Work-up times in an integrated brain cancer pathway.
The integrated brain cancer pathway (IBCP) aims to ensure fast-track diagnostics and treatment for brain cancers in Denmark. This paper focuses on the referral pattern and the time frame of key pathway elements during the first two years following implementation of the IBCP in a regional neurology department. All patients (n = 241) enrolled in the IBCP during the two-year period were included. Times from admission to completion of the key elements of the IBCP were used. The referral manner and changes in total neurology work-up time over eight quarters were assessed. The monthly patient enrollment decreased over the eight quarters studied. Primary care physicians accounted for nearly half of referrals, while one-third were referred from other hospital departments. The mean time from admission to end of diagnostic work-up fell from three days (0-10 days) to two days (0-6 days). Within 24 hours of admission, all patients were seen by a specialist in neurology, 90% had an electrocardiogram and 93% had the required blood-work performed. 94% of the included patients had magnetic resonance imaging of the cerebrum performed. The diagnostic process which was accelerated in the study-period and the total work-up time were generally low throughout. Key work-up items are currently being completed timely. Further improvements are possible. The enrollment rate has fallen to what we expect will be a steady level. This study was funded by a grant from the Danish Ministry of Health and Interior Affairs 2009 and the Helen Rude Foundation and was approved by the Danish Data Protection Agency. not relevant.


Effect of prostaglandins on the increased corticosterone output induced by caffeine in the rat.
The effect of prostaglandins on the increase of corticosterone output induced by caffeine was investigated in rats. PGE2 and some synthetic prostaglandins (11-deoxy-derivatives), which stimulate steroid output in vitro, enhanced the effect of caffeine. Pretreatment with indomethacin inhibited the effect of caffeine.


Comorbid anxiety in late-life depression: Relationship with remission and suicidal ideation on venlafaxine treatment.
The purpose of this study was to examine the influence of comorbid anxiety symptoms on antidepressant treatment remission in older adults with major depressive disorder (MDD). In this multisite clinical trial, 468 older adults aged 60 years or older with MDD received open-label protocolized treatment with venlafaxine extended release (ER) titrated to a maximum of 300 mg daily. At baseline, anxiety was assessed with the Anxiety Sensitivity Index, the Brief Symptom Inventory (BSI) anxiety subscale, and the Penn State Worry Questionnaire. To measure treatment response, depressive symptoms and suicidality were assessed every 1-2 weeks with the Montgomery-Asberg Depression Rating Scale and the 19-item Scale for Suicide Ideation; anxiety was assessed with the BSI. Logistic regression and survival analysis were used to evaluate whether anxiety symptoms predicted depression remission. We also examined the relationships between anxiety scores and suicidality at baseline. Baseline anxiety symptoms did not predict remission or time to remission of depressive symptoms. Depressive, worry, and panic symptoms decreased in parallel in patients with high anxiety. Anxiety symptoms were associated with the severity of depression and with suicidality. In older adults with MDD, comorbid anxiety symptoms are associated with symptom severity but do not affect antidepressant remission or time to remission.


Failed tubal sterilization as an etiologic factor in ectopic tubal pregnancy.
An indirect statistical method was used to demonstrate that failed tubal sterilization must be considered as a significant etiologic factor in tubal ectopic pregnancy. Since the exact incidence of poststerilization pregnancies was unknown in our population, a "theoretical" incidence of a 0.71% failure rate was used as the most realistic estimate on the basis of published reports of failed tubal sterilizations. From this figure the "expected" number of poststerilization conceptions, both total and tubal, was computed. The observed incidence of poststerilization ectopic tubal pregnancy was found to be 20 times the "expected" incidence in our population.


Sex chromosomes: evolving dosage compensation.
Dosage compensation of some X-linked genes varies among mammals. Inactivation of an X-linked copy of a gene in females appears to correlate with lack of an active homologue on the Y chromosome, implying that dosage compensation evolves in response to the loss of function of genes on the Y.


An experimental study on the physiological significance of the mode of cupular movement.
Isolated frog posterior semicircular canals were used. The ampullary nerve action potentials were recorded under three kinds of cupular movement, i.e., swing-door deflection, "cupula fixation-1" and "cupula fixation-2". Cupula fixation-1 was achieved by immobilizing the central top portion of the cupula, while cupula fixation-2 was achieved by immobilizing the entire top of the cupula. Cupula fixation-1 resulted in action potentials which were comparable to those of the swing-door deflection in terms of the maximum spike count and the stimulus-response curve. Cupula fixation-2 resulted in potentials with the maximum spike count comparable to the swing-door deflection; however, the response increase rate was very low. The time courses of the potentials in those cases of cupula fixation-1 and -2 were extremely short (about 2-3s) when compared to that of the swing-door deflection. These findings suggest that the swing-door deflection is physiologically more relevant in giving the optimum increase in response rate, as well as maintaining the time course of the tonic response.


[Seroprevalence and risk factors associated with Neospora caninum in dairy farms from the Province of Salta, Argentina].
The objective of this work was to determine the seroprevalence of Neospora caninum in cattle in Valle de Lerma, province of Salta, Argentina, and the risk factors associated with the disease. Serum samples were taken from 40 cows in each dairy herd, which were analyzed by indirect ELISA to detect antibodies against N. caninum. Chronic and acute infections were discriminated by measuring the avidity of these antibodies. All the herds exhibited at least one seropositive animal, the mean being 35.3 ± 14.9% of positive animals. Specific antibodies were also detected in dogs present in 9of the herds, which showed a seropositivity value of 71.7% ± 19.9%. Among the seropositive animals, 56.3% showed acute infections. A negative association was found between seroprevalence and the avidity index of specific antibodies, indicating that the presence of animals with acute infections is associated with higher seroprevalence. Fields with grazing showed more recent infections. These results show for the first time the importance of this parasite in this particular region and the need to promote the development of control programs considering the different risk factors that affect the epidemiological situation of the disease.


The Cedar Project: historical trauma, sexual abuse and HIV risk among young Aboriginal people who use injection and non-injection drugs in two Canadian cities.
Recent Indigenist scholarship has situated high rates of traumatic life experiences, including sexual abuse, among Indigenous peoples of North America within the larger context of their status as colonized peoples. Sexual abuse has been linked to many negative health outcomes including mental, sexual and drug-related vulnerabilities. There is a paucity of research in Canada addressing the relationship between antecedent sexual abuse and negative health outcomes among Aboriginal people including elevated risk of HIV infection. The primary objectives of this study were to determine factors associated with sexual abuse among participants of the Cedar Project, a cohort of young Aboriginal people between the ages of 14 and 30 years who use injection and non-injection drugs in two urban centres in British Columbia, Canada; and to locate findings through a lens of historical and intergenerational trauma. We utilized post-colonial perspectives in research design, problem formulation and the interpretation of results. Multivariate modeling was used to determine the extent to which a history of sexual abuse was predictive of negative health outcomes and vulnerability to HIV infection. Of the 543 eligible participants, 48% reported ever having experienced sexual abuse; 69% of sexually abused participants were female. The median age of first sexual abuse was 6 years for both female and male participants. After adjusting for sociodemographic variables and factors of historical trauma, sexually abused participants were more likely to have ever been on the streets for more than three nights, to have ever self-harmed, to have suicide ideation, to have attempted suicide, to have a diagnosis of mental illness, to have been in the emergency department within the previous 6 months, to have had over 20 lifetime sexual partners, to have ever been paid for sex and to have ever overdosed. The prevalence and consequences of sexual abuse among Cedar Project participants are of grave concern. Sexual trauma will continue to impact individuals, families and communities until unresolved historical trauma is meaningfully addressed in client-driven, culturally safe programming.


Reliability and validity of a self-administration version of DEMQOL-Proxy.
This study aimed to investigate the reliability and validity of a self-administered version of DEMQOL-Proxy, a disease-specific instrument that measures health-related quality of life in people with dementia. The sample consisted of 173 informal carers of people with dementia, aged 29 to 89 years old. Carers were mostly female, White/White British and closely related to the patient. They completed DEMQOL-Proxy (self-administered), EQ-5D-3L (proxy reported about the person with dementia), EQ-5D-3L (self-reported about their own health) and the Zarit Burden Interview. Using well-established methods from classical test theory, we evaluated scale level acceptability, reliability and convergent, discriminant and known-groups validity of DEMQOL-Proxy. DEMQOL-Proxy (self-administered) showed high acceptability (3.5% missing data and 0% scores at floor or ceiling), high internal consistency reliability (α = 0.93) and good convergent and discriminant validity. Amongst others, we found a moderately high correlation with EQ-5D-3L proxy reported (r = 0.52) and low to essentially zero correlations with EQ-5D-3L self-reported (r = 0.20) and carer and patient background variables (r ≤ 0.20). As predicted, DEMQOL-Proxy (self-administered) showed a modest correlation with DEMQOL (r = 0.32). Known-groups differences on health-related quality of life (comparing people with versus people without cognitive impairment) were of moderate effect size (d = 0.38) and in the expected direction. DEMQOL-Proxy (self-administered) has comparable acceptability, reliability and validity with DEMQOL-Proxy (interviewer administered). DEMQOL-Proxy (self-administered) can be used in a wider variety of contexts than its interviewer-administered version, including routine use in busy clinics. Copyright © 2016 John Wiley & Sons, Ltd.


Malignant schwannoma of the clitoris in a 1-year-old child.
A 1-year-old infant with von Recklinghausen's neurofibromatosis was seen because of increasing clitoral enlargement over a 7-month period. The mother, who also had neurofibromatosis, was treated 2 years beforehand for an acoustic neuroma. The child was treated by radical clitorectomy. Pathologic examination revealed malignant schwannoma, a tumor not previously described in this site. Vincristine, dactinomycin, and cyclophosphamide chemotherapy was given for 2 years to prevent local recurrence and metastatic spread. The child remains tumor free 2.5 years after diagnosis.


Ethyl pyruvate ameliorates intracerebral hemorrhage-induced brain injury through anti-cell death and anti-inflammatory mechanisms.
Ethyl pyruvate (EP) is a pyruvate derivative and known to be cytoprotective in various pathological conditions through anti-cell death and anti-inflammatory mechanisms. The present study investigated the neuroprotective effect of ethyl pyruvate using a mouse model of collagenase-induced intracerebral hemorrhage (ICH). Our results showed that EP treatment to mice reduced brain edema and improved neurological function after ICH. Delayed treatment with EP until 6h after ICH to mice was still neuroprotective. We further demonstrated that EP protected neurons from hemoglobin-induced cell death in vitro and neuronal cell degeneration in ICH mice. Moreover, EP exerted anti-inflammatory effects by inhibiting microglia activation, nuclear factor-κB (NF-κB) DNA binding activity and subsequent downstream pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)) production. Taken together, these results suggest that EP exerts neuroprotective effect via anti-cell death and anti-inflammatory actions. EP is a potential novel treatment for ICH patients and deserves further investigation.


Enhanced adherence activity of OK-432-induced peritoneal neutrophils to tumor cells correlates to their increased expression of CD11b/CD18.
We previously found that activated peritoneal neutrophils adhered to tumor cells and destroyed them in the cancer ascites of patients who had received intraperitoneal (ip) OK-432 injection therapy. Since tight adhesion to the tumor cell is essential for effective neutrophil-mediated tumor cell destruction, we investigated the mechanism of peritoneal neutrophil adhesion to tumor cells, using a microplate adhesion assay. An in vitro study demonstrated that the adherence activity of the peritoneal neutrophils of patients who received OK-432 injection therapy to tumor cells increased greatly compared to that of blood neutrophils. The expression of the adhesion molecules (CD11a,b,c/CD18) of peritoneal neutrophils, which was determined by an immunofluorescence study, was about four times as much in CD11b and twice as much in CD11c and CD18 compared to that in blood neutrophils. In vitro OK-432 stimulation of normal blood neutrophils increased neither the adhesion to PLC nor the CD11b expression. The enhanced adherence activity of peritoneal neutrophils to tumor cells was significantly inhibited by pretreatment of the neutrophils with anti-CD11b and anti-CD18 monoclonal antibodies (mAb), but not by pretreatment with anti CD11a or anti-CD11c mAb. These results indicated that the increased adhesiveness of OK-432-induced peritoneal neutrophils to tumor cells was due to the enhanced expression of CD11b/CD18. We concluded that CD11b/CD18 molecules on OK-432-induced peritoneal neutrophils play a crucial role in the neutrophil adherence activity against tumor cells, and these results are the first demonstration in the field of human neutrophil function.


A cost-effective method for producing custom dental teaching aids using RTV silicone.
A method for making low-cost custom dental teaching aids, using components of standard models and a silicone replication technique, is described. The process is quick, and is suitable for both small and large numbers of individual model types.


Uptake of immune RNA by normal mouse spleen cells.
Normal mouse spleen cells take up in vitro radioactively labeled immune RNA. RNA taken up is present in nuclei, polysomes, membranes and cytoplasm. About 20-40% of immune RNA is nonspecifically associated with cell surface. 45% of RNA taken up is degraded and reutilized inside the cells within 2 hours.


Assessing the risk of false-negative fine-needle aspiration cytology and of incidental cancer in nodular goiter.
In cases of multinodular goiter with negative cytologic result, reasonable management options include surgical treatment, simple follow-up, or more recently introduced conservative therapies such as laser or radiofrequency ablation, and recombinant human thyroid-stimulating hormone-augmented radioiodine. For patients who are eligible for follow-up or nonsurgical treatments, the possibility that they may have an undiagnosed malignancy (false-negative [FN]-fine-needle aspiration cytology [FNAC] result or incidental thyroid cancer [ITC]) should be considered. The aim of our study was to assess the risk of malignancy in patients known to have presumably benign thyroid disease. Surgical series of patients who underwent total thyroidectomy for benign disease between 2000 and 2010 at two Italian centers were reviewed. Patients with any preoperative suspicion of malignancy were excluded. Histologic examination revealed that 84 of 970 (8.6%) thyroidectomized patients had malignancy (5% ITC and 3.6% FN-FNAC), with 89.8% of ITCs having a diameter <10 mm, and 65.7% of FN-FNAC cancers having a diameter >30 mm. Sixty-seven thyroid malignancy patients (79.8%) had stage I disease (American Joint Committee on Cancer criteria). The risk of FN-FNAC increases with increasing size of the nodule, while the risk of ITC increases as nodule size decreases. The risk of malignancy in presumably benign thyroid disease cannot be overlooked, but can be minimized through skillfully performed ultrasonography (US) examination and FNAC. Once a patient with multinodular goiter is referred for follow-up or nonsurgical therapy, careful US surveillance is mandatory.


Nucleotide sequence of the 18-25 S ribosomal RNA intergenic region from a thermophile, Thermomyces lanuginosus.
To identify important structural features in the intergenic sequences of ribosomal DNAs, the nucleotide sequence of the 18-25 S rRNA intergene region was determined in a thermophilic fungus, Thermomyces lanuginosus, and compared to that of common yeasts. While a striking sequence homology was observed in the mature ribosomal sequences, the two internal transcribed spacer regions were found to be unusually G + C rich and significantly shorter than any other organism. An extensive secondary structure could be predicted but estimates of the secondary structure did not reveal a minimum structure which is common to other species; rather, in all rDNA transcripts the intergenic regions appear organized into a secondary structure in which all of the mature rRNA junctions are localized within one domain. This suggests that a role of the internal transcribed spacer in ribosome maturation may be that of a "biological spring" which maintains processed sites in close proximity.


Adipose tissue inflammation in the pathogenesis of type 2 diabetes.
At least 2.8 million people die each year as a result of being overweight or obese, and the biggest burden being obesity-related diseases. Overweight and obesity account for a major proportion of type 2 diabetes (T2D) cases. Obesity is associated with inflammation in adipose tissue, namely an infiltration and expansion of macrophages, which produce inflammatory cytokines that interfere with insulin signaling, and a loss of protective cells that promote adipose homeostasis. Thus, it is now clear that inflammation is an underlying cause or contributor to T2D as well as many other obesity-induced diseases, including atherosclerosis and cancer. Inflammatory pathways contribute to impaired glucose handling by adipocytes, hepatocytes, and muscle cells and interfere with insulin production and insulin signaling. This review highlights the roles of the different immune populations in lean adipose tissue and their importance in tissue homeostasis to keep inflammation at bay. We also discuss the changes that occur in these immune cells during the development of obesity, which has detrimental effects on the health of adipose tissue, and local and systemic insulin resistance.


[Tracheobronchial stents: a retrospective analysis of indications, results and in particular complications].
Tracheobronchial stents are inserted mainly in cases of malignant and benign airway stenosis. Further indications are esophago-tracheal fistulas, mediastinal fistulas and tracheomalacia. A retrospective analysis was conducted on patients' records, information provided by the general practitioners and relatives of the patients from July 1993 to December 2006 in the Department of Pneumology of the Heidehaus Hospital Hannover (since 6/05 Department of Pneumology and Internal Intensive Care Medicine, Oststadt-Heidehaus Hospital). During the observation period of 13 years a total of 269 stents (177 permanent, 92 temporary) were implanted in 207 patients (1.3 stents per patient). The vast majority of patients (173/207) suffered from an underlying malignancy. About half of the stents were deployed in the trachea. The median length of placement was 116 days in patients with malignancies and 313 days in patients with benign diseases. In about 40 % of the patients notable complications were observed which were directly or indirectly associated with the stents. These findings show the importance of a critical indication for stent implantation. In benign diseases a stent can remain for years inside the tracheobronchial system, if it is well tolerated in the beginning. In malignant diseases the result depends decisively on the stage of the tumour: has the stent been implanted before any other tumour therapy is started or is it an end-stage tumor with no other therapeutic option? In general, complications of stents occur quite frequently. The analysis of stent data leads to some aspects for the prevention of stent-related complications. There should be a strict indication and appropriate choice of stent material. Nevertheless, there remains an ethical dilemma in patients with end-stage disease as to whether to implant a stent or to do nothing against the tumor, because the benefit immediately after stent insertion vanishes with progression of the tumour, so causing extra complications.


On the translation of a soliton-like kink along the stack of a coiled chromatid.
The theory of solitons is applied to the normalisation of a malformed loop from a kinked chromatid. When interpreted in the context of dividing cells, the proposed mechanism adds novel functions to those traditionally attributed to the mitotic spindle.


Cell and Gene Therapy for Spine Regeneration: Mammalian Protein Production Platforms for Overproduction of Therapeutic Proteins and Growth Factors.
This article provides an evidence-based personal perspective on the future of cell and gene therapy for degenerative diseases of the intervertebral disc. This paper focuses on how mammalian protein production platforms and transfected and irradiated protein packaging cell lines may be used as "cellular factories" for overproduction of therapeutic proteins and proanabolic growth factors, particularly in the context of regenerative therapies. This paper also speculates on future opportunities and challenges in this area of research and how new innovations in biotechnology affect cell and gene therapy for degenerative diseases.


Shaping the breast in secondary microsurgical breast reconstruction: single- vs. two-esthetic unit reconstruction.
The esthetic outcome is dictated essentially not only by the position, size, and shape of the reconstructed breast, but also by the extra scaring involved. In the present study, we conducted a visual analog scale survey to compare the esthetic outcome in delayed autologous breast reconstruction following two different abdominal flaps inset. Twenty-five patients had their reconstruction using the Single-esthetic Unit principle and were compared with 25 patients that their breast was reconstructed using the Two-Esthetic Unit principle. Photographic images were formulated to a PowerPoint presentation and cosmetic outcomes were assessed from 30 physicians, by means of a Questionnaire and a visual analog scale. Our data showed that the single-esthetic unit breast reconstruction presents significant advantages over the traditional two-esthetic units, due to inconspicuous flap reconstruction, better position of the inframammary fold, and more natural transition from native and reconstructed tissues. Moreover, patient self-evaluation of esthetic outcome and quality of life showed that single-esthetic unit reconstruction is associated with higher patient satisfaction, therefore should be considered the method of choice.


Retraction: First Report of Vibrio tubiashii Associated with a Massive Larval Mortality Event in a Commercial Hatchery of Scallop Argopecten purpuratus in Chile.
[This retracts the article DOI: 10.3389/fmicb.2016.01473.].


Porcine reproductive and respiratory syndrome virus infection inhibits NF-κB signaling pathway through cleavage of IKKβ by Nsp4.
Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious porcine pathogen that causes serious economic losses to the world swine industry. The inhibitor kappa B kinase β (IKKβ), a catalytic subunit of the IKK complex, plays multiple roles in regulating the nuclear transcription factor kappa B (NF-κB) activity and a variety of cytokines transcription involved in immune responses. Here, we reported that the nonstructural protein 4 (Nsp4) of PRRSV cleaved IKKβ at the E378 site to inhibit the activation of NF-κB signaling pathway. Additionally, we clearly showed that cleavage of IKKβ by PRRSV Nsp4 depends on the 3 C-like serine protease activity of Nsp4 because the catalytically inactivate mutants of Nsp4 lost the function to cleave IKKβ. Furthermore, we found that hydrophobic patch at the KD-ULD junction of IKKβ could be disrupted by PRRSV Nsp4 via the cleavage of the E378 site, resulting in disruption of NF-κB activity. Of note, the two cleavage fragments of IKKβ lose their function to phosphorylate IκBα and activate NF-κB signaling pathway. Our findings provide a clue to better understand the pathogenic mechanism of PRRSV involved in PRRSV evasion of host antiviral innate immune responses.


G protein modulation of omega-conotoxin binding sites in neuroblastoma x glioma NG 108-15 hybrid cells.
Electrophysiological evidence shows that voltage-dependent calcium channel (VDCC) activity can be regulated by a large number of neurotransmitters. In particular, guanine nucleotide binding regulatory protein (G protein)-mediated inhibitory modulation of the channel activity has been deduced from evidence that GTP analogues and purified G proteins are able to mimic this effect. The G proteins involved are pertussis toxin (PTx) sensitive. The purpose of the present study was to investigate, using biochemical techniques, whether G protein activation modulates the recognition site for omega-conotoxin GVIA (CgTx), a peptide neurotoxin that selectively labels a population of high-threshold VDCC. Undifferentiated and differentiated (1 mM dibutyryl cyclic AMP, 4 days) NG 108-15 cells were used. In both crude cellular extracts specific binding of 125I-CgTx was characterized. Differentiation induced a sixfold increase in the number of binding sites and doubled the KD value. The in vitro addition of guanylylimidodiphosphate (GMP-PNP; a nonhydrolyzable analogue of GTP) to extracts prepared from differentiated cells reduced the 125I-CgTx binding by 48%. This effect, observed in undifferentiated cells as well, was also caused by other triphosphate guanine nucleotides, such as GTP, but not by guanosine 5'-O-(2-thiodiphosphate) or adenine nucleotides. Treatment of the cells with PTx prevented the GMP-PNP effect. Moreover, the results obtained after preincubation with specific antisera raised against the alpha subunits of Gi1-2 and Go suggest that Go is the G protein responsible for the observed effect.


A new peptide (1150Da) selectively activates the calcium-calmodulin sensitive isoform of cyclic nucleotide phosphodiesterase from human myometrium.
The cyclic nucleotide phosphodiesterase enzymatic system is examined in extracts of human myometrium and four individual phosphodiesterase isoforms have been isolated and characterized. A new thermostable peptide, recently purified in rat and calf myometrium, is able to stimulate up to 55-fold, the calcium-calmodulin dependent phosphodiesterase isoform. Activation of cAMP hydrolysis is by far the most marked with a 55-fold maximal stimulation at a concentration of 0.1 microM peptide and a IC50 value estimated at 30nM. For cGMP hydrolysis, the maximal effect (x25) obtained at 40nM peptide is lesser and the IC50 value is in the 10nM range. Furthermore, we verified that classical calmodulin antagonists such as calmidazolium or trifluoroperazine did not change stimulation of the calcium-calmodulin phosphodiesterase by the peptide, indicating that the myometrial peptide is different from calmodulin. To our knowledge, this is the first evidence for such a strong and selective stimulation of one isoform of the phosphodiesterase enzymatic system by a natural peptide.


Expression profiles of microRNAs in midbrain of MPTP-treated mice determined by microRNA sequencing.
MPTP models have been developed to mimic human Parkinson's disease and serve as an indispensable tool for studying PD. Among them, subacute MPTP PD models are popular due to their short modeling period and similarity to PD pathology. However, the early pathophysiological mechanism of the model remains to be further clarified. More and more studies have shown that dysregulation of miRNAs plays an important role in the occurrence and development of neurodegenerative diseases, including PD. In this study, we identified 43 differentially expressed microRNAs (miRNAs) in the ventral midbrain of MPTP-induced subacute PD mouse by RNA sequencing. Further bioinformatics analysis revealed that these miRNAs were significantly enriched in axon guidance/neuron projection, metabolic pathways/cellular macromolecule metabolic process and PI3K/AKT signaling pathways, which were involved in the occurrence and development of early PD. Thus, targeted regulation of these miRNAs may reverse the neurodegeneration of early PD.


Adsorption of the disinfectant benzalkonium chloride on montmorillonite. Synergistic effect in mixture of molecules with different chain lengths.
The biocide benzalkonium chloride (BAC) is a mix of cationic alkylbenzyldimethylammonium surfactants having different alkyl chain lengths. A comparative study of adsorption on the phyllosilicate clay montmorillonite of two of these surfactants, with alkyl chains having respectively 12 C atoms (BAC-12) and 14 C atoms (BAC-14), and a mixture of both surfactants is presented in this work. Adsorption isotherms were performed for individual surfactants and for a 1:1 mixture BAC-12+BAC-14. The adsorption was investigated in an ample concentration range that covers almost seven orders of magnitude in concentrations (from 1 nM to 10 mM), range that includes environmentally relevant concentrations. Quantification of BAC was performed by HPLC-UV and LC-MS and the results were completed with powder X-Ray diffraction. The adsorption of both surfactants leads to adsorption isotherms with two well differentiated steps. The first step corresponds almost exclusively to a cation exchange process, and the binding constant is very similar for both surfactants. The second step of the isotherms is observed at higher concentrations and adsorption is mainly driven by lateral interactions between surfactant molecules. The binding constant of this step is larger for BAC-14 than for BAC-12. Adsorption from a BAC-12+BAC-14 mixture shows a synergistic behaviour, possibly due to a better packing arrangement in the interlayer. Calculations show that in natural systems silicate clays are major sorbents of BAC at low concentrations whereas binding to humic acid is predominant at high concentrations.


Vitamin K2 ameliorates experimental autoimmune encephalomyelitis in Lewis rats.
Vitamin K2 (VK2), which has been in wide use for the management of hypoprothrombinemia and osteoporosis in Japan, was tested for its efficacy on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). The severity of EAE was significantly ameliorated by the prophylactic administration of VK2, though it was not effective when given after the onset. Inflammatory cellular infiltration and the expression of both MHC class II and inducible nitric oxide synthase (iNOS) were reduced in the spinal cords of VK2-treated rats with EAE. The inhibitory effect of VK2 on the iNOS expression in glial cells was also observed in vitro. Considering the long use of VK2 without noticeable untoward effects, it may be applicable to the patients with MS.


Vitamin D deficiency and graft-versus-host disease in hematopoietic stem cell transplant population.
Vitamins are the organic compounds that have long been known to play a significant role in our body by functioning as hormones and antioxidants. Vitamin D, a fat-soluble vitamin, is the main regulator of calcium hemostasis in our body. At the same time, it is also known to show its potential effects on the immune system by modulating the differentiation, activation, and proliferation of T and B lymphocytes. The immunomodulatory properties of vitamin D are also known to have a crucial role in the prevention and treatment of graft-versus-host disease. Patients undergoing hematopoietic stem cell transplantation are particularly at risk of vitamin D deficiency. This review article expands our understanding of vitamin D, its immunomodulatory effects, and its role in prevention and treatment of graft-versus-host disease.


Lipiodol avidity of neuroendocrine liver metastases.
Lipiodol has been shown to concentrate in most hepatocellular carcinomas as well as in some liver metastases, including those of neuroendocrine origin. Our aim was to determine the proportion of neuroendocrine liver metastases that take up lipiodol and to identify tumour characteristics that predict avidity. Avidity was assessed in 12 patients with neuroendocrine liver metastases by performing an abdominal CT scan immediately after selective hepatic arterial injection of 5 ml of unlabelled lipiodol and this was correlated with number and size of lesions as well as angiographic and plain CT scan features. In seven patients the tumours displayed lipiodol avidity (four solitary, three multiple); five patients had non-avid lesions (all multiple). A large dominant liver tumour was the only predictor of avidity (mean diameter of largest lesion 9 cm vs. 3 cm for patients with non-avid tumours: P=0.01). Avidity was not related to vascularity or CT density of lesions. Although this is a small study, it would appear that approximately 50% of neuroendocrine liver metastases selectively concentrate lipiodol, which could have implications for targeted cancer therapy.


Area postrema mediation of physiological and behavioral effects of lithium chloride in the rat.
The area postrema (AP), a chemoreceptor trigger zone for nausea and vomiting, has been implicated in taste aversion conditioning with LiCl. In addition to taste aversion acquisition, the present studies indicate that a number of other responses to LiCl administration are eliminated by lesions of the AP. These include a behavioral response, 'lying-on-belly' as well as two physiological responses, delayed stomach emptying and hypothermia. These findings suggest that the area postrema is critically involved in the detection of LiCl and in a wide range of responses to this toxin. They also provide strong evidence that the failure to acquire conditioned taste aversions to LiCl-paired flavors after AP lesions can be attributed to the absence of a significant 'illness' response in lesioned animals.


A self-administered behavioral intervention using tailored messages for migraine.
The objective of this study was to evaluate the effectiveness of a Self-Administered Behavioral Intervention using Tailored messages (SEABIT) for migraine. The primary measures were headache days, headache-related disability, behavioral/emotional factors, and headache-related beliefs. Behavioral and cognitive-behavioral interventions for migraine treatment are well established and possess "Grade-A" evidence based on the U.S. Headache Consortium evidence-based guidelines. To increase the accessibility of behavioral interventions in primary and other settings, treatment can be delivered in self-administered formats. Incorporating tailored health communication strategies (via tailored messages) into a self-administered format can help maintain a level of personalization without requiring regular visits to a behavioral specialist. Tailored messages are created using individual-level assessment data to educate and motivate the patient to develop behavioral skills and strategies for migraine prevention and management. Twenty-five individuals (95% female, 90% Caucasian, mean headache years = 21.0) began and 84% (21/25) completed all phases of the 8-week SEABIT developed for migraine prevention (preceded by a 1-month baseline phase and followed by a 1-month postintervention phase). Overall, 62% (13/21) reported at least a 50% reduction in headache frequency, and mean headache frequency for the group was also significantly reduced from baseline to postintervention (16.9 vs. 10.7, P < .001; eta2= .61). Headache-related disability, behavioral/emotional factors, and headache-management self-efficacy also showed significant improvement. The findings suggest that the SEABIT for migraine prevention is an effective behavioral intervention that potentially could be accessed and distributed in a variety of settings including primary care.


Inventory and biological impact of polycyclic carcinogens in the environment.
The rapid development of the natural sciences and the technical progress during the last century have significantly changed our society and environment. During this period the average life expectancy for people in industrialized countries has doubled. A prolongation of life expectancy to this extent, due to for example, understanding of the relationship between various diseases and their corresponding causative agents, had never before occurred in mankind's history. It resulted in specific hygiene precautions. The recognition of such causal relationship was facilitated by the fact that infection diseases generally become apparent after a short incubation time, i.e. that an environmental situation causes health damage. At present, we are searching for origins of diseases of which the causal correlations with environmental influences are far more difficult to recognize than those of infection diseases, since long-term effects have to be observed. Do we have a situation similar to that which we had for infections at the end of the last century ? For diseases such as lung and larynx cancer, there are significant indications of carcinogenic compounds in the environment. Since both types of cancer are about 10 times more common among cigarette smokers who inhale than among non-smokers, a correlation to the risk factor "smoking" is beyond doubt. Living and working in larger cities or highly populated areas are additional factors which many enhance the lung cancer incidence ("urbanisation factor"). The air quality of these areas is supposed to be the reason for this effect. However, the present "bad air quality" at most doubles the disease incidence. A large number of epidemiological studies report on local differences of the incidence rates as well as significant increases or decreases of the mortality rates for some cancer diseases during comparatively short periods. A summary recently has been published by Misfeld (1). As an example, the mortality rate due to lung cancer for males in the F.R.G. has almost doubled during 1955-1975 from 36.5 per 100,000 to 65.9 per 100,000. This holds true for cancer of the rectum which increased from 8.8 per 100,000 to 18.9 per 100,000 during the same period. In contrast, mortality due to stomach cancer decreased from 59.3 to 36.6 per 100,000 and uterine cancer in females decreased from 16.6. to 8.5 per 100,000 (2). The pronounced changes in mortality rates cannot be explained by alterations of the genetic disposition during such a short period. Improved diagnostic and therapeutic techniques might explain decreases but not increases of mortality rates.(ABSTRACT TRUNCATED AT 400 WORDS)


Identification of a possible respiratory arsenate reductase in Denitrovibrio acetiphilus, a member of the phylum Deferribacteres.
Denitrovibrio acetiphilus N2460(T) is one of the few members of the phylum Deferribacteres with a sequenced genome. N2460(T) was capable of growing with dimethyl sulfoxide, selenate, or arsenate provided as a terminal electron acceptor, and we identified 15 genes that could possibly encode respiratory reductases for these compounds. The protein encoded by one of these genes, YP_003504839, clustered with respiratory arsenate reductases on a phylogenetic tree. Transcription of the gene for YP_003504839, Dacet_2121, was highly induced when arsenate was provided as a terminal electron acceptor. Dacet_2121 exists in a possible operon that is distinct from the previously characterized respiratory arsenate reductase operon in Shewanella sp. ANA-3.


The 10-second stroke: a case report.
Acute infarction is detected in a third of patients undergoing diffusion-weighted magnetic resonance imaging (DW-MRI) with clinically suspected transient ischemic attack. The longer symptoms are present, the more likely an infarct will be identified on DW-MRI. Events as short as 10 minutes have been reported in association with a DW-MRI lesion. We present a case of an otherwise healthy man with a 10-second episode of neurologic dysfunction associated with DW-MRI lesions from a cardioembolic source. The atypical symptoms and lack of risk factors for cerebrovascular disease made his diagnosis easy to miss. Early DW-MRI may be of benefit beyond clinical judgment in patients with fleeting symptoms of neurologic dysfunction.


Natalizumab disproportionately increases circulating pre-B and B cells in multiple sclerosis.
Natalizumab, a humanized anti-alpha4 integrin monoclonal antibody, reduces relapses and disease progression in patients with multiple sclerosis (MS). Whereas its presumed mode of action is inhibition of T cell/monocyte entry into the brain, little is known about its specific effect on B cells, which are increasingly recognized to participate in MS pathogenesis. We obtained serial blood samples from 17 patients before and during natalizumab therapy for relapsing-remitting MS for up to 16 months, and blood samples from 10 untreated patients with MS and 13 healthy donors. We determined numbers of mature and immature lymphocyte subsets by flow cytometry for CD3, CD4, CD8, CD19, CD138, and CD10 in 111 samples. We analyzed marker transcripts for immature hematopoietic cells by quantitative PCR for CD34, Vprebeta1 (pre-B lymphocyte gene 1), and DNTT (terminal deoxynucleotidyltransferase) in 65 samples. Natalizumab therapy increased CD19(+) mature B cells more than other lymphocytes/monocytes in blood (2.8-fold versus 1.3-1.8-fold increase in cells/microL; p < 0.01). Even greater was the increase of immature CD19(+)CD10(+) pre-B cells (7.4-fold; p < 0.01). This pattern remained stable during treatment for up to 16 months. Transcripts of lymphocyte precursors (Vprebeta1 and DNTT) were elevated more than transcripts for CD34. Circulating B cells and especially pre-B cells are most prominently elevated among the studied immune cell subsets, raising the possibility that the effects and side effects of natalizumab are partly mediated by actions on B cells.


Effects of age and period of fattening on carcass and non-carcass characteristics of one-humped camels.
This study was conducted to compare the carcass characteristics and quantity of carcass and non-carcass components of 2- and 3-year-old male camels fattened for either 3 or 6 months. Twelve 2-year-old camels with an average body live weight of 268.5 ± 21.4 kg and twelve 3-year-old camels with an average body live weight of 307.5 ± 29.9 kg were used in a completely randomized design with a 2 × 2 factorial arrangement. For carcass analysis, three camels from each group were selected and slaughtered. The results showed that camel age and fattening period had no significant effect on average daily gain (ADG). Older camels and a longer fattening period resulted in heavier hot and cold carcass weights. Three-year-old camels had a higher dressing percentage compared to 2-year-old camels, regardless of the period of fattening. Analysis of non-carcass components showed that the heaviest component was the hide and 2-year-old camels fattened for 90 days had the greatest weight of hide as percentage of cold carcass weight. Total muscle weight was greater for the 3-year-old camels compared to the 2-year-old ones, regardless of the fattening period, and camels fattened for 180 days had heavier weight than those fattened for 90 days, regardless of age at fattening. However, the greatest weight of total muscle was detected in camels at 2 years of age fattened for 180 days when it was expressed as percentage of carcass weight. The highest and the lowest total fat content as kilogram or as percentage of cold carcass was observed in 3-year-old camels fattened for 180 days and 2-year-old camels fattened for 180 days, respectively. Our results suggested that the best age for slaughtering is 2 years old with the fattening period of 180 days.


Long-term Results of the Treatment of Scapholunate Instability with Dynamic Extensor Carpi Radialis Brevis Tenodesis.
Scapholunate dissociation is the most common form of carpal instability. This retrospective case series aimed to assess long-term results obtained by treating scapholunate instability with dynamic tenodesis using the entire extensor carpi radialis brevis tendon, which is detached from the base of the third metacarpal, rerouted in the third extensor compartment, and fixed at the distal portion of the scaphoid to maintain reduced rotatory subluxation. Nine patients with scapholunate instability were treated. We reviewed eight patients with a mean follow-up of 12 years. One subgroup of four patients was affected by static scapholunate instability, and the other by dynamic scapholunate instability. Disability of the Arm, Shoulder, and Hand score, Patient Rated Wrist Evaluation score, modified Mayo score, and radiographs were used to determine functional and anatomical outcomes. Excellent functional results did not correlate with radiological outcome in patients with static scapholunate instability. In this subgroup, scapholunate angle and gap and radiolunate angle improved in average but remained in the pathologic range. In only one of these patients, osteoarthritis was observed. In the subgroup of patients affected by dynamic instability, very good functional outcomes correlate with radiological results, except in one patient who developed arthritic changes. Dynamic tethering of the scaphoid with the extensor carpi radialis brevis tendon might be indicated in the treatment not only in patients affected by dynamic scapholunate instability but also in patients with static instability. Prospective studies with a larger number of patients are required to evaluate this method.


1-Alkynyltriazenes as Functional Analogues of Ynamides.
The chemical reactivity of 1-alkynyltriazenes has been investigated and is found to parallel the reactivity of ynamides. The similarity in reactivity of these two classes of compounds is demonstrated by addition reactions with acids, by cycloaddition reactions with ketenes, tetracyanoethene, and cyclopropanes, as well as by intramolecular cyclization reactions. The presence of reactive triazene groups in the products enables subsequent transformations. Overall, our results suggest that 1-alkynyltriazenes should become valuable reagents in synthetic organic chemistry.


[Investigation of nociceptive trigeminal inhibitory tension suppression system and occlusal stabilization splint on bruxism patients by using polysomnography].
To study the short-term effects of nociceptive trigeminal inhibitory tension suppression system (NTI-tss) and occlusal stabilization splint (OS) on sleep bruxism patients. Ten patients received the two splint treatments in a randomized cross-over fashion: An NTI-tss and an OS for a 1-week period, respectively. Record the bruxism episodes per hour, micro-arousals per hour of the patients before wearing the splints (baseline), the first night and 1 week after wearing the splints with polysomnography. Statistical analysis was performed with SAS 9.1 by means of mixed effect model analysis. There were no differences among the micro-arousal index of the baseline, the first night and 1 week later with both types of the splints (P>0.05). The NTI-tss was associated with a significant reduction in bruxism index compared with baseline. The bruxism index of baseline, the first night and 1 week later were 7.50 +/- 1.11, 3.45 +/- 1.22, and 3.51 +/- 1.03 per hour(the first night vs baseline, t=26.52, P<0.01; 1 week vs baseline, t=26.12, P<0.01). There were also significant differences in the bruxism index after wearing the OS. The bruxism index of baseline, the first night and 1 week later were 7.44 +/- 1.23, 2.97 +/- 0.91 and 6.43 +/- 1.02 per hour(the first night vs baseline, t=16.79, P<0.01; 1 week vs baseline, t=3.79, P<0.01). Compared with the NTI-tss group, the reduction was much less, especially 1 week later. Both the NTI-tss and the OS splints can reduce the bruxism index, and have no affect the incidence of micro-arousal. In this short term study, the NTI-tss was more effective than the OS for the treatment of sleep bruxism.


Ophthalmologic effects of bowel disease.
Ocular findings in diseases affecting primarily the digestive tract are relatively rare; however, it is important for the physician to recognize these relationships, appropriately uncover symptoms related to the eye disease, and have the patient evaluated by an ophthalmologist if indicated. In addition, ocular inflammation may be the first indication of bowel disease (e.g., uveitis in Crohn's disease). This article describes the associations between ocular diseases and gastrointestinal diseases and their causes, signs, symptoms, prognosis, and treatment.


[Lymphocytis meningitis: Listeria monocytogenes is a potential risk in a immunocompetent child].
Meningoencephalitis due to Listeria monocytogenes is a rare and serious form of brainstem infection in childhood. We report the case of a 7 year-old girl presenting lymphocytic meningitis with a high CRP level. Parenteral antibiotics combining ceftriaxone and vancomycine led initially to clinical improvement. Ten days later, secondary brainstem inflammation with hydrocephalus appeared and led to the detection of L. monocytogenes during external ventricular bypass. This observation of paediatric lymphocytic meningoencephalitis suggests a prescription of amoxicillin in association with first line antibiotics, particularly when an important inflammatory syndrome exists, immunocompetent children included.


The "Hand as Foot" teaching method in calcaneal skeletal traction nursing.
To introduce the application of "Hand as Foot" teaching method in calcaneal skeletal traction nursing.


[Support at home for a patient with cancer of the jaw].
Home care presents specific difficulties. The support of Ms. C, suffering from a malignant tumour of the lower jaw illustrates a difficult care context due to a painful and poorly-healing wound, low self-esteem and communication difficulties. Maintaining the right distance and providing professional support are therefore essential in order to give high quality care to this patient.


On the Fourier transform of a quantitative trait: Implications for compressive sensing.
This paper explores the genotype-phenotype relationship. It outlines conditions under which the dependence of a quantitative trait on the genome might be predictable, based on measurement of a limited subset of genotypes. It uses the theory of real-valued Boolean functions in a systematic way to translate trait data into the Fourier domain. Important trait features, such as the roughness of the trait landscape or the modularity of a trait have a simple Fourier interpretation. Ruggedness at a gene location corresponds to high sensitivity to mutation, while a modular organization of gene activity reduces such sensitivity. Traits where rugged loci are rare will naturally compress gene data in the Fourier domain, leading to a sparse representation of trait data, concentrated in identifiable, low-level coefficients. This Fourier representation of a trait organizes epistasis in a form which is isometric to the trait data. As Fourier matrices are known to be maximally incoherent with the standard basis, this permits employing compressive sensing techniques to work from data sets that are relatively small-sometimes even of polynomial size-compared to the exponentially large sets of possible genomes. This theory provides a theoretical underpinning for systematic use of Boolean function machinery to dissect the dependency of a trait on the genome and environment.


Parental maltreatment and proximal risk factors using the Childhood Experience of Care & Abuse (CECA) instrument: a life-course study of adult chronic depression - 5.
This is the final paper of a series concerning parental maltreatment and chronic depression in women. It extends the scope of the analysis to take account of proximal risk factors, present within at most six months of an onset. It deals with the contribution of factors influencing onset of a depressive episode as well as those related to whether this takes a chronic course. Once a two-stage model dealing with both sets of risk factors has been developed we explore how far distal factors (more than at least one year earlier) influence each stage. Three studies are employed. All take account of parental maltreatment. Two prospective studies deal with proximal risk factors, and a retrospective one with distal and proximal factors. For the first stage of the model concerning onset the influence of parental maltreatment and its correlated risk factors (e.g. conduct problems) are almost entirely mediated by proximal factors (e.g. quality of core relationships). However, for the second stage concerning course parental maltreatment makes a direct contribution that is independent of all other risk factors. The retrospective nature of some of the data may introduce bias (But see the second paper in the present series [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L., 2007b. Validity of retrospective measures of early maltreatment and depressive episodes using the Childhood Experience of Care & Abuse (CECA) instrument - a life-course study of adult chronic depression - 2. J. Affect. Dis., 103, 217-224]). Only females have been considered. The influence of parental maltreatment on the onset of adult depression is largely indirect and the mechanisms involved are reasonably clear. However, the mechanisms involved in the substantial direct contribution of maltreatment to course are as yet unclear. Some interplay of maltreatment and early brain development is one of a number of interesting possibilities.


Optimization of IPG strip equilibration for the basic membrane protein mABC1.
Many proteins with extreme physical properties, including basic and acidic proteins, membrane proteins, and very large proteins, present specific challenges to 2-DE separation. Using a pressure-blotting approach, we demonstrate that a basic integral membrane protein, mitochondrial ATP-binding cassette protein 1 (mABC1), focuses in the IPG strip, but fails to enter into the 2-D SDS-PAGE gel. Through modifying the equilibration conditions between the IPG strip and 2nd dimension, we demonstrate that only by increasing both the volume (from 3 to 6 mL for a 7-cm strip) and SDS concentration (from 2 to 10%) of the equilibration buffer is migration of mABC1 into the 2nd dimension achieved. While 2-DE remains one of the core separation technologies of proteomic analysis, proteins that are extremely basic, hydrophobic, or of large mass present significant challenges to 2-DE separation due to aggregation, oxidation, precipitation, and the physical limitations of the 1-D IPG strip. Since the advent of commercially available IPG strips, numerous groups have experimented with IEF conditions using various detergents alone or in combination, alternative denaturants, and thiol oxidation agents to improve protein focusing. Effective 2-DE separation of membrane proteins has been affected dramatically by these advances in protein solubilization, as well as improvements in isolation of membranes, delipidation, and active in-gel rehydration. Since the development of commercially available basic IPG strips, the most significant advance in the separation of basic proteins has been the introduction of hydroxyethyldisulfides, either alone or in combination with DTT. While hydrophobic proteins were once virtually absent from the 2-D gel, and basic proteins were only visible as dense streaks, now many groups are undertaking large-scale analyses of membranes and basic proteins. Using this base of experimental tools, we embarked on a proteomic analysis of cardiac mitochondrial membranes, hoping to combine the knowledge gained from ongoing targeted protein chemistry and molecular biology studies with a broader-based proteomic analysis. Of particular interest is the inner mitochondrial membrane protein mABC1 (mitochondrial ATP-binding cassette protein 1), which may play a significant role in cardioprotection as part of the mitochondrial ATP-sensitive potassium channels. Therefore, in designing our 2-DE approach, it was crucial to ensure that mABC1 is focused, observable, and quantifiable, despite being an integral membrane protein of pI 9.37.


Clinical Effects and Safety of Auricular Acupressure as an Adjunct Therapy on Postoperative Pain among Patients with Hip Fracture: A Meta-Analysis.
To evaluate the short-term outcome of treatment by auricular acupressure (AA) on postoperative pain among hip fracture (HF) patients. A systematic search for randomized controlled trials on this topic was conducted through May 2022 by searching multiple English and Chinese databases. The methodological quality of the included trails was assessed by the Cochrane Handbook tool, and relevant data were extracted and statistically analyzed by RevMan 5.4.1 software. The quality of the evidence supporting each outcome was evaluated by GRADEpro GDT. Fourteen trials with a total of 1390 participants were included in this study. Compared with conventional treatment (CT) alone, the combination of AA and CT had a significantly greater effect on the visual analog scale at 12 h (MD -0.53, 95% CI -0.77 to -0.30), 24 h (MD -0.59, 95% CI -0.92 to -0.25), 36 h (MD -0.07, 95% CI -0.13 to -0.02), 48 h (MD -0.52, 95% CI -0.97 to -0.08), and 72 h (MD -0.72, 95% CI -1.02 to -0.42), amount of analgesics used (MD -12.35, 95% CI -14.21 to -10.48), Harris Hip Score (MD 6.58, 95% CI 3.60 to 9.56), effective rate (OR 6.37, 95% CI 2.68 to 15.15), and adverse events (OR 0.35, 95% CI 0.17 to 0.71). Compared with CT alone, the combination of AA and CRT had a significantly greater effect on postoperative pain in HF patients. However, trails with a rigorous methodology, including standard protocols for AA and multiethnic subjects, are still needed.


Synthesis of dolichol derivatives in human erythrocyte membranes.
Human erythrocyte membranes contain the enzymes responsible for the synthesis of dolichol-P-glucose, dolichol-P-mannose, dolichol-PP-N-acetylglucosamine, dolichol-PP-NN' diacetylchitobiose and of dolichol-PP-oligosaccharides containing NN' diacetylchitobiose and mannose or the same sugar residues plus glucose. The transfer of the oligosaccharide moieties from the dolichol-PP-oligosaccharides to endogenous proteins could not be detected. These enzymes appeared to be integral membrane proteins.


Successful bilateral lung transplantation for pulmonary fibrosis associated with the Hermansky-Pudlak syndrome.
Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by oculocutaneous albinism, a bleeding diathesis, and in a subset of patients, pulmonary fibrosis. Lung transplantation, the only curative therapy for pulmonary fibrosis, has not been previously reported as a successful treatment strategy for patients with HPS because the bleeding diathesis was thought to contraindicate major thoracic surgery. We successfully performed bilateral sequential lung transplantation in a patient with pulmonary fibrosis and HPS after transfusion of 6 units of platelets. Lung transplantation is a viable therapeutic option in patients with pulmonary fibrosis and only a mild bleeding diathesis associated with HPS.


Human Th1 and Th2 lymphocytes are distinguished by calcium flux regulation during the first 10 min of lymphocyte activation.
Preliminary data suggest different intracellular calcium handling of Th1 and Th2 lymphocytes that may contribute to distinct cytokine production patterns. In this study we explored the contribution of the main mechanisms in charge of the elevation and decrease of cytoplasmic free calcium levels, i.e., the endoplasmic calcium release, the calcium release activated calcium (CRAC) channel, the mitochondrial calcium uniporter (MCU), the sarco/endoplasmic reticulum calcium ATPase (SERCA), and the plasma membrane calcium ATPase (PMCA) during the first 10 min of activation in human Th1 and Th2 lymphocytes applying a kinetic flow cytometry approach. We isolated peripheral blood mononuclear cells from 10 healthy individuals. Cells were stained with CD4, CXCR3 and CCR4 cell surface markers to identify Th1 and Th2 cells, respectively and loaded with Fluo-3/AM calcium sensitive dye. Cells were activated with phytohemagglutinine and alterations of cytoplasmic free calcium levels were monitored for 10 min after specific inhibition of the above mechanisms. Our results revealed delicate differences in calcium flux kinetics of Th1 and Th2 lymphocytes. The lower activity of MCU, and therefore of CRAC channels, along with the higher activity of the SERCA pump account for the notion that Th2 cells go through a lower level of lymphocyte activation compared with Th1 cells upon identical activating stimuli. The observed differences in calcium flux of Th1 and Th2 cells may contribute to different calcium handling kinetics and, hence, to distinct cytokine production patterns by these subsets.


Phenotype variability and histopathological findings in patients with a novel DNM2 mutation.
Mutations of Dynamin 2 (DNM2) are responsible for several forms of neuromuscular disorder such as centronuclear myopathy, Charcot-Marie-Tooth disease (CMT) dominant intermediate type B, CMT 2M, and lethal congenital contracture syndrome 5. We describe a young man manifesting as length-dependent sensorimotor neuropathy with hypertrophic cardiomyopathy, but his mother only had very mild symptoms of peripheral neuropathy. The electrophysiological data meet the criteria of intermediate CMT. The main pathological findings of sural nerve biopsy reveal a severe loss of large myelinating fibers and some clusters of regenerative fibers in fascicles, which are consistent with an axonal neuropathy. However, myopathological changes show a chronic myopathy-like pattern characterized by great variations of fiber size, increased connective tissue, rimmed vacuoles and predominance of type 2 fibers. A novel DNM2 mutation (p.G359D) in the middle domain is identified, which is highly evolutionarily conserved. DNM2-related CMT disease is phenotypically heterogeneous in age at onset, clinical features and electrophysiological changes. The histopathological findings indicate the coexistence of typical axonal neuropathy and chronic myopathy in DNM2-related neuromuscular diseases.


Oligonucleotide arrays: information from replication and spatial structure.
The introduction of oligonucleotide DNA arrays has resulted in much debate concerning appropriate models for the measurement of gene expression. By contrast, little account has been taken of the possibility of identifying the physical imperfections in the raw data. This paper demonstrates that, with the use of replicates and an awareness of the spatial structure, deficiencies in the data can be identified, the possibility of their correction can be ascertained and correction can be effected (by use of local scaling) where possible. The procedures were motivated by data from replicates of Arabidopsis thaliana using the GeneChip ATH1-121501 microarray. Similar problems are illustrated for GeneChip Human Genome U133 arrays and for the newer and larger GeneChip Wheat Genome microarray. R code is freely available on request.


Drug delivery systems for treatment of systemic hypertension.
Novel drug delivery systems are available in many areas of medicine. Their application in the treatment of hypertension continues to widen. Oral drug delivery systems permit antihypertensive agents that were previously administered two to four times daily to be administered once daily. Biotechnical use of chemical-dispensing systems has been applied to propranolol (polymer coated beads), clonidine (transdermal therapeutic system), nifedipine (osmotic pump and coat-core), isradipine (osmotic pump), verapamil (sodium alginate and spheroidal oral delivery absorption system), felodipine (coat-core), nisoldipine (coat-core) and diltiazem (polymer coated beads and Geomatrix. The initial goal was to lower blood pressure by a uniform amount throughout the entire day. Now, new drug delivery systems are being developed to target blood pressure in the early morning hours when most cardiovascular events occur. Two chronotherapeutic drug delivery systems are now available for verapamil (chronotherapeutic oral delivery absorption system and delayed coat osmotic pump). Disadvantages of sustained-release products include delayed achievement of pharmacodynamic effect, unpredictable bioavailability, enhanced first-pass hepatic metabolism, dose dumping, sustained toxicity, dosage inflexibility and increased cost. Potential advantages include reduced administration frequency, enhanced adherence and convenience, reduced toxicity, stable drug concentrations, uniform drug effect, decreased cost (occasionally) and decreased daily dosage.


Clearing the air on surgical plume.
Surgical smoke or plume is produced by a variety of surgical coagulators and dissectors. A number of jurisdictions have recently introduced policies to reduce the associated occupational health risks including WorkSafe Victoria and New South Wales Health. This paper is a narrative review of potential risks, including any associated with COVID-19, and options for mitigation. Surgical smoke or plume contains potentially toxic chemicals, some of which are carcinogens. Plume may also contain live virus, notably Human Papilloma and Hepatitis B, though any possible viral transmission is limited to a few case reports. Despite identifying COVID-19 ribonucleic acid fragments in various body tissues and fluids there are no current reports of COVID-19 transmission. Although plume is rapidly removed from the atmosphere in modern operating rooms, it is still inhaled by the operative team. Mitigation should include ensuring diathermy devices have evacuators while plume extraction should be standard for laparoscopic procedures. Consideration needs to be given to the potential to compromise the operating field of view, or the noise of the extractor impairing communication. There is an increasing range of suitable products on the market. The future includes pendant systems built into the operating room. The potential risks associated with surgical plume cannot be ignored. Health services should invest in plume extraction devices with a view to protecting their staff. The conduct of the operation should not be compromised by the devices chosen. Future operating theatres need to be designed to minimize exposure to plume.


The laboratory diagnosis of Legionnaires' disease.
Legionnaires' disease can be diagnosed by culture, by direct detection of the bacterium or its products by using immunologic means, with a DNA probe, and by serologic means. Culture diagnosis is the most specific and sensitive test. Legionellae can be isolated from sputum samples by using selective techniques. Antibody detection is more suited for epidemiologic purposes than for use in individual cases. Immunofluorescent microscopy is a useful and rapid means of diagnosis. Alternative rapid and specific tests are urinary antigen detection and the use of a DNA probe. Culture must always be performed for optimal sensitivity and for epidemiologic purposes.


Pharmacokinetics of the main compounds absorbed into blood after oral administration of Liu Wei Di Huang Wan, a typical combinatorial intervention of Chinese medical formula.
Liu Wei Di Huang Wan (LW) has been used as an active Chinese patent formula for "Five Late Syndrome" of Children for thousands of years. Due to the complexity in its chemical constituents, the pharmacokinetics of this formula have not been elucidated clearly, and the understanding of its pharmacological properties has been delayed. Previous studies have identified the constituents absorbed into blood after the oral administration of LW; moreover, 5-hydroxymethyl-2-furoic acid (HMFA), loganin and paeonol have been proved as surrogate markers. In this study, a rapid validated high-performance liquid chromatography method was developed for determining three marker compounds in plasma. The analysis was performed on a Waters Symmetry Shield™ RP(18) column with acetonitrile and 0.15% phosphoric acid as the mobile phase, which showed acceptable linearity, intra- and inter-day precision, and accuracy. By using the established method, the pharmacokinetic analysis of LW was carried out. The t (1/2)α and t (1/2)β were 2.62/32.66, 0.46/4.71 and 1.30/23.51 h and the climax times and concentrations were 0.56/683.75, 0.70/2826.11 and 0.62 h/4030.48 ng ml(-1) for HMFA, loganin and paeonol, respectively. Especially, both the absorption and disposition of HMFA were swift (t (1/2) kα 0.1 h, t (1/2)α 2.62 h), but the elimination was quite slow (t (1/2)β 32.66 h); this phenomenon reflected the synergetic effect of LW combinatorial intervention and the value of compatibility can be more clearly understood. The pharmacokinetic characters of HMFA, loganin and paeonol not only elucidated the steady and long-lasting pharmacological properties, but they also revealed the practical value of the compatibility of Chinese medical formula.


Genetics of esterases in Drosophila. V. Characteristics of the "pupal" esterase in D. virilis.
From analysis of the properties of the "pupal" esterase (p-esterase) in Drosophila virilis, it is concluded that it is heat stable, its electrophoretic detection depends on culture density, its expression is stage specific, and it is not a variant of esterase 2. It was also demonstrated that p-esterase, like esterase 6, is activated by injections of the juvenile hormone into larvae. Heat treatment of heat-resistant D. virilis stocks led to decreased activities of the juvenile hormone dependent esterases but did not affect those of the heat-sensitive stocks. It is suggested that heat resistance in D. virilis is related to some functional features of the system of modifier genes controlling the phenotypic expression of esterases.


Structural and Functional Correlates of Gradient-Area Patterns in Severe Aortic Stenosis and Normal Ejection Fraction.
The authors sought to characterize the functional and structural myocardial phenotypes of patients with moderate-to-severe aortic stenosis (AS) and to determine whether severe paradoxical low-gradient AS (LG-AS) is specifically associated with left ventricular (LV) remodeling and fibrosis. Recently, it was suggested that severe paradoxical LG-AS is a more advanced form of AS, with greater reduction of longitudinal deformation, adverse LV remodeling, and more interstitial fibrosis. The study population includes 147 patients with moderate-to-severe AS and a normal LV ejection fraction, and 75 normal control subjects. They prospectively underwent 2-dimensional speckle-tracking echocardiography and cardiac magnetic resonance to evaluate myocardial deformation, LV remodeling, and age- and sex-adjusted extravascular volume fraction (ECV, %). Among AS patients, 18 had moderate AS, 74 had severe high-gradient AS (HG-AS), and 55 had severe paradoxical LG-AS. Reduced longitudinal and circumferential deformation was observed in 21% and 6% of the AS patients, respectively. Multivariate analyses identified increased ECV (ß = 1.99; p = 0.001) and the absence of normal LV geometry (ß = -1.37; p = 0.007) and as independent predictors of reduced longitudinal deformation. Increased ECV was an independent predictor of reduced circumferential deformation (ß = 2.19; p = 0.001). Over a median follow-up of 29 months, reduced longitudinal deformation (hazard ratio: 0.82; p = 0.023) and higher transvalvular gradients (hazard ratio: 1.05; p < 0.001) increased the risk of death or need for aortic valve replacement. LV hypertrophy was more frequently observed among patients with severe HG-AS (65%) than among the other AS patients (14%; p < 0.001). On average, ECV was within normal limits and did not differ among gradient-area subgroups. When present, increased ECV was associated with reduced longitudinal deformation. This study's data show that patients with severe paradoxical LG-AS less frequently display reduced longitudinal deformation, LV hypertrophy, or myocardial fibrosis than patients with HG-AS. Also, interstitial fibrosis only occurs when reduced longitudinal deformation and severe HG-AS are present together. Finally, this study suggests that reduced longitudinal deformation and higher transvalvular gradients adversely affect patients' outcomes.


Laboratory methods for the diagnosis of disseminated histoplasmosis: clinical importance of the lysis-centrifugation blood culture technique.
Disseminated histoplasmosis, an uncommon disease that is usually fatal if not treated, is being recognized with increasing frequency in immunosuppressed patients. We retrospectively reviewed the laboratory methods used to establish the diagnosis of disseminated histoplasmosis in 28 patients examined at our institution. Tissue stains provided the initial diagnosis in 13 of the patients (46%). Serologic tests (complement fixation or immunodiffusion) were positive in 25 patients (89%); the frequencies of positive serologic results were similar in immunocompetent and in immunosuppressed patients. Blood cultures were positive in 20 of the patients (71%) and provided the initial diagnosis in 7 (25%); 5 of these 7 cases (71%) were detected with use of the lysis-centrifugation method. Furthermore, the recovery time for this blood culture method was less than that for a conventional blood culture method (brain-heart infusion biphasic technique). The lysis-centrifugation blood culture technique is an important laboratory method for the diagnosis of disseminated histoplasmosis.


The hippocampus supports high-resolution binding in the service of perception, working memory and long-term memory.
It is well established that the hippocampus plays a critical role in our ability to recollect past events. A number of recent studies have indicated that the hippocampus may also play a critical role in working memory and perception, but these results have been highly controversial because other similar studies have failed to find evidence for hippocampal involvement. Thus, the precise role that the hippocampus plays in cognition is still debated. In the current paper, I propose that the hippocampus supports the generation and utilization of complex high-resolution bindings that link together the qualitative aspects that make up an event; these bindings are essential for recollection, and they can also contribute to performance across a variety of tasks including perception and working memory. An examination of the existing patient literature provides support for this proposal by showing that hippocampal damage leads to impairments on perception and working memory tasks that require complex high-resolution bindings. Conversely, hippocampal damage is much less likely to lead to impairments on tasks that require only low-resolution or simple associations/relations. The current proposal can be distinguished from earlier accounts of hippocampal function, and it generates a number of novel predictions that can be tested in future studies.


Design and validation of a homogeneous time-resolved fluorescence-based leptin receptor binding assay.
The pleiotropic cytokine hormone leptin, by activating its receptor OB-R, plays a major role in many biological processes, including energy homeostasis, immune function, and cell survival and proliferation. Abnormal leptin action is associated with obesity, autoimmune diseases, and cancer. The pharmacological characterization of OB-R and the development of synthetic OB-R ligands are still in their infancy because currently available binding assays are not compatible with ligand saturation binding experiments and high-throughput screening (HTS) approaches. We have developed here a novel homogeneous time-resolved fluorescence-based binding assay that overcomes these limitations. In this assay, fluorescently labeled leptin or leptin antagonist binds to the SNAP-tagged OB-R covalently labeled with terbium cryptate (Tb). Successful binding is monitored by measuring the energy transfer between the Tb energy donor and the fluorescently labeled leptin energy acceptor. Ligand binding saturation experiments revealed high-affinity dissociation constants in the subnanomolar range with an excellent signal-to-noise ratio. The assay performed in a 384-well format shows high specificity and reproducibility, making it perfectly compatible with HTS applications to identify new OB-R agonists or antagonists. In addition, fluorescently labeled leptin and SNAP-tagged OB-R will be valuable tools for monitoring leptin and OB-R trafficking in cells and tissues.


Effects of transurethral resection of prostate on the quality of life of patients with benign prostatic hyperplasia.
This article investigated the effects of transurethral resection of prostate on quality of life (QOL) and urinary symptoms in patients with benign prostatic hyperplasia (BPH). In a prospective study, 30 patients without significant comorbidities undergoing transurethral resection of prostate for BPH were studied. Patients completed four validated questionnaires: the International Prostate Symptom Score and the associated QOL index because urinary symptoms, the Montgomery and Asberg Depression Rating Scale, the McGill Pain Questionnaire, and the QOL questionnaire Short Form-36. These were completed preoperatively, on the first postoperative day, on discharge from hospital, and at 1 and 3 months postoperatively. The QOL of patients who undergo transurethral resection of prostate for BPH had significantly improved at 3 months after their operation. The International Prostate Symptom Score scores at 1 month (9.3+/-4.6) and 3 months (5.4+/-5.6) were less than they were preoperatively (19.9+/-7.1). The QOL index because urinary symptoms was less at 1 month (2.4+/-1.9) and at 3 months postoperatively (1.5+/-1.4) in comparison with the preoperative scores (4.5+/-1.2). The Montgomery and Asberg Depression Rating Scale scores at 1 month (5.4+/-6.8) and 3 months (4.9+/-6.5) were less than they were preoperatively (9.2+/-8.3). The McGill Pain Questionnaire sensory and pain rating index scores were less at 3 months than they were preoperatively (p=0.02 and p<0.02 respectively). The McGill Pain Questionnaire affective score was less at 1 month than it was preoperatively (p<0.03). The McGill Pain Questionnaire evaluative scores were less than the preoperative score at all times postoperatively. The role physical (p=0.007), bodily pain (p=0.006), social function (p=0.007), and physical component summary (p=0.007) subsections of the Short Form-36 were greater at 3 months postoperatively when compared with the preoperative scores. Transurethral resection of prostate is associated with significant improvement in the overall QOL, in addition to urinary symptoms, of patients with BPH at 3 months postoperatively. The magnitude and timing of this improvement may serve as a useful comparator in determining the optimal treatment of patients with BPH.


Dorsally recumbent female equine urogenital endoscopic surgery.
The ventral abdominal approach for laparoscopy is versatile. Reported techniques using a ventral approach in the mare include bilateral ovariectomy and granulosa cell tumor removal. Laparoscopic ovariectomy is performed by way of four instrument portals in the caudoventral aspect of the insufflated abdomen. The procedure has several advantages over the traditional approaches of colpotomy and celiotomy, including tension-free closure of all incisions and minimal invasiveness.


Effect of GA3 and 2,4-D foliar application on the anatomy of date palm (Phoenix dactylifera L.) seedling leaf.
Two concentrations (10-5M and 10-3M) of both GA3 and 2,4-D were used as foliar spray to evaluate the response of date palm (Phoenix dactylifera L.) cv. Khedri seedlings. They affected some of the anatomical characteristics of the first leaf emerging after the beginning of the spray. The high concentration of GA3 increased the size of the midrib and its vascular bundle numbers. Both low and high concentrations of 2,4-D inhibited the formation of the midrib. 2,4-D in both low and high concentrations decreased the number of vessels in both protoxylem and metaxylem and also decreased their diameters, where as GA3 in low and high concentrations have less effect on the number of vessels and its diameters. GA3 in high concentration increased the number of vascular bundles in 1mm long of the leaf blade, while 2,4-D in low and high concentrations decreased their numbers. 10-3M of 2,4-D increased the size and layers of special hypodermal cells.


Design and optimization of three-dimensional composite multilayer cylindrical pentamode metamaterials for controlling low frequency acoustic waves.
For three-dimensional pentamode metamaterials, it is of great significance to realize underwater low frequency acoustic wave control. Therefore, in order to compare with traditional double-cone pentamode metamaterials, two multilayer composite cylindrical three-dimensional pentamode metamaterials with low frequency and broad band gaps are proposed in this paper. By using pentamode metamaterials with lattice constants on the order of centimeters, the phononic band gaps below 60 Hz and the single-mode area below 30 Hz can be obtained. In addition, compared with asymmetrical double-cone locally resonant pentamode metamaterials, the lower edge frequency, relative bandwidth and figure of merit of the first phononic band gap can be reduced by up to 61.4%, 10.3% and 40.6%, respectively. It will provide reference and guidance for the engineering application of pentamode metamaterials in controlling the ultra-low frequency broadband acoustic waves, vibration and noise reduction.


Predicting joint toxicity of chemicals by incorporating a weighted descriptor into a mixture model: Cases for binary antibiotics and binary nanoparticles.
A prediction method that integrated a mixture descriptor with an established mixture toxicology method was proposed for the joint toxicity of chemical pollutants. A weighted descriptor derived from the single descriptor of each component was employed to calculate a mixture descriptor, which was successfully embedded into the generalized concentration addition (GCA) model named the extended GCA (XGCA) model. To develop and validate the proposed approach, binary antibiotic mixtures (ciprofloxacin and oxytetracycline) and metal-oxide (copper oxide and zinc oxide) nanoparticle mixtures were selected to study their toxicity to freshwater green algae. The results showed that concentration-response curve (CRC) derived from the XGCA model was closer to the observed CRC than those from the GCA, Concentration Addition (CA), and Independent Action (IA) models. The difference between effect concentrations predicted by the XGCA model and observed did not exceed a factor of 1.6. The XGCA model was relatively more accurate at predicting joint toxicity (in terms of effect concentrations and effect errors) than the reference models, independent of component types and mixture ratios. The XGCA model predicts the joint toxicity through molecular structural or nanostructural characters, thus modes of toxic action are not preconditions for predicting the toxicity of the mixtures. This result demonstrates the practicability of using the XGCA method in toxicity assessments of mixture pollutants with unknown modes of action.


Isolation of viral ribonucleoprotein complexes from infected cells by tandem affinity purification.
The biochemical purification and analysis of viral ribonucleoprotein complexes (RNPs) of negative-strand RNA viruses is hampered by the lack of suitable tags that facilitate specific enrichment of these complexes. We therefore tested whether fusion of the tandem-affinity-purification (TAP) tag to the main component of viral RNPs, the nucleoprotein, might allow the isolation of these RNPs from cells. We constitutively expressed TAP-tagged nucleoprotein of Borna disease virus (BDV) in cells persistently infected with this virus. The TAP-tagged bait was efficiently incorporated into viral RNPs, did not interfere with BDV replication and was also packaged into viral particles. Native purification of the tagged protein complexes from BDV-infected cells by two consecutive affinity columns resulted in the isolation of several viral proteins, which were identified by MS analysis as the matrix protein, the two forms of the nucleoprotein and the phosphoprotein. In addition to the viral proteins, RT-PCR analysis revealed the presence of viral genomic RNA. Introduction of further protease cleavage sites within the TAP-tag significantly increased the purification yield. These results demonstrate that purification of TAP-tagged viral RNPs is possible and efficient, and may therefore provide new avenues for biochemical and functional studies of these complexes.


Associations between Interleukin-32 Gene Polymorphisms rs12934561 and rs28372698 and Susceptibilities to Bladder Cancer and the Prognosis in Chinese Han Population.
The proinflammatory chemokine interleukin-32 is related to various diseases, including cancer. However, it has never been associated with bladder cancer (BC). To detect whether there is a relationship between the IL-32 gene polymorphisms (rs12934561 C/T and rs28372698 T/A) and BC, the study enrolled 170 non-muscle-invasive bladder cancer (NMIBC) patients, 151 muscle-invasive bladder cancer (MIBC) patients, and 437 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for the IL-32 single-nucleotide polymorphism (SNP) genotyping. Statistical analysis was performed using SNPstats online analysis software and SPSS software. Our data revealed that the CC homozygous genotype of rs12934561 in BC patients was significantly higher than that in controls (P = 0.03, OR = 1.47, 95%CI = 1.04-2.08), and the percentage of TC genotype carriers was relatively less than that of controls (P = 0.001, OR = 0.61, 95%CI = 0.45-0.82). Furthermore, the TT homozygous genotype of rs28372698 was associated with a significantly lower overall survival rate in MIBC patients (P = 0.028, OR = 2.77, 95%CI = 1.11-6.90). The IL-32 gene polymorphism rs12934561 might be associated with increased BC risk, and the rs28372698 might participate in the prognosis of BC patients. Therefore, they could be potential forecasting factors for the prognosis of MIBC patients.


Effect of fucoidan on gut microbiota and its clinical efficacy in Helicobacter pylori eradication: A randomized controlled trial.
To assess the clinical efficacy of fucoidan-assisted standard quadruple therapy (SQT) in Helicobacter pylori (H. pylori) eradication and the improvement of gut microbiota. An open-label randomized controlled trial was conducted at the Affiliated Hospital of Qingdao University in Shandong Province, China. Ninety patients who tested positive for H. pylori were randomized to the standard quadruple therapy (SQT) group (SQ), SQT + fucoidan combination group (SF), and fucoidan + sequential SQT group (FS), respectively. Stool samples were collected for gut microbiota composition at baseline and after treatment. After H. pylori eradication, the relative abundances of most conditional pathogens in the SQ decreased, while those of several beneficial bacteria increased or decreased (P < 0.05). In FS, the abundances of most beneficial bacteria increased gradually from baseline to week 12, while those of the conditional pathogens decreased (P < 0.05). The abundance of Bifidobacterium had a decreasing trend in SQ, but remained unchanged in SF and increased in FS (P < 0.05). The abundances of most beneficial bacteria were significantly higher in FS than in SQ and SF (P < 0.05). Addition of fucoidan enhanced symptom improvement during H. pylori eradication compared with SQT alone. Fucoidan considerably improved gut dysbiosis during SQT for H. pylori eradication. Gut microbiota can be maintained by the addition of fucoidan before eradication therapy with SQT rather than by concomitant addition with therapy. Fucoidan-assisted SQT could relieve gastrointestinal symptoms during H. pylori eradication.


Vectorial redox reactions of physiological quinones. II. A study of transient semiquinone formation.
Transient absorption changes during reduction of quinone in liposomes by external dithionite, in the absence and presence of initially trapped ferricyanide, were matched with absorption spectra of semiquinone and quinone in the blue region. Plastoquinone, ubiquinone-9 and phylloquinone, each having an isoprenoid side chain were compared with trimethyl-p-benzoquinone, ubiquinone-9 and menadione, which lack a long side chain. Semiquinone transients could only be observed by our spectroscopic technique during reduction of quinones lacking the chain. If Triton X-100 was added to the liposomes preparation semiquinone transients were also observed with the isoprenoid quinones. This result is consistent with the view that isoprenoid quinones build domains in the membranes, in which the life time of the semiquinone might be decreased by fast disproportionation, and to which dithionite has limited access.


Postoperative infection with meticillin-resistant Staphylococcus aureus and socioeconomic background.
Infectious disease can be linked to social deprivation. We investigated whether postoperative infection with meticillin-resistant Staphylococcus aureus (MRSA) is related to socioeconomic background. Patients were stratified by social deprivation according to postcode. In a consecutive series of 1739 UK residents undergoing isolated coronary artery bypass grafting, 23 (1.3%) were infected with MRSA. We noted a graded relation between incidence of infection and social deprivation. Patients from the most deprived areas had a seven-fold higher infection rate (13 of 579 [2.2%]) than those from the least deprived areas (two of 580 [0.3%]; p=0.0040). Patients with MRSA infection had a six-fold higher mortality rate and a longer hospital stay than patients with no such infection. Our findings suggest that patients from deprived areas might be especially susceptible to postoperative infection with MRSA.


Multifaceted role of RNA editing in promoting loss-of-function of PODXL in cancer.
PODXL, a protein that is dysregulated in multiple cancers, plays an important role in promoting cancer metastasis. In this study, we report that RNA editing promotes the inclusion of a PODXL alternative exon. The resulting edited PODXL long isoform is more prone to protease digestion and has the strongest effects on reducing cell migration and cisplatin chemoresistance among the three PODXL isoforms (short, unedited long, and edited long isoforms). Importantly, the editing level of the PODXL recoding site and the inclusion level of the PODXL alternative exon are strongly associated with overall patient survival in Kidney Renal Clear Cell Carcinoma (KIRC). Supported by significant enrichment of exonic RNA editing sites in alternatively spliced exons, we hypothesize that exonic RNA editing sites may enhance proteomic diversity through alternative splicing, in addition to amino acid changes, a previously under-appreciated aspect of RNA editing function.


Early postnatal dexamethasone diminishes transforming growth factor alpha localization within the ileal muscularis propria of newborn mice and extremely low-birth-weight infants.
Focal small bowel perforation (FSBP) occurs most commonly in the ileum of extremely low-birth-weight (ELBW) infants. Early postnatal dexamethasone (EPD) administration results in an increased risk for FSBP in this patient population, but the mechanism by which this occurs is unknown. Infants with FSBP have healthy mucosa but thinned smooth muscle, suggesting a mechanism involving the muscularis propria for these perforations. One explanation for these findings would be that dexamethasone alters the tissue availability of pertinent growth factors to the smooth muscle. To explore this possibility, we administered dexamethasone or saline by intraperitoneal injection to newborn mice for 3 days (dosed at 1 microg/g of body weight/day) to simulate EPD protocols. The animals were sacrificed after 72 h of treatment and their ileums harvested and prepared for microscopy. Immunolocalization was performed for three related growth factors (epidermal growth factor [EGF], heparin-binding EGF [h-EGF], and transforming growth factor alpha [TGF-alpha]) and their common receptor. We found TGF-alpha to be abundant and discretely localized in the muscularis propria in control animals but to be diminished in dexamethasone-treated animals. EGF-receptor immunostaining was also decreased with dexamethasone but there was minimal to no detection of EGF or h-EGF in either treatment condition. Surgical and autopsy specimens of the ileum were obtained from seven ELBW infants who either received EPD or not. These tissues were used for immunolocalization of the same growth factors and similar distributions for TGF-alpha were observed in several of these cases. These findings are consistent with an autocrine role for TGF-alpha in ileal smooth muscle proliferation and suggest a mechanism by which EPD might mediate smooth muscle thinning.


Low doses of 15d-PGJ2 induce osteoblast activity in a PPAR-gamma independent manner.
Peroxisome proliferator-activated receptor-gamma (PPARγ) regulates both glucose metabolism and bone mass. Evidence suggests that the therapeutic modulation of PPARγ with synthetic agonists activity may elicit undesirable effects on bone. However, there is no information regarding its natural agonist 15d-PGJ2, besides its excellent anti-inflammatory action. In the present study the effects of 15d-PGJ2 on osteoblastic cells were determined. Osteoblastic cells (MC3T3) were cultured in an osteogenic medium in the presence of 1, 3 or 10 μM of 15d-PGJ2 during 21 days and alizarin and Von Kossa staining were employed. The protein expression (type-I collagen, osteonectin, osteopontin, RANKL, osteoprotegerin, HDAC-9c and PPAR-γ) was evaluated after 3 days in the presence of 15d-PGJ2 by western blotting and indirect immunofluorescence methods. The production of mineralized extracellular matrix was observed by transmission electron microscopy. After 72 h of culture, the mRNA was extracted for RT-qPCR analysis of RUNX expression. In the presence of all 3 tested 15d-PGJ2 doses, alizarin red and Von kossa staining were positive demonstrating the ability to the osteoblast differentiation. Type-I collagen and osteonectin proteins expression were up-regulated (p < 0.05) after 72 h in the presence of the smaller doses of 15d-PGJ2. In contrast, osteopontin, RANKL and OPG expression did not significantly alter. In the presence of 15d-PGJ2 it was possible to visualize mineralized nodules in the extracellular matrix confirmed with the increased RUNX mRNA expression. 15d-PGJ2 at small doses increased the osteoblast activity and the bone-related proteins expression.


Rheumatoid Factor and Disease Activity Are Independent Predictors of Lymphoma in Primary Sjögren's Syndrome.
To define parameters predictive of lymphoma development in patients with primary Sjögren's syndrome (SS). A multicenter case-control survey was performed to identify predictors of lymphoma. Cases were patients who developed lymphoma after diagnosis of primary SS and were mainly recruited through the Club Rhumatismes et Inflammation network. For each case, 2 controls (matched for disease duration and age) were randomly selected among patients with primary SS and without lymphoma. Cases and controls were compared using univariate analysis and then using multivariate analysis to identify independent predictors of lymphoma. One hundred one patients with primary SS and lymphoma were included. Eighty-seven patients were women (86.1%), and the mean ± SD age at lymphoma diagnosis was 57.4 ± 12.6 years. The most frequent histologic type was B cell non-Hodgkin's lymphoma (NHL) in 99 of 101 patients, with marginal-zone lymphoma in 76 of the 99 patients (76.8%) including 58 (58.6%) with lymphoma of the mucosa-associated lymphoid tissue type. Lymphomas were most frequently located in the salivary glands (43 patients). A specific treatment was initiated at diagnosis in 87 patients with B cell NHL, and 61 patients (61.6%) achieved complete sustained remission after the first line of treatment. In the multivariate analysis, salivary gland enlargement, the presence of rheumatoid factor (RF), low C4, cryoglobulinemia, lymphopenia, and disease activity according to the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (excluding the lymphoma domain) were found to be predictors of lymphoma. No previous treatment for primary SS was associated with any effect on lymphoma occurrence. In addition to previously known factors predictive of lymphoma occurrence, the independent roles of RF and disease activity were demonstrated in this case-control study of primary SS-associated lymphoma. Our findings highlight the roles of chronic antigenic stimulation and disease activity in the development of this severe complication.