Leptin inhibits bone formation not only in rodents, but also in sheep.
This study examines the effect of long-term ICV administration of leptin in ewes. We found that central application significantly decreased osteoblast activity as measured by serum analysis as well as by histomorphometry, resulting in decreased trabecular bone volume. These data provide additional evidence that bone formation and therefore bone remodeling is at least in part centrally controlled. Genetic studies in mice have identified leptin as a potent inhibitor of bone formation acting through the central nervous system and unraveled the central nature of bone mass control and its disorders. Although these studies have radically enhanced our understanding of skeletal physiology because they have established a hypothalamic regulation of bone remodeling through the sympathetic nervous system, controversy remains about the physiological relevance of these observations because leptin's effect on bone after intracerebroventricular (ICV) application has only been shown in mice. To address whether leptin has a role in regulating bone mass beyond rodents, we treated ewes with long-term ICV application of leptin and analyzed the bone phenotype after a treatment period of 3 months. Three groups of corriedale sheep were compared: (1) control entire (control), (2) ovariectomy (OVX) and ICV application of cerebrospinal fluid (CSF); and (iii) OVX and ICV application of leptin (leptin). Analysis included histomorphometric characterization of iliac crest, spine and femur by histology and biomechanical testing and measurement of bone turnover parameters in serum and urine. Central application of leptin decreased bone formation by 70% and mineralizing surface (MS/BS, 39.4 +/- 3.3% versus 16.1 +/- 2.1%) significantly (p < 0.01). Whereas OVX increased osteoclast indices and urinary cross-lap excretion by two and three times, respectively, serum parameters of osteoblast activity were significantly reduced by ICV application of leptin (p < 0.01). Consequently, ewes treated with leptin were osteopenic (iliac crest BV/TV entire, 22.7 +/- 1.3%; CSF, 18.9 +/- 2.4%; leptin, 12.4 +/- 2.6%), whereas bone torsional failure load reflecting the cortex of the tibia was not yet changed after 3 months of treatment (p < 0.01). Taken together, these data suggest that leptin controls bone formation after ICV application, leading to reduction of trabecular bone mass in sheep. Most importantly, however, they show that the central regulation of bone formation is not limited to rodents, but is also found in large animals, providing further evidence that bone remodeling in vertebrates is centrally controlled.


Rapid picture processing: affective primes and targets.
In rapid serial visual presentation of pictures, an early ERP component shows enlarged negativity over occipital regions for emotional, compared to neutral, pictures. The present study examined the processing of emotional target pictures as a function of the hedonic valence of a preceding prime picture. Dense sensor ERPs were measured while subjects viewed a continuous stream of pleasant, neutral, and unpleasant pictures, presented for 335 ms each. Two main findings were observed: First, replicating previous results, emotional target pictures were associated with a larger posterior negativity, compared to neutral pictures. Second, the emotional content of the preceding prime picture affected target processing, with pleasant or unpleasant primes resulting in reduced negativity of the following picture, irrespective of its emotional valence. These findings are discussed within a framework of competition among successive pictures.


Immunocytochemical study of tissue parasitism of dog adrenal glands in experimental Chagas' disease.
In human beings, the central vein of the adrenal glands has been considered by some authors to be one of the preferential sites of Trypanosoma cruzi settling in the chronic form of Chagas' disease. This appears to be due to the local corticoid-rich environment that may protect the parasite against the immunological defences of the host. An immunocytochemical study of the adrenal glands of 15 dogs was carried out for the detection of tissue parasitism in the acute and chronic phases of experimental T. cruzi infection. No amastigote nests or isolated amastigotes were detected in the adrenal parenchyma or adrenal central vein of the animals studied. Minimal nonspecific inflammatory changes were found in some glands of both infected and noninfected animals. The present results show that the adrenal glands of the dog are not injured and do not constitute a site of escape or reservoir of parasites in experimental Chagas' disease.


Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease.
Probiotics are microorganisms that are ingested either in combination or as a single organism in an effort to normalize intestinal microbiota and potentially improve intestinal barrier function. Recent evidence has suggested that inflammatory bowel disease (IBD) may result from an inappropriate immunologic response to intestinal bacteria and a disruption in the balance of the gastrointestinal microbiota in genetically susceptible individuals. Prebiotics, synbiotics, and probiotics have all been studied with growing interest as adjuncts to standard therapies for IBD. In general, probiotics have been shown to be well-tolerated with few side effects, making them a potential attractive treatment option in the management of IBD. To perform a systematic review of randomized controlled trials on the use of probiotics, prebiotics, and synbiotics in IBD. In our systematic review we found 14 studies in patients with Crohn's disease (CD), 21 studies in patients with ulcerative colitis (UC), and five studies in patients with pouchitis. These were randomized controlled trials using probiotics, prebiotics, and/or synbiotics. In patients with CD, multiple studies comparing probiotics and placebo showed no significant difference in clinical outcomes. Adding a probiotic to conventional treatment improved the overall induction of remission rates among patients with UC. There was also a similar benefit in maintaining remission in UC. Probiotics have also shown some efficacy in the treatment of pouchitis after antibiotic-induced remission. To date, there is insufficient data to recommend probiotics for use in CD. There is evidence to support the use of probiotics for induction and maintenance of remission in UC and pouchitis. Future quality studies are needed to confirm whether probiotics, prebiotics, and synbiotics have a definite role in induction or maintenance of remission in CD, UC, and pouchitis. Similar to probiotics, fecal microbiota transplantation provides an alternate modality of therapy to treat IBD by influencing the intestinal flora.


Lipid Metabolism: Immune Regulation and Therapeutic Prospectives in Systemic Lupus Erythematosus.
Systemic lupus erythematosus (SLE) is a heterogeneous disease characterized by the production of abnormal autoantibodies and immune complexes that can affect the organ and organ systems, particularly the kidneys and the cardiovascular system. Emerging evidence suggests that dysregulated lipid metabolism, especially in key effector cells, such as T cells, B cells, and innate immune cells, exerts complex effects on the pathogenesis and progression of SLE. Beyond their important roles as membrane components and energy storage, different lipids can also modulate different cellular processes, such as proliferation, differentiation, and survival. In this review, we summarize altered lipid metabolism and the associated mechanisms involved in the pathogenesis and progression of SLE. Furthermore, we discuss the recent progress in the role of lipid metabolism as a potential therapeutic target in SLE.


Making sense of self-care practices at the intersection of severe mental illness and physical health-An Australian study.
The poor physical health of people who experience severe mental illness (SMI) is an important public health issue that has been acknowledged, yet not properly addressed. People who live with SMI perform a myriad of complex tasks in order to take care of their physical health, while receiving unpredictable levels of support and assistance from health professionals. In this qualitative study, we aimed to uncover the kinds of work people with SMI do in order to look after their physical health. In a metropolitan area in Queensland, Australia, 32 people with lived experience of SMI participated in semi-structured, face-to-face interviews. Data were digitally recorded, transcribed verbatim and open coded. They were then themed using a constant comparative process. We found that people with SMI were engaged in a "rhythm of life with illness" that consisted of relatively short, acute and chaotic cycles of mental and physical illness, accompanied by much longer mental and physical illness recovery cycles. Participants engaged in three specific types of health-related work to manage these cycles: discovery work (and the associated role of the health professional); sense-making work to meaningfully interpret health and illness; and embedding work to become engaged self-managers of illness and producers of health. We discuss how varying levels of support from health professionals impact consumers' self-management of their physical and mental health; how health professionals influence consumers' experience of treatment burden; and implications for practice.


Detection of prostate cancer by integration of line-scan diffusion, T2-mapping and T2-weighted magnetic resonance imaging; a multichannel statistical classifier.
A multichannel statistical classifier for detecting prostate cancer was developed and validated by combining information from three different magnetic resonance (MR) methodologies: T2-weighted, T2-mapping, and line scan diffusion imaging (LSDI). From these MR sequences, four different sets of image intensities were obtained: T2-weighted (T2W) from T2-weighted imaging, Apparent Diffusion Coefficient (ADC) from LSDI, and proton density (PD) and T2 (T2 Map) from T2-mapping imaging. Manually segmented tumor labels from a radiologist, which were validated by biopsy results, served as tumor "ground truth." Textural features were extracted from the images using co-occurrence matrix (CM) and discrete cosine transform (DCT). Anatomical location of voxels was described by a cylindrical coordinate system. A statistical jack-knife approach was used to evaluate our classifiers. Single-channel maximum likelihood (ML) classifiers were based on 1 of the 4 basic image intensities. Our multichannel classifiers: support vector machine (SVM) and Fisher linear discriminant (FLD), utilized five different sets of derived features. Each classifier generated a summary statistical map that indicated tumor likelihood in the peripheral zone (PZ) of the prostate gland. To assess classifier accuracy, the average areas under the receiver operator characteristic (ROC) curves over all subjects were compared. Our best FLD classifier achieved an average ROC area of 0.839(+/-0.064), and our best SVM classifier achieved an average ROC area of 0.761(+/-0.043). The T2W ML classifier, our best single-channel classifier, only achieved an average ROC area of 0.599(+/-0.146). Compared to the best single-channel ML classifier, our best multichannel FLD and SVM classifiers have statistically superior ROC performance (P=0.0003 and 0.0017, respectively) from pairwise two-sided t-test. By integrating the information from multiple images and capturing the textural and anatomical features in tumor areas, summary statistical maps can potentially aid in image-guided prostate biopsy and assist in guiding and controlling delivery of localized therapy under image guidance.


FLT3-ITD impedes retinoic acid, but not arsenic, responses in murine acute promyelocytic leukemias.
Acute promyelocytic leukemia (APL) is often associated with activating FLT3 signaling mutations. These are highly related to hyperleukocytosis, a major adverse risk factor with chemotherapy-based regimens. APL is a model for oncogene-targeted therapies: all-trans retinoic acid (ATRA) and arsenic both target and degrade its ProMyelocytic Leukemia/Retinoic Acid Receptor α (PML/RARA) driver. The combined ATRA/arsenic regimen now cures virtually all patients with standard-risk APL. Although FLT3-internal tandem duplication (ITD) was an adverse risk factor for historical ATRA/chemotherapy regimens, the molecular bases for this effect remain unknown. Using mouse APL models, we unexpectedly demonstrate that FLT3-ITD severely blunts ATRA response. Remarkably, although the transcriptional output of initial ATRA response is unaffected, ATRA-induced PML/RARA degradation is blunted, as is PML nuclear body reformation and activation of P53 signaling. Critically, the combination of ATRA and arsenic fully rescues therapeutic response in FLT3-ITD APLs, restoring PML/RARA degradation, PML nuclear body reformation, P53 activation, and APL eradication. Moreover, arsenic targeting of normal PML also contributes to APL response in vivo. These unexpected results explain the less favorable outcome of FLT3-ITD APLs with ATRA-based regimens, and stress the key role of PML nuclear bodies in APL eradication by the ATRA/arsenic combination.


Apoptotic efficacy of etomoxir in human acute myeloid leukemia cells. Cooperation with arsenic trioxide and glycolytic inhibitors, and regulation by oxidative stress and protein kinase activities.
Fatty acid synthesis and oxidation are frequently exacerbated in leukemia cells, and may therefore represent a target for therapeutic intervention. In this work we analyzed the apoptotic and chemo-sensitizing action of the fatty acid oxidation inhibitor etomoxir in human acute myeloid leukemia cells. Etomoxir caused negligible lethality at concentrations up to 100 µM, but efficaciously cooperated to cause apoptosis with the anti-leukemic agent arsenic trioxide (ATO, Trisenox), and with lower efficacy with other anti-tumour drugs (etoposide, cisplatin), in HL60 cells. Etomoxir-ATO cooperation was also observed in NB4 human acute promyelocytic cells, but not in normal (non-tumour) mitogen-stimulated human peripheral blood lymphocytes. Biochemical determinations in HL60 cells indicated that etomoxir (25-200 µM) dose-dependently inhibited mitochondrial respiration while slightly stimulating glycolysis, and only caused marginal alterations in total ATP content and adenine nucleotide pool distribution. In addition, etomoxir caused oxidative stress (increase in intracellular reactive oxygen species accumulation, decrease in reduced glutathione content), as well as pro-apoptotic LKB-1/AMPK pathway activation, all of which may in part explain the chemo-sensitizing capacity of the drug. Etomoxir also cooperated with glycolytic inhibitors (2-deoxy-D-glucose, lonidamine) to induce apoptosis in HL60 cells, but not in NB4 cells. The combined etomoxir plus 2-deoxy-D-glucose treatment did not increase oxidative stress, caused moderate decrease in net ATP content, increased the AMP/ATP ratio with concomitant drop in energy charge, and caused defensive Akt and ERK kinase activation. Apoptosis generation by etomoxir plus 2-deoxy-D-glucose was further increased by co-incubation with ATO, which is apparently explained by the capacity of ATO to attenuate Akt and ERK activation. In summary, co-treatment with etomoxir may represent an interesting strategy to increase the apoptotic efficacy of ATO and (with some limitations) 2-deoxy-D-glucose which, although clinically important anti-tumour agents, exhibit low efficacy in monotherapy.


Preoperative Therapeutic Plasma Exchange and Surgical Treatment in Thyrotoxicosis Patients: A Single-Centre Retrospective Cohort Study.
Therapeutic plasma exchange (TPE) provides time for thyroidectomy in thyrotoxic patients. TPE is indicated in cases where antithyroid medications cannot be used due to the side effects or attain no adequate hormonal suppression response at the highest dosage and in cases of rapid onset of clinical symptoms. This study presents the treatment results of patients who underwent TPE and were subsequently operated for thyrotoxicosis. The patients who underwent thyroidectomy and TPE between January 1999 and February 2019 were retrospectively analyzed. The files of 27 patients with thyrotoxicosis who performed TPE prior to surgery were analyzed in relation to the demographic and clinical features. We included 15 (55.6%) females, 12 (44.4%) males with a mean age of 44 (23-82) years. The pre-TPE mean free thyroxine (fT4) level was 12 (5-46) pmol/L while free tri-iodothyronine (fT3) level was 34 (17-141) pmol/L. The post-TPE fT4 level was 6 (3-10) pmol/L while the fT3 level was 21 (12-41). There was one case of an allergic reaction during the procedure. In the postoperative follow-up, there was transient hypocalcemia in 8 (29%) patients, permanent hypocalcemia in 1 (3.7%) patient, and surgical site infection in 1 (3.7%) patient. Preoperative TPE is an alternative treatment option for thyrotoxic patients. This is an especially effective treatment for patients with inadequate response or adverse reaction to antithyroid drugs or patients who need urgent surgery for thyroid storm.


Genotype, phenotype, and follow-up in Taiwanese patients with salt-losing tubulopathy associated with SLC12A3 mutation.
Genotype, phenotype, and follow-up analysis is rarely performed in a large number of patients with Gitelman's syndrome (GS) caused by mutations in SLC12A3 encoding the thiazide-sensitive NaCl cotransporter. One hundred seventeen Taiwanese GS patients (70 males and 47 females, age 24 ± 10 yr) with SLC12A3 mutations belonging to 92 unrelated families were investigated. Genomic DNA and/or cDNA from blood leukocytes were analyzed for SLC12A3 mutations and haplotype analysis with intragenic and extragenic markers for recurrent SLC12A3 mutations. Clinical symptoms and biochemical studies at the first presentation as well as follow-up were examined. Forty different SLC12A3 mutations were identified. Approximately 12% of patients had triple SLC12A3 mutations. Fourteen mutations were recurrent with only one founder effect (S710X). Typical hypocalciuria and hypomagnesemia were not found in seven and nine patients, respectively. In addition to male patients having an earlier age of onset, more severe hypokalemia, and significantly lower serum aldosterone concentration, patients with homozygous and deep mutations in intron 13 (c.1670-191C → T) had more severe phenotype. Seven and five patients had chronic kidney disease (stage III-IV) and type 2 diabetes at the follow-up, respectively. Screening of recurrent hot spot SLC12A3 mutations may provide an early diagnosis of GS. Besides gender effect, the nature of homozygous and deep intronic mutations may influence the phenotype. Patients with GS may be at increased risk for the development of chronic kidney disease and type 2 diabetes.


ITER LIDAR performance analysis.
The core LIDAR Thomson scattering for ITER is specified for core profile measurements with a spatial resolution of 7 cm (a/30) for the range of 500 eV<T(e)<40 keV and n(e)>3x10(19) m(-3) at an accuracy of <10% for T(e). These specifications are verified using a full profile Monte Carlo simulation code. In the simulations it is assumed that the input transmission is 50% and the collection transmission is 10% for lambda=300-1200 nm and F/#=6-17. A crucial design decision lies on the choice of laser and detector combination. It is evaluated that the system can meet its spatial and accuracy specifications for higher temperatures of T(e)>5 keV with a combination of a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (lambda(0)=1064 nm, Delta lambda<1 nm, 5 J, and Delta t(FWHM)=250 ps, 5-10 Hz) and S20, GaAs, and GaAsP microchannel plate photomultipliers (Delta t(FWHM)<300 ps, effective quantum efficiency, EQE=3%-4%, and D=18 mm). In order to reach the required T(e) of 500 eV with Nd:YAG first harmonic, this choice requires a development of fast near infrared detectors.


Auditing an organization's interprofessional learning and interprofessional practice: the interprofessional praxis audit framework (IPAF).
Interprofessional learning (IPL) and interprofessional practice (IPP) are strategies for healthcare services' striving to improve patient care. While health professionals are enacting IPL and IPP, the capacity to understand and comprehensively map IPL and IPP activities has remained elusive. Additionally, understanding and accounting for the impact of organizational context and culture on IPL and IPP requires attention. This paper presents the "interprofessional praxis audit framework" (IPAF), which is a unique tool to address these two issues. The IPAF comprises five components: context, culture, conduct, attitudes and information. Conjoined, the components facilitate examination of an organization's enactment of IPL and IPP. Utilized within an action research methodology, the IPAF enables a synchronized inspection, whereby similarities and differences of the components are considered simultaneously, and the knowledge developed is used to promote change projects to improve patient care.


Short-term administration of alibernet red wine extract failed to affect blood pressure and to improve endothelial function in young normotensive and spontaneously hypertensive rats.
As wine polyphenols were shown to possess many positive effects in mammals, including improvement of vascular function, this study investigated the effect of the Slovak Alibernet red wine extract (AWE) on blood pressure and vascular function in young normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Six weeks old, male, WKY and SHR were treated with AWE for three weeks at the dose of 24.2 mg/kg/day. Blood pressure (BP), determined by tail-cuff plethysmography, was significantly elevated in SHR vs. WKY and AWE failed to affect it. Lipid peroxidation was evaluated by determination of thiobarbituric acid-reactive substances. Vascular function was assessed in rings of the femoral artery using Mulvany-Halpern's myograph. Maximal endothelium-dependent acetylcholine (ACh)-induced relaxation was reduced in control SHR vs. WKY rats by approximately 9.3 %, which was associated with a significant decrease of its NO-independent component. AWE failed to affect maximal ACh-induced relaxation, both its NO-dependent and independent components, compared to controls of the same genotype. AWE however reduced lipid peroxidation in the left ventricle of both WKY and SHR and in the liver of SHR. In conclusion, three-week administration of AWE failed to reduce BP and to improve endothelial function in the femoral arteries of both genotypes investigated.


[Late presentation of a traumatic pulmonary arteriovenous malformation].
Pulmonary arteriovenous malformations (PAVM) are rare, and most often of congenital origin. Among secondary causes of PAVM, trauma is exceptional. We describe here one such case, discovered very late over twenty years after a thoracic perforing wound. Recent vascular imaging techniques (angio-CT scanning and -RMI) have largely contributed to their diagnosis, but direct pulmonary arteriography remains the reference technique preoperatively when surgery is required. In all cases, treatment is as conservative as possible, and embolization of small sized PAVM, even multiple, by coils has become the standard procedure. However, surgery is required when the PAVM is large and/or proximal, particularly when its feeding vessel is complex. Itwas the case of our patient, who has been cured by a lobectomy. PAVM are rare but should be sytematically searche for in case of hypoxemia along with a pulmonary nodule.


Non-redundant functions of H2A.Z.1 and H2A.Z.2 in chromosome segregation and cell cycle progression.
H2A.Z is a H2A-type histone variant essential for many aspects of cell biology, ranging from gene expression to genome stability. From deuterostomes, H2A.Z evolved into two paralogues, H2A.Z.1 and H2A.Z.2, that differ by only three amino acids and are encoded by different genes (H2AFZ and H2AFV, respectively). Despite the importance of this histone variant in development and cellular homeostasis, very little is known about the individual functions of each paralogue in mammals. Here, we have investigated the distinct roles of the two paralogues in cell cycle regulation and unveiled non-redundant functions for H2A.Z.1 and H2A.Z.2 in cell division. Our findings show that H2A.Z.1 regulates the expression of cell cycle genes such as Myc and Ki-67 and its depletion leads to a G1 arrest and cellular senescence. On the contrary, H2A.Z.2, in a transcription-independent manner, is essential for centromere integrity and sister chromatid cohesion regulation, thus playing a key role in chromosome segregation.


Spatial relationships among dairy farms, drinking water quality, and maternal-child health outcomes in the San Joaquin Valley.
Access to clean and affordable water is a significant public health issue globally, in the United States, and in California where land is heavily used for agriculture and dairy operations. The purpose of this study was to explore the geographic relationships among dairy farms, nitrate levels in drinking water, low birth weight, and socioeconomic data at the ZIP code level in the San Joaquin Valley. This ecological study used a Geographic Information System (GIS) to explore and analyze secondary data. A total of 211 ZIP codes were analyzed using spatial autocorrelation and regression analysis methods in ArcGIS version 10.1. ZIP codes with dairies had a higher percentage of Hispanic births (p = .001). Spatial statistics revealed that ZIP codes with more dairy farms and a higher dairy cow density had higher levels of nitrate contamination. No correlation was detected between LBW and unsafe nitrate levels at the ZIP code level. Further research examining communities that use private and small community wells in the San Joaquin Valley should be conducted. Birth data from smaller geographic areas should be used to continue exploring the relationship between birth outcomes and nitrate contamination in drinking water.


Associations between sexual partner number and HIV risk behaviors: implications for HIV prevention efforts in a Treatment as Prevention (TasP) environment.
Previous research indicates that gay and bisexual men (GBM) have significantly more sexual partners than same-aged heterosexual men and women. As a result, some HIV intervention programs have focused on partner reduction. However, new research findings question the relevance of sexual partner number as a sexual risk measure for GBM given Treatment as Prevention (TasP) programs and new seroadaptive strategies which have led to lower GBM community viral load and new HIV prevention behaviors. To assess if sexual partner number continues to remain an important measure of sexual risk for GBM living in a city that actively promotes TasP as provincial policy, we analysed cross-sectional data from 719 GBM recruited through respondent-driven sampling in Vancouver, Canada. Multivariable negative binomial regression analysis showed that partner number was significantly associated with previously identified HIV risk factors including condomless anal intercourse with serodiscordant and/or unknown serostatus partners, using sex toys, attending group sex events, receiving money for sex, and sex drug use. These results indicate that sexual partner number remains an important proximate HIV risk measure. However, more nuanced measures of HIV treatment status and greater understanding of the possible causes of increased partner number among GBM are needed.


An improved procedure for shipboard enumeration of faecal indicator bacteria in marine sediments from sewage sludge disposal areas.
An improved membrane filtration procedure for use on board ship to enumerate Escherichia coli and Group D faecal streptococci in marine sediments is described. Ultrasonication extraction combined with resuscitation of sublethally-injured cells yielded significantly higher counts of E. coli than sediments shaken by hand. Counts of E. coli were also higher on mFC agar (without rosalic acid) after a period of resuscitation on tryptone-soy agar supplemented with 0.1% yeast extract than on a 4% Teepol-lactose medium. Ultrasonication of sediments made no significant difference to counts of Group D faecal streptococci on KF-streptococcus agar. These improved isolation procedures allowed better discrimination of the area affected by sewage sludge at a disposal site off the northeast coast of England.


Polymeric microfluidic continuous flow mixer combined with hyperspectral FT-IR imaging for studying rapid biomolecular events.
Early reaction intermediates in protein folding, such as those resulting in β-amyloid formation due to transient misfolding, emerge within a few hundred microseconds. Here, we report a method to obtain sub-millisecond temporal resolution and molecular structural information of protein (mis-)folding events by using a microfluidic continuous-flow mixer (MCFM) in combination with Fourier transform infrared (FT-IR) imaging. The MCFMs are made out of cyclic olefin copolymer (COC) films, because this approach allows for rapid prototyping of different mixer designs. Furthermore, COC offers high IR transparency between 1500 and 2500 cm-1, thus maximizing the signal to noise ratio of the IR data obtained from a sample of interest. By combining narrow and wide channel widths in MCFM design, the platform provides fast mixing (460 μs) to induce protein (mis-)folding, and it maximizes the residence time in the observing area, so a wide range of reaction timescales can be captured in a single image. We validated the platform for its ability to induce and observe sub-millisecond processes by studying two systems: (i) the mixing of H2O and D2O and (ii) the mixing induced deprotonation of carboxylic acid. First, we observed excellent agreement between simulated and experimental data of the on-chip mixing of H2O and D2O, which verifies the distance-reaction time relationships based on simulation. Second, deprotonation of carboxylic acid by on-chip mixing with sodium hydroxide solution validates the ability of the platform to induce rapid pH jump that is needed for some biomolecular reactions. Finally, we studied the methanol-induced partial-unfolding of ubiquitin to show that our platform can be used to study biomolecular events 'on-pathway' using FT-IR imaging. We successfully extracted kinetic and structural details of the conformational changes along the channel. Our results are in agreement with prior studies that required more elaborate stopped flow approaches to acquire data for different time points. In summary, the reported method uses an easy-to-fabricate microfluidic mixer platform integrated with hyperspectral FT-IR imaging for rapid acquisition of structural details and kinetic parameters of biomolecular reactions. This approach does not need stopped flow or molecular imaging probes, as required respectively for alternative FT-IR spectroscopy and fluorescence approaches.


[Comparative evaluation of influence of low-intensity laser radiation of different spectrum components and regimen of laser work upon microcirculation in comprehensive treatment of chronic parodontitis].
Comparative study of the influence details of low-intensity pulse and continuous oscillation of laser radiation of red and infrared parts of spectrum upon microcirculation indices in comprehensive treatment of chronic parodontitis of light and middle severity was performed. For the first time the predominantly activating influence upon microcirculation in gingival tissues of the pulsed laser radiation in the red part of spectrum was established.


Exploring quality perceptions of health care operations: a study of public hospitals of Mauritius.
Patient care has become increasingly important in the health care environment of Mauritius. Patients' satisfaction and their expectations of health care are valid indicators of quality health care. The present paper reports the results of a survey of patient satisfaction with heath care, administered by face-to-face interview to 300 in-patient adults discharged from five main regional hospitals based in Mauritius. It examines the predictors and level of patients' satisfaction across the five regional hospitals of Mauritius. In this study, a modified version of HEALTHQUAL scale was used for determining patient satisfaction with health care in the regional public hospitals. Multiple regression analysis was conducted to understand the relationships among patients' perceptions of in-patient services and their overall perceptions of health care quality, and also satisfaction with their care and willingness to return or recommend the same hospital's services to others. The dimensions labelled as "Patients' perceptions of ward/hospital environment" and "Patients' perceptions of medical and nursing staff" served a significant impact on nearly all measures of patient satisfaction in the regional public hospitals of Mauritius.


Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy.
To evaluate the clinical significance of detecting serum IgG4 and the IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy (TAO) and to explore whether high serum IgG4 levels and the IgG4/IgG ratio are associated with the severity and activity of TAO, we retrospectively assessed the records of 78 TAO patients and 32 controls collected in our hospital from July 2020 to July 2022. The TAO patients were divided into TAO inactive and TAO active phase groups according to the clinical activity score (CAS), and we evaluated the association between the serum IgG4 levels, the IgG4/IgG ratio, and the clinical data of the participants. The levels of IgG4 significantly increased in the TAO active group compared to those in the inactive and control groups (P < 0.05). Additionally, the number of patients with increased IgG4 levels (≥135 mg/dL) in the TAO active group was markedly higher than that in the inactive and control groups (P < 0.05). The IgG4/IgG ratio was also significantly enhanced in the TAO active group compared to the inactive and control groups (P < 0.05). CAS was identified as an independent factor influencing IgG4 levels in patients with TAO. The levels of serum IgG4, as well as the IgG4/IgG ratio, were significantly increased in some patients with active TAO, and they were related to the CAS, suggesting that the pathogenesis of TAO may be heterogeneous.


Enhancement of the Magnetoelectric Effect Using the Dynamic Jahn-Teller Effect in a Transition-Metal Complex.
In this Letter, a novel mechanism to enhance the magnetoelectric (ME) coupling between electric polarization and magnetism using the dynamic Jahn-Teller (JT) effect is demonstrated. Electric polarization of over 100 μC/m^{2} is induced by the magnetic field owing to the second-order ME effect in the noncentrosymmetric transition metal complex [Mn^{III}(taa)]. This appearance of electric polarization does not require magnetic order in contrast to the linear ME effect in ME multiferroic materials. The value of the electric polarization is 1 order larger than that induced by the second-order ME effect, which originates from the p-d hybridization. Our calculation, taking into account the single-ion-type magnetic anisotropy originating from the spin-orbit interaction and ferrodistortive intermolecular interaction, verifies that the alignment of the JT distortion by the magnetic field results in the large electric polarization observed. Thus, our results provide a new method to gain strong ME coupling by tuning the atomic displacement using a magnetic field.


Visible-Light-Induced Palladium-Catalyzed Carbocyclization of Unactivated Alkyl Bromides with Alkenes Involving C-I or C-B Coupling.
A palladium-catalyzed, photochemical tandem cyclization/dicarbofunctionalization of unactivated alkyl halides containing an alkene moiety offers an appealing route to produce five- or six-membered rings in a redox-neutral fashion. Multisubstituted carbo- and heterocyclic compounds were prepared through the formation of new C-B or C-O bonds, which provides a convenient synthetic route for further transformations. This protocol is characterized by the reaction of alkene regio- and stereoselectivities, good functional group compatibility, wide substrate scope, and mild reaction conditions.


Medical and dietary therapy for kidney stone prevention.
The prevalence of kidney stone disease is increasing, and newer research is finding that stones are associated with several serious morbidities. These facts suggest that emphasis needs to be placed not only on stone treatment but also stone prevention. However, there is a relative dearth of information on dietary and medical therapies to treat and avoid nephrolithiasis. In addition, studies have shown that there are many misconceptions among both the general community and physicians about how stones should be managed. This article is meant to serve as a review of the current literature on dietary and drug therapies for stone prevention.


Clinical ladders: do they reflect levels of competence?
Staff nurses positioned within two discrete clinical ladder levels were surveyed for their responses to two components of clinical competence: job performance and problem-solving tactics. Although findings suggest that clinical ladders do not seem to provide clear delineation of competence levels, several interventions with staff nurses may increase clinical ladder viability: 1) opportunity to practice and utilize mixed and integrative problem-solving styles, 2) challenging work experiences, and 3) opportunity to mentor and be mentored.


Myelopathy in Holstein x Gir calves in Brazil.
This case report contains clinical and pathologic features of a degenerative myelopathy in Holstein X Gir crossbred calves in Brazil. The bilateral and symmetrical spinal cord white matter lesions were interpreted as a primary axonopathy that may be of the dying-back type.


Microscopic dynamics research on the "mature" process of dye-sensitized solar cells after injection of highly concentrated electrolyte.
After injection of electrolyte, the internal three-dimensional solid-liquid penetration system of dye-sensitized solar cells (DSCs) can take a period of time to reach "mature" state. This paper studies the changes of microscopic processes of DSCs including TiO2 energy-level movement, localized state distribution, charge accumulation, electron transport, and recombination dynamics, from the beginning of electrolyte injection to the time of reached mature state. The results show that the microscopic dynamics process of DSCs exhibited a time-dependent behavior and achieved maturity ∼12 h after injecting the electrolyte into DSCs. Within 0-12 h, several results were observed: (1) the conduction band edge of TiO2 moved slightly toward negative potential direction; (2) the localized states in the band gap of TiO2 was reduced according to the same distribution law; (3) the transport resistance in TiO2 film increased, and electron transport time was prolonged as the time of maturity went on, which indicated that the electron transport process is impeded gradually; (4) the recombination resistance at the TiO2/electrolyte (EL) interface increases, and electron lifetime gradually extends, therefore, the recombination process is continuously suppressed. Furthermore, results suggest that the parameters of EL/Pt-transparent conductive oxide (TCO) interface including the interfacial capacitance, electron-transfer resistance, and transfer time constant would change with time of maturity, indicating that the EL/Pt-TCO interface is a potential factor affecting the mature process of DSCs.


[Pharmacokinetics of propofol and ketamine during and after total intravenous anesthesia with propofol, fentanyl and ketamine for pediatric patients].
Pharmacokinetics of propofol and ketamine during propofol-fentanyl-ketamine (PFK) anesthesia for pediatric surgery was studied. Plasma levels of propofol (Pp) were maintained approximately at 2.5 micrograms.ml-1 during surgery. Fifteen minutes after the cessation of propofol infusion, Pp decreased to 1.5 micrograms.ml-1. Plasma levels of ketamine (Pk) were maintained at 150-200 ng.ml-1 during the surgery. After the cessation of ketamine infusion, Pk decreased as quickly as Pp. Pk values at 15 minutes and 120 minutes after the cessation of the infusion were 93 ng.ml-1, 24 ng.ml-1, respectively. On the other hand, plasma norketamine (Pn) levels increased gradually during surgery and stayed at 100-150 ng.ml-1 after the end of ketamine infusion to play an important role in post-operative sedation and pain relief. In conclusion, pharmacokinetics of propofol and ketamine in pediatric patients was similar to that in adult patients. PFK anesthesia can be used safely for pediatric as well as for adult patients.


Angiotensin-Converting Enzyme 2 Inhibits Lipopolysaccharide-Caused Lung Fibrosis via Downregulating the Transforming Growth Factor β-1/Smad2/Smad3 Pathway.
In our previous studies, angiotensin-converting enzyme 2 (ACE2) was shown to alleviate the severity of acute lung injury, but its effects on the development of lung injury-caused lung fibrosis have not been studied. In the present study, the effects of ACE2 on lipopolysaccharide (LPS)-induced fibrosis in the lung were studied. The role of epithelial-mesenchymal transition (EMT) and that of the transforming growth factor β-1 (TGF-β1)/Smad2/Smad3 pathway in LPS-induced fibrosis in the lung were investigated. ACE2 expression in the mouse model of LPS-induced lung fibrosis was significantly increased. ACE2 activator diminazene aceturate (DIZE) significantly reduced pulmonary fibrosis, decreased alpha-smooth muscle actin expression, collagen I, hydroxyproline, and TGF-β1 in the lung. DIZE significantly decreased TGF-β1 expression and the activation of Smad2 and Smad3. ACE2 overexpression inhibited the LPS-induced EMT in MLE-12 cells (lung epithelial cells) and small interfering RNA treatment of ACE2 stimulated EMT. ACE2 overexpression also inhibited TGF-β1 expression and activation of Smad2 and Smad3 in MLE-12 cells. Finally, after MLE-12 cells were treated with both ACE2 and TGF-β1 plasmid, TGF-β1 plasmid significantly abolished the effect of ACE2 plasmid on the EMT in MLE-12 cells. Combined with the in vivo study, it was revealed that ACE2 can suppress the TGF-β1/Smad2/Smad3 pathway in lung type II epithelial cells, thus reversing their EMT and lung fibrosis. The present study provides basic research data for the application of ACE2 in lung injury-caused lung fibrosis treatment and clarifies the intervention mechanism of ACE2 in pulmonary fibrosis, which has potential value for clinical application. Angiotensin-converting enzyme 2 (ACE2) can inhibit the epithelial-mesenchymal transition (EMT) in lung type II epithelial cells and lung fibrosis. ACE2 can regulate the transforming growth factor β-1/Smad2/Smad3 pathway in lung type II epithelial cells, which may be the underlying mechanism of ACE2's effect on EMT and lung fibrosis.


New standards of ossification of the newborn.
Physical and neurological examinations of American and Swedish populations confirm that epiphyseal ossification of the newborn in the shoulder, knee, and foot is related to gestational age. The causes of accelerated, retarded, and dysharmonic osseous maturation of the neonate are reviewed.


Zhx2 (zinc fingers and homeoboxes 2) regulates major urinary protein gene expression in the mouse liver.
The mouse major urinary proteins (Mups) are encoded by a large family of highly related genes clustered on chromosome 4. Mups, synthesized primarily and abundantly in the liver and secreted through the kidneys, exhibit male-biased expression. Mups bind a variety of volatile ligands; these ligands, and Mup proteins themselves, influence numerous behavioral traits. Although urinary Mup protein levels vary between inbred mouse strains, this difference is most pronounced in BALB/cJ mice, which have dramatically low urinary Mup levels; this BALB/cJ trait had been mapped to a locus on chromosome 15. We previously identified Zhx2 (zinc fingers and homeoboxes 2) as a regulator of numerous liver-enriched genes. Zhx2 is located on chromosome 15, and a natural hypomorphic mutation in the BALB/cJ Zhx2 allele dramatically reduces Zhx2 expression. Based on these data, we hypothesized that reduced Zhx2 levels are responsible for lower Mup expression in BALB/cJ mice. Using both transgenic and knock-out mice along with in vitro assays, our data show that Zhx2 binds Mup promoters and is required for high levels of Mup expression in the adult liver. In contrast to previously identified Zhx2 targets that appear to be repressed by Zhx2, Mup genes are positively regulated by Zhx2. These data identify Zhx2 as a novel regulator of Mup expression and indicate that Zhx2 activates as well as represses expression of target genes.


Sarcoidosis associated with infliximab therapy in ulcerative colitis: A case report.
Although immunomodulatory therapy has been clearly stated as an important landmark in treatment of ulcerative colitis, significantly improving the quality of life for patients with inflammatory bowel disease, there are several aspects to be considered regarding the possible side-effects of anti-TNF alpha agents. In spite of a good safety profile, biologic TNF antagonists may induce paradoxical inflammation, which can manifest as sarcoid-like granulomatosis, consisting of noncaseating granulomas in the affected organs. We report the case of a 30-year-old male patient, with no personal or familial history of lung disease, with a personal history of ulcerative colitis (UC), under clinical remission following infliximab therapy in maintenance dose, who was admitted for treatment administration, but also for dyspnea, nocturnal sweating, and nonproductive cough. Based on clinical manifestations, biological landmarks excluding various infections, CT scan, fibrobronchoscopy with bronchoalveolar lavage for culture and immunohistochemical examination, followed by mediastinoscopy with sampling of paratracheal lymph node, which underwent histopathological examination, the patient was diagnosed with drug- induced stage II pulmonary sarcoidosis. Since the patient had developed severe allergic reaction after being administered Infliximab at admission, the biological treatment was immediately discontinued. Following the diagnosis of pulmonary sarcoidosis, corticotherapy was initiated. After corticotherapy was initiated, the patient had a favorable outcome at 3 months reevaluation, both regarding the course of ulcerative colitis and sarcoidosis. Patients under biological therapy using anti-TNF alpha agents must be carefully monitored, in order to early identify potential paradoxical inflammation (such as sarcoidosis) as a side-effect. The drug-related pulmonary disease tends to improve upon withdrawal of the drug, with occasional requirement of steroid treatment. However, a thorough strategy should be assembled in the case of UC relapse in this patient category, with switching to adalimumab or surgical approach as main possibilities.


Stress reduces the neuroprotective effect of exercise in a rat model for Parkinson's disease.
Parkinson's disease (PD) is a progressive neurodegenerative disease of nigrostriatal dopamine (DA) neurons that project from the substantia nigra pars compacta (SNc) to the striatum. To further understand PD, researchers have developed standardized animal models of PD. In this study, Long Evans (LE) rats were unilaterally lesioned by injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), into the medial forebrain bundle (MFB) of the left hemisphere. The rats were divided into three groups randomly; group 1 (runners) were housed in individual cages with attached running wheels, group 2 (stressed-runners) had access to individual free running wheels, except post-lesion when the rats were subjected to immobilization of the running wheel for 1 h per day for 14 days, as well as one session of 24-h food deprivation and a 7-h shift in the light/dark cycle. Group 3 (non-runnners) were housed individually in cages with attached running wheels that were permanently immobilized. Subcutaneous injection of the DA agonist, apomorphine, caused stressed-runners and non-runners to rotate vigorously away from the side of the lesion (contralaterally). Apomorphine-induced rotations provide a behavioural measure of the extent of the lesion, a depletion of more than 80% of DA neurons is required to produce vigorous contralateral rotations in response to apomorphine injection. Runners rotated significantly less than non-runners and stressed-runners. The number of rotations performed by stressed-runners was not significantly different from non-runners, suggesting that stress had cancelled the neuroprotective effect of running. Immunohistochemical staining for tyrosine hydroxylase in the SNc revealed slightly less destruction of DA neurons in the runners than in stressed-runners or non-runners, although these differences did not achieve statistical significance. The behavioural results confirm a previous finding suggesting that voluntary exercise is neuroprotective. A novel finding is that mild stressors cancel the neuroprotection afforded by voluntary exercise.


Increased risk of osteomyelitis and septic arthritis in osteogenesis imperfecta.
We investigated the prevalence of osteomyelitis and septic arthritis in individuals with osteogenesis imperfecta (OI) as compared to the general population. We performed a retrospective cohort study utilizing the TriNetX Analytics platform, a federated, aggregated electronic health record (EHR) research network containing national, deidentified EHR data. We queried patients with OI, based on encounter diagnoses. Patients in this group with any occurrence of osteomyelitis or septic arthritis were recorded. A control cohort was established to compare the prevalence in patients without OI. Of 8444 individuals with OI, 433 (5.13%) had encounter diagnoses for osteomyelitis and 61 (0.72%) had encounter diagnoses for septic arthritis. In comparison, of 79 176 436 patients without OI, 352 009 (0.44%) had encounter diagnoses for osteomyelitis, while 106 647 (0.13%) had encounter diagnoses for septic arthritis. The relative risk for osteomyelitis in OI patients was 11.53 (95% CI: 10.52-12.64), while the relative risk for septic arthritis was 5.36 (95% CI: 4.18-6.89). The relative risk for osteomyelitis in pediatric OI patients was 30.55 (95% CI: 24.35-38.28). To our knowledge, this is the first study investigating musculoskeletal infections in patients with OI, as well as the first to report the overall prevalence in the general population. Clinicians may benefit from a high index of suspicion for musculoskeletal infections in OI patients with corresponding symptoms. Further study is warranted to investigate if modifications to conventional diagnostic pathways and criteria are valuable in this population. Level of evidence: Retrospective Cohort Study - Level II.


Richner-Hanhart syndrome detected by expanded newborn screening.
Richner-Hanhart syndrome (tyrosinemia type 2) is an inborn error of tyrosine metabolism which is clinically characterized mainly by oculocutaneous symptoms including corneal opacities and keratosis palmoplantaris. Skin symptoms usually develop after the first year of life. We report a neonate in whom already on the third day of life diagnosis of Richner-Hanhart syndrome could be suspected because of elevated tyrosine levels in newborn screening by tandem mass spectrometry. Analysis of the tyrosine aminotransferase gene revealed a homozygous missense mutation p.R433W (c.1297C>T). An 8-year-old brother with persistent plantar hyperkeratotic plaques of the soles of yet unknown origin was subsequently identified to be also affected with Richner-Hanhart syndrome. This demonstrates that early diagnosis of Richner-Hanhart syndrome is possible in neonates by extended newborn screening. Early introduction of dietary treatment is a prerequisite to reduce the risk of clinical symptoms.


Micropollutants removal by full-scale UV-C/sulfate radical based Advanced Oxidation Processes.
The high chemical stability and the low biodegradability of a vast number of micropollutants (MPs) impede their correct treatment in urban wastewater treatment plants. In most cases, the chemical oxidation is the only way to abate them. Advanced Oxidation Processes (AOPs) have been experimentally proved as efficient in the removal of different micropollutants at lab-scale. However, there is not enough information about their application at full-scale. This manuscript reports the application of three different AOPs based on the addition of homogeneous oxidants [hydrogen peroxide, peroxymonosulfate (PMS) and persulfate anions (PS)], in the UV-C tertiary treatment of Estiviel wastewater treatment plant (Toledo, Spain) previously designed and installed in the facility for disinfection. AOPs based on the photolytic decomposition of oxidants have been demonstrated as more efficient than UV-C radiation alone on the removal of 25 different MPs using low dosages (0.05-0.5 mM) and very low UV-C contact time (4-18 s). Photolysis of PMS and H2O2 reached similar average MPs removal in all the range of oxidant dosages, obtaining the highest efficiency with 0.5 mM and 18 s of contact time (48 and 55% respectively). Nevertheless, PMS/UV-C reached slightly higher removal than H2O2/UV-C at low dosages. So, these treatments are selective to degrade the target compounds, obtaining different removal efficiencies for each compound regarding the oxidizing agent, dosages and UV-C contact time. In all the cases, H2O2/UV-C is more efficient than PMS/UV-C, comparing the ratio cost:efficiency (€/m3·order). Even H2O2/UV-C treatments are more efficient than UV-C alone. Thus, the addition of 0.5 mM of H2O2 compensates the increased of UV-C contact time and therefore the increase of electrical consumption, that it should be need to increase the removal of MPs by UV-C treatments alone.


The incidence rate of chemical food poisonings in the Lublin province between 1976 and 1998.
The aim of the study was to analyse the chemical poisonings in the Lublin province in the years 1976-1998. The analysis was based on the archive materials obtained from the Regional Unit for Control of Epidemics and Hygiene Promotion in Lublin. The findings demonstrate that chemical poisonings in the Lublin province compared to the whole country are a relevant epidemiological problem and that their most common causes include the consumption of toxic alcohols--mainly ethanol or other chemical substances and ethanol overdosage. Moreover, the health education system of the society should be systematically improved.


Postoperative sepsis after colorectal surgery: a prospective single-center observational study and review of the literature.
Postoperative sepsis represents a significant problem in colorectal surgery patients. To identify the etiology as well as the risk factors associated with the development of postoperative sepsis, based on prospective data of patients undergoing colorectal surgery at a single large-volume institution. Between November 2019 and February 2021, 141 patients underwent an elective operation for colorectal cancer at a tertiary hospital center. The following variables were recorded for each patient: age, gender, American Society of Anesthesiologists Classification (ASA class), duration of surgery, surgical approach, comorbidities (diabetes, cardiovascular disease, respiratory disease). Univariate analysis was performed using χ2 tests for categorical variables. A total of 69 males and 72 females were enrolled. Postoperative sepsis was diagnosed in 18 (12.77%) cases, with anastomotic leakage being the most frequent cause (3.55%). There was no statistically significant difference in the presence of sepsis among patients when gender, surgical approach, duration of surgery, and respiratory disease were taken into account. Sixty-nine patients were > 65 years old, with sepsis being statistically significant in this group (p = 0.034). Furthermore, patients with ASA class ≤ 2 developed postoperative sepsis less frequently than patients with advanced ASA scores (p = 0.008). Diabetes and cardiovascular disease also reach statistical significance; sepsis was more frequent in this group of patients (p = 0.013 and p = 0.009, respectively). Following colorectal cancer procedures, postoperative sepsis was significantly more common among patients over 65 years old, ASA score > 2, and also with associated comorbidities such as diabetes and cardiovascular disease.


Cellular retinoic acid binding protein (CRABP) in retinoblastoma.
Binding proteins for retinoic acid (cellular retinoic acid binding protein, CRABP) have been demonstrated in various cell types, and display the characteristics of receptors. Three retinoblastomas are described. The clinical diagnosis of retinoblastoma was established by ophthalmoscopic echographic and histological examination. One part of the tumor was frozen in liquid nitrogen immediately after surgery and used for the determination of CRABP. CRABP was present in cells from all three tumors. This may indicate sensitivity of this tumor to retinoic acid or synthetic retinoic acid derivatives with biologic activity.


Changes in primary glomerulonephritis in Singapore over four decades .
This review of 3,289 native kidney biopsies over the past four decades in Singapore documents the changing pattern of biopsy-proven glomerulonephritis (GN)from that of a third world country to that of a developed nation. In the 1st decade, mesangial proliferative GN was the most common form of primary GN, similar to the Asian region. In the 2nd decade, the percentage of mesangial proliferative GN decreased, but membranous GN became more common, as was seen in China and Thailand. In the 3rd decade, focal segmental glomerulosclerosis (FSGS) and membranous nephropathy continued to rise, but it was only recently, in the 4th decade, that FSGS prevalence increased dramatically, although membranous nephropathy continues to increase in some Asian countries. In the last decade in Singapore, Malaysia, and Japan, prevalence of IgA nephritis has decreased but remains the most common GN. The percentage of FSGS continues to increase in many countries like in Italy, United States of America, United Kingdom, China, and Malaysia. We surmise that socioeconomic factors play significant roles in the evolution of the renal biopsy pattern. .


The neutrophil in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide and has few effective therapies. It is characterized by anomalous and persistent inflammation, both local and systemic. Neutrophilic inflammation predominates in the COPD airway wall and lumen, but, despite the presence of abundant innate immune cells, the progressive clinical course of the disease is punctuated by recurrent infection-driven exacerbations. An extensive body of evidence (from cell culture to murine models and finally to the susceptibility of human patients with α1-antitrypsin deficiency to develop COPD) implicates neutrophil elastase and other neutrophil-derived proteases as key mediators of the tissue damage and relentless decline in lung function that occurs in this condition. In addition to the well recognized role of cytokines in modulating neutrophil function and survival, it has recently become apparent that hypoxia can influence neutrophil function, with impaired killing of pathogenic bacteria, enhanced release of proteases, and delayed apoptosis. This destructive neutrophil phenotype is predicted to be highly detrimental in the setting of the COPD microenvironment.


Sex pheromone monitoring as a versatile tool for determining presence and abundance of Cydia pomonella (Lep.: Tortricidae) in German apple orchards.
Cydia pomonella (Lep.: Tortricidae), the codling moth, is an apple, pear, quince and walnut pest with considerable impact on horticultural production systems in many parts of the world. In commercial apple production, it is responsible for a yearly damage level of 40 billion dollars. In response to the need of tight codling moth control there are several options for intervention by pest managers in commercially operated orchards. Spray and count methods have been used for decades with success, but at considerable external costs for the integrity of ecological cycles. Also, problems with pesticide residues and with resistant strains are an issue of concern. For environmental reasons, toxicological means are discounted here. Instead, flight curves based on sex pheromone trapping and monitoring are preferred means towards determining the optimal timing of interventions by biotechnical and biological control methods. Finally, ecological reasons are discussed for vastly different population levels of C. pomonella developing in closely neighboring field sections which operated under different environmental management.


Lupus miliaris disseminatus faciei.
Lupus miliaris disseminatus faciei is a rare inflammatory dermatosis of unknown etiology that primarily affects young adults. Clinically, it is characterized by an asymptomatic papular eruption mainly involving the central face, typically on and around the eyelids. Characteristic histopathological features include dermal epithelioid cell granulomas with central necrosis and surrounding lymphocytic infiltrate with multinucleate giant cells. Lupus miliaris disseminatus faciei has a spontaneously resolving course, yet can be cosmetically debilitating given the location and potential for scarring. Treatment is difficult and there is a lack of controlled studies. We report a new case of lupus miliaris disseminatus faciei successfully treated with minocycline and systemic steroids, and briefly discuss its nosology and therapeutic options.


Interventional management of tracheobronchial strictures.
Tracheobronchial balloon dilation and stent placement have been well used in the treatment of patients with benign and/or malignant diseases. Balloon dilation is the first option in the treatment of benign airway stenosis. Although balloon dilation is simple and fast, recurrence rate is high. Stent placement promptly relieves acute airway distress from malignant extraluminal and intraluminal airway obstruction. Temporary stent placement may be an alternative for benign airway strictures refractory to balloon dilation. This article reviews the indications, pre-procedure evaluation, technique, outcomes and complications of balloon dilation and stent placement with regard to benign and malignant tracheobronchial stenoses.


Quantification and mapping of urban fluxes under climate change: Application of WRF-SUEWS model to Greater Porto area (Portugal).
Climate change and the growth of urban populations are two of the main challenges facing Europe today. These issues are linked as climate change results in serious challenges for cities. Recent attention has focused on how urban surface-atmosphere exchanges of heat and water will be affected by climate change and the implications for urban planning and sustainability. In this study energy fluxes for Greater Porto area, Portugal, were estimated and the influence of the projected climate change evaluated. To accomplish this, the Weather Research and Forecasting Model (WRF) and the Surface Urban Energy and Water Balance Scheme (SUEWS) were applied for two climatological scenarios: a present (or reference, 1986-2005) scenario and a future scenario (2046-2065), in this case the Representative Concentration Pathway RCP8.5, which reflects the worst set of expectations (with the most onerous impacts). The results show that for the future climate conditions, the incoming shortwave radiation will increase by around 10%, the sensible heat flux around 40% and the net storage heat flux around 35%. In contrast, the latent heat flux will decrease about 20%. The changes in the magnitude of the different fluxes result in an increase of the net all-wave radiation by 15%. The implications of the changes of the energy balance on the meteorological variables are discussed, particularly in terms of temperature and precipitation.


Phylogenetic evidence of mitochondrial DNA introgression among pocket gophers in New Mexico (family Geomyidae).
Mitochondrial DNA (mtDNA) variation in the cytochrome b gene was determined for two divergent taxa of pocket gophers, Thomomys bottae actuosus and T. b. ruidosae. These two taxa hybridize in a narrow contact zone, but introgression of nuclear markers such as allozymes or chromosomes does not extend much beyond the hybrid zone (Patton et al. 1979). We found that despite their distinctness, the two subspecies shared very similar mtDNA haplotypes. By a comparison of phylogenetic histories derived from nuclear markers (allozymes) and from mtDNA haplotypes sampled in different populations of T. bottae from New Mexico, we show that apparent similarity is due to an introgression of T. b. ruidosae mtDNA into T. b. actuosus nuclear background. Evidence of introgression is not limited to the present-day contact zone between these two taxa, but extends at least 75 km away from it. The actuosus haplotype coexists along with the ruidosae mtDNA in the Gallinas Mts., which are inhabited by otherwise pure T. b. actuosus, while further north only typical actuosus haplotypes were detected. Of several potential mechanisms which could lead to such a geographical pattern of variation, we argue that a combination of range shifts due to climatic fluctuations, and genetic drift are most likely. Horizontal gene transfers due to hybridization are historical events which seem rather common among pocket gophers. Although they can be identified with careful phylogenetic study using independent data sets, the potential for misinterpreting a gene tree as an organismal tree is great in this and other groups of animals.


Polymorphism in human cytomegalovirus UL40 impacts on recognition of human leukocyte antigen-E (HLA-E) by natural killer cells.
Natural killer (NK) cell recognition of the nonclassical human leukocyte antigen (HLA) molecule HLA-E is dependent on the presentation of a nonamer peptide derived from the leader sequence of other HLA molecules to CD94-NKG2 receptors. However, human cytomegalovirus can manipulate this central innate interaction through the provision of a "mimic" of the HLA-encoded peptide derived from the immunomodulatory glycoprotein UL40. Here, we analyzed UL40 sequences isolated from 32 hematopoietic stem cell transplantation recipients experiencing cytomegalovirus reactivation. The UL40 protein showed a "polymorphic hot spot" within the region that encodes the HLA leader sequence mimic. Although all sequences that were identical to those encoded within HLA-I genes permitted the interaction between HLA-E and CD94-NKG2 receptors, other UL40 polymorphisms reduced the affinity of the interaction between HLA-E and CD94-NKG2 receptors. Furthermore, functional studies using NK cell clones expressing either the inhibitory receptor CD94-NKG2A or the activating receptor CD94-NKG2C identified UL40-encoded peptides that were capable of inhibiting target cell lysis via interaction with CD94-NKG2A, yet had little capacity to activate NK cells through CD94-NKG2C. The data suggest that UL40 polymorphisms may aid evasion of NK cell immunosurveillance by modulating the affinity of the interaction with CD94-NKG2 receptors.


Review on dry reforming of methane, a potentially more environmentally-friendly approach to the increasing natural gas exploitation.
With the actual growth of the natural gas industry in the US as well as the potential and availability of this non-renewable carbon source worldwide, reforming of methane gas is getting increasing attention. Methane can be used for the production of heat or electricity, as well, it can be converted to syngas, a building block that could lead to the production of liquid fuels and chemicals, a very promising pathway in light of the increasing price of oil. Amongst the different reforming techniques, dry reforming could represent a very interesting approach both to valorize a cheap source or carbon (CO2) as well as to reduce the overall carbon footprint of the increasing worldwide fossil-based methane consumption. In this short review, attention will be given to the thermodynamics of dry reforming followed by an investigation on dry reforming using heterogeneous catalyst by focusing on the most popular elements used in literature for dry reforming. Attention will as well be given to other emerging techniques that may allow countering at one point the high thermodynamic penalties that accompanies conversion of methane using carbon dioxide.


Long-lasting functional disabilities in patients who recover from coma after cardiac operations.
Uncertainty regarding the long-term functional outcome of patients who awaken from coma after cardiac operations is difficult for families and physicians and may delay rehabilitation. We studied the long-term functional status of these patients to determine if duration of coma predicted outcome. We followed 71 patients who underwent cardiac operations; recovered their ability to respond to verbal commands after coma associated with postoperative stroke, encephalopathy, and/or seizures; and were discharged from the hospital. The Glasgow Outcome Scale Extended (GOSE) was used to assess functional disability 2 to 4 years after discharge. Outcomes were classified as favorable (GOSE scores 7 and 8) and unfavorable (GOSE scores 1-6). Of 71 patients identified, 39 were interviewed, 15 died, 1 refused to be interviewed, and 16 were lost to follow-up. Of the 54 patients with completed GOSE evaluations, only 15 (28%) had favorable outcomes. Among patients with unfavorable outcomes, 15 (28%) died, 14 (26%) survived with moderate disabilities, and 10 (18%) had severe disabilities. Factors associated with unfavorable outcomes were increases in duration of coma (p = 0.007), time in intensive care (p = 0.006), length of hospitalization (p = 0.004), and postoperative serum creatine kinase levels (p = 0.006). Only duration of coma was an independent predictor of unfavorable outcome (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.008-1.537; p = 0.042). Patients with durations of coma greater than 4 days were more likely to have unfavorable outcomes (OR, 5.1; 95% CI, 1.3-21.3; p = 0.02). Two thirds of comatose patients who survived to discharge after cardiac operations had unfavorable long-term functional outcomes. A longer duration of unconsciousness is a predictor of unfavorable outcome.


Anticonvulsant hypersensitivity syndrome.
Anticonvulsant hypersensitivity syndrome is an acute, life-threatening, idiosyncratic drug reaction seen with the aromatic antiepileptic drugs, phenytoin, carbamazepine, phenobarbital, and primidone, with frequent cross sensitivity. It usually occurs 2-8 weeks after initiation of therapy and the hallmark clinical features are fever, rash, and lymphadenopathy. Hematologic abnormalities such as eosinophilia, atypical lymphocytes, and internal organ involvement also occur with varying severity. A case of hypersensitivity syndrome due to carbamazepine with cross sensitivity to phenytoin is reported. It is emphasized that this serious drug reaction with diverse clinical presentations should be recognized and treated promptly.


Analysis of attempted suicide episodes presenting to the emergency department: comparison of young, middle aged and older people.
Attempted suicide remains difficult for clinicians to predict with some established risk factors. We investigate the detailed characteristics of attempted suicide especially according to age and methods of suicide attempts. A retrospective study was conducted to evaluate patients who visited the emergency department due to attempted suicide. A retrospective medical record review of all patients who presented to the emergency department (ED) of two tertiary teaching hospitals in Korea after suicide attempt between January 1, 2010, and December 31, 2017 was performed. Demographic information and detailed variables (methods and reasons of suicide attempts and variables regarding reattempts) were investigated. Total participants were classified into 3 groups according to age, young group, middle aged group and the older group, and each characteristics were compared. A total of 3698 patients were enrolled in this study. Deliberate self-poisoning (DSP) was the most common method of attempted suicide (66.5%) followed by cutting (24.4%), hanging (7.9%), falling (2.6%), and drowning (1.1%). In patients who had previous suicide attempts (n = 1029, 27.8%), attempted methods were likely to be concordant with previous attempted methods. The most common reason for suicide attempts was interpersonal relationship issues followed by socio-economic reasons. Older patients (n = 412, 11.2%) were significantly different from other 2 groups (n = 3286, 88.8%) regarding gender, suicide re-attempt, occupation, alcohol co-ingestion, previous psychiatric history, and discharge outcomes (all p-values < 0.001). Especially, in older patients, use of critical method and reason of physical illness were more common. Our findings indicated that people who attempted suicide might have different sociodemographic and clinical factors depending on age group. Depending on age, it is necessary to apply additional suicide intervention programs in different ways.


Participant characteristics predicting voluntary early withdrawal from a multidisciplinary program providing home-delivered meals and dietitian/social work case management to homebound elders.
We examine whether baseline characteristics of participants enrolled in a multidisciplinary program providing home-delivered meals and dietitian/social work case management to homebound seniors predicted voluntary early withdrawal. Sixty-nine participants voluntarily withdrew early and 111 completed the project. Six hypotheses were based on a conceptual framework incorporating (1) agreement between project elements and needs/preferences of individuals and (2) whether participants would improve and no longer require or desire the intervention. Three of the hypotheses were supported by means of logistic regression analysis. Voluntary early withdrawers at baseline: (1) were more mobile, (2) ate less often, and (3) responded that food tastes good less often. The results suggest that carefully considering the interaction of potential participant characteristics and project interventions will improve nutrition project retention.


Traumatic ligamentous instability of the cervical spine in children.
Sixteen cases of dislocation and ligamentous disruptions of the cervical spine in children are reported. In five cases resulting from injury to the upper cervical spine, the roentgenographical features of the instability at the C1-C2 level are documented and their therapeutic orientation is defined. Eleven injuries were of the lower cervical spine: three dislocations, two of which were old cases, and eight serious ligamentous disruptions. Diagnosis of serious ligamentous disruptions was based on precise radiographic criteria: increase of the interspinous distance, loss of parallelism between the articular processes, and posterior widening of the disc space. The indications for surgical fixations in serious ligamentous disruptions depend on persistence of the clinical and radiological signs after a long orthopedic immobilization.


Cross-regulatory Circuit Between AHR and Microbiota.
The gut microbes have a close symbiotic relationship with their host. Interactions between host and the microbiota affect the nutritional, immunological, and physiological status of the host. The Aryl Hydrocarbon Receptor (AHR) is a ligand activated transcription factor that mediates the toxicity of xenobiotics. Recently, the relationship between the gut microbiota and AHR has attracted the attention of many researchers. We undertook a structured search of bibliographic databases for peer-reviewed research literature. We found and reviewed 49 peer-reviewed papers dealing with the major aspects related to the crosstalk between AHR and microbiota. The AHR influences the intestinal microbiota population and mediates host-microbe homeostasis. Interestingly, the gut microbiota also produces ligands of AHR from bacterial metabolism and thereby activates the AHR signaling pathway. Concusion: This review presents current knowledge of the cross-regulatory circuit between the AHR and intestinal microbiota. The findings of this review confirm the importance of AHR-microbiota interactions in health and disease.


Solution structure and proposed domain domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase.
Polyketides are a medicinally important class of natural products. The architecture of modular polyketide synthases (PKSs), composed of multiple covalently linked domains grouped into modules, provides an attractive framework for engineering novel polyketide-producing assemblies. However, impaired domain-domain interactions can compromise the efficiency of engineered polyketide biosynthesis. To facilitate the study of these domain-domain interactions, we have used nuclear magnetic resonance (NMR) spectroscopy to determine the first solution structure of an acyl carrier protein (ACP) domain from a modular PKS, 6-deoxyerythronolide B synthase (DEBS). The tertiary fold of this 10-kD domain is a three-helical bundle; an additional short helix in the second loop also contributes to the core helical packing. Superposition of residues 14-94 of the ensemble on the mean structure yields an average atomic RMSD of 0.64 +/- 0.09 Angstrom for the backbone atoms (1.21 +/- 0.13 Angstrom for all non-hydrogen atoms). The three major helices superimpose with a backbone RMSD of 0.48 +/- 0.10 Angstrom (0.99 +/- 0.11 Angstrom for non-hydrogen atoms). Based on this solution structure, homology models were constructed for five other DEBS ACP domains. Comparison of their steric and electrostatic surfaces at the putative interaction interface (centered on helix II) suggests a model for protein-protein recognition of ACP domains, consistent with the previously observed specificity. Site-directed mutagenesis experiments indicate that two of the identified residues influence the specificity of ACP recognition.


Anti-Müllerian hormone levels in serum 1 year after unilateral orchiopexy.
The aim of this study was to determine the serum anti-Müllerian hormone (AMH levels) in a group of boys with cryptorchidism before and 1 year after surgery. Additionally, the effect of orchiopexy, based on the testicular position and morphology, was evaluated. Fifty boys who were 1-4 years old (median, 2.4 years) with unilateral cryptorchidism were evaluated before and 1 year after they underwent orchiopexy. Prior to the procedure, all of the patients had undergone karyotyping to exclude chromosomal abnormalities. Blood samples were collected while obtaining blood for standard laboratory tests routinely performed just before and 12 months after surgery. Twelve months after the orchiopexy, in most cases surgically treated testes were in the middle or lower pole of the scrotum. The descended glands were of comparable size and density in comparison with the testes on the opposite side. In the treated children, serum AMH levels measured at 12 months after orchiopexy were similar to preoperative basal levels. The authors found that AMH levels in children with unilateral undescended testes do not change significantly 1 year after surgical procedure. We still do not have trustworthy factors to predict fertility in children affected with cryptorchidism. We observed an upward trend in AMH concentration 1 year after orchiopexy, but it was statistically insignificant. Therefore, we plan further measurements of AMH in boys after orchiopexy to assess the influence of this procedure on gonadal function.


A comprehensive longitudinal study of magnetic resonance imaging identifies novel features of the Mecp2 deficient mouse brain.
Rett syndrome (RTT) is a X-linked neurodevelopmental disorder which represents the leading cause of severe incurable intellectual disability in females worldwide. The vast majority of RTT cases are caused by mutations in the X-linked MECP2 gene, and preclinical studies on RTT largely benefit from the use of mouse models of Mecp2, which present a broad spectrum of symptoms phenocopying those manifested by RTT patients. Neurons represent the core targets of the pathology; however, neuroanatomical abnormalities that regionally characterize the Mecp2 deficient mammalian brain remain ill-defined. Neuroimaging techniques, such as MRI and MRS, represent a key approach for assessing in vivo anatomic and metabolic changes in brain. Being non-invasive, these analyses also permit to investigate how the disease progresses over time through longitudinal studies. To foster the biological comprehension of RTT and identify useful biomarkers, we have performed a thorough in vivo longitudinal study of MRI and MRS in Mecp2 deficient mouse brains. Analyses were performed on both genders of two different mouse models of RTT, using an automatic atlas-based segmentation tool that permitted to obtain a detailed and unbiased description of the whole RTT mouse brain. We found that the most robust alteration of the RTT brain consists in an overall reduction of the brain volume. Accordingly, Mecp2 deficiency generally delays brain growth, eventually leading, in heterozygous older animals, to stagnation and/or contraction. Most but not all brain regions participate in the observed deficiency in brain size; similarly, the volumetric defect progresses diversely in different brain areas also depending on the specific Mecp2 genetic lesion and gender. Interestingly, in some regions volumetric defects anticipate overt symptoms, possibly revealing where the pathology originates and providing a useful biomarker for assessing drug efficacy in pre-clinical studies.


MicroRNA-9 controls dendritic development by targeting REST.
MicroRNAs (miRNAs) are conserved noncoding RNAs that function as posttranscriptional regulators of gene expression. miR-9 is one of the most abundant miRNAs in the brain. Although the function of miR-9 has been well characterized in neural progenitors, its role in dendritic and synaptic development remains largely unknown. In order to target miR-9 in vivo, we developed a transgenic miRNA sponge mouse line allowing conditional inactivation of the miR-9 family in a spatio-temporal-controlled manner. Using this novel approach, we found that miR-9 controls dendritic growth and synaptic transmission in vivo. Furthermore, we demonstrate that miR-9-mediated downregulation of the transcriptional repressor REST is essential for proper dendritic growth.


[Effect of podophyllin resine on the mobility of langerhans cells (author's transl)].
The application of an alcoholic solution of podophyllin resin at concentrations above 10 p. 100 on guinea-pig udders, produces in epidemic Langerhans cells the same cytological effects as those by colchicine and vinca alcaloid in culture cells. The Langerhans cells are a suitable experimental model in vivo because of its easy ultrastructural identification, its migratory character and its preferential localization in epidermis.


WITHDRAWN: Abrogation of heat shock factor 1 (Hsf1) phosphorylation deregulates its activity and lowers activation threshold, leading to obesity in mice.
This article has been withdrawn by the authors. During preparation of this manuscript, a number of errors occurred in the preparation/assembly of Figs 2D, 2E, S1C, S1E, and S4. The authors apologize for not acknowledging that Fig. 6E and 6J represented the same samples and therefore the β-actin immunoblot was reused. These presentation errors do not impact the underlying scientific findings of the article and the article is being withdrawn so that a corrected manuscript can be submitted for publication. We are sorry for any problems or issues that this may have caused the scientific community.


Gram-negative infections in adult intensive care units of latin america and the Caribbean.
This review summarizes recent epidemiology of Gram-negative infections in selected countries from Latin American and Caribbean adult intensive care units (ICUs). A systematic search of the biomedical literature (PubMed) was performed to identify articles published over the last decade. Where appropriate, data also were collected from the reference list of published articles, health departments of specific countries, and registries. Independent cohort data from all countries (Argentina, Brazil, Chile, Colombia, Cuba, Mexico, Trinidad and Tobago, and Venezuela) signified a high rate of ICU infections (prevalence: Argentina, 24%; Brazil, 57%). Gram-negative pathogens, predominantly Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli, accounted for >50% of ICU infections, which were often complicated by the presence of multidrug-resistant strains and clonal outbreaks. Empirical use of antimicrobial agents was identified as a strong risk factor for resistance development and excessive mortality. Infection control strategies utilizing hygiene measures and antimicrobial stewardship programs reduced the rate of device-associated infections. To mitigate the poor health outcomes associated with infections by multidrug-resistant Gram-negative bacteria, urgent focus must be placed on infection control strategies and local surveillance programs.


Hormonal and metabolic responses to the stress of transport and slaughterhouse procedures in clenbuterol-fed pigs.
The aim of this study was to evaluate if metabolic and endocrine adaptive responses to stressful stimuli are influenced by clenbuterol treatment in pigs. Two groups of nine Goland barrows of 167 kg liveweight, fed diets containing 0 (control) or 1 ppm of clenbuterol (clenbuterol-treated) for 40 days, were used. Blood samples were collected by jugular venipuncture the day before (day 40) and at slaughter (day 41). On day 40 clenbuterol-treated pigs had lower levels of thyroxin, tri-iodothyronine, insulin, urea and higher levels of lactate and creatine phosphokinase activity. On day 41, thyroxin concentration was lower and creatine phosphokinase activity higher in clenbuterol-treated pigs than in controls. In response to transport and slaughterhouse procedures, most of the parameters considered both in clenbuterol-treated and in control pigs increased.


Effects of aging and body size on proximal and ascending aorta and aortic arch: inner edge-to-inner edge reference values in a large adult population by two-dimensional transthoracic echocardiography.
Aortic size is known to vary significantly by age and body size and to be an important predictor of cardiovascular diseases. The aim of this study was to determine reference values for proximal thoracic aorta diameters, using the inner edge technique and two-dimensional transthoracic echocardiography. Diameters of the aortic annulus, sinuses of Valsalva, sinotubular junction, arch, and ascending aorta and the angle of insertion of the aorta were measured in 500 subjects (231 women; mean age, 48 ± 18 years) with normal echocardiographic findings, retrospectively enrolled. The relations of age and body size with aortic measurements were investigated using bivariate and multiple linear regressions. Measurements were highly feasible (83% for the aortic arch, 100% for the other segments). All aortic diameters significantly related to age, weight and body surface area, while height was correlated only with annular diameter. In predictive models adjusted for gender, older age was associated with increased aortic diameters (R(2) values ranged from 0.36 for the sinotubular junction to 0.52 for the sinuses of Valsalva). Adjustments for height and weight led to significant improvements (R(2) values ranged from 0.43 for the sinotubular junction to 0.58 for the sinuses of Valsalva). Similar correlations were observed for men and women. Angle was found to be dependent only on age and gender. Reproducibility analysis showed good to excellent accordance between repeated measurements. The results of this study show the effect of aging on the proximal thoracic aorta and emphasize the importance of accounting for gender and body size when assessing aortic size. The obtained reference ranges will help standardize the assessment of aortic dimensions by applying inner edge convention and facilitate comparisons with other imaging techniques.


Active and separate secretion of fiber and penton base during the early phase of Ad2 or Ad5 infection.
Fiber and penton base overproduced in adenovirus (Ad) infected cells can be secreted prior to progeny release and thereby regulate progeny spread. We aimed to investigate the mechanisms of fiber and penton base secretion in Ad2- or Ad5-infected A549 cells. Our flow cytometry analyses detected abundant surface fiber molecules, but little penton base molecules at 12h post infection. Immunogold staining combined with transmission electron microscopic analyses revealed separate, non-co-localized release of fiber and penton base in the proximity of the plasma membrane. Depolymerization of microtubule and actin cytoskeletons, and inhibition of Rock kinase and myosin II activity together demonstrated cytoskeletal network-dependent fiber secretion. Inhibition of intracellular calcium [Ca2+]i signaling caused diminished fiber secretion, which was associated with diminished progeny production. Thus, fiber and penton base are actively and separately secreted during the early stages of Ad2 or Ad5 infection, their secretion may play important role in Ad life cycle.


The risk of abuse of vitamin supplements.
The article presents the results of studies on potential risks associated with the abuse of vitamin supplements which until recently had been considered not only highly effica- cious, but also completely safe. Particular consideration is given to vitamins A, E, D and C. The necessity to control the intake of vitamin supplements and even to strictly super- vise the supply to high risk patients is highlighted.


Serum C-reactive protein increases the risk of venous thromboembolism: a prospective study and meta-analysis of published prospective evidence.
Evolving debate suggests that C-reactive protein (CRP) might be associated with the development of venous thromboembolism (VTE); however, the evidence is conflicting. We aimed to assess the prospective association of CRP with VTE risk. C-reactive protein was measured in serum samples at baseline from 2420 men aged 42-61 years, from the Kuopio Ischemic Heart Disease study. Within-person variability in CRP levels was corrected for using repeat measurements of CRP taken 11 years after baseline. Incident VTE events (n = 119) were recorded during a median follow-up of 24.7 years. The age-adjusted regression dilution ratio for loge CRP was 0.57 [95% confidence interval (CIs): 0.51-0.64]. In age-adjusted Cox regression analysis, the hazard ratio (95% CIs) for VTE per 1 standard deviation (SD) increase in loge baseline CRP was 1.17 (0.98-1.40). Further adjustment for several established and emerging risk factors did not alter the association. In a meta-analysis of nine population-based studies (including the current study) comprising 81,625 participants and 2225 VTE cases, the fully-adjusted risk estimate for VTE was 1.14 (1.08-1.19) per SD increase in loge baseline CRP. In a pooled dose-response analysis, a linear association between CRP and VTE risk was suggested (P for nonlinearity = 0.272). The pooled risk estimate for VTE per 5 mg/l increment in CRP levels was 1.23 (1.09-1.38). C-reactive protein was only modestly associated with VTE risk in the primary analysis. Pooled evidence, however, suggests that elevated CRP is associated with greater VTE risk, consistent with a linear dose-response relationship.


Effect of homocysteinylation on structure, chaperone activity and fibrillation propensity of lens alpha-crystallin.
Various chemical modifications can reduce chaperone activity of α-crystallin (α-Cry) and the loss of which has been implicated in the development of cataract diseases. The side chains of lysine residues are the target of both glycation and homocysteinylation, and lysine modification by the two reactions may similarly affect the structure and function of α- Cry. In this study, α-Cry was incubated with homocysteine thiolactone (HCTL), resulting in significant protein homocysteinylation, as determined with Ellman's assay. Homocysteinylation of α-Cry resulted in the reduction in surface hydrophobicity and alpha-helix to beta-sheet transition, as observed respectively with fluorescence and circular dichroism (CD) spectroscopy. The structural alteration of homocysteinylated α-Cry was accompanied by protein aggregation, including the formation of amyloid fibrils as detected by thioflavin T (ThT) fluorescence and Congo red (CR) absorption spectroscopy. The mobility shifts of homocysteinylated α-Cry on reducing and non-reducing SDS-PAGEs suggest that disulfide cross-linking in addition to lysine modification, also plays a role in aggregation of this protein. The chaperone activities of α-Cry, namely to prevent aggregation, to assist refolding and to restore activity of thermally stressed α-glucosidase (α-Gls) were reduced after homocysteinylation. Overall, this study suggests that similar to non-enzymatic glycation, homocysteinylation of α-Cry is a risk factor for the development of cataract disorders, for instance during hyperhomocysteinemia which is linked to the various ocular pathological disorders.


A "benign" sphenoid ridge meningioma manifesting as a subarachnoid hemorrhage associated with tumor invasion into the middle cerebral artery.
Meningioma rarely manifests as a subarachnoid hemorrhage (SAH), and invasion directly into a major intracranial artery is extremely rare. To the best of our knowledge, meningioma presenting with an SAH associated with major intracranial arterial invasion has never been reported. We present a case of sphenoid ridge meningotheliomatous meningioma manifesting as an SAH without pathologically atypical or malignant features, due to direct tumor invasion into the middle cerebral artery.


[Open colon surgery].
Open resection of the colon is one of the most frequent abdominal operations, which clearly indicates the great importance of colon carcinomas. The surgical aim is resection of the affected intestinal region and the according lymph drainage region. In this respect, the techniques employed are strictly standardized: right hemicolectomy for right colon carcinoma, transverse resection for right colon carcinoma, left hemicolectomy for descendent colon carcinoma, and sigmoid resection for sigmoid carcinoma. In case of benign underlying disease, the operational method depends largely on the extent to which the intestine is affected and can include anything from simple colotomy and polyp removal to colectomy for toxic megacolon. Elective colon surgery is usually primary, but in emergencies a protective stoma might be necessary. Standardized indication and operational techniques enable low perioperative mortality and complication rates that make open colon resection usually un-problematic even in very old patients.


Protective effect of telmisartan treatment against arsenic-induced testicular toxicity in rats.
Oxidative/nitrosative stress, inflammation, and apoptosis play a crucial role in the pathogenesis of arsenic-induced testicular injury. Telmisartan, the angiotensin II-receptor antagonist, possesses antioxidant and anti-inflammatory activities. The protective effect of telmisartan against arsenic-induced testicular damage was investigated in rats. Testicular damage was induced by sodium arsenite (10 mg kg-1/day, p.o., for 2 consecutive days). Telmisartan (10 mg kg-1/day, i.p.) was given for 3 consecutive days, starting 1 day before sodium arsenite administration. Telmisartan significantly attenuated the arsenic-induced decrease in the levels of serum testosterone and testicular reduced glutathione, and significantly decreased the elevation of the levels of testicular malondialdehyde, nitric oxide, and arsenic levels, as well as myeloperoxidase activity resulting from sodium arsenite administration. Histopathological and immunohistochemical examination revealed that telmisartan markedly attenuated testicular tissue changes, and decreased the arsenic-induced expression of vascular endothelial growth factor, inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB, and caspase-3. Telmisartan, via its antioxidant and/or anti-inflammatory effects, may represent a potential candidate to protect against the deleterious effects of arsenic on testicular tissue.


Association of Kruppel-like factor 4 expression with the prognosis of esophageal squamous cell carcinoma patients.
To investigate the association of Kruppel-like factor 4 (KLF4) expressions with the prognosis of esophageal squamous cell carcinoma (SCC) patients. Ninety-eight cases of esophageal carcinoma patients were enrolled. The expression of KLF4 in the esophageal SCC and normal esophageal mucosa tissues were examined by immunohistochemistry. The correlations between the expression of KLF4 protein and patients' clinical characteristics and prognosis were analyzed. We observed higher expressed KLF4 in normal esophageal mucosa tissues than esophageal SCC tissues, with positive rate of 82.7% (81/98) and 43.8% (43/98) respectively. In patients with lymphatic metastasis, the positive rate of KLF4 was 24.4% (10/41), whereas it was 57.9% (33/57) in patients without lymphatic metastasis, and the difference was significant (x(2) = 10.871, P = 0.001). The positive rates of KLF4 were 62.5% (5/8), 53.1% (26/49) and 29.3% (12/41) in stage I, II and III patients, respectively. There were no correlations between the expression of KLF4 and gender, age, tumor size, location, differentiation grade and infiltration depth. The 5-year survival rates and median survival times were 48.8% and 25.5%, and 55 and 26 months for the patients with KLF4 positive and negative expression, respectively. There were significant differences between the patients with KLF4 positive expression and negative expression in the 5-year survival rates and median survival times (x(2) = 5.747 and 4.493, P = 0.017 and 0.034). KLF4 might act as a tumor suppressor in esophageal SCC and the expression status of KLF4 could be considered as a prognosis predictor for esophageal SCC patients.