Derivation of neuronal cells from fetal normal human astrocytes (NHA).
Pathological changes in most neurological diseases are marked by cell loss. To understand the mechanisms of neurogenesis and brain repair at a cellular level, observation on less complex systems provide valuable knowledge which offer the basis for therapeutic interventions. This has been the impetus for neural cell culture studies and the development of in vitro models. Here, we provide protocols for differentiation into neuronal lineage of commercially available normal human astrocytes (NHA) that are isolated from normal fetal human brain (Lonza, Inc.). It is known that some of GFAP positive astrocytic cells have stem/progenitor cell characteristics; however, understanding of the human GFAP positive cells with these characteristics remains limited. The genesis of neuronal lineage cells from the NHA occurs in adherent culture conditions by removal of serum and exposure to bFGF. When transferred to serum-free medium supplemented with bFGF, NHA cells generate neuronal precursors that express doublecortin, nestin and are negative for GFAP. After withdrawal of bFGF they mature into neurons. The average time required for generation of neuronal cells using this protocol is about 3 weeks. Our model of neurogenesis captures a contained in vitro system consisting of both neurons and glia. This "human brain in a dish" model can be used to assay the effects of interventions on developing human neurons at a cellular and molecular level and is also suitable for modeling of various aspects of human diseases and testing of novel therapeutic strategies.


Geomedical warning system against epidemics.
We describe aims, usage and evaluation of the computer-based early warning system telecommunication on medical events (TeCoMed), which achieves tracking down of temporal and spatial spread of epidemics for seasonal communicable diseases. It uses experiences from former waves of communicable diseases down to fine-grained local areas. Data is delivered by the biggest German insurance scheme. The results are presented by means of a commercial, geomedical information system. The evaluation of the system's performance concerning influenza shows that timely risk assessment and warnings are possible.


Effect of backlash hysteresis of surgical tool bending joints on task performance in teleoperated flexible endoscopic robot.
The tendon-sheath mechanism provides flexibility but degrades the task performance of the flexible endoscopic robot because of the inherent backlash hysteresis problem. Previous studies have only focused on reducing backlash hysteresis. The goal of this study is to identify the backlash hysteresis criteria of surgical tool bending joints to maintain efficient surgical performance. A test platform for a surgical tool has been developed that has initial backlash hysteresis under 5° and can adjust the backlash hysteresis intentionally. Performance variation has been investigated in three bench-top endoscopic tasks in which various backlash hysteresis conditions were intentionally adjusted. A clear drop-off in task performance has been observed when the backlash hysteresis of the bending joints was greater than 10° regardless of the type of task and link length. The backlash hysteresis of surgical tool bending joints should be reduced to at least 10° to maintain efficient performance in robotic endoscopic surgery.


The effect of the chemical character of certain penicillins on the resistance of the beta-lactam group in their molecules. Part 5: Kinetics of thermal decomposition in solid state.
The decomposition rate at elevated temperature was studied of the following penicillins: ampicillin trihydrate (1), 6-aminopenicillanic acid (2; 6-APA), amoxicillin trihydrate (3), piperacillin (4), amoxicillin sodium (5), azlocillin sodium (6), mezlocillin sodium monohydrate (7) and azidocillin sodium (8). The pattern of decomposition was found to comply with the first-order reaction. The thermal stability of the compounds at 25 degrees C increased in accordance with the sequence 1 less than 2 less than 3 much less than 6 less than 5 less than 8 less then 7 much less than 4, which was connected with the hydrophilic and lipophilic properties of these penicillins. An isokinetic enthalpy-entrophy correlation was demonstrated. The calculated beta value was 420 K.


Streptogramins and their potential role in geriatric medicine.
Despite advances in antimicrobial chemotherapy over recent decades, morbidity and mortality secondary to infection continues to rise. In addition, the incidence of infection caused by resistant organisms has also increased. Concurrently, the elderly are living longer than prior generations, often with disabling chronic diseases. The more debilitated of the geriatric population are at greater risk for infection, and more likely to acquire or develop antimicrobial resistant organisms. Gram-positive organisms are a source of resistance and commonly cause infection in older patients. Whereas resistance is a concern in all patients, in the elderly this is magnified by limitations in treatment options because of differences in pharmacokinetics and tolerance as compared with younger counterparts. Pharmacokinetic differences include changes in drug distribution and may arise as a result of diminished end organ function. Age-related decreases in renal function often impact on commonly prescribed antimicrobials. In addition, the elderly are more susceptible to drug-drug interactions because polypharmacy is common in this patient population. Streptogramins may offer a useful alternative in the treatment of infections in the elderly due to their coverage of organisms commonly causing infections in this population and because of their favourable pharmacokinetic profiles. While published experience is limited, streptogramins are not appreciably eliminated by the kidney and, therefore, they are less subject to age-related changes in renal elimination. What is required is multi-dose pharmacokinetic analysis of streptogramins in geriatric populations and subset analysis of patient use data on file. The following will provide the reader with the most recently presented data on streptogramin use and their potential. While focusing on potential use in the elderly, we have cited data and issues which we believe will be relevant in the geriatric population.


Light sheet microscopy for real-time developmental biology.
Within only a few short years, light sheet microscopy has contributed substantially to the emerging field of real-time developmental biology. Low photo-toxicity and high-speed multiview acquisition have made selective plane illumination microscopy (SPIM) a popular choice for studies of organ morphogenesis and function in zebrafish, Drosophila, and other model organisms. A multitude of different light sheet microscopes have emerged for the noninvasive imaging of specimens ranging from single molecules to cells, tissues, and entire embryos. In particular, developmental biology can benefit from the ability to watch developmental events occur in real time in an entire embryo, thereby advancing our understanding on how cells form tissues and organs. However, it presents a new challenge to our existing data and image processing tools. This review gives an overview of where we stand as light sheet microscopy branches out, explores new areas, and becomes more specialized.


PM2.5 from a broiler breeding production system: The characteristics and microbial community analysis.
Particulate matter (PM) released from the processes of livestock production has a negative impact on the health of animals and workers. Herein, the concentration, major chemical components, morphology and microbiological compositions of particulate matter 2.5 (PM2.5, particles with aerodynamic diameter less than 2.5 μm) in a broiler breeding house were investigated. The results showed that the PM2.5 distribution in the chicken house was affected by the illumination, draught fans, chicken frame structure and activity of the chickens in the broiler breeding house. Component analysis showed that organic carbon (OC) accounted for the largest proportion, and followed by element carbon (EC), SO42-, NO3-, NH4+, Na+, K+ and Ca2+. Ultrastructural observations revealed that the shape of PM2.5 had a round, rectangular, chain-like and irregular shape. The concentration of endotoxin was approximately 0.3 EU/m3. Microbiological analysis showed that at the genus level, the pathogenic bacteria included Staphylococcus, Corynebacterium, Enterococcus, Parabacteroides, Escherichia and Megamonas. The abundant harmful fungi were Aspergillus, Scopulariopsis, Wallemia, and Fusarium. Through redundancy analysis (RDA) analysis, we determined that OC, EC, Na+, K+, and NH4+ had strong correlations with Brachybacterium, Brevibacterium, Corynebacterium, Escherichia, Scopulariopsis and Microascus. SO42- was closely related to Scopulariopsis and Salinicoccus. Salinicoccus was also strongly correlated with NO3-. Our results indicated that feed, faeces, and outside soot are contributed to the increase in PM2.5 concentration in the chicken house, while the sources of the dominant bacterial and fungi might be feed, faeces, suspended outside soil and cereal crops.


Evaluation of Presto(plus) assay and LightMix kit Trichomonas vaginalis assay for detection of Trichomonas vaginalis in dry vaginal swabs.
This is an evaluation study of the Presto(plus) Assay for T. vaginalis by comparing to the TIB MOLBIOL LightMix Kit Trichomonas vaginalis Assay using 615 dry collected vaginal and rectal swabs. Discordant samples were analyzed by the Qiagen® Microbial DNA qPCR for TV Assay. Both assays showed comparable performances (McNemar p>0.05).


Allyl ether of mansonone G as a potential anticancer agent for colorectal cancer.
Mansonone G (MG), a 1,2-naphthoquinone isolated from the heartwood of Mansonia gagei Drumm, exhibited several pharmacological activities such as anti-bacterial, anti-estrogenic and anti-adipogenic effect. This study evaluated the cytotoxicity of MG and its derivatives as well as determined the mechanism(s) underlying the cytotoxic activity of the most potent MG derivative on two CRC cell lines, HCT-116 cells carrying p53 wild-type and HT-29 cells carrying p53 mutant. We found that MG and its derivatives could inhibit viability of HCT-116 and HT-29 cells in a concentration-dependent manner. Of all semi-synthetic derivatives of MG, allyl ether mansonone G (MG7) was the most potent cytotoxic agent toward cancer cells and less toxic to normal cells. MG7 could induce ROS generation which was associated with cytotoxicity and apoptosis in both HCT-116 and HT-29 cells. Western blot analysis revealed that MG7 downregulated the expression of Bcl-2 and Bcl-xL proteins in both CRC cell lines and upregulated the expression of BAK protein in HT-29 cells. Moreover, MG7 inhibited AKT signaling pathway in both CRC cell lines and modulated ERK1/2 signaling pathway by inhibiting ERK1/2 phosphorylation in HCT-116 cells and activating ERK1/2 phosphorylation in HT-29 cells. Molecular docking revealed that MG7 could bind to the ATP-binding pocket of AKT and ERK1 via hydrophobic interactions.


Prevalence and clinical significance of heart murmurs detected in routine neonatal examination.
To determine the prevalence and clinical impact of murmurs detected during routine physical examination in neonates. In a 4 years retrospective study, 6333 healthy newborn babies were screened for the presence of a heart murmur during routine neonatal physical examination. Prematures or those who were admitted to neonatal intensive care unit or any neonate with a risk factor that is known to be associated with increased incidence of congenital heart disease were excluded from the study. All those with murmurs underwent echocardiography examination and color Doppler study. Murmurs were detected in 87 neonate (1.37%) of whom 37 (42.5%) had a structural cardiac malformation. Ventricular septal defect (62%) was the most common diagnosis, followed by atrial septal defect, pulmonary stenosis and patent ductus arteriosus. The prevalence of heart murmur was 13.7 per 1000 neonate. If a murmur is heard there is a (42.5%) chance of their being underlying structural defects. Therefore, detection of a murmur should prompt early referral for investigation and diagnosis or appropriate family reassurance.


The role of genetically engineered pigs in xenotransplantation research.
There is a critical shortage in the number of deceased human organs that become available for the purposes of clinical transplantation. This problem might be resolved by the transplantation of organs from pigs genetically engineered to protect them from the human immune response. The pathobiological barriers to successful pig organ transplantation in primates include activation of the innate and adaptive immune systems, coagulation dysregulation and inflammation. Genetic engineering of the pig as an organ source has increased the survival of the transplanted pig heart, kidney, islet and corneal graft in non-human primates (NHPs) from minutes to months or occasionally years. Genetic engineering may also contribute to any physiological barriers that might be identified, as well as to reducing the risks of transfer of a potentially infectious micro-organism with the organ. There are now an estimated 40 or more genetic alterations that have been carried out in pigs, with some pigs expressing five or six manipulations. With the new technology now available, it will become increasingly common for a pig to express even more genetic manipulations, and these could be tested in the pig-to-NHP models to assess their efficacy and benefit. It is therefore likely that clinical trials of pig kidney, heart and islet transplantation will become feasible in the near future.


Less is more: partial larvicidal efficacy of plant leachate leads to larger Aedes aegypti mosquitoes.
Major efforts to control the population of Aedes aegypti mosquitoes involve the use of synthetic insecticides, which can be harmful to the environment. Most plant compounds are eco-friendly and some of them have biocontrol potential, whereas a fraction of these compounds is released into the environment through the leaf-leaching process. We evaluated the effects of secondary compounds from Ateleia glazioviana and Eucalyptus grandis senescent leaf leachates on Ae. aegypti larval mortality, adult emergence time, and wing size using a microcosm approach. The microcosms consisted of 10 larvae kept in water (control) and under four treatments with leachates from a combination of plant species and leaching time (7 or 14 days). Chemical analyses of the leachates showed the presence of carboxaldehyde and Heptatriocotanol, which have antimicrobial properties, potentially reducing the food available for larvae. β-Sitosterol, Stigmasterol, α-Amyrin, and Lupeol are compounds with inhibitory, neurotoxic, and larvicidal effects. Both plant species' leachates increased larval mortality and decreased emergence time due to the presence of compounds toxic to the larvae. Larger organisms emerged in treatments with 7-days leachates, likely due to the high concentration of dissolved organic matter in the leachates. The higher mortality in 7-days leachates may also increase the organic matter from co-specific decomposition, improving adult size. Therefore, if the mosquito population is not locally extinct, compounds present in leaf leachates may act as a resource enhancing larvae growth, potentially increasing survivors' fitness. In conclusion, biocontrol attempts using urban green spaces may have unexpected outcomes, such as resulting in larger pest organisms.


Gene expression profile of Th1 and Th2 cytokines and their receptors in human and nonhuman primates.
To date comparative knowledge concerning gene expression profiles of T-helper 1(Th1)/Th2 cytokines and their receptors between human and non-human primates is scarce. We assessed the gene expression level of both Th1 [interleukin-4(IL-4)] and Th2 [IL-12, interferon-gamma(IFN-gamma)] cytokines and the receptors (IL-4Ralpha, IFN-gammaR1, IFN-gammaR2) in peripheral blood mononuclear cells (PBMC) from humans, chimpanzee, baboon, and macaque by a quantitative real-time reverse transcriptase-polymerase chain reaction(RT-PCR). The expression level of the IFN-gamma gene was markedly lower in humans than that in non-human primates. The IL-4 gene expression was significantly higher, whereas that of IL-12 was distinctly lower, in human/chimpanzee than in baboon/macaque. The IFN-gammaR2 gene expression was especially higher in the macaque than in the other three primates. These results indicate distinct gene expression of Th1/Th2 cytokines and their receptors in primates. These also suggest characteristic differences in Th1/Th2 immune responses affecting host defense and/or disease susceptibility among these primates.


Parasites and Other Infectious Agents in Non-human Primates of Argentina.
In Argentina, there are five non-human primate (NHP) species: Sapajus nigritus cucullatus, Sapajus cay, Alouatta caraya, Alouatta guariba clamitans, and Aotus azarae. All of them inhabit protected and non-protected areas and face severe threats due anthropization. We aim to summarize the information available about parasites and infectious diseases of these NHPs and suggest further research on primate diseases in Argentina. NHPs of Argentina are hosts of several parasites and pathogens important for conservation as well as public health. Alouatta species are lethally susceptible to yellow fever virus, which makes them suitable health sentinels of possible outbreaks. For other primate species, few parasite surveys have been carried out. Assessing the presence of infectious diseases and long-term surveillance on NHP allow the development of strategies to help in the early detection of pathogens that may threat public health. Increasing the knowledge about parasites and infectious diseases and their consequences in NHP of Argentina is needed, considering a One Health approach.


[Indications and results of colon-rectoplasty using the modified soave method in surgical treatment of megacolon in adults].
Variations of Soave's operation for the correction of dolichocolon are described. The indications for this form are explained and a personal series is described. Reference is made to the complications observed and the advantages and disadvantages associated with the method which, it is hoped, will be more widely employed.


[Medical counseling of public health-insurances in questions of occupational diseases in regard to economical benefits--project of cooperation between AOK Hesse and the Medical Advisory and Expertising Service Hesse].
Since September 1998 exists a project of cooperation and consultation between the AOK Hesse and the Medical Advisory and Expertising Service Hesse with the aim to identify occupational diseases and to survey decisions of the Employer's Liability Insurance Association. The procedure is based on a computer-added recognition-system, a profound preparation of the single cases by the employees of the health-insurance and a very intensively carried out deliberation by Medical Doctors of occupational medicine. In a period of four and a half year 8391 cases have been reviewed of which 4859 have already been determined. An approval as occupational disease by the Employer's Liability Insurance Association has been determined in 1954 cases, in 2905 cases the acknowledgement has not been determined. Regarding the determined cases a recourse of 10,078,922.27 EUR has been realized. In regard to the invested small resources of personnel the procedure has proved itself as highly effective to discover and to assert recourses. Beside the economical aspects for the public health-insurance, other results of the project were the assurance of the entitlement to benefits of people coming down with occupational diseases or their relatives. New insights about the actual development of occupational diseases in Germany als well as their prevention can be proceeded.


Excitotoxic basolateral amygdala lesions potentiate the memory impairment effect of muscimol injected into the medial septal area.
In rats, the septo-hippocampal system is important for memory encoding. Previous reports indicate that muscimol, a specific GABAergic agonist induces learning and memory deficits when infused into the medial septal area. The basolateral nucleus of the amygdala (BLA) modulates memory encoding in other brain areas, including the hippocampus. To explore the interactions between the septo-hippocampal system and amygdala in memory, we studied the effects of intra-medial septal infusions of muscimol in rats with BLA lesions. Animals received sham surgery or excitotoxic BLA lesions and were given infusions of either vehicle or muscimol (5 nmol) into the medial septal area 5 min prior to training sessions in inhibitory avoidance and water maze tasks. In the inhibitory avoidance task, muscimol-induced memory impairment was potentiated by BLA amygdala lesions. Additionally, in the water maze task, BLA-lesioned rats given muscimol infusions into the medial septal also showed memory impairment. These findings indicate that the MSA interacts with the BLA in the processing of memory storage.


[The pathogenetic therapy of patients with food poisonings and a complicated course].
The complicated and combined course of alimentary toxicoinfections are practically the main causes of all the lethal outcomes in these diseases. In this work the data on the recent progress in the rehydration therapy of acute enteric infections are presented. The authors established that combined forms constituted 15.3% and complicated ones constituted 2% of alimentary toxicoinfections. The results of the treatment of alimentary toxicoinfections combined with ischemic heart disease, hypertension and chronic alcoholism, as well as complicated by shock and pneumonia, are presented. The general principles of treatment in combined and complicated cases are the maintenance of the usual (under given conditions) volume of liquid for rehydration with the limitation of the rate of its introduction.


Physical layout of workspace: a driver for productivity in drug discovery.
Connecting knowledge islands is of paramount importance to create a competitive edge in science-driven companies. From a constructive perspective, new knowledge is created when individuals communicate. The most intensive level of connection is face-to-face encounters. Short feedback loops are essential for high productivity in research. We analyze the results from a study performed at Novartis's 'Knowledge Campus' in Basel, Switzerland. A change from conventional cellular offices to an ultramodern multispace concept radically changed the patterns of face-to-face encounters between individuals. In this article, we derive implications for the management of R&D and show that multispace concepts are advantageous when individuals depend on one another within multidisciplinary groups.


Domestic LED bulb induced photodynamic effect of Toluidine Blue O-embedded silicone catheters against urinary tract infection.
Novel combination of Toluidine Blue O (TBO) embedded silicone catheter with domestic/household LED bulb has a potential in clinical infection such as prevention of multi drug resistant catheter-associated urinary tract infections (CAUTIs) through photodynamic therapy. Preliminarily, TBO was entrapped into silicone catheter by swell-encapsulation-shrink method. Further, in vitro study was carried out to check the antimicrobial photodynamic efficacy of TBO with domestic/household LED light. Antibiofilm activity was evaluated by scanning electron microscopy. The results showed that these modified TBO embedded silicone catheters showed significant antimicrobial and antibiofilm activity against vancomycin resistant Staphylococcus aureus VRSA. Small piece (1 cm) of TBO-embedded silicone catheter (700 µM) showed 6 log10 reduction in the viable count when exposed for only 5 min of domestic/household LED bulb, while 1 cm piece of 500 µM and 700 µM concentration of TBO-embedded catheter eradicated all bacterial load when exposed to 15 min of light. Segment of medical grade TBO-embedded silicone catheters were used to carry out investigation of reactive oxygen species generation mainly singlet oxygen that contributes to type II phototoxicity. These modified catheter provides cost effective, easy to manage and less time consuming therapy to eliminate CAUTIs.


Differential expression and comparative subcellular localization of estrogen receptor beta isoforms in virally transformed and normal cultured human lens epithelial cells.
A number of variants of the wild-type (wt) estrogen receptor beta (ERbeta-1) coexist in a wide range of tissues. In the human these include, together with others, the expression of several isoforms (ERbeta-2-ERbeta-5) due to alternative splicing of exons encoding the carboxy terminus. In this study, we determined whether virally transformed cell cultures of human lens epithelial cells (HLE-B3) express both full length (or wt) and variant isoforms of ERbeta in comparison to normal secondary cultures of human lens epithelial cells (nHLE) and furthermore, identify the subcellular localization of the wtERbeta-1 and ERbeta isoform variants in HLE-B3 and nHLE cells, as well as from human breast adenocarcinoma cells (MCF-7) which provided a positive control. ERbeta isoform mRNA expression was evaluated by coupled RT-PCR. Subcellular localization of ERbeta isoforms was determined on formaldehyde-fixed, Saponin-permeabilized cells using conventional immunofluorescence techniques and affinity purified polyclonal antibodies specific for ERbeta-1 as well as to two of the truncated carboxy terminus isoforms (beta-2 and beta-5). Total RNA was extracted from HLE-B3 and nHLE cells and lens tissue, as well as from human breast adenocarcinoma cells (MCF-7) and subjected to RT-PCR using specific estrogen receptor primers intended to distinguish ERbeta-1-ERbeta-5 mRNA. The PCR products corresponded to wtERbeta-1 as well as to the isoform variants beta-2 and beta-5. The proportional distribution of wtERbeta-1, beta-2 and beta-5 PCR products differed between the normal lens epithelial cells and the SV-40 transformed lens epithelial cell line; the nHLE being similar to lens tissue with respect to relative expression of ERbeta isoform cDNAs. Confocal microscopy and immunofluorescence revealed ERbeta-2 was distributed throughout the cytosol and was associated with the nucleus of all cells examined, although sporadic immunostaining was observed with the nuclei of MCF-7. Prominent immunostaining of ERbeta-1 appeared in the mitochondria (along with weaker staining in the nucleus) of all cell types as authenticated by co-localization with Mitotrack-633. ERbeta-5 immunostaining was diffuse in the cytosol and also associated with the nuclei of all cell types. The differential subcellular partitioning of ERbeta-1 to the mitochondria and ERbeta-2 to the nucleus suggests a new aspect of regulation and function of the estrogen signalling system.


Environmental determinants of distribution of freshwater snails and trematode infection in the Omo Gibe River Basin, southwest Ethiopia.
Determination of infection rates of snail populations is one of the basic tools for epidemiological studies of snail borne diseases. In this study, we opted to determine the trematode infection of freshwater snails in the Omo-Gibe River Basin, southwest Ethiopia. We collected snail samples from 130 observation sites in lakes, wetlands, rivers, reservoirs and irrigation canals surveyed during the dry season (March to May) in 2016. The snail samples were examined for trematode infections by cercarial shedding immediately after collection. Habitat conditions, water quality, human water contact practices and other human activities were assessed at each survey site. A redundancy analysis (RDA) was used to examine the relationship between cercarial infection and environmental variables. The statistical significance of eigenvalues and cercariae-environment correlations generated by the RDA were tested using Monte Carlo permutations at 499 permutations. A total of 3107 snails belonging to five species were collected. The most abundant species was Biomphalaria pfeifferi, representing 66% of the total collection. Overall, 109 (3.6%) of the snails were found infected with trematodes (cercariae). Biomphalaria pfeifferi was found to be the most highly infected, accounting 85% of all infected snails. A total of eight morphologically different types of cercariae were recorded, which included: Echinostoma cercariae, brevifurcate apharyngeate distome cercariae, amphistome cercariae, brevifurcate apharyngeate monostome cercariae, xiphidiocercariae, longifurcate pharyngeate distome cercariae, strigea cercariae and unidentified cercariae. Brevifurcate apharyngeate distome cercariae, and Echinostoma cercariae were the most abundant cercariae, accounting for 36 and 34% of all infection, respectively. The mean concentration of water conductivity and 5 days biological oxygen demand were higher in irrigation canals and lake sampling points. Human activities such as open field defecation, urination, livestock grazing, farming, and swimming were highly correlated with trematode infection. The abundance, occurrence and infection rates of snail species were largely influenced by water physicochemical quality, sanitation and water contact behaviour of the inhabitants. Human activities, such as open field defecation and urination, livestock grazing, farming, and swimming were important predictors of the abundance of cercariae. Therefore, awareness creation should be implemented for proper containment of excreta (urine and faeces) and reducing human and animal contacts with surface waters to reduce snail-borne disease transmission.


Concentrations and speciation of polybrominated diphenyl ethers in human amniotic fluid.
Polybrominated diphenyl ethers (PBDEs) are persistent organic chemicals used as flame retardants in textiles, plastics, and consumer products. Although PBDE accumulation in humans has been noted since the 1970s, few studies have investigated PBDEs within the gestational compartment, and none to date has identified levels in amniotic fluid. The present study reports congener-specific brominated diphenyl ether (BDE) concentrations in second-trimester clinical amniotic fluid samples collected in 2009 from fifteen women in southeast Michigan, USA. Twenty-one BDE congeners were measured by GC/MS/NCI. The average total PBDE concentration was 3795 pg/ml amniotic fluid (range: 337-21,842 pg/ml). BDE-47 and BDE-99 were identified in all samples. Based on median concentrations, the dominant congeners were BDE-208, 209, 203, 206, 207, and 47 representing 23, 16, 12, 10, 9 and 6%, respectively, of the total detected PBDEs. PBDE concentrations were identified in all amniotic fluid samples from southeast Michigan, supporting a need for further investigations of fetal exposure pathways and potential impacts on perinatal health.


Heme oxygenase-1 is an anti-inflammatory host factor that promotes murine plasmodium liver infection.
The clinically silent Plasmodium liver stage is an obligatory step in the establishment of malaria infection and disease. We report here that expression of heme oxygenase-1 (HO-1, encoded by Hmox1) is upregulated in the liver following infection by Plasmodium berghei and Plasmodium yoelii sporozoites. HO-1 overexpression in the liver leads to a proportional increase in parasite liver load, and treatment of mice with carbon monoxide and with biliverdin, each an enzymatic product of HO-1, also increases parasite liver load. Conversely, mice lacking Hmox1 completely resolve the infection. In the absence of HO-1, the levels of inflammatory cytokines involved in the control of liver infection are increased. These findings suggest that, while stimulating inflammation, the liver stage of Plasmodium also induces HO-1 expression, which modulates the host inflammatory response, protecting the infected hepatocytes and promoting the liver stage of infection.


Risk factors for hepatitis B in an outbreak of hepatitis B and D among injection drug users.
During January-April, 2000, 12 cases of acute hepatitis B were reported in Pierce County, Washington, compared with seven in all of 1999. Seven (58.3%) case patients were injection drug users (IDUs), three of whom were coinfected with hepatitis D virus (HDV) and died of fulminant hepatitis. Vaccination clinics were implemented at the local health department and needle exchange program to control the outbreak. We investigated this outbreak to determine risk factors for hepatitis B virus (HBV) transmission among IDUs. Hepatitis B cases were ascertained through routine surveillance and prevaccination testing at vaccination clinics. We conducted a case-control study comparing IDU case patients with HBV-susceptible IDUs identified at the vaccination clinics. Fifty-eight case patients were identified during January-December, 2000, 20 (34.5%) of whom were coinfected with HDV. Thirty-eight case patients (65.5%) reported current IDU. In the case-control study, the 17 case patients were more likely than the 141 controls to report having more than one sex partner [odds ratio (OR) =4.8, 95% confidence interval (CI) =1.5-15.0], injecting more than four times a day (OR = 4.5, 95% CI =1.2-15.6) and sharing drug cookers with more than two people (58.8% vs. 14.0%, OR =14.0, 95% CI =2.4-81.5). Results were similar after controlling for syringe sharing in multivariable analysis. IDUs should be vaccinated against hepatitis B and should be advised against sharing drug injection equipment.


C-type virus particles in human urogenital tumours after heterotransplantation into nude mice.
C-type viruses were formed in heterotransplants of 5/14 human urogenital tumours which had been serially transferred in nude mice of NIH(S) background. Except for one case in which C-type particles were present in the epithelial cells as well as the connective tissue, the viruses were only found within the stroma of the heterotransplanted tumours. Peroxidase labelling with anti-mouse serum demonstrated that the connective tissue supporting the transplanted human tumours was of mouse origin. Competition radioimmunoassays demonstrated that MuLV interspecies viral protein was present in high titre in the transplanted tumour extracts and also in extracts of 2 spontaneous mouse-tumour extracts. These data suggest that endogenous viruses of the nude mice are activated by the graft, and only subsequently infect the human tumour cells and form particles.


Spin-reorientation magnetic transitions in Mn-doped SmFeO3.
Spin reorientation is a magnetic phase transition in which rotation of the magnetization vector with respect to the crystallographic axes occurs upon a change in the temperature or magnetic field. For example, SmFeO3 shows a magnetization rotation from the c axis above 480 K to the a axis below 450 K, known as the Γ4 → Γ2 transition. This work reports the successful synthesis of the new single-crystal perovskite SmFe0.75Mn0.25O3 and finds interesting spin reorientations above and below room temperature. In addition to the spin reorientation of the Γ4 → Γ2 magnetic phase transition observed at around TSR2 = 382 K, a new spin reorientation, Γ2 → Γ1, was seen at around TSR1 = 212 K due to Mn doping, which could not be observed in the parent rare earth perovskite compound. This unexpected spin configuration has complete antiferromagnetic order without any canting-induced weak ferromagnetic moment, resulting in zero magnetization in the low-temperature regime. M-T and M-H measurements have been made to study the temperature and magnetic-field dependence of the observed spin reorientation transitions.


Activation of D-tyrosine by Bacillus stearothermophilus tyrosyl-tRNA synthetase: 1. Pre-steady-state kinetic analysis reveals the mechanistic basis for the recognition of D-tyrosine.
Tyrosyl-tRNA synthetase (TyrRS) is able to catalyze the transfer of both l- and d-tyrosine to the 3' end of tRNA(Tyr). Activation of either stereoisomer by ATP results in formation of an enzyme-bound tyrosyl-adenylate intermediate and is accompanied by a blue shift in the intrinsic fluorescence of the protein. Single turnover kinetics for the aminoacylation of tRNA(Tyr) by D-tyrosine were monitored using stopped-flow fluorescence spectroscopy. Bacillus stearothermophilus tyrosyl-tRNA synthetase binds d-tyrosine with an 8.5-fold lower affinity than that of l-tyrosine (K (D-Tyr)(d) = 102 microm) and exhibits a 3-fold decrease in the forward rate constant for the activation reaction (k (D-Tyr)(3) = 13 s(-1)). Furthermore, as is the case for l-tyrosine, tyrosyl-tRNA synthetase exhibits "half-of-the-sites" reactivity with respect to the binding and activation of D-tyrosine. Surprisingly, pyrophosphate binds to the TyrRS.d-Tyr-AMP intermediate with a 14-fold higher affinity than it binds to the TyrRS.l-Tyr-AMP intermediate (K (PPi)(d) = 0.043 for TyrRS.d-Tyr-AMP.PP(i)). tRNA(Tyr) binds with a slightly (2.3-fold) lower affinity to the TyrRS.d-Tyr-AMP intermediate than it does to the TyrRS.l-Tyr-AMP intermediate. The observation that the K (Tyr)(d) and k(3) values are similar for l- and d-tyrosine suggests that their side chains bind to tyrosyl-tRNA synthetase in similar orientations and that at least one of the carboxylate oxygen atoms in d-tyrosine is properly positioned for attack on the alpha-phosphate of ATP.


A recombinant enolase from Anisakis simplex is differentially recognized in natural human and mouse experimental infections.
A 1,963-bp cDNA was isolated from an Anisakis simplex cDNA library by immunoscreening with a hyperimmune rabbit serum raised against a crude extract of A. simplex L3 larvae. The open reading frame encodes a putative protein of 436 amino acid residues, which exhibits high similarity (70-80%) to enolase molecules from various other organisms, including helminth parasites. After subcloning and expression of the A. simplex cDNA in PGEX-4T-3, the resulting glutathione S-transferase fusion protein, purified by glutathione-Sepharose-4B chromatography, showed functional enolase activity. The immunogenicity of the recombinant A. simplex enolase was analyzed by immunoblotting using sera obtained from (a) mice immunized with crude extracts (CE) of A. simplex, or other nematode species, (b) mice immunized with excretory-secretory (ES) antigens from A. simplex, or (c) mice infected with L3 larvae by the intraperitoneal route. In addition, we used ELISA, to investigate the presence of IgG1 and IgE antibodies against this molecule in sera from patients infected with A. simplex. Mouse sera obtained after infection with L3 or raised against CE antigens, but not sera raised against ES antigens, showed strong reactivity with the recombinant A. simplex enolase. We also obtained good reactivity in Western blotting with sera from mice immunized with CE antigens from Ascaris suum and Toxocara canis, but not with sera from mice immunized with CE antigens from Trichuris muris, Trichinella spiralis or Hysterothylacium aduncum. In contrast to the experimental infections/immunizations in mice, we were unable to detect anti-enolase IgE antibodies in sera from human patients infected with A.simplex (15 sera), and the levels of anti-enolase IgG1 antibodies in these sera were low and apparently nonspecific. These results seem to indicate that, during natural infection in humans, A. simplex larvae do not offer sufficient antigenic stimulus to induce anti-enolase antibodies.


Factors affecting mental health service utilization among Latino Americans with mental health issues.
In contrast to their white counterparts, Latino Americans are less likely to utilize mental health services. Guided by the Behavioral Model of Health Service Utilization, this study examined factors affecting use of mental health services and dropouts from mental health services among Latino Americans with mental health issues. This is a secondary analysis utilizing data from the National Latino and Asian American Study. Seven hundred 88 Latinos with mental health issues were included in this study. Logistic regression analyses were conducted. Being older, having health insurance, having self-perceived need for mental health services, having mental health service need perceived by others and a greater number of probable psychiatric disorders were associated with the use of mental health services among Latinos with mental health issues. Among 194 Latino mental health service users, being younger, not having health insurance, and having a lower level of family support were associated with dropouts from mental health services. The findings suggest that education is needed to help Latino Americans recognize the need for mental health services. In addition, policies are needed to address financial difficulties in accessing mental health services.


The staphylococcal scalded skin syndrome. An experimental histochemical and electron microscopic study.
Histochemical and electron microscopic studies were carried out on the newborn mouse model of the staphylococcal scalded skin syndrome to investigate the mechanism of action of the staphylococcal epidermolytic toxin that causes it. Histochemical studies showed that an intra-epidermal split develops below the subcorneal zone which is rich in catabolic enzymes (the so-called esterase-acid phosphatase-rich band). However, histochemical alterations in the enzyme pattern could not be demonstrated. The earliest change revealed by electron microscopy was a widening of the intercellular space, with the formation of microvilli at the level between the stratum spinosum and stratum granulosum where the split later occurs. A clearing of the peripheral cytoplasm along the cell membranes was also revealed. In pre-split areas, adhesion between cell membranes of adjacent cells seems to be lost; desmosomes continue to hold the cells together but the split develops when these are broken by mechanical pressure. Later, damaged cell membranes may be seen. Extracellular keratinosomes remain unchanged. Although these findings do not agree with the already divergent results of other studies, they help support the findings of all groups that cases of the Lyell syndrome produced by staphylococci do not occur through necrolysis; it is therefore inappropriate to continue applying the term 'toxic epidermal necrolysis' to such cases.


Sex differences in magnetic field inhibition of morphine-induced responses of wild deer mice, Peromyscus maniculatus triangularis.
An exposure for 60 min to a 0.5 Hz weak rotating magnetic field (1.5-90 G) reduced the day-time locomotory and analgesic effects of morphine (10 mg/kg) in a wild population of deer mice. Peromyscus maniculatus triangularis. Females displayed significantly lower levels of morphine-induced responses and sensitivity to the inhibitory effects of the magnetic fields than did the males. These responses indicate that there are sex differences in the effects of weak magnetic fields on the opiate-mediated responses of a wild rodent, with males being more responsive to the magnetic stimuli than females.


CORT0C04210 is required for Candida orthopsilosis adhesion to human buccal cells.
Candida orthopsilosis is a human fungal pathogen belonging to the Candida parapsilosis sensu lato species complex. C. orthopsilosis annotated genome harbors 3 putative agglutinin-like sequence (ALS) genes named CORT0B00800, CORT0C04210 and CORT0C04220. The aim of this study was to investigate the role played by CORT0C04210 (CoALS4210) in the virulence and pathogenicity of this opportunistic yeast. Heterozygous and null mutant strains lacking one or both copies of CoALS4210 were obtained using the SAT1-flipper cassette strategy and were characterized in in vitro, ex vivo and in vivo models. While no differences between the mutant and the wild-type strains were observed in in vitro growth or in the ability to undergo morphogenesis, the CoALS4210 null mutant showed an impaired adhesion to human buccal epithelial cells compared to heterozygous and wild type strains. When the pathogenicity of CoALS4210 mutant and wild type strains was evaluated in a murine model of systemic candidiasis, no statistically significant differences were observed in fungal burden of target organs. Since gene disruption could alter chromatin structure and influence transcriptional regulation of other genes, two independent CRISPR/Cas9 edited mutant strains were generated in the same genetic background used to create the deleted strains. CoALS4210-edited strains were tested for their in vitro growing ability, and compared with the deleted strain for adhesion ability to human buccal epithelial cells. The results obtained confirmed a reduction in the adhesion ability of C. orthopsilosis edited strains to buccal cells. These findings provide the first evidence that CRISPR/Cas9 can be successfully used in C. orthopsilosis and demonstrate that CoALS4210 plays a direct role in the adhesion of C. orthopsilosis to human buccal cells but is not primarily involved in the onset of disseminated candidiasis.


Rapid molecular tests for detection of antimicrobial resistance determinants in Gram-negative organisms from positive blood cultures: a systematic review and meta-analysis.
Timely detection of antimicrobial (cephalosporin/carbapenem) resistance (AMR) determinants is crucial to the clinical management of bloodstream infections caused by Gram-negative bacteria (GNB). To review and meta-analyse the evidence for using commercially available molecular tests for the direct detection of AMR determinants in GNB-positive blood cultures (PBCs). PubMed, Scopus and ISI Web of Knowledge. Clinical studies evaluating the performance of two major commercial systems, namely the Verigene® and FilmArray® systems, for rapid testing of GNB-PBCs, in comparison with the phenotypic or genotypic methods performed on GNB-PBC isolates. Literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria and, for meta-analysis of sensitivity and specificity of both systems, bivariate random-effects model. Twenty studies were identified (3310 isolates) from 2006 to 2019. Nine studies were conducted in East Asia. In 15 studies using phenotypic comparators (1930 isolates), 1014 (52.5%) isolates were Escherichia coli, and 287 (14.9%) of all the isolates displayed AMR phenotypes. In five studies using genotypic comparators (1380 isolates), 585 (42.4%) were E. coli, and 100 (7.2%) of all the isolates displayed AMR genotypes. Pooled sensitivity and specificity estimates for detection of AMR determinants by the Verigene (i.e. CTX-M, IMP, KPC, NDM, OXA and VIM) and/or FilmArray (i.e. KPC) systems were 85.3% (95% CI 79.9%-89.4%) and 99.1% (95% CI 98.2%-99.5%), respectively, across the 15 studies, and 95.5% (95% CI 89.2%-98.2%) and 99.7% (95% CI 99.1%-99.9%), respectively, across the five studies. Our findings show that the Verigene and FilmArray systems may be a valid adjunct to the conventional microbiology (phenotypic or genotypic) methods used to identify AMR in GNBs. The FilmArray system detects only one AMR genotype, namely KPC, limiting its use. Both Verigene and FilmArray systems can miss important cephalosporin/carbapenem resistance phenotypes in a minority of cases. However, the sensitivity and specificity of both systems render them valuable clinical tools in timely identification of resistant isolates. Further studies will establish the prominence of such rapid diagnostics as standard of care in individuals with bloodstream infections.


Generation of flavor compounds by biotransformation of genetically modified hairy roots of Hypericum perforatum (L.) with basidiomycetes.
Altogether, 14 basidiomycetes (12BAD, 95PCH, 9WCOC, 5PSA, 96BCI, 331SHIBD, 4MSC, 74HFA, 220MPS, 115PFLA, 111 ICO C, 16LED, 6TSU, and 61LYP) were grown on solid and in liquid media using hairy roots of genetically modified Hypericum perforatum (L.) as the only source of carbon and nitrogen. After the first screening by GC-MS/MS-O, two fungi (115PFLA and 61LYP) which resulted in the most pleasant complex natural flavor by biotransformation were selected for further analysis. Twenty-four new volatile compounds were produced, from which 21 were identified (ethyl hexanoate, ethyl octanoate, benzaldehyde, 2-undecanone, (E,E)-2,4-decadienal, 1-octen-3-one, (E)-2-nonenal, ethyl nonanoate, 2-heptenal, 1-methoxy-4-methylbenzene, 3-octanone, 1-decen-3-one, (E)-2-octenal, 1-octen-3-ol, β-linalool, ±trans-nerolidol, anisole, methyl benzoate, 2-pentylfuran, 1,3-dichloro-2-methoxybenzene, and 1-dodecanol). Thereof, 15 compounds were perceived at the ODP, from which 13 were identified. Compound identification was performed by comparison of Kovats indices (KI) and mass spectra to those of authentic reference compounds on a polar VF-WAXms column using headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS).


Comparison of the Effects of KE and AED Peptides on Functional Activity of Human Skin Fibroblasts during Their Replicative Aging.
We studied the effect of KE and AED peptides on the expression of sirtuin-1, sirtuin-6, collagen I, cytokines (IL-1, TGF-β), and transcription factor NF-κB in human skin fibroblasts during their replicative aging. Immunocytochemical analysis and confocal microscopy showed that KE peptide reduces the synthesis of factors of the inflammatory response IL-1, NF-κB, and TGF-β and stimulates the synthesis of sirtuin-6. KE peptide normalizes the immunological function of human skin fibroblasts during their aging. AED peptide activates the synthesis of sirtuin-1, sirtuin-6, and collagen I in human skin fibroblasts during their replicative aging, which attests to its geroprotective effect.


Mechanistic Insights into the Anti-angiogenic Activity of Trypanosoma cruzi Protein 21 and its Potential Impact on the Onset of Chagasic Cardiomyopathy.
Chronic chagasic cardiomyopathy (CCC) is arguably the most important form of the Chagas Disease, caused by the intracellular protozoan Trypanosoma cruzi; it is estimated that 10-30% of chronic patients develop this clinical manifestation. The most common and severe form of CCC can be related to ventricular abnormalities, such as heart failure, arrhythmias, heart blocks, thromboembolic events and sudden death. Therefore, in this study, we proposed to evaluate the anti-angiogenic activity of a recombinant protein from T. cruzi named P21 (rP21) and the potential impact of the native protein on CCC. Our data suggest that the anti-angiogenic activity of rP21 depends on the protein's direct interaction with the CXCR4 receptor. This capacity is likely related to the modulation of the expression of actin and angiogenesis-associated genes. Thus, our results indicate that T. cruzi P21 is an attractive target for the development of innovative therapeutic agents against CCC.


Robust and High-Throughput Analytical Flow Proteomics Analysis of Cynomolgus Monkey and Human Matrices With Zeno SWATH Data-Independent Acquisition.
Modern mass spectrometers routinely allow deep proteome coverage in a single experiment. These methods are typically operated at nanoflow and microflow regimes, but they often lack throughput and chromatographic robustness, which is critical for large-scale studies. In this context, we have developed, optimized, and benchmarked LC-MS methods combining the robustness and throughput of analytical flow chromatography with the added sensitivity provided by the Zeno trap across a wide range of cynomolgus monkey and human matrices of interest for toxicological studies and clinical biomarker discovery. Sequential Window Acquisition of All Theoretical Fragment Ion Mass Spectra (SWATH) data-independent acquisition (DIA) experiments with Zeno trap activated (Zeno SWATH DIA) provided a clear advantage over conventional SWATH DIA in all sample types tested with improved sensitivity, quantitative robustness, and signal linearity as well as increased protein coverage by up to 9-fold. Using a 10-min gradient chromatography, up to 3300 proteins were identified in tissues at 2 μg peptide load. Importantly, the performance gains with Zeno SWATH translated into better biological pathway representation and improved the ability to identify dysregulated proteins and pathways associated with two metabolic diseases in human plasma. Finally, we demonstrate that this method is highly stable over time with the acquisition of reliable data over the injection of 1000+ samples (14.2 days of uninterrupted acquisition) without the need for human intervention or normalization. Altogether, Zeno SWATH DIA methodology allows fast, sensitive, and robust proteomic workflows using analytical flow and is amenable to large-scale studies.


Muscle fiber conduction velocity in the diagnosis of sporadic hypokalemic periodic paralysis.
A 6-year-old girl presented with episodes of profound muscle weakness since the age of 2 years. On the basis of decreased ictal serum potassium level and lack of metabolic disorder, primary hypokalemic periodic paralysis (HPP) was diagnosed. Both parents and 3 sibs were unaffected clinically. In all of them asymptomatic heterozygosity was very unlikely by the finding of normal muscle fiber conduction velocities, whereas in the patient interictal muscle fiber conduction velocity was lowered. Determination of muscle fiber conduction velocity can be helpful in documenting sporadic occurrence of HPP.


Association of physical activity with blood pressure and blood glucose among Malaysian adults: a population-based study.
The health-enhancing benefits of physical activity (PA) on hypertension and diabetes have been well documented for decades. This study aimed to determine the association of PA with systolic and diastolic blood pressure as well as blood glucose in the Malaysian adult population. Data were extracted from the 2011 National Health and Morbidity Survey (NHMS), a nationally representative, cross-sectional study. A two-stage stratified sampling method was used to select a representative sample of 18,231 Malaysian adults aged 18 years and above. The PA levels of the respondents were categorised as low, moderate or high according to the International Physical Activity Questionnaire (IPAQ)-short form. Blood pressure and fasting blood glucose levels were measured using a digital blood pressure-measuring device and finger-prick test, respectively. Systolic blood pressure (SBP) level was positively associated with PA level (p = 0.02) whilst no significant association was noted between PA level and diastolic blood pressure (DBP). In contrast, respondents with low (adjusted coefficient = 0.17) or moderate (adjusted coefficient = 0.03) level of PA had significantly higher blood glucose level as compared to those who were highly active (p = 0.04). A significant negative association was observed between PA level and blood glucose only. Future studies should employ an objective measurement in estimating PA level in order to elucidate the actual relationship between PA, hypertension and diabetes for the development of effective interventions to combat the increasing burden of premature-mortality and cardiovascular disease-related morbidity in Malaysia.


Patient satisfaction following transcervical resection of the endometrium.
Menorrhagia affects 20-30% of healthy women, many of whom undergo hysterectomy. In recent years, transcervical resection of the endometrium (TCRE) has become an alternative surgical option. This observational study assesses patient satisfaction following TCRE. The case notes of 55 patients who had a TCRE in the Coombe Womens' Hospital, Dublin, in 1992 were reviewed. Patients were sent a postal questionnaire at an interval ranging from 3 to 15 months post TCRE. 49 patients responded, of whom 76% were satisfied with TCRE. Thirty one per cent experienced amenorrhoea, 55% hypomenorrhoea, and 14% had no change in menstrual blood loss. Twenty two per cent required subsequent treatment. The complication rate was 11% (2 uterine perforations, 3 endometritis, 1 laparoscopic wound infection). We conclude that TCRE is an effective and safe treatment for menorrhagia, and is associated with a high rate of patient satisfaction.


Pathogens in ectoparasites from free-ranging animals: Infection with Rickettsia asembonensis in ticks, and a potentially new species of Dipylidium in fleas and lice.
Vector-borne infections are persistent public health threats worldwide. In recent years, a number of mosquito-borne viruses have emerged or re-emerged to cause major disease outbreaks. Other vector-borne pathogens, however, remain understudied and much neglected especially in the developing regions of the world including Southeast Asia. In this study, the brown dog tick Rhipicephalus sanguineus sensu lato, cat louse Felicola subrostratus, and cat fleas Ctenocephalides felis and Ctenocephalides orientis collected from free-ranging cats and dogs in Malaysia were molecularly screened for the presence of Bartonella and Rickettsia bacteria, and Dipylidium tapeworm. Our results showed the presence of Bartonella clarridgeiea, Bartonella henselae (lineage Marseille and lineage Houston-1), and Rickettsia sp. in C. felis. We also detected Rickettsia asembonensis in C. orientis and R. sanguineus s.l. Additionally, this study provides the first documentation on a potentially new species of Dipylidium infecting F. subrostratus and C. felis. Our results highlight the role of ectoparasites from free-ranging animals including cats and dogs, in harboring multiple transmissible pathogens.


Fine structure of a membrane anchor domain.
We describe a detailed deletion analysis of the anchoring domain of a model membrane protein. Removal of the 23 contiguous uncharged amino acids from the carboxy terminus of the bacteriophage fl gene III protein (pIII) converts it from an integral membrane protein to a secreted periplasmic form. Deletions that remove six or fewer residues of the hydrophobic core result in no diminution of the protein's capacity to anchor in the membrane. Longer deletions into this hydrophobic domain gradually destablize the protein-membrane association. pIII derivatives with over half of the hydrophobic core deleted retain substantial residual anchor function. The basic residues, arginine and lysine, which provide a carboxy-terminal boundary for this domain, can be deleted without loss of anchoring capacity.


Development and evaluation of tetrapod-shaped granular artificial bones.
We have developed a novel form of granular artificial bone "Tetrabones" with a homogeneous tetrapod shape and uniform size. Tetrabones are four armed structures that accumulate to form the intergranular pores that allow invasion of cells and blood vessels. In this study we evaluated the physicochemical characteristics of Tetrabones in vitro, and compared their biological and biomechanical properties in vivo to those of conventional β-tricalcium phosphate (β-TCP) granule artificial bone. Both the rupture strength and elastic modulus of Tetrabone particles were higher than those of β-TCP granules in vitro. The connectivity of intergranular pores 100, 300, and 400 μm in size were higher in Tetrabones than in the β-TCP granules. Tetrabones showed similar osteoconductivity and biomechanical stiffness to β-TCP at 2 months after implantation in an in vivo study of canine bone defects. These results suggest that Tetrabones may be a good bone graft material in bone reconstruction.


GYKI 52466, a 2,3-benzodiazepine, is a highly selective, noncompetitive antagonist of AMPA/kainate receptor responses.
In whole-cell voltage-clamp recordings from cultured rat hippocampal neurons, the 2,3-benzodiazepine GYKI 52466 was a potent antagonist of kainate- and AMPA-activated currents (IC50 values, 7.5 and 11 microM, respectively), but was inactive against N-methyl-D-aspartate (NMDA) or gamma-aminobutyric acid responses. The block produced by GYKI 52466 occurred in a noncompetitive fashion, was voltage independent, and failed to show use dependence, indicating an allosteric blocking mechanism. In kinetic experiments with kainate as the agonist, the GYKI 52466 binding and unbinding rates were 1.6 x 10(5) M-1 s-1 and 3.2 s-1, respectively. GYKI 52466 also suppressed non-NMDA receptor-mediated spontaneous synaptic currents via a postsynaptic action. Non-competitive AMPA/kainate antagonists such as GYKI 52466 could offer advantages over competitive antagonists in the treatment of glutamate-associated neurological disorders, particularly under conditions in which high levels of the amino acid would render the competitive antagonists relatively ineffective. Moreover, the results demonstrate the existence of a novel recognition site for an atypical benzodiazepine on non-NMDA receptors.


A computer program to calculate mean skin temperature from measurements available from field trials.
Attempts to estimate mean skin temperature for subjects during prolonged experiments in field conditions are often made difficult because probes become disconnected or cease to function. There are several equations which allow estimation of mean skin temperature from a reduced number of functioning probes. The Fortran program described chooses the appropriate equation, calculates the mean skin temperature using whichever readings are available from the six selected sites and calculates mean body temperature using also rectal temperature. The organization of the program is such that it could easily be modified for use on results from a wide range of experimental conditions.


Consenting for risk in common ENT operations: an evidence-based approach.
Pre-operative consent discussion and documentation is an essential process that should follow relevant guidance, and include all serious or frequently occurring risks. We assessed the appropriateness of consent for grommet insertion, tonsillectomy, septoplasty, and hemithyroidectomy, by comparing the risks listed in current consenting practice to published complication data for the relevant operation. 120 consent forms and associated clinic letters were analysed. A literature search identified published complication data for comparison. There was great variation in consent practice for each operation type, and poor correlation with published risk incidence. Only 'bleeding' post-tonsillectomy and 'recurrent laryngeal nerve injury' post hemithyroidectomy were listed in 100 % of relevant cases. Common and serious complications were frequently omitted from forms. The number and type of risks consented for a procedure significantly differed between consultant and non-consultant staff. The potential requirement for blood transfusion was discussed in only 20 % of tonsillectomy cases. Currently, the pre-operative consent for commonly performed ENT operations does not reflect operative risks. Consenting for surgical complications should be evidence based using published or personal data. A change in the consent process is required to protect patient autonomy and meet both legal and professional body requirements.


Acorn (Quercus spp.) as a novel source of oleic acid and tocopherols for livestock and humans: discrimination of selected species from Mediterranean forest.
The aim of the present work was to characterization and compare acorns from selected Quercus spp. from the Mediterranean forest in Spain, namely, Portuguese oak (QF, Quercus faginea Lam.), Cork oak (QS, Quercus suber L.), Pyrenean oak (QP, Quercus pyrenaica Wild), Kermes oak (QC, Quercus coccifera L.), Holm oak (QB, Quercus ilex L. subsp. ballota [Desf.]). All physicochemical attributes varied significantly between species. Fat contents ranged from 1.30 to 4.70 g 100 g-1 fresh matter. The most abundant fatty acids were oleic (62.44, 56.25, 57.46, 48.02, 65.83%), followed by linoleic (16.42, 20.73, 21.30, 25.38, 14.17%) and palmitic (11.69, 14.27, 12.17, 16.22, 12.28) acids in QF, QS, QP, QC and QB species, respectively. The tocopherol content was high in the range of 31.83-45.25 mg kg-1, and γ-tocopherol constituted 67-78% of total tocopherols. Only an effect of the location on γ-tocopherol content in QB was observed. The present results show the potential of different species of acorn to be used as agricultural and food resources and that geographical location plays a secondary role.


Spirituality in medical education: a concept analysis.
Spirituality in medical education is an abstract multifaceted concept, related to the healthcare system. As a significant dimension of health, the importance and promotion of this concept has received considerable attention all over the world. However, it is still an abstract concept and its use in different contexts leads to different perceptions, thereby causing challenges. In this regard, the study aimed to clarify the existing ambiguities of the concept of spirituality in medical education. Walker and Avant (Strategies for theory construction in nursing, Prentice Hall, Boston, 2011) concept analysis eight-step approach was used. After an extensive review of online national and international databases from 2000 to 2015, 180 articles and 3 books in English and Persian were retrieved for the purposes of the study. Analysis revealed that the defining attributes of spirituality in medical education are: teaching with all heart and soul, Life inspiring, ontological multidimensional connectedness, religious-secular spectrum, and socio-cultural intricacies. Moreover, innate wisdom, skillful treatment, transcendent education, and environmental requirements were antecedents to this concept, with the health of body and soul, intrapersonal development and elevation, and responsive treatment and education being its consequences. The defining attributes provided in this study can assist physicians, instructors, and professors to develop and implement evidence-based, health based and comprehensive education plans according to the guidelines of professional ethics and qualification of using spirituality in practice. The clarification of the noted concept facilitates further development of medical knowledge, research, and research instruments.


Nurse practitioners & genetic counselors: Collaborative roles in a complex system.
In the United States, the lifetime risk of cancer is approximately 50% for men and 33% for women. Approximately 10% of these individuals have an inherited predisposition and substantially increased cancer risk. This article discusses an approach to identifying and managing patients based on a high-risk breast clinic model.


Identification of a population of amacrine cells rich in insulin receptors.
Insulin receptor immunoreactivity in the developing chick retina was examined by immunocytochemistry. Insulin receptor immunoreactivity could be detected throughout the retina at all stages studied. Beginning at E12, a limited number of amacrine cells located in the inner level of the inner nuclear layer were strongly immunoreactive. By E19 there was a decrease in immunoreactivity throughout the retina, with the exception of the ganglion cell layer and a few amacrine cells and their process; this distribution was present in 3-day-old posthatched chick retina. The pattern of immunoreactivity of insulin receptors may indicate a unique role for insulin in the development and physiology of some amacrine cells.


Resource distribution and its effect on the mating system of a longhorned beetle, Perarthrus linsleyi (Coleoptera: Cerambycidae).
Adults of Perarthrus linsleyi feed on flowers of creosote bush, Larrea tridentata. Mating also occurs on the flowers and foliage of this plant. This food resource is widely and evenly distributed in space, and is usually abundant. The spatial distribution of the beetles bore no relationship to the spatial distribution of flowers among creosote bushes, nor were female beetles distributed predictably with respect to flower distribution. Males moved widely over the area under study, and moved much more frequently than females. Males actively searched for females, and mounted and began copulation attempts without preliminary courtship. Males did not engage in aggressive defense of females, creosote flowers, or creosote bushes. This species exhibits a scramble competition mating system. The spatial distribution of the food resource is a primary factor in the evolution of the mating system of Perarthrus linsleyi.


Treatment of the dyslipidemia of insulin resistance.
The increase in ischemic cardiovascular mortality and morbidity in persons with insulin resistance has been adequately documented elsewhere in this issue. Some of the most important risk factors for this increased mortality and morbidity are the lipid abnormalities, which form two out of five criteria for defining the metabolic syndrome, a definition focusing on risk factors for ischemic cardiovascular disease. This article explores the description, pathophysiology, and treatment of these atherogenic lipid abnormalities.


Resistive training and selected effects.
This article has briefly discussed the various modes and methods of resistive training, and their relative values and effectiveness in achieving desired goals. Evidence has been presented indicating that resistive training can enhance both "physical and emotional fitness as well as reduce some cardiovascular disease risk factors." This may allow a greater satisfaction and enjoyment in daily activities as well as improve athletic performance.


Central venous catheters are an important factor in paediatric thrombosis.
To establish the incidence and characteristics of paediatric thrombosis (PT) in a Canadian tertiary care centre during the era of low molecular weight heparin (LMWH). A retrospective observational case study of all patients <18 years of age evaluated for arterial and venous thrombosis from May 2008 to July 2018 at McMaster Children's Hospital was conducted through the electronic medical record. The incidence of PT was 52.2 per 10 000 hospital admissions (n = 477/91 462). Provoked thrombosis was more prevalent (88.9%, n = 424/477) than unprovoked (2.9%, n = 14/477) or idiopathic thrombosis (4%, n = 19/477). Half of PT were in children <2 years (51.2%, n = 244/477). Central vascular catheterisation was a contributory factor in more than half of thrombotic events (56.2%, n = 268/477), while trauma (1.1%, n = 5/477), oral contraceptives (4%, n = 19/477), infection (4%, n = 19/477), surgery (6.9%, n = 33/477) and malignancy (8.4%, n = 40/477) were also risk factors. Arterial ischaemic stroke was diagnosed in 11.1% of cases (n = 53/477), while pulmonary embolism was identified in 7.1% (n = 34/477) and 1.7% of cases were fatal (n = 8/477). LMWH was the first-line therapeutic of choice (47.8%, n = 228/477), with 28.1% (n = 134/477) requiring no intervention. These data reiterate the elevated thrombosis risk to which infants and children with central vascular access are exposed.


Baseline isotopic data of polyhalogenated compounds.
The delta2H- and delta13C-values of polyhalogenated compounds were determined by EA-IRMS. Most of the compounds were related to the chloropesticides DDT and its metabolites, hexachlorocyclohexanes, and toxaphene, as well as several polybrominated compounds such as bromophenols and -anisoles. delta2H-values ranged between -235 per thousand and +75 per thousand whereas delta13C-values were found in the range -22 per thousand to -38 per thousand. No correlation between delta2H- and delta13C-values could be identified. Comparative analysis clarified that bromophenols and the corresponding bromoanisoles may vary in their isotopic distribution. 2H NMR was used to quantify abundances of 2H isotopomers. Quantification of isotopomers of 2,4-dibromophenol and 2,4-dibromoanisole proved that both compounds from different suppliers do not originate from the same source. Differences in the delta2H-values of two toxaphene products were further investigated by the synthesis of products of different degree of chlorination from camphene. It was shown that the delta13C-values remained mostly unaltered as was expected since no carbon is lost in this procedure. However, the reaction products became enriched in 2H with increasing degree of chlorination. Different delta2H-values of the starting material will also impact the delta2H-values of the chlorination products.


Relationship of the angle between the A1 and A2 segments of the anterior cerebral artery with formation and rupture of anterior communicating artery aneurysm.
To measure the angle between A1 and A2 segments of the anterior cerebral artery and analyze the relationship of this angle with the formation and rupture of anterior communicating artery aneurysm (ACoAA). Patients with ACoAA (n=64) and with non-ACoAA (n=187) randomly chosen were included. The A1-A2 segment angles were measured using multislice spiral computed tomography angiography. The angular dimensions and differences were recorded and compared between the ACoAA and non-ACoAA groups and the ruptured (n=23) and unruptured group (n=41). The A1 segment morphology was divided into predominant and balanced type. The ACoAA aneurysm protrusion direction was divided into five types. The incidence of ACoAA was significantly higher in patients with A1 predominance compared to A1 balance (p<0.05). The mean A1-A2 segment angle was significantly smaller in the ACoAA group compared with the non-ACoAA group (p<0.001). There was no significant difference in mean A1-A2 segment angle between ruptured and unruptured groups. There was no significant relationship between aneurysm protrusion rupture and direction. The formation of ACoAA is more likely when there is A1 segment predominance in the anterior cerebral artery. The A1-A2 angle can help predict the formation of ACoAA but not useful for rupture predicting.


DNA alkylation and interstrand cross-linking by treosulfan.
The anti-tumour drug treosulfan (L-threitol 1,4-bismethanesulphonate, Ovastat) is a prodrug for epoxy compounds by converting non-enzymatically to L-diepoxybutane via the corresponding monoepoxide under physiological conditions. The present study supports the hypothesis that this conversion of treosulfan is required for cytotoxicity in vitro. DNA alkylation and interstrand cross-linking of plasmid DNA is observed after treosulfan treatment, but this is again produced via the epoxide species. Alkylation occurs at guanine bases with a sequence selectivity similar to other alkylating agents such as the nitrogen mustards. In treosulfan-treated K562 cells, cross-links form slowly, reaching a peak at approximately 24 h. Incubation of K562 cells with preformed epoxides shows faster and more efficient DNA cross-linking.


Budget-makers and health care systems.
Health programs are shaped by the decisions made in budget processes, so how budget-makers view health programs is an important part of making health policy. Budgeting in any country involves its own policy community, with key players including budgeting professionals and political authorities. This article reviews the typical pressures on and attitudes of these actors when they address health policy choices. The worldview of budget professionals includes attitudes that are congenial to particular policy perspectives, such as the desire to select packages of programs that maximize population health. The pressures on political authorities, however, are very different: most importantly, public demand for health care services is stronger than for virtually any other government activity. The norms and procedures of budgeting also tend to discourage adoption of some of the more enthusiastically promoted health policy reforms. Therefore talk about rationalizing systems is not matched by action; and action is better explained by the need to minimize blame. The budget-maker's perspective provides insight about key controversies in healthcare policy such as decentralization, competition, health service systems as opposed to health insurance systems, and dedicated vs. general revenue finance. It also explains the frequency of various "gaming" behaviors.


Monolithic 3D structural-substrate SERS sensing platform for ultrasensitive and highly-specific analysis of trace bisphenol A.
Constructing advanced substrates with excellent features is promising for sensitive surface-enhanced Raman spectroscopy (SERS) detection. Here a novel capillary monolithic 3D structural-substrate SERS platform with Au@cDNA@Ag@Cyanine 3-aptamer nanoparticles (Au@cDNA@Ag@Cy3-Apt NPs) was fabricated for rapid, highly specific profiling of ultra-trace Bisphenol A (BPA). The proposed SERS platform combined both in-capillary SERS and aptamer-affinity recognition strategies, in which the superior SERS properties of Au-Ag NPs, aptamer selectivity, and the advantages of capillary monolith were integrated. A 3D hierarchically porous network was constructed in the monolithic column, which was endowed with rich hotspots for SERS, rapid sample permeation, and better analysis efficiency than most plane-shaped SERS modes. By varying the amount of Ag+ precursor, the Ag-shell thickness on SERS was finely tuned to guarantee Cy3 label in proximity to the plasmonic surface. Based on the biorecognition of aptamer, the selective identification of BPA occurred and exhibited a significant change in SERS intensity without obvious interference. As a result, the monolithic SERS platform featured facile operation, excellent specificity, and rapid analysis (10 min, much less than the solution-based or planar substrate SERS modes). Ultra-high sensitivity and robust reproducibility for BPA analysis was achieved with a low limit of detection (LOD) at 9.12 × 10-4 ng/L. The feasibility of this SERS platform for monitoring BPA in water and milk samples was also validated. This work lights a new access to capillary monolithic SERS-sensing platform for ultrasensitive and specific analysis of BPA.


First year clinical experience with six levonorgestrel rods as subdermal contraception.
Previous clinical experience with six levonorgestrel subdermal capsules showed a very good contraceptive effectiveness and continuation rate, but with a high proportion of bleeding disturbances, particularly of increased bleeding. It was hypothesized that bleeding could be reduced by higher plasma levels of the steroid, using subdermal rods instead of capsules, as rods have been shown to have a release rate 3 or 4 times that of the capsules. Fifty volunteers were enrolled in a study of the clinical performance of 6 subdermal levonorgestrel rods. Results were compared with a previous experience with 100 volunteers who wore 6 levonorgestrel capsules for a year in the same clinic. Requirement for volunteers to enter the study were the same for capsules and rods. The proportion of women wearing 6 subdermal rods who had increased bleeding was about one half as for the women using 6 levonorgestrel capsules. On the other hand, women using rods had about twice the incidence of amenhorrea, and about four times more hypomenorrhea (4 days or less of bleeding in a 90-day period). There were no pregnancies among the rod users and the discontinuation rate for medical reasons was not higher than for capsule users in the same clinic.


Left atrial myxoma diagnosed and characterized by cardiac magnetic resonance imaging.
A 71 year old man was referred for MRI investigation of the heart. He had a history of progressive dyspnea. Due to his echocardiographical findings and the known history of permanent atrial fibrillation, his cardiologist suspected atrial thrombi. MRI investigation of the heart showed a left atrial mass pedunculated at the atrial septum which showed signal enhancement after intravenous administration of gadolinium-DTPA. Left atrial myxoma was suspected. The patient underwent surgery with resection of the tumor and patch-occlusion of the atrial septum. Histology confirmed a polypoid cardial myxoma.


Carbapenem-Resistant Klebsiella pneumoniae in COVID-19 Era-Challenges and Solutions.
The COVID-19 era brought about new medical challenges, which, together with nosocomial bacterial infections, resulted in an enormous burden for the healthcare system. One of the most alarming nosocomial threats was carbapenem-resistant Klebsiella pneumoniae (CRKP). Monitoring CRKP incidence and antimicrobial resistance globally and locally is vitally important. In a retrospective study, the incidence of CRKP in the pre-COVID-19 period (2017-2019) and the COVID-19 pandemic (2020-2022) was investigated in the Central Military Hospital in Ružomberok, Slovak Republic. The relative incidence of CRKP significantly increased during the COVID-19 period-by 4.8 times, from 0.18 to 0.76%. At the same time, 47% of CRKP-positive patients also had COVID-19. Twenty-six KPC and sixty-nine NDM-producing isolates were identified. CRKPs isolated in the year 2022 were submitted to whole genome sequencing, and their susceptibility was tested to cefiderocol, ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam, with excellent results. KPC-producing isolates were also highly susceptible to colistin (92%). The NDM isolates revealed lower susceptibility rates, including only 57% colistin susceptibility. ST-307 prevailed in KPC and ST-11 in NDM isolates. Despite the excellent activity of new antimicrobials, rational antibiotic policy must be thoroughly followed, supported by complementary treatments and strict anti-epidemic precautions.


Short-term impact of fampridine on motor and cognitive functions, mood and quality of life among multiple sclerosis patients.
Previous studies have predominantly investigated the effect of fampridine on lower extremities motor functions while data on its impact on other symptoms of multiple sclerosis (MS) are scarce. The aim of our study was to assess the impact of fampridine on walking, arm/hand function, fatigue, cognitive function, mood and quality of life among responders. Our prospective non-randomized study included 30 patients with different types of MS, aged 35-70, EDSS value 3.5-6.5. They were treated with 10mg of fampridine twice daily. The examinations were performed before the treatment, after 14 days, when responders were defined by T25FW (Timed 25-Foot Walk) and 2-min walk test (2MWT) was performed, and after 28 days of treatment, when only the responders were examined. Standardized protocols and questionnaires were used to evaluate the impact of fampridine on walking speed (T25FW, 2MWT), arm/hand function (9-HPT - Nine-Hole Peg Test), cognitive function (PASAT - Paced Auditory Serial Addition Test), total MSFC score (Multiple Sclerosis Functional Composite), fatigue (MFIS - Modified Fatigue Impact Scale), mood (BDI - Beck Depression Inventory) and quality of life (EQ-5D index, EQ-VAS - Euro Quality of Life - 5 Dimension questionnaire and visual analogue scale) in responders. Response rate was 56.7%. Average improvement of T25FW and 2MWT after 14 days of treatment in responders was 3.6s (34.5%) and 37.4m (42.3%), respectively. This improvement persisted after 28 days of treatment. In non-responders there was no significant improvement of T25FW after 14 days (p=0.689), but there was improvement of 2MWT for 13.4m (14.3%) (p=0.000). After 28 days of treatment significant improvement among responders occurred in total MSFC score (p=0.001), 9-HPT (p=0.002), BDI (p=0.005), MFIS total score (p=0.003), physical (p=0.001), cognitive (p=0.008) MFIS subscales, and EQ-5D index (p=0.012). There were implied trends towards improvement in EQ-VAS and psychosocial MFIS subscale, yet not significant (p=0.057 and p=0.127, respectively). There was no statistically significant improvement of PASAT (p=0.432). The results of our study highlight the potential of fampridine for improving not only walking speed but also arm/hand function, physical and cognitive fatigue, mood and quality of life. There was no objective improvement of cognitive function. Further placebo-controlled studies will be needed for precise definition of fampridine's action beyond its impact on walking.


Participation of adolescents from the Quilombola community in the creation of an educational game about alcohol consumption.
To describe and discuss the participation of adolescents from a quilombola community in the transformation of the comic "Possible Story" ("Uma História Possível"), from the Comic on alcohol, into an educational game. Implementation of the creative and sensitive method of art-based research, with adolescents from a quilombola community in the state of Espírito Santo, for the development of a board game. The democratic and interactive space favored the problematization of images and narratives about alcohol consumption mediated in the comic book. The group selected scenes, reordered the story, devised questions and riddles, formulated true and false assertions in a 17-card composition of the board game. The potential of the game as a content mediating tool to promote learning, reinforcement, and fixation of scientific content was evaluated. The active and dynamic participation of adolescents took place from conception to evaluation of the board game, encouraging them to reflect on a community context of cultural permissiveness of alcohol use.


Natural killer cell cytotoxic potential of patients with ovarian carcinoma and its modulation with virus-modified tumor cell extract.
We have demonstrated that cancer patients with ovarian carcinoma display deficient peripheral blood NK-cell cytotoxic potential against the K-562 target cell line. Furthermore, no NK-cell activity against the same tumor was detected in ascitic fluids of these patients. The inferior peripheral blood NK-cell cytotoxicity of ovarian carcinoma patients was significantly augmented after ID inoculation with virus-modified tumor cell extract. Similarly, NK-cell activity in the ascitic fluids was dramatically increased after IP in vivo therapy with the same tumor extract preparation. Interestingly, in some of the cancer patients the augmentation of NK-cell activity in ascitic fluids after IP injection of virus-modified tumor cells extract was associated with a clinical response of the patients, as demonstrated by regression of ascitic tumors. These studies indicate, first, that virus-modified tumor extract displays immunopotentiating activity, as reflected by its marked NK cell-augmenting potential, and secondly, that regional activation of NK cells could underlie the mechanism of regression of ascitic tumors.


Ultrastructural investigation on the cell membranes of the vomeronasal organ in the rat: a freeze-etching study.
The free surfaces and cell contacts in the epithelia of the vomeronasal organ of the rat were investigated by freeze-etching. The microvilli of receptor cells show a lower density of intramembranous particles (IMP) than the microvilli in the receptor-free epithelium. The ratio between the IMP on P- and E-face is approximately 11 : 1 in the receptor terminals, and 3.5 : 1 in the cilia and microvilli of the receptor-free epithelium. Although atypical in length and only poorly equipped with rootlet fibers, the cilia of the receptor-free epithelium are furnished with typical ciliary necklace structures of up to 10 rows of membrane particles. Differences in the density of IMP on the P-faces of different cilia are probably due to continual ciliogenesis and also due to the different age of cilia in the receptor-free epithelium. Zonulae occludentes show different configurations in the neuroepithelium and in the receptor-free epithelium. In the former, they show a tendency to cross-link and form facet-like patterns, reflecting a constant morphology and relative stability for this apical region. In the receptor-free epithelium the junctional rows of zonulae occludentes display only loosely interconnected networks and a tendency to orient parallel to each other and to the free surface. In addition to zonulae occludentes, typical square aggregations of IMP are observed in the receptor-free epithelium. They are not exclusively restricted to the zone of intensive cell contacts by means of fine interdigitating cell processes, and their function has yet to be identified experimentally.


Intracavity-pumped Cr2+:ZnSe laser with ultrabroad tuning range between 1880 and 3100 nm.
We obtained, what is to our knowledge, record tuning from an intracavity-pumped gain-switched Cr2+:ZnSe laser. In the experiments, a polycrystalline Cr2+:ZnSe sample with an absorption of about 43% at 1570 nm was used to minimize reabsorption losses at the lasing wavelengths below 2000 nm. By placing the gain medium inside the cavity of a pulsed KTP optical parametric oscillator (OPO) operating at 1570 nm, smooth, continuous tuning was achieved in the 1880-3100 nm range with four different sets of cavity optics. As high as 145 mW of average laser output power was obtained at 2365 nm with 1.2 W of intracavity OPO power.


Phosphaturic mesenchymal tumor, nonphosphaturic variant, causing fatal pulmonary metastasis.
Phosphaturic mesenchymal tumors of the mixed connective tissue type (PMT-MCTs) are rare neoplasms, most of which are benign and cause tumor-induced osteomalacia because of overproduction of a phosphaturic hormone, fibroblast growth factor 23 (FGF23). This entity may have been unrecognized or misdiagnosed as other mesenchymal tumors, such as giant cell tumor, hemangiopericytoma, and osteosarcoma. Ten percent of these tumors, without phosphaturia, were diagnosed only by their histologic features. We report here the first case of malignant PMT-MCT, nonphosphaturic variant, resulting in fatal multiple lung metastases. Chondromyxoid matrix with "grungy" calcification, multinucleated giant cell proliferation, and expression of FGF23 mRNA (reverse transcription-polymerase chain reaction) and fibroblast growth factor 23 protein (immunohistochemistry) were seen in the primary and recurrent tumors of the right foot. The lung metastases showed flocculent calcification and FGF23 protein expression as well as giant cell proliferation. This unique case highlights the need for careful histologic assessment of PMT-MCTs, especially the nonphosphaturic variant, and the need for recognition of its rare malignant behavior.


A morphological study of human rotavirus.
Human rotavirus has a characteristic icosahedral structure which has a honeycomb-like appearance on the surface of the smooth particles and 42 polygonal capsomeres in the rough particles.


Granulomatous hypophysitis causing compression of the internal carotid arteries reversible with azathioprine and rituximab treatment.
Compression of the internal carotid artery (ICA) in the cavernous sinus area is a rare event and is mostly associated with pituitary adenomas and meningiomas. Other causes of ICA compression are less well known. We present a rare case of granulomatous hypophysitis causing compression of the ICA, which was treated successfully with immune-suppressive agents. The electronic database MEDLINE (PubMed) was searched systematically and other cases with ICA compression were identified and analyzed. A female patient with a history of two previous transsphenoidal operations for suspected pituitary adenoma and post-operative complete pituitary insufficiency presented with severe headaches, nausea, fatigue, and diplopia. Pituitary MRI scan suggested relapse of the pituitary lesion with atypical bilateral infiltration of cavernous sinuses and compression of ICAs. After histological reevaluation of her previous pituitary operations, granulomatous hypophysitis was diagnosed. Treatment was started with high doses of prednisolone. With decreasing doses of prednisolone, symptoms recurred, and azathioprine was started, followed by administration of rituximab resulting in clinical recovery and regression of ICA compression. Literature analysis disclosed 36 case reports with ICA compression in the cavernous sinus region (12 pituitary adenoma, 6 meningioma, 7 hypophysitis, 5 other tumors, and 4 other etiologies). Two cases of hypophysitis recovered completely; five cases improved only partly. In the case of ICA compression, clinical signs, onset of symptoms, radiological findings and pituitary insufficiencies should be thoroughly evaluated, and hypophysitis should be considered as a possible cause. In our patient, treatment with azathioprine and, finally, rituximab was successful.


Antigen receptor-triggered apoptosis in immature B cell lines is associated with the binding of a 44-kDa phosphoprotein to the PTP1C tyrosine phosphatase.
While cross-linking of the membrane IgM (mIgM) molecules expressed on WEHI 231 lymphoma cells induces these cells to undergo apoptosis, we have previously observed that ligation of the mIgD expressed on IgD-transfected WEHI 231 (W delta) cells is not associated with induction of cell death. Thus mIgM+IgD+ W delta cells provide a valuable reagent for delineating the molecular events which modulate the physiologic outcome of B cell antigen receptor (BCR) engagement. In view of recent data implicating the cytosolic phosphotyrosine phosphatase PTP1C in the regulation of BCR signaling capacity, we used W delta cells to investigate the potential role for PTP1C in modulating the cell response to BCR activation. The results of this analysis revealed PTP1C to undergo rapid tyrosine phosphorylation following mIgM or mIgD cross-linking and to associate with a number of other phosphoproteins in stimulated W delta cells. Among these latter phosphoproteins, one prominent species of about 44 kDa (pp44) which co-precipitated with PTP1C in mIgM-ligated cells was not detected in PTP1C immunoprecipitates from mIgD-ligated cells. The association of PTP1C with this 44-kDa phosphoprotein following mIgM cross-linking was also observed in two additional B cell lines representing an immature state of differentiation, but was not detected after BCR engagement in two representative mature B cell lines or in splenic B cells. Initial data concerning the identity of pp44 indicate that this molecule does not represent the Shc, MAPK or Ig-beta proteins and may, therefore, constitute a previously unidentified signaling effector. While the structural and biochemical properties of pp44 require further definition, the findings suggest that BCR-triggered interactions of PTP1C with pp44 occur only in the context of an immature state of cellular differentiation and the induction of apoptosis. These data therefore suggest that PTP1C interactions with pp44 may be relevant to the transduction of BCR signals which evoke cell death.


Echinococcal cyst of the kidney.
A renal echinococcal cyst presenting with ureteral obstruction is described. Characteristic diagnostic features, including renal angiography, are discussed. Whereas partial nephrectomy is appropriate for a small closed renal cyst, total nephrectomy is indicated for most large or open cysts.


Preventing the return of fear in humans using reconsolidation update mechanisms: A verification report of Schiller et al. (2010).
In a highly influential report, Schiller et al. (2010) demonstrated long-lasting fear reduction in humans when conducting extinction training shortly following fear memory reactivation. While trying to experimentally replicate the critical conditions of Schiller et al. (2010, Experiment 1), we discovered several irregularities in their paper. Criteria for participant exclusion and the number of excluded participants were misreported; qualitative experimenter decisions actually determined their participant inclusions. Moreover, their statistical analyses were internally inconsistent. After corresponding with the original authors, we received their original data files, allowing us to replicate the reported analyses to verify their results. Here, we report the results of seven separate sets of analyses, three replicating the analyses reported by Schiller et al. (2010) and four applying more principled approaches to participant exclusion, thus including different subsets of the total datasets available, to deduce the influence of specific exclusions and experimenter decisions on the results. For Experiment 1, we were mostly able to replicate the analyses contained in the original report when applying the same qualitative exclusions. However, we found that all of the differences in fear recovery between reactivation-extinction and regular extinction reported by Schiller et al. (2010) were dependent on the qualitative exclusions that they made. With any of the principled approaches to participant exclusion, the degree of fear recovery was highly similar between groups. For Experiment 2, a similar analysis was not possible due to a lack of available data for the excluded participants. Hence, we conducted a verification analysis on the original sample only, which failed to confirm the differences in fear recovery reported by Schiller et al. (2010). Together with the re-analyses, we report a number of additional issues with the way Schiller et al. (2010) processed, analyzed, and reported their data that indicate that their results are unreliable and flawed.


Acute kidney injury secondary to traumatic rhabdomyolysis in a dog.
To describe the clinical course and successful management of a dog with crush syndrome, rhabdomyolysis, myoglobinuria, and associated acute kidney injury (AKI). An 8-year-old female, neutered, mixed-breed dog was referred to the Veterinary Teaching Hospital due to crush injury and suspected AKI. Blood tests and urinalysis showed markedly increased serum creatine kinase activity, myoglobinuria, and AKI. The dog was managed successfully with intermittent hemodialysis, and completely recovered. This is the first report of a dog with crush syndrome with secondary myoglobinuria and AKI.


A transgene expression system for the marine microalgae Aurantiochytrium sp. KRS101 using a mutant allele of the gene encoding ribosomal protein L44 as a selectable transformation marker for cycloheximide resistance.
In the present study, we established a genetic system for manipulating the oleaginous heterotrophic microalgae Aurantiochytrium sp. KRS101, using cycloheximide resistance as the selectable marker. The gene encoding ribosomal protein L44 (RPL44) of Aurantiochytrium sp. KRS101 was first identified and characterized. Proline 56 was replaced with glutamine, affording cycloheximide resistance to strains encoding the mutant protein. This resistance served as a novel selection marker. The gene encoding the Δ12-fatty acid desaturase of Mortierella alpina, used as a reporter, was successfully introduced into chromosomal DNA of Aurantiochytrium sp. KRS101 via 18S rDNA-targeted homologous recombination. Enzymatic conversion of oleic acid (C18:1) to linoleic acid (C18:2) was detected in transformants but not in the wild-type strain.