Clinical significance of serum and urinary neopterin levels in patients with various liver diseases.
Serum and urinary neopterin levels were measured by radioimmunoassay in 120 healthy controls, 16 asymptomatic HBsAg carriers, 12 patients with acute hepatitis, 13 with chronic inactive hepatitis, 35 with chronic active hepatitis, 46 with liver cirrhosis, 18 with hepatocellular carcinoma, and 6 with alcoholic liver disease. Serum and urinary neopterin levels were significantly higher in almost all patients than in normal subjects. Neopterin levels were highest in acute hepatitis and correlated with the results of liver function tests, but did not show this correlation in chronic liver disease. In chronic liver disease, the levels of serum neopterin in non-A non-B viral patients was significantly increased, compared with those in B viral and alcoholic patients. The rate of abnormal urinary neopterin levels in chronic liver disease was higher than the rate of abnormal serum neopterin levels, but no difference was observed between the rates of abnormal serum and urinary levels in acute hepatitis and asymptomatic HBsAg carriers. These results indicate that serum and urinary neopterin levels may be useful markers for cell-mediated immunity in liver disease, and that the immune system response in chronic liver disease may be different for different pathogens.


[The effect of ticlid on the late result after the surgery of the brachiocephalic trunk arteries].
No ischemic insult, myocardial infarction, death due to cardiovascular pathology was observed in 138 patients, to whom after the operation on the arteries of truncus brachiocephalicus the ticlid was administered. At a comparison group (120 patients) in 3 the myocardial infarction have occurred (one patient died), in 2--an ischemic insult. After the ticlid application the positive late follow-up result was noted in 93.1% patients, without it--in 70.5%. The preparation compliance is good.


Risk of severe acute liver injury among patients with brain cancer treated with temozolomide: a nested case-control study using the healthcore integrated research database.
Temozolomide (TMZ) is used to treat adult patients with glioblastoma multiforme (GBM). Cases of hepatotoxicity have been reported among patients using TMZ. The objective of the study was to assess the relation, if any, between exposure to TMZ and serious acute liver injury (SALI). We used the HealthCore Integrated Research Database to perform a case-control study nested within a retrospective cohort of adult patients aged 18-100 years with at least two diagnoses of brain cancer anytime between 2006 and 2014. Patients without continuous eligibility or with a SALI diagnosis within 6 months prior to the date of incident brain cancer diagnosis were excluded. Medical records were sought for potential SALI cases and reviewed by two hepatologists. Five controls were selected for each case using incidence density sampling, matched on age and calendar year of index date. The analysis included 61 confirmed SALI cases and 305 selected controls. Exposure to TMZ was classified according to dispensing date and days supply of medication dispensed. We estimated odds ratios using conditional logistic regression models. The odds ratio for any exposure to TMZ was 0.91 (95% CI 0.44-1.91), for recent exposure to TMZ was 0.62 (95% CI 0.21-1.85). There was no increased risk of SALI with increasing duration of exposure to TMZ. When patients with unconfirmed SALI were included in the analysis, results were similar (OR 1.04; 95% CI 0.70-1.54). In conclusion, this study did not find an association between TMZ and SALI risk among patients with brain cancer.


Asymmetric Synthesis of Carbocyclic Propellanes.
A modular synthesis of functionalized carbocyclic propellanes was developed. Formation of the first of two quaternary bridgehead centers has been achieved by desymmetrization of prostereogenic ketones by either Hajos-Parrish-Eder-Sauer-Wiechert-type processes or Werner's catalytic asymmetric Wittig reaction. The obtained bicyclic enones were subjected to conjugate additions upon which the remaining ring was formed by olefin metathesis. All bridges are amenable to further derivatization, which renders those compounds useful as central units in fragment-based drug discovery or as ligand scaffolds.


Simultaneous extraction and enrichment of polyphenol and lutein from marigold (Tagetes erecta L.) flower by an enzyme-assisted ethanol/ammonium sulfate system.
Enzyme-assisted aqueous two-phase extraction (EA-ATPE) using ethanol/ammonium sulfate system was investigated for total polyphenol (TP) and lutein from marigold flowers. The important factors were investigated by single factor experiment and response surface methodology combined with Box-Behnken design to optimize the operating parameters of EA-ATPE. The maximum yields of TP and lutein were 83.56 ± 0.69 mg g-1 and 5.59 ± 0.13 mg g-1, respectively. Compared with aqueous two-phase extraction and Soxhlet extraction (SE), the extraction yield of TP by EA-ATPE is 64.91% higher and the extract of EA-ATPE has better antioxidant activity. The pretreatment effect was also researched by scanning electron microscopy. Thus, EA-ATPE is an efficient method for extracting bioactive components from plants.


Isolation and characterization of a polyubiquitin gene and its promoter region from Mesembryanthemum crystallinum.
Transcript levels of the polyubiquitin gene McUBI1 had been reported to be constant during Crassulacean acid metabolism (CAM) induction in the facultative CAM plant, Mesembryanthemum crystallinum. Here, we report the sequences of the full-length cDNA of McUBI1 and its promoter, and validation of the McUBI1 promoter as an internal control driving constitutive expression in transient assays using the dual-luciferase system to investigate the regulation of CAM-related gene expression. The McUBI1 promoter drove strong, constitutive expression during CAM induction. We compared the activities of this promoter with those of the cauliflower mosaic virus (CaMV) 35S promoter in detached C3- and CAM-performing M. crystallinum and tobacco leaves. We confirmed stable expression of the genes controlled by the McUBI1 promoter with far less variability than under the CaMV 35S promoter in M. crystallinum, whereas both promoters worked well in tobacco. We found the McUBI1 promoter more suitable than the CaMV 35S promoter as an internal control for transient expression assays in M. crystallinum.


Who should be offered fetal echocardiography? One center's experience with 3965 cases.
Although the comprehensive evaluation of the fetal heart includes echocardiography by an experienced pediatric cardiologist, economic constraints sometimes dictate the need to select patients. To analyze the usefulness of fetal echocardiography in the detection of congenital heart disease according to the referral indication. This retrospective survey relates to all 3965 FE studies performed in our center from January 2000 to December 2004. The diagnosed cardiac anomalies were classified as significant and non-significant malformations. All FE studies were done by a single operator (A.L.) at Meir Medical Center, a referral center for a population of about 400,000. The 3965 FE studies were performed for the following indications: abnormal obstetric ultrasound scans, maternal and family history of cardiac malformations, medication use during the pregnancy, and maternal request. The relative risk of detecting CHD was calculated according to the various referral indications. Overall, 228 (5.8%) cases of CHD were found. The most common indication for referral was suspicion of CHD during a four-chamber view scan in a basic system survey or during a level II ultrasound survey. No correlation was found between maternal age and gestational age at the time of scanning and the likelihood of finding CHD. Our data suggest that a suspicious level II ultrasound orthe presence of polyhydramnios is an important indication for FE in the detection of significant CHD.


Update on Sepsis Treatment in the Emergency Department.
Sepsis continues to be a devastating, costly, and challenging syndrome to manage in emergency departments (ED) across the nation, and its impact seems to be only increasing. Recently, consensus recommendations have made some profound changes in the way we approach, classify, and treat sepsis. The ED serves as an important initial screening and intervention point for sepsis, and ED care can have a profound impact on overall morbidity and mortality. The provision of early fluid resuscitation, antimicrobial therapy, and vasopressor therapy, if appropriate, is essential in early care. The intent of this review was to compare and contrast changes associated with the management of sepsis in the ED, with particular focus on guideline recommendations for pharmacotherapeutic management.


Syndecan proteoglycan contributions to cytoskeletal organization and contractility.
Cells exert tension on the extracellular matrix through specific receptors that link to the actin cytoskeleton. The best characterized are the integrins, which, when activated and clustered, can link to the extracellular matrix at specialized adhesion zones, known as focal contacts or focal adhesions. However, other transmembrane receptors can also localize there, including one transmembrane proteoglycan, syndecan-4. This heparan sulfate proteoglycan can also link directly to the cytoskeleton through alpha-actinin, and can signal through protein kinase C. In turn, the pathway leads to RhoA and Rho kinases that control actomyosin contractility. Syndecan-4 may, therefore, be a sensor of tension exerted on the matrix. These processes are described here, their significance being potential roles in wound contraction, tumor-stroma interactions, fibrosis and the regulation of motility.


O2-. release by activated Kupffer cells upon hypoxia-reoxygenation.
Primary cultures of rat liver Kupffer cells generated large amounts of superoxide anion radical (O2-.) when subjected to reoxygenation after a hypoxic period of at least 2 h. O2-. formation reached its maximum rate of approximately 25 nmol/10(6) cells within 1 h after reoxygenation. Two to four hours after reoxygenation, the number of injured cells began to increase and after 10 h approximately 60% of the cells were dead. During the period of O2-. release no significant difference in cell viability was observed between reoxygenated and hypoxically incubated cells, indicating a distinct time lag between O2-. release and onset of cell damage. Addition of diphenyliodonium, a specific inhibitor of the neutrophilic NADPH oxidase, to the Kupffer cells just before reoxygenation diminished both O2-. formation and cell injury up to 70%. Reoxygenation injury was completely prevented when superoxide dismutase and catalase were added immediately before reoxygenation. The results indicate that Kupffer cells subjected to hypoxia-reoxygenation generate a burst of reactive oxygen species and that this kind of "activation," probably by activating the NADPH oxidase, contributes to the self-destruction of the cells.


The influence of patient-practitioner agreement on outcome of care.
A previous study suggested that patient-practitioner agreement and follow-up in ambulatory care facilitates problem resolution as judged by patients. In this study in another medical practice, practitioner-patient agreement on what problems required follow-up was associated with greater problem resolution as judged by the practitioners regardless of the severity of the problems. In this study, patients did not judge problems mentioned only by themselves to be less improved than problems mentioned by both them and their practitioners. However, in this study more of the problems mentioned only by patients were mentioned in the note of the visit contained in the medical record. Patients expected less and reported less improvements of problems that were neither mentioned by the practitioner nor written in the medical record than was the case for problems listed both by patients and practitioners. The findings of this study confirm those of the previous study in suggesting that practitioner-patient agreement about problems is associated with greater expectations for improvement and with better outcome as perceived by patients. In addition, they indicate that practitioners also report better outcome under the same circumstances.


Pulse of atmospheric oxygen during the late Cambrian.
A rise in atmospheric O(2) has been linked to the Cambrian explosion of life. For the plankton and animal radiation that began some 40 million yr later and continued through much of the Ordovician (Great Ordovician Biodiversification Event), the search for an environmental trigger(s) has remained elusive. Here we present a carbon and sulfur isotope mass balance model for the latest Cambrian time interval spanning the globally recognized Steptoean Positive Carbon Isotope Excursion (SPICE) that indicates a major increase in atmospheric O(2). We estimate that this organic carbon and pyrite burial event added approximately 19 × 10(18) moles of O(2) to the atmosphere (i.e., equal to change from an initial starting point for O(2) between 10-18% to a peak of 20-28% O(2)) beginning at approximately 500 million years. We further report on new paired carbon isotope results from carbonate and organic matter through the SPICE in North America, Australia, and China that reveal an approximately 2‰ increase in biological fractionation, also consistent with a major increase in atmospheric O(2). The SPICE is followed by an increase in plankton diversity that may relate to changes in macro- and micronutrient abundances in increasingly oxic marine environments, representing a critical initial step in the trophic chain. Ecologically diverse plankton groups could provide new food sources for an animal biota expanding into progressively more ventilated marine habitats during the Ordovician, ultimately establishing complex ecosystems that are a hallmark of the Great Ordovician Biodiversification Event.


Computational Design of Crescent Shaped Promising Nonfullerene Acceptors with 1,4-Dihydro-2,3-quinoxalinedione Core and Different Electron-withdrawing Terminal Units for Photovoltaic Applications.
This study aims to design a series of nonfullerene acceptors (NFAs) for photovoltaic applications having 1,4-dihydro-2,3-quinoxalinedione fused thiophene derivative as the core unit and 1,1-dicyanomethylene-3-indanone (IC) derivatives and different π-conjugated molecules other than IC as terminal acceptor units. All the investigated NFAs are found air-stable as the computed highest occupied molecular orbitals (HOMOs) are below the air oxidation threshold (ca. -5.27 eV vs saturated calomel electrode). The studied NFAs can act as potential nonfullerene acceptor candidates as they are found to have sufficient open-circuit voltage (Voc) and fill factor (FF) ranging from 0.62 to 1.41 V and 83%-91%, respectively. From the anisotropic mobility analysis, it is noticed that the studied NFAs except dicyano-rhodanine terminal unit containing NFA, exhibit better electron mobility than the hole mobility, and therefore, they can be more promising electron transporting acceptor materials in the active layer of an organic photovoltaic cell. From the optical absorption analysis, it is noted that all the designed NFAs have the maximum absorption spectra ranging from 597 nm-730 nm, which lies in the visible region and near-infrared (IR) region of the solar spectrum. The computed light-harvesting efficiencies for the PM6 (thiophene derivative donor selected in our study):NFA blends are found to lie in the range of 0.96-0.99, which indicates efficient light-harvesting by the PM6:NFA blends during photovoltaic device operation.


Colonic availability of polyphenols and D-(-)-quinic acid after apple smoothie consumption.
The aim of this study was to determine the amounts of polyphenols and D-(-)-quinic acid reaching the ileostomy bags of probands (and thus the colon in healthy humans) after ingestion of apple smoothie, a beverage containing 60% cloudy apple juice and 40% apple puree. Ten healthy ileostomy subjects each ingested 0.7 L of apple smoothie (a bottle). Their ileostomy bags were collected directly before and 1, 2, 4, 6 and 8 h after smoothie consumption, and the polyphenol and D-(-)-quinic acid contents of the ileostomy fluids were examined using HPLC-DAD and HPLC-MS/MS. The total polyphenol and D-(-)-quinic acid content of the apple smoothie was determined to be 1955.6±124.6 mg/0.7 L, which is very high compared to cloudy apple juices. The most abundant substances found in the ileostomy bags were oligomeric procyanidins (705.6±197.9 mg), D-(-)-quinic acid (363.4±235.5 mg) and 5-caffeoylquinic acid (76.7±26.8 mg). Overall recovery of ingested polyphenols and D-(-)-quinic acid in the ileostomy bags was 63.3±16.1%. The amounts of polyphenol and D-(-)-quinic acids reaching the ileostomy bags are considerably higher after apple smoothie consumption than after the consumption of cloudy apple juice or cider. These results suggest that the food matrix might affect the colonic availability of polyphenols, and apple smoothies could be more effective in the prevention of chronic colon diseases than both cloudy apple juice and apple cider.


Stable, Free-space Optical Trapping and Manipulation of Sub-micron Particles in an Integrated Microfluidic Chip.
We demonstrate stable, free-space optical trapping and manipulation in an integrated microfluidic chip using counter-propagating beams. An inverted ridge-type waveguide made of SU8 is cut across by an open trench. The design of the waveguide provides low propagation losses and small divergence of the trapping beam upon emergence from the facet, and the trench designed to be deeper and wider than the optical mode enables full utilization of the optical power with an automatic alignment for counter-propagating beams in a trap volume away from all surfaces. After integration with polydimethylsiloxane (PDMS) microfluidic channel for particle delivery, 0.65 μm and 1 μm diameter polystyrene beads were trapped in free space in the trench, and manipulated to an arbitrary position between the waveguides with a resolution of < 100 nm. Comparison with numerical simulations confirm stable trapping of sub-micron particles, with a 10 kBT threshold power of less than 1 mW and a stiffness that can be 1 order of magnitude larger than that of comparable fiber-based trapping methods.


Tuning the tautomeric behavior of tris(salicylaldimines).
Five new tris(N-salicylaldimine) (TSAN) analogues were prepared and characterized. NMR and single-crystal X-ray diffraction studies showed that they are found in different tautomeric forms, ranging from keto-enamine to enol-imine, with two showing intermediate behavior. We present a simple structural model governing the relative stability of the keto-enamine versus enol-imine tautomeric form of TSANs, based on experimental and theoretical findings on the new and existing TSAN analogues. Examination of electron delocalization throughout this range reveals a connection between tautomeric state and whether the substituent is σ or π electron withdrawing/donating. This can be used as a qualitative guide to design TSANs with controlled tautomeric behavior. These results will be helpful to the growing number of researchers in supramolecular chemistry who use TSANs to construct new materials and cages.


Association of miR-149C>T and miR-499A>G polymorphisms with the risk of hepatocellular carcinoma in the Chinese population.
We investigate the potential association of miR-149C>T and miR-499A>G polymorphisms and the risk of hepatocellular carcinoma (HCC). A matched case-control study of 152 cases and 304 controls were conducted. The miR-149C>T and miR-499A>G genotypes were analyzed using duplex polymerase chain reaction with restricted fragment length polymorphism. HCC patients were more likely to be smokers and drinkers, have hepatitis B and C virus infections, and a family history of cancer. The miR-149 CC genotype was associated with a reduced risk of HCC, while the miR-499 GG genotype was associated with an increased risk of HCC. However, we did not find that the miR-149 CC and miR-499 GG genotypes were associated with risk of HCC, and no interaction was found between miR-149C>T and miR-499A>G polymorphisms and hepatitis B virus infection. In conclusion, the miRNA-149C>T and miR-499A>G polymorphisms were found to play an important role for HCC risk in China. This finding could be useful in identifying people at high risk for the disease for early intervention.


Platelet hyperactivation in multiple myeloma is also evident in patients with premalignant monoclonal gammopathy of undetermined significance.
Thrombotic events are common in patients with multiple myeloma (MM), smouldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS). Previous studies have indicated platelet hyperactivation as a feature of thrombotic risk in MM, but there is a dearth of data in MGUS. In the present study, multiparameter analysis of platelet activation and responsiveness was investigated by flow cytometry in patients with MGUS, SM/MM and healthy controls (HCs). The median platelet surface CD63 levels, annexin V and PAC-1 antibody (specific for activated integrin αIIbβ3) binding were significantly elevated in patients with MGUS versus the HCs. These markers were also elevated in SM/MM, but not significantly. In all, 74% of MGUS and 38% of SM/MM patients had one or more elevated marker of platelet activation, compared to 19% of the HCs. Marker-specific hyporesponsiveness of platelets to agonist [adenosine diphosphate (ADP), thrombin receptor-activating peptide 6] stimulation in vitro was observed, with significantly reduced surface levels of P-selectin in response to ADP in patients with MGUS. Platelet-leucocyte aggregates were not altered in patients, while platelet-associated immunoglobulins were elevated in a subset of patients. Overall, we found that platelet hyperactivation is prevalent in both MGUS and SM/MM patients and is potentially related to hyporesponsiveness. These observations suggest that further investigation of the predictive and prognostic value of platelet hyperactivation in such patients is warranted.


'Responsible drinking' programs and the alcohol industry in Brazil: killing two birds with one stone?
Over the last decade, the Brazilian alcohol industry - which for years has ignored alcohol problems - inaugurated responsible drinking programs (RDPs). This paper reports findings from an exploratory study that investigated the RDP-related activities of six leading alcohol companies in Brazil (three national, three transnational) focusing on program goals and components, target populations and evaluation methods. Interviews were conducted from October 2007 to February 2008 with nine key-informants, and 71 corporate documents were collected along with additional web information about the programs. Content analysis of interviews and institutional documents was used to identify the companies' RDP activities. Three types of RDPs were found that focused respectively on institutional action, drinking and driving, and underage drinking. All three transnational firms were involved in RDPs, whereas national firms demonstrated limited involvement. The majority of RDPs were implemented using television. No targeted research appears to have been undertaken by the companies to assess the efficacy of the strategies in terms of changes in drinking behavior. The evidence for both national and transnational firms means that is difficult to confirm that the responsible drinking programs produced so far in Brazil have been undertaken to systematically reduce alcohol problems, or mainly as part of a public relations strategy to reduce criticism and potentially forestall government regulations (Babor, 2006, 2009; Jernigan, 2009).


Determinants of 25(OH)D sufficiency in obese minority children: selecting outcome measures and analytic approaches.
To highlight complexities in defining vitamin D sufficiency in children. Serum 25-(OH) vitamin D [25(OH)D] levels from 140 healthy obese children age 6 to 21 years living in the inner city were compared with multiple health outcome measures, including bone biomarkers and cardiovascular risk factors. Several statistical analytic approaches were used, including Pearson correlation, analysis of covariance (ANCOVA), and "hockey stick" regression modeling. Potential threshold levels for vitamin D sufficiency varied by outcome variable and analytic approach. Only systolic blood pressure (SBP) was significantly correlated with 25(OH)D (r = -0.261; P = .038). ANCOVA revealed that SBP and triglyceride levels were statistically significant in the test groups [25(OH)D <10, <15 and <20 ng/mL] compared with the reference group [25(OH)D >25 ng/mL]. ANCOVA also showed that only children with severe vitamin D deficiency [25(OH)D <10 ng/mL] had significantly higher parathyroid hormone levels (Δ = 15; P = .0334). Hockey stick model regression analyses found evidence of a threshold level in SBP, with a 25(OH)D breakpoint of 27 ng/mL, along with a 25(OH)D breakpoint of 18 ng/mL for triglycerides, but no relationship between 25(OH)D and parathyroid hormone. Defining vitamin D sufficiency should take into account different vitamin D-related health outcome measures and analytic methodologies.


Computed tomography in the evaluation of pediatric genitourinary disease.
Traditionally, urography has been the diagnostic imaging technique of choice in children with renal and retroperitoneal diseases. However, ongoing experience with abdominal CT in the pediatric patient suggests that CT may be superior to more conventional modes of evaluation for certain urologic conditions, including renal masses and blunt abdominal trauma.


Functional analysis of the Pseudomonas putida regulatory protein CatR: transcriptional studies and determination of the CatR DNA-binding site by hydroxyl-radical footprinting.
CatR, a LysR family protein, positively regulates the Pseudomonas putida catBC operon, which is required for growth on benzoate as a sole carbon source. Transcriptional studies show that the catR and catBC promoters are divergent and overlapping by 2 bp. A beta-galactosidase promoter probe vector was constructed to analyze expression from the catR and catBC promoters under induced and uninduced conditions. As predicted, the catBC promoter is expressed only under induced conditions, while the catR promoter is constitutive. CatR has been shown to specifically bind the catRBC promoter region, and this property was used to devise a purification protocol for CatR. Linear M13 DNA containing the catRBC control region was covalently bound to cyanogen bromide-activated Sepharose in order to construct a DNA affinity column. Crude extracts containing hyperproduced CatR protein were then incubated with the affinity resin under binding conditions, and the CatR protein was eluted with 1 M NaCl. CatR was also purified by heparin-agarose chromatography. This highly purified protein was used for gel retardation and hydroxyl-radical footprinting studies. From this analysis, it was shown that CatR binds upstream of the catBC promoter within the transcribed region of catR.


"I made a mistake!": A narrative analysis of experienced physicians' stories of preventable error.
The complexity of healthcare systems makes errors unavoidable. To strengthen the dialogue around how physicians experience and share medical errors, the objective of this study was to understand how generalist physicians make meaning of and grow from their medical errors. This study used a narrative inquiry approach to conduct and analyse in-depth interviews from 26 physicians from the generalist specialties of emergency, internal, and family medicine. We gathered stories via individual interview, analysed them for key components, and rewrote a "meta-story" in a chronological sequence. We conceptualized the findings into a metaphor to draw similarities, learn from, and apply new principles from other fields of practice. Through analysis we interpreted the story of a physician who is required to make numerous decisions in a short period of time in different clinical environments among the patient's family and whilst abiding by existing rules and regulations. Through sharing stories of success and failure, the clinical supervisor can help optimize the physician's emotional growth and professional development. Similarly, through sharing and learning from stories, colleagues and trainees can also contribute to the growth of the protagonist's character and the development of clinic, hospital, and healthcare system. We draw parallels between the clinical setting and a generalist physician's experiences of a medical error with the environment and practices within professional sports. Using this comparison, we discuss the potential for meaningful coaching in medical education.


Potential protective effects of Spirulina platensis on liver, kidney, and brain acrylamide toxicity in rats.
Acrylamide (AA) is a hazardous chemical that is widely used in industrial practices. Spirulina platensis (SP) is a blue green alga that is rich in bioactive compounds with many medicinal benefits. The aim of the present study was to evaluate the ameliorative effect of SP against AA toxicity in rats. Animals were divided into six groups: Group (1) was normal rats, groups (2) and (3) received SP at 500 and 1000 mg/kg BW orally respectively for 21 days, group (4) was administered 20 mg/kg BW AA daily for 14 days, while groups (5) and (6) were given orally SP at the same doses of groups (2) and (3), then AA at similar dose of group (4). Rats that received AA alone displayed markedly increased serum levels of liver enzymes (ALT, AST, and ALP), kidney function parameters (urea and creatinine), DNA damage marker (8-OHdG), and proinflammatory cytokines (IL-1β, IL-6, and TNF-α), compared to control rats. Furthermore, tissue analysis revealed marked increases in hepatic, renal, and brain MDA and NO, as well as marked reductions in the antioxidant biomarkers (GSH, GSH-Px, SOD, and CAT) in acrylamide-intoxicated rats. Spirulina ameliorated the alterations in serum biochemical parameters and reduced MDA and NO, as well as improved antioxidant biomarkers in AA-intoxicated rats in a dose-dependent manner. Our results show that SP has a powerful protective effect on serum biochemistry and liver, kidney, and brain antioxidant machinery in AA-intoxicated rats.


CT angiography in pediatric extremity trauma: preoperative evaluation prior to reconstructive surgery.
Computed tomographic angiography (CTA) is a noninvasive modality for evaluating the vascular system and planning treatment strategies. The goal of this study was to validate the clinical utility of CTA in assessment of suspected pediatric extremity traumatic vascular injury, prior to emergent and delayed reconstructive surgery. A retrospective review was performed of all operative patients under 18 years of age who underwent multidetector-row CTA for evaluation of suspected extremity vascular injury. Parameters investigated included age, type of injury, referral source, temporal relationship between the injury and the CTA, CTA findings, operations performed, intraoperative findings, and clinical outcome. Between January 2002 and September 2005, 10 pediatric patients (6 males/4 females; mean age 8 years old, range 3-17) sustained either blunt (N = 8) or penetrating (N = 2) trauma and underwent CTA of the upper (N = 5) or lower extremities (N = 5). A total of 30% (3/10) of patients were referred from the emergency department acutely, 50% (5/10) were referred from the inpatient wards subacutely, and 20% (2/10) were referred from the outpatient clinics electively. Half (N = 5) underwent CTA to evaluate need for vascular repair, whereas half (N = 5) underwent CTA to evaluate local vasculature for flap reconstruction. Overall, 40% (4/10) of CTA findings were normal, whereas 60% (6/10) revealed traumatic vascular injuries. Pertinent nonvascular findings included soft tissue defects (60%, 6/10), fractures (40%, 4/10), and contracture deformities (20%, 2/10). In all cases, procedures were completed without complications, and intraoperative findings confirmed those from CTA. At a mean follow-up of 28 months, all injuries have healed without complications. CTA is a reliable noninvasive modality to evaluate pediatric patients with suspected traumatic extremity vascular injury and to plan treatment strategies for both vascular repair and extremity reconstruction.


A first look at HealthCyberMap medical semantic subject search engine.
HealthCyberMap (http://healthcybermap.semanticweb.org) is a Semantic Web project that aims at mapping selected parts of health information resources in cyberspace in novel semantic ways to improve their retrieval and navigation. This paper describes HealthCyberMap semantic subject search engine methodology and early prototype which attempt to overcome the limitations of conventional free text search engines. Explicit concepts in resource metadata map onto a brokering domain ontology (a clinical terminology or classification) allowing a Semantic Web search engine to infer implicit meanings (synonyms and semantic relationships) not directly mentioned in either the resource or its metadata. Similarly, user queries would map to the same ontology allowing the search engine to infer the implicit semantics of user queries and use them to optimise retrieval. Related issues of metadata, clinical terminologies and automatic vs. manual indexing of medical Web resources are also discussed, together with future methodological directions, which include the use of a true terminology server as an intelligent broker between user queries and HealthCyberMap pool of resource metadata. A comparative evaluation of the new engine based on relevance metrics is also proposed.


[Global trends in food consumption and nutrition].
Obesity and lifestyle diseases increase all over the world, especially in developing countries. One reason is the change in diet. This nutrition transition is characterised by improvement in dietary variation, but also by increase in the content of fat and sugar. The transition seems to start at a lower level of income, compared to what occurred in the Western countries after the Second World War. The reason is that many foods are relatively cheaper, especially fat and sugar. The world market is presently flooded with cheap vegetable fat. Urbanisation leads to over-consumption by increasing market access to fatty and sugary foods, including fast foods. Globalization increases the consumption of sweet soda pops, biscuits and snacks produced by multinational companies. Western supermarkets and fast food franchises also promote these dietary changes (McDonaldization). It has been proposed that the population in developing countries is more vulnerable towards these dietary changes in regard to obesity and chronic diseases, due to undernutrition in early life (the Barker hypothesis). We may therefore expect an unprecedented increase in the prevalence of chronic diseases, especially diabetes type 2 in the developing countries. One may question if this increase will be a transient phenomenon, or if we can expect the same pattern as we have seen in the West, namely that the poor become the fat-test segment of the population, with the highest prevalence of chronic diseases.


Targeting STATs in neuroinflammation: The road less traveled!
JAK/STAT transduction pathway is a highly conserved pathway implicated in regulating cellular proliferation, differentiation, survival and apoptosis. Dysregulation of this pathway is involved in the onset of autoimmune, haematological, oncological, metabolic and neurological diseases. Over the last few years, the research of anti-neuroinflammatory agents has gained considerable attention. The ability to diminish the STAT-induced transcription of inflammatory genes is documented for both natural compounds (such as polyphenols) and chemical drugs. Among polyphenols, quercetin and curcumin directly inhibit STAT, while Berberis vulgaris L. and Sophora alopecuroides L extracts act indirectly. Also, the Food and Drug Administration has approved several JAK/STAT inhibitors (direct or indirect) for treating inflammatory diseases, indicating STAT can be considered as a therapeutic target for neuroinflammatory pathologies. Considering the encouraging data obtained so far, clinical trials are warranted to demonstrate the effectiveness and potential use in the clinical practice of STAT inhibitors to treat inflammation-associated neurodegenerative pathologies.


Environmental force sensing helps robots traverse cluttered large obstacles.
Robots can traverse sparse obstacles by sensing environmental geometry and avoiding contact with obstacles. However, for search and rescue in rubble, environmental monitoring through dense vegetation, and planetary exploration over Martian and lunar rocks, robots must traverse cluttered obstacles as large as themselves by physically interacting with them. Previous work discovered that the forest floor-dwelling discoid cockroach and a sensor-less minimalistic robot can traverse cluttered grass-like beam obstacles of various stiffness by transitioning across different locomotor modes. Yet the animal was better at traversal than the sensor-less robot, likely by sensing forces during obstacle interaction to control its locomotor transitions. Inspired by this, here we demonstrated in simulation that environmental force sensing helps robots traverse cluttered large obstacles. First, we developed a multi-body dynamics simulation and a physics model of the minimalistic robot interacting with beams to estimate beam stiffness from the sensed contact forces. Then, we developed a force feedback strategy for the robot to use the sensed beam stiffness to choose the locomotor mode with a lower mechanical energy cost. With feedforward pushing, the robot was stuck in front of stiff beams if it has a limited force capacity; without force limit, it traversed but suffered a high energy cost. Using obstacle avoidance, the robot traversed beams by avoiding beam contact regardless of beam stiffness, resulting in a high energy cost for flimsy beams. With force feedback, the robot determined beam stiffness, then traversed flimsy beams by pushing them over and stiff beams by rolling through the gap between them with a low energy cost. Stiffness estimation based on force sensing was accurate across varied body oscillation amplitude and frequency and position sensing uncertainty. Mechanical energy cost of traversal increased with sensorimotor delay. Future work should demonstrate cluttered large obstacle traversal using force feedback in a physical robot.


Acute airway obstruction, an unusual presentation of vallecular cyst.
A 18-year-old female presented to us with acute respiratory obstruction, unconsciousness, severe respiratory acidosis, and impending cardiac arrest. The emergency measures to secure the airway included intubation with a 3.5-mm endotracheal tube and railroading of a 6.5-mm endotracheal tube over a suction catheter. Video laryngoscopy done after successful resuscitation showed an inflamed swollen epiglottis with a swelling in the left vallecular region, which proved to be a vallecular cyst. Marsupialisation surgery was performed on the 8(th) post admission day and the patient discharged on 10(th) day without any neurological deficit.


Study of interaction between agonists and asn293 in helix VI of human beta(2)-adrenergic receptor.
Previously, we demonstrated the involvement of Asn293 in helix VI of the human beta(2)-adrenergic receptor in stereoselective agonist recognition and activation. In the present study, we have further explored the role of this residue by synthesizing derivatives of isoproterenol and clenbuterol, two beta-adrenergic receptor agonists. We analyzed their efficacy and affinity on the wild-type and a mutant receptor (Asn293Leu). Each compound had similar efficacy (tau values) on both the wild-type and mutant receptor, although tau values varied considerably among the eight compounds studied. It appeared that one derivative of isoproterenol, but not of clenbuterol, showed a gain in affinity from the wild type to the mutant receptor. This derivative had a methyl substituent instead of the usual beta-OH group in the aliphatic side chain of isoproterenol, compatible with the more lipophilic nature of the leucine side chain. Such a "gain of function" approach through a combination of synthetic chemistry with molecular biology, may be useful to enhance our insight into the precise atomic events that govern ligand-receptor interactions.


A multidisciplinary stroke clinic for outpatient care of veterans with cerebrovascular disease.
Managing cerebrovascular risk factors is complex and difficult. The objective of this program evaluation was to assess the effectiveness of an outpatient Multidisciplinary Stroke Clinic model for the clinical management of veterans with cerebrovascular disease or cerebrovascular risk factors. The Multidisciplinary Stroke Clinic provided care to veterans with cerebrovascular disease during a one-half day clinic visit with interdisciplinary evaluations and feedback from nursing, health psychology, rehabilitation medicine, internal medicine, and neurology. We conducted a program evaluation of the clinic by assessing clinical care outcomes, patient satisfaction, provider satisfaction, and costs. We evaluated the care and outcomes of the first consecutive 162 patients who were cared for in the clinic. Patients had as many as six clinic visits. Systolic and diastolic blood pressure decreased: 137.2 ± 22.0 mm Hg versus 128.6 ± 19.8 mm Hg, P = 0.007 and 77.9 ± 14.8 mm Hg versus 72.0 ± 10.2 mm Hg, P = 0.004, respectively as did low-density lipoprotein (LDL)-cholesterol (101.9 ± 23.1 mg/dL versus 80.6 ± 25.0 mg/dL, P = 0.001). All patients had at least one major change recommended in their care management. Both patients and providers reported high satisfaction levels with the clinic. Veterans with stroke who were cared for in the clinic had similar or lower costs than veterans with stroke who were cared for elsewhere. A Multidisciplinary Stroke Clinic model provides incremental improvement in quality of care for complex patients with cerebrovascular disease at costs that are comparable to usual post-stroke care.


Neuromotor effects of acute ethanol inhalation exposure in humans: a preliminary study.
Ethanol (ETOH) is added to unleaded gasoline to decrease environmental levels of carbon monoxide from automobiles emissions. Therefore, addition of ETOH in reformulated fuel will most likely increase and the involuntarily human exposure to this chemical will also increase. This preliminary study was undertaken to evaluate the possible neuromotor effects resulting from acute ETOH exposure by inhalation in humans. Five healthy non-smoking adult males, with no history of alcohol abuse, were exposed by inhalation, in a dynamic, controlled-environment exposure chamber, to various concentrations of ETOH (0, 250, 500 and 1,000 ppm in air) for six hours. Reaction time, body sway, hand tremor and rapid alternating movements were measured before and after each exposure session by using the CATSYS 7.0 system and a diadochokinesimeter. The concentrations of ETOH in blood and in alveolar air were also measured. ETOH was not detected in blood nor in alveolar air when volunteers were exposed to 250 and 500 ppm, but at the end of exposure to 1,000 ppm, blood and alveolar air concentrations were 0.443 mg/100ml and 253.1 ppm, respectively. The neuromotor tests did not show conclusively significant differences between the exposed and non-exposed conditions. In conclusion, this study suggests that acute exposure to ethanol at 1,000 ppm or lower or to concentrations that could be encountered upon refueling is not likely to cause any significant neuromotor alterations in healthy males.


Linkage of rheumatoid arthritis to the candidate gene NRAMP1 on 2q35.
The macrophage resistance gene NRAMP1 regulates priming/activation of macrophages for enhanced TNF alpha, IL 1 beta, and MHC class II expression. Since all of these functions are of potential importance in the induction or maintenance or both of autoimmune disease, samples from the Arthritis and Rheumatism Council's repository of multicase rheumatoid arthritis families were typed for a dinucleotide repeat in the NRAMP1 promoter region and four other 2q34 (TNP1) or 2q35 (IL8R, VIL1, DES) marker genes. Identity by descent (IBD) sib pair analysis using a three locus haplotype NRAMP1-IL8RB-VIL1, or NRAMP1 alone, provided preliminary evidence (maximum lod score = 1.01, p = 0.024) for a gene in this region contributing to suceptibility to rheumatoid arthritis. Candidacy for NRAMP1 as the disease susceptibility gene was supported by a significant bias (p = 0.048) towards transmission of the NRAMP1 promoter region allele 3 in affected offspring.


Phasing-out of legacy brominated flame retardants: The UNEP Stockholm Convention and other legislative action worldwide.
Due to their toxicity and persistence, several families of brominated flame retardants (BFRs) have been listed as persistent organic pollutants (POPs) in the Stockholm Convention, a multilateral treaty overseen by the United Nations Environment Programme. This treaty mandates that parties who have signed must take administrative and legislative actions to prevent the environmental impacts that POPs pose, both within their jurisdictions and in the global environment. The specific BFRs listed in the Stockholm Convention are Polybrominated Diphenyl Ethers (PBDEs), Hexabromocyclododecane (HBCDD), and Hexabromobiphenyl (HBB), chemicals which must therefore be heavily restricted within the jurisdictions of the signatories. As an example, within the EU, hexabromobiphenyl (HBB), the PBDE commercial mixtures, and HBCDD are almost entirely prohibited in terms of both production and use in commercial goods. Waste articles containing excess concentrations of these BFRs are similarly restricted and must be disposed of in a manner that destroys or irreversible transforms the BFR in question. In some cases, specific exemptions for these limits are defined by the Convention for certain parties: for example, Penta- and Octa-BDE can be present in waste materials for recycling until 2030, while Deca-BDE can be applied to some aviation and automotive applications until 2036. However, in such cases, very specific criteria and guidelines apply for their use and/or production. Worldwide, China, Japan, India, and the United States of America have made significant advances in the regulation of POPs, in line with the provisions of the Stockholm Convention. China has established concentration limits for Penta- and Octa-BDEs in electronic goods. It is also currently availing of an exemption to allow for the use of HBCDD and has not yet ratified the Convention with regards to Deca-BDE. Japan meanwhile has classified HBB and Penta-/Octa-BDE compounds as Class I Specified Chemical Substances which virtually prohibits the manufacture, import, and use of these chemicals in all applications. India has banned the manufacture, trade, import, and use of HBB, HBCDD and some PBDEs, and has established concentration limits for all PBDEs in certain electrical goods. Finally, the United States has no federal mandate for the restriction of POPs and has not ratified the annexes to the Convention requiring them to do so. However, thirteen states have implemented their own state-wide concentration limits on a variety of flame retarding chemicals in various commercial applications. Though these limits worldwide are a very positive step for the removal of POP-BFRs from the environment, the increased use of replacement flame retardants renders such legislation only partially effective. The lack of effective screening mechanisms in waste management facilities means that BFR-treated plastics can be inadvertently recycled and remain in circulation. The rise in the use of novel BFRs (NBFRs) can furthermore hinder screening methods currently being developed and the additives themselves may pose similar issues to their predecessors owing to their similar chemical properties. Thus, restrictions on current BFRs will result in the use of new flame retardants, which may in turn be banned and replaced once again. Further research into and development of methods to screen for hazardous chemicals in end of life materials is therefore of the utmost importance. This must be coupled with pro-active legislation that eliminates the need for using such persistent and potentially harmful chemicals in the future.


Medication Reconciliation at Discharge from Hospital: A Systematic Review of the Quantitative Literature.
Medicines reconciliation is a way to identify and act on discrepancies in patients' medical histories and it is found to play a key role in patient safety. This review focuses on discrepancies and medical errors that occurred at point of discharge from hospital. Studies were identified through the following electronic databases: PubMed, Sciences Direct, EMBASE, Google Scholar, Cochrane Reviews and CINAHL. Each of the six databases was screened from inception to end of January 2014. To determine eligibility of the studies; the title, abstract and full manuscript were screened to find 15 articles that meet the inclusion criteria. The median number of discrepancies across the articles was found to be 60%. In average patient had between 1.2-5.3 discrepancies when leaving the hospital. More studies also found a relation between the numbers of drugs a patient was on and the number of discrepancies. The variation in the number of discrepancies found in the 15 studies could be due to the fact that some studies excluded patient taking more than 5 drugs at admission. Medication reconciliation would be a way to avoid the high number of discrepancies that was found in this literature review and thereby increase patient safety.


Self-Reference enhances memory for multi-element events judged likely to happen in young and older adults.
We investigated whether the strategy of self-reference can benefit memory for multi-element events, a kind of relational memory that is relatively less studied but highly relevant to daily life. Young and older adults imagined different person-object-location events with reference to themselves and two famous others (i.e., George Clooney and Oprah Winfrey), rated the likelihood that each event would happen, and then completed incidental memory tests on different pairs of elements within the event. We found that self-reference enhanced memory for object-location and person-object pairs in both age groups. Such self-reference effects were observed consistently only for events rated as likely to happen. There was also an overall memory advantage for the higher-likelihood events, which did not differ between young and older adults. Further, the self-reference effects were not correlated with memory functioning in either age group. Retrieval of within-event associations showed a significant level of dependency, which did not differ as a function of reference condition or likelihood category. These findings highlight the ways in which self-reference and prior knowledge improve relational memory, and suggest that the advantage of self-reference is not attributable to increased dependence of elements within complex events.


Enzyme-responsive micellar JQ1 induces enhanced BET protein inhibition and immunotherapy of malignant tumors.
Bromodomain and extra-terminal (BET) proteins are attractive targets for treating various malignancies including melanoma. The inhibition of BET bromodomains, e.g. with JQ1, is found to downregulate the expression of both c-MYC oncoprotein and programmed cell death ligand 1 (PD-L1), which play a crucial role in tumor growth and the immunosuppressive tumor microenvironment, respectively. The BET bromodomain inhibitors like JQ1 though exhibiting high selectivity and affinity show usually low bioavailability and efficacy in vivo due to fast clearance and inferior uptake by tumor cells. The therapeutic effect of JQ1 might further be lowered by drug resistance. Here, enzyme-responsive micellar JQ1 (mJQ1) was fabricated from a poly(ethylene glycol)-b-poly(L-tyrosine) copolypeptide to enhance JQ1 delivery and the immunotherapy of malignant melanoma. The in vitro results showed that mJQ1 induced clearly better repression of c-MYC and PD-L1 proteins, cell cycle arrest, cell inhibition, and apoptotic activity than free JQ1 in B16F10 cancer cells. The intratumoral administration of mJQ1 at 2.5 mg of JQ1 equiv. per kg was found to show better inhibition of B16F10 tumors in C57BL/6 mice than the intraperitoneal administration of free JQ1 at 50 mg kg-1. In particular, when combined with radiotherapy, mJQ1 effectively suppressed tumor growth and brought about strong local and systemic antitumor immunity as evidenced by elevated CD8+ T cells and increased ratios of CD8+ T cells to Tregs, affording significantly improved survival of B16F10 tumor-bearing mice than their JQ1 counterparts and marked growth suppression of distant tumors. The great potency of enzyme-responsive micellar JQ1 makes it interesting for immunotherapy of various tumors.


[Determination of 2,4,6-trinitromethylbenzene in biological material].
The objective of this study was to search for the optimal conditions necessary to extract 2,4,6-trinitromethylbenzene (2,4,6-TNMB) from biological material with acetonitrile. It is shown that 2,4,6-TNMB can be purified from the coextracted components of the biological material on a silica gel column, L 40/100 mcm. Methods are described for the identification and quantitative measurement of 2,4,6-trinitromethylbenzene in the cadaveric liver tissue by thin layer paper chromatography, IR spectrophotometry, and reverse phase high-performance liquid chromatography (rp-HPLC) with the use of a diode-matrix detector.


Comparison of early mortality between leukapheresis and non-leukapheresis in adult acute myeloid leukemia patients with hyperleukocytosis: a systematic review and meta-analysis.
One of the treatment modalities that can be used for hyperleukocytosis is leukapheresis. However, the result of studies showing the benefit of early mortality through the use of leukapheresis versus no leukapheresis is still inconclusive. Hence, we aimed to conduct a systematic review with meta-analysis to determine the effect of leukapheresis on early mortality in AML patients with hyperleukocytosis. We conducted a literature search on five databases (PubMed, EBSCOhost, Scopus, Clinicalkey, and JSTOR) up to October 2021 for studies comparing early mortality outcomes between hyperleukocytosis AML patients treated with leukapheresis versus no leukapheresis. Summary odds ratios (OR) and 95% confidence intervals (CI) were calculated using random-effects models. Heterogeneity tests were presented in I2 value and publication bias was analyzed using a funnel plot. Eleven retrospective cohort studies were eligible based on the inclusion and exclusion criteria. Pooled analysis showed that there was no significant difference in early mortality between patients receiving leukapheresis and not receiving leukapheresis in studies using hyperleukocytosis cutoff of 95,000/mm3 or 100,000/mm3 (OR: 1.17; 95% CI: 0.74-1.86; p: 0.50; I2: 0%). Similarly, studies using hyperleukocytosis cutoff of 50,000/mm3 also showed no benefits of early mortality (OR: 0.67; 95% CI: 0.43-1.05; p: 0.08; I2: 0%). Most of the studies used had a moderate risk of bias due to being observational studies. Funnel plot showed an indication of publication bias on studies using hyperleukocytosis cutoff of ≥50,000/mm3. The use of leukapheresis does not provide early mortality benefit in adult AML patients with hyperleukocytosis.


Determinants for an impaired quality of life 10 years after coronary artery bypass surgery.
To identify determinants of an inferior quality of life (QoL) 10 years after coronary artery bypass grafting (CABG). Sahlgrenska University Hospital, Göteborg, Sweden. All patients from Western Sweden who underwent CABG between 1988 and 1991 without simultaneous valve surgery and no previous CABG. Questionnaires for evaluating QoL 10 years after the operation. Three different instruments were used: The Nottingham health profile (NHP), the psychological general wellbeing index (PGWI), and the Physical Activity Score (PAS). 2000 patients underwent CABG, of whom 633 died during 10 years of follow-up. Information on QoL at 10 years was available in 976 patients (71% of survivors). A history of diabetes and chronic obstructive pulmonary disease were the two independent predictors for an inferior QoL with all three instruments. Furthermore, there were three predictors of an inferior QoL with two of the instruments: high age, female sex and a history of hypertension. A number of factors predicted an inferior QoL with one of the instruments. These were the duration of angina pectoris and functional class prior to CABG, renal dysfunction, a history of cerebrovascular disease, obesity, height, duration of respirator treatment and requirement of inotropic drugs postoperatively. In addition, when introducing preoperative QoL into the model a low QoL before surgery was a strong independent predictor also of an inferior QoL 10 years after CABG. Variables independently predictive of an impaired QoL 10 years after CABG, irrespective of the instrument used, were an impaired QoL prior to surgery, chronic obstructive pulmonary disease and a history of diabetes. However, other factors reflecting gender, the previous history as well as postoperative complications were also associated with the QoL 10 years later in at least one of these instruments.


Lactation associated with herpes zoster pectoralis.
The phenomenon of lactation associated with herpes zoster is unexpected. To our knowledge such an association has been reported only once. A case is reported in whom spontaneous lactation occurred in the ipsilateral breast following herpes zoster. It is believed to have resulted from stimulation of the intercostal nerve endings supplying the overlying skin of the breast.


5,6,7,3',4',5'-Hexamethoxyflavone inhibits growth of triple-negative breast cancer cells via suppression of MAPK and Akt signaling pathways and arresting cell cycle.
Natural components continue to be an important source for the discovery and development of novel anticancer agents. Polymethoxyflavones are a class of flavonoids found in citrus fruits and medicinal plants used in traditional medicine. In the present study, the anticancer activity of the well-known nobiletin (5,6,7,8,3',4'-hexamethoxyflavone) was compared against its less studied structural isomer 5,6,7,3',4',5'-hexamethoxyflavone. These compounds were evaluated on the Hs578T triple-negative breast cancer cell line and its more migratory subclone Hs578Ts(i)8. 5,6,7,3',4',5'-hexamethoxyflavone was found to be less toxic than nobiletin, while a similar growth inhibitory effect was observed after 72 h. Additionally, 5,6,7,3',4',5'-hexamethoxyflavone arrested the cell cycle in the G2/M phase, while no effect was observed on apoptosis or the migratory behavior of these cells. Furthermore, mechanistic studies revealed that the growth inhibition was concomitant with reduced phosphorylation levels of signaling molecules in the MAPK and Akt pathways as well as cell cycle regulators, involved in regulating cell proliferation, survival and cell cycle. In summary, the present study is the first to report on the anticancer activities of 5,6,7,3',4',5'-hexamethoxyflavone and to provide evidence that this flavone could have a greater potential than nobiletin for prevention or treatment of triple- negative breast cancer.


[Ways to decrease lethality in mechanical injuries to the liver].
An analysis of 135 observations of injuries of the liver and literature data of the recent 5 years (3931 cases) have shown that lethality resulting from trauma of the liver remains high and makes 20-78% of patients with closed injuries. Main causes of death of such patients are shock and blood loss. Optimization of the surgical treatment of injuries of the liver may be achieved by the introduction of reliable sources of hemostasis which are thought to be laser and plasma radiation, and by the development of effective methods of temporary hemostasis.


Undergraduate Implant Dentistry Training In Saudi Dental Schools.
Implant dentistry training at the undergraduate level has been introduced only recently in Saudi dental schools and there is only limited data available about it. The objective of the present study was to evaluate the current status of undergraduate dental implant education in Saudi Dental Schools. A two-part questionnaire-based study was conducted in Saudi university dental schools targeted towards undergraduate program directors to assess the quantity and quality of implant dentistry training being integrated into the curriculum. In addition, interns were asked to assess the degree of exposure and their satisfaction regarding implant dentistry education. Five program directors (83.3%) and 195 interns (82.9%) responded to the questionnaires. Implant dentistry was taught to the undergraduate students in multidisciplinary departments with teaching hours ranging from 22-30 hours. Only three schools exposed students to laboratory (workshop) or clinical training. There was agreement among the program directors in respect of the didactic contents. Majority of the interns reportedly acquired knowledge regarding implant dentistry based on theoretical (96.1%), laboratory (33.5%) and/or clinical (30%) training. While 50% of the interns agreed to acquire knowledge by assisting and observing dental implant procedures, only 52.8% of the interns expressed satisfaction regarding implant dentistry training obtained during their undergraduate period. The present study revealed variability in undergraduate implant dentistry training offered at Saudi dental schools. In order to optimize this and to produce competent dentists, learning guidelines for such courses should be developed and implemented by competent authorities.


Phenolic compounds profile of different berry parts from novel Vitis vinifera L. red grape genotypes and Tempranillo using HPLC-DAD-ESI-MS/MS: A varietal differentiation tool.
The detailed phenolic composition of different berry parts from two novel V. vinifera L. red grape genotypes (Moribel and Tinto Fragoso), together the well-known Tempranillo, was established using high performance liquid chromatography-diode array detection-electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI-MS/MS) over two consecutive vintages (2016 and 2017). More than 50 phenolic compounds were identified and quantified: 25 anthocyanins, 17 flavonols, 7 hydroxycinnamic acid derivatives, 2 stilbenes, and several flavan-3-ols. As far as we know, some anthocyanin and flavonol dihexosides were reported for the first time in V. vinifera L. grapes. Application of Principal Component Analysis (PCA) to experimental data showed a good separation of the novel grape genotypes and Tempranillo according to the phenolic profile of skins and seeds, mainly based on the proportion of trisubstituted anthocyanin derivatives, flavonols and flavan-3-ols, being a useful tool to differentiate these grape varieties.


Goniothalamin induces coronary artery smooth muscle cells apoptosis: the p53-dependent caspase-2 activation pathway.
Goniothalamin (GN), a styryl-lactone isolated from Goniothalamus andersonii, has been demonstrated to possess antirestenostic properties by inducing apoptosis on coronary artery smooth muscle cells (CASMCs). In this study, the molecular mechanisms of GN-induced CASMCs apoptosis were further elucidated. Apoptosis assessment based on the externalization of phosphatidylserine demonstrated that GN induces CASMCs apoptosis in a concentration-dependent manner. The GN-induced DNA damage occurred with concomitant elevation of p53 as early as 2 h, demonstrating an upstream signal for apoptosis. However, the p53 elevation in GN-treated CASMCs was independent of NAD(P)H: quinone oxidoreductase 1 and Mdm-2 expression. An increase in hydrogen peroxide and reduction in free thiols confirmed the role for oxidative stress in GN treatment. Pretreatment with the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-FMK) that significantly abrogated GN-induced CASMCs apoptosis suggested the involvement of caspase(s). The role of apical caspase-2, -8, and -9 was then investigated, and sequential activation of caspase-2 and -9 but not caspase-8 leading to downstream caspase-3 cleavage was observed in GN-treated CASMCs. Reduction of ATP level and decrease in oxygen consumption further confirmed the role of mitochondria in GN-induced apoptosis in CASMCs. The mitochondrial release of cytochrome c was seen without mitochondrial membrane potential loss and was independent of cardiolipin. These data provide insight into the mechanisms of GN-induced apoptosis, which may have important implications in the development of drug-eluting stents.


Elevated serum glucose-6-phosphate isomerase correlates with histological disease activity and clinical improvement after initiation of therapy in patients with rheumatoid arthritis.
To determine serum glucose-6-phosphate isomerase (GPI) concentrations in patients with rheumatoid arthritis (RA), and to test whether they correlate with objective measures of disease activity. Sera from 116 patients with RA, 69 patients with non-RA rheumatic diseases, and 101 healthy controls were analyzed. Levels of soluble serum GPI were measured by ELISA. Histological disease activity was determined with the synovitis score in synovial needle biopsies from 58 of the 116 patients with RA. Thirty-one of the 58 synovium samples were stained for CD68, CD3, CD20, CD38, CD79a, and CD34 by immunohistochemistry. Demographic data were collected, as well as serological and clinical variables that indicate RA disease activity, for Spearman correlation analysis. Serum GPI level correlated positively with the synovitis score (r = 0.278, p = 0.034). Significantly higher soluble GPI levels were detected in the RA sera compared with sera from healthy controls and the non-RA disease controls (2.25 ± 2.82 vs 0.03 ± 0.05 and 0.19 ± 0.57 μg/ml, respectively; p < 0.0001). The rate of serum GPI positivity was significantly higher in the RA patients than in the non-RA disease controls (64.7% vs 10.1%; p < 0.0001). Spearman analysis showed no significant correlation between serum GPI level and Disease Activity Score in 28 joints at baseline. After initiation of antirheumatic treatments, GPI levels decreased significantly (2.81 ± 3.12 vs 1.44 ± 2.09 μg/ml; p = 0.016), paralleling improvement of the disease activity indices. Elevated serum GPI may be involved in the synovitis of RA and may prove useful as a serum marker for disease activity of RA.


From stress to inflammation and major depressive disorder: a social signal transduction theory of depression.
Major life stressors, especially those involving interpersonal stress and social rejection, are among the strongest proximal risk factors for depression. In this review, we propose a biologically plausible, multilevel theory that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental stress with internal biological processes that drive depression pathogenesis. Central to this social signal transduction theory of depression is the hypothesis that experiences of social threat and adversity up-regulate components of the immune system involved in inflammation. The key mediators of this response, called proinflammatory cytokines, can in turn elicit profound changes in behavior, which include the initiation of depressive symptoms such as sad mood, anhedonia, fatigue, psychomotor retardation, and social-behavioral withdrawal. This highly conserved biological response to adversity is critical for survival during times of actual physical threat or injury. However, this response can also be activated by modern-day social, symbolic, or imagined threats, leading to an increasingly proinflammatory phenotype that may be a key phenomenon driving depression pathogenesis and recurrence, as well as the overlap of depression with several somatic conditions including asthma, rheumatoid arthritis, chronic pain, metabolic syndrome, cardiovascular disease, obesity, and neurodegeneration. Insights from this theory may thus shed light on several important questions including how depression develops, why it frequently recurs, why it is strongly predicted by early life stress, and why it often co-occurs with symptoms of anxiety and with certain physical disease conditions. This work may also suggest new opportunities for preventing and treating depression by targeting inflammation.


Sites of action of elevated CO2 on leaf development in rice: discrimination between the effects of elevated CO2 and nitrogen deficiency.
Elevated CO2 concentrations (eCO2) trigger various plant responses. Despite intensive studies of these responses, the underlying mechanisms remain obscure. In this work, we investigated when and how leaf physiology and anatomy are affected by eCO2 in rice plants. We analyzed the most recently fully expanded leaves that developed successively after transfer of the plant to eCO2. To discriminate between the effects of eCO2 and those of nitrogen deficiency, we used three different levels of N application. We found that a decline in the leaf soluble protein content (on a leaf area basis) at eCO2 was only observed under N deficiency. The length and width of the leaf blade were reduced by both eCO2 and N deficiency, whereas the blade thickness was increased by eCO2 but was not affected by N deficiency. The change in length by eCO2 became detectable in the secondly fully expanded leaf, and those in width and thickness in the thirdly fully expanded leaf, which were at the leaf developmental stages P4 and P3, respectively, at the onset of the eCO2 treatment. The decreased blade length at eCO2 was associated with a decrease in the epidermal cell number on the adaxial side and a reduction in cell length on the abaxial side. The decreased width resulted from decreased numbers of small vascular bundles and epidermal cell files. The increased thickness was ascribed mainly to enhanced development of bundle sheath extensions at the ridges of vascular bundles. These observations enable us to identify the sites of action of eCO2 on rice leaf development.


Dietary intake of different carbohydrates among incident stroke patients during previous year.
Stroke is a leading cause of preventable morbidity and mortality in the United States. Numerous studies have shown that dietary carbohydrates play an important role in stroke incident. Therefore, this study aimed to assess the association between dietary intake of carbohydrate and its types and stroke incidence among Iranian adults. A case-control study was performed among 46 men (5618) and 23 women (527) admitted to the Al Zahra hospital with stroke and 60 healthy people were chosen in control group. Dietary intake was measured by food frequency questionnaire (FFQ) including 168 items. Food processor software (version 2) was used to analyze data. ANTHROPOMETRIC INDICES OF MALE AND FEMALE PATIENTS WERE (BMI: 297.5), (Waist: 11215) and (BMI: 25.53.5), (Waist: 925) respectively. Energy intake and carbohydrate consumption of patients in both genders was higher than the healthy subjects which was statistically significant among men (P < 0.05). Across different carbohydrate sources, refined carbohydrates consumption was higher among patients in both gender rather than the healthy subjects While, the healthy people had a higher whole grain consumption. High carbohydrate intake specially refined sources with high glycemic index (GI) and glycemic load (GL) is associated with increased risk of stroke. Hence, dietary intake requires improvement to provide protection from life threatening outcomes.


Genetic, geographic, and environmental correlates of human temporal bone variation.
Temporal bone shape has been shown to reflect molecular phylogenetic relationships among hominoids and offers significant morphological detail for distinguishing taxa. Although it is generally accepted that temporal bone shape, like other aspects of morphology, has an underlying genetic component, the relative influence of genetic and environmental factors is unclear. To determine the impact of genetic differentiation and environmental variation on temporal bone morphology, we used three-dimensional geometric morphometric techniques to evaluate temporal bone variation in 11 modern human populations. Population differences were investigated by discriminant function analysis, and the strength of the relationships between morphology, neutral molecular distance, geographic distribution, and environmental variables were assessed by matrix correlation comparisons. Significant differences were found in temporal bone shape among all populations, and classification rates using cross-validation were relatively high. Comparisons of morphological distances to molecular distances based on short tandem repeats (STRs) revealed a significant correlation between temporal bone shape and neutral molecular distance among Old World populations, but not when Native Americans were included. Further analyses suggested a similar pattern for morphological variation and geographic distribution. No significant correlations were found between temporal bone shape and environmental variables: temperature, annual rainfall, latitude, or altitude. Significant correlations were found between temporal bone size and both temperature and latitude, presumably reflecting Bergmann's rule. Thus, temporal bone morphology appears to partially follow an isolation by distance model of evolution among human populations, although levels of correlation show that a substantial component of variation is unexplained by factors considered here.


High accuracy of arterial spin labeling perfusion imaging in differentiation of pilomyxoid from pilocytic astrocytoma.
Pilomyxoid astrocytoma (PMA) is a relatively new tumor entity which has been added to the 2007 WHO Classification of tumors of the central nervous system. The goal of this study is to utilize arterial spin labeling (ASL) perfusion imaging to differentiate PMA from pilocytic astrocytoma (PA). Pulsed ASL and conventional MRI sequences of patients with PMA and PA in the past 5 years were retrospectively evaluated. Patients with history of radiation or treatment with anti-angiogenic drugs were excluded. A total of 24 patients (9 PMA, 15 PA) were included. There were statistically significant differences between PMA and PA in mean tumor/gray matter (GM) cerebral blood flow (CBF) ratios (1.3 vs 0.4, p < 0.001) and maximum tumor/GM CBF ratio (2.3 vs 1, p < 0.001). Area under the receiver operating characteristic (ROC) curves for differentiation of PMA from PA was 0.91 using mean tumor CBF, 0.95 using mean tumor/GM CBF ratios, and 0.89 using maximum tumor/GM CBF. Using a threshold value of 0.91, the mean tumor/GM CBF ratio was able to diagnose PMA with 77 % sensitivity, 100 % specificity, and a threshold value of 0.7, provided 88 % sensitivity and 86 % specificity. There was no statistically significant difference between the two tumors in enhancement pattern (p = 0.33), internal architecture (p = 0.15), or apparent diffusion coefficient (ADC) values (p = 0.07). ASL imaging has high accuracy in differentiating PMA from PA. The result of this study may have important applications in prognostication and treatment planning especially in patients with less accessible tumors such as hypothalamic-chiasmatic gliomas.


Encapsulation of probiotic bacteria in biopolymeric system.
Encapsulation of probiotic bacteria is generally used to enhance the viability during processing, and also for the target delivery in gastrointestinal tract. Probiotics are used with the fermented dairy products, pharmaceutical products, and health supplements. They play a great role in maintaining human health. The survival of these bacteria in the human gastrointestinal system is questionable. In order to protect the viability of the probiotic bacteria, several types of biopolymers such as alginate, chitosan, gelatin, whey protein isolate, cellulose derivatives are used for encapsulation and several methods of encapsulation such as spray drying, extrusion, emulsion have been reported. This review focuses on the method of encapsulation and the use of different biopolymeric system for encapsulation of probiotics.


Apoptotic bone marrow CD34+ cells in cirrhotic patients.
To access the frequency and level of apoptotic CD34+ cells isolated from the marrow fluid of patients with post-hepatitis cirrhosis. The frequency of bone marrow CD34+ cells and apoptotic bone marrow CD34+ cells in 31 in-patients with post-hepatitis cirrhosis (cirrhosis group), and 15 out-patients without liver or blood disorders (control group) was calculated by flow cytometry. Parameters were collected to evaluate liver functions of patients in cirrhosis group. The percentage of normal bone marrow CD34+ cells was 6.30% ± 2.48% and 1.87% ± 0.53% (t = 3.906, P < 0.01) while that of apoptotic marrow CD34+ cells was 15.00% ± 15.81% and 5.73% ± 1.57% (t = 2.367, P < 0.05) in cirrhosis and control groups, respectively. The percentage of apoptotic marrow CD34+ cells was 6.25% ± 3.30% and 20.92 ± 18.5% (t = 2.409, P < 0.05) in Child-Pugh A and Child-Pugh B + C cirrhotic patients, respectively. The percentage of late apoptotic marrow CD34+ cells was positively correlated with the total bilirubin and aspartate aminotransferase serum levels in patients with cirrhosis. The status of CD34+ marrow cells in cirrhotic patients may suggest that the ability of hematopoietic progenitor cells to transform into mature blood cells is impaired.


A TCR targeting the HLA-A*0201-restricted epitope of MAGE-A3 recognizes multiple epitopes of the MAGE-A antigen superfamily in several types of cancer.
Adoptive immunotherapy using TCR-engineered PBLs against melanocyte differentiation Ags mediates objective tumor regression but is associated with on-target toxicity. To avoid toxicity to normal tissues, we targeted cancer testis Ag (CTA) MAGE-A3, which is widely expressed in a range of epithelial malignancies but is not expressed in most normal tissues. To generate high-avidity TCRs against MAGE-A3, we employed a transgenic mouse model that expresses the human HLA-A*0201 molecule. Mice were immunized with two HLA-A*0201-restricted peptides of MAGE-A3: 112-120 (KVAELVHFL) or MAGE-A3: 271-279 (FLWGPRALV), and T cell clones were generated. MAGE-A3-specific TCR α- and β-chains were isolated and cloned into a retroviral vector. Expression of both TCRs in human PBLs demonstrated Ag-specific reactivity against a range of melanoma and nonmelanoma tumor cells. The TCR against MAGE-A3: 112-120 was selected for further development based on superior reactivity against tumor target cells. Interestingly, peptide epitopes from MAGE-A3 and MAGE-A12 (and to a lesser extent, peptides from MAGE-A2 and MAGE-A6) were recognized by PBLs engineered to express this TCR. To further improve TCR function, single amino acid variants of the CDR3 α-chain were generated. Substitution of alanine to threonine at position 118 of the α-chain in the CDR3 region of the TCR improved its functional avidity in CD4 and CD8 cells. On the basis of these results, a clinical trial is planned in which patients bearing a variety of tumor histologies will receive autologous PBLs that have been transduced with this optimized anti-MAGE-A3 TCR.


Free hydatid cyst only covered with germinative membrane disrupted from fibrotic capsule in the peritoneal cavity: a case report.
Echinococcosis, an endemic disease on the Asian continent, is caused by ecinococcus granulosus and rarely ecinococcus alveolaris. Although it occurs frequently in the liver and the lung, it can be localized in all tissues and organs. The purpose of this study is to report a rare localization and the complication of hydatid cyst in the pelvis : it pushed forward and upward the urine bladder and there was bilateral hydroureteronephrosis causing uraemia because of outflow obstruction. To our knowledge, a similar case has not been published before in English literature.


Morphine Pharmacodynamics in Mechanically Ventilated Preterm Neonates Undergoing Endotracheal Suctioning.
To date, morphine pharmacokinetics (PKs) are well quantified in neonates, but results about its efficacy are ambiguous. This work presents an analysis of a previously published study on pain measurements in mechanically ventilated preterm neonates who received either morphine or placebo to improve comfort during invasive ventilation. The research question was whether morphine reduces the pain associated with endotracheal or nasal suctioning before, during, and after suctioning. Because these neonates cannot verbalize their pain levels, pain was assessed on the basis of several validated pain measurement instruments (i.e., COMFORT-B, preterm infant pain profile [PIPP], Neonatal Infant Pain Scale (NIPS), and visual analogue scale (VAS)). The item response theory (IRT) was used to analyze the data in order for us to handle the data from multiple-item pain scores. The analysis showed an intra-individual relationship between morphine concentrations and pain reduction, as measured by COMFORT-B and VAS. However, the small magnitude of the morphine effect was not considered clinically relevant for this intervention in preterm neonates.


[Failed epidural analgesia during birth].
Epidural analgesia is regarded as the most effective pain relief option, and it is used in 25% of all child births in Denmark. Despite the large number of epidural blocks, there is no consensus on, how failed epidural analgesia (FEA) should be defined. There are several different definitions and probably therefore a wide incidence (8.5-23%). In this review, we attempt to provide an overview of the many definitions of FEA and to identify the risk factors. In addition, we suggest recommendations on how to reduce the number of FEA in the future.


[Fatal course of generalized BCG histiocytosis in congenital immune deficiency (author's transl)].
Severe combined X-linked immune deficiency ended fatally in a six-month-old male infant after generalized BCG infection. Damage in the cell-bound thymus-dependent immune system is decisive in the development of "BCG histiocytosis". As a result of absent immunocompetent sensitized T-lymphocytes there is insufficient information and stimulation of macrophages to kill the micro-organsims. The disorder of bactericidal properties of macrophages results in an overwhelming infection with BCG bacteria with a characteristic morphological picture.


A dominant form of congenital stationary night blindness (adCSNB) in a large Chinese family.
Summary A pedigree of congenital stationary night blindness (CSNB) is described in a large Chinese family. The clinical description, pedigree, dark adaptation and elctroretinogram (ERG) studies indicate that the patients have an autosomal dominant form (ad) of CSNB. The disorder has been transmitted through at least 12 generations with over 40 affected individuals identified. The ERG data reveal that affected persons have severely diminished b-wave responses to dim light, but normal a-wave and subnormal b-wave responses to maximum light stimuli. The dark adaptation curves of three patients show a monophase curve, typical for night blindness. We have excluded the five previously known mutations in the three genes (RHO, PDE6B and GNAT1) associated with adCSNB, and linkage studies have excluded tight linkage between the disease locus and markers associated with these three genes. Thus, this family has adCSNB caused by a different gene from the previously identified RHO, PDE6B, and GNAT1.


A bead-based immunofluorescence-assay on a microfluidic dielectrophoresis platform for rapid dengue virus detection.
The proof of concept of utilizing a microfluidic dielectrophoresis (DEP) chip was conducted to rapidly detect a dengue virus (DENV) in vitro based on the fluorescence immunosensing. The mechanism of detection was that the DEP force was employed to capture the modified beads (mouse anti-flavivirus monoclonal antibody-coated beads) in the microfluidic chip and the DENV modified with fluorescence label, as the detection target, can be then captured on the modified beads by immunoreaction. The fluorescent signal was then obtained through fluorescence microscopy, and then quantified by ImageJ freeware. The platform can accelerate an immuno-reaction time, in which the on-chip detection time was 5min, and demonstrating an ability for DENV detection as low as 104 PFU/mL. Furthermore, the required volume of DENV samples dramatically reduced, from the commonly used ~50µL to ~15µL, and the chip was reusable (>50x). Overall, this platform provides a rapid detection (5min) of the DENV with a low sample volume, compared to conventional methods. This proof of concept with regard to a microfluidic dielectrophoresis chip thus shows the potential of immunofluorescence based-assay applications to meet diagnostic needs.


Chemoenzymatic synthesis and chemical recycling of sustainable polyurethanes.
Two novel types of chemically recyclable ester-containing polyurethanes, namely, a diol-diacid-type poly(diester-urethane) (PDEU) and a hydroxy acid type poly(ester-urethane) (PEU), were prepared by a green synthetic route that avoids the use of hazardous diisocyanate. The urethane linkage was introduced by the reaction of ethylene carbonate with amino alcohols and amino acids to form urethanediol and urethane-containing hydroxy acids, respectively. The urethanediol underwent polymerization with dimethyl adipate in the presence of lipase to produce a high-molecular-weight PDEU, while PEU was prepared by the lipase-catalyzed direct polycondensation of the urethane-containing hydroxy acid monomer. The periodic introduction of ester linkages into the polyurethane chain afforded primary biodegradation points and chemically recyclable segments. Both PDEU and PEU were readily degraded in the presence of lipase into oligomers which were readily repolymerized in the presence of the same enzyme.


Dorsal Augmentation-Diced Cartilage Techniques: The Diced Cartilage Glue Graft.
The quest for the ideal method for augmenting the nasal dorsum continues to be a matter of debate, with both most surgeons and patients preferring autologous tissue. This article reviews the current use of diced cartilage for nasal augmentation, emphasizing the diced cartilage in fibrin glue (DCG) graft. It offers the first collation of unfavorable outcomes and complications of the DCG graft seen in a series of 108 patients treated at the author's institution. The DCG graft continues to be a versatile graft that is stable over time and combines unique features. It has proved to be particularly well suited for segmental augmentations of the dorsum. Resorption of the graft has been rare and infrequent unfavorable outcomes have all been amenable to successful minor surgical revisions.


Microcomputer applications in health population surveys: experience and potential in developing countries.
Regrettably, because the content and technology are evolving so rapidly the literature on the application of microcomputer technology to health and development is either out of date, or hard to find (e.g. unpublished reports from consultants working with development agencies or universities). The time needed to review and publish an article or a book dictates that by the time it is published, any statements about current hardware will be obsolete. For example, a recent volume by Ingle et al., quite sound from the theoretical and practical point of view is already out of date with respect to hardware details. For that reason no hardware suggestions are made in this article. On the other hand, detailed reports of experience with first-generation microcomputers are very useful to the individual planning a developing country application. From the literature and our own field experience with respect to microcomputer applications in health/population surveys in developing countries, the following are useful summary points for projects currently going into the field. Careful planning is absolutely necessary if microcomputer technology is to be applied successfully to field data collection problems. Search out organizations with similar experiences. Collaboration among staff at all levels is essential for a system to be installed and utilized effectively. The particular technology combination selected must be adapted to the field situation. Remember survey complexity and size. Training is essential, and should be on-the-job and oriented towards specific tasks. If time consuming and repetitive tasks are given over to the microcomputer the technology will be readily accepted and fully utilized. To the extent that a community of users can be formed, the entire adoption process will be stimulated and results improved. Most maintenance and some repairs should be carried out in the field by local project personnel. For most survey and data acquisition problems some custom programming will be needed; this requires a good working knowledge of a powerful programming language (although this is likely to change in the near future). For descriptive statistics and small data management problems off-the-shelf software is appropriate but can be expensive. Compare options. Standardization and compatibility must be considered in all applications. This is important!(ABSTRACT TRUNCATED AT 400 WORDS)


Holographic method of measuring scintillation effects.
A method is described by which a wavefront-reconstruction technique is utilized to record the effects of a turbulent medium on the propagation of optical beams. By this technique both amplitude and phase information in a two-dimensional cross section of a received optical beam are recorded. The mode structure of the source is not seen to be critical in this application.


Sustained Disease Control in Immune Checkpoint Blockade Responders with Microsatellite Instability-high Colorectal Cancer after Treatment Termination.
Immune checkpoint inhibitors improve survival in patients with mismatch repair deficiency/microsatellite instability-high (MSI-H) colorectal cancer. The recurrence outcomes following discontinuation of immunotherapy after prolonged disease control have not been definitively reported in large series. Records from patients with advanced MSI-H colorectal cancer from The University of Texas - MD Anderson Cancer Center who received immunotherapy between 2014 and 2022 and stopped after prolonged clinical benefit were reviewed. Median progression-free and overall survival were estimated. Associations between the event of recurrence and coexisting mutations (KRAS/NRAS, BRAFV600E), metastatic organ involvement (lung, liver, lymph node, or peritoneum), metastatic timing (synchronous vs. metachronous), prior immunotherapy [anti-PD-(L)1 alone or in combination with anti-CTLA antibodies], etiology of MSI status (sporadic vs. hereditary non-polyposis colorectal cancer), and duration of immunotherapy were assessed. Sixty-four patients with MSI-H colorectal cancer without progression on immunotherapy were reviewed. Of these 48 and 16 received anti-PD(L)1 antibody alone or in combination with anti-CTLA-4 antibody, respectively. Median exposure to immunotherapy was 17.6 months (range, 1.3-51.9). After a median follow-up of 22.6 months (range, 0.3-71.7) after stopping immunotherapy, 56 of 64 patients (88%) remained without disease progression. Lung metastases were associated with recurrence/progression (OR, 6.1; P = 0.04), but coexisting mutation, primary tumor sidedness, and immunotherapy were not. These data provide a retrospective, single-institution analysis that showed that most patients with advanced MSI-H colorectal cancer do not recur after treatment cessation, regardless of the reason for stopping treatment or a variety of patient and disease features, supporting an optimistic prognosis of sustained disease control. Outcomes for patients with MSI-H colorectal cancer stopping immunotherapy after disease control remain unknown. Sixty-four patients with MSI-H colorectal cancer from our institution stopping treatment for sustained benefit or toxicity were retrospectively assessed. After median follow up of 22 months and median immunotherapy exposure of 18 months, 88% patients remained without progression. All patients who recurred or progressed and were rechallenged with immunotherapy have continued to experience disease control.


[Indications for venous thrombectomy].
Thrombectomy has a place in the treatment of acute venous thrombosis. However, this is only the case in certain conditions. Its use is indisputable in true blue venous thrombosis which is a rarely occurring pathology. It may be proposed and discussed for recent thrombosis, of a known and correctable cause, blocking one or several important venous channels in a patient likely to develop an invalidating postthrombotic syndrome.


Pars plana vitrectomy for acute retinal detachment in penetrating ocular injuries.
We studied 41 eyes with acute retinal detachment after penetrating ocular trauma in a retrospective cohort analysis. Pars plana vitrectomy was performed in 28 eyes, while the remaining 13 eyes had only primary repair and closure of the wound. The two groups differed in the type of trauma (more gunshot wounds in the vitrectomy group and more blunt injuries in the nonvitrectomized group). Visual success (visual acuity of 5/200 or better) was observed in 10 (37%) of the eyes treated by vitrectomy compared with one (8%) of the eyes in the nonvitrectomy group. Anatomic success was achieved in 21 (75%) of the eyes in the vitrectomy group but in only one (8%) of those in the nonvitrectomy group. Enucleation or phthisis was observed in seven (54%) of the eyes in the nonvitrectomy group compared with only five (18%) in the vitrectomy group. Significant prognostic factors for anatomic outcome in the vitrectomy group were the location of the laceration and the presence of the lens.


Performance evaluation of Samsung LABGEO(HC10) Hematology Analyzer.
The Samsung LABGEO(HC10) Hematology Analyzer (LABGEO(HC10)) is a recently developed automated hematology analyzer that uses impedance technologies. The analyzer provides 18 parameters including 3-part differential at a maximum rate of 80 samples per hour. To evaluate the performance of the LABGEO(HC10). We evaluated precision, linearity, carryover, and relationship for complete blood cell count parameters between the LABGEO(HC10) and the LH780 (Beckman Coulter Inc) in a university hospital in Korea according to the Clinical and Laboratory Standards Institute guidelines. Sample stability and differences due to the anticoagulant used (K₂EDTA versus K₃EDTA) were also evaluated. The LABGEO(HC10) showed linearity over a wide range and minimal carryover (<1%) for white blood cell, hemoglobin, red blood cell, and platelet parameters. Correlation between the LABGEO(HC10) and the LH780 was good for all complete blood cell count parameters (R > 0.92) except for mean corpuscular hemoglobin concentration. The bias estimated was acceptable for all parameters investigated except for monocyte count. Most parameters were stable until 24 hours both at room temperature and at 4°C. The difference by anticoagulant type was statistically insignificant for all parameters except for a few red cell parameters. The accurate results achievable and simplicity of operation make the unit recommendable for small to medium-sized laboratories.


The mean field theory in EM procedures for blind Markov random field image restoration.
A Markov random field (MRF) model-based EM (expectation-maximization) procedure for simultaneously estimating the degradation model and restoring the image is described. The MRF is a coupled one which provides continuity (inside regions of smooth gray tones) and discontinuity (at region boundaries) constraints for the restoration problem which is, in general, ill posed. The computational difficulty associated with the EM procedure for MRFs is resolved by using the mean field theory from statistical mechanics. An orthonormal blur decomposition is used to reduce the chances of undesirable locally optimal estimates. Experimental results on synthetic and real-world images show that this approach provides good blur estimates and restored images. The restored images are comparable to those obtained by a Wiener filter in mean-square error, but are most visually pleasing.


Decreased nitric oxide production accounts for secondary arteriolar constriction after retinal branch vein occlusion.
After retinal branch vein occlusion (BVO), the arteriole crossing the occluded territories is often constricted. This constriction persists up to several weeks and is correlated with the development of extended territories of nonperfused capillaries. These are results of an investigation supporting the hypothesis that decrease in the production of nitric oxide (NO) accounts for the observed arteriolar constriction. Preretinal [NO] was measured using an NO microprobe in the anesthetized miniature pigs, before and during the first 4 hours after experimental branch vein occlusion. Modifications of arteriolar diameter were correlated to preretinal [NO] changes. The retinal arteriolar sensitivity to constitutive NO was checked by applying preretinal puff injections of nitro-L-arginine (L-NA) after both systemic hypoxia and branch vein occlusion. Two hours after branch vein occlusion there was a 73.7 +/- 4% decrease in preretinal [NO] and a simultaneous 25.4 +/- 3.4% decrease in the diameter of the arteriole in the affected territory. Both persisted for at least 4 hours after branch vein occlusion. Applying a puff of L-NA to an arteriole previously dilated by systemic hypoxia induced a vasoconstriction. However, no arteriolar constriction was observed when a puff was applied to an arteriole after branch vein occlusion. These results show that experimental branch vein occlusion induces in the affected retina an impairment in the release of constitutive NO and an arteriolar constriction, which, in turn, contributes to the development of hypoxia in tissue and neuronal swelling and death in the inner retina.