Methergin testing with angiographically normal coronary arteries.
To evaluate the incidence of spasm in patients with angiographically normal coronary arteries or with stenosis less than or equal to 50%, methergin testing was done consecutively in 1,200 patients (742 men and 458 women). The methergin test was performed 850 times during coronary angiography and 350 times after it. The test was globally positive in 11% (127 of 1,200 patients), positive in 7% among 921 patients presenting with atypical chest pain, 13% of 31 patients with effort angina, 54% of 54 with angina at rest, 57% of 53 with Prinzmetal's angina, 3% of 59 with acute myocardial infarction and 1% of 82 miscellaneous patients without chest pain. Another test was done in 291 patients after blockade of the cardiac autonomous nervous system with 0.04 mg/kg of atropine and 2 mg/kg of labetolol. The frequency of positive results in the methergin test increased after blockade from 8 to 19% (p less than 0.01). The increase of positive results was especially obvious among patients with atypical chest pain (from 6 to 14%). Thus, frequency of spasm in these patients with normal coronary arteries or without significative lesions was 11%. This incidence was influenced by the composition of the patient population and increased with blockade of the cardiac autonomous nervous system.


Anthralin stability in various vehicles.
The stability of anthralin in white soft paraffin, Lassar's paste, and Unguentum Merck was assessed using a sensitive assay for degradation products, over a 1-year period. The stability was found to vary with concentration, weaker preparations being less stable. Significant degradation was observed in Unguentum Merck, and this increased when salicylic acid was present. Preparations with Unguentum Merck could be stabilized with ascorbic or oxalic acid. Salicylic acid stabilized anthralin in Lassar's paste but had a negligible effect in white soft paraffin. Preparations with white soft paraffin were relatively stable.


Effects of ACTH6-9-Pro-Gly-Pro Peptide on the Levels of Pro- and Anti-Inflammatory Cytokines in Wistar Rats under Conditions of Chronic Restraint Stress.
We evaluated the effect of ACTH6-9-Pro-Gly-Pro (ACTH6-9-PGP) peptide on the serum levels of pro- and anti-inflammatory cytokines in experimental animals under conditions of chronic restraint stress. Stress exposure over 2 weeks led to an increase in the levels of IL-1β, IL-6, and IFNγ in rats. Daily intraperitoneal injection of ACTH6-9-PGP in a dose of 5 μg/kg before stress exposure significantly decreased the levels of IL-6 and IFNγ by 4.8 and 49.3% respectively. Administration of the peptide in a dose of 50 μg/kg decreased the levels of IL-1β and IFNγ by 51.2 and 39.7%, respectively. However, no changes in the cytokine levels were observed after injection of the peptide in a dose of 500 μg/kg. Thus, ACTH6-9-PGP administered in doses of 5 and 50 μg/kg prevented the stress-induced changes in the levels of pro- and inflammatory cytokines.


Use of hydrogen peroxide vapour & plasma irradiation in combination for quick decontamination of closed chambers.
Various conventional methods such as gaseous, vapour and misting systems, fogging, manual spray and wipe techniques employing a number of chemical agents are used for decontamination of enclosed spaces. Among all these methods, use of aerosolized formaldehyde is the most preferred method due to cost-effectiveness and practical aspects. However, being extremely corrosive in nature generating very irritating fumes and difficulty in maintaining a high level of gas concentration, many laboratories prefer the vaporization of hydrogen peroxide (H 2 O 2 ) as an alternative. We present here the results of using H 2 O 2 vapour in combination with plasma irradiation for quick decontamination of closed chambers. The present study describes a decontamination method, using plasma irradiation in combination with H 2 O 2 (5%). Effect of plasma irradiation and H 2 O 2 on the viability of bacterial spores (Bacillus subtilis), Chikungunya and Kyasanur Forest Disease viruses was assessed. Data suggest that with the combination of H 2 O 2 vapour and plasma irradiation, within short time (three minutes), decontamination of surfaces and space volume could be achieved. Although it showed damage of spores present on the strips, it did not show any penetration power. The results were encouraging, and this method was found to be efficient for achieving surface sterilization in a short time. This application may be useful in laboratories and industries particularly, those working on clean facility concept following good laboratory and manufacturing practices.


Role of endoscopic third ventriculostomy in patients with communicating hydrocephalus: an evaluation by MR ventriculography.
Post-tubercular meningitic hydrocephalus (TBMH) and post-traumatic hydrocephalus (PTH) is often considered a contraindication for endoscopic third ventriculostomy (ETV), as it is mostly of communicating type in these cases. The aim of the present study was to define the role of ETV in patients with communicating hydrocephalus. Ten consecutive patients of TBMH, PTH and postneurocysticercus (NCC) hydrocephalus were formed the study group. Diagnosis of communicating hydrocephalus was made using magnetic resonance ventriculography (MRV). If contrast was seen coming out from the ventricular system into the basal cisterns, it was considered as communicating hydrocephalus. Patients with clinical and imaging evidence of raised intracranial pressure and failed medical treatment were taken up for ETV. All patients were studied by preoperative and postoperative MRV. Success of the procedure was assessed by the improvement in clinical and imaging parameters on postprocedure follow-up in all these cases. Technically successful ETV was performed in all 10 patients. Overall success rate of ETV in communicating hydrocephalus was 70% (n = 7). The shunt surgery was performed in the remaining three patients with ETV failure. One patient developed complication following postoperative MRV and was managed conservatively. We conclude that ETV is effective in post-TBM, post-traumatic communicating and post-NCC communicating hydrocephalus and should be considered as initial surgical option for cerebrospinal fluid diversion in these patients. MRV is a relatively safe technique to ascertain the patency of subarachnoid space as well as ETV stoma.


Quantitation of the effect of L-carnitine on the levels of acid-soluble short-chain acyl-CoA and CoASH in rat heart and liver mitochondria.
The steady state levels of mitochondrial acyl-CoAs produced during the oxidation of pyruvate, alpha-ketoisovalerate, alpha-ketoisocaproate, and octanoate during state 3 and state 4 respiration by rat heart and liver mitochondria were determined. Addition of carnitine lowered the amounts of individual short-chain acyl-CoAs and increased CoASH in a manner that was both tissue- and substrate-dependent. The largest effects were on acetyl-CoA derived from pyruvate in heart mitochondria using either state 3 or state 4 oxidative conditions. Carnitine greatly reduced the amounts of propionyl-CoA derived from alpha-ketoisovalerate, while smaller effects were obtained on the branched-chain acyl-CoA levels, consistent with the latter acyl moieties being poorer substrates for carnitine acetyltransferase and also poorer substrates for the carnitine/acylcarnitine translocase. The levels of acetyl-CoA in heart and liver mitochondria oxidizing octanoate during state 3 respiration were lower than those obtained with pyruvate. The rate of acetylcarnitine efflux from heart mitochondria during state 3 (with pyruvate or octanoate as substrate, in the presence or absence of malate with 0.2 mM carnitine) shows a linear response to the acetyl-CoA/CoASH ratio generated in the absence of carnitine. This relationship is different for liver mitochondria. These data demonstrate that carnitine can modulate the aliphatic short-chain acyl-CoA/CoA ratio in heart and liver mitochondria and indicate that the degree of modulation varies with the aliphatic acyl moiety.


Aerosol capture and coronavirus spike protein deactivation by enzyme functionalized antiviral membranes.
The airborne nature of coronavirus transmission makes it critical to develop new barrier technologies that can simultaneously reduce aerosol and viral spread. Here, we report nanostructured membranes with tunable thickness and porosity for filtering coronavirus-sized aerosols, combined with antiviral enzyme functionalization that can denature spike glycoproteins of the SARS-CoV-2 virus in low-hydration environments. Thin, asymmetric membranes with subtilisin enzyme and methacrylic functionalization show more than 98.90% filtration efficiency for 100-nm unfunctionalized and protein-functionalized polystyrene latex aerosol particles. Unfunctionalized membranes provided a protection factor of 540 ± 380 for coronavirus-sized particle, above the Occupational Safety and Health Administration's standard of 10 for N95 masks. SARS-CoV-2 spike glycoprotein on the surface of coronavirus-sized particles was denatured in 30 s by subtilisin enzyme-functionalized membranes with 0.02-0.2% water content on the membrane surface.


Implantable Cardioverter-Defibrillator for Primary Prevention in Asia.
In a contemporary setting, where the risk of sudden cardiac death (SCD) is low, heart failure management is improved, and technology is advanced, identifying the patients who would benefit the most from an implantable cardioverter-defibrillator (ICD) treatment for primary prevention remains a challenge. The prevalence of SCD is lower in Asia when compared with the United States/Europe (35-45 per 100,000 person-years vs 55-100 per 100,000 person-years, respectively). Nevertheless, this should not explain the enormous gap in ICD's utilization among eligible candidates (∼12% in Asia vs ∼45% in the United States/Europe). The disparity between Asia and Western countries, together with significant variation among the Asian population and the previously mentioned challenges, requires an individualized approach and specific regional recommendation, especially in countries with limited resources where ICDs are being extremely underutilized This review focuses on the current knowledge of ICD therapy for SCD prevention and how to improve patient and device selection.


IARC and HHS lists of carcinogens: regulatory use based on misunderstanding of the scope and purpose of the lists.
In the last two decades there has been a tremendous increase in data on carcinogenic activity in experimental animals. While there have been few additions to the list of human carcinogens based on human data, the number of carcinogens based on animal data continues to increase unabated. The International Agency for Research on Cancer (IARC) list of carcinogens grew out of the IARC Monograph Series. The evidence classification system used to prepare the IARC lists in 1980, 1982, and 1988 is based on the sufficiency, i.e., strength, of the evidence of carcinogenic activity in one or more studies, not a full weight-of-the-evidence evaluation of all relevant data. Titles of categories of animal evidence referring to human risk potential were based on a presumption: "for practical purposes . . . as if." No evaluation was made of the predictive relevance of animal data to human risk. The IARC listing did not involve evaluation of potency or mechanism and was intended as a useful input but not as a basis for regulatory or legislative decisions. The Department of Health and Human Services (HHS) lists in the Annual Reports on Carcinogens are selected from the IARC lists and from reports of positive bioassay experiments conducted by the National Toxicology Program (NTP). The reports on the NTP bioassays relate to the strength of the evidence in each experiment and recognize that a "wider analysis" is necessary for determination of human risk. Because of a misunderstanding of the limited scope of the analysis involved, the IARC and HHS lists have recently been used as a basis for legislative and regulatory decisions. Examples of unanticipated use of the lists as triggers for regulatory and legislative decisions will be discussed. Some recommendations to mitigate the consequences of past unanticipated use of the lists and to prevent further misuse are discussed.


Biologic disease-modifying anti-rheumatic drugs and the risk of non-vertebral osteoporotic fractures in patients with rheumatoid arthritis aged 50 years and over.
Prevention of bone mineral density loss in rheumatoid arthritis (RA) has been associated with use of biologic disease-modifying anti-rheumatic drugs (DMARDs). However, in this study, we could not demonstrate a reduction in the risk of non-vertebral fractures. Additional research is required to clarify the impact of biologic DMARDs on fracture risk in RA. Small studies have suggested biologic DMARDs preserve bone mineral density at 6-12 months. Our objective was to determine the association between biologic DMARD use and the risk of non-vertebral osteoporotic fractures in RA subjects aged ≥50 years. A nested case-control study was conducted using Quebec physician billing and hospital discharge data. RA subjects were identified from International Classification of Disease-9/10 codes in billing and hospitalisation data and followed from cohort entry until the earliest of non-vertebral osteoporotic fracture, death, or end of study period. Controls were matched to cases (4:1 ratio) on age, sex, and date of cohort entry. Biologic DMARD exposure was defined as being on treatment for ≥180 days pre-fracture (index). Conditional logistic regression was used, adjusting for indicators of RA severity, comorbidity, drugs influencing fracture risk, and measures of health care utilisation. Over the study period, 1,515 cases were identified (6,023 controls). The most frequent fracture site was hip/femur (42.3%). In total, 172 subjects (49 cases and 123 controls) were exposed to biologic DMARDs. The median duration of exposure was 735 (interquartile range (IQR), 564) and 645 (IQR, 903) days in cases and controls, respectively. We were unable to demonstrate an association between biologic DMARDs and fracture risk (odds ratio, 1.03; 95% confidence interval, 0.42-2.53). RA duration significantly increased the fracture risk. Despite the positive impact of biologic DMARDs on bone remodelling observed in small studies, we were unable to demonstrate a reduction in the risk of non-vertebral osteoporotic fractures in older adults with RA.


Berberine protects against lipopolysaccharide-induced intestinal injury in mice via alpha 2 adrenoceptor-independent mechanisms.
To investigate the mechanisms responsible for the protective action of berberine (Ber) against gut damage in endotoxemic mice. Male BALB/c mice were administered intragastrically with distilled water (0.1 mL/10 g), Ber (50 mg/kg) alone, yohimbine (2 mg/kg) alone, or Ber (50 mg/kg) in combination with yohimbine (2 mg/kg) for 3 d. On the third day, lipopolysaccharide (LPS, 18 mg/kg) or normal saline was intraperitoneally injected one hour after the intragastric administration. Following the treatment, intestinal injury in the ileum was histopathologically accessed; enterocyte apoptosis was examined using TUNEL method; Toll-like receptor 4 (TLR4) mRNA expression was measured using RT-PCR assay; inhibitor protein-κBα (I-κBα) phosphorylation and myeloperoxidase content were examined using Western blloting. The macrophage inflammatory protein-2 (MIP-2) production was measured using ELISA assay. Mice challenged with LPS caused extensive ileum injury, including a significantly increased injury score, decreased intestinal villus height, reduced gut mucosal weight and increased intestinal permeability. Furthermore, LPS significantly induced enterocyte apoptosis, increased TLR4 mRNA expression, I-κBα phosphorylation, MIP-2 production and myeloperoxidase content in the ileum. Pretreatment with Ber significantly alleviated all the alterations in the ileum in the endotoxemic mice. Pretreatment with the α2-adrenoceptor antagonist yohimbine did not block the protective action of Ber against LPS-induced intestinal injury. In addition, treatment with yohimbine alone did not prevent LPS-induced intestinal injury. Pretreatment with Ber provides significant protection against LPS-induced intestinal injury in mice, via reducing enterocyte apoptosis, inhibiting the TLR4-nuclear factor κB-MIP-2 pathway and decreasing neutrophil infiltration that are independent of α2-adrenoceptors.


Regional variations in particulate cyclic AMP dependent-protein kinase binding activity in the gerbil hippocampus following transient forebrain ischemia by [3H]cyclic AMP binding.
Changes in the binding of [3H]cyclic AMP as an indicator of particulate cyclic AMP-dependent protein kinase (AMP-DPK) binding activity following transient forebrain ischemia were studied in the gerbil using in vitro autoradiography. [3H]Cyclic AMP binding in the strata pyramidale and lacunosum-moleculare of the hippocampal CA1, the stratum pyramidale of the CA3, and the dentate gyrus decreased transiently in the early postischemic phase but then recovered. However, [3H]cyclic AMP binding in the strata pyramidale and radiatum of the CA1, the granular layer of the dentate gyrus, and the upper layer of the cortex decreased again 7 days after ischemia. In the CA4 subfield and the lower layer of the cortex, the binding showed no significant alterations after ischemia. Administration of pentobarbital prior to the induction of ischemia prevented the decrease in [3H]cyclic AMP binding in the CA1 subfield 6 h and 7 days after ischemia, and showed protective effects against neuronal death of the CA1 pyramidal cells 7 days after ischemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 subfield. Furthermore, postischemic reduction of [3H]cyclic AMP binding in the histologically intact cerebral cortex, CA3, and dentate gyrus may be the reflection of cellular dysfunction after energy failure.


Complete Genome Sequence of a Strain of Bifidobacterium pseudolongum Isolated from Mouse Feces and Associated with Improved Organ Transplant Outcome.
Here, we report the complete genome sequence of Bifidobacterium pseudolongum strain UMB-MBP-01, isolated from the feces of C57BL/6J mice. This strain was identified in microbiome profiling studies and associated with improved transplant outcome in a murine model of cardiac heterotypic transplantation.


Phosphoinositides in chemotaxis.
Phosphatidylinositol lipids generated through the action of phosphinositide 3-kinase (PI3K) are key mediators of a wide array of biological responses. In particular, their role in the regulation of cell migration has been extensively studied and extends to amoeboid as well as mesenchymal migration. Through the emergence of fluorescent probes that target PI3K products as well as the use of specific inhibitors and knockout technologies, the spatio-temporal distribution of PI3K products in chemotaxing cells has been shown to represent a key anterior polarity signal that targets downstream effectors to actin polymerization. In addition, through intricate cross-talk networks PI3K products have been shown to regulate signals that control posterior effectors. Yet, in more complex environments or in conditions where chemoattractant gradients are steep, a variety of cell types can still chemotax in the absence of PI3K signals. Indeed, parallel signal transduction pathways have been shown to coordinately regulate cell polarity and directed movement. In this chapter, we will review the current role PI3K products play in the regulation of directed cell migration in various cell types, highlight the importance of mathematical modeling in the study of chemotaxis, and end with a brief overview of other signaling cascades known to also regulate chemotaxis.


Effect of oxidative stress on membrane phospholipid and protein organization in human erythrocytes.
Membrane phospholipid and protein organization was studied in intact human erythrocytes exposed to phenylhydrazine, an oxidative agent inducer. The evaluation of the membrane phospholipid and protein organization was carried out in terms of asymmetric distribution across the membrane bilayer for the phospholipids, and in terms of accessibility of cleavable sites present on the outer membrane surface for the proteins. Treatment of phenylhydrazine-exposed erythrocytes either with bee venom phospholipase A2 or with trinitrobenzenesulfonic acid indicated that phosphatidylserine (PS), which is the only phospholipid not formally present on the outer leaflet of the membrane, was translocated to the outer surface of the cell membrane. The extent of this phenomenon was directly proportional to the concentration of the oxidant having a peak value at 0.1 mM. Phosphatidylcholine and phosphatidylethanolamine conserved their original distribution across the erythrocyte membrane throughout the study. The oxidant, at a dose which did not induce any modification of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis cytoskeleton membrane protein pattern, did not provoke any alteration of the membrane protein surface architecture, although the translocation of PS to the membrane outer leaflet in intact erythrocytes was present.


Mapping unmet supportive care needs, quality-of-life perceptions and current symptoms in cancer survivors across the Asia-Pacific region: results from the International STEP Study.
To assess the supportive care needs, quality of life (QoL) and symptoms of patients with cancer after the end of first-line treatments and into survivorship in Asian countries using Australian data as benchmark. A cross-sectional survey was carried out in Australia and eight high-income (HICs) and low-/middle-income (LMICs) Asian countries (China, Japan, Hong Kong SAR, South Korea, Myanmar, Thailand, India, Philippines) using validated scales (Cancer Survivors Unmet Needs scale), physical-symptom concerns (Cancer Survivors Survey of Needs subscale) and a single-item measure of global QoL perception. Data were collected from 1873 patients. QoL was highest in Australia and all other countries had significantly lower QoL than Australia (all P < 0.001). One-quarter of the patients reported low QoL (scores 1-3/10). The most frequently reported symptoms were fatigue (66.6%), loss of strength (61.8%), pain (61.6%), sleep disturbance (60.1%), and weight changes (57.7%), with no difference in symptom experience between Australian data and all other countries, or between HICs and LMICs. Unmet needs of moderate/strong level were particularly high in all aspects assessed, particularly in the area of existential survivorship (psychosocial care) and receiving comprehensive cancer care. Australia and HICs were similar in terms of unmet needs (all low), but LMICs had a significantly higher number of needs both compared with Australia and HICs (all P < 0.001). Health care systems in Asian countries need to re-think and prioritize survivorship cancer care and put action plans in place to overcome some of the challenges surrounding the delivery of optimal supportive cancer care, use available resource-stratified guidelines for supportive care and test efficient and cost-effective models of survivorship care.


Hydroxyapatite and ionic liquid coupled with hybrid membranes for toxic pollutant removal and remediation.
Access to clean water is the mandatory requirement for every living being to sustain life. So, membrane-based integrated approach of adsorption and separation technology has recently been preferred by scientists over other conventional techniques, for wastewater treatment. Current research focused on the synthesis of novel imidazolium (A1) based IL, which was further functionalized with hydroxyapatite (HAp; extracted from Labeo rohita scales), to create possible solutions towards environmental remediation. Cellulose acetate (CA) was used for the fabrication of three different ionic liquid membranes. All the synthesized products were characterized by FTIR, XRD and TGA. Two dyes of different nature, i.e., congo red (anionic) and crystal violet (cationic) were selected because of their highly toxic and carcinogenic effects, for batch adsorption experiments. Antibacterial activity of the synthesized membranes was also evaluated against S. aureus. Results of the study revealed that CA-HA1 1:2 acted as the best adsorbent towards the removal of crystal violet, exhibiting removal efficiency of 98% with the contact time of 24 h while in case of congo red adsorption, CA-HA1 (1:2) proved as prime adsorbent with the removal efficiency of 96% for the same preceding contact time. Considering the antibacterial character of the synthesized membranes, CA-A1 (1:1) emerged as very efficient antibacterial agent with the inhibition zone of 50 mm after 48 h. The overall behavior of monolayer and multilayer adsorption was witnessed for both dyes while kinetic studies favored the pseudo-second order reaction for all adsorbents.


Begomovirus characterization, and development of phenotypic and DNA-based diagnostics for screening of okra genotype resistance against Bhendi yellow vein mosaic virus.
The leaf sample from okra plants showing the yellow vein mosaic disease symptoms was collected in Karnataka state, India. The genome of the virus was amplified, cloned and sequenced. Sequence analysis revealed that the viral genome (GU112065) is 2,741 bp in length and genome is similar to that of monopartite begomoviruses originating from the Old World, with seven conserved ORFs. Further nucleotide (nts) sequence comparisons showed that the genome has the highest sequence identities of 96.1 % with Bhendi yellow vein mosaic virus (BYVMV) (GU112057) and 89.7 % with okra yellow vein mosaic virus (OYVMV) (AJ002451) infecting okra in India and Indian subcontinent. These results suggested that the isolate is a new strain of BYVMV. To identify the resistance source to BYVMV, the okra genotypes were screened under both artificial and natural conditions. None of the genotypes showed immunity to the disease. However, the genotypes Nun 1145 and Nun 1144 showed moderate resistance and genotypes M10, Nun 1142, Nun 1140 showed moderately susceptible reactions under both glass house and field conditions. Further, dot-blot hybridization using nonradioactive (digoxigenin) DNA probe showed that the virus was also detected in the symptomless plants.


Evaluation of the nutrient foramen as a suitable landmark in spinal surgery.
The posterior cervical approach is a very popular surgical procedure. Because of the slope-shaped laminae, a suitable landmark for laminectomy, laminoplasty, and pedicle screw placement does not exist. We investigated the association between the nutrient foramen and spinal canal, and the safety of bone gutter placement using nutrient foramina for safe and effective spinal surgery. Observational SETTING: University Hospital PATIENT SAMPLES: Two hundred and sixty-six consecutive patients treated for cervical pathologies in our university hospital between January 2005 and December 2019. We identified the location of nutrient foramina and their anatomical association with the spinal canal using preoperative three-dimensional CT scanning. We studied the distance between each foramen and the spinal canal, and the angle of the nutrient foramen at each vertebral level. The nutrient foramina were always located outside the spinal canal, with an average distance of +3.06±1.74 mm. The lower the spinal level, the closer the nutrient foramen to the spinal canal. The nutrient foramen can be considered a reliable landmark when using the posterior cervical approach.


Trends in overweight and obesity prevalence in Chilean children: comparison of three definitions.
To compare trends in prevalence of overweight and obesity among Chilean children using three different criteria. Descriptive cross-sectional school-based study to analyse these trends in 6-y-old boys and girls who entered first grade in 1987, 1990, 1993, 1996 and 2000. Gender-specific prevalence of overweight and obesity were determined with three criteria: weight for height (W-H) Z-scores compared to NCHS 1977; present reference used by the Ministry of Health; and body mass index (BMI) compared to the revised US CDC Growth Charts with cut-off values of P85-95 and P-95 and IOTF reference with cut-offs extrapolated from an adult BMI of 25 and 30. The prevalence of overweight determined by W-H (WHO) increased from 15% in 1987 to 20% in 2000 for boys and from 17.2 to 21.8% for girls. With BMI-CDC, the increase was from 13.2 to 19.2% for boys and 12 to 18.5% for girls. With BMI-IOTF, rates were very similar. Prevalence of obesity using W-H (WHO) increased from 6.5% in 1987 to 17% in 2000 for boys and from 7.8 to 18.6% for girls. Using BMI-CDC, the increase was from 5.1 to 14.7% for boys and from 4 to 15.8% for girls; using BMI-IOTF prevalence estimates were much lower. Obesity prevalence in children has increased over time, and trends are similar independent of criteria. The reference used to define prevalence is important since it provides different estimates. Policy makers should be aware that a spurious drop in prevalence may appear if the IOTF reference is compared to the other criteria.


Spectral changes resulting from the interaction of some N-alkyl nitrosamines and rat liver microsomes.
Dimethyl (DMN) and diethyl nitrosamine (DEN) do not give characteristic spectral changes upon interaction with rat liver microsomes, while dipropyl (DPN) and dibutyl (DBN) nitrosamine cause type I spectral changes. The spectral binding constant is 100 mM for DPN and 1.17 mM for DBN. The maximal spectral change is 3.2 X 10(6) and 1.0 X 10(6) absorbance units per milligram protein for DPN and DBN respectively.


A comparison of signal detection techniques in the multifocal electroretinogram.
A common task in the analysis of the multifocal electroretinogram (mfERG) is determining which retinal areas have preserved signal in recordings which are attenuated by the effects of disease. Several automated methods have been proposed for signal detection from multifocal recordings, but no systematic study has been published comparing the performance of each. This article compares the sensitivity and specificity of expert human scoring with three different automated methods of mfERG signal detection. Recordings from control subjects were artificially modified to simulate decrease in signal amplitudes (attenuation) as well as total signal loss. Human scorers were able to identify areas with preserved signal at both low and high attenuation levels with a high specificity (minimum 0.99), sensitivities ranged from 0.2 to 0.94. Automated methods based on template correlation performed better than chance at all attenuation levels, with a slide fit method having the best performance. Signal detection based on signal to noise ratio performed poorly. In conclusion automated methods of signal detection can be used to increase signal detection sensitivity in the mfERG.


[Relation of short-latency processes in the visual system of the rabbit to pre-excitation inhibition in the retina].
Low-amplitude early negative potential preceding the positive component of primary responses to light was observed in the optic tract, superior colliculus, lateral geniculate body and visual cortex in chronic experiments with special recording schedule in rabbits. The early negative potential proved to be genetically connected with the "a"-wave of the electroretinogram. During the suppression of all but the "a"-wave ERG components with glycine, the early negative potential alone is preserved in the central structures of the visual system.


Nicardipine HCl: clinical experience in patients undergoing anaesthesia for intracranial aneurysm clipping.
Previous studies have reported haemodynamic interactions between dihydropyridine calcium antagonists and general anaesthesia. During anaesthesia for intracranial aneurysm surgery, we prospectively compared haemodynamic values obtained from 13 patients being treated with nicardipine HCl (0.15 mg.kg-1.hr-1 IV) for cerebral vasospasm against values obtained from 11 untreated controls. Prior to induction of anaesthesia, nicardipine-treated patients had significantly elevated mean +/- SD cardiac index (5.67 +/- 1.30 vs 3.99 +/- 0.73 L.min-1.m-2) while MAP (86 +/- 10 vs 99 +/- 14 mmHg) and systemic vascular resistance (647 +/- 227 vs 1141 +/- 404 dynes.sec-1.cm-5) were reduced. Heart rate, CVP, and PACWP were similar between groups. Anaesthesia induction and tracheal intubation resulted in similar haemodynamic values between groups with the exception of CVP (10 +/- 5 vs 5 +/- 2 mmHg) and PACWP (15 +/- 5 vs 8 +/- 3 mmHg) which were elevated in the nicardipine group (P less than 0.01). Mannitol infusion and deliberate hypotension resulted in nearly identical haemodynamic responses in both groups. Nicardipine-treated patients required more intravenous fluids during the operative procedure (2.4 +/- 0.3 L vs 1.5 +/- 0.4 L, P less than 0.05) and were less likely to require isoflurane supplementation to morphine sulphate/nitrous oxide anaesthesia (P less than 0.01). In summary, our experience with nicardipine HCl revealed no major untoward effects with respect to maintenance of intraoperative haemodynamic stability despite continuous antivasospasm therapy with this vasodilator.


The mouse Kin-17 gene codes for a new protein involved in DNA transactions and is akin to the bacterial RecA protein.
We have sought to characterize the molecular basis of the sensitivity to ionising radiation and to identify the genes involved in the cellular response of mammalian cells to such radiation. Using the Escherichia coli model, we tested the hypothesis that functional domains of RecA protein are represented in proteins of mammalian cells. We review here the results obtained in the detection of nuclear proteins of mammalian cells that are recognized by anti-RecA antibodies. We have called them kin proteins. Kin proteins likely play a role in DNA metabolism. We summarize the cloning of the mouse Kin-17 cDNA and our work on the identification and preliminary characterisation of the biochemical properties of mouse kin17 protein, a new nuclear protein able to recognize bent DNA and suspected to be involved in illegitimate recombination. We briefly describe our latest experiments on the molecular characterisation of the mouse Kin-17 gene. Finally, we discuss the properties of kin17 protein and the possible participation of kin17 protein in DNA transactions like transcription or recombination.


Temporal lobe seizures triggering recurrent syncope by ictal asystole.
Described here is a case of a patient with left temporal lobe epilepsy and recurrent complex partial seizures associated with asystole. The posturing and myoclonus caused by the nonepileptogenic syncope during the asystole gave the appearance of secondary generalization prompting a surgical evaluation. A distinct atonic phase that interrupts the transition from a complex partial semiology to generalization is a critical clue to the presence of ictal asystole and is easily detected by video/EEG monitoring.


Blood levels of dioxins, furans, dioxin-like PCBs, and TEQs in general populations: a review, 1989-2010.
A comprehensive worldwide literature review of blood levels of dioxins and dioxin-like compounds in non-exposed adult general populations was performed. The studies published in 1989-2010 reporting information on polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-ortho-PCBs (nPCBs), mono-ortho-PCBs (mPCBs) levels and Toxic Equivalencies (TEQs, a summary weighted measure of their combined toxicity) were reviewed. TEQs were calculated using as standard the most recent WHO 2005 reevaluation of Toxic Equivalency Factors (TEFs). Weighted multiple regression analyses adjusted for year, subject's age, type of sample analyzed, method used for values below detection limit, and central tendency measure used were performed for each congener and standardized TEQs (log-transformed). We identified 187 studies regarding 29,687 subjects of 26 countries. Year of blood collection ranged from 1985 to 2008. The studies reporting congener levels 161. In adjusted analyses, European countries showed higher levels of most dioxin-like congeners and TEQs. A strong positive association of subjects' age with most congeners and with TEQ values was found, confirming previous findings. Significant decreases over time (1985-2008) were documented for PCCDs, PCDFs, and TEQs including their contributions. No significant decrease was found for non-ortho-PCBs, notably PCB 126. Only some mono-ortho-PCBs showed clear significant declines. Accordingly, TEQs including only PCB contribution did not decrease over time. In interpreting these findings, it should be considered that for dioxin-like PCBs the analysis period was shorter (17 years), since these compounds were first measured in 1992.


Dramatic nondipole effects in low-energy photoionization: experimental and theoretical study of Xe 5s.
The Xe 5s nondipole photoelectron parameter gamma is obtained experimentally and theoretically from threshold to approximately 200 eV photon energy. Significant nondipole effects are seen even in the threshold region of this valence shell photoionization. In addition, contrary to previous understanding, clear evidence of interchannel coupling among quadrupole photoionization channels is found.


Role of the haem oxygenase-carbon monoxide pathway in insulin-induced hypothermia: evidence for carbon monoxide involvement.
A reduction of body temperature (T(b)) is a phenomenon concomitant with hypoglycaemia in mammals. Haem oxygenase (HO) catalyses the metabolism of haem to biliverdin, free iron and carbon monoxide (CO). Recently, the HO pathway has been shown to play an important role in thermoregulation. The present study was designed to test the hypothesis that the HO pathway plays a role in insulin-induced hypothermia and that CO, rather than free iron or biliverdin, is the HO product involved in this response. Body temperature (T(b)) of Wistar rats was measured by biotelemetry. Infusion of insulin (0.2 U/kg per h, i.v.) caused a significant drop in T(b). Intracerebroventricular (i.c.v.) administration of zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG, a HO inhibitor, 200 nmol) combined with saline infusion had no effect on T(b) but increased insulin-induced hypothermia significantly. The i.c.v administration of neither the iron chelator deferoxamine (250 microg) nor biliverdin (152 nmol) altered the hypothermic response to insulin, whereas CO-saturated saline significantly reduced insulin-induced hypothermia. These data indicate that the HO pathway prevents excessive drops in T(b) in insulin-induced hypothermia. Because biliverdin and iron had no effect, while CO significantly reduced the hypothermic response elicited by insulin infusion, these data imply that CO is the HO product involved in the thermoregulatory effect of insulin-induced hypothermia.


Pancreatic imaging using diffusivity mapping - Influence of sequence technique on qualitative and quantitative analysis.
To compare image quality of an optimized diffusion weighted imaging (DWI) sequence with advanced post-processing and motion correction (advanced-EPI) to a standard DWI protocol (standard-EPI) in pancreatic imaging. 62 consecutive patients underwent abdominal MRI at 1.5 T were included in this retrospective analysis of data collected as part of an IRB approved study. All patients received a standard-EPI and an advanced-EPI DWI with advanced post-processing and motion correction. Two blinded radiologists evaluated the parameters image quality, detail of parenchyma, sharpness of boundaries and discernibility from adjacent structures on b = 900 s/mm2 images using a Likert-like scale. Segmentation of pancreatic head, body and tail were obtained and apparent diffusion coefficient (ADC) was calculated separately for each region. Apparent tissue-to-background ratio (TBR) was calculated at b = 50 s/mm2 and at b = 900 s/mm2. The advanced-EPI yielded significantly higher scores for pancreatic parameters of image quality, detail level of parenchyma, sharpness of boundaries and discernibility from adjacent structures in comparison to standard-EPI (p < 0.001 for all, kappa = [0.46,0.71]) and was preferred in 96% of the cases when directly compared. ADC of the pancreas was 7% lower in advanced-EPI (1.236 ± 0.152 vs. 1.146 ± 0.126 μm2/ms, p < 0.001). ADC in the pancreatic tail was significantly lower for both sequences compared to head and body (all p < 0.001). There was comparable TBR for both sequences at b = 50 s/mm2 (standard-EPI: 19.0 ± 5.9 vs. advanced-EPI: 19.0 ± 6.4, p = 0.96), whereas at b = 900 s/mm2, TBR was 51% higher for advanced-EPI (standard-EPI: 7.1 ± 2.5 vs. advanced-EPI: 10.8 ± 5.1, p < 0.001). An advanced DWI sequence might increase image quality for focused imaging of the pancreas and providing improved parenchymal detail levels compared to a standard DWI.


The Role of Hydrolases in Biology and Xenobiotics Metabolism.
Chemical exposure can profoundly affect our health, some being voluntary (food and drugs) and some involuntary (environmental contaminants) [...].


Investigation of antidiabetic properties of shikonin by targeting aldose reductase enzyme: In silico and in vitro studies.
Diabetes is a complicated multifactorial disorder in which the patient generally observes polyphagia, polydipsia, and polyuria due to uncontrolled growth in blood sugar levels. For its management, the pharmaceutical industry is working day and night to find a better drug with no or least toxicity. That's why nowadays a more focused branch is to use herbal phytoconstituents for its prevention. Shikonin is a naphthoquinone natural dye that is isolated from the plants of the Boraginaceae family and has proven its role as an anti-cancer, anti-inflammatory, and anti-gonadotrophic agent. In our previous study, we have published its anti-diabetic action by inhibiting the enzyme protein tyrosine phosphatase 1B. In this study, we were more focused on finding out the role of Shikonin and its pharmacophores by inhibiting the action of aldose reductase (AR) enzyme. The study was conducted using pharmacophore modeling, molecular docking, and molecular dynamics simulation studies. The absorption, distribution, metabolism, excretion (ADME), and toxicity profile were also evaluated in this study. Along with all the computational biology parameters we also focused on the in vitro activity and kinetic study of inhibitory activity of Shikonin against aldose reductase.


Proximal colon distension induces Fos expression in oxytocin-, vasopressin-, CRF- and catecholamines-containing neurons in rat brain.
Little is known about the chemical coding of the brain neuronal circuitry activated by nociceptive signals of visceral origin. We characterized brain nuclei activated during isovolumetric phasic distension of the proximal colon (10 ml, 30 s on/off for 10 min) in conscious male rats, using Fos as a marker of neuronal activation and dual immunohistochemistry to visualize co-localization of Fos expression and oxytocin (OT), arginine-vasopressin (AVP), corticotrophin-releasing factor (CRF) or tyrosine hydroxylase (TH). Proximal colon distension, compared with sham distension, induced a robust increase in Fos-like immunoreactive (IR) neurons in the paraventricular nucleus (PVN), supraoptic nucleus (SON) and accessory neurosecretory nuclei of the hypothalamus, nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM), and to a lower extent, in the locus coeruleus (LC) and Barrington nucleus. Fos-IR neurons in the PVN after colon distension were identified in 81% of OT-IR, 18% AVP-IR and 16% CRF-IR neurons, while in the SON it represented 36% of OT-IR and 16% AVP-IR. Catecholaminergic cell groups in the pons (LC) and medulla (VLM, NTS) were also activated by proximal colon distension. Of the TH-IR neurons in VLM and NTS, 74% and 42% respectively were double labeled. These results indicate that colon distension stimulates OT-, AVP- and CRF-containing hypothalamic neurons, likely involved in the integration of colonic sensory information to modulate autonomic outflow and pain-related responses. Activation of medullary catecholaminergic centers might reflect the afferent and efferent limbs of the functional responses associated to visceral pain.


Resveratrol-nitric oxide donor hybrid effect on priapism in sickle cell and nitric oxide-deficient mouse.
Children and adult with sickle cell disease (SCD) display priapism associated with low nitric oxide (NO) bioavailability and oxidative stress in penis. This study aimed to evaluate the effects of hybrid compound RVT-FxMe, derived from resveratrol bearing a NO-donor subunit, on two murine model that display priapism phenotype, SCD transgenic mice and endothelial NO synthase gene-deficient (eNOS-/-) mice. Wild-type, SCD, and eNOS-/- mice were treated with RVT-FxMe (25 mg/kg/d, 2 weeks). Hematological parameters, concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP), as well as to electrical field stimulation (EFS), were obtained in mice corpus cavernosum strips. Corpus cavernosum relaxations to SNP and EFS were increased in eNOS-/- group, which were normalized by RVT-FxMe treatment. SCD mice exhibited an excessive CC relaxant response induced by ACh, EFS and SNP RVT-FxMe treatment did not change the increased relaxant responses to ACh, EFS and SNP in corpus cavernosum from SCD group. Excess of plasma hemoglobin in SCD may interfere in pharmacological activity of NO donors compounds. While mechanistic data with promising potential is showed, the current study is not without limitations. RVT-FxMe effects in the mid- and long-term warrant complementary studies. Treatment with RVT-FxMe reversed the enhanced NO-cGMP-mediated CC relaxations in eNOS-/- mice, but not in SCD mice; it is likely that excess of plasma hemoglobin in SCD mice act to inactivate NO before it reaches soluble guanylyl cyclase, avoiding restoration of NO bioavailability in penis.


[Anticoagulant-induced prophylaxis of thrombosis (author's transl)].
In postoperative and posttraumatic states, thromboembolic prophylaxis results in tenfold lower occurrence of pulmonary embolism and venous thrombisis--on which the postthrombotic syndrome is based--without a determinable increase of bleeding risk. Heparin is the treatment of choice. The dosage should be calculated on the basis of body weight. A minimal laboratory program of control measurements can diminish side effects.


Abusive parents' perceptions of child problem behaviors: an example of parental bias.
The behavior of children in 21 child abusive and 21 nonabusive matched comparison families were compared using home observations performed by professional independent observers and parental report measures (Becker Bipolar Adjective Checklist, Child Behavior Checklist, Parent Daily Report). Parental report measures of child conduct problems differed significantly between the two groups, independent observations showed few significant differences in rates of either child or parental behaviors. Results are discussed in terms of the validity of parental perceptions and reports of child problem behaviors, the informativeness of differing reports for diagnosis and clinical treatment, and the need to gather corroboration across various sources and settings before clinical decisions are made that may irrevocably alter a child's future development.


Clinicopathological characteristics and prognostic factors in axial chondroblastomas: a retrospective analysis of 61 cases and comparison with extra-axial chondroblastomas.
A comprehensive understanding of the clinical characteristics and prognostic factors associated with axial chondroblastoma (ACB) is still lacking. This study aimed to understand the clinical characteristics and prognostic factors of axial chondroblastoma (ACB) and compare them with extra-axial chondroblastoma (EACB). A retrospective review of our institution's local database was conducted, encompassing a total of 132 CB patients, of which 61 were diagnosed with ACB and 71 with EACB. Immunohistochemistry was employed to evaluate the expression levels of vimentin, S100, and cytokeratin. ACB and EACB shared similar characteristics, with the exception of advanced age, tumor size, elevated Vim expression, incidence of surrounding tissue invasion, and postoperative sensory or motor dysfunction. While wide resection and absence of surrounding tissue invasion consistently showed a favorable association with survival in both ACB and EACB cohorts during univariate analysis, most parameters exhibited differential prognostic significance between the two groups. Notably, the significant prognostic factors for local recurrence-free survival in the ACB cohort included the type of resection and the presence of chicken-wire calcification. In the multivariate analysis of overall survival, the type of resection emerged as a significant predictor in the ACB cohort, whereas in the EACB group, the type of resection and the occurrence of postoperative sensory or motor dysfunction were predictive of overall survival. There may exist distinct biological behaviors between ACB and EACB, thereby providing valuable insights into the prognostic characteristics of ACB patients and contributing to enhanced outcome prediction in this particular patient population.


Drivers of illegal resource extraction: an analysis of Bardia National Park, Nepal.
While park-people conflicts have received worldwide attention, the extent of illegal resource extraction and the relationship with communities' livelihoods has gained little attention in the literature. Thus this paper investigates the impact of socio-economic factors involved in illegal fuel wood and fodder extraction at Bardia National Park in Nepal. Household questionnaires, key-informant interviews and focus groups were conducted to identify different plant species used by households and explore the causes and mode of resource extraction in three buffer zone villages in the park. Altogether 50 different plants were identified by villagers that were used regularly for different livelihood purposes. Almost half of the respondents met their needs by illegally and regularly extracting resources from the park. Incentive schemes in the form of development projects were important but not sufficient in meeting the basic needs of households' especially for such daily items such as fuel wood and fodder. The results described in this paper showed that proximity and access to resources either in the national park, the buffer zone community forest or the government forest, and impact on the livelihoods significantly influenced the likelihood of illegal resource extraction activities. Villages that differed in terms of their location to the resource base, the provision of alternative resources and influence of these on their livelihoods showed significant differences in terms of their patterns of resource extraction and use of these resources. As resource use options, resource interest, and resource extraction patterns were different between villages and dependent on circumstances specific to villages, site-specific management strategies were necessary and more influential than the enforcement of 'one-size fits all' policies. It is suggested that park management plans should be flexible and adaptive enough to meet site-specific contexts and to endear wider support from local communities.


Occurrence and prognostic implications of micrometastases in lymph nodes from patients with submucosal gastric carcinoma.
The aims of this study were to assess the incidence of micrometastases of lymph nodes in patients with early gastric cancer invading the submucosal layer and to investigate the correlation between nodal micrometastases and malignancy potential to determine whether micrometastases of lymph nodes have prognostic significance, by use of an anticytokeratin immunohistochemical technique. A total of 2272 lymph nodes taken from 88 patients (25.8 per case) were assessed by immunohistochemical technique by use of monoclonal anti-human cytokeratin 8 antibodies. Clinicopathologic parameters and prognosis were compared between patients with and without micrometastases. The incidence of nodal involvement by tumor cells in 88 patients with submucosal gastric cancer increased from 19.3% (17 patients) by hematoxylin-eosin (H&E) staining to 31.8% (28 patients) by cytokeratin immunostaining. The rate of positive node in this study increased from 1.0% (23 of 2272 nodes) by H&E staining to 2.5% (57 of 2272 nodes) by immunostaining (P = .0002). No correlation was observed between the incidence of lymph node micrometastases and various clinicopathologic parameters, including tumor site and size, histological differentiation, Lauren classification, gross tumor type, vascular and lymphatic invasion, and perineural invasion. There was no difference in disease-free survival, estimated by the Kaplan-Meier life-table method, between the micrometastasis-negative and -positive groups (95% and 92.9%, respectively). Multivariate analyses showed that tumor size and diffuse subtype by the Lauren classification were significant factors for survival time (P = .0042 and .014, respectively). Immunohistochemical staining with an anticytokeratin antibody seems to be of little prognostic value in patients with submucosal gastric carcinoma. Thus, this immunostaining technique does not offer a significant benefit of different strategies for additional therapy or follow-up over conventional pathologic staging with H&E staining.


Generation of microalga Chlamydomonas reinhardtii expressing shrimp antiviral dsRNA without supplementation of antibiotics.
RNA interference (RNAi) is an effective way of combating shrimp viruses by using sequence-specific double-stranded (dsRNA) designed to knock down key viral genes. The aim of this study was to use microalgae expressing antiviral dsRNA as a sustainable feed supplement for shrimp offering viral protection. In this proof of concept, we engineered the chloroplast genome of the green microalga Chlamydomonas reinhardtii for the expression of a dsRNA cassette targeting a shrimp yellow head viral gene. We used a previously described chloroplast transformation approach that allows for the generation of stable, marker-free C. reinhardtii transformants without the supplementation of antibiotics. The generated dsRNA-expressing microalgal strain was then used in a shrimp feeding trial to evaluate the efficiency of the algal RNAi-based vaccine against the virus. Shrimps treated with dsRNA-expressed algal cells prior to YHV infection had 50% survival at 8 day-post infection (dpi), whereas 84.1% mortality was observed in control groups exposed to the YHV virus. RT-PCR using viral specific primers revealed a lower infection rate in dsRNA-expressing algae treated shrimp (55.6 ± 11.1%) compared to control groups (88.9 ± 11.1% and 100.0 ± 0.0%, respectively). Our results are promising for using microalgae as a novel, sustainable alternative as a nutritious, anti-viral protective feedstock in shrimp aquaculture.


Mechanism of traumatic knee injuries and MRI findings.
Bone bruises are focal abnormalities in subchondral bone marrow due to trabecular microfractures as a result of traumatic force. These trauma-induced lesions are better detected with magnetic resonance (MR) imaging using water-sensitive sequences. Moreover, the pattern of bone bruise is distinctive and allows us to understand the dynamics of trauma and to predict associated soft injuries. This article discusses the mechanism of traumatic injury and MR findings.


Oral health and risk of cognitive disorders in older adults: A biannual longitudinal follow-up cohort.
Oral health may be associated with cognitive disorders such as mild cognitive impairment or dementia. This study elucidates the effects of oral health conditions on the progression of cognitive disorders. Data were collected from 153 participants of the Korean Longitudinal Study on Cognitive Aging and Dementia cohort who completed the longitudinal dental examinations and cognitive function assessments using the three-wave biannual survey. We analysed the relationship between dental factors and the conversion of cognitive function. The ratio of maxillary removable partial denture use (p = .03) was high in the converter and mild cognitive impairment/dementia groups. The low-grade ratio of posterior masticatory performance increased in the converter and mild cognitive impairment/dementia groups (modified Eichner index 2, p = .04). The mild cognitive impairment/dementia group had a higher rate of complete mandibular denture use (p < .001). The converter and mild cognitive impairment/dementia groups had fewer remaining teeth (p < .05) or removable prostheses (p < .01) than the normal group. Masticatory performance is associated with the conversion of cognitive disorders. Our findings suggest that oral health management can help delay the progression of cognitive disorders.


Crystallization of human neutrophil elastase.
Human neutrophil elastase was inactivated by methoxysuccinyl-L-Ala-L-Ala-L-Pro-L-Ala-chloromethane. The modified enzyme was crystallized from 40 mM ammonium phosphate, pH 7.0 in the hexagonal space group P6(3) with unit cell parameters a = 74.53 A, b = 74.53 A, c = 70.88 A, alpha = beta = 90 degrees, gamma = 120 degrees. These crystals were resistant to radiation damage and diffracted beyond 1.84-A resolution. The asymmetric unit contained one 25,000-dalton monomer of human neutrophil elastase. Crystals were also grown from the enzyme modified with the analogous iodinated inactivator, p-iodoanilinosuccinyl-L-Ala-L-Ala-L-Pro-L-Ala-chloromethane. These crystals proved to be isomorphous with those of methoxysuccinyl-L-Ala-L-Ala-L-Pro-L-Ala-chloromethane-modified human neutrophil elastase, and served as a single-site, heavy atom derivative for solving the tertiary structure of the enzyme.


Medicinal foods from marine animals: current status and prospects.
The lifestyle of human being is changing day by day toward the simplified and more convenient way of living. Human wellbeing is majorly dependent on the daily food habits that are in accordance with the habits of individual community and the surrounding environments. Although the food habits are simplified and fashioned according to the current lifestyle, many of the Asians are still showing much importance to the naturally derived and traditional foods. One such medicinally important natural source is the foods from marine organisms, which are an important growing notion for the development of marine nutraceuticals and functional foods. In this context, we have already brought the recent trends and applications of marine algal (macro and micro) foods in my previous volume. The current preliminary chapter of this book volume on marine animals and microbes describes about the prospects of various marine animals and their derived substances/materials as medicinal foods. In addition, this chapter encourages the new researchers as well as various health communities to implement the marine animal-based medicinal foods and their applications.


Characteristics of Ophthalmology Trials Registered in ClinicalTrials.gov, 2007-2018.
To perform a comprehensive analysis of characteristics of ophthalmology trials registered in ClinicalTrials.gov. Cross-sectional study. All 4,203 ophthalmologic clinical trials registered on ClinicalTrials.gov between October 1, 2007, and April 30, 2018, were identified by using medical subject headings (MeSH). Disease condition terms were verified by manual review. Trial characteristics were assessed through frequency calculations. Hazard ratios and 95% confidence intervals were determined for characteristics associated with early discontinuation. The majority of trials were multiarmed (73.6%), single-site (69.4%), randomized (64.8%), and had <100 enrollees (66.3%). A total of 33% used a data-monitoring committee (DMC), and 50.6% incorporated blinding. Other groups (51.6%) were funded by industry, whereas 2.6% were funded by the US National Institutes of Health (NIH). NIH trials were significantly more likely to address oncologic (NIH = 15.5%, Other = 3%, Industry = 1.5%; P < 0.001) or pediatric disease (NIH = 20.9%, Other = 5.9%, Industry = 1.4%; P < 0.001). Industry-sponsored trials (69.6% of phase 3 trials) were significantly more likely to be randomized (Industry = 68.7%, NIH = 58.9%, Other = 60.8%; P < 0.001) and blinded (Industry = 57.2%, NIH = 42.7%, Other = 43.5%; P < 0.001). A total of 359 trials (8.5%) were discontinued early, and 530 trials (12.6%) had unknown status. Trials were less likely to be discontinued if funded by sources other than industry (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.55-0.95; P = 0.021) and/or had a DMC (HR, 0.71; 95% CI, 0.55-0.92; P = 0.010). Ophthalmology trials in the past decade reveal heterogeneity across study funding sources. NIH trials were more likely to support historically underfunded subspecialties, whereas Industry trials were more likely to face early discontinuation. These trends emphasize the importance of carefully monitored and methodologically sound trials with deliberate funding allocation.


Relation of lateral ST-segment elevation pattern to myocardial salvage in patients with recanalized anterolateral acute myocardial infarction.
Although anterior acute myocardial infarction (AMI) with ST-segment elevation in lateral leads is associated with a poor prognosis, the significance of the pattern of lateral ST-segment elevation has not been examined. The aim of the study was to examine the relation of the pattern of lateral ST-segment elevation to myocardial reperfusion and infarct size in patients with AMI. We studied 111 patients who had a first AMI presenting with anterolateral ST-segment elevation and Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow of the left anterior descending coronary artery within 6 h from symptom onset. Patients were classified into two groups according to the pattern of lateral ST-segment elevation on the admission electrocardiogram: Group 1, 42 patients with equivalent or greater ST-segment elevation in lead I than in lead aVL, and Group 2, 69 patients with lesser ST-segment elevation in lead I in than in lead aVL. Left ventricular ejection fraction (LVEF) was measured by predischarge left ventriculography. There were no differences between the two groups in age, gender, time from onset to recanalization, culprit lesion, or collateral development. Group 1 patients had a higher probability of impaired myocardial reperfusion as indicated by a myocardial blush grade of 0 or 1 after recanalization, a higher peak creatine kinase level, and a lower LVEF than Group 2 patients (p = 0.0001, respectively). We conclude that equivalent or greater ST-segment elevation in lead I than in lead aVL is associated with impaired myocardial reperfusion and less myocardial salvage in patients with recanalized AMI who present with anterolateral ST-segment elevation on the admission electrocardiogram.


A new approach in the active site investigation of an inverting β-D-xylosidase from Thermobifida fusca TM51.
The catalytic amino acid residues of the β-D-xylosidase (EC 18.104.22.168; GH43), from Thermobifida fusca TM51 (TfBXyl43), were investigated by direct chemical modifications. The pH dependence curves of the kinetic parameters (k(cat) and k(cat)/K(M)) gave pK values for the free enzyme (5.55 ± 0.19; 6.44 ± 0.19), and pK values of for the enzyme-substrate complex (4.85 ± 0.23; 7.60 ± 0.28) respectively, by using an artificial substrate p-nitrophenyl-β-D-xylopyranoside (pNP-Xyl). The detailed inhibition studies demonstrated well the hydrophobic character of the glycon binding site. Carbodiimide-mediated chemical modifications of the enzyme with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) in the presence of glycine methyl ester supports the conclusion that a carboxylate residue can be fundamental in the catalytic process. We have also synthesized and tested N-bromoacetyl-β-D-xylopyranosylamine (NBAXA) for TfBXyl43 as an affinity label, which also inactivated the enzyme irreversible. The pH dependence studies in both cases of inactivation revealed that the modified group is the catalytic proton donor (NBAXA pK(A) = 6.68 ± 0,1; EDAC pK(A) = 7.42 ± 0.22) which displays its essential role in the hydrolytic process. The β-D-xylopyranosylazide as competitive inhibitor protected the enzyme in all cases against the inactivation, suggesting that the chemical modification which has an impact on the activity took place in the active center. Changing of the enzyme conformation was followed by CD spectroscopy, as a result of the NBAXA inactivation. Our study is important because to our knowledge no similar investigations were made in the case of an inverting β-D-xylosidase.


Synthesis of thiiranes by rhodium-catalyzed sulfur addition reaction to reactive alkenes.
A rhodium complex derived from RhH(PPh3)4, dppe, and 4-ethynyltoluene catalyzes the addition reaction of sulfur to norbornenes giving the corresponding thiiranes under acetone reflux conditions. The rhodium complex effectively transfers a sulfur atom to the double bond from sulfur, and exo-adducts are obtained. The reaction is also applicable to (E)-cyclooctene and cyclic allenes. The ring-opening reaction of the thiiranes with lithium aluminium hydride gives the corresponding thiols.


Angiographic And Clinical Response Of Intracranial Atherosclerotic Disease Large Vessel Occlusion Stroke Undergoing Mechanical Thrombectomy.
To identify whether intracranial atherosclerotic disease large vessel occlusion strokes differ compared to embolic large vessel occlusion strokes in angiographic response to mechanical thrombectomy and clinical course. Retrospective analysis of acute ischemic stroke patients with large vessel occlusion, due to intracranial atherosclerotic disease or embolic etiology, who underwent mechanical thrombectomy in a primary stroke center from 11/2015 to 4/2018. We categorized patients into intracranial atherosclerotic disease or embolic large vessel occlusion based on the procedural findings. We compared pretreatment, procedural variables, and post-procedural outcomes. Ninety-five patients were included, 13 with intracranial atherosclerotic disease large vessel occlusion strokes and 82 with embolic large vessel occlusion strokes. Between the two groups, there was no statistically significant difference in angiographic success (100% for intracranial atherosclerotic disease and 89% for embolic large vessel occlusion strokes); first pass success (38% for intracranial atherosclerotic disease and 34% for embolic large vessel occlusion strokes); puncture-to-first-pass time; puncture-to-recanalization time (68 minutes for intracranial atherosclerotic disease and 62 minutes for embolic large vessel occlusion strokes); number of passes; or clinical outcomes. Intracranial angioplasty was performed in 6 (46%) of intracranial atherosclerotic disease large vessel occlusion patients, and in 5 (6%) of embolic large vessel occlusion patients (p < 0.0001). Similar angiographic success and procedural time metrics are achievable with intracranial atherosclerotic disease large vessel occlusion and embolic large vessel occlusion therapy. This occurred with more frequent intracranial angioplasty for intracranial atherosclerotic disease large vessel occlusion strokes.


Nuclear magnetic resonance-based metabolomic investigation reveals metabolic perturbations in PM2.5-treated A549 cells.
Exposure to PM2.5 is associated with an increased risk of lung diseases, and oxidative damage is the main reason for PM2.5-mediated lung injuries. However, little is known about the early molecular events in PM2.5-induced lung toxicity. In the present study, the metabolites in PM2.5-treated A549 cells were examined via a robust and nondestructive nuclear magnetic resonance (NMR)-based metabolic approach to clarify the molecular mechanism of PM2.5-induced toxicity. NMR analysis revealed that 12 metabolites were significantly altered in PM2.5-treated A549 cells, including up-regulation of alanine, valine, lactate, ω-6 fatty acids, and citrate and decreased levels of gamma-aminobutyric acid, acetate, leucine, isoleucine, D-glucose, lysine, and dimethylglycine. Pathway analysis demonstrated that seven metabolic pathways which included alanine, aspartate and glutamate metabolism, aminoacyl-tRNA biosynthesis, taurine and hypotaurine metabolism, arginine and proline metabolism, starch and sucrose metabolism, valine, leucine and isoleucine biosynthesis, and tricarboxylic acid cycle were mostly influenced. Our results indicate that NMR technique turns out to be a simple and reliable method for exploring the toxicity mechanism of air pollutant.


A comparison study of deep muscle sparing transverse rectus abdominis musculocutaneous flap for breast reconstruction.
Breast reconstruction by deep inferior epigastric perforator flap (DIEP) involves only little rectus abdominis muscle sacrifice. However, the operative procedure may get complicated. We propose here a novel method involving two adjacent perforators and requiring the addition of only the superficial muscle to the flap. This novel technique, termed "deep muscle sparing transverse rectus abdominis musculocutaneous flap (DMS-TRAM)," was compared to DIEP and MS-TRAM groups. The subjects were 70 patients. The indication of DMS-TRAM was the distance between two perforators penetrating the deep fascia was <3 cm, and the two perforators ran through the superficial layer of the muscle until they became confluent. All patients were evaluated by contrasting computed tomography. The data of age, body mass index, flap volume, operative time, blood loss, laterality, immediate reconstruction, prior radiation, smoking, re-exploration, total flap necrosis, partial fat necrosis, and abdominal bulging were compared. Ultimately, DMS-TRAM was applied in 20 subjects (28.6%), DIEP in 31 (44.3%), and MS-TRAM in 19 (27.1%). The volume of blood loss in the DIEP group was significantly higher than that in the DMS-TRAM group (328 ± 182 vs 454 ± 217 mL, p = 0.02), the other factors did not significantly influence. The rate of fat necrosis in DIEP tended to be high (10.0% vs 22.6%, p = 0.22). Because DMS-TRAM could preserve the deep muscle and penetrating side of intercostal nerve, it could be performed less sacrifice and there were few bleeding and partial necrosis at the same level as MS-TRAM. DMS-TRAM was effective in the applied cases.


[A drug addict presenting with complicated tricuspid valve endocarditis].
The right-sided heart valves are affected in about 10% of patients with infective endocarditis. However, the tricuspid valve is the most frequently involved valve in intravenous drug users with infective endocarditis. When treated with antibiotics, the prognosis is considered favorable. Reported here is the case of a drug-addicted patient with polymicrobial (Staphylococcus aureus and Streptococcus pneumoniae) infective endocarditis of the tricuspid valve and a lethal outcome due to multiple organ failure. The indications and options to perform cardiac surgery in patients with infective endocarditis of the tricuspid valve are discussed.


Evaluation of the Real-Q BRAF V600E Detection Assay in Fine-Needle Aspiration Samples of Thyroid Nodules.
Recently, several molecular assays for detecting the BRAF V600E mutation in fine-needle aspiration (FNA) specimens have been developed. Herein, we tested 294 consecutive FNA samples from patients with thyroid nodules with the Real-Q BRAF V600E detection assay (Real-Q). These results were compared with an allele-specific PCR-based kit using dual-priming oligonucleotides (AS-PCR). Any discordant results between the two tests were also analyzed by mutant enrichment with 3'-modified oligonucleotide sequencing. A total of 128 cases were confirmed histologically; of these, 121 were diagnosed as papillary thyroid carcinoma (PTC). The BRAF mutation was detected by Real-Q and AS-PCR testing in 80.2% (95% CI, 71.9%-86.9%) and 76.9% (95% CI, 68.3%-84.0%), respectively, of FNA specimens with PTC. Combining the BRAF V600E molecular assays (Real-Q and AS-PCR) with cytological diagnoses of malignant and suspicious for malignant cells, the detection rates (sensitivity) of Real-Q and AS-PCR for diagnosis of PTC increased to 94.2% (95% CI, 88.4%-97.6%) and 92.6% (95% CI, 86.4%-96.5%), respectively. In conclusion, the detection of BRAF V600E mutations in PTC by Real-Q is compatible to that of AS-PCR.


Implementation of evidence-based strategies to reduce catheter-associated urinary tract infections among hospitalized, post-surgical adults.
Several catheter-associated urinary tract infection (CAUTI) prevention interventions were successfully implemented and evaluated on a surgical unit in a community-based hospital. Sustainability of CAUTI prevention efforts requires daily communication between multidisciplinary staff. In our hospital, daily report on CAUTI events and indwelling catheters at a hospital-wide, multidisciplinary safety huddle contributed to an enhanced focus on CAUTI-prevention strategies and unit-level reduction in device use days and CAUTI rates.


Preparation of silane-dispersed graphene crosslinked vinyl carboxymethyl chitosan temperature-responsive hydrogel with antibacterial properties.
We synthesized a temperature-sensitive antibacterial hydrogel, defined as NIPAM-CG/GM hydrogel. First, vinyl carboxymethyl chitosan (CG) was synthesized as a crosslinking carrier and silane dispersed graphene (GM) was synthesized as a reinforcer. Then, the N-isopropylacrylamide (NIPAM) monomer was free-radical polymerized with the vinyl groups of CG and GM to form a NIPAM-CG/GM hydrogel without any crosslinking agent. The influences of different hydrogel compositions on the microstructure, compressive properties, swelling, drug loading, and drug release properties of the hydrogels were discussed, and its temperature sensitivity was also demonstrated. The results showed that the lower critical solution temperature (LCST) and mechanical properties of the hydrogel could be adjusted by controlling the amount of CG and GM. Next, its biocompatibility was characterized, and its antibacterial performance was tested against Escherichia coli and Staphylococcus aureus. The antibacterial mechanism was explained by measuring the difference in the ion concentration outside the membrane and changes in the morphology of live/dead bacteria. NIPAM-CG/GM had a high drug loading and nearly complete drug release at a physiological temperature of 37 °C. Its moderate mechanical properties, excellent biocompatibility, and antibacterial effects give NIPAM-CG/GM great potential applications as a wound dressing.


Normal mitogen-induced suppression of the interleukin-6 (IL-6) response and its deficiency in systemic lupus erythematosus.
A low-frequency suppressor-cell population in normal peripheral blood inhibits the B-cell CESS response to IL-6, following pokeweed mitogen stimulation. The suppression of IL-6 responsiveness is (i) radiation sensitive, (ii) directed against CESS targets and not mediated by inhibition of IL-6 production, and (iii) associated with nonspecific cytotoxic activity against CESS targets. The generation of these cytolytic cells is also radiation sensitive. A correlation was found between PWM-induced cytotoxicity against CESS and the suppression of IL-6-dependent IgG production. But cytotoxicity toward CESS targets is not responsible for this suppression because (i) IL-2 induces equivalent or greater nonspecific cytotoxicity against CESS in the total absence of suppression of CESS-derived IgG production and (ii) suppression is also induced by mitogen-activated PBL separated from CESS targets by a cell-impermeable membrane. This suppression was not mediated by TNF alpha/beta or IFN-gamma. In systemic lupus erythematosus, suppression of IL-6-dependent IgG production is impaired in patients with active disease (29.2 +/- 13.7%) compared to patients with inactive disease (70 +/- 19.5%) or normal controls (82.8 +/- 9.2%). There is also a defect in mitogen-induced nonspecific cytotoxicity in active SLE (specific lysis 15.1 +/- 3.5%, compared to 34 +/- 4% in normals). Pokeweed mitogen-activated PBL can therefore normally induce suppression of B-cell IL-6 responses and this response is deficient in lupus.


Ca++ antagonists and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms. II. Characterization of intracellular morphologic changes.
The effects of the slow Ca++ channel blocker, nifedipine, and ACAT inhibitor, octimibate, on cholesterol-loaded macrophages were compared at the ultrastructural level. The Ca++ antagonist induced the formation of membrane-surrounded "lamellar bodies" originating from lysosomes. The macrophages secreted these lamellar bodies, which were rich in phospholipids and cholesterol, into the culture medium even in the absence of cholesterol acceptors. In contrast, the ACAT inhibitor induced the formation of lamellar bodies originating from lipid droplets, which were also surrounded by membranes. There is strong evidence that these latter membranes were newly synthesized at the margin of the lipid droplets by the endoplasmic reticulum. The lamellar bodies descending from lipid droplets after ACAT inhibitor treatment were not secreted by the cells. They were stored in the cytoplasmic compartment in the absence of high density lipoproteins (HDL). When HDL were added to the medium, the lamellar bodies specifically interacted with endosomes containing the internalized HDL particles and disappeared concomitantly with an enhanced HDL-mediated cholesterol efflux. From the biochemical data in the accompanying article and the morphological data here, we conclude that macrophages release cholesterol by two major pathways: 1) an HDL-independent secretion of lamellar bodies containing cholesterol, which originate from lysosomes, and 2) an HDL-dependent release of cholesterol via the formation of lamellar bodies descending from lipid droplets, which intracellularly fuse with HDL-containing endosomes. The cholesterol-enriched HDL are then secreted as intact lipoproteins.


Smoking Cessation Strategies in Pregnancy.
Although pregnancy often motivates women to quit smoking, 20% to 25% will continue to smoke. Smoking is associated with adverse obstetric and neonatal outcomes such as placental abruption, stillbirth, preterm birth and sudden infant death syndrome, and it is therefore important to motivate women to quit during pregnancy. In this review, we explore the efficacy and evidence for safety of strategies for smoking cessation in pregnancy, including behavioural and pharmacologic therapies. The PubMed, Medline, EMBASE, and Cochrane databases (1990 to 2014) were accessed to identify relevant studies, using the search terms "smoking cessation," "pregnancy," "medicine, behavioural," "nicotine replacement products," "bupropion," and "varenicline." Studies were selected based on the levels of evidence presented by the Canadian Task Force on Preventative Health Care. Based on our review of the evidence, incentives combined with behavioural therapy appear to show the greatest promise for abstaining from smoking in the pregnant population. Nicotine replacement therapy administered in the form of gum may be better than using transdermal forms to avoid high levels of nicotine in the fetal circulation. One small trial demonstrated that bupropion is an effective aid for smoking cessation and that it does not appear to be associated with an increased risk of major congenital malformations. The currently available studies of varenicline in pregnancy are insufficient to provide evidence for the safety or efficacy of its use.


Antitumour effects and pharmacokinetics of combination of vinblastine with a staurosporine derivative, NA-382, in P388/ADR-bearing mice.
The effects of a staurosporine derivative, N-ethoxycarbonyl-7-oxostaurosporine (NA-382), on the pharmacokinetics of vinblastine were evaluated, compared with those of verapamil, in multidrug-resistant P388/ADR-bearing mice. At first, the in-vitro experiments indicated that NA-382 permeated into the cells better and were more effective in combined cytotoxicity with vinblastine and on accumulation of vinblastine than with verapamil in P388/ADR cells. In combined intraperitoneal injection with vinblastine (200 micrograms kg-1) into P388/ADR-bearing mice, NA-382 in a suspension form (10 mg kg-1) prolonged the life-span of the mice near to that of P388/S-bearing mice treated with vinblastine alone, but verapamil even at the maximum tolerated dosage (30 mg kg-1) barely affected the in-vivo antitumour effect of vinblastine. When simultaneously administered with vinblastine to P388/ADR-bearing mice, NA-382 maintained significantly higher vinblastine levels in the tumour cells for 24 h and gave a larger area under the time-intracellular vinblastine concentration curve (0 to 24 h) than those receiving vinblastine alone, with long retention of the agent in ascitic fluid. Verapamil increased the cellular vinblastine content for only 6 h, accompanying a rapid elimination of the agent from the ascitic fluid. This study indicates that NA-382 is more effective against multidrug-resistance than verapamil, and its suspension is also advantageous for cancer chemotherapy of multidrug-resistant tumours.


Self-guided management of exome and whole-genome sequencing results: changing the results return model.
Researchers and clinicians face the practical and ethical challenge of if and how to offer for return the wide and varied scope of results available from individual exome sequencing and whole-genome sequencing. We argue that rather than viewing individual exome sequencing and whole-genome sequencing as a test for which results need to be "returned," that the technology should instead be framed as a dynamic resource of information from which results should be "managed" over the lifetime of an individual. We further suggest that individual exome sequencing and whole-genome sequencing results management is optimized using a self-guided approach that enables individuals to self-select among results offered for return in a convenient, confidential, personalized context that is responsive to their value system. This approach respects autonomy, allows individuals to maximize potential benefits of genomic information (beneficence) and minimize potential harms (nonmaleficence), and also preserves their right to an open future to the extent they desire or think is appropriate. We describe key challenges and advantages of such a self-guided management system and offer guidance on implementation using an information systems approach.


Homotypic targeted nanoplatform enable efficient chemoimmunotherapy and reduced DOX cardiotoxicity in chemoresistant cancer via TGF-β1 blockade.
Doxorubicin (DOX) with broad-spectrum antitumor activity has been reported to induce effective immunogenic cell death (ICD) effect. However, the serious cardiotoxicity and chemoresistance severely restrict the widely clinical application of DOX. Herein, for the first time, a bio-inspired nanoplatform via co-assembly of DOX-conjugated polyethyleneimine (PEI-DOX), cancer cell membrane (CCM) and TGF-β1 siRNA (siTGF-β1) was rationally designed, which can not only overcome the drawbacks of DOX but also display high capability to modulate the tumor microenvironment and prevent the tumor progressing and metastasis. Experimental studies confirmed the pH-sensitivity of PEI-DOX and the homotypic-targeting and immuno-escapable ability of CCM, resulting an enhanced accumulation of DOX and siTGF-β1 in tumor sites. In addition to this, the bio-inspired nanoplatform could also improve the stability and facilitate the endosomal escape of siTGF-β1. All these effects ensured the silence efficiency of siTGF-β1 in tumor sites, which could further modulate the chemoresistant and immunosuppressive tumor microenvironment, resulting a synergistic effect with DOX to prevent tumor progressing and metastasis. Additionally, even trapped in cardiac tissues, siTGF-β1 could inhibit the production of TGF-β1 and ROS induced by DOX, resulting a reduced myocardial damage. Therefore, our newly designed bio-inspired nano-delivery system may be a promising nanoplatform with efficient chemoimmunotherapy to ameliorate DOX-induced cardiotoxicity and combat tumor growth and metastasis in chemoresistant cancer.


Liquid biopsies for solid tumors: Understanding tumor heterogeneity and real time monitoring of early resistance to targeted therapies.
In the era of personalized medicine detection of the molecular drivers of tumors and of specific DNA mutations predicting response or resistance to targeted agents has become routine practice in clinical oncology. The tumor biopsy depicts only a single timeframe from a single site, and might be inadequate to characterize a tumor because of intratumoral and intermetastatic heterogeneity. Circulating tumor DNA offers a "real time" tool for serially monitoring tumor genomes in a non-invasive manner providing accessible genetic biomarkers for cancer diagnosis, prognosis, and response to therapy. The liquid biopsy can be used for a variety of clinical and investigational applications. Future development will have to provide a cost effective analysis mainly identifying the genes known to be recurrently mutated in each tumor. Therefore, developing standardized methodologies for DNA analyses and validation in large prospective clinical studies is mandatory to implement the 'liquid biopsy' approach in the clinical management of cancer patients. In our review, we will focus on the clinical applications of liquid biopsies and on the recent findings in this field.


Lactate Decreases Bortezomib Sensitivity and Predicts Poor Clinical Outcomes of Multiple Myeloma.
Metabolic disorders are regarded as hallmarks of multiple myeloma (MM) and are responsible for rapid cancer cell proliferation and tumor growth. However, the exact biological roles of metabolites in MM cells have not been fully explored. This study aimed to explore the feasibility and clinical significance of lactate for MM and investigate the molecular mechanism of lactic acid (Lac) in the proliferation of myeloma cells and cell sensitivity to bortezomib (BTZ). Metabolomic analysis of the serum was carried out to obtain metabolites expression and clinical characteristics in MM patients. The CCK8 assay and flow cytometry were used to detect cell proliferation, apoptosis, and cell cycle changes. Western blotting was used to detect the potential mechanism and apoptosis- and cycle-related protein changes. Lactate was highly expressed in both the peripheral blood and bone marrow of MM patients. It was significantly correlated with Durie-Salmon Staging (DS Staging) and the International Staging System (ISS Staging) and the serum and urinary involved/uninvolved free light chain ratios. Patients with relatively high lactate levels had a poor treatment response. Moreover, in vitro experiments showed that Lac could promote the proliferation of tumor cells and decrease the proportion of G0/G1-phase cells, which was accompanied by an increased proportion of S-phase cells. In addition, Lac could decrease tumor sensitivity to BTZ by disrupting the expression of nuclear factor kappa B subunit 2 (NFkB2) and RelB. Metabolic changes are important in MM cell proliferation and treatment response; lactate could be used as a biomarker in MM and as a therapeutic target to overcome cell resistance to BTZ.


Use of transcutaneous nerve stimulation in the attacks of acute intermittent porphyria.
A 38-year-old female with acute intermittent porphyria (AIP) was having regular recurrent premenstrual severe attacks of abdominal and chest pain due to the disease. Low-frequency transcutaneous nerve stimulation (TNS) premenstrually prevented or markedly reduced the severity of clinical attacks, associated with a reduced urinary porphyrin excretion. The possible mechanisms of the TNS-induced effects are discussed. This experience suggests that TNS may be an effective and simple prophylactic method in the management of the attacks in AIP. The method can be administered easily by the patient himself as home-treatment and is free of side-effects.


Optical coherence tomography angiography artifacts in retinal pigment epithelial detachment.
To describe optical coherence tomography angiography (OCTA) reflectance artifacts secondary to retinal pigment epithelial detachment (RPED). Retrospective review. Four eyes from 4 subjects were included. Three presented with RPED and 1 eye was a normal control. Two eyes diagnosed with RPED and the normal eye were evaluated using en face OCTA centred at the fovea acquired using the RTVue XR Avanti (Optovue Inc). In the third eye with RPED, OCTA imaging was performed using a CIRRUS 5000 prototype modified to do OCTA imaging on a spectral domain OCT platform provided by Carl Zeiss Meditec, Inc. The segmented OCTA angiograms were overlaid to determine if the flow patterns seen at the edge of the RPEDs were due to reflectance from the inner retinal vessels, also known as "decorrelation tails." OCTA projection artifacts were noted when segmentation lines intersected with the boundary of the RPED. The overlaid segmented OCTA from the 3 RPED eyes imaged using each system revealed the same vasculature pattern at the edges of the RPED as that of the inner retina, demonstrating the "decorrelation tails" artifact, which caused the RPED to appear as a bright ring on the segmented OCTA. OCTA images are susceptible to various known artifacts. This series describes the impact of the projection artifact seen at the edges of an RPED that simulates appearance of flow but is actually due to reflectance of the inner retinal vasculature on the RPED.


Exploring the impact of new particle formation events on PM2.5 pollution during winter in the Yangtze River Delta, China.
New particle formation (NPF) events are an increasingly interesting topic in air quality and climate science. In this study, the particle number size distributions, and the frequency of NPF events over Hefei were investigated from November 2018 to February 2019. The proportions of the nucleation mode, Aitken mode, and accumulation mode were 24.59%, 53.10%, and 22.30%, respectively, which indicates the presence of abundant ultrafine particles in Hefei. Forty-six NPF events occurred during the observation days, accounting for 41.82% of the entire observation period. Moreover, the favorable meteorological conditions, potential precursor gases, and PM2.5 range of the NPF events were analyzed. Compared to non-NPF days, the NPF events preferentially occurred on days with lower relative humidity, higher wind speeds, and higher temperatures. When the PM2.5 was 15-20, 70-80, and 105-115 μg/m3, the frequency of the NPF events was higher. Nucleation mode particles were positively related to atmospheric oxidation indicated by ozone when PM2.5 ranged from 15 to 20 μg/m3, and related to gaseous precursors like SO2 and NO2 when PM2.5 was located at 70-80 and 105-115 μg/m3. On pollution days, NPF events did not directly contribute to the increase in the PM2.5 in the daytime, however, NPF events would occur during the night and the growth of particulate matter contributes to the nighttime PM2.5 contents. This could lead to pollution that lasted into the next day. These findings are significant to the improvement of our understanding of the effects of aerosols on air quality.


Nature and the time course of the effect of CO2 on electroretinogram (ERG) in an arachnid.
Electroretinogram recorded from the median eye of the scorpion, Heterometrus fulvipes before and after exposure to CO2 indicated that the rate of recovery of 'b' wave to pre-CO2 level was slow and delayed as compared to 'a' wave. 'b' wave may therefore have a more central origin than that of 'a' wave, which finds corroboration in the results of the depth recording in this eye with the microelectrode.


Spectrofluorimetric studies on the binding of salicylic acid to bovine serum albumin using warfarin and ibuprofen as site markers with the aid of parallel factor analysis.
The interactions of salicylic acid (SL) and two different site markers (warfarin for site I and ibuprofen for site II) with bovine serum albumin (BSA) in pH 7.4 Tris-HCl buffer have been investigated with the use of spectrofluorimetry. An equilibrium solution of BSA and SA was titrated separately with the two markers. This initial work showed that the binding of SL with BSA could be quite complex, and that there was probably a competitive interaction occurring between ibuprofen and SL. However, the spectral results were difficult to interpret clearly for the interaction of warfarin and SL in similar circumstances. To extract more information from the resolution of fluorescence excitation-emission spectra, the contour plots of the fluorescence spectra indicated that the optimal excitation wavelengths for BSA, SL, warfarin and ibuprofen were different, and were found to be at 278, 295, 306 and 218 nm, respectively. The spectral information was arranged into three-way excitation-emission fluorescence matrix (EEM) stack arrays, and was submitted for analysis by the parallel factor analysis (PARAFAC) algorithm. Firstly, it was demonstrated that the estimated excitation and emission spectral responses for SL, BSA and the site markers, warfarin and ibuprofen, agreed well with the measured spectra. Then, the interpretation of the plots of simultaneously extracted (by PARAFAC) equilibrium concentrations for the above four reactants, showed that: (i) the SL primarily appears to bind in site I but at a different location from the high-affinity binding site (HAS) for warfarin, and the interaction partially overlaps with the low-affinity binding site (LAS) for warfarin. (ii) The SL may have two LAS-one in site II where the HAS for ibuprofen is located, and the other in site I at the LAS for ibuprofen. Thus, application of the PARAFAC method for the study of competitive interaction of SL and BSA with the aid of two different site markers has extracted information unobtainable by traditional methods such as the Scatchard plot, and provided useful means of data visualization.


Favorable outcome of renal grafts with multiple arteries: a series of 198 patients.
We sought to report the postoperative complications, vascular reconstruction techniques and graft outcomes among our series of renal transplantations performed using grafts with multiple renal arteries. We reviewed retrospectively the medical records of 196 renal transplant patients of mean age 35.6 ± 13.3 years (range, 6-68) including 130 males and 66 females whose grafts from living (n = 164) or deceased (n = 32) donor with multiple arteries between 2006-2012. We noted the number of renal arteries, graft function, surgical technique, as well as vascular, urological and other complications. Of the 196 patients, 182 had 2 and 14 had ≥ 3 renal arteries. The surgical technique was separate anastomosis of renal arteries to the external and/or common iliac artery in the majority of patients (86.2%), while 13.8% of patients underwent anastomosis as a single renal artery after cuff reconstruction. Three patients experienced a lymphocele and only 1, a urinary leak from lower end of ureter, which was repaired surgically. Graft survival was 96.9% with losses in 6 cases due to rejection. Grafts bearing multiple renal arterial displayed low postoperative complication rates and good outcomes.


Ductal approaches to assessment and management of women at high risk for developing breast cancer.
The ductal approach to breast cancer, encompassing nipple aspiration, ductal lavage and duct endoscopy, allows assessment of breast ductal epithelial cells and their local microenvironment in a graded process of increasing invasiveness. Samples of ductal epithelial cells sufficient for cytological diagnosis may be safely collected, titres of individual proteins showing variation with breast cancer status may be measured, and abnormal pathology within the breast ducts may be directly visualized. Identification of surrogate molecular markers may facilitate early breast cancer detection, in conjunction with cytological assessment, and be useful for individual prediction of breast cancer risk and assessment of treatment response. However, the sensitivity and specificity of the ductal approach require further evaluation. The small quantities of nipple aspiration fluid available for analysis, and difficulties identifying and cannulating ducts remain important limitations of these techniques.


Pyroglutamic aciduria: a cause of high anion-gap metabolic acidosis associated with common drugs.
Pyroglutamic aciduria is a rare and probably under-recognised cause of metabolic acidosis which may be precipitated by certain common drugs.


The preferential binding of a sensory organ specific odorant binding protein of the alfalfa plant bug Adelphocoris lineolatus AlinOBP10 to biologically active host plant volatiles.
Semiochemicals such as sex pheromones and plant volatiles are crucial components of insect mating systems and host plant localization. In the olfactory signal transduction pathway, odorant-binding proteins (OBPs) are important elements that function in the first step of the pathway by carrying hydrophobic semiochemicals across the sensillum lymph to the olfactory receptors (ORs). In this study, we examined the binding affinities of semiochemicals to AlinOBP10, a putative OBP from the alfalfa plant bug, Adelphocoris lineolatus, that we demonstrate is expressed mainly in sensory organs. We then characterized the biological activities of the high affinity semiochemicals by measuring their electrophysiological activities in antennae and behavioral responses in the plant bug. AlinOBP10 displayed weak binding affinities to two major putative pheromone components, hexyl butyrate and (E)-2-hexenyl butyrate. In contrast, AlinOBP10 exhibited higher binding affinities to six host plant volatiles, namely myrcene, β-pinene, β-ionone, 3-hexanone, (E)-2-hexenal, and 1-hexanol. The biological activities of these six putative ligands were further studied in electroantennogram recordings and Y-tube olfactometer trials. The three compounds, (E)-2-hexenal, 1-hexanol, and 3-hexanone elicited strong electrophysiological responses, but elicited distinct behaviors. While 3-hexanone was attractive to female adults, (E)-2-hexenal and 1-hexanol were significant repellents. Although a weak electrophysiological response was elicited with β-pinene, it was a strong repellent. These results demonstrate that AlinOBP10 can interact with attractants, as well as repellents, with some specificity toward plant volatiles over sex pheromones.