Pro-Con Debate: 1- vs 2-Hour Fast for Clear Liquids Before Anesthesia in Children.
Perioperative fasting guidelines are designed to minimize the risk of pulmonary aspiration of gastrointestinal contents. The current recommendations from the American Society of Anesthesiologists (ASA) and the European Society of Anaesthesiology and Intensive Care (ESAIC) are for a minimum 2-hour fast after ingestion of clear liquids before general anesthesia, regional anesthesia, or procedural sedation and analgesia. Nonetheless, in children, fasting guidelines also have consequences as regards to child and parent satisfaction, hemodynamic stability, the ability to achieve vascular access, and perioperative energy balance. Despite the fact that current guidelines recommend a relatively short fasting time for clear fluids of 2 hours, the actual duration of fasting time can be significantly longer. This may be the result of deficiencies in communication regarding the duration of the ongoing fasting interval as the schedule changes in a busy operating room as well as to poor parent and patient adherence to the 2-hour guidelines. Prolonged fasting can result in children arriving in the operating room for an elective procedure being thirsty, hungry, and generally in an uncomfortable state. Furthermore, prolonged fasting may adversely affect hemodynamic stability and can result in parental dissatisfaction with the perioperative experience. In this PRO and CON presentation, the authors debate the premise that reducing the nominal minimum fasting time from 2 hours to 1 hour can reduce the incidence of prolonged fasting and provide significant benefits to children, with no increased risks.


[Diagnosis and surgical treatment of symptomic stomach diverticulum].
Gastric diverticulum is a rather rare disease. This lesion is diagnosed in about 0.01% of cases during contrast-enhanced X-ray examination and in 0.04-0.11% of patients undergoing endoscopic examination. Symptomatic diverticulum is complicated by diverticulitis, bleeding, perforation and malignant transformation. Therefore, surgical resection is indicated. We report surgical treatment of a patient with diverticulum of the cardiac part of the stomach. Endoscopic and X-ray examination was valuable to establish the correct diagnosis. Laparoscopic approach minimized surgical trauma and reduced surgery time.


The future of B-cell lymphoma therapy: the B-cell receptor and its downstream pathways.
It is becoming increasingly apparent that tonic signaling through the B cell receptor provides a growth and survival signal in many types of B cell lymphomas, and that disruption of B cell receptor signaling can be lethal to malignant B cells. Several small molecule tyrosine kinase inhibitors, which block signaling pathways downstream from the B cell receptor, are in active clinical development. Preliminary data suggests impressive activity in relapsed and refractory B cell lymphomas. Among the kinases which have been targeted are Spleen tyrosine kinase (Syk), the Bruton's tyrosine kinase (BTK), and phosphoinositide 3-kinase (PI3K). This article discusses the rationale for targeting these pathways and summarizes the current clinical trial data for agents targeting Syk, BTK, and PI3K.


Effects of interface mutations on association modes and electron-transfer rates between proteins.
Although bonding networks determine electron-transfer (ET) rates within proteins, the mechanism by which structure and dynamics influence ET across protein interfaces is not well understood. Measurements of photochemically induced ET and subsequent charge recombination between Zn-porphyrin-substituted cytochrome c peroxidase and cytochrome c in single crystals correlate reactivity with defined structures for different association modes of the redox partners. Structures and ET rates in crystals are consistent with tryptophan oxidation mediating charge recombination reactions. Conservative mutations at the interface can drastically affect how the proteins orient and dispose redox centers. Whereas some configurations are ET inactive, the wild-type complex exhibits the fastest recombination rate. Other association modes generate ET rates that do not correlate with predictions based on cofactor separations or simple bonding pathways. Inhibition of photoinduced ET at <273 K indicates gating by small-amplitude dynamics, even within the crystal. Thus, different associations achieve states of similar reactivity, and within those states conformational fluctuations enable interprotein ET.


[Clinical observations on the mobility of natural teeth in patients with partial dentures].
During the course of the study treatment consisted of individual motivation training and instruction in basic dental hygiene, two thorough cleansings, and careful daily plaque controls. The effect of periodontal treatment on the degree of inflammation, mobility, and periodontal pocket depth was determined at the end of a 20 day period of observation. Plaque controls appear to be more significant for the periodontium than stress exerted on the residual teeth.


Peptide-templating dye-sensitized solar cells.
A hollow TiO(2) nanoribbon network electrode for dye-sensitized solar cells (DSSC) was fabricated by a biotemplating process combining peptide self-assembly and atomic layer deposition (ALD). An aromatic peptide of diphenylalanine was assembled into a three-dimensional network consisting of highly entangled nanoribbons. A thin TiO(2) layer was deposited at the surface of the peptide template via the ALD process. After the pyrolysis of the peptide template, a highly entangled nanotubular TiO(2) framework was successfully prepared. Evolution of the crystal phase and crystallite size of the TiO(2) nanostructure was exploited by controlling the calcination temperature. Finally, the hollow TiO(2) nanoribbon network electrode was integrated into DSSC devices and their photochemical performances were investigated. Hollow TiO(2) nanoribbon-based DSSCs exhibited a power conversion efficiency of 3.8%, which is comparable to the conventional TiO(2) nanoparticle-based DSSCs (3.5%). Our approach offers a novel pathway for DSSCs consisting of TiO(2) electrodes via biotemplating.


Launching native health leaders: students as community-campus ambassadors.
Ancient teaching styles such as storytelling can help Native students to navigate the educational pipeline, and become forces for shaping health and research landscapes. Many experience isolation on campuses where these worldviews are marginalized. Launching Native Health Leaders (LNHL) reduces academic isolation by creating an environment where students identify with Native values while exposing them to health and research career opportunities and interdisciplinary professional and community networks. Student experiences and the LNHL mentoring approach are described through phases of the Hero's Journey, a universal mythic story of human struggle and transformation. Undergraduates were recruited to attend health and research conferences through college and university student service programs. Tribal community representatives led group discussions focused on tribal health issues, and students explored intersections of indigenous knowledge with community-based participatory research (CBPR) and their educational journeys. LNHL supported more than sixty students to attend eight professional conferences since 2006 that included themes of cancer control, tribal wellness, and indigenous knowledge systems for health. Students pursuing higher degrees and community service careers participated in conference sessions, small group discussions, and reflection activities with professional and tribal community mentors. Mainstream academic systems must include indigenous voices at all levels of leadership to shift the direction of health trends. LNHL builds capacity for community-based efforts by balancing Indigenous and academic mentoring and empowering Native students to navigate their personal journeys and create pathways to serve the needs of Indigenous peoples. Students from other marginalized groups may benefit from an LNHL mentoring approach.


Are sodium lauryl sulfate-containing toothpastes suitable vehicles for xylitol?
The hypothesis to be tested in this study was that toothpastes containing sodium lauryl sulfate (SLS) is unsuitable vehicles for xylitol. The bacteriostatic (and cariostatic) effect of xylitol is assumed to be caused by intracellular accumulation of xylitol-5-P in plaque bacteria. Experiments were designed to investigate whether presence of SLS would affect the uptake of xylitol by interacting with the bacterial membranes and thus inhibit xylitol-5-P formation. It was shown in an in vitro study that even very low concentrations of the strong anionic detergent SLS inhibited uptake of xylitol and xylitol-5-phosphate formation by dental plaque totally. The mild nonionic detergent ethoxylated stearyl alcohol (30x EO) had no such effect. In vivo experiments with toothpastes containing xylitol and either the strong or the mild detergent, showed that xylitol in toothpaste with SLS was not available for the plaque bacteria and gave no adaptation to xylitol, whereas in the presence of 30x EO it was available, and a xylitol adaptation was observed. Glucose metabolism, which was also studied for the plaque samples, was not significantly affected by presence of any of the 2 detergents, indicating that the amounts of xylitol in toothpastes were presumably too low to give clinical significant effects, even when mild detergents are used.


Chemicals and cancer in humans: first evidence in experimental animals.
Certain human diseases have been traced to exposure to environmental and occupational chemicals. In many instances the first evidence of potential adverse effects came from experimental studies and were subsequently discovered in humans. Associations of human cancers, as a diverse group of diseases, and chemicals have been made since the middle 1700s. Since then, nearly 100 chemicals, mixtures of chemicals, or exposure circumstances are now recognized as being or strongly implicated as being carcinogenic to humans. Of the less than 1000 agents evaluated adequately for carcinogenicity in laboratory animals, a varying spectrum of data from studies on humans are available for only about 20-25%. So far, more than 60 agents are linked unequivocally as causing cancer in humans, and another 50 or so are strongly suspected of being carcinogenic to humans. Not all of these have been or can be evaluated in animals because some are industrial processes or "occupations," some are environmental and cultural risk factors, and some are mixtures of agents. For those that can be studied experimentally, the qualitative concordance between humans and animals approaches unity, and in every case there is at least one common organ site of cancer in both species. The evidence of carcinogenicity in experimental animals preceded that observed in humans for nearly 30 agents and is the subject of this paper.


[Pharmacokinetics of skin and blood of Tripterygium wilfordii and Paeonia lactiflora micro-emulsion gel based on micro-dialysis technology].
To further investigate the metabolism of Tripterygium wilfordii and Paeonia lactiflora micro-emulsion gel in vivo,an LCMS/MS method was established for the determination of triptolide and paeoniflorin in T. wilfordii and P. lactiflora micro-emulsion gel.The extracorporeal recovery rate of blood probe was measured by concentration difference methods( incremental method and decremental method). Meanwhile,the skin and blood micro-dialysis methods of tripterine and paeoniflorin were established,and the pharmacokinetics of T. wilfordii microemulsion gel in skin and blood was studied by micro-dialysis combined with LC-MS/MS quantitative analysis. The results showed that the established method for the determination of triptolide and paeoniflorin in T. wilfordii microemulsion gel was well linear within the required range,and the specificity,recovery rate and degree of precision of the chromatography all conformed to the research requirements of micro-dialysis samples. The stability of freeze-thawing and the residual effect all conformed to the criteria of biological sample methodology. The probe recovery rates measured by incremental method and decremental method were almost consistent with the extracorporeal recovery rate test. The recovery rates of paeoniflorin in skin and blood micro-dialysis were( 30. 60±1. 09) % and( 28. 01± 1. 75) %,respectively. And the recovery rates of skin and blood micro-dialysis were( 26. 79 ± 2. 78) % and( 25. 39±1. 86) %,respectively. The intraday recovery rate of probes was stable within 11 h. The results of pharmacokinetic study showed that the Cmaxvalues of triptolide in skin and blood were( 148. 03±41. 51) and( 76. 77±15. 27) μg·L-1,respectively. And the Tmaxvalues were( 2. 33±0. 29) and( 3. 00± 0) h,respectively. The AUC0-11 hvalues were( 2 814. 05± 1 070. 37) and( 1 580. 63±208. 27) μg·h·L-1,respectively. The MRT0-11 hvalues were( 4. 20± 0. 33) and( 4. 54± 0. 34) h,respectively. The T1/2 values were( 4. 61±4. 11) and( 1. 07± 0. 13) h,respectively. The Cmaxvalues of paeoniflorin in skin and blood were( 991. 88 ± 152. 22) and( 407. 02±120. 06) μg·L-1,respectively. The Tmaxvalues were( 2. 00±0) h and( 2. 83±0. 29) h,respectively. The AUC0-11 hvalues were( 18 430. 27±3 289. 35) and( 6 338. 59 ± 1 659. 32) μg·h·L-1,respectively. The MRT0-11 hvalues were( 4. 29 ± 0. 16) and( 4. 00±0. 05) h,respectively. The T1/2 values were( 2. 16±0. 43) and( 1. 78±0. 48) h,respectively. The results suggested that micro-emulsion gel played a role in forming skin reservoir through percutaneous penetration. It not only could improve drug transdermal efficiency,but also control the sustained release of drug and form a long-term effect.


Management of patients at risk of acute kidney injury.
Acute kidney injury (AKI) is a multifaceted syndrome that occurs in different settings. The course of AKI can be variable, from single hit and complete recovery, to multiple hits resulting in end-stage renal disease. No interventions to improve outcomes of established AKI have yet been developed, so prevention and early diagnosis are key. Awareness campaigns and education for health-care professionals on diagnosis and management of AKI-with attention to avoidance of volume depletion, hypotension, and nephrotoxic interventions-coupled with electronic early warning systems where available can improve outcomes. Biomarker-based strategies have not shown improvements in outcome. Fluid management should aim for early, rapid restoration of circulatory volume, but should be more limited after the first 24-48 h to avoid volume overload. Use of balanced crystalloid solutions versus normal saline remains controversial. Renal replacement therapy should only be started on the basis of hard criteria, but should not be delayed when criteria are met. On the basis of recent evidence, the risk of contrast-induced AKI might be overestimated for many conditions.


Peutz-Jeghers syndrome manifesting complete intussusception of the appendix and associated with a focal cancer of the duodenum and a cystadenocarcinoma of the pancreas: report of a case.
The unusual occurrence of an "inside-out" appendix reported here is a case of complete intussusception of the appendix of a 45-year-old woman with Peutz-Jeghers syndrome in whom the diagnosis of intussusception was made preoperatively. At laparotomy, the lead point of intussusceptum was revealed to be a Peutz-Jeghers syndrome polyp of the appendix. There was also a cystic lesion in the pancreas, and subsequent distal pancreatectomy revealed a cystadenocarcinoma of the pancreas. Two jejunal Peutz-Jeghers syndrome polyps and two duodenal Peutz-Jeghers syndrome polyps were found via intraoperative endoscopies. The duodenal polyps were endoscopically removed, whereas a jejunal wedge resection was performed for the adjoining jejunal polyps. One of the two duodenal polyps possessed an adenocarcinoma focus. To our knowledge, this is the first report of complete intussusception of the appendix caused by a Peutz-Jeghers syndrome polyp.


[Which Screening Instruments are used in Kindergarten for Developmental Assessment and Identification of Developmental Needs? Quality and Usefulness Criteria of the Instruments].
On the basis of the educational plans of the federal states, kindergartens have the duty to observe the development of children.There are various instruments for developmental observations and the identification of developmental needs.However, the quality and content of these instruments vary greatly. To date, there has been little systematic research on the use of screening instruments in kindergarten.Therefore, the aim of this study was to investigate the use and the satisfaction with instruments for developmental observations and the identification of support needs. Additionally, an analysis of the used instruments in regard of their psychometric quality was conducted. N = 190 kindergarten fromThuringia participated in the study. An online questionnaire was completed, which particularly addressed the question of whether and, if so, which screening instruments were used for developmental observations or for the identification of support needs. In addition, specific information on these instruments (e. g. duration, satisfaction) was collected. Nearly 94 % of participating kindergarten used screening instruments for developmental observations, and 69 % used instruments for identifying support needs. For most frequently used instruments the psychometric quality was weak and only few practice criteria were considered.


The key phytochemistry of rosemary (Salvia rosmarinus) contributing to hair protection against UV.
Extracts from rosemary (Salvia Rosmarinus) are analysed for their phytochemistry using LC-MS and the phytochemistry identified. The same extracts were tested for their efficacy to act as antioxidants by both hydrogen-atom transfer (ORAC) and single electron transfer (FRAP). A correlation analysis was performed to identify the key phytochemistry responsible for antioxidant efficacy. The top performing extracts were then tested in a peptide model and in hair with the presence of UV to measure ability to protect against UV-induced peptide and protein damage. Polyphenols (e.g. rosmarinic acid, glycosides of selgin) and abietane diterpenes (e.g. carnosic acid) in rosemary were identified as the principal compounds which enables the extracts to protect hair from UV. The objective of this work was to correlate the phytochemistry of rosemary (Salvia rosmarinus), a botanical with known antioxidant properties, to a UV protection benefit in hair. These data will give insights into mechanisms of UV damage, the ROS formed and their reactivity. LC-MS was used to compare the compounds in 10 commercial extracts of rosemary. ORAC (oxygen radical antioxidant capacity) and FRAP (ferric reducing antioxidant power) were used to measure the antioxidant capacity of the rosemary extracts. The ORAC assay measures ability of an antioxidant to react with a peroxyl radical via hydrogen atom extraction and FRAP measures electron transfer through reduction of ferric iron (Fe3+ ) to ferrous iron (Fe2+ ) by antioxidants present in the samples. Correlation of extract composition with antioxidant measures was performed using principal component analysis. Selected extracts were assessed for their ability to protect hair from UV damage in a model peptide system and on hair. In addition, the same methods were used to test rosmarinic acid and carnosic acid, key phytochemistries in the rosemary extracts. The model system was a peptide and its decomposition on exposure to UV was monitored by LC-MS in the absence and presence of the rosemary extracts. Hair degradation in the presence of UV was measured by exposure of UV in an Atlas weatherometer followed by extraction of degraded protein in water. A fragment of the S100A3 protein was used as a marker of UV damage (m/z = 1278) and quantified via LC-MS. Ten rosemary extracts were assessed for antioxidant performance and correlated with their compositions. The phytochemistry in each extract varied widely with a total of 33 individual compounds identified. The differences were most likely driven by the solvent and extraction method used by the supplier with extracts varying in the proportion of polar or non-polar compounds. This did influence their reactivity in the ORAC and FRAP assays and their efficacy in preventing protein damage. Two of the key compounds identified were rosmarinic acid and carnosic acid, with rosmarinic acid dominating in extracts with mainly polar compounds and carnosic acid dominating in extracts with mainly nonpolar compounds. Extracts with higher rosmarinic acid correlated with ORAC and FRAP scores, with UV protection on hair and in the peptide model system. The extracts chosen for hair experiments showed hair protection. UV protection was also measured for rosmarinic and carnosic acid. Despite the variation in the profile of phytochemistries in the 10 rosemary extracts, likely driven by the chosen extraction method, all rosemary extracts had antioxidant activity measured. This study suggests that the polyphenols (e.g. rosmarinic acid, glycosides of selgin) and abietane diterpenes (e.g. carnosic acid) are the principal compounds which enables the extracts to protect hair from UV.


Advanced Gastric Cancer Perforation Mimicking Abdominal Wall Abscess.
Surgeons occasionally encounter a patient with a gastric cancer invading an adjacent organ, such as the pancreas, liver, or transverse colon. Although there is no established guideline for treatment of invasive gastric cancer, combined resection with radical gastrectomy is conventionally performed for curative purposes. We recently treated a patient with a large gastric cancer invading the abdominal wall, which was initially diagnosed as a simple abdominal wall abscess. Computed tomography showed that an abscess had formed adjacent to the greater curvature of the stomach. During surgery, we made an incision on the abdominal wall to drain the abscess, and performed curative total gastrectomy with partial excision of the involved abdominal wall. The patient received intensive treatment and wound management postoperatively with no surgery-related adverse events. However, the patient could not receive adjuvant chemotherapy and expired on the 82nd postoperative day.


Altruistic behavior in a sphecid wasp: support for kin-selection theory.
Trigonopsis cameronii females often work in groups of up to four individuals on single nests, and because of inbreeding and a tendency to return to the mother nest, nestmates are likely to be highly related. The altruistic behavior associated with group living, most notably the failure to steal prey from nestmates, can thus be explained by kin-selection theory.


New records and a new species of the cavernicolous genus Guiodytes Tian, 2013 from Guangxi, China (Coleoptera: Carabidae: Scaritinae).
A new species of the genus Guiodytes Tian, 2013 is described from a limestone cave called Shuiku Dong in Huanjiang County of northernmost Guangxi, southern China. G. deharvengi n. sp. is the first depigmented species of Guiodytes. It is close to G. cavicola Tian, 2013, but easily recognized by its broader and yellowish brown body. In addition, new records for G. cavicola Tian, 2013 are provided from two caves in Du'an County of northern Guangxi, with description of the male genitalia. A key to all three known species and a distributional map of Guiodytes are also given.


A sero-epidemiological study of Haemophilus somnus infection in dairy cattle.
Five repeated cross-sectional serological surveys of 790 dairy cattle in 4 dairy herds between December 1985 and February 1987 provided an opportunity to study the changes in the seroprevalence of Haemophilus somnus across the 5 surveys and with respect to some demographic and disease variables. The demographic variables included were age (heifers or cows) and farm, representing two groups of herds (two herds in each group, located in the Central and Northern Valleys of California). The serological status of cattle as either negative or positive against H. somnus, Campylobacter fetus and Leptospira hardjo were determined with enzyme linked-immunosorbent assays. Logistic regression analysis was used to compute maximum likelihood estimates of adjusted odds ratios and their respective 95% confidence intervals. The baseline risk of being H. somnus seropositive in the cattle observed at first sampling did not vary significantly during the study period after adjustment for the effects of covariates. Only at first sampling were cows about twice as likely to be H. somnus seropositive than heifers. At samplings 1 and 3, but not at 2 and 5, being in the herds of the Central Valley appeared protective. In contrast, at sampling 4 the cattle in herds in the Central Valley were about 7 times more likely to be H. somnus seropositive. C. fetus-positive cattle were about 3 times more likely to be H. somnus seropositive at sampling 1 only. The relationship between H. somnus status and L. hardjo was not significant during the study period.


Relative accuracy of fine-needle aspiration and frozen section in the diagnosis of well-differentiated thyroid cancer.
The need for and extent of thyroid surgery for a thyroid nodule is usually primarily based on fine-needle aspiration (FNA) and frozen section diagnosis. The relative role of these modalities in 66 patients who had undergone FNA and subsequent thyroidectomy with frozen section was investigated. Cases that demonstrated discordance between FNA and frozen section (n = 22; 33%) were identified, and all slides were re-reviewed by a cytopathologist using current established cytologic criteria. A change in diagnosis was made in 13 cases with an increase in accuracy of FNA from 71% to 88%. The accuracy of frozen section (92%) did not change appreciably with re-review (94%). The accuracy of FNA and frozen section combined was found to be 98%. The rate of discordance decreased from 33% to 13% with re-review. When strict histologic and cytologic criteria are applied, FNA and frozen section are accurate and complementary methods that help in determining the operative management of thyroid masses. However, when FNA yields a diagnosis of "follicular neoplasm," frozen section is unlikely to change this diagnosis.


Structure and dynamics of flour by solid state NMR: effects of hydration and wheat aging.
The effects of accelerated aging of wheat seeds on structural and dynamic properties of dry and hydrated (ca 10 wt % H(2)O) flour at a molecular level were investigated by several high and low resolution solid-state NMR techniques. Identification and characterization of domains with different mobility was performed by (13)C direct excitation (DE) and cross-polarization (CP) magic angle spinning (MAS), as well as by (1)H static and MAS experiments. (1)H spin-lattice relaxation times (T(1) and T(1)(rho)) measurements were carried out to investigate molecular motions in different frequency ranges. Experimental data show that the main components of flour (starch and gluten proteins) are in a glassy phase, whereas the mobile fraction is constituted by lipids and, in hydrated samples, absorbed water. A lower proportion of rigid domains, as well as an increased dynamics of all flour components are observed after both seeds aging and flour hydration. Linear average dimensions between 20 and 200 A are estimated for water domains in hydrated samples.


Detecting hemodynamic changes in the foot vessels of diabetic patients by photoacoustic tomography.
Limb perfusion monitoring is critical for diabetes mellitus (DM) patients as they are vulnerable to vascular complications due to prolonged hyperglycemia. However, current clinical approaches are ineffective in vascular imaging and in assessing vascular function in lower limbs. In this work, a concave ultrasound transducer array-based photoacoustic tomography (PAT) system was used to image the foot dorsal section of a subject, and a total of seven DM patients and seven healthy volunteers were enrolled in this study. Hemodynamic changes in foot vessels during vascular occlusion as well as oxygen saturation (SO2 ) in rest were analyzed for both groups. The results obtained showed that DM patients have a unique peripheral hemodynamic response to occlusion and a lower level SO2 , compared to that for healthy subjects. This suggests that PAT has the potential to detect vascular dysfunction in DM patients and to measure the effect of treatment.


[Effect of sulfasalazine and its metabolites on prostaglandin and leukotriene liberation from human synovial tissue].
The effects of sulfasalazine (SASP) and its metabolites sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA) were investigated on release of prostaglandins (PG) and leukotrienes (LT) from synovial tissue of 37 patients with osteoarthritis, chondrocalcinosis and rheumatoid arthritis. Calcium ionophore A23187 significantly increased the release of PGE2, 6-keto-PGF1 alpha, LTB4, and LTC4 from human synovial tissue irrespective of the underlying joint disease. SASP inhibited release of LTC4 and increased release of PGE2. On the other hand, 5-ASA and SP inhibited the release of all eicosanoids measured. The effective concentrations of SASP and SP were found to be in the range which can be reached during SASP therapy. On the other hand, blood and synovial fluid levels of 5-ASA are considerably lower than those which inhibit eicosanoid synthesis in vitro. While nonsteroidal anti-inflammatory drugs, which are used for symptomatic therapy of rheumatoid arthritis, inhibit cyclooxygenase only, SP, the active metabolite of the second line anti-rheumatic drug SASP, inhibits both PG and LT release. Inhibition of LT synthesis by SASP and SP could contribute to the second line efficacy of SASP therapy in rheumatoid arthritis.


Effect of Metabolic Syndrome Score, Metabolic Syndrome, and Its Individual Components on the Prevalence and Severity of Angiographic Coronary Artery Disease.
The clinical significance of metabolic syndrome (MS) score, MS, and its individual components with respect to risk prediction of coronary artery disease (CAD) remains unclear. The objective of this study was to investigate whether and to what extent MS score, MS, and its individual components were related to the risk of CAD. Among 1191 participants who underwent coronary angiography for the confirmation of suspected myocardial ischemia, 858 were included in this study according to the inclusion criteria from September 2010 to June 2013. MS was diagnosed with the 2005 National Cholesterol Education Program Adult Treatment Panel III criteria. The severity of coronary atherosclerosis was assessed by Gensini score. The results showed that the age- and sex-adjusted odds ratios (OR s) for CAD were as follows: MS score, 1.327; MS, 2.013; elevated waist circumference, 1.447; reduced high-density lipoprotein cholesterol, 1.654; and elevated fasting glucose, 1.782; all P < 0.05; whereas for elevated triglycerides, 1.324, and elevated blood pressure, 1.342, both P > 0.05. After multivariate adjustment, results showed that only MS and elevated fasting glucose were significantly associated with CAD (OR, 1.628, 95% confidence interval [CI], 1.151-2.305, P = 0.006 for elevated fasting glucose, and OR, 1.631, 95% CI, 1.208-2.203, P = 0.001 for MS). The study showed that only MS score and elevated fasting glucose were significantly associated with Gensini score (standardized coefficient, 0.101, P = 0.031 for elevated fasting glucose and standardized coefficient, 0.103, P = 0.009 for MS score). The present study demonstrated that MS score, MS, and its individual components might have different contributions to CAD prevalence and severity. MS and elevated fasting glucose were independent risk factors for the prevalence of angiographic CAD whereas MS score and elevated fasting glucose were significantly associated with the severity of CAD.


Method for validating cloud mask obtained from satellite measurements using ground-based sky camera.
Error propagation in Earth's atmospheric, oceanic, and land surface parameters of the satellite products caused by misclassification of the cloud mask is a critical issue for improving the accuracy of satellite products. Thus, characterizing the accuracy of the cloud mask is important for investigating the influence of the cloud mask on satellite products. In this study, we proposed a method for validating multiwavelength satellite data derived cloud masks using ground-based sky camera (GSC) data. First, a cloud cover algorithm for GSC data has been developed using sky index and bright index. Then, Moderate Resolution Imaging Spectroradiometer (MODIS) satellite data derived cloud masks by two cloud-screening algorithms (i.e., MOD35 and CLAUDIA) were validated using the GSC cloud mask. The results indicate that MOD35 is likely to classify ambiguous pixels as "cloudy," whereas CLAUDIA is likely to classify them as "clear." Furthermore, the influence of error propagations caused by misclassification of the MOD35 and CLAUDIA cloud masks on MODIS derived reflectance, brightness temperature, and normalized difference vegetation index (NDVI) in clear and cloudy pixels was investigated using sky camera data. It shows that the influence of the error propagation by the MOD35 cloud mask on the MODIS derived monthly mean reflectance, brightness temperature, and NDVI for clear pixels is significantly smaller than for the CLAUDIA cloud mask; the influence of the error propagation by the CLAUDIA cloud mask on MODIS derived monthly mean cloud products for cloudy pixels is significantly smaller than that by the MOD35 cloud mask.


Blood transport method for chromosome analysis of residents living near Semipalatinsk nuclear test site.
A study was conducted to compare the storage conditions and transportation period for blood samples collected from residents living in areas near the Semipalatinsk nuclear test site (SNTS). Experiments were performed to simulate storage and shipping environments. Phytohaemagglutinin (PHA)-stimulated blood was stored in 15-ml tubes (condition A: current transport method) in the absence or in 50-ml flasks (condition B: previous transport method) in the presence of RPMI-1640 and 20% fetal bovine serum (FBS). Samples were kept refrigerated at 4 degrees C and cell viability was assessed after 3, 8, 12 and 14 days of storage. RPMI-1640, 20% FBS and further PHA were added to blood samples under condition A in 50-ml flasks for culture. Whole-blood samples under condition B were directly incubated without further sub-culturing process, neither media nor PHA were added, to adopt a similar protocol to that employed in the previous transport method. Samples in condition A and condition B were incubated for 48 hr at 37 degrees C and their mitotic index was determined. The results showed that viable lymphocytes were consistent in both storage conditions but the mitotic index was higher in condition A than in condition B. Although further confirmation studies have to be carried out, previous chromosomal studies and the present experiment have shown that PHA-stimulated blood could be stored without culture medium for up to 8 days under condition A. The present results will be useful for cytogenetic analysis of blood samples that have been transported long distances wherever a radiation accident has occurred.


Biomarkers in hepatocellular carcinoma: an overview.
Current methods for HCC diagnosis have not an optimal diagnostic accuracy. The detection of more than one biomarker seems to improve their individual performance and provide an accurate HCC diagnosis approach. Individual gene expression seems to influence whether or not the treatment is successful, since several molecules have interfere with cancer associated pathways and have been related to poor prognosis which condition the lack of effective treatment options. Areas covered: Novel biomarkers have been proposed as a useful tool in each patient prognosis. This article aims to review the recent evidence based on HCC biomarkers which seems to have a regulative role according to tumor cell development leading to a specific biological response. Epigenetic regulation, miRNAs, and genome sequencing analysis propose molecular expression signatures as novel biomarkers which allowed achieve the major goal for the use of biomarkers in clinical practice. Moreover, a deeper analysis for determine the diagnostic accuracy of biomarkers has been made. Expert commentary: To improve of methodological designs and sample sizes are needed in order to support the role of biomarkers in HCC. Furthermore, is necessary to consider HCC etiologies and all clinic disease context to carried out clinical phase studies to thrust biomarkers application.


Mitogen-associated protein kinase- and protein kinase A-dependent regulation of rhodopsin promoter expression in zebrafish rod photoreceptor cells.
Mitogen-associated protein kinase (MAPK)- and protein kinase A (PKA)-dependent signal transductions play important roles in the regulation of gene expression. Both MAPK and PKA pathways can be activated by light exposure. In this study, we investigated the effect of light on MAPK and PKA signal transduction and their roles in the regulation of rhodopsin promoter expression by using transgenic zebrafish [Tg(rhod::GFP)]. The Tg(rhod::GFP) fish express short half-life GFP that is under the transcriptional control of the zebrafish rhodopsin promoter and can therefore be used for in vivo studies of rhodopsin gene transcription in live cells. Blue light plays a role in the regulation of rhodopsin promoter expression via an MAPK-mediated signal transduction cascade. Blue light excites cryptochromes (CRY), which activate the downstream PKC-dependent MAPK signal pathway. White light, on the other hand, regulates rhodopsin promoter expression via a G-protein-coupled cAMP-dependent PKA pathway. White light promotes dopamine release in the retina, which activates dopamine receptors and the downstream PKA pathway. Blocking MAPK signaling diminishes the blue light-induced increases in rhodopsin promoter expression, but this treatment has no effect on white light-mediated rhodopsin promoter expression. Conversely, blocking the PKA pathway diminishes the white light-induced rhodopsin promoter expression but does not affect rhodopsin promoter expression regulated by blue light. Together, the data suggest that MAPK and PKA regulate rhodopsin transcription through parallel signal transduction pathways.


Structural, institutional and organizational factors associated with successful pay for performance programmes in improving quality of maternal and child health care in low and middle income countries: a systematic literature review.
Pay for Performance (P4P) mechanisms to health facilities and providers have been implemented in several low- and middle-income countries (LMIC) to improve maternal and child health (MCH). These are tied to predetermined quality and quantity indicators. There is limited synthesized information on the structural, institutional and organizational factors that influence the success of P4P programmes with respect to quality of care. This review, which builds on a previously published review sets out to synthesize existing literature on the factors that influence the outcome of P4P programmes and quality of care. A literature review was conducted of published studies documenting implementation of P4P interventions and quality of care in low and middle income countries. Records published between June 2014 and September 2017 were selected and combined with articles from January 1990 to June 2014 previously identified by colleagues. 13 studies were included in the final analysis. The majority of studies found a positive impact on quality of care scores and at least one study showed significant reductions in mortality outcomes in newborns. One study from Afghanistan did not show any positive effects. Structural factors associated with likely success of P4P programmes included: explicit acceptance and understanding by health workers; limiting the number of indicators measured with inputs from health workers. Organisational factors included sufficient incentive payments. Notably the main positive outcome identified was facility financial autonomy from additional payments. Verification by external assessors revealed no major manipulation to achieve payment trigger levels. The primary institutional factors identified that P4P programmes fared better when introduced alongside other health reforms and increased funding. This review has found that P4P is not a uniform intervention, but rather a range of approaches with a substantial variation and complexity in how programmes incorporate quality of care considerations. P4P has shown to have an impact on the quality of a number of limited aspects of maternal and child health care. Further research is needed to understand whether additional aspects of the quality of MCH care could be positively influenced by P4P programmes and how health worker motivation and acceptance are linked to this.


The reinforced full-root technique for the Ross operation: surgical considerations and operative insights.
Surgical treatment of young and middle-aged patients suffering from aortic valve disease remains an unresolved issue due to the limited durability of bioprosthetic heart valve replacements and the valve-related morbidity of patients with mechanical valve substitutes. Theoretically, the "living valve" principle of the Ross operation may represent a potentially viable solution to this dilemma. In this paper, we report on the surgical techniques of the Ross procedure and present long-term post-operative outcomes using the reinforced full-root technique. From 1995 to 2020, a total of 832 consecutive patients (mean age, 43.4±13.7 years; 617 males) underwent a Ross operation using the full-root technique. Patients were prospectively monitored with clinical and echocardiographic follow-up. Total follow-up was 9,046 patients-years and was 92% complete. Mean-follow-up was 10.9±6.9 years (range, 0-24.9 years). Survival at twenty years was 92% (95% CI: 90-94%). Freedom from autograft or right ventricle to pulmonary artery connection reoperation at twenty years was 79% (95% CI: 74-85%). Eighty-nine pulmonary autograft reoperations had to be performed in eighty patients; salvage of the pulmonary autograft could be performed in forty-six of them. Fifty-seven patients required sixty-three reoperations on the right ventricle to pulmonary artery connection. Major cerebral bleeding occurred in one patient and neurological events in seventeen patients, respectively. Over a follow-up interval of up to twenty-five years, the Ross operation with the reinforced full-root technique demonstrated excellent survival in young and middle-aged patients. The rate of pulmonary autograft and right ventricular outflow graft reoperations were low in this patient subset. Therefore, the Ross operation with the reinforced full-root technique represents an enduring and valid treatment option in young and middle-aged patients suffering from aortic valve disease.


Effect of supplementation with cobalamin carried either by a milk product or a capsule in mildly cobalamin-deficient elderly Dutch persons.
A high prevalence of cobalamin deficiency occurs in the elderly population, which may be treated orally or with injections. Little is known about the relative bioavailability of crystalline cobalamin added to food products. The objective was to assess the effect of supplementation with 1000 microg crystalline cobalamin, carried either by a milk product or a capsule, on cobalamin status in mildly cobalamin-deficient elderly Dutch persons. Two double-blind randomized controlled intervention studies, each covering a 12-wk supplementation period, were carried out in parallel. Mildly cobalamin-deficient elderly persons (n = 112) were separately recruited for the milk and capsule trials. Mild cobalamin deficiency was defined as a cobalamin concentration between 100 and 300 pmol/L and a plasma methylmalonic acid (MMA) concentration > or = 0.30 micromol/L. Allocation to the placebo or cobalamin carrier was carried out independently in both trials. In the fortified-milk group, the mean (+/-SD) increase in serum cobalamin was 250 +/- 96 pmol/L, the median (5th and 95th percentiles) decrease in plasma MMA was 0.19 (-0.76, -0.04) micromol/L, and the median decrease in plasma homocysteine was 4.0 (-7.3, 3.0) micromol/L. All changes were significantly different from those in the placebo milk group (P < 0.01). Likewise, in the cobalamin-capsule group, the mean increase in serum cobalamin was 281 +/- 136 pmol/L, the median decrease in plasma MMA was 0.18 (-2.95, 0.14) micromol/L, and the median decrease in plasma homocysteine was 1.8 (-10.6, 2.4) micromol/L; all changes were significantly different from those in the placebo capsule group (P < 0.01). No significant differences were observed between the fortified-milk and capsule groups (P > 0.40). Crystalline cobalamin added to milk is an effective alternative to cobalamin capsules for improving cobalamin status.


Structural-acoustic modeling of automotive vehicles in presence of uncertainties and experimental identification and validation.
The design of cars is mainly based on the use of computational models to analyze structural vibrations and internal acoustic levels. Considering the very high complexity of such structural-acoustic systems, and in order to improve the robustness of such computational structural-acoustic models, both model uncertainties and data uncertainties must be taken into account. In this context, a probabilistic approach of uncertainties is implemented in an adapted computational structural-acoustic model. The two main problems are the experimental identification of the parameters controlling the uncertainty levels and the experimental validation. Relevant experiments have especially been developed for this research in order to constitute an experimental database devoted to structural vibrations and internal acoustic pressures. This database is used to perform the experimental identification of the probability model parameters and to validate the stochastic computational model.


Database analysis of patients with hepatocellular carcinoma and treatment flow in early and advanced stages.
Despite recent developments in treatment modalities and diagnosis, the prognosis of advanced hepatocellular carcinoma (HCC) remains unsatisfactory. To gain insight into treatment decisions for HCC patients, their characteristics and treatment flow in the early and advanced stages were examined. HCC patients' characteristics and treatment flow were retrospectively analyzed using the Japanese medical claims database. The 8999 patients' mean age at HCC diagnosis was 71.1 years, with no difference between early (Stage I/II) and advanced (Stage III/IV) stages. The mean observation period was 26.2 months, shorter in advanced than in early stages. HCV hepatitis was reported in 52.0% of HCC patients, with concomitant hypertension in 53.4%, type 2 diabetes in 45.8%, cirrhosis in 39.3%, and hyperlipidemia in 15.5%. The rates of HCV hepatitis, hypertension, and hyperlipidemia decreased with stage progression. Analysis of treatment flow showed that, at all disease stages, transcatheter arterial chemoembolization (TACE) was the most common first to fourth-line treatment. Epirubicin was the most frequently (44.1%) used chemotherapeutic agent for first-line TACE, followed by miriplatin (23.6%) and cisplatin (12.3%). With stage progression, cisplatin use increased. Sorafenib was used concomitantly for first-line TACE in 3.2% of patients, and its use increased significantly in advanced stages. Clear differences in baseline characteristics and treatment flow between early and advanced stages were identified. Continuous analysis of the database with longer follow-up may provide useful information about treatment selection and prediction of outcome such as survival.


Somatostatin analogues for pancreatic surgery.
Pancreatic resections are associated with high morbidity (30% to 60%) and mortality (5%). Synthetic analogues of somatostatin are advocated by some surgeons to reduce complications following pancreatic surgery, however their use is controversial. To determine whether prophylactic somatostatin analogues should be used routinely in pancreatic surgery. We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 12), MEDLINE, EMBASE and Science Citation Index Expanded to December 2011. We included randomised controlled trials comparing prophylactic somatostatin or one of its analogues versus no drug or placebo during pancreatic surgery (irrespective of language or publication status). Two authors independently assessed trials for inclusion and independently extracted data. We analysed data with both the fixed-effect and random-effects models using Review Manager (RevMan). We calculated the risk ratio (RR), mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) based on an intention-to-treat or available case analysis. When it was not possible to perform either of the above, we performed per protocol analysis. We identified 19 trials (17 trials of high risk of bias) involving 2245 patients. There was no significant difference in the perioperative mortality (RR 0.80; 95% CI 0.56 to 1.16; N = 2210) or the number of patients with drug-related adverse effects between the two groups (RR 2.09; 95% CI 0.83 to 5.24; N = 1199). Quality of life was not reported in any of the trials. The overall number of patients with postoperative complications was significantly lower in the somatostatin analogue group (RR 0.69; 95% CI 0.60 to 0.79; N = 1858) but there was no significant difference in the re-operation rate (RR 1.26; 95% CI 0.58 to 2.70; N = 687) or hospital stay (MD -1.04 days; 95% CI -2.54 to 0.46; N = 1269) between the groups. The incidence of pancreatic fistula was lower in the somatostatin analogue group (RR 0.63; 95% CI 0.52 to 0.77; N = 2161). The proportion of these fistulas that were clinically significant was not mentioned in most trials. On inclusion of trials that clearly distinguished clinically significant fistulas, there was no significant difference between the two groups (RR 0.69; 95% CI 0.34 to 1.41; N = 247). Somatostatin analogues may reduce perioperative complications but do not reduce perioperative mortality. Further adequately powered trials with low risk of bias are necessary. Based on the current available evidence, somatostatin and its analogues are recommended for routine use in patients undergoing pancreatic resection.


Comparison of the Effects of Metoclopramide and Ondansetron on Emergency Service Observation Times in Acute Gastroenteritis-Related Nausea and Vomiting Cases.
The aim of the present study was to compare the effect of metoclopramide and ondansetron treatments on the emergency department observation time in acute gastroenteritis-related nausea and vomiting (NV). The study was conducted retrospectively on 297 patients diagnosed with acute gastroenteritis in a training and research hospital's emergency service observation unit within 6 months. Patients with gastroenteritis who were diagnosed with NV were divided into two groups according to the treatment they received in the observation unit. Patients who received 4 mg ondansetron slow infusion therapy were classified as Group 1, and patients who received 10 mg metoclopramide slow infusion therapy were classified as Group 2. The average age of the patients was 39.57±18.75 years. Of the 297 participants, 56.6% (168) were female. Among them, 51.5% (153) received ondansetron (Group 1), and 48.5% (144) received metoclopramide (Group 2). 6.9% weakness-numbness and 4.9% akathisia were detected due to metoclopramide use. There were no adverse effects related to ondansetron use. The duration of observation ranged from 19 to 75 min in Group 1 and from 42 to 122 min in Group 2. Nineteen (13.2%) patients in Group 2 and 5 (3.3%) patients in Group 1 revisited the emergency department within 24 h due to ongoing complaints. In conclusion, side effects of weakness and akathisia due to metoclopramide use were observed. However, no side effects were observed due to ondansetron use. Additionally, the use of ondansetron showed a shorter observation time and less recurrent admission to the emergency department. Therefore, ondansetron is a more effective drug in the treatment of NV associated with acute gastroenteritis.


Providing the right environment to develop new clinical nurse leaders.
Jacqueline Leigh, Reader, Teaching and Learning, School of Health and Society, University of Salford, firstname.lastname@example.com , and Lisa Littlewood, Director of Placement and Practice Learning, School of Health and Society, University of Salford, evaluate the changes in the delivery of nurse education as a result of the devolution of health and social care decision-making from Westminster to Greater Manchester.


Invasive adenylyl cyclase of Bordetella pertussis. Physical, catalytic, and toxic properties.
A rapid two-step purification to homogeneity of the calmodulin-activated adenylyl cyclase from urea extracts of Bordetella pertussis organisms (strain 114) is described. Catalytic and invasive activities are purified 30- and 177-fold, respectively, and virtually no degraded forms are found. Specific activities are 0.4 mmol/min/mg and 0.5 mumol/mg of enzyme protein/mg of cell protein/min for catalytic and invasive activities, respectively. The 15 amino-terminal amino acids agree with those deduced from the DNA sequence, as does the molecular mass of 175 kDa (guanidine) or 177 kDa (urea) obtained by equilibrium sedimentation. The larger apparent molecular mass seen in sodium dodecyl sulfate-polyacrylamide gel electrophoresis can be ascribed to anomalous migration. Half-maximal cyclase activation occurs at 3-4 X 10(-10) M calmodulin in the presence of Ca2+ and at 2 X 10(-8) M calmodulin in its absence. Ca2+ activation is maximal at 60-100 microM free CaCl2 (at low calmodulin concentrations), and free Ca2+ concentrations above approximately 125 microM are inhibitory at any calmodulin concentration. Extracellular Ca2+ is essential for intoxication. In Chinese hamster ovary cells, exogenous calmodulin does not inhibit penetration of the cyclase.


Identification of sequences required for the import of human protoporphyrinogen oxidase to mitochondria.
Protoporphyrinogen oxidase (PPOX; EC 220.127.116.11), the penultimate enzyme of haem biosynthesis, is a nucleus-encoded flavoprotein strongly associated with the outer surface of the inner mitochondrial membrane. It is attached to this membrane by an unknown mechanism that appears not to involve a membrane-spanning domain. The pathway for its import to mitochondria and insertion into the inner membrane has not been established. We have fused human PPOXs containing N-terminal deletions, C-terminal deletions or missense mutations to yellow fluorescent protein (YFP) and have used these constructs to investigate the mitochondrial import of PPOX in human cells. We show that all the information required for efficient import is contained within the first 250 amino acid residues of human PPOX and that targeting to mitochondria is prevented by fusion of YFP to the N-terminus. Deletion of between 151 and 175 residues from the N-terminus is required to abolish import, whereas shorter deletions impair its efficiency. Fully efficient targeting appears to require both a major targeting signal, the whole or part of which is contained between residues 151 and 175, and which may be involved in anchoring to the inner mitochondrial membrane, together with interaction between this region and a sequence(s) within the first 150 residues. These features suggest that the mechanism for import of human PPOX to mitochondria differs from those identified for the translocation of nucleus-encoded, membrane-spanning, inner membrane proteins. In addition, a missense mutation outside this region (Val(335)-->Gly) prevented targeting to mitochondria and delayed the appearance of YFP fluorescence. This mutation appeared to prevent import by a direct effect on protein folding rather than by altering a sequence required for targeting. It may lead to sequestration of the PPOX-YFP construct in an unfolded conformation, followed by proteolytic degradation, possibly through enhanced binding to a cytosolic chaperone protein.


[Treatment of malignant fibrous histiocytoma of soft tissues].
Thirty-six patients with soft tissue malignant fibrous histiocytoma were followed up. At the time of this study, 14 of the 36 patients were alive and the average follow-up period was 59.3 months. The average age at initial diagnosis was 62.1 years. Of the 36 patients, 13 were initially treated by us. All of the marginal excision cases (17) showed recurrence. Five of 8 additional excision cases had residual tumor and three of these showed recurrence. Those cases given primary wide excision (5) showed no local recurrence. One out of 3 amputation cases showed recurrence five years after the operation. Thus, the total recurrence rate was 64%. The average period of recurrence was 9.3 months (n = 21). Radiotherapy was effective in four patients among 11 irradiated cases. Chemotherapy is difficult to apply, since patients are generally too old to tolerate intensive chemotherapy and also the drug-sensitivity is low. For this reason, we have insufficient clinical experience to make an evaluation. Five-year survival rate was 45% and 10-year survival, 30%. Early detection of the tumor and adequate initial surgery are the best ways of improving the results of treatment for MFH. Chemotherapy and radiotherapy might achieve adjuvant effects and produce better results.


Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects.
Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata, 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person.


In Memoriam - Prof. Andrzej Krzysztof Tarkowski (1933-2016).
Professor Andrzej Krzysztof Tarkowski passed away last September (2016) at the age of 83. His findings, have become indispensable tools for immunological, genetic, and oncological studies, as well as for generating transgenic animals which are instrumental for studying gene function in living animals. His work and discoveries provided a tremendous input to the contemporary developmental biology of mammals.


Identifying the binding mechanism of LEAP2 to receptor GHSR1a.
Liver-expressed antimicrobial peptide 2 (LEAP2) is a highly conserved secretory peptide first isolated in 2003. However, its exact biological functions remained elusive until a recent study identified it as an endogenous antagonist for the growth hormone secretagogue receptor (GHSR1a), a G protein-coupled receptor for which the gastric peptide ghrelin is the endogenous agonist. By tuning the ghrelin-GHSR1a system, LEAP2 has an important function in energy metabolism. In the present study, we first demonstrated that LEAP2 and ghrelin actually bound to GHSR1a in a competitive manner, rather than in a non-competitive manner as previously reported, by binding assays and activation assays. Subsequently, we demonstrated that the antagonistic function of LEAP2 was drastically affected by the manner of its addition. LEAP2 primarily affected the maximal activation effect when added before ghrelin, whereas it primarily affected half-maximal effective concentration when added at the same time as ghrelin. Thus, LEAP2 behaved as a competitive antagonist if added at the same time as the agonist and a non-competitive antagonist if added before the agonist. This unusual property of LEAP2 might be caused by its slow dissociation from receptor GHSR1a. We also found that the N-terminal fragment of LEAP2 was important for receptor binding. Our present study revealed an antagonistic mechanism for LEAP2, and will facilitate the design of novel antagonists for receptor GHSR1a in future studies.


Wetting Dynamics of a Water Droplet on Micropillar Surfaces with Radially Varying Pitches.
The wetting dynamics of a sessile droplet on square micropillar substrates with radially varying pitches, prepared on silicon wafers using a photolithography technique, is investigated experimentally. Two configurations are considered, namely, substrates with radially increasing pitch and radially decreasing pitch. The droplet initially placed at the center experiences a wettability gradient because of the variation in pitch of the micropillar substrate leading to complex wetting dynamics. We observed that the droplet remains in the Cassie-Baxter state in the case of a radially increasing pitch and exhibits a higher contact angle than that on a smooth surface during its spreading stage. In contrast, the droplet experiences the Wenzel condition in the case of a radially decreasing pitch and assumes a lower contact angle relative to that observed on a smooth surface. The wetted diameter of the droplet in the radially decreasing pitch configuration is found to be smaller than that observed in the radially increasing pitch configuration. Our study also reveals that increasing the size of the pillars increases the wetted diameter of the droplet in both configurations. Theoretical models developed using the Cassie-Baxter and Wenzel states for the radially increasing and radially decreasing pitches satisfactorily predict the experimental behaviors.


Clinical and immunologic effects of monoclonal antibody CC49 and interleukin-2 in patients with metastatic colorectal cancer.
We examined the possibility that prior exposure to the murine monoclonal antibody (mAb), CC49, which recognizes the pancarcinoma antigen, TAG-72, would modify the clinical activity of interleukin-2 (IL-2) in patients with metastatic colorectal cancer. Fourteen patients received 2 mg of unconjugated CC49 on Day 1; on Day 22, they began human recombinant IL-2 at 1 mg/m2/day for 4 days by continuous IV infusion. Four-day cycles of IL-2 were repeated weekly for 8 weeks unless there was evidence of unacceptable toxicity or progressive disease. Therapy was well tolerated. Proliferative responses of peripheral blood mononuclear cells (PBMC) to CC49, its Fab fragment, isotype matched murine immunoglobulin, and CC49 complexed with TAG-72+ mucin increased after CC49 administration (Day 21). These proliferative responses decreased after IL-2 administration. PBMC proliferative responses to AI49, an anti-CC49 idiotype antibody (Ab2), and TAG-72+ mucin was not induced. No complete or partial clinical responses were observed; one patient manifested a transient mixed response. A single infusion of CC49 does have biologic activity; it is, however, unlikely to substantially modify tumor response rates effected by IL-2 in patients with metastatic colorectal cancer.


Tumor-like amyloid formation (amyloidoma) in the brain.
An almost walnut-sized tumor was removed surgically from the left occipital lobe of a 46-year-old woman, who had suffered for 4 year from progressive visual loss with scotoma and finally from hemianopia, associated with attacks of headaches and recurrent episodes of depression each lasting for some weeks or months. Neuropathological examination, including polarization, thioflavine, fluorescence, immunofluorescence staining, and electron microscopy, revealed an amyloidoma, which consisted of broad appositionally grown amyloid deposits surrounded by some plasma cells, monocytic or foreign body cell types. The massive accumulations, often associated not only with blood vessels or perivascular collagenous fibers but also lying in the cerebral tissue not unlike senile plaques in the cortical gray matter corresponded to gradually growing masses as seen in the repeated CT scans. This unique lesion in the brain of a patient who did not show any evidence of systemic disorder, seems to confirm that the spontaneous tumor-like amyloid, which gave an immunofluorescent staining mainly with anti-IgM, is a special variant of primary amyloidosis (amyloid L) or of so-called paramyloid.


Fast and efficient genetic transformation of oleaginous yeast Rhodosporidium toruloides by using electroporation.
Metabolic engineering of Rhodosporidium toruloides, a robust lipid and caroteinoid producer, is of great importance for oleochemicals and carotenoids production. However, the Agrobacterium-mediated gene transformation is tedious and time consuming. Here, we described a fast and efficient genetic transformation of R. toruloides using electroporation with linear DNA fragments, and the process was optimized. The results showed that 2 × 103 transformants can be obtained at 0.7 kV/μg linear DNA by using hygromycin and bleomycin as selection markers after the competent cells pretreated with 25 mM DTT and 100 mM LiAc. Our results would facilitate mutant library construction and metabolic engineering of R. toruloides for production of oleochemicals and carotenoids. We further demonstrated that all transformants arose due to illegitimate integration of transforming DNA fragments by colony PCR.


The complete mitochondrial genome of the white seabream Diplodus sargus (Perciformes: Sparidae) from the Tyrrhenian sea.
The white seabream Diplodus sargus (Linnaeus, 1758) is a species of interest for commercial fisheries throughout its range of distribution and it is also reared using aquaculture techniques. Herein, we present the first complete sequence and annotation of the mitochondrial genome of this species. The D. sargus mitogenome is 16,515 base pairs in length and contains 13 protein-coding genes, 2 rRNA, 22 tRNA, and 2 non-coding regions (D-loop and L-origin). The overall nucleotide composition is: 27.3% A, 28.9% C, 26.8% T, and 17.0% G. Maximum likelihood analyses placed D. sargus as a sister species of Diplodus puntazzo. This study provides valuable information for further studying identification methods and evolutionary relationships of Sparidae species.


Studying mixing in Non-Newtonian blue maize flour suspensions using color analysis.
Non-Newtonian fluids occur in many relevant flow and mixing scenarios at the lab and industrial scale. The addition of acid or basic solutions to a non-Newtonian fluid is not an infrequent operation, particularly in Biotechnology applications where the pH of Non-Newtonian culture broths is usually regulated using this strategy. We conducted mixing experiments in agitated vessels using Non-Newtonian blue maize flour suspensions. Acid or basic pulses were injected to reveal mixing patterns and flow structures and to follow their time evolution. No foreign pH indicator was used as blue maize flours naturally contain anthocyanins that act as a native, wide spectrum, pH indicator. We describe a novel method to quantitate mixedness and mixing evolution through Dynamic Color Analysis (DCA) in this system. Color readings corresponding to different times and locations within the mixing vessel were taken with a digital camera (or a colorimeter) and translated to the CIELab scale of colors. We use distances in the Lab space, a 3D color space, between a particular mixing state and the final mixing point to characterize segregation/mixing in the system. Blue maize suspensions represent an adequate and flexible model to study mixing (and fluid mechanics in general) in Non-Newtonian suspensions using acid/base tracer injections. Simple strategies based on the evaluation of color distances in the CIELab space (or other scales such as HSB) can be adapted to characterize mixedness and mixing evolution in experiments using blue maize suspensions.


Assessment of Elastic Fibers in Tumor Stroma as a New Method to Predict 6-Year Outcomes for Gastric Cancer Patients.
Purpose: This study aimed to determine whether detecting elastic fibers in tumor stroma (EFTS) could be used as a new method for predicting the prognosis of gastric cancer (GC) patients. Materials and Methods: EFTS expression was determined by histochemistry in 160 GC patients who underwent gastrectomy. Based on the staining results, the patients were divided into three groups according to their EFTS expression level: low (n = 57), moderate (n = 50), and high (n = 53). The clinicopathological data and 6-year survival data were analyzed among different EFTS groups. Results: The expression of EFTS was closely related to lymphovascular invasion (P = 0.010), blood transfusion in operation (P < 0.001), recurrence rate (P < 0.001), and motility (P < 0.001). High expression of EFTS was also correlated with recurrence-free survival (RFS) and overall survival (OS) in GC patients by Kaplan-Meier curve (P < 0.001 for RFS and P < 0.001 for OS). Conclusions: Multivariate analysis showed that EFTS was an independent prognostic factor for RFS and OS. In conclusion, detecting EFTS to predict the prognosis of GC patients is effective and highly feasible.


Aerosol transmission in passenger car cabins: Effects of ventilation configuration and driving speed.
Identifying the potential routes of airborne transmission during transportation is of critical importance to limit the spread of the SARS-CoV-2 virus. Here, we numerically solve the Reynolds-averaged Navier-Stokes equations along with the transport equation for a passive scalar in order to study aerosol transmission inside the passenger cabin of an automobile. Extending the previous work on this topic, we explore several driving scenarios including the effects of having the windows fully open, half-open, and one-quarter open, the effect of opening a moon roof, and the scaling of the aerosol transport as a function of vehicle speed. The flow in the passenger cabin is largely driven by the external surface pressure distribution on the vehicle, and the relative concentration of aerosols in the cabin scales inversely with vehicle speed. For the simplified geometry studied here, we find that the half-open windows configuration has almost the same ventilation effectively as the one with the windows fully open. The utility of the moonroof as an effective exit vent for removing the aerosols generated within the cabin space is discussed. Using our results, we propose a "speed-time" map, which gives guidance regarding the relative risk of transmission between driver and passenger as a function of trip duration and vehicle speed. A few strategies for the removal of airborne contaminants during low-speed driving, or in a situation where the vehicle is stuck in traffic, are suggested.


Intermittent depolymerization of actin filaments is caused by photo-induced dimerization of actin protomers.
Actin, one of the most abundant proteins within eukaryotic cells, assembles into long filaments that form intricate cytoskeletal networks and are continuously remodelled via cycles of actin polymerization and depolymerization. These cycles are driven by ATP hydrolysis, a process that also acts to destabilize the filaments as they grow older. Recently, abrupt dynamical changes during the depolymerization of single filaments have been observed and seemed to imply that old filaments are more stable than young ones [Kueh HY, et al. (2008) Proc Natl Acad Sci USA 105:16531-16536]. Using improved experimental setups and quantitative theoretical analysis, we show that these abrupt changes represent actual pauses in depolymerization, unexpectedly caused by the photo-induced formation of actin dimers within the filaments. The stochastic dimerization process is triggered by random transitions of single, fluorescently labeled protomers. Each pause represents the delayed dissociation of a single actin dimer, and the statistics of these single molecule events can be determined by optical microscopy. Unlabeled actin filaments do not exhibit pauses in depolymerization, which implies that, in vivo, older filaments become destabilized by ATP hydrolysis, unless this aging effect is overcompensated by actin-binding proteins. The latter antagonism can now be systematically studied for single filaments using our combined experimental and theoretical method. Furthermore, the dimerization process discovered here provides a molecular switch, by which one can control the length of actin filaments via changes in illumination. This process could also be used to locally "freeze" the dynamics within networks of filaments.


Pharmacy surveys.
The Division of Drug Control, Maryland Department of Health and Mental Hygiene, conducts approximately two pharmacy surveys per month on health care practitioners. These surveys determine whether a practitioner has prescribed controlled and dangerous substances appropriately. In some cases, dentists who may be suffering from drug dependence are identified through these pharmacy surveys and referred to the Maryland State Board of Dental Examiners (SBDE). In addition to this disciplinary process, the SBDE may refer dentists to the Dentists' Well-Being Committee of the Maryland State Dental Association for evaluation and treatment. This paper reviews the procedures for requesting and conducting pharmacy surveys.


FDG uptake in splenic epidermoid cyst with hemorrhage.
Splenic epidermoid cyst is a rare entity and rarely becomes complicated by hemorrhage. We present a case of splenic epidermoid cyst with old hemorrhage showing strong FDG uptake in the cyst wall. Histopathology revealed granulation tissue with abundant inflammatory cells, including many hemosiderin-laden macrophages, in the inner layer of the cyst wall. The abundant inflammatory cells in the granulation tissue may contribute to the strong FDG uptake of the cyst wall. This case highlights that a benign lesion with hemorrhage should be included in the differential diagnosis of abnormal splenic FDG uptake along with tumor and inflammatory processes.


[Breech presentation at term: evolution of French practices and an analysis of neonatal results in regards to obstetrical management of breech presentation, from AUDIPOG Database].
To describe the evolution of medical practices in breech presentation at term and to compare early neonatal complications according to initial obstetrical decision on the type of delivery. 71919 pregnancies are included in the AUDIPOG Database from 1994 to 2000. Among this cohort, pregnant women with a singleton in breech, at term were selected which represented 2136 women after the exclusion of in utero deaths and medical abortions. The first outcome was global criteria of severe early neonatal complications ("death during per or immediate post partum or transfer of the newborns to an intensive care or surgery unit"). The size of the sample authorized a power of 90%. The rate of cesarean section before labor was 40%. We found 2.3% of early neonatal complications in the group in which labor was accepted vs. 1.9% in the group with cesarean section performed before labor (p>0.05). After having taken into account prognostic factors, we do not see a significant difference for the risk of neonatal complications between the two groups (OR=1.33; 95% CI: 0.63-2.80). The analysis of the AUDIPOG Database describes the French obstetrical practice in breech presentation at term. We do not find a different risk in morbi-mortality as regards to the initial obstetrical choice regarding the type of delivery, but the absence of randomization in our study does not authorize a strong medical evidence to guide national recommendations.


[A case of gastric cancer in which long-term administration of 5'-deoxy-5-fluorouridine (5'-DFUR) proved effective].
A patient with gastric cancer (mucinous adenocarcinoma), classified as Borrmann Type 4, refused surgery and a chemotherapy regimen was applied. 5'-DFUR (5'-deoxy-5-fluorouridine) was administered orally at 1,200 mg/day for 23 weeks, for a total dosage of 110.8 g. The patient showed marked remission: the tumor nearly disappeared, distensibility reappeared from the central region of the corpus ventriculi to the incisura angularis, and only small protrusions classified by Yamada's criteria as Type I, remained on the anterior and posterior wall and pars pylorica of the lesser curvature. Side effects were slight anorexia and diarrhea. These could be avoidable by temporal interruption of administration or dosage reduction, to allow long-term treatment. This case can be considered to be one example in which 5'-DFUR proved effective against gastric cancer.


The nos gene cluster from gram-positive bacterium Geobacillus thermodenitrificans NG80-2 and functional characterization of the recombinant NosZ.
The nos gene cluster encoding the activity of nitrous oxide reductase (N2OR) for the final step of the denitrification pathway has been well studied in gram-negative bacteria. Our previous study on the genome of Geobacillus thermodenitrificans NG80-2 revealed the presence of the nos gene cluster in this gram-positive bacterium. In this follow-up study, the nos gene cluster of G. thermodenitrificans NG80-2 was further analyzed and compared with those of other origins. The structural gene nosZ was heterologously expressed in Escherichia coli and the product was purified as a His-tagged fusion protein. The recombinant NosZ as prepared showed detectable N2OR activity, and the activity was enhanced by preincubation of the protein under argon and with copper compounds. The recombinant NosZ contains 2.5 atoms of copper per dimer and exhibits weak spectral features in the visible range, indicating that spontaneous incorporation of copper compounds into the NG80-2 NosZ can result in some but not full activity of the authentic NG80-2 N2OR. The enzymatic properties of the NosZ were also investigated. This is the first functional characterization of nosZ gene from gram-positive bacteria. This study indicates that the molecular mechanism for N2O reduction is conserved between gram-negative and gram-positive bacteria.


Antitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor.
Signaling through the erbB receptor family of tyrosine kinases contributes to the proliferation, differentiation, migration, and survival of a variety of cell types. Abnormalities in members of this receptor family have been shown to play a role in oncogenesis, thus making them attractive targets for anticancer treatments. PF-00299804 is a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor currently in phase I clinical trials. PF-00299804 is believed to irreversibly inhibit erbB tyrosine kinase activity through binding at the ATP site and covalent modification of nucleophilic cysteine residues in the catalytic domains of erbB family members. Oral administration of PF-00299804 causes significant antitumor activity, including marked tumor regressions in a variety of human tumor xenograft models that express and/or overexpress erbB family members or contain the double mutation (L858R/T790M) in erbB1 (EGFR) associated with resistance to gefitinib and erlotinib. Furthermore, PF-00299804 shows exceptional distribution to human tumor xenografts and excellent pharmacokinetic properties across species.


[Meningioma following irradiation for vascular nevus. A case report].
A case of meningioma that developed 37 years after irradiation therapy for vascular nevus of the scalp over the right frontoparietal region was reported. A 49-year-old male was admitted to the hospital of Gifu University on October 26, 1979, because of a generalized seizure. He had been born with a vascular nevus affecting the right frontoparietal scalp, for which he began receiving local irradiation at the age of 12. The total dose was not known because the only source of information regarding this treatment was the patient's memory. From the age of 17, the suffered from occasional attacks of dysesthesia in the left side of his body without consciousness disorder. He otherwise remained well for the intervening 37 years. Upon admission, he had a vascular nevus remaining with post irradiation skin changes over the right frontoparietal region. General and neurological examination were not remarkable. Right carotid angiogram and CT scan disclosed the presence of a right frontal tumor. A right frontotemporal craniotomy was performed on December 4, 1979 and a hard tumor was found firmly attached to the dura and bone at the right site. All visible tumor and involved bone were completely removed without difficulty. Histological examination of the surgical specimen showed the characteristic features of a transitional meningioma. There was no evidence of malignancy in the sections examined. Since Mann et al reported a malignant meningioma following irradiation therapy for optic nerve glioma, there have been many reports, over seventy cases of so-called radiation-induced meningioma. However, a meningioma following irradiation therapy for vascular nevus of scalp or face is exceedingly rare.(ABSTRACT TRUNCATED AT 250 WORDS)


The impact of frailty on the economic evaluation of geriatric surgery: hospital costs and opportunity costs based on meta-analysis.
Objectives: We used a systematic review and meta-analysis to analyze the difference in costs between surgery for frail and non-frail elderly patients. The opportunity cost of frailty in geriatric surgery is estimated using the results.Methodology: Two literature reviews were carried out between 2000 and 2019: (1) studies comparing total hospital costs of frail and non-frail surgical patients; (2) studies evaluating the length of hospital stay and cost for surgical geriatric patients. We performed a meta-analysis of the items selected in the first review. We subsequently calculated the opportunity cost of frail patients, based on the design of a cost/time variable.Results: Twelve articles in the first review were selected (272,717 non-frail and 16,461 frail). Fourteen articles were selected from the second review. Frail patients had higher hospital costs than non-frail patients (22,282.541 € and 16,388.844, p < .001) and a longer hospital stay (10.16 days and 8.4 (p < .001)). The estimated opportunity cost in frail patients is 1,019.56 € (cost/time unit factor of 579.30 €/day).Conclusions: Frail surgical geriatric patients generate a higher total hospital cost, and an opportunity cost arising from not operating in the best possible state of health. Preoperatively treating the frailty of elderly patients will improve the use of health resources.


Enhanced surveillance for childhood hepatitis B virus infection in Canada, 1999-2003.
Since hepatitis B virus (HBV) infection can have serious sequelae, especially if infection occurs during childhood, there is a continuing need to examine its epidemiology so as to inform control measures. We analyzed trends in disease incidence and patterns of hepatitis B virus (HBV) transmission in both Canadian-born and non-Canadian-born children from 1999 to 2003, through the Enhanced Hepatitis Strain Surveillance System. Amongst Canadian-born children, the incidence of newly identified HBV infection per 100,000 declined significantly during the study period from 1.4 in 1999, to 0.5 in 2003 (RR, 0.75 per year; 95% CI, 0.60-0.95). Amongst non-Canadian-born children, the incidence of HBV infection per 100,000 ranged from 9.4 to 16.3, during the study period (linear trend test, p=0.69). Poisson regression analysis revealed that non-Canadian-born children were more likely to have HBV infection (RR, 12.3; 95% CI, 7.6 to 19.8), than Canadian-born children. HBV infection was found to be more common among children emigrating from high endemic area, than among Canadian-born children. Current Canadian immunization policy should take into consideration the protection of all children against HBV infection, including those coming from countries where mass hepatitis B vaccination programs have still not been launched.


Universal function of the nonequilibrium phase transition of a nonlinear Pólya urn.
We study the phase transition and the critical properties of a nonlinear Pólya urn, which is a simple binary stochastic process X(t)∈{0,1},t=1,⋯, with a feedback mechanism. Let f be a continuous function from the unit interval to itself, and z(t) be the proportion of the first t variables X(1),⋯,X(t) that take the value 1. X(t+1) takes the value 1 with probability f[z(t)]. When the number of stable fixed points of f(z) changes, the system undergoes a nonequilibrium phase transition and the order parameter is the limit value of the autocorrelation function. When the system is Z_{2} symmetric, that is, f(z)=1-f(1-z), a continuous phase transition occurs, and the autocorrelation function behaves asymptotically as ln(t+1)^{-1/2}g[ln(t+1)/ξ], with a suitable definition of the correlation length ξ and the universal function g(x). We derive g(x) analytically using stochastic differential equations and the expansion about the strength of stochastic noise. g(x) determines the asymptotic behavior of the autocorrelation function near the critical point and the universality class of the phase transition.


Anharmonic vibrational spectra and mode-mode couplings analysis of 2-aminopyridine.
Vibrational spectra of 2-aminopyridine (2AP) have been analyzed using the vibrational self-consistence field theory (VSCF), correlated corrected vibrational self-consistence field theory (CC-VSCF) and vibrational perturbation theory (VPT2) at B3LYP/6-311G(d,p) framework. The mode-mode couplings affect the vibrational frequencies and intensities. The coupling integrals between pairs of normal modes have been obtained on the basis of quartic force field (2MR-QFF) approximation. The overtone and combination bands are also assigned in the FTIR spectrum with the help of anharmonic calculation at VPT2 method. A statistical analysis of deviations shows that estimated anharmonic frequencies are closer to the experiment over harmonic approximation. Furthermore, the anharmonic correction has also been carried out for the dimeric structure of 2AP. The fundamental vibration bands have been assigned on the basis of potential energy distribution (PED) and visual look over the animated modes. Other important molecular properties such as frontier molecular orbitals and molecular electrostatics potential mapping have also been analyzed.


Activity of Omadacycline and Other Tetracyclines Against Contemporary Gram-Negative Pathogens from New York City Hospitals.
Antibiotic-resistant Enterobacteriaceae and Acinetobacter baumannii are problematic pathogens, with few treatment options for multidrug-resistant (MDR)-A. baumannii and few oral options for extended spectrum β-lactamase (ESBL)-producing and MDR-Enterobacteriaceae. Omadacycline, a newer tetracycline derivative, has activity against some of these pathogens. We tested the in vitro activity of omadacycline against a contemporary collection of over 2,600 consecutive unique clinical isolates of Enterobacteriaceae and A. baumannii, a previous collection of carbapenem-resistant Klebsiella pneumoniae and A. baumannii from a surveillance study in 2013-2014, and a group of K. pneumoniae and A. baumannii isolates with previously defined resistance mechanisms. For the contemporary collection, over 96% of Escherichia coli and 70% of K. pneumoniae isolates were inhibited by omadacycline at ≤4 μg/mL including 95% of E. coli and 49% of K. pneumoniae with presumptive ESBLs. Nearly 90% of A. baumannii were inhibited by omadacycline at ≤4 μg/mL. The omadacycline MIC50/90 was 1/4 μg/mL, 4/>8 μg/mL, and 0.5/8 for E. coli, K. pneumoniae, and A. baumannii, respectively. For the carbapenem-resistant collection of isolates, 56% of A. baumannii were inhibited by omadacycline at ≤4 μg/mL, but only 30% of Klebsiella pneumoniae carbapenemase (KPC)-possessing K. pneumoniae were susceptible. Expression of the efflux gene adeB appeared to affect the activity of omadacycline against A. baumannii, but could not fully explain resistance to this agent. Omadacycline may prove to be a parenteral or oral option for some infections due to ESBL-producing Enterobacteriaceae and carbapenem-resistant A. baumannii, and clinical studies are warranted.


Chronological changes in incidences of polymorphic reticulosis in Korea and Japan.
Lethal midline granuloma (LMG) is a clinical term, which describes a group of diseases histologically comprising Wegener's granulomatosis, polymorphic reticulosis (PR), and malignant lymphoma of the ordinary type (ML). PR is a variant of ML, and is considered to be a type of NK/T cell lymphoma. Our previous study revealed the clustering of patients with PR in East Asia including China, Korea and Japan. However, the frequency rate of PR varied even among these countries, with that of Korea being approximately 5 times higher than that of Japan. In the present study, we examined the incidences of each type of LMG, especially PR, in Korea (Yonsei University) and Japan (59 university hospitals) over time. A total of 102 cases and 655 cases of LMG admitted to Yonsei University, Korea from 1977 to 1996 and 59 university hospitals in Japan between 1965 and 1996, respectively, were examined. The frequency rate of PR per 100,000 outpatients of ears, nose and throat (ENT) clinics in Korea decreased from 40 to 20 between the periods of 1977-1989 and 1990-1996. However, there were no significant changes in Japan during the period studied.


The transverse musculocutaneous gracilis flap for breast reconstruction: guidelines for flap and patient selection.
The transverse musculocutaneous gracilis (TMG) flap has received little attention in the literature as a valuable alternative source of donor tissue in the setting of breast reconstruction. The authors give an in-depth review of their experience with breast reconstruction using the TMG flap. A retrospective review of 111 patients treated with a TMG flap for breast reconstruction in an immediate or a delayed setting between August of 2002 and July of 2007 was undertaken. Of these, 26 patients underwent bilateral reconstruction and 68 underwent unilateral reconstruction, and 17 patients underwent reconstruction unilaterally with a double TMG flap. Patient age ranged between 24 and 65 years (mean, 37 years). Twelve patients had to be taken back to the operating room because of flap-related problems and nine patients underwent successful revision microsurgically, resulting in three complete flap losses in a series of 111 patients with 154 transplanted TMG flaps. Partial flap loss was encountered in two patients, whereas fat tissue necrosis was managed conservatively in six patients. Donor-site morbidity was an advantage of this flap, with a concealed scar and minimal contour irregularities of the thigh, even in unilateral harvest. Complications included delayed wound healing (n = 10), hematoma (n = 5), and transient sensory deficit over the posterior thigh (n = 49). The TMG flap is more than an alternative to the deep inferior epigastric perforator (DIEP) flap in microsurgical breast reconstruction in selected patients. In certain indications, such as bilateral reconstructions, it possibly surpasses the DIEP flap because of a better concealed donor scar and easier harvest.


Efficient algorithms for accurate hierarchical clustering of huge datasets: tackling the entire protein space.
UPGMA (average linking) is probably the most popular algorithm for hierarchical data clustering, especially in computational biology. However, UPGMA requires the entire dissimilarity matrix in memory. Due to this prohibitive requirement, UPGMA is not scalable to very large datasets. We present a novel class of memory-constrained UPGMA (MC-UPGMA) algorithms. Given any practical memory size constraint, this framework guarantees the correct clustering solution without explicitly requiring all dissimilarities in memory. The algorithms are general and are applicable to any dataset. We present a data-dependent characterization of hardness and clustering efficiency. The presented concepts are applicable to any agglomerative clustering formulation. We apply our algorithm to the entire collection of protein sequences, to automatically build a comprehensive evolutionary-driven hierarchy of proteins from sequence alone. The newly created tree captures protein families better than state-of-the-art large-scale methods such as CluSTr, ProtoNet4 or single-linkage clustering. We demonstrate that leveraging the entire mass embodied in all sequence similarities allows to significantly improve on current protein family clusterings which are unable to directly tackle the sheer mass of this data. Furthermore, we argue that non-metric constraints are an inherent complexity of the sequence space and should not be overlooked. The robustness of UPGMA allows significant improvement, especially for multidomain proteins, and for large or divergent families. A comprehensive tree built from all UniProt sequence similarities, together with navigation and classification tools will be made available as part of the ProtoNet service. A C++ implementation of the algorithm is available on request.


Relational coordination and healthcare management in lung cancer.
In the current socio-economic scenario characterized by a growing shortage of resources and progressive budget constraints, the need to better coordinate processes in health institutions appears as a relevant aspect to ensure the future sustainability of system. In this sense, Relational Coordination (RC) provides a valuable opportunity for the reconfiguration of clinical guidelines concerning isolated single-level considerations. In this research the RC model has been applied to explain best results in the process of diagnosing and offering clinical treatments for lung cancer. Lung cancer presents the higher rates of tumor's mortality worldwide. Through unstructured and informal interviews with clinicians at both levels (Primary/Specialist Care), a diagnosis of the situation in relation to joint management of lung cancer is provided. Solutions of continuity in terms of coordination are explained due to the observation of lack of effective knowledge transfer between the two levels. It is this disconnection which justifies the introduction of a modified model of RC for the study and implementation of transfer relations between the knowledge holders, in order to structure consolidated and cooperative evidence-based models that lead to a substantial shortening in the response times with a marked outcomes improvement. To our knowledge, the application of this model to a Public Health problem bringing together both levels of care, hasn't been made till now.


[Role of estrogen and selective estrogen receptor modulators in anti-aging].
Changes in bone mass and estrogen levels occur in almost total sync with one another in a woman's lifecycle, with bone mass shown to increase in response to increases in estrogen in early adolescence and to decrease in response to decreases in estrogen during perimenopause. Therefore, menopause as it leads to estrogen deficiency is among the greatest causes of osteoporosis, and estrogen replacement therapy represents a highly rational therapeutic approach. However, it is of note that estrogen is associated with increased risk for breast cancer, while selective estrogen receptor modulators (SERM) are associated with no such risk and thus represent prophylactic and therapeutic agents for breast cancer. Of all SERMs, raloxifene is currently the only agent covered by insurance and available for the prophylaxis and treatment of osteoporosis. The current review therefore focuses on the role of estrogen and raloxifene in the management of osteoporosis.


Genome constellations of 24 porcine rotavirus group A strains circulating on commercial Thai swine farms between 2011 and 2016.
Rotavirus A (RVA) infection is a major cause of diarrhea-related illness in young children. RVA is also one of the most common enteric viruses detected on pig farms and contributes to substantial morbidity and mortality in piglets. Long-term multi-site surveillance of RVA on Thai swine farms to determine the diversity of RVA strains in circulation is currently lacking. In this study, we characterized the 11 segments of the RVA genome from 24 Thai porcine RVA strains circulating between 2011 and 2016. We identified G9 (15/24) and P[13] (12/24) as the dominant genotypes. The dominant G and P combinations were G9P[13] (n = 6), G9P[23] (n = 6), G3P[13] (n = 5), G9P[19] (n = 3), G4P[6] (n = 2), G4P[19] (n = 1), and G5P[13] (n = 1). Genome constellation of the Thai strains showed the predominance of Wa-like genotype (Gx-P[x]-I1/I5-R1-C1-M1-A8-N1-T1/T7-E1/E9-H1) with evidence of reassortment between the porcine and human RVA strains (e.g., G4-P[6]-I1-R1-C1-M1-A8-N1-T1-E1-H1 and G9-P[19]-I5-R1-C1-M1-A8-N1-T7-E9-H1). To assess the potential effectiveness of rotavirus vaccination, the Thai RVA strains were compared to the RVA strains represented in the swine rotavirus vaccine, which showed residue variations in the antigenic epitope on VP7 and shared amino acid identity below 90% for G4 and G5 strain. Several previous studies suggested these variations might effect on virus neutralization specificity and vaccine efficacy. Our study illustrates the importance of RVA surveillance beyond the G/P genotyping on commercial swine farms, which is crucial for controlling viral transmission.