbazomycins A and B were demonstrated using a ytterbium-catalyzed Diels-Alder reaction with (silyloxyvinyl)indole as a diene. The densely substituted benzene ring of the target compound was successfully constructed by functionalization of a hydrocarbazolone intermediate and subsequent aromatization using N-bromosuccinimide.


The impact of identifying laryngeal obstruction syndromes on reducing treatment of pediatric asthma: A systematic review.
Inducible laryngeal obstruction (ILO) in children is underrecognized. This systematic review characterizes the scientific evidence on the impact of pediatric ILO diagnosis and treatment on asthma medication use. This review, registered with PROSPERO (CRD42020209168), utilized database searches in MEDLINE, EMBASE, CINAHL, and Web of Science from inception to October 2020. Both experimental and observational studies on ILO and asthma outcomes in patients ≤18 years were included. Population characteristics (sample size, sex, age, and comorbidities) and study outcomes (medication usage and respiratory symptoms) were extracted. The risk of bias was assessed with the National Toxicology Program's Office of Health Assessment and Risk of Bias Rating Tool. Data are presented narratively due to study heterogeneity. Of 1091 studies, 1076 titles and abstracts were screened after duplicate removal. Screening 31 full texts yielded eight pre-post studies. Patients were an average of 14.1 years old, 15% male, and >90% used asthma medication; 40% reported allergies, 30% gastroesophageal reflux, and 20% anxiety or depression. Most patients received at least one intervention, with 75% showing symptomatic improvement and >75% decreasing or stopping asthma medications. Studies were small with a high risk of selection, confounding, and detection bias. Asthma management was not a primary outcome in any of the studies. Overall, ILO patients were often diagnosed with or treated for asthma before ILO diagnosis. Evidence from individual studies suggests that comorbidities including ILO, gastroesophageal reflux, allergies, and anxiety should be considered in pediatric patients with asthma not responsive to medical therapy. Further research is required to determine the proportion of impacted asthma patients.


Mechanisms of the hypolipidemic effect of NIP-200 in rats.
We studied the mechanisms of hypolipidemic effects of NIP-200 (3,5-dimethyl-4,6-diphenyltetrahydro-2H-1,3,5-thiadiazine- 2-thione), a potent hypolipidemic compound, in cholesterol biosynthesis in the liver, cholesterol absorption in small intestine, and cholesterol catabolism and excretion in rats. NIP-200 did not reduce cholesterol biosynthesis and had no effects on cholesterol absorption in the small intestine. In the cholesterol catabolism and excretion, NIP-200 induced increases in cholesterol and bile acids levels in the bile and acidic steroids in the feces, and it enhanced cholesterol 7 alpha-hydroxylase activity in the liver. These results suggest that NIP-200 increases the synthesis of bile acids as a result of the activation of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the conversion of cholesterol to bile acids. Therefore, it is considered that one of the probable mechanisms of the serum total cholesterol lowering action of NIP-200 involves the enhancement of catabolism and excretion of cholesterol in the liver.


Computational Analysis of the Potential Impact of MTC Complex Missenses SNPs Associated with Male Infertility.
Meiotic chromosomes endure rapid prophase movements that ease the formation of interhomologue recombination intermediates that drive synapsis, crossing over, and segregation process. To generate these fast moves, the meiotic telomere complex (MTC) enables telomere-inner nuclear membrane attachment during meiotic prophase I and transfers cytoskeletal signals via another complex: the LINC complex. Furthermore, disruption or mutations of any of the MTC genes (TERB1, TERB2, and MAJIN) alters telomere association with the nuclear envelope leading to impairment of homologous pairing and synapsis, a meiotic arrest, and consequently to male infertility. To decipher the effect of TERB1, TERB2, and MAJIN missense mutations on protein structure, stability, and function, different bioinformatic tools were used in this study including VEP, Mutabind2, Haddock, Prodigy, Ligplot, ConSurf, DUET and MusiteDeep. In total, thirty mutations were predicted to be deleterious using VEP web server: seventeen for TERB1, eleven for TERB2, and two for MAJIN. All these single nucleotide polymorphisms were further analyzed and only 11 SNPs (W8R, G25R, P649A, I624T, C618R, F607V, S604G, C592Y, C592R, G187W, and R53C) were found to be the most damaging by at least six software tools and exert deleterious effect on the TERB1, TERB2, and MAJIN protein structures and likely functions. They revealed high conservation, less stability, and having a role in posttranslational modifications. This in silico approach provides information to gain further insights about variants that might affect stability, change binding affinity, and edit protein-protein interactions to facilitate their identification and functional characterization associated with male infertility.


Integrated HIV prevention and care strengthens primary health care: lessons from rural Haiti.
Three decades ago, the world's ministries of health declared primary health care--the delivery of basic preventive and curative services--a top priority. Since then, however, the world's poorest countries have not met most primary health care goals. Twenty-six years after the Declaration of Alma Ata, we are said to be living in a time of "limited resources," a phrase that construes various health interventions as competing priorities. As HIV has become the leading infectious cause of adult death in much of the world, it is difficult to argue that AIDS prevention and care are not ranking priorities for primary health care, yet precisely such arguments have held sway among international health policy makers. We present new information emerging from the scale-up of an established and integrated AIDS prevention-and-care program, based initially in a squatter settlement in central Haiti, to a second site in rural Haiti. The program includes robust prevention efforts as well as community-based therapy for advanced AIDS; three related components--women's health and active case finding and therapy for tuberculosis and sexually transmitted infections--were central to this effort. We tracked changes in key indices over the 14 months following the introduction of these services to a public clinic in central Haiti. We found that integrated AIDS prevention and care, including the use of antiretroviral agents, to be feasible in resource-poor settings and that such efforts may have favorable and readily measured impact on a number of primary health care goals, including vaccination, family planning, tuberculosis case finding and cure, and health promotion. Other collateral benefits, though less readily measured, include improved staff morale and enhanced confidence in public health and medicine. We conclude that improving AIDS prevention and treatment can help to reinvigorate flagging efforts to promote universal primary health care.


Acute Proximal Myopathy in a Young Male-A Case of Infectious Myositis.
Background and objectives: Acute proximal muscle weakness has a broad differential. Infectious myositis is difficult to differentiate clinically from inflammatory myopathy, often causing a delayed diagnosis. Infectious myositis should be thought of as a differential for proximal muscle pain and weakness in the right context. Case Presentation: A 40-year-old male with diabetes presented with exquisite pain and weakness of proximal extremities. He denied trauma, recent travel, new medications, or substance use. He denied prior rheumatologic, thyroid, or musculoskeletal disorders. The urine culture revealed staphylococcal infection with negative blood cultures. Rheumatologic and endocrine workups were negative. Random muscle biopsy was negative for inflammatory infiltrate. MRI of thighs and arms showed innumerable foci of nodular and ring enhancement in the proximal muscle groups. The patient noted improvement after about 10 days of antibiotics with complete resolution at 2 months. Discussion and Conclusion: Bacterial myositis is most often due to Staphylococcus aureus (70%) and affects a single muscle. Multifocal abscesses are rare and strongly suggest transient bacteremia. Our patient most likely had transient initiating staphylococcal bacteremia leading to diffuse myositis and hematogenous urinary tract infection (UTI). A delay in treatment can be life-threatening.


Conservation and variation in the hemagglutinins of Hong Kong subtype influenza viruses during antigenic drift.
The nucleotide sequence was determined for the hemagglutinin gene of the Hong Kong subtype influenza strain A/Bangkok/1/79. The amino acid sequence predicted from these data shows a total of 36 amino acid changes as compared with hemagglutinin for a 1968 Hong Kong strain, 11 more than had occurred in a 1975 strain. The distribution of these changes confirmed that there are conserved and highly variable regions in hemagglutinin as the viral gene evolves during antigenic drift in the Hong Kong subtype. Of the four variable regions found in this study, only two have been seen previously. Correlation of highly variable areas in the hemagglutinins of Hong Kong subtype field strains with sites of amino acid changes in antigenically distinct influenza variants enabled us to predict likely antigenic regions of the protein. The results support and extend similar predictions made recently, based on the three-dimensional arrangement of hemagglutinin from a 1968 influenza strain.


Explaining information technology use with the usefulness scale: a comparison with user age.
Understanding and predicting the use of information technology is an important problem in healthcare management. The relationships among user characteristics and information technology have generally been weak. This paper describes a recently developed scale that measures perceived usefulness of information technology. Following this description, the scale is compared with user age in ability to explain information technology use. The results suggest perceived usefulness explains a significant proportion of the variance in use (r2 = .13, p < or = 0.0001), while age was not a significant predictor. Implications and suggestions for use of the usefulness scale are discussed.


Matrix metalloproteinase 2 degrades collagen I to regulate ovarian development by association with an insulin-like peptide.
The ovary generally undergoes tissue remodeling during larval to pupal transition, which includes membrane degeneration and ovariole growth. At the same time, the hormones produced by insects significantly change during metamorphosis. However, the regulatory mechanism for ovarian development and hormones is not fully understood in insects. Herein, we found that matrix metalloproteinase 2 (MMP2) was highly expressed in the ovarian capsules and ovarioles, and the development was abnormal after knocking out MMP2 in Bombyx mori. The process of abnormal degradation of collagen I due to MMP2 deletion, which resulted in abnormal development of ovarioles and eggs, was analyzed in detail. The proteomics of ovaries in the MMP2-knock out and wild type strains showed a critically significant difference in the expression of a protein, insulin-like peptide (ILP). Additional analysis revealed significant alteration of ILP during ovarian development, and abnormal expression of ILP significantly affected ovarian development in vivo and MMP2 expression in vitro and in vivo. These results showed that MMP2 regulation of ovarian tissue remodeling is closely related to ILP expression. Our study provides new insights into the regulatory mechanism of MMP2 and ovarian development in B. mori.


Challenges facing physician scientist trainees: a survey of trainees in Canada's largest undergraduate and postgraduate programs in a single centre.
A number of indicators suggest that the physician scientist career track is threatened. As such, it is an opportune time to evaluate current training models. Perspectives on physician scientist education and career path were surveyed in trainees at the University of Toronto, home to Canada's longest standing physician scientist training programs. Trainees from the Clinician Investigator Program (CIP) and MD/PhD Program at the University of Toronto were surveyed. Liekert-style closed-ended questions were used to assess future career goals, present and future perspectives and concerns about and beliefs on training. Demographic information was collected regarding year of study, graduate degree program and focus of clinical and health research. Statistical analysis included non-parametric tests for sub-group comparisons. Both groups of trainees were motivated to pursue a career as a physician scientist. While confident in their decision to begin and complete physician scientist training, they expressed concerns about the level of integration between clinical and research training in the current programs. They also expressed concerns about career outlook, including the ability to find stable and sustainable careers in academic medicine. Trainees highlighted a number of factors, including career mentorship, as essential for career success. These findings indicate that while trainees at different stages consistently express career motivation, they identified concerns that are program- and training stage-specific. These concerns mirror those highlighted in the medical education literature regarding threats to the physician scientist career path. Understanding these different and changing perspectives and exploring those differences could form an important basis for trainee program improvements both nationally and internationally.


Dynamics of membranes driven by actin polymerization.
A motile cell, when stimulated, shows a dramatic increase in the activity of its membrane, manifested by the appearance of dynamic membrane structures such as lamellipodia, filopodia, and membrane ruffles. The external stimulus turns on membrane bound activators, like Cdc42 and PIP2, which cause increased branching and polymerization of the actin cytoskeleton in their vicinity leading to a local protrusive force on the membrane. The emergence of the complex membrane structures is a result of the coupling between the dynamics of the membrane, the activators, and the protrusive forces. We present a simple model that treats the dynamics of a membrane under the action of actin polymerization forces that depend on the local density of freely diffusing activators on the membrane. We show that, depending on the spontaneous membrane curvature associated with the activators, the resulting membrane motion can be wavelike, corresponding to membrane ruffling and actin waves, or unstable, indicating the tendency of filopodia to form. Our model also quantitatively explains a variety of related experimental observations and makes several testable predictions.


Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease: Presentation and outcomes of adults at a single center.
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a chronic demyelinating disorder that has been increasingly recognized since the serum antibody became commercially available in 2017. The most common clinical presentation is optic neuritis, and first line acute treatment is intravenous (IV) steroids. However, there are many questions that remain unanswered. For clinicians and patients, the primary question is whether relapses will occur and whether to treat with chronic therapy. This retrospective chart review examined characteristics of thirty-three known adult MOGAD cases at a single institute. Data was collected on patient demographics, clinical presentation, objective diagnosis with MRI and serum antibody levels, acute and chronic treatment and disease outcomes. Our MOGAD cases revealed a slight female to male predominance of 1.5:1. No racial groups were affected disproportionately, and age of symptom onset spanned a large range with a median of 40 years. The most common clinical and radiologic presentation was optic neuritis followed by transverse myelitis and brainstem symptoms/lesions. IV methylprednisolone was used in the vast majority of cases for acute treatment. 83.3% of our patients were treated with chronic therapy at some point during their disease course. Therapies include rituximab, IVIG, ocrelizumab, mycophenolate mofetil and ofatumumab. The majority of our patients were treated with rituximab and we did not see a significant benefit of yearly relapse reduction for rituximab versus other therapies. Our cohort had a higher-than- expected percentage of cases with relapsing disease (56.3%) compared to monophasic (43.8%). Our study confirms prior data regarding the demographics, clinical presentation and radiologic presentation of MOGAD. There is no consensus on whether maintenance therapy should be started for MOGAD cases with a single clinical event. Our cohort showed a higher relapse rate than has been reported previously and all known relapses occurred within one year of diagnosis. More data is necessary to confirm risk of relapse in the years following diagnosis. In addition, further data on biomarkers are needed to predict the disease course could help guide management.


Neuroprotective effects of Ginkgo biloba extract.
Ginkgo biloba extract has been therapeutically used for several decades to increase peripheral and cerebral blood flow as well as for the treatment of dementia. The extract contains multiple compounds such as flavonoids and terpenoids that are thought to contribute to its neuroprotective and vasotropic effects. In this review, we summarize the experimental results on the mechanism of neuroprotection induced by standardized extract of Ginkgo biloba leaves (EGb 761) and its constituents. The effects described mostly in animals include those on cerebral blood flow, neurotransmitter systems, cellular redox state and nitric oxide level. Furthermore, we discuss the current status of clinical trials as well as undesired side effects of EGb 761.


Epitaxy and photoresponse of two-dimensional GaSe crystals on flexible transparent mica sheets.
We present the controlled synthesis of high-quality two-dimensional (2D) GaSe crystals on flexible transparent mica substrates via a facile van der Waals epitaxy method. Single- and few-layer GaSe nanoplates with the lateral size of up to tens of micrometers were produced. The orientation and nucleation sites of GaSe nanoplates were well-controlled. The 2D GaSe crystal-based photodetectors were demonstrated on both mechanically rigid SiO2/Si and flexible mica substrates. Efficient photoresponse was observed in 2D GaSe crystal devices on transparent flexible mica substrates, regardless of repeated bending with different radii. The controlled growth of 2D GaSe crystals with efficient photoresponsivity opens up opportunities for both fundamental aspects and new applications in photodetectors.


Integrating cell-signalling pathways with NF-kappaB and IKK function.
Nuclear factor (NF)-kappaB and inhibitor of NF-kappaB kinase (IKK) proteins regulate many physiological processes, including the innate- and adaptive-immune responses, cell death and inflammation. Disruption of NF-kappaB or IKK function contributes to many human diseases, including cancer. However, the NF-kappaB and IKK pathways do not exist in isolation and there are many mechanisms that integrate their activity with other cell-signalling networks. This crosstalk constitutes a decision-making process that determines the consequences of NF-kappaB and IKK activation and, ultimately, cell fate.


The effect of antibiotic therapy on intrauterine infection-induced preterm parturition in rabbits.
The purpose of this study was to determine whether early antibiotic administration to pregnant rabbits with intrauterine infection could prevent preterm delivery and perinatal mortality. Under hysteroscopic guidance, pregnant rabbits at 70% gestation (21 days) were allocated to three groups: (1) control group, transcervical inoculation of 0.2 ml phosphate-buffered saline (n = 16); (2) infection group, transcervical inoculation of 0.2 ml of 10(5) colony-forming units (CFU) of Escherichia coli (n = 21); (3) infection and antibiotics group, transcervical inoculations of 0.2 ml of 10(5) CFU of E. coli and ampicillin-sulbactam 150 mg/kg every 8 h intramuscularly (n = 32). To examine the consequences of treatment delay, animals in the latter group were subdivided to receive antibiotics at different time intervals of 0, 6, 11 and 18 h after bacterial inoculation. The intervals from bacterial inoculation to delivery and litter survival were documented. Systemic (rectal) temperatures were recorded at 4 h intervals through the first 36 h and every 12 h until delivery. A p value of < 0.05 was considered significant. All rabbits inoculated with E. coli without antibiotic treatment delivered prematurely. The median inoculation-to-delivery interval was significantly shorter in the infected group than in the control group (median 32 h, range 14.9-76.5 h vs. median 219 h, range 173-246 h, respectively; p < 0.0001). Antibiotic administration within 12 h of inoculation, but not after 18 h, increased duration of pregnancy (by reducing the rate of preterm delivery) and neonatal survival (0% vs. 71%; p < 0.0001). The mean temperatures at delivery of animals whose treatments began at 6 and 11 h post-inoculation were significantly lower than those untreated with antibiotics or those treated at 18 h post-inoculation (p < 0.0001 for each comparison). Antibiotic administration can prolong pregnancy and reduce perinatal mortality if administered early (within 12 h of microbial inoculation) in a rabbit model of ascending intrauterine infection.


On sexual apathy in the male.
Ever since World War II, there has been a noticeable change in the sexual behavior and responses in men and women. Women, in general, are becoming sexually more assertive and demanding and men more indifferent and lethargic. In patients of middle age, sexual boredom is particularly pronounced in men, whereas the post-menopausal female becomes more interested in sexual pleasure. In the youth of the "cool" generation, both boys and girls are quite open about sex, but their sexual activities precede emotional involvement. The similarities in dress and behavior of both sexes indicate a wish for a twin rather than a search for a lover. In the age group between 25 and 45, women demand equal orgasms since they have become economically independent and are relatively free of the fear of pregnancy. This seems to have mobilized a deep-seated unconscious fear and hatred of women in the male, making him sexually apathetic. In both sexes there is a growing alienation between romantic love and sex.


[Shaker extract of roots].
The origins of "Shaker Extract of Roots" or "Mother Siegel's Curative Syrup". Its introduction into the market in 1876 by A.J. White in accordance with the Shaker community. Its expansion into twenty-four countries world-wide. Its distribution in France by O.-J. Fanyau and his successors. Its demise in 1957-1959.


Primary dissecting aneurysm of the right coronary artery.
Coronary arterial dissection is extremely rare. Such dissections have been reported to occur secondary to atherosclerosis, trauma, the postpartum state, and cystic medial necrosis and to be iatrogenically induced during catheterization. The clinical picture of coronary arterial dissection is usually sudded death. A review of the literature reveals that our case is the second in which a spontaneous coronary arterial dissection has been diagnosed during life and documented by coronary arteriographic studies. This report describes a 31-year-old man who presented with an acute inferior myocardial infarction. Coronary arteriographic studies demonstrated a dissection of the right coronary artery.


Gender and sleep in nightworkers: a quantitative analysis of sleep in days off.
Differences in sleep patterns between workdays and days off contribute to shiftwork effects on workers' health and well-being. But regardless of shift schedules, female workers face more difficulties in fulfilling their sleep need because of housework. This study analyzes gender differences concerning sleep in days off by comparing sleep patterns in male and female nightworkers, analyzing sleep as related to the presence of children and testing the association of sleep features between workdays and days off. Male (n = 16) and female (n = 30) workers at a plastic plant, working from 10 p.m. to 6 a.m., on weekdays, filled sleep logs for seven consecutive weeks. Male and female samples did not differ in length of night sleep or in total length of sleep. For both samples, sleep length/day in days off increased, but the difference was lager among females. Also important were the relations between sleep in workdays and days off, specially among women. Among female workers, the results indicated that workers with children tended to sleep less in Saturday mornings, suggesting a negative effect of motherhood on sleep not restricted to workdays. The general results indicate that sleep need on the one hand, and social factors on the other determine the actual amount of sleep.


Early versus late administration of amino acids in preterm infants receiving parenteral nutrition.
Observational studies in preterm newborns suggest that delay in administering amino acids could result in a protein catabolic state and could impact on growth and development. To determine the effect of early administration of amino acids in premature newborns on growth, neurodevelopmental outcome, mortality and clinically important side effects. The standard search strategy of the Neonatal Review Group as outlined in The Cochrane Library was used. Relevant randomised controlled trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012 I ssue 9 ), MEDLINE, EMBASE and CINAHL from their earliest dates to September 2012. The trial registry portal of the World Health Organization's International Cilinical Trial Registry Platform and ClinicalTrials.gov (US National Institute of Health) was searched to identify ongoing and completed but unpublished studies. Randomised controlled trials comparing early administration of amino acids with late administration in premature newborn infants were included. Early administration of amino acid solution was defined as the administration of amino acids in isolation or with total parenteral nutrition within the first 24 hours of birth; late initiation was defined as the administration of amino acids in isolation or with total parenteral nutrition after the first 24 hours of birth. The primary outcome measures were growth, neurodevelopmental outcome and mortality at 28 days. The secondary outcomes were biochemical abnormalities, sepsis and mortality. Both review authors independently selected trials, assessed trial quality and extracted data from the included studies. We contacted authors for further information. Fixed-effect analyses were performed. The treatment effect was expressed as mean difference for continuous variables and as risk difference and risk ratio for dichotomous variables. All results included 95% confidence intervals (CIs). Seven randomised controlled trials were included in this review. One randomised controlled trial reported no difference in crown-heel length and occipitofrontal head circumference by day 10. Four trials that enrolled 93 premature infants showed positive nitrogen balance (The mean difference with 95% CI was 250.42 (224.91 to 275.93 P value < 0.00001). Four trials showed a significant difference in the level of blood urea nitrogen (BUN) in the first 48 hours (P value < 0.00001). Early administration of amino acids did not result in metabolic acidosis in the first 24 hours. There is no available evidence of the benefits of early administration of amino acids on mortality, early and late growth and neurodevelopment. There is evidence from four randomised controlled trials included in this review that early administration of amino acids is associated with a positive nitrogen balance. The clinical relevance of this finding is not known. Acid-base status and ammonia levels were normal in the infants who received amino acids early. Given the small number of infants in the randomised controlled trials included in this review, the clinical heterogeneity among them, and the lack of data on important clinical outcomes, there is insufficient evidence to guide practice regarding the early versus late administration of amino acids to infants less than 37 weeks gestation.


Bioactive oxylipins in type 2 diabetes mellitus patients with and without hypertriglyceridemia.
Dyslipidemia, in particular elevated triglycerides (TGs) contribute to increased cardiovascular risk in type 2 diabetes mellitus (T2DM). In this pilot study we aimed to assess how increased TGs affect hepatic fat as well as polyunsaturated fatty acid (PUFA) metabolism and oxylipin formation in T2DM patients. 40 patients with T2DM were characterized analyzing routine lipid blood parameters, as well as medical history and clinical characteristics. Patients were divided into a hypertriglyceridemia (HTG) group (TG ≥ 1.7mmol/l) and a normal TG group with TGs within the reference range (TG < 1.7mmol/l). Profiles of PUFAs and their oxylipins in plasma were measured by gas chromatography and liquid chromatography/tandem mass spectrometry. Transient elastography (TE) was used to assess hepatic fat content measured as controlled attenuation parameter (CAP) (in dB/m) and the degree of liver fibrosis measured as stiffness (in kPa). Mean value of hepatic fat content measured as CAP as well as body mass index (BMI) were significantly higher in patients with high TGs as compared to those with normal TGs, and correlation analysis showed higher concentrations of TGs with increasing CAP and BMI scores in patients with T2DM. There were profound differences in plasma oxylipin levels between these two groups. Cytochrome P450 (CYP) and lipoxygenase (LOX) metabolites were generally more abundant in the HTG group, especially those derived from arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), γ-linolenic acid (γ-LA), and α-linolenic acid (α-LA), and a strong correlation between TG levels and plasma metabolites from different pathways was observed. In adult patients with T2DM, elevated TGs were associated with increased liver fat and BMI. Furthermore, these patients also had significantly higher plasma levels of CYP- and LOX- oxylipins, which could be a novel indicator of increased inflammatory pathway activity, as well as a novel target to dampen this activity.


Persistent hand spasm: movement disorder or seizure?
Dystonia is a movement disorder characterized by involuntary, sustained or repetitive, patterned muscle contractions or spasms, frequently causing squeezing and twisting movements or abnormal postures. Dystonic posturing could be one of the accompanying features of epilepsy. We report an elderly lady with intractable focal seizure who presented with more than a year of persistent hand spasms. The clinical importance of differentiating epilepsy from movement disorders is discussed.