Association between site of infection and in-hospital mortality in patients with sepsis admitted to emergency departments of tertiary hospitals in Medellin, Colombia.
To determine the association between the primary site of infection and in-hospital mortality as the main outcome, or the need for admission to the intensive care unit as a secondary outcome, in patients with sepsis admitted to the emergency department. This was a secondary analysis of a multicenter prospective cohort. Patients included in the study were older than 18 years with a diagnosis of severe sepsis or septic shock who were admitted to the emergency departments of three tertiary care hospitals. Of the 5022 eligible participants, 2510 were included. Multiple logistic regression analysis was performed for mortality. The most common site of infection was the urinary tract, present in 27.8% of the cases, followed by pneumonia (27.5%) and intra-abdominal focus (10.8%). In 5.4% of the cases, no definite site of infection was identified on admission. Logistic regression revealed a significant association between the following sites of infection and in-hospital mortality when using the urinary infection group as a reference: pneumonia (OR 3.4; 95%CI, 2.2 - 5.2; p < 0.001), skin and soft tissues (OR 2.6; 95%CI, 1.4 - 5.0; p = 0.003), bloodstream (OR 2.0; 95%CI, 1.1 - 3.6; p = 0.018), without specific focus (OR 2.0; 95%CI, 1.1 - 3.8; p = 0.028), and intra-abdominal focus (OR 1.9; 95%CI, 1.1 - 3.3; p = 0.024). There is a significant association between the different sites of infection and in-hospital mortality or the need for admission to an intensive care unit in patients with sepsis or septic shock. Urinary tract infection shows the lowest risk, which should be considered in prognostic models of these conditions.


Vertebral artery stenting in a patient with reversed flow in the anterior spinal artery.
We present neuroimages for a patient in a locked-in state with reversed flow in the anterior spinal artery as a result of bilateral distal vertebral artery occlusion. Following vertebral artery stenting, there is markedly improved flow in the posterior circulation and significant neurological recovery.


Ageing, cellular senescence and chronic kidney disease: experimental evidence.
Chronic kidney disease (CKD) is often viewed as an accelerated and premature ageing of the kidney, as they share common pathological features characterized by cellular senescence. In this review, we summarize the experimental evidence linking cellular senescence to the pathobiology of kidney ageing and CKD, and discuss the strategies for targeting senescent cells in developing therapeutics for ageing-related kidney disorders. Kidney ageing and CKD are featured with increased cellular senescence, an irreversible state of cell cycle arrest and the cessation of cell division. Senescent cells secrete a diverse array of proinflammatory and profibrotic factors known as senescence-associated secretory phenotype (SASP). Secondary senescence can be induced by primary senescent cells via a mechanism involving direct contact or the SASP. Various senolytic therapies aiming to selectively remove senescent cells in vivo have been developed. Senostatic approaches to suppress senescence or inhibit SASP, as well as nutrient signalling regulators are also validated in animal models of ageing. These recent studies provide experimental evidence supporting the notion that accumulation of senescent cells and their associated SASP is a main driver leading to structural and functional organ degeneration in CKD and other ageing-related disorder.


Insulin resistance is an independent correlate of high serum levels of advanced glycation end products (AGEs) and low testosterone in non-diabetic men.
Advanced glycation end products (AGEs) are involved in cardiovascular disease. Low testosterone level is associated with increased risks of cardiometabolic disorders as well. However, which anthropometric and metabolic variables, including AGEs, are independently correlated with low testosterone is largely unknown. In this study, we investigated whether high serum level of AGEs is one of the independent determinants of low testosterone in non-diabetic men. One hundred thirteen non-diabetic men who did not receive any drugs for hypertension and dyslipidemia underwent a complete history and physical examination, determination of blood chemistries, including serum AGEs and testosterone. Univariate analysis showed that testosterone levels were associated with waist circumference (inversely), diastolic blood pressure (BP) (inversely), mean BP (inversely), triglycerides (inversely), HDL-cholesterol, fasting plasma glucose (inversely), fasting insulin (inversely), homeostasis model assessment of insulin resistance (HOMA-IR) (inversely), AGEs (inversely) and uric acid (inversely). By the use of multiple stepwise regression analyses, HOMA-IR (p = 0.005) and triglycerides levels (p < 0.05) remained significant and were independently related to testosterone levels (R(2) = 0.168). HOMA-IR index was one of the independent determinants of serum levels of AGEs as well. The present study demonstrated for the first time that HOMA-IR was independently associated with high serum levels of AGEs and low testosterone in non-diabetic men. Insulin resistance could link elevation of AGEs to testosterone deficiency in non-diabetic men.


Adduct formation of pyrroloquinoline quinone and amino acid.
When pyrroloquinoline quinone (PQQ) is mixed with an amino acid, a corresponding Schiff base PQQ adduct is readily formed between carbonyl groups of PQQ and the primary amino group. A potent growth stimulating effect for microorganisms was observed with the PQQ adduct when it was administered in a culture medium. Although PQQ itself shows a marked growth stimulating effect, PQQ adducts appeared to be more active than authentic PQQ when compared on a molar basis. Conversely, unlike authentic PQQ, PQQ adducts were shown to be less active (greater than or equal to 100-fold) as the prosthetic group for a quinoprotein apo-glucose dehydrogenase when examined by holoenzyme formation by exogenous addition of PQQ or PQQ adducts. These observations suggested that PQQ adduct formation readily occurs during isolation procedures for PQQ from biological materials or PQQ - chromophore from quinoproteins. Therefore, the presence of such adducts gives a PQQ estimation much lower than theoretically expected. As an example, formation, isolation and characterization of PQQ - serine are described.


Asymptomatic Spontaneous Pneumopericardium, Pneumomediastinum, and Subcutaneous Emphysema: A Case Report of an Incidental Rare Presentation.
Pneumopericardium (PP), pneumomediastinum (PM), epidural pneumatosis, and subcutaneous emphysema (SE) are identified by the existence of free air or gas in the associated spaces. They are normally self-limited unless tension pneumothorax, tension PM, cardiac herniation, air tamponade, and esophageal rupture accompany these disorders. PM and PP can be divided into "spontaneous" or "secondary" based on the preceding etiologies. Spontaneous PM is often extremely rare and benign in course. On the other hand, secondary PM and PP are more common and result from intrathoracic infections, trauma-related esophageal rupture, or tears along the tracheobronchial tree. Our patient presented four days after a fall from a chair and was found to have suffered a stroke, with complete left side paralysis. CT imaging on arrival was significant for PM, PP, and SE, the cause of which remains unclear. The patient was diagnosed with COVID-pneumonia approximately six months prior to presentation. As the COVID-19 pandemic has evolved, several scientific papers have been published reporting infected patients who had developed spontaneous PT, PM, or even PP, in the absence of invasive mechanical ventilation. Is it possible that the spontaneous findings in our patient were COVID-related? Or could the spontaneous PP, PM, and SE be a sequel to the trauma of her fall from a chair? The answer still remains unclear.


[DNA damage to somatic cells of mice exposed to nonylphenol and to a combination of ionizing radiation and nonylphenol].
Nonylphenol (NP) has been found in daily used products reach in polyvinyl chloride (PVC). The main routes of human exposure are consumption of contaminated food and water. Radiation comes from natural and man-made sources, and is used in medicine, science and industry. Both agents are widely present in environment, therefore human exposure to their combined effect seems to be highly probable. The aim of the study was the estimation of the effects of subchronic exposure of male mice to nonylphenol alone and in a combination with ionizing radiation on the induction of DNA strand breaks of multiple somatic cells. Pzh:SFIS male mice were exposed for 8 weeks, 5 days/week to nonylphenol alone (25 mg/kg bw or 50 mg/kg bw ) or in a combination with X-rays (0.05 Gy + 25 mg/kg bw NP). Animal were killed at 24 h, 1,4 and 8 weeks after the end of exposure. The bone marrow, spleens, livers, kidneys and lungs were isolated from mice. The estimation of DNA damage was carried out by using Comet assay. The most sensitive to nonylphenol occurred bone marrow lymphocytes, less sensitive were cells of spleen and lungs. NP did not induce the strand breaks in cells coming from liver and kidneys. Eight-weeks combined exposure to ionizing radiation and nonylphenol (0.05 Gy + 25 mg/kg bw NP) caused significantly enhanced level of DNA strand breaks in all tested cells. The most sensitive occurred bone marrow lymphocytes and spleen cells, whereas cells from kidneys and lungs were the least sensitive. Subchronic application ofnonylphenol to mice induced damage to genetic material of bone marrow lymphocytes and cells of spleen and lungs. Combined exposure to ionizing radiation and nonylphenol caused, significantly higher than NP alone, level of DNA strand breaks of bone marrow lymphocytes, cells of liver, spleen, lungs and kidneys. Such damages might be stimulated by ionizing radiation.


AC and Phase Sensing of Nanowires for Biosensing.
Silicon nanowires are label-free sensors that allow real-time measurements. They are economical and pave the road for point-of-care applications but require complex readout and skilled personnel. We propose a new model and technique for sensing nanowire sensors using alternating currents (AC) to capture both magnitude and phase information from the sensor. This approach combines the advantages of complex impedance spectroscopy with the noise reduction performances of lock-in techniques. Experimental results show how modifications of the sensors with different surface chemistries lead to the same direct-current (DC) response but can be discerned using the AC approach.


Effects of exercise training on SFO-mediated sympathoexcitation during chronic heart failure.
Exercise training (ExT) has been shown to reduce sympathetic drive during heart failure (HF). The subfornical organ (SFO) is involved in the neural control of sympathetic drive. We hypothesized that an activated SFO contributes to enhanced sympathetic activity in HF. We also postulated that ExT would reduce the activation of the SFO and its contribution to the sympathetic drive during HF. Sprague-Dawley rats were subjected to coronary artery ligation to induce HF. Rats were assigned to ExT for 3-4 wk. Rats with HF had a 2.5-fold increase in FosB-positive cells in the SFO compared with sham-operated rats, and this was normalized by ExT. Microinjection of ANG II (100 pmol) into the SFO resulted in a greater increase in renal sympathetic nerve activity (RSNA), blood pressure, and heart rate in the HF group than in the sham-operated group. These responses were normalized after ExT (change in RSNA: 23 ± 3% vs. 8 ± 2%). ExT also abolished the decrease in RSNA in HF rats after the microinjection of losartan (200 pmol) into the SFO (-21 ± 4% vs. -2 ± 3%). Finally, there was elevated mRNA (5-fold) and protein expression (43%) of ANG II type 1 receptors in the SFO of rats with HF, which were reversed after ExT. These data suggest that the enhanced activity of the SFO by elevated tonic ANG II contributes to the enhanced sympathoexcitation exhibited in HF. The decrease in ANG II type 1 receptor expression in the SFO by ExT may be responsible for reversing the neuronal activation in the SFO and SFO-mediated sympathoexcitation in rats with HF.


[Cardiogenic shock in acute myocardial infarction--what we know in 2005].
Cardiogenic shock represents a complication in up to 10% of patients with acute myocardial infarction. Cardiogenic shock mortality remains high. In the contemporary treatment inhibitors of NO synthase are studied, apart from classic medications. Mechanical circulatory support is also important in majority of patients with cardiogenic shock: intraaortic balloon contrapulsation, left ventricular assist device systems. Prognosis is improved by percutaneous coronary intervention.


Peptides at the tRNA binding site of the crystallizable monomeric form of E. coli methionyl-tRNA synthetase.
A protein affinity labeling derivative of E. coli tRNA(fMet) carrying lysine-reactive cross-linking groups has been covalently coupled to monomeric trypsin-modified E. coli methionyl-tRNA synthetase. The cross-linked tRNA-synthetase complex has been isolated by gel filtration, digested with trypsin, and the tRNA-bound peptides separated from the bulk of the free tryptic peptides by anion exchange chromatography. The bound peptides were released from the tRNA by cleavage of the disulfide bond of the cross-linker and purified by reverse-phase high-pressure liquid chromatography, yielding three major peptides. These peptides were found to cochromatograph with three peptides of known sequence previously cross-linked to native methionyl-tRNA synthetase through lysine residues 402, 439 and 465. These results show that identical lysine residues are in close proximity to tRNA(fMet) bound to native dimeric methionyl-tRNA synthetase and to the crystallizable monomeric form of the enzyme, and indicate that cross-linking to the dimeric protein occurs on the occupied subunit of the 1:1 tRNA-synthetase complex.


Catecholthioether derivatives: preliminary study of in-vitro antimicrobial and antioxidant activities.
In this research, synthesis, antimicrobial and antioxidant activities of a series of catecholthioethers having benzoxazole and tetrazole moieties are described. Antimicrobial activity was evaluated by minimum inhibitory concentration (MIC) assay. The synthesized compounds were tested in vitro against three Gram-positive bacteria including Staphylococcus aureus (clinical isolated), Staphylococcus aureus ATCC 25922, Enterococcus faecium (clinical isolated), and two Gram-negative bacteria including Klebsiella pneumoniae (clinical isolated) and Pseudomonas aeruginosa 27853 and the yeast Candida albicans in comparison with control drugs. Microbiological results indicated that the synthesized compounds possessed a broad spectrum of activity against the tested microorganisms at MIC values between 4-256 μg/ml. This shows compounds having tetrazole moiety were the most active against Gram-negative strains, whereas compounds having benzoxazole moiety were more active against Gram-positive ones. Also both of them showed significant antifungal activity against Candida albicans and had lower activity than the compared control drugs (Sulfamethoxazole and Fluconazole). The antioxidant activity was assessed using two methods, including, 1,1-biphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and reducing power assays. Some of the catecholthioether derivatives showed antioxidant activity more than Trolox and butylated hydroxyanisole (BHA) as reference antioxidants.


The potential role of prebiotic fibre for treatment and management of non-alcoholic fatty liver disease and associated obesity and insulin resistance.
Non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH) represent a spectrum of diseases involving hepatic fat accumulation and histological features essentially identical to alcoholic liver disease; however, they occur in the absence of excessive alcohol intake. They typically arise in conjunction with one or more features of the metabolic syndrome. Lifestyle mediated weight loss remains the primary mode of therapy for NAFLD and NASH, but this is often ineffective and adjunctive medical and surgical treatments are presently lacking. Prebiotic fibres are a group of non-digestible carbohydrates that modulate the human microbiota in a manner that is advantageous to host health. Rodent studies suggest that dietary supplementation with prebiotic fibres positively impacts NAFLD by modifying the gut microbiota, reducing body fat, and improving glucoregulation. Future research should focus on placebo-controlled, human, clinical trials using histological endpoints to address the effects of prebiotics on NAFLD and NASH. The aim of this review is to summarize current knowledge about prebiotics as an emerging therapeutic target for NAFLD.


Universal electric-field-driven resistive transition in narrow-gap Mott insulators.
A striking universality in the electric-field-driven resistive switching is shown in three prototypical narrow-gap Mott systems. This model, based on key theoretical features of the Mott phenomenon, reproduces the general behavior of this resistive switching and demonstrates that it can be associated with a dynamically directed avalanche. This model predicts non-trivial accumulation and relaxation times that are verified experimentally.


Apoptosis is initiated by myocardial ischemia and executed during reperfusion.
Ischemia/reperfusion leading to myocyte cell death has been reported as either necrotic or apoptotic or a combination of both. The importance of necrosis is well established but the role of apoptosis and the time of initiation are still unknown. Normothermic global ischemia of either 45 or 90 min duration followed by 6 h of reperfusion were induced in isolated canine hearts. After 45 min of ischemia, left ventricular function and adenine nucleotide (AN) content had recovered during reperfusion indicating reversible injury. DNA fragmentation determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) was absent as was the 85 kDa fragment of poly-(ADP-ribose) polymerase (PARP). After 90 min of ischemia, electron microscopy indicated necrotic cell death in 90% of myocytes. Recovery of function and AN content during reperfusion was minimal. At the end of ischemia, caspase-3 was activated in 30% of all myocytes and PARP 85 kDa fragments were present by Western blot, indicating initiation of the apoptotic cascade. Lamin-B(1)labeling was significantly reduced from 90% in myocytes in control and ischemia to 30% in early reperfusion. Completion of apoptosis seen by TUNEL was evident in late reperfusion (7.6% of myocytes and 8.3% of non-myocytes). Experiments with 6 h ischemia without reperfusion showed absence of DNA fragmentation. We conclude that apoptotic cell death is initiated by ischemia but that reperfusion is needed for completion of the apoptotic cascade. Furthermore, it is concluded that cell death in acute global ischemia followed by reperfusion occurs predominantly by necrosis and that apoptosis is of minor importance in this pathophysiological situation.


Dietary influences on bone mass and bone metabolism: further evidence of a positive link between fruit and vegetable consumption and bone health?
The role of nutritional influences on bone health remains largely undefined because most studies have focused attention on calcium intake. We reported previously that intakes of nutrients found in abundance in fruit and vegetables are positively associated with bone health. We examined this finding further by considering axial and peripheral bone mass and markers of bone metabolism. This was a cross-sectional study of 62 healthy women aged 45-55 y. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck and by peripheral quantitative computed tomography at the ultradistal radial total, trabecular, and cortical sites. Bone resorption was calculated by measuring urinary excretion of pyridinoline and deoxypyridinoline and bone formation by measuring serum osteocalcin. Nutrient intakes were assessed by using a validated food-frequency questionnaire; other lifestyle factors were assessed by additional questions. After present energy intake was controlled for, higher intakes of magnesium, potassium, and alcohol were associated with higher total bone mass by Pearson correlation (P < 0.05 to P < 0.005). Femoral neck BMD was higher in women who had consumed high amounts of fruit in their childhood than in women who had consumed medium or low amounts (P < 0.01). In a regression analysis with age, weight, height, menstrual status, and dietary intake entered into the model, magnesium intake accounted for 12.3% of the variation in pyridinoline excretion and 12% of the variation in deoxypyridinoline excretion. Alcohol and potassium intakes accounted for 18.1% of the variation in total forearm bone mass. The BMD results confirm our previous work (but at peripheral bone mass sites), and our findings associating bone resorption with dietary factors provide further evidence of a positive link between fruit and vegetable consumption and bone health.


Longitudinal register study of attendance frequencies in public and private dental services in Finland.
The Public Dental Service (PDS) in Finland was recently opened to all adults. According to annual statistics, 75% of children and 51% of adults made dental attendances in 2008. This study aimed to survey the frequency of dental attendance across three years and compared attendance frequencies between age groups and treatment sectors. Data from municipal databases and the reimbursement register of the Social Insurance Institution were collected on all who had attended the PDS (733,000) or the private sector (473,000) in 2008 and they were retrospectively followed from 2008 to 2006. Most children had attended the PDS in each year (57.4%) or in two of the three years (32.2%). Most working aged (57.3%) and elderly (69.1%) were annual attenders in the private sector. In addition, 27.1% of the former and 19.8% of the latter had attended in two of the three years. Attending in one year only was unusual. In the PDS, adult annual attendance was uncommon (31.9%), and adult attenders were fairly evenly distributed over the three categories, attending in one, two or all three years. Annual or biannual attendances seemed to be the norm among children in the PDS and adults in the private sector. Adults in the PDS showed irregular attendance patterns probably partly due to scarcity of resources for recall patients in the PDS.


Angiotensin AT1 receptor antagonism by losartan stimulates adipocyte browning via induction of apelin.
Adipocyte browning appears to be a potential therapeutic strategy to combat obesity and related metabolic disorders. Recent studies have shown that apelin, an adipokine, stimulates adipocyte browning and has negative cross-talk with angiotensin II receptor type 1 (AT1 receptor) signaling. Here, we report that losartan, a selective AT1 receptor antagonist, induces browning, as evidenced by an increase in browning marker expression, mitochondrial biogenesis, and oxygen consumption in murine adipocytes. In parallel, losartan up-regulated apelin expression, concomitant with increased phosphorylation of protein kinase B and AMP-activated protein kinase. However, the siRNA-mediated knockdown of apelin expression attenuated losartan-induced browning. Angiotensin II cotreatment also inhibited losartan-induced browning, suggesting that AT1 receptor antagonism-induced activation of apelin signaling may be responsible for adipocyte browning induced by losartan. The in vivo browning effects of losartan were confirmed using both C57BL/6J and ob/ob mice. Furthermore, in vivo apelin knockdown by adeno-associated virus carrying-apelin shRNA significantly inhibited losartan-induced adipocyte browning. In summary, these data suggested that AT1 receptor antagonism by losartan promotes the browning of white adipocytes via the induction of apelin expression. Therefore, apelin modulation may be an effective strategy for the treatment of obesity and its related metabolic disorders.


Dual sensitivity of inferior colliculus neurons to ITD in the envelopes of high-frequency sounds: experimental and modeling study.
Human listeners are sensitive to interaural time differences (ITDs) in the envelopes of sounds, which can serve as a cue for sound localization. Many high-frequency neurons in the mammalian inferior colliculus (IC) are sensitive to envelope-ITDs of sinusoidally amplitude-modulated (SAM) sounds. Typically, envelope-ITD-sensitive IC neurons exhibit either peak-type sensitivity, discharging maximally at the same delay across frequencies, or trough-type sensitivity, discharging minimally at the same delay across frequencies, consistent with responses observed at the primary site of binaural interaction in the medial and lateral superior olives (MSO and LSO), respectively. However, some high-frequency IC neurons exhibit dual types of envelope-ITD sensitivity in their responses to SAM tones, that is, they exhibit peak-type sensitivity at some modulation frequencies and trough-type sensitivity at other frequencies. Here we show that high-frequency IC neurons in the unanesthetized rabbit can also exhibit dual types of envelope-ITD sensitivity in their responses to SAM noise. Such complex responses to SAM stimuli could be achieved by convergent inputs from MSO and LSO onto single IC neurons. We test this hypothesis by implementing a physiologically explicit, computational model of the binaural pathway. Specifically, we examined envelope-ITD sensitivity of a simple model IC neuron that receives convergent inputs from MSO and LSO model neurons. We show that dual envelope-ITD sensitivity emerges in the IC when convergent MSO and LSO inputs are differentially tuned for modulation frequency.


Seasonal variation in penicillin use in Mexico and Brazil: analysis of the impact of over-the-counter restrictions.
During 2010, Mexico and Brazil implemented policies to enforce existing laws of restricting over-the-counter sales of antibiotics. We determined if the enforcement led to more appropriate antibiotic use by measuring changes in seasonal variation of penicillin use. We used retail quarterly sales data in defined daily doses per 1,000 inhabitant-days (DDD/TID) from IMS Health from the private sector in Mexico and Brazil from the first quarter of 2007 to the first quarter of 2013. This database contains information on volume of antibiotics sold in retail pharmacies using information from wholesalers. We used interrupted time-series models controlling for external factors with the use of antihypertensives with interaction terms to assess changes in trend, level, and variation in use between quarters for total penicillin use and by active substance. The most used penicillin was amoxicillin, followed by amoxicillin-clavulanic acid and ampicillin (minimal use in Brazil). Before the restrictions, the seasonal variation in penicillin use was 1.1 DDD/TID in Mexico and 0.8 DDD/TID in Brazil. In Mexico, we estimated a significant decrease in the seasonal variation of 0.4 DDD/TID after the restriction, mainly due to changes in seasonal variation of amoxicillin and ampicillin. In Brazil, the seasonal variation did not change significantly, overall and in the breakdown by individual active substances. For Mexico, inappropriate penicillin use may have diminished after the restrictions were enforced. For Brazil, increasing use and no change in seasonal variation suggest that further efforts are needed to reduce inappropriate penicillin use.


The impact of trauma case management on patient outcomes.
Previous investigations demonstrate that nursing case management in the acute care setting improves patient outcomes. However, these findings provide limited information specific to trauma patients. The effect of trauma case management (TCM) was measured using practice-specific variables such as in-hospital complications, missed injury rates, and length of stay. Other measures included staff satisfaction and use of allied health services. Data from 148 patients with an Injury Severity Score < 16 in the 5 months after the introduction of TCM were compared with 327 patients from the previous 12 months. Results demonstrated a trend toward reduced length of stay overall, more so in the older and more severely injured. TCM greatly improved missed injury detection rates (p < 0.0015) and coordinated allied health use more efficiently (p < 0.0001). Staff surveys exhibited a perceived dramatic improvement in the effectiveness of patient care (p < 0.0001). The introduction of TCM improved the efficiency and effectiveness of trauma patient care in our institution.


Enantioselective Friedel-Crafts alkylation for synthesis of 2-substituted indole derivatives.
An efficient catalytic asymmetric intermolecular C2 Friedel-Crafts alkylation reaction between N-methyl skatole and β,γ-unsaturated α-ketoesters has been realized by a chiral N,N'-dioxide-Ni(II) complex. The corresponding indole derivatives were obtained in good yield (up to 96%) with excellent enantioselectivities (up to 99% ee) under mild reaction conditions.


Purification of messenger RNA coding for glycine methyltransferase from rat liver.
Rat liver messenger RNA coding for glycine methyltransferase was associated preferentially with free polysomes. The mRNA was purified about 1000-fold over the total poly(A)-containing RNA by specific immunoadsorption of polysomes to protein A-Sepharose followed by oligo(dT)-cellulose column chromatography. Sodium dodecyl sulfate-gel electrophoresis of the in vitro translation products in a rabbit reticulocyte lysate system revealed only one major band which migrated to the position of the purified glycine methyltransferase subunit. The result shows that the mRNA isolated is nearly homogeneous and suggests that no precursor form of the enzyme existed. The mRNA sedimented at the position slightly smaller than 18 S rRNA in a sucrose density-gradient centrifugation and was shown to contain about 1,300 nucleotides by the Northern blot hybridization analysis with a cDNA probe.


Protective effect of curcumin against ultraviolet A irradiation‑induced photoaging in human dermal fibroblasts.
Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in skin, resulting in photoaging. Natural botanicals have gained considerable attention due to their beneficial protection against the harmful effects of UV irradiation. The present study aimed to evaluate the ability of curcumin (Cur) to protect human dermal fibroblasts (HDFs) against ultraviolet A (UVA)‑induced photoaging. HDFs were treated with 0‑10 µM Cur for 2 h and subsequently exposed to various intensities of UVA irradiation. The cell viability and apoptotic rate of HDFs were investigated by MTT and flow cytometry assays, respectively. The effect of UVA and Cur on the formation of reactive oxygen species (ROS), malondialdehyde levels, which are an indicator of ROS, and the levels/activity of antioxidative defense proteins, including glutathione, superoxide dismutase and catalase, were evaluated using 2',7'-dichlorofluorescin diacetate and commercial assay kits. Furthermore, western blotting was performed to determine the levels of proteins associated with endoplasmic reticulum (ER) stress, the apoptotic pathway, inflammation and the collagen synthesis pathway. The results demonstrated that Cur reduced the accumulation of ROS and restored the activity of antioxidant defense enzymes, indicating that Cur minimized the damage induced by UVA irradiation in HDFs. Furthermore, western blot analysis demonstrated that Cur may attenuate UVA‑induced ER stress, inflammation and apoptotic signaling by downregulating the protein expression of glucose‑regulated protein 78, C/EBP‑homologous protein, nuclear factor‑κB and cleaved caspase‑3, while upregulating the expression of Bcl‑2. Additionally, it was demonstrated that Cur may regulate collagen metabolism by decreasing the protein expression of matrix metalloproteinase (MMP)‑1 and MMP‑3, and may promote the repair of cells damaged as a result of UVA irradiation through increasing the protein expression of transforming growth factor‑β (TGF‑β) and Smad2/3, and decreasing the expression of the TGF‑β inhibitor, Smad7. In conclusion, the results of the present study indicate the potential benefits of Cur for the protection of HDFs against UVA‑induced photoaging and highlight the potential for the application of Cur in skin photoprotection.


Low Social Support and Risk for Depression in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.
Depression is a frequent complication of type 2 diabetes mellitus. This study aimed to investigate the relationship between low social support and risk for depression in people with type 2 diabetes through a meta-analysis. PubMed, ProQuest, SpringerLink, ScienceDirect, Scopus, the Cochrane Library, Embase, and Google Scholar were searched for English-language articles published up to 2021. Pooled adjusted odds ratios (aORs) were calculated using a random-effect model with 95% confidence intervals (CIs). Heterogeneity was evaluated by using the Cochrane Q test and I2 statistics. The risk of publication bias was estimated using a funnel plot, the Egger test, and the Begg test. The Joanna Briggs Institute Critical Appraisal Tools were used to assess the quality of evidence and the risk of bias. Eleven studies were included in this meta-analysis, containing a total of 3151 people with type 2 diabetes mellitus. The pooled analysis showed that people with type 2 diabetes mellitus who had low social support had twice as high a risk of depression as those with high social support (aOR, 2.02; 95% CI, 1.51 to 2.70; p<0.001). A random-effect model was used because the heterogeneity was high (I2= 87%). Low social support was found to increase the risk of depression among people with type 2 diabetes mellitus. Further investigation into factors that may moderate this relationship is required.


Metabolism of benzoate, cyclohex-1-ene carboxylate, and cyclohexane carboxylate by "Syntrophus aciditrophicus" strain SB in syntrophic association with H(2)-using microorganisms.
The metabolism of benzoate, cyclohex-1-ene carboxylate, and cyclohexane carboxylate by "Syntrophus aciditrophicus" in cocultures with hydrogen-using microorganisms was studied. Cyclohexane carboxylate, cyclohex-1-ene carboxylate, pimelate, and glutarate (or their coenzyme A [CoA] derivatives) transiently accumulated during growth with benzoate. Identification was based on comparison of retention times and mass spectra of trimethylsilyl derivatives to the retention times and mass spectra of authentic chemical standards. (13)C nuclear magnetic resonance spectroscopy confirmed that cyclohexane carboxylate and cyclohex-1-ene carboxylate were produced from [ring-(13)C(6)]benzoate. None of the metabolites mentioned above was detected in non-substrate-amended or heat-killed controls. Cyclohexane carboxylic acid accumulated to a concentration of 260 microM, accounting for about 18% of the initial benzoate added. This compound was not detected in culture extracts of Rhodopseudomonas palustris grown phototrophically or Thauera aromatica grown under nitrate-reducing conditions. Cocultures of "S. aciditrophicus" and Methanospirillum hungatei readily metabolized cyclohexane carboxylate and cyclohex-1-ene carboxylate at a rate slightly faster than the rate of benzoate metabolism. In addition to cyclohexane carboxylate, pimelate, and glutarate, 2-hydroxycyclohexane carboxylate was detected in trace amounts in cocultures grown with cyclohex-1-ene carboxylate. Cyclohex-1-ene carboxylate, pimelate, and glutarate were detected in cocultures grown with cyclohexane carboxylate at levels similar to those found in benzoate-grown cocultures. Cell extracts of "S. aciditrophicus" grown in a coculture with Desulfovibrio sp. strain G11 with benzoate or in a pure culture with crotonate contained the following enzyme activities: an ATP-dependent benzoyl-CoA ligase, cyclohex-1-ene carboxyl-CoA hydratase, and 2-hydroxycyclohexane carboxyl-CoA dehydrogenase, as well as pimelyl-CoA dehydrogenase, glutaryl-CoA dehydrogenase, and the enzymes required for conversion of crotonyl-CoA to acetate. 2-Ketocyclohexane carboxyl-CoA hydrolase activity was detected in cell extracts of "S. aciditrophicus"-Desulfovibrio sp. strain G11 benzoate-grown cocultures but not in crotonate-grown pure cultures of "S. aciditrophicus". These results are consistent with the hypothesis that ring reduction during syntrophic benzoate metabolism involves a four- or six-electron reduction step and that once cyclohex-1-ene carboxyl-CoA is made, it is metabolized in a manner similar to that in R. palustris.


Plasmodium gallinaceum: sporozoite invasion of Aedes aegypti salivary glands is inhibited by anti-gland antibodies and by lectins.
There is evidence which suggests that malaria sporozoites recognize mosquito salivary glands by specific receptor-ligand interactions. We are interested in identifying the putative salivary gland receptor(s) for sporozoite invasion. We used an in vivo bioassay for sporozoite invasion of salivary glands. In this assay, purified sporozoites from mature oocytes of Plasmodium gallinaceum were injected into Aedes aegypti mosquitoes and salivary glands were dissected at different time points after injection. One half of the maximum invasion of salivary glands by sporozoites occurred by 6 hr, and salivary gland sporozoite load did not increase further after 24 hr postinjection. This assay was used to determine the effect of experimental treatments with antibodies and lectins at 24 hr postinjection. We raised a rabbit polyclonal antiserum against female Ae. aegypti salivary glands which recognized tissue-specific determinants in the basal lamina of salivary glands. Purified IgG antibody fraction of the immune serum blocked sporozoite invasion in vivo. We tested a panel of 19 lectins and found 7 which bound to salivary glands. Of these 7, succinylated wheat germ agglutinin and wheat germ agglutinin completely blocked sporozoite invasion; Pisum sativum agglutinin and soybean agglutinin partially blocked; and concanavalin A, Dolichos biflorus agglutinin, and Phaseolus vulgaris erythroagglutinin did not block. Our results suggest that sporozoites interact with glycosylated salivary gland surface molecules which serve as receptors for invasion, and which may be in the salivary gland basal lamina. Because the putative sporozoite receptors contain immunogenic determinants, it is feasible to identify them by an immunological strategy.


Bridging the Gap Between Academic Research and Pragmatic Needs in Usability: A Hybrid Approach to Usability Evaluation of Health Care Information Systems.
Technology is increasingly embedded into the full spectrum of health care. This movement has benefited from the application of software development practices such as usability testing and agile development processes. These practices are frequently applied in both commercial or operational and academic settings. However, the relative importance placed on rapid iteration, validity, reproducibility, generalizability, and efficiency differs between the 2 settings and the needs and objectives of academic versus pragmatic usability evaluations. This paper explores how usability evaluation typically varies on key dimensions in pragmatic versus academic settings that impact the rapidity, validity, and reproducibility of findings and proposes a hybrid approach aimed at satisfying both pragmatic and academic objectives. We outline the characteristics of pragmatic versus academically oriented usability testing in health care, describe the tensions and gaps resulting from differing contexts and goals, and present a model of this hybrid process along with 2 case studies of digital development projects in which we demonstrate this integrated approach to usability evaluation. The case studies presented illustrate design choices characteristic of our hybrid approach to usability evaluation. Designed to leverage the strengths of both pragmatically and academically focused usability studies, a hybrid approach allows new development projects to efficiently iterate and optimize from usability data as well as preserves the ability of these projects to produce deeper insights via thorough qualitative analysis to inform further tool development and usability research by way of academically focused dissemination.


Tuning primary metabolism for heterologous pathway productivity.
Tuning expression of competing endogenous pathways has been identified as an effective strategy in the optimization of heterologous production pathways. However, intervention at the first step of glycolysis, where no alternate routes of carbon utilization exist, remains unexplored. In this work we have engineered a viable E. coli host that decouples glucose transport and phosphorylation, enabling independent control of glucose flux to a heterologous pathway of interest through glucokinase (glk) expression. Using community sourced and curated promoters, glk expression was varied over a 3-fold range while maintaining cellular viability. The effects of glk expression on the productivity of a model glucose-consuming pathway were also studied. Through control of glycolytic flux we were able to explore a number of cellular phenotypes and vary the yield of our model pathway by up to 2-fold in a controllable manner.


In vivo visualization and monitoring of viable neural stem cells using noninvasive bioluminescence imaging in the 6-hydroxydopamine-induced mouse model of Parkinson disease.
Transplantation of neural stem cells (NSCs) has been proposed as a treatment for Parkinson disease (PD). The aim of this study was to monitor the viability of transplanted NSCs expressing the enhanced luciferase gene in a mouse model of PD in vivo. The PD animal model was induced by unilateral injection of 6-hydroxydopamine (6-OHDA). The behavioral test using apomorphine-induced rotation and positron emission tomography with [18F]N-(3-fluoropropyl)-2'-carbomethoxy-3'-(4-iodophenyl)nortropane ([18F]FP-CIT) were conducted. HB1.F3 cells transduced with an enhanced firefly luciferase retroviral vector (F3-effLuc cells) were transplanted into the right striatum. In vivo bioluminescence imaging was repeated for 2 weeks. Four weeks after transplantation, [18F]FP-CIT PET and the rotation test were repeated. All 6-OHDA-injected mice showed markedly decreased [18F]FP-CIT uptake in the right striatum. Transplanted F3-effLuc cells were visualized on the right side of the brain in all mice by bioluminescence imaging. The bioluminescence intensity of the transplanted F3-effLuc cells gradually decreased until it was undetectable by 10 days. The behavioral test showed that stem cell transplantation attenuated the motor symptoms of PD. No significant change was found in [18F]FP-CIT imaging after cell transplantation. We successfully established an in vivo bioluminescence imaging system for the detection of transplanted NSCs in a mouse model of PD. NSC transplantation induced behavioral improvement in PD model mice.


Cranial sutures require tissue interactions with dura mater to resist osseous obliteration in vitro.
A chemically defined serum-free medium, which supports the development of bones and fibrous tissues of rat calvaria from nonmineralized mesenchymal precursor tissues, was employed to investigate tissue interactions between the dura matter and overlying tissues. Fetal calvarial rudiments from stages prior to bone and suture morphogenesis (fetal days 19 and 20) and neonatal calvarial rudiments with formed sutures (day 1) were cultured with and without associated dura mater. Removal of calvaria for in vitro culture allowed the examination of suture morphogenesis in the absence of tensional forces exerted on the sutures via fiber tracts in the dura mater originating in the cranial base. Ossification of frontal and parietal bones proceeded in a fashion comparable to development in vivo, but the cranial (coronal) sutures--primary sites for subsequent skull growth--were obliterated by osseous tissue union in the absence of dura mater. Bony fusion did not occur when rudiments were cocultured with dura mater on the opposite sides of 0.45 microns polycarbonate transwell filters, suggesting that the influence of dura mater on sutural obliteration was mediated by soluble factors rather than cell-cell or cell-matrix interactions. These results indicate that cell signaling mechanisms rather than biomechanical tensional forces are required for morphogenesis of the calvaria.


[Nausea and vomiting induced by chemotherapy].
Nausea and vomiting induced by chemotherapy. Nausea and vomiting induced by chemotherapy impact heavily anticancer treatment safety. It is necessary to define correctly, assess frequently and treat perfectly, following national or international guidelines. New treatment are currently developed in the field of emesis protection. Old drugs may help patients. Physicians as well as nurses and caregivers have to be involved in emesis protection. It is one of the key topic in cancer care management.


Atrial fibrillatory frequency predicts atrial defibrillation threshold and early arrhythmia recurrence in patients undergoing internal cardioversion of persistent atrial fibrillation.
This study was conducted to analyze the meaning of AF frequency obtained from the surface ECG for prediction of energy requirements and early arrhythmia relapse in patients undergoing internal cardioversion of persistent AF. Nineteen consecutive patients (mean age 58 +/- 11 years; 11 men, 8 women) with persistent AF (> 7 days) underwent internal cardioversion. A biphasic shock synchronized to the R wave was delivered between two catheters positioned in the high right atrium (HRA) and the coronary sinus (CS). AFfrequency was estimated prior to cardioversion from surface ECG lead V1. After filtering, QRST complexes were subtracted using a template matching and averaging algorithm. The resulting fibrillatory baseline signal was subjected to Fourier transformation, displayed as a frequency power spectrum and the peak frequency was determined in the 3-12 Hzfrequencyband. Atrial defibrillation threshold (ADFT) was determined using a step-up protocol. All patients were cardioverted successfully with a mean ADFT of 7.6 +/- 6.5 J(range 0.5-25). There was a strong positive correlation between fibrillatory frequency and ADFT (R = 0.71, P = 0.001). AF recurrence within 30 days after successful cardioversion occurred in 11 (58%) patients. Receiver operating characteristic (ROC) analysis revealed a fibrillatory frequency > or = 7 Hz to be 64% sensitive and 88% specific to predict AF recurrence. It was observed in 4 (36%) of 11 cases with a fibrillatory frequency < 7 Hz, as opposed to 7 (88%) of 8 cases with a fibrillatory frequency > or = 7 Hz (P = 0.02). Fibrillatory frequency obtained from the surface ECG predicts ADFT and early AF recurrence in patients with persistent AF undergoing internal cardioversion.


Morphological assessment of bone mineralization in tibial metaphyses of ascorbic acid-deficient ODS rats.
Osteogenic disorder shionogi (ODS) rats carry a hereditary defect in ascorbic acid synthesis, mimicking human scurvy when fed with an ascorbic acid-deficient (aa-def) diet. As aa-def ODS rats were shown to feature disordered bone formation, we have examined the bone mineralization in this rat model. A fibrous tissue layer surrounding the trabeculae of tibial metaphyses was found in aa-def ODS rats, and this layer showed intense alkaline phosphatase activity and proliferating cell nuclear antigen-immunopositivity. Many osteoblasts detached from the bone surfaces and were characterized by round-shaped rough endoplasmic reticulum (rER), suggesting accumulation of malformed collagen inside the rER. Accordingly, fine, fragile fibrillar collagenous structures without evident striation were found in aa-def bones, which may result from misassembling of the triple helices of collagenous α-chains. Despite a marked reduction in bone formation, ascorbic acid deprivation seemed to have no effect on mineralization: while reduced in number, normal matrix vesicles and mineralized nodules could be seen in aa-def bones. Fine needle-like mineral crystals extended from these mineralized nodules, and were apparently bound to collagenous fibrillar structures. In summary, collagen mineralization seems unaffected by ascorbic acid deficiency in spite of the fine, fragile collagenous fibrils identified in the bones of our animal model.


Recurrent antinociception induced by intrathecal or peripheral oxytocin in a neuropathic pain rat model.
The search for new ligands to treat neuropathic pain remains a challenge. Recently, oxytocin has emerged as an interesting molecule modulating nociception at central and peripheral levels, but no attempt has been made to evaluate the effect of recurrent oxytocin administration in neuropathic pain. Using male Wistar rats with spinal nerve ligation, we evaluated the effects of recurrent spinal (1 nmol; given by lumbar puncture) or peripheral (31 nmol; given by intraplantar injection in the ipsilateral paw to spinal nerve ligation) oxytocin administration on pain-like behavior in several nociceptive tests (tactile allodynia and thermal and mechanical hyperalgesia) on different days. Furthermore, we used an electrophysiological approach to analyze the effect of spinal 1 nmol oxytocin on the activity of spinal dorsal horn wide dynamic range cells. In neuropathic rats, spinal or peripheral oxytocin partially restored the nociceptive threshold measured with the von Frey filaments (tactile allodynia), Hargreaves (thermal hyperalgesia) and Randall-Selitto (mechanical hyperalgesia) tests for 12 days. These results agree with electrophysiological data showing that spinal oxytocin diminishes the neuronal firing of the WDR neurons evoked by peripheral stimulation. This effect was associated with a decline in the activity of primary afferent Aδ- and C-fibers. The above findings show that repeated spinal or peripheral oxytocin administration attenuates the pain-like behavior in a well-established model of neuropathic pain. This study provides a basis for addressing the therapeutic relevance of oxytocin in chronic pain conditions.


(±)-Japonicols A-D, Acylphloroglucinol-Based Meroterpenoid Enantiomers with Anti-KSHV Activities from Hypericum japonicum.
(±)-Japonicols A-D (1a/1b-4a/4b), four pairs of new phloroglucinol-based terpenoid enantiomers, were isolated from Hypericum japonicum. Their absolute configurations were confirmed through comparison of their experimental and calculated electronic circular dichroism spectra and single-crystal X-ray diffraction analyses. Compounds 1a/1b, 2a/2b, and 3a/3b possess 2-oxabicyclo[3.3.1]nonane, pyrano[3,2-b]pyran, and benzo[b]cyclopenta[e]oxepine ring systems, respectively. The effects of the phloroglucinols on anti-Kaposi's sarcoma-associated herpesvirus were assessed, and 2a exhibited a moderate inhibitory effect, with an EC50 value of 8.75 μM and a selectivity index of 16.06.


Effect of aerosol surface lubricants on the abundance and richness of selected forest insects captured in multiple-funnel and panel traps.
Survey and detection programs for native and exotic forest insects frequently rely on traps baited with odorants, which mediate the orientation of target taxa (e.g., the southern pine beetle, Dendroctonusfrontalis Zimmermann) toward a resource (e.g., host material, mates). The influence of trap design on the capture efficiency of baited traps has received far less empirical attention than odorants, despite concerns that intercept traps currently used operationally have poor capture efficiencies for some target taxa (e.g., large woodborers). Several studies have recently demonstrated that treating traps with a surface lubricant to make them "slippery" can increase their capture efficiency; however, previously tested products can be expensive and their application time-consuming. The purpose of this study was to evaluate the effect of alternate, easier to apply aerosol lubricants on trap capture efficiency of selected forest insects. Aerosol formulations of Teflon and silicone lubricants increased both panel and multiple-funnel trap capture efficiencies. Multiple-funnel traps treated with either aerosol lubricant captured significantly more Monochamus spp. and Acanthocinus obsoletus (Olivier) than untreated traps. Similarly, treated panel traps captured significantly more Xylotrechus sagittatus (Germar), Ips calligraphus (Germar), Pissodes nemorensis (Germar), Monochamus spp., A. obsoletus, Thanasimus dubius (F.), and Ibalia leucospoides (Hochenwarth) than untreated traps. This study demonstrates that treating multiple-funnel and panel traps with an aerosol dry film lubricant can increase their capture efficiencies for large woodborers (e.g., Cerambycidae) as well as bark beetles, a weevil, a woodwasp parasitoid and a bark beetle natural enemy (Coleoptera: Cleridae).


Recurrent Neck Lymphangioma in a Young Adult: Twenty-Three Years After Successful Treatment.
Lymphangiomas are rare benign malformations of the lymphatic system, commonly present in children, over the head and neck area. Occasionally, they can grow significantly in size and especially those located over the cervical region can cause airway obstruction and become life-threatening. Recurrent lymphangiomas usually occur during the early postsurgical period and 80% of them within the first 3 to 5 years. However, in a new onset of clinical manifestations affecting the head and neck, even many years after the successful surgical treatment, a recurrent lymphangioma should be considered in the differential diagnosis. We present herein the second reported case, to our knowledge, of a recurrent left-sided neck lymphangioma in a young man, 23 years after a successful surgical treatment that initially took place 6 weeks after his birth.


Neural control of cerebral blood flow: scientific basis of scalp acupuncture in treating brain diseases.
Scalp acupuncture (SA), as a modern acupuncture therapy in the treatment of brain diseases, especially for acute ischemic strokes, has accumulated a wealth of experience and tons of success cases, but the current hypothesized mechanisms of SA therapy still seem to lack significant scientific validity, which may not be conducive to its ultimate integration into mainstream medicine. This review explores a novel perspective about the mechanisms of SA in treating brain diseases based on its effects on cerebral blood flow (CBF). To date, abundant evidence has shown that CBF is significantly increased by stimulating specific SA points, areas or nerves innervating the scalp, which parallels the instant or long-term improvement of symptoms of brain diseases. Over time, the neural pathways that improve CBF by stimulating the trigeminal, the facial, and the cervical nerves have also been gradually revealed. In addition, the presence of the core SA points or areas frequently used for brain diseases can be rationally explained by the characteristics of nerve distribution, including nerve overlap or convergence in certain parts of the scalp. But such characteristics also suggest that the role of these SA points or areas is relatively specific and not due to a direct correspondence between the current hypothesized SA points, areas and the functional zones of the cerebral cortex. The above evidence chain indicates that the efficacy of SA in treating brain diseases, especially ischemic strokes, is mostly achieved by stimulating the scalp nerves, especially the trigeminal nerve to improve CBF. Of course, the mechanisms of SA in treating various brain diseases might be multifaceted. However, the authors believe that understanding the neural regulation of SA on CBF not only captures the main aspects of the mechanisms of SA therapy, but also facilitates the elucidation of other mechanisms, which may be of greater significance to further its clinical applications.


Maternal platelets in missed abortion; from a clinical perspective.
To assess the significance of platelet indices, mean platelet volume, and platelet distribution width in patients with missed abortion as an earlier and cost-benefit screening test. The prospective case-control study was conducted at the University Hospital, Baghdad, Iraq, from April to September 2021, and comprised women with missed abortion as well as healthy controls. Anthropometric parameters were recorded alongside complete blood count, platelet count, mean platelet volume, and platelet distribution width were evaluated and compared between the two groups. Data was analysed using Medcalc 20. Of the 60 subjects, 30(50%) were cases with a mean age of 27.8±6.1 years, and 30(50%) were healthy controls with a mean age of 25.7±5.2 years (P>0.05). All platelets parameters were significantly high among the cases compared to the controls (P<0.05). Platelet distribution width was found to have the highest sensitivity in predicting missed abortion.


Left sided inferior vena cava: a case report.
To report a case of left sided inferior vena cava (IVC). The authors carried out the standard dissection survey of939 embalmed cadavers between 1974 and 2008. The authors encountered a case of left sided IVC in a male donated cadaver aged 65 years at decease. The IVC formed behind the left common iliac artery at the L5 vertebra and coursed proximally on the left of the aorta until it reached the left renal vein and then crossed anterior to the abdominal aorta to assume the normal right side. At the point of crossing, it received the left renal vein. The right renal vein emptied into the IVC on the right side. In the era of laparoscopic urological surgery, preoperative diagnosis of this uncommon but important entity is essential to prevent unwarranted surgical mishaps.


Is Mo involved in hydride binding by the four-electron reduced (E4) intermediate of the nitrogenase MoFe protein?
We here report the first direct evidence addressing the possible involvement of Mo in substrate interactions during catalytic turnover. When the alpha-70(Ile) MoFe protein is freeze-trapped during H(+) reduction under Ar, the majority of the resting state EPR signal from the molybdenum-iron cofactor (FeMo-co) disappears and is replaced by the S = 1/2 signal of an intermediate that has been shown to be the E(4) MoFe state, which is activated for N(2) binding and reduction through the accumulation of 4 electrons/protons by FeMo-co. ENDOR studies of E(4) showed that it contains two hydrides bound to FeMo-co. We calculate that Mo involvement in hydride binding would require a vector-coupling coefficient for Mo of |K(Mo)| approximately > 0.2 and determine K(Mo) for the E(4) intermediate state through 35 GHz ENDOR measurements of a (95)Mo enriched MoFe protein, further comparing the results with those for the E(0) resting state. The experiments show that Mo of the resting-state FeMo-co is perturbed by the alpha-70(Ile) substitution and that the isotropic (95)Mo hyperfine coupling in E(4) is a(iso) approximately 4 MHz, less than that for the resting state. The decrease in a(iso) for (95)Mo of E(4) from the already small value in the resting state MoFe protein strongly suggests that the resting Mo(IV) is not one-electron reduced during the accumulation of the four electrons of E(4). In any case, the effective K for Mo is very small; |K(Mo)| approximately < 0.04, at least 5-fold less than the lower bound required for Mo to be involved in forming a Mo-H-Fe, hydride. As the hydride couplings also are both far too small and of the wrong symmetry to be associated with a terminal hydride on Mo, we may thus conclude that Mo does not participate in binding a hydride of the catalytically central E(4) intermediate and that only Fe ions are involved. Nonetheless, the response of the Mo coupling to subtle conformational changes in E(0) and to the formation of E(4) suggests that Mo is intimately involved in tuning the geometric and electronic properties of FeMo-co in these states.


Compliance of licensed child care centers with the American Academy of Pediatrics' recommendations for infant sleep positions.
Sudden Infant Death Syndrome is an elusive and tragic cause of infant mortality. In 1992, the American Academy of Pediatrics (AAP) recommended that healthy term infants be placed in the supine or lateral positions for sleep, based on research conducted in Europe, Australia, and New Zealand. The AAP modified its recommendation in 1994, indicating a preference for the supine position. Since the initial AAP proposal, national educational programs have worked to encourage parents and health care providers to utilize AAP guidelines. Studies have been done on parental use of the supine position. However, very little information exists about the procedures utilized in licensed child care facilities. A survey of child care providers was conducted to determine the risk for Sudden Infant Death Syndrome, as indicated by rates of compliance with AAP guidelines. Results show that although the majority of the child care providers knew the AAP recommendations, only 14.3% were in complete compliance. We make recommendations for the role of the public health nurse in facilitating compliance in child care centers along with suggestions for future research.


Refractory diffuse bony pain 20 years after jejunoileal bypass.
Osteomalacia can be a late but unrecognized complication following jejunoileal bypass. We describe a 53-year-old man who underwent jejunoileal bypass for morbid obesity twenty years earlier who suffered from progressive diffuse bony pain refractory to nonsteroidal anti-inflammatory drugs. He was initially diagnosed with a malignancy with bone metastasis. However, pertinent laboratory data were notable for hypocalcemia (7.5 mg/dL, albumin 4.1 mg/dL) with low urinary calcium excretion (14 mg/day), hypophosphatemia (2.0 mg/dL) with low urinary phosphate excretion (53 mg/day), hypomagnesemia (1.5 mg/dL) with low urine magnesium excretion (23 mg/day), low 1, 25 (OH)2 vitamin D3, and elevated serum alkaline phosphatase and intact parathyroid hormone (iPTH). These laboratory findings pointed to a defect in calcium, phosphate, and magnesium handling in the gastrointestinal tract. Bone biopsy of the iliac crest clearly demonstrated typical changes of osteomalacia with excessive osteoid accumulation and reduced mineralization. His clinical symptoms were refractory to oral 1, 25 (OH)2 vitamin D3 and calcium supplementation but significantly improved with the addition of intermittent intravenous active 1, 25 (OH)2 vitamin D3, calcium, phosphate, and magnesium supplementation. Osteomalacia is an easily misdiagnosed late complication of jejunoileal bypass. Early recognition can avoid circuitous diagnosis and inappropriate management.


Can Routine Patients Be Safely Discharged After Neodymium-Doped Yttrium Aluminium Garnet Laser Posterior Capsulotomy?
Background Neodymium-doped yttrium aluminium garnet (Nd:YAG) posterior capsulotomy is a common treatment for posterior capsular opacification. Practice varies regarding routine follow-up. In this study, we reviewed follow-up rates and treatment-related complications from a district general hospital's ophthalmology unit to assess areas for improvement and cost-effectiveness. Methodology We conducted a retrospective review of electronic patient records for all patients treated with Nd:YAG capsulotomy in 2019 at our hospital. Primary outcomes included visual acuity, complications, and follow-up data. Secondary outcomes included medication prescribing and the grade of surgeon. Results In total, 912 eyes of 744 patients were included. Overall, 536 (58.8%) eyes were discharged immediately following their laser. Complication rate was 4.3% (39 eyes). Junior training grades had a higher rate of medication prescribing (40/46 eyes; 87.0%) and follow-up (36/40 eyes; 78.3%). Conclusions Certain selected patients may be safely discharged following capsulotomy with safety-netting advice. This strategy increases the capacity to follow-up patients at higher risk of complications. Higher rates of follow-up among junior ophthalmologists offers potential for training.


Safety of oral and intravenous mycophenolate mofetil in healthy cats.
Objectives The aim of this study was to evaluate the safety and clinical effects of intravenous (IV) and oral mycophenolate mofetil (MMF) in healthy cats. Methods A total of 24 healthy adult cats weighing >3.5 kg were either given IV MMF (over a 2 h infusion) or oral MMF. The dosages used were as follows: 5 mg/kg IV once (n = 2), 10 mg/kg q12h IV for 1 day (n = 1), 20 mg/kg q12h IV for 1 day (n = 6) and 10 mg/kg q12h IV for 3 days (n = 5). Blood was collected from each cat at intervals of up to 12 h from the last dose for analysis purposes. Oral MMF was given at 10 mg/kg q12h for 7 days (n = 3), 15 mg/kg q12h for 7 days (n = 3) and 15 mg/kg q8h for 7 days (n = 4). Results Side effects to MMF were minimal. There was no anorexia or vomiting noted in any of the cats during or after IV medication administration. Only 4/14 cats had diarrhea from 12-48 h after IV administration. There was hyporexia in 1/10 cats given oral MMF and no vomiting noted. In 5/10 cats given oral MMF, there was diarrhea between days 2 and 7 of the study. Conclusions and relevance Cats tolerate MMF at an IV dose of 10 mg/kg q12h for 3 days and an oral dose ⩽15 mg/kg q12h for up to 7 days. There seems to be a dose-dependent incidence of gastrointestinal side effects. MMF may be a useful alternative immunosuppressant to be considered for use in some cats.


The hippocampus and memory of verbal and pictorial material.
Recognition of words and kaleidoscope pictures showed a double dissociation of left and right hippocampal activity using magnetic source imaging (MSI). MSI has advantages over alternative imaging techniques that measure hemodynamic changes for identifying regional changes in brain activity in real time and on an individual subject basis without the need for image subtraction. In this study, lists of words or kaleidoscope pictures were presented for memorization followed by tests of list items and foils during which brain activity was recorded. There was greater activation in the left than the right hippocampus with abstract nouns (e.g., relief) and greater activation in the right than the left hippocampus with kaleidoscope pictures. This dissociation was evident on a case by case basis. This study demonstrates the specialization of the two medial temporal lobe (MTL) regions, including the hippocampi, for mnemonic processing of verbal and pictorial items that are difficult to encode verbally.


Myocardial Injury Is Distinguished from Stable Angina by a Set of Candidate Plasma Biomarkers Identified Using iTRAQ/MRM-Based Approach.
The lack of precise biomarkers that identify patients at risk for myocardial injury and stable angina delays administration of optimal therapy. Hence, the search for noninvasive biomarkers that could accurately stratify patients with impending heart attack, from patients with stable coronary artery disease (CAD), is urgently needed in the clinic. Herein, we performed comparative quantitative proteomics on whole plasma sampled from patients with stable angina (NMI), acute myocardial infarction (MI), and healthy control subjects (Ctrl). We detected a total of 371 proteins with high confidence (FDR < 1%, p < 0.05) including 53 preliminary biomarkers that displayed ≥2-fold modulated expression in patients with CAD (27 associated with atherosclerotic stable angina, 26 with myocardial injury). In the verification phase, we used label-free LC-MRM-MS-based targeted method to verify the preliminary biomarkers in pooled plasma, excluded peptides that were poorly distinguished from background, and performed further validation of the remaining candidates in 49 individual plasma samples. Using this approach, we identified a final panel of eight novel candidate biomarkers that were significantly modulated in CAD (p < 0.05) including proteins associated with atherosclerotic stable angina that were implicated in endothelial dysfunction (F10 and MST1), proteins associated with myocardial injury reportedly involved in plaque destabilization (SERPINA3, CPN2, LUM), and in tissue protection/repair mechanisms (ORM2, ACTG1, NAGLU). Taken together, our data showed that candidate biomarkers with potential diagnostic values can be successfully detected in nondepleted human plasma using an iTRAQ/MRM-based discovery-validation approach and demonstrated the plausible clinical utility of the proposed panel in discriminating atherosclerotic stable angina from myocardial injury in the studied cohort.


Myelokathexis, a congenital disorder of severe neutropenia characterized by accelerated apoptosis and defective expression of bcl-x in neutrophil precursors.
Myelokathexis is a congenital disorder that causes severe chronic leukopenia and neutropenia. Characteristic findings include degenerative changes and hypersegmentation of mature neutrophils and hyperplasia of bone marrow myeloid cells. The associated neutropenia can be partially corrected by treatment with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). These features led us to propose that accelerated apoptosis of neutrophil precursors might account for the neutropenic phenotype. Blood and bone marrow aspirates were obtained from 4 patients (2 unrelated families) with myelokathexis before G-CSF therapy and from 2 of the affected persons after G-CSF therapy (1 microg/kg per day subcutaneously for 3 weeks). Bone marrow was fractionated using immunomagnetic bead cell sorting into CD34(+), CD33(+)/CD34(-), and CD15(+)/CD34(-)/CD33(- )cell populations. Examination of these cells by flow cytometry and electron microscopy revealed abundant apoptosis in the CD15(+) neutrophil precursor population, characterized by enhanced annexin-V binding, extensive membrane blebbing, condensation of heterochromatin, and cell fragmentation. Colony-forming assays demonstrated significant reduction in a proportion of bone marrow myeloid-committed progenitor cells. Immunohistochemical analysis revealed a selective decrease in bcl-x, but not bcl-2, expression in the CD15(+)/CD34(-)/CD33(-)cell population compared with similar subpopulations of control bone marrow-derived myeloid precursors. After G-CSF therapy, apoptotic features of patients' bone marrow cells were substantially reduced, and the absolute neutrophil counts (ANC) and expression of bcl-x in CD15(+)/CD34(-)/CD33(-)cells increased. The authors concluded that myelokathexis is a disease characterized by the accelerated apoptosis of granulocytes and the depressed expression of bcl-x in bone marrow-derived granulocyte precursor cells. These abnormalities are partially corrected by the in vivo administration of G-CSF. (Blood. 2000;95:320-327)


[Visceral pain--a neglected phenomenon in pain therapy and research?].
The topic "visceral pain"is hardly covered in basic research and pain therapy. After low back pain, headache and musculosceletal pain is abdominal pain the 4th frequent chronic pain syndrome in the general population with considerable direct and indirect disease related costs.An interdisciplinary multimodal treatment of chronic abdominal pain syndromes is rarely practiced in clinical care.


Stress-induced analgesia.
For over 30 years, scientists have been investigating the phenomenon of pain suppression upon exposure to unconditioned or conditioned stressful stimuli, commonly known as stress-induced analgesia. These studies have revealed that individual sensitivity to stress-induced analgesia can vary greatly and that this sensitivity is coupled to many different phenotypes including the degree of opioid sensitivity and startle response. Furthermore, stress-induced analgesia is influenced by age, gender, and prior experience to stressful, painful, or other environmental stimuli. Stress-induced analgesia is mediated by activation of the descending inhibitory pain pathway. Pharmacological and neurochemical studies have demonstrated involvement of a large number of neurotransmitters and neuropeptides. In particular, there are key roles for the endogenous opioid, monoamine, cannabinoid, gamma-aminobutyric acid and glutamate systems. The study of stress-induced analgesia has enhanced our understanding of the fundamental physiology of pain and stress and can be a useful approach for uncovering new therapeutic targets for the treatment of pain and stress-related disorders.


Orbito-frontal epilepsy masquerading as temporal lobe epilepsy-a case report.
Temporal lobectomy fails to control seizures in a considerable percentage of patients who do not have hippocampal sclerosis. One theoretical reason for failure of surgery is that some of these patients may in fact have extratemporal epilepsy. We present a 28-year-old woman with clinical and scalp electroencephalogram (EEG) evidence of right temporal lobe epilepsy (TLE) supported by functional imaging with interictal positron emission tomography (PET) and ictal single-photon emission computerized tomography (SPECT). An invasive EEG monitoring was prompted by the discovery of a small right orbito-frontal lesion on MRI. Monitoring documented seizure onset at the lesion, with rapid right temporal involvement. The patient was almost seizure-free after a lesionectomy. The index of suspicion of orbito-frontal epilepsy should be high in patients with apparent TLE when the scalp EEG and neuroimaging data are not congruent, or if temporal lobe pathology cannot be identified on structural imaging.


Association of Potassium and Some Other Monovalent Cations with Occurrence of Polyphosphate Bodies in Chlorella pyrenoidosa.
Phosphate-starved Chlorella pyrenoidosa cells formed polyphosphate bodies (PB) upon transfer into nutrient solutions containing phosphate and potassium, or another monovalent cation, such as Na(+), NH(4) (+), Li(+), or Rb(+). The phenomenon was studied by chemical analyses, light microscopy, and electron microscopy.When the P-starved cells were transferred into a complete nutrient solution containing 100 micromolar P, they accumulated large quantities of P and K within several hours. The accumulation was accompanied by a corresponding appearance of PB in the cells. The absence of K from the medium prevented appreciable P accumulation and PB formation, but omitting Ca or Mg did not.The P-starved cells exposed to a simple solution of at least 20 micromolar H(3)PO(4) and 100 micromolar KHCO(3) responded in a similar manner as the cells exposed to the complete nutrient solution. However, the PB appeared structurally different.It is proposed that monovalent cations are essential for PB formation in C. pyrenoidosa. K is suggested to be a major component of PB formed in K-sufficient media.


A comparative study of cricotracheal resection and staged laryngotracheoplasty for adult subglottic stenosis.
Cricotracheal resection (CTR) and laryngotracheoplasty (LTP) are open surgical treatments for severe subglottic stenosis. This study aims to compare the applications and outcomes of these techniques. Patients with subglottic stenosis at a tertiary academic institution from 2000 to 2012 were identified by diagnosis codes. Patients who underwent LTP or CTR were included. Records were reviewed for treatment data and outcomes. Patients with a history of head and neck malignancy or stenosis without cricoid involvement were excluded. Sixty-one and 20 patients underwent LTP and CTR, respectively. When comparing patients receiving LTP and CTR, there was a significant difference in stenosis etiology (P=.014). The groups were similar in Cotton-Myer grade (P=.102). At last follow-up, 80.3% of LTP patients and 90.0% of CTR patients were decannulated. On multivariate analysis, there was a significant association between stenosis grade and decannulation in the LTP group (P=.01). Decannulation was not associated with stenosis grade in the CTR group. In both groups, there was no significant association between decannulation and sex, stenosis etiology, or stenosis length. Cricotracheal resection and LTP have both shown excellent long-term decannulation rates. Etiology and stenosis grade are likely to be determining factors when recommending specific surgical interventions for subglottic stenosis.


Magnesium(II) is a crucial constituent of the blood coagulation cascade. Potentiation of coagulant activities of factor IX by Mg2+ ions.
We recently showed that not only Ca2+ ions but also Mg2+ ions play a crucial role in stabilizing the native conformation of coagulation factor IX. We here report that Mg2+ ions at physiological concentrations greatly augment the biological activities of factor IX. In clotting assays with dialyzed plasma, addition of Mg2+ ions enhanced the apparent coagulant activity of factor IXa, while that of factor Xa was scarcely affected. Activation of factor X by factor IXa in the presence of factor VIIIa, phospholipids, and Ca2+ ions was accelerated by Mg2+ ions. It appeared that the cation increased the affinity between factor IXa and factor VIIIa, thereby increasing the apparent catalytic efficacy of the enzyme. We also evaluated the effect of Mg2+ ions in the coagulation pathway initiated by tissue factor and found that activation of factor IX by factor VIIa*tissue factor was accelerated by the cation. Consequently, clotting of normal plasma induced by factor VIIa*tissue factor was shortened by the cation, while no such effect was observed in plasma deficient in factor IX or VIII. These results indicate that the previously unrecognized plasma component, Mg2+ ions, plays crucial roles in blood coagulation and, moreover, that contributions of factors IX and VIII in the coagulation cascade have been seriously underestimated in previous investigations.


[Molecular mechanism of cyclooxygenase-2 inhibitor in inhibition of proliferation of colon cancer cells by modulating Stat5 signal transduction pathway].
To investigate the role of NS398, a selective cyclooxygenase (COX)-2 inhibitor, in proliferation and apoptosis of colorectal cancer, and to reveal the mechanism of inhibiting colon cancer by NS-398 Independent of COX-2. Human colon cancer cells of the line SW480 were cultured and then divided into 2 groups: experimental group and control group. NS398 of the concentrations of 12.5, 25, 50, 75, 100, and 125 micromol/L was added into the culture fluid of the experimental group. MTT assay was used to observe the proliferation of the cells, flow cytometry was used to test the cell cycle, RT-PCR analysis was performed to examine COX-2 mRNA expression, and Western blotting analysis was performed to detect the expression of Stat5, peroxisome proliferators-activated receptors (PPARs), cyclin D1 and Bcl-x(L). Expression of COX-2 mRNA was not detected in the SW480 colon cancer cells. 72 hours after the addition of NS398 75 micromol/L the proliferative level of the SW480 cells was decreased; the rate of the cells at the G(1) stage increased from 31.2% to 40.6%, and the rate of cells at the S stage decreased from 52.8% to 41.2%. The expression of Stat5, PPARdelta, cyclin D1 and Bcl-x(L) decreased along with the elongation of time of NS398 action. COX-2 inhibitor, such as NS-398 inhibits the colon cancer cell proliferation and induces apoptosis of colon cancer cells with the possible mechanism of inhibiting the proliferation and inducing the apoptosis of colon cancer cells through a pathway independent of COX-2.


Human skeletal muscle nebulin sequence encodes a blueprint for thin filament architecture. Sequence motifs and affinity profiles of tandem repeats and terminal SH3.
Analysis of deduced protein sequence and structural motifs of approximately 5500 residues of human fetal skeletal muscle nebulin reveals the design principles of this giant multifunctional protein in the sarcomere. The bulk of the sequence is constructed of approximately 150 tandem copies of approximately 35-residue modules that can be classified into seven types. The majority of these modules form 20 super-repeats, with each super-repeat containing a 7-module set (one of each type in the same order). These super-repeats are further divided into eight segments: with six segments containing adjacent, highly homologous super-repeats, one single repeat segment consisting of 8 nebulin modules of the same type, and a non-repeat segment terminating with a SH3 domain at the C terminus. The interactions of actin, tropomyosin, troponin, and calmodulin with nebulin fragments consisting of either repeating modules or the SH3 domain support its role as a giant actin-binding cofilament of the composite thin filament. Such affinity profiles also suggest that nebulin may bind to tropomyosin and troponin to form a composite calcium-linked regulatory complex on the thin filament. The modular construction, super-repeat structure, and segmental organization of nebulin sequence appear to encode thin filament length, periodicity, insertion, and sarcomere proportion in the resting muscle.


Incomplete recovery of working heart function after twenty-four-hour preservation with a modified University of Wisconsin solution.
This study was designed to determine the function of isolated rabbit hearts after static preservation with modified University of Wisconsin solution for 24 hours. Commercially available University of Wisconsin solution, modified with CaCl2 1 mmol/L and 2,3-butanedione monoxime 30 mmol/L, was used as the preservative. After flushing the coronary vasculature with medium, hearts were submersion stored at 1 degree C to 4 degrees C. After preservation, isolated heart function at 37 degrees C was quantified for 30 minutes in a non-ejecting mode and for 4 hours ejecting at a physiologic workload. Fresh control hearts (n = 5) and University of Wisconsin solution-preserved hearts (n = 6) were studied. Nonworking (non-ejecting) left ventricular function of the two groups did not differ, except for peak rate of left ventricular pressure development which was higher for the University of Wisconsin solution hearts than for controls. When the hearts were subjected to a physiologic workload, however, left ventricular function of the two groups differed significantly. Three of the six University of Wisconsin solution hearts failed before the 4-hour perfusion end point, whereas all five control hearts maintained stable working function for the full 4 hours. The University of Wisconsin solution hearts, while in the ejecting mode, exhibited significantly impaired function. Mean values were as follows (p < 0.05): left ventricular systolic pressure (in millimeters of mercury), control 105 +/- 1, University of Wisconsin solution 86 +/- 4; peak rate of left ventricular pressure development (in millimeters of mercury per millisecond), control 3.33 +/- 0.11, University of Wisconsin solution 2.39 +/- 0.24; cardiac output (in milliliters per minute per gram), control 400 +/- 25, University of Wisconsin solution 288 +/- 26; stroke work (in milliJoules per gram), control 20.1 +/- 1.3, University of Wisconsin solution 11.9 +/- 1.1; left ventricular end-diastolic pressure (in millimeters of mercury), control 5.4 +/- 0.3, University of Wisconsin solution 10.2 +/- 1.3; peak aortic flow rate (in milliliters per minute), control 946 +/- 9, University of Wisconsin solution 659 +/- 44; millimoles of lactate produced in 30 min/Joule stroke work, control 0.50 +/- 0.06, University of Wisconsin solution 6.99 +/- 0.37. These results indicate that (1) hypothermic storage in this modified University of Wisconsin solution does not preserve hearts sufficiently to support a physiologic workload for an extended period and (2) assessment of post-preservation function with a non-ejecting heart model does not accurately predict the ability of the preserved heart to support a physiologic workload.


Operative management of skull base malignant tumors arising from the nasal cavity and paranasal sinus: recent strategies used in 25 cases.
Cancers of the paranasal sinuses and nasal cavity are the most common malignant tumors of the anterior and anterolateral skull base. The treatment of these tumors affecting the skull base is complex due to the significant anatomical features. We examined 25 patients, 17 males and 8 females with mean age 61 +/- 2 years. En bloc resections using anterior skull base resection, orbital resection, middle fossa resection, and combined procedures of these three resections were performed. Using a combination of adjuvant radiation and chemotherapy, we have achieved a 2-year disease-free survival rate of 90% in these cases. However, potential complications include cerebrospinal fluid leakage, meningitis, abscess formation, pneumocephalus, frontal brain contusion, trismus, and dysphagia as a functional complication. We believe that the optimal management of such malignant tumors involves a multimodal and multidisciplinary team approach. Here we present our recent institutional experience and treatment policy employed during the past 3 years.


The design trend in tissue-engineering scaffolds based on nanomechanical properties of individual electrospun nanofibers.
This paper especially highlights the finding that the mechanical properties of polymeric nanofibers can be tuned by changing the fiber size as well as the composition. For this purpose, the bending Young's modulus was determined using atomic force microscope by involving single-material (polyvinyl alcohol (PVA), polyethylene oxide (PEO 400K)) and composite nanofibers (polyvinyl alcohol/hyaluronic acid (PVA/HA), polyethylene oxide/chitosan (PEO 400K/CS)). The mechanical property, namely the bending Young's modulus, increases as the diameter of the fibers decreases from the bulk down to the nanometer regime (less than 200 nm). The ranking of increasing stiffness according to the AFM measurements of the three-point beam bending test are in agreement, and can be ranked: PEO 400K<PVA/HA≈PVA<PEO<400K/CS. According to our results, CS-based nanofibers are the stiffest (15 GPa) and the most resilient to erosion in an aqueous medium. Consequently, they possess the most appropriate attributes for bone, tendon, and cartilage tissue scaffold engineering. Nanofibers based on PVA (6 GPa) and PEO (3 GPa) are more elastic (a smaller bending Young's modulus) and therefore are the most suitable for skin and wound tissue scaffolds.


Metabolism of pyrene, a polycyclic aromatic hydrocarbon in freshwater turtles.
Reptile population decrease is an alarming trend all around the world. Yet little is known about the role of xenobiotics in this decrease. In this study, we investigated the metabolism of pyrene in three freshwater turtle species (Red-EARED sliders (Trachemys scripta elegans), Chinese pond turtles (Mauremys reevesii) and Chinese softshell turtles (Pelodiscus sinensis). Compared to other vertebrates, all turtles showed an unique metabolite distribution, pyrene-1-sulfate being the main metabolite. The observed low phase II enzyme metabolic rates raises the question of the effect of long-time exposure.


Surgical management for fecal incontinence.
Fecal incontinence is a socially debilitating condition that can lead to social isolation, loss of self-esteem and self-confidence, and depression in an otherwise healthy person. After the appropriate clinical evaluation and diagnostic testing, medical management is initially instituted to treat fecal incontinence. Once medical management fails, there are a few surgical procedures that can be considered. This article is devoted to the various surgical options for fecal incontinence including the history, technical details, and studies demonstrating the complication and success rate.


NMDA induces protein kinase C translocation in guinea pig cerebral synaptoneurosomes.
N-methyl-D-aspartate (NMDA)-induced translocation of protein kinase C from the cytosol to membrane fractions was examined by the [3H]phorbol 12,13-dibutyrate (PDBu) binding method in guinea pig cerebral synaptoneurosomes. Pretreatment of synaptoneurosomes with NMDA, but not that with quisqualate or kainate, induced changes in the distribution of [3H]PDBu binding in the cytosol and membrane fractions in a dose-dependent manner. The NMDA-induced changes of the binding were completely dependent on Ca2+ and inhibited by NMDA receptor antagonists Mg2+, 2-amino-5-phosphonovaleric acid and ketamine, but not by Zn2+. Glycine slightly potentiated the NMDA-induced changes of [3H]PDBu binding. NMDA stimulated Ca2+ uptake but not the phosphoinositide hydrolysis in the synaptoneurosomes. These results suggest that NMDA enhances Ca2+ influx through receptor-operated Ca2+ channels, increasing intracellular calcium concentration and thereby induces translocation of protein kinase C.


Development and Validation of the Korean Version of Hand-Foot Skin Reaction and Quality of Life Questionnaire (HF-QoL-K).
Given the growing number of cancer patients and the resulting increase in the administration of chemotherapeutic agents, convenient and effective methods for measuring the symptoms and quality of life associated with the hand-foot syndrome (HFS) are needed. Therefore, the aim of this study was to develop and validate the Korean version of the hand-foot skin reaction and quality of life questionnaire (HF-QoL-K), comprising a 20-item symptom domain and an 18-item daily activity domain. After we developed the HF-QoL-K, 209 Korean patients with gynecologic cancer who were undergoing chemotherapeutic agents relating the HFS were asked to fill in the questionnaire. The content validity, internal consistency reliability, and test-retest reliability were evaluated. The internal validity index, Cronbach's alpha coefficient, and intra-class correlation coefficient of the HF-QoL-K were 0.90, 0.958, and 0.825 (95% confidence interval [CI], 0.774-0.865), respectively. The scatter plot (Pearson correlation coefficient, 0.826) and the Bland-Altman plot for test-retest reliability were also acceptable. The HF-QoL-K instrument is a valid and reliable questionnaire for the measurement of the symptoms and quality of life in Korean cancer patients suffering HFS.


A comparative study between the effect of 17-β estradiol and angiotensin converting enzyme inhibitor on osteoporosis in ovariectomized rats.
Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) have been revealed in the pathogenesis of primary osteoporosis and other metabolic bone diseases. This study was designed to assess the effect of 17-β estradiol (E2) treatment and angiotensin converting enzyme inhibitor (ACEI), captopril, on osteoporosis induced by ovariectomy in rats and discussing the role of OPG/RANKL ratio in their action. Thirty two adult female rats were divided into four equal groups. Group I: control group, Group II: ovariectomized (OVX) non treated group, Group III: OVX rats treated with E2, Group IV: OVX rats treated with captopril. OVX rats showed a significant decrease in serum Ca2+ and OPG levels with significant increase in serum RANKL, osteocalcin, alkaline phosphatase activity and urinary hydroxyproline levels. Treatment with captopril as well as E2 led to a significant improvement in bone markers levels with a significant increase in OPG/RANKL ratio. Image analysis technique revealed that there was a significant improvement in cortical bone thickness (CBT) and mean trabecular bone density (TBD) in OVX rats treated with either E2 or ACEI. So, we can conclude that the protective effect of E2 and ACEI on osteoporosis may be mediated by influencing OPG/RANKL signaling.


AIEgens/Nucleic Acid Nanostructures for Bioanalytical Applications.
DNA occupies significant roles in life processes, which include encoding the sequences of proteins and accurately transferring genetic information from generation to generation. Recent discoveries have demonstrated that a variety of biological functions are correlated with DNA's conformational transitions. The non-B form has attained great attention among the diverse forms of DNA over the past several years. The main reason for this is that a large number of studies have shown that the non-B form of DNA is associated with gross deletions, inversions, duplications, translocations as well as simple repeating sequences, which therefore causes human diseases. Consequently, the conformational transition of DNA between the B-form and the non-B form is important for biology. Conventional fluorescence probes based on the conformational transitions of DNA usually need a fluorophore and a quencher group, which suffers from the complex design of the structure and tedious synthetic procedures. Moreover, conventional fluorescence probes are subject to the aggregation-caused quenching (ACQ) effect, which limits their application toward imaging and analyte detection. Fluorogens exhibiting aggregation-induced emission (AIE) have attracted tremendous attention over the past decade. By taking advantage of this unique behavior, plenty of fluorescent switch-on probes without the incorporation of fluorescent quenchers/fluorophore pairs have been widely developed as biosensors for imaging a variety of analytes. Herein, the recent progress in bioanalytical applications on the basis of aggregation-induced emission luminogens (AIEgens)/nucleic acid nanostructures are presented and discussed.


Work role inventory: a guide to job satisfaction.
The Miller-Carey Work Role Expectations model helps the nurse executive understand the dynamics which motivate managerial teams. The application of this model emphasizes the importance of assessing nurse manager's functions and responsibilities and suggests specific ways to enhance work motivation.


Degradation of pyrene by indigenous fungi from a former gasworks site.
Indigenous fungi isolated from soil of a former gasworks site were investigated in submerged cultures with pyrene as the sole carbon source. Five fungal strains capable of degrading pyrene included one strain of Trichoderma harzianum and four strains with characteristics of the genus Penicillium. These are identified as Penicillium simplicissimum, Penicillium janthinellum, Penicillium funiculosum and Penicillium terrestre. A maximum of 75% of 50 mg l(-1) and 67% of 100 mg l(-1) of pyrene was removed by the fast degrading strain P. terrestre at 22 degrees C during 28 days of incubation. The slower degrader P. janthinellum was able to remove 57% of 50 mg l(-1) and about 31.5% of 100 mg l(-1) pyrene. Degradation of pyrene is directly correlated with biomass development. To the best of our knowledge, this is the first time that fungi have been reported to use pyrene as the sole carbon and energy source. They may be ideal candidates for effective bioremediation of polycyclic aromatic hydrocarbons.


Is there a relationship between the structure of Irish psychiatric multidisciplinary teams and patient outcome?
This study evaluated the structure of psychiatric multidisciplinary teams within eight Irish Health Boards over a two year period (1997 and 1998). Furthermore, it assessed the relationship between team structure and three measures of psychiatric outcome within individual Health Board areas. The findings suggest a significant variation between Health Boards in relation to the staffing of psychiatric multidisciplinary teams. Although there was no evidence that the structure of multidisciplinary teams influenced suicide rates or duration of hospitalization, it had a significant independent effect on admission rates to psychiatric units.


Whole blood long-chain n-3 fatty acids as a measure of fish oil compliance in children with acute lymphoblastic leukemia: a pilot study.
Long-chain n-3 fatty acids (n-3 LCPUFA) may prevent chemotherapy-induced hyperlipidemia in children with acute lymphoblastic leukemia (ALL). However, compliance could be a problem and intake-biomarker correlations may be affected by bodyweight and blood transfusions. We assessed whole blood n-3 LCPUFA three times during the first 83 days of treatment in six 1-17-year-old children with ALL, who received 2.4-4.9 g/d n-3 LCPUFA depending on bodyweight. Mean compliance was 73%, which resulted in a 2.5-fold increase in blood n-3 LCPUFA irrespective of blood transfusions. The correlation between relative blood content of n-3 LCPUFA and intake in g/d across the study period was strong (r=0.76, p=0.001). When n-3 LCPUFA was expressed in absolute concentrations and intake per kg bodyweight the correlation decreased (r=0.39, p=0.164) and was driven by baseline values. Thus, relative content of n-3 LCPUFA in blood reflects fish oil compliance in children with ALL despite blood transfusions and differences in bodyweight.


[Cataract surgery in 2000].
The authors evaluate a questionnaire survey concern to cataract surgery in the Czech Republic. They present the results of all 58 ophthalmological departments where cataract is operated. In the CR in 2000 a total of 49,804 eyes were operated. In 94.4% of operations the technique of phacoemulsification was used. Primary implantation of an intraocular lens was used in 99% of the operated patients. In more than 27% for correction of aphakia a soft intraocular lens was used. Almost 30% of the operated patients had one-day surgery. In coming years a greater need for these operations may be foreseen. To avoid longer waiting periods more financial means will be needed for new types of materials or a solution of the problem of financial participation of the patient in meeting the costs of surgery.


Evaluating diagnostic tests.
Although much has been written on the role of randomized controlled trials and mechanistic reasoning in the evaluation of therapeutic treatments, philosophers of medicine have not yet turned their attention to the question of how diagnostic tests and procedures should be evaluated. I aim to begin to fill this gap by examining each of the following questions: What is the best way to determine the accuracy of a diagnostic test? What is the best way to determine the clinical effectiveness of a diagnostic test? Can an accurate diagnostic test be considered medically valuable even if it is not clinically effective? I argue that while diagnostic accuracy is a minimum requirement for both clinical effectiveness and medical value, accuracy and effectiveness are not sufficient for determining the value of a diagnostic test, because diagnostic value extends beyond patient outcomes.