Simultaneous thrombosis of cerebral artery and venous sinus.
Cerebral venous thrombosis (CVT) is infrequent among cerebrovascular diseases. The simultaneous thrombosis involving both cerebral artery and venous sinus is even extremely rare. We reported a 41-year-old woman who presented with acute headache and left hemiparesis due to concomitant arterial ischemic stroke and recurrent CVT. Extensive investigation disclosed acquired protein C and protein S deficiency, iron deficiency anemia (IDA) and cryoglobulinemia. She was treated with intravenous injection of heparin followed by oral anticoagulant therapy. The headache rapidly subsided; however, left hemiparesis persisted over five months. The rare condition of simultaneous thrombosis of cerebral artery and venous sinus may be caused by the synergistic effect of coagulation disorders, IDA and cryoglobulinemia.


SDS-soluble and peptidoglycan-bound proteins in the outer membrane-peptidoglycan complex of Brucella abortus.
Outer membrane-peptidoglycan complex from Brucella abortus was separated from cytoplasmic membrane and cytosol by either sucrose density gradient fractionation or differential (rate) centrifugation of surface labeled cells disrupted by sonication without the use of detergents. The outer membrane-peptidoglycan complex had a buoyant density of 1.22 gm/ml and contained 67 labeled SDS-soluble proteins when examined by SDS-PAGE. Included were four major bands exhibiting molecular masses of 88k, 40k, 35.7k and 26k daltons corresponding to previously described group 1, 2 and 3 outer membrane proteins. Lysozyme treatment of outer membrane-peptidoglycan complex increased its buoyant density to 1.25 gm/ml and released eight additional peptidoglycan-linked proteins.


Adherence to medication: A nation-wide study from the Children's Cancer Hospital, Egypt.
To investigate adherence to medical regimen and predictors for non-adherence among children with cancer in Egypt. We administered two study specific questionnaires to 304 parents of children diagnosed with cancer at the Children's Cancer Hospital in Cairo, Egypt, one before the first chemotherapy treatment and the other before the third. The questionnaires were translated to colloquial Egyptian Arabic, and due, to the high illiteracy level in Egypt an interviewer read the questions in Arabic to each parent and registered the answers. Both questionnaires consisted of almost 90 questions each. In addition, a Case Report Form was filled in from the child's medical journal. The study period consisted of 7 mo (February until September 2008) and we had a participation rate of 97%. Descriptive statistics are presented and Fisher's exact test was used to check for possible differences between the adherent and non-adherent groups. A P-value below 0.05 was considered significant. Software used was SAS version 9.3 for Windows (SAS Institute Inc., Cary, NC, United States). Two hundred and eighty-one (90%) parents answered the second questionnaire, regarding their child's adherence behaviour. Approximately two thirds of the children admitted to their third chemotherapy treatment had received medical recommendations upon discharge from the first or second chemotherapy treatment (181/281, 64%). Sixty-eight percent (123/181) of the parents who were given medical recommendations reported that their child did not follow the recommendations. Two main predictors were found for non-adherence: child resistance (111/123, 90%) and inadequate information (100/123, 81%). In the adherent group, 20% of the parents (n = 12/58) reported trust in their child's doctor while 14 percent 8/58 reported trust in the other health-care professionals. Corresponding numbers for the non-adherent group are 8/123 (7%) for both their child's doctor and other health-care professionals. Almost all of the parents expressed a lack of optimism towards the treatment (116/121, 96%), yet they reported an intention to continue with the treatment for two main reasons, for the sake of their child's life (70%) (P = 0.005) and worry that their child would die if they discontinued the treatment (81%) (P < 0.0001). Non-adherence to medical regimen is common among children diagnosed with cancer in Egypt, the main reasons being child resistance and inadequate information.


Evoked alpha- and mu-rhythm in humans: a neuromagnetic study.
We present the results of a neuromagnetic study on the spatial structure of brain rhythms enhanced by photic and somatosensory stimulation, as measured on the occipital, rolandic and frontorolandic regions in humans. It emerges that, while it is always possible to drive the cerebral activity during sustained stimulation at any given frequency, only certain specific frequencies can produce prolonged synchronization (i.e. the oscillating activity elicited by the repetitive stimulation continues well beyond its termination). In both studied modalities we were able to localize equivalent sources for the synchronized responses; their relationship with the known evoked responses is discussed. In the visual modality the synchronization was characterized by a potentiation of the subjects' alpha-rhythm. In the somatosensory modality synchronization was reflecting two different activities: one probably related to the rolandic mu-rhythm, the second suggesting the presence of two widely separated and time correlated sources possibly driven by a unique, deep clock. Possible implications for other studies of the dominant brain rhythms, or experimental checks on specific brain models, as well as of the visual and somatosensory evoked responses are discussed.


Safety and efficacy of sofosbuvir plus ledipasvir with and without ribavirin for chronic HCV genotype-1 infection: a systematic review and meta-analysis.
Ledipasvir and sofosbuvir are new direct-acting antiviral agents for patients with HCV infection. Ledipasvir inhibits the HCV non-structural 5A protein, while sofosbuvir is a nucleotide polymerase inhibitor. Many studies have evaluated the safety and efficacy of ledipasvir and sofosbuvir combination with and without ribavirin for patients with chronic HCV genotype-1. A computer literature search of PubMed, SCOPUS, Web of Knowledge and Cochrane CENTRAL has been conducted. Studies were screened for eligibility and data were extracted. Sustained virological response (SVR) rate and commonly reported adverse events were pooled as risk ratio (RR) using Review Manager version 5.3 for windows and OpenMeta (Analyst) software. Eight randomized controlled trials (n=1,892) were pooled in the final analysis. A 12-week ledipasvir and sofosbuvir regimen achieved SVR in 97.5% and 89% of non-cirrhotic and cirrhotic patients, respectively. A 24-week ledipasvir and sofosbuvir regimen achieved SVR in 99.6% and 92.6% in non-cirrhotic and cirrhotic patients, respectively. When ribavirin was added to the treatment regiment, the SVR did not differ significantly in either of the treatment regimens (12-week SVR: 93.9% versus 96.7%, RR=0.97, P=0.19 and 24-week SVR: 94.8% versus 97.2%, RR=0.98, P=0.24). The combination of sofosbuvir and ledipasvir achieved high SVR rates (>90%) in both cirrhotic and non-cirrhotic patients with HCV genotype-1. The addition of ribavirin to this regimen did not significantly increase the SVR rates.


Vaccines against cervical cancer.
Cervical cancer and precancerous lesions of the genital tract are a major threat to women's health worldwide. Although the introduction of screening tests to detect cervical cancer and its precursor lesions has reduced overall cervical cancer rates in the developed world, the approach was largely unsuccessful for developing countries, primarily due to a lack of appropriate infrastructures and high costs. Annually, 470,000 cervical cancer cases are diagnosed worldwide, of which 80% occur in developing countries. Despite advances in treatment of cervical cancer, approximately half of the women afflicted with the disease will die. Over 20 years of dedicated research has provided conclusive evidence that a subset of human papillomaviruses are the aetiological agents for cervical cancer. Finding a viral origin for this disease provided the basis to fight cervical cancer using prophylactic or therapeutic vaccination. Both vaccine approaches are reviewed here, with an emphasis on recent clinical data.


Wet oxidation of aqueous phase from hydrothermal liquefaction of sewage sludge.
Hydrothermal liquefaction (HTL) is a thermochemical process for the conversion of biomass into bio-crude oil. However, treatment of post-HTL aqueous by-products is an emerging issue towards the commercialisation of HTL technology. This study investigates the use of non-catalytic wet oxidation (WO) for the reduction of organic compounds and heat production at different temperatures (200-350 °C), residence times (RT) (2-180 min) and excess oxygen. The aqueous phase from HTL of sewage sludge is investigated, and 97.6% of the chemical oxygen demand (COD) and 96.1% of the total organic carbon (TOC) were removed at the highest temperature and retention time. The minimum energy requirement achieved was 9.6 kWh/kg COD removed at 200 °C for 180 min, and the exothermic reactions of the process can generate 28.3% of the required heat. GC-FID and -MS analysis revealed that the degradation of different groups of organic compounds generates acetic acid as an intermediate by-product of WO, being further oxidised at temperatures higher than 300 °C. NH4+and NH3 are generated from the decomposition of nitrogenated organic compounds showing the highest concentration of 704.5 mg NH4+ /L at 350 °C after 180 min.


Superficial Anterior Lamellar Keratoplasty (SALK) for Trauma-induced Post Refractive Surgery Corneal Opacity.
To report a case of post laser in situ keratomileusis (LASIK), nebulomacular corneal opacity following a trauma induced flap dehiscence and was managed with superficial anterior lamellar keratoplasty (SALK). A 32-year-old female underwent LASIK 2.5 years back, with a postoperative unaided visual acuity (VA) of 6/6 in both eyes. She was involved in a road traffic accident and sustained blunt trauma to the right eye 5 months before. At the time of presentation, the VA was 1/60 in the right eye. Slit lamp examination revealed flap dehiscence, stromal scar and descemet folds in that eye. There was a small macular scar in the parafoveal area due to a resolved Berlin's edema. SALK was performed in the affected eye. Unaided VA of 6/36 was noted on post- operative day 1. After 4 weeks of SALK surgery, best corrected VA was 6/24. This case highlights that flap adhesions are not very strong even years after LASIK and SALK may be an effective treatment option for post refractive surgery corneal opacities.


Preventing Suture Extrusion and Recurrence in Mustarde and Furnas Otoplasties by Using Laterally Based Postauricular Dermal Flap, Long-Term Results.
Prominent ear deformity (PD) is an unacceptable condition of pinna that affects 5% of the population and is associated with emotional stress, behavioral disturbances, and social restrictions in relationships. Conchal hypertrphy, inadequate formation of antihelical fold, earlobe placement ahead than it should be, or various combinations of these changes are main characteristics of PD. Many surgical techniques have been described for the PD.The authors' aim was to present laterally based postauricular dermal flap combination with cartilage-sparing methods and effectiveness of this technique in suture extrusion prevention and reducing the rate of recurrence with long-term results. Forty-one patients had bilateral and 6 patients had unilateral PD, a total of 47 patients with a mean age of 14.48 were operated by using this combined procedure. A laterally based supraperichondrial dermal flap was prepared from a deepithelized elliptical postauricular incision. Mustarde and Furnas suture techniques were used solely for PD correction. The dissected laterally based dermal flap was fixed to the mastoid bone with sutures in stretched position after reshaping the auricular cartilage with sutures. The average helix-mastoid distance was (mm) 16.28 ± 2.36, concha-mastoid angle was 25.71 ± 0.96° on 12-month measurements. The helix-mastoid distance showed an increase of 1 to 3 mm, in the concha-mastoid angle measurements of 1° to 2°. Statistically significant changes were observed between the average preoperative, postoperative 1. month, postoperative 12. month helix-mastoid distances (mm), and month concha-mastoid angle (°) measurements (P = 0.0001). The laterally based postauricular dermal flap technique is an effective method to prevent suture extrusion and recurrence which are the most important complications of otoplasty procedure and easy to apply.


Prolactin (PRL)-releasing peptide stimulates PRL secretion from human fetal pituitary cultures and growth hormone release from cultured pituitary adenomas.
The hypothalamic peptide PRL-releasing peptide (PrRP) has recently been cloned and identified as a ligand of an orphan pituitary receptor that stimulates in vitro PRL secretion. PrRP also induces PRL release in rats in vivo, especially in normal cycling females. However, no information on the effects of PrRP in the human is available. To elucidate the role of PrRP in regulating human anterior pituitary hormones, we used human PrRP-31 in primary cultures of human pituitary tissues, including fetal (20--27 weeks gestation) and normal adult pituitaries, as well as PRL- and GH-secreting adenomas. PrRP increased PRL secretion from human fetal pituitary cultures in a dose-dependent manner by up to 35% (maximal effect achieved with 10 nM), whereas TRH was slightly more potent for PRL release. Coincubation with estradiol resulted in enhanced fetal PRL response to PrRP, and GH release was only increased in the presence of estradiol. Although PRL secretion from PRL-cell adenomas was not affected by PrRP, PrRP induced PRL release from cultures of a GH-cell adenoma that cosecreted PRL. PrRP enhanced GH release in several GH-secreting adenomas studied by 25--27%, including GH stimulation in a mixed PRL-GH-cell tumor. These results show for the first time direct in vitro effects of PrRP-31 on human pituitary cells. PrRP is less potent than TRH in releasing PRL from human fetal lactotrophs and is unable to release PRL from PRL-cell adenomas in culture, but stimulated GH from several somatotroph adenomas. Thus, PrRP may participate in regulating GH, in addition to PRL, in the human pituitary.


Cell signaling, internalization, and nuclear localization of the angiotensin converting enzyme in smooth muscle and endothelial cells.
The angiotensin converting enzyme (ACE) catalyzes the extracellular formation of angiotensin II, and degradation of bradykinin, thus regulating blood pressure and renal handling of electrolytes. We have previously shown that exogenously added ACE elicited transcriptional regulation independent of its enzymatic activity. Because transcriptional regulation generates from protein-DNA interactions within the cell nucleus we have investigated the initial cellular response to exogenous ACE and the putative internalization of the enzyme in smooth muscle cells (SMC) and endothelial cells (EC). The following phenomena were observed when ACE was added to cells in culture: 1) it bound to SMC and EC with high affinity (K(d) = 361.5 +/- 60.5 pM) and with a low binding occupancy (B(max) = 335.0 +/- 14.0 molecules/cell); 2) it triggered cellular signaling resulting in late activation of focal adhesion kinase and SHP2; 3) it modulated platelet-derived growth factor receptor-beta signaling; 4) it was endocytosed by SMC and EC; and 5) it transited through the early endosome, partially occupied the late endosome and the lysosome, and was localized to the nuclei. The incorporation of ACE or a fragment of it into the nuclei reached saturation at 120 min, and was preceded by a lag time of 40 min. Internalized ACE was partially cleaved into small fragments. These results revealed that extracellular ACE modulated cell signaling properties, and that SMC and EC have a pathway for delivery of extracellular ACE to the nucleus, most likely involving cell surface receptor(s) and requiring transit through late endosome/lysosome compartments.


Intracellular Localization of Two Enzymes Involved in Coumarin Biosynthesis in Melilotus alba.
The localization of phenylalanine ammonia-lyase [EC 126.96.36.199] within sweet clover (Melilotus alba) leaves was investigated. Apical buds and axillary leaves contained 15 to 30 times more enzyme activity than did mature leaves. Mesophyll protoplasts were prepared by digesting young leaves with Cellulysin and Macerase and were gently ruptured yielding intact chloroplasts. These chloroplast preparations exhibited neither phenylalanine ammonia-lyase nor o-coumaric acid O-glucosyltransferase activities. The general enzymic properties of sweet clover leaf phenylalanine ammonia-lyase were similar to those described for this enzyme isolated from other plant species. The conversion of l-phenylalanine to trans-cinnamic acid, which occurred at an optimum pH of about 8.7, was strongly inhibited by the metabolites trans-cinnamic and o-coumaric acids. In contrast, o-coumaric acid glucoside, coumarin, p-coumaric acid, and melilotic acid had no significant effect on the reaction rate.


Sperm transport in the human female reproductive tract in relation to semen analysis characteristics and time of ovulation.
Laparoscopic sperm recovery from the pouch of Douglas and tubal fimbriae was performed in 64 infertile couples. Spermatozoa were recovered from 16/35 couples investigated after AIH, and from 13/29 couples post coitum. The method of insemination had no effect on the result, which was positive in 45.3% of all couples, although AIH did result in significantly larger numbers of peritoneal spermatozoa. The number of peritoneal spermatozoa did not show any direct correlation with the number inseminated, but there were reductions along the tract of 5.83 (+/- 1.4 s.d.) orders of magnitude for total sperm count, and 5.52 (+/- 1.21 s.d.) for the number of motile spermatozoa. Only sperm motility had a significant influence on the success of sperm transport; spermatozoa were recovered from patients with sperm densities as low as 3.0 and 3.5 x 10(6)/ml, but with 56 and 44% motile spermatozoa. No influence of cycle day within the range +/- 4 days of ovulation on sperm transport was found. In 45 couples, routine semen analyses were apparently completely normal, but the incidence of sperm recovery was still only 49% (22/45), suggesting that a failure of sperm transport may have been a significant causative factor in their infertility.


The photodissociation of oxetane at 193 nm as the reverse of the Paterno-Buchi reaction.
We investigated the photodissociation of oxetane (1,3-trimethylene oxide) at 193.3 nm in a molecular-beam apparatus using photofragment-translational spectroscopy and selective photoionization. We measured time-of-flight (TOF) spectra and angular anisotropy parameters beta(t) as a function of flight time of products at m/z=26-30 u utilizing photoionization energies from 9.8 to 14.8 eV. The TOF distributions of the products alter greatly with the employed photon energy, whereas their beta(t) distributions are insensitive to the photon energy. Dissociation to H(2)CO+C(2)H(4) is the major channel in the title reaction. Three distinct dissociation paths with branching ratios 0.923:0.058:0.019 are responsible for the three features observed in the distribution of kinetic energy released in the channel H(2)CO+C(2)H(4). The observation of H(2) and H atoms, approximately 1% in branching, indicates that products H(2)CO and C(2)H(4) spontaneously decompose to only a small extent. Most HCO, C(2)H(3), and C(2)H(2) ions originate from dissociative photoionization of products H(2)CO and C(2)H(4). Except atomic H and H(2), the photoproducts have large angular anisotropies, beta>or=-0.8, which reflects rapid dissociation of oxetane following optical excitation at 193.3 nm. The mechanisms of dissociation of oxetane are addressed. Our results confirm the quantum-chemical calculations of Palmer et al. and provide profound insight into the Paterno-Buchi reaction.


Breast arterial calcifications on mammograms do not predict coronary heart disease at coronary angiography.
To examine, in women who underwent cardiac catheterization, whether breast arterial calcifications (BACs) seen at screening mammography correlate with coronary heart disease (CHD) seen at coronary angiography. In an institutional review board-approved, HIPAA-compliant study, 172 women (mean age, 64.29 years +/- 11.97 [standard deviation]) who underwent coronary angiography were recruited, interviewed, and assigned to two groups: those with (CHD+) and those without (CHD-) CHD. The severity and location of the CHD were considered. Their mammograms were reviewed by a breast imaging specialist who was blinded to the CHD status. Student t test, chi(2), and multiple logistic regression tests were performed as appropriate. Presence of BAC was noted and correlated with presence of CHD and presence of cardiac risk factors. There were 104 women with and 68 women without CHD. Thirty-seven (36%) women in the CHD+ group versus 20 (29%) in the CHD-group (P = .40) had BAC. The mean age of the patients with BAC, 72 years +/- 9.8, was significantly older than the mean age of the patients without BAC, 60.4 years +/- 11.1 (P < .001). Therefore, subjects were divided into those younger than 65 years and those 65 years and older. No correlation existed, despite the fact that BAC was associated with some cardiac risk factors. The authors did not observe a correlation between BAC and coronary angiography-detected CHD, even when CHD severity was considered. On the basis of these results, caution should be exercised when using screening mammography-detected BAC to identify patients with CHD.


Direct measurement of the percolation probability in carbon nanofiber-polyimide nanocomposites.
We present the first experimental measurement of the geometric critical exponent beta associated with the percolation probability, the probability a metallic filler belongs to the conducting network, of an electrical composite. The technique employs conducting-tip atomic force microscopy to obtain a conducting areal density, and is demonstrated on polyimide nanocomposites containing different concentrations of carbon nanofibers. We find beta approximately 1 and t (the exponent for bulk conductivity) approximately 3. These values are consistent with the predictions for the Bethe lattice and larger than the values predicted in the 3D lattice percolation model. Hence, this electrical composite likely belongs to the same universality class as the Bethe lattice. The ability to measure geometric and transport critical exponents on the same material is critical to drawing this conclusion.


Vulnerable plaque: the pathology of unstable coronary lesions.
Vulnerable plaques have been defined as precursors to lesions that rupture. However, coronary thrombosis may occur from other lesions like plaque erosion and calcified nodules, although to a lesser frequency than rupture. Therefore, the definition of vulnerable plaque should be all-inclusive. Using descriptive terminology, the authors define the precursor lesion of plaque rupture as "thin-cap fibroatheroma" (TCFA). Morphologically, TCFAs have a necrotic core with an overlying thin fibrous cap (< 65 mm) consisting of collagen type I, which is infiltrated by macrophages. These lesions are most frequent in the coronary tree of patients dying with acute myocardial infarction and least common in those with plaque erosion. TCFAs are more common in patients with high serum total cholesterol (TC) and a high TC to high density cholesterol ratio, in women > 50 years, and in those patients with elevated levels of high sensitivity C-reactive protein. TCFAs are mostly found in the proximal left anterior descending coronary arteries and less commonly in the proximal right or the proximal left circumflex coronary arteries. In TCFAs, necrotic core length is approximately 2-17 mm (mean 8 mm) and the underlying cross-sectional luminal narrowing in over 75% of cases is < 75% (< 50% diameter stenosis). The area of the necrotic core in at least 75% of cases is < or = 3 mm2. Clinical studies of TCFAs are limited as angiography and intravascular ultrasound (IVUS) catheters cannot precisely identify these lesions. Newer catheters and other techniques are at various stages of development and will play a significant role in the understanding of plaque progression and the development of symptomatic coronary artery disease.


Role of Conventional Dynamic Myelography for Detection of High-Flow Cerebrospinal Fluid Leaks : Optimizing the Technique.
Spinal imaging is essential to identify and localize cerebrospinal fluid (CSF) leaks in spontaneous intracranial hypotension (SIH) patients when targeted treatment is necessary. Provide an in-depth presentation of the conventional dynamic myelography (CDM) technique for localizing spinal CSF leaks in SIH patients. Consecutive SIH patients with a CSF leak confirmed on CDM and postmyelography computed tomography (CT) investigated at our institution between 2013 and 2019 were retrospectively analyzed. Intraoperative reports were reviewed to confirm the accuracy of CDM. In total, 62 patients (mean age 45 years) were included; 48 with a ventral dural tear, 12 with a meningeal diverticulum, and in 2 patients positive for spinal longitudinal extradural CSF collection the site remained unclear. The leak was identified during the first and the second CDM in 43 and 17 patients, respectively. The use of CDM correctly identified the site of the CSF leak in all but one patient undergoing surgical closure (45/46, 98%). The mean fluoroscopy time was 7.8 min (range 1.8-14.4 min) with a radiation dose for a single examination of 310 mGy (range 28-1237 mGy). The CDM procedure has a high accuracy for spinal CSF leak localization including dural tears and spinal nerve diverticula. It is the technique with the highest temporal resolution, is robust to breathing artifacts, allows great flexibility regarding patient positioning, compares favorably to other dynamic examinations with respect to the radiation dose and does not require general anesthesia. For CSF venous fistulas, however, other dynamic examinations, such as digital subtraction myelography, seem more appropriate.


Climate change expands the spatial extent and duration of preferred thermal habitat for lake Superior fishes.
Climate change is expected to alter species distributions and habitat suitability across the globe. Understanding these shifting distributions is critical for adaptive resource management. The role of temperature in fish habitat and energetics is well established and can be used to evaluate climate change effects on habitat distributions and food web interactions. Lake Superior water temperatures are rising rapidly in response to climate change and this is likely influencing species distributions and interactions. We use a three-dimensional hydrodynamic model that captures temperature changes in Lake Superior over the last 3 decades to investigate shifts in habitat size and duration of preferred temperatures for four different fishes. We evaluated habitat changes in two native lake trout (Salvelinus namaycush) ecotypes, siscowet and lean lake trout, Chinook salmon (Oncorhynchus tshawytscha), and walleye (Sander vitreus). Between 1979 and 2006, days with available preferred thermal habitat increased at a mean rate of 6, 7, and 5 days per decade for lean lake trout, Chinook salmon, and walleye, respectively. Siscowet lake trout lost 3 days per decade. Consequently, preferred habitat spatial extents increased at a rate of 579, 495 and 419 km(2) per year for the lean lake trout, Chinook salmon, and walleye while siscowet lost 161 km(2) per year during the modeled period. Habitat increases could lead to increased growth and production for three of the four fishes. Consequently, greater habitat overlap may intensify interguild competition and food web interactions. Loss of cold-water habitat for siscowet, having the coldest thermal preference, could forecast potential changes from continued warming. Additionally, continued warming may render more suitable conditions for some invasive species.


Direct analysis of Stevia leaves for diterpene glycosides by desorption electrospray ionization mass spectrometry.
The analysis of Stevia leaves has been demonstrated without any sample preparation using desorption electrospray ionization (DESI) mass spectrometry. Direct rapid analysis was achieved using minimal amounts of sample ( approximately 0.15 cm x 0.15 cm leaf fragment). Characteristic constituents of the Stevia plant are observed in both the positive and negative ion modes including a series of diterpene 'sweet' glycosides. The presence of the glycosides was confirmed via tandem mass spectrometry analysis using collision-induced dissociation and further supported by exact mass measurements using an LTQ-Orbitrap. The analysis of both untreated and hexane-extracted dry leaves proved that DESI can be successfully used to analyze untreated leaf fragments as identical profiles were obtained from both types of samples. Characterization and semi-quantitative determination of the glycosides was achieved based on the glycoside profile within the full mass spectrum. In addition, the presence of characteristic glycosides in an all-natural commercial Stevia dietary supplement was confirmed. This study provides an example of the application of DESI to direct screening of plant materials, in this case diterpene glycosides.


Stable protein device platform based on pyridine dicarboxylic acid-bound cubic-nanostructured mesoporous titania films.
Here we shortly report a protein device platform that is extremely stable in a buffer condition similar to human bodies. The protein device platform was fabricated by covalently attaching cytochrome c (cyt c) protein molecules to organic coupler molecules (pyridine dicarboxylic acid, PDA) that were already covalently bound to an electron-transporting substrate. A cubic nanostructured mesoporous titania film was chosen as an electron-transporting substrate because of its large-sized cubic holes (∼7 nm) and highly crystalline cubic titania walls (∼0.4 nm lattice). Binding of PDA molecules to the mesoporous titania surface was achieved by esterification reaction between carboxylic acid groups (PDA) and hydroxyl groups (titania) in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) mediator, whereas the immobilization of cyt c to the PDA coupler was carried out by the EDC-mediated amidation reaction between carboxylic acid groups (PDA) and amine groups (cyt c). Results showed that the 2,4-position isomer among several PDAs exhibited the highest oxidation and reduction peak currents. The cyt c-immobilized PDA-bound titania substrates showed stable and durable electrochemical performances upon continuous current-voltage cycling for 240 times (the final current change was less than 3%) and could detect superoxide that is a core indicator for various diseases including cancers.


Nickel sensitization in patients with gastro-esophageal reflux disease.
Gastro-esophageal reflux disease (GERD) leads to frequent medical visits, and available therapies fail in up to 40% of patients. Food allergies may be involved in GERD pathogenesis; however, allergens other than food have received little attention. Nickel allergy is common in the general population and some high-nickel foods are associated with GERD. However, the potential relationship between nickel allergy and GERD remains unaddressed. This study aimed to evaluate the prevalence of nickel sensitization in patients with and without GERD and to compare clinical and demographic features. This prospective, multicenter study included 210 adult GERD patients and 140 patients without GERD who presented at the general practitioner. All GERD patients had undergone treatment with proton pump inhibitors and upper digestive endoscopy within the previous five years. Demographic and clinical data were collected by questionnaire and patients underwent a nickel patch allergy test. Patients with and without GERD presented similar characteristics, with the exception of nickel sensitization, which was significantly more prevalent among GERD patients than controls (39.5% vs. 16.4%; p = 0.001). Nickel-positive GERD patients were more frequently female (90.4% vs. 65.4%, p = 0.003) and asthmatic (18.1% vs. 4.7%; p = 0.038), compared to nickel-negative GERD patients. At six-month follow-up, most of the patients, with or without nickel sensitization, reported improved symptoms without differences in drug prescription. Nickel sensitization is particularly prevalent in GERD patients seen in general practice. Whether allergies other than food allergy play a role in GERD remains to be elucidated.


Hemimandibular hyperplasia.
True hemimandibular hyperplasia is an uncommon maxillofacial deformity. Patients with this affliction present clinically with varying degrees of asymmetry characterized by an increase in ramus height, a rotated facial appearance with kinking at the mandibular symphysis, and prominence of the lower border of the mandible. In the advanced form, maxillary and mandibular alveolar bone overgrowth result in a compensatory canting of the occlusal plane and a significant functional malocclusion requiring bimaxillary surgical correction. Nine patients with the above condition were treated with various surgical methods over a 9-year period. The clinical results were satisfying and the long-term results showed good postoperative stability. The pathology of hemimandibular hyperplasia is described and the preexisting nomenclature further defined.


Posttraumatic stress and related symptoms among neglected and physically and sexually maltreated adolescents.
Posttraumatic stress disorder (PTSD) is common among maltreated youth, but few investigations compare neglect with other maltreatment types. This study examined 84 adolescents who experienced neglect only, physical and/or sexual maltreatment only, or neglect with physical and/or sexual maltreatment. Symptoms of PTSD, dissociation, and depression were measured. Adolescents who experienced physical and/or sexual maltreatment, whether neglected or not, reported significantly greater symptomatology than adolescents who experienced neglect only (η2 = .094). This difference applied to PTSD symptoms, dissociative amnesia, depersonalization and derealization, negative mood, and anhedonia. Adolescents exposed to neglect only displayed substantial psychopathology but less than that of other groups. The findings may reflect emerging cascade models of the etiology of symptoms of PTSD following extensive maltreatment history.


Milk Formula Diet Alters Bacterial and Host Protein Profile in Comparison to Human Milk Diet in Neonatal Piglet Model.
The metaproteome profiling of cecal contents collected from neonatal piglets fed pasteurized human milk (HM) or a dairy-based infant formula (MF) from postnatal day (PND) 2 to 21 were assessed. At PND 21, a subset of piglets from each group (n = 11/group) were euthanized, and cecal contents were collected for further metaproteome analysis. Cecal microbiota composition showed predominantly more Firmicutes phyla and Lachnospiraceae family in the lumen of cecum of HM-fed piglets in comparison to the MF-fed group. Ruminococcus gnavus was the most abundant species from the Firmicutes phyla in the cecal contents of the HM-fed piglets at 21 days of age. A greater number of expressed proteins were identified in the cecal contents of the HM-fed piglets relative to the MF-fed piglets. Greater abundances of proteins potentially expressed by Bacteroides spp. such as glycoside enzymes were noted in the cecal lumen of HM-fed piglets relative to the MF. Additionally, lyases associated with Lachnospiraceae family were abundant in the cecum of the HM group relative to the MF group. Overall, our findings indicate that neonatal diet impacts the gut bacterial taxa and microbial proteins prior to weaning. The metaproteomics data were deposited into PRIDE, PXD025432 and 10.6019/PXD025432.


Ultratrace Determination of Cr(VI) and Pb(II) by Microsample Injection System Flame Atomic Spectroscopy in Drinking Water and Treated and Untreated Industrial Effluents.
Simple and robust analytical procedures were developed for hexavalent chromium (Cr(VI)) and lead (Pb(II)) by dispersive liquid-liquid microextraction (DLLME) using microsample injection system coupled with flame atomic absorption spectrophotometry (MIS-FAAS). For the current study, ammonium pyrrolidine dithiocarbamate (APDC), carbon tetrachloride, and ethanol were used as chelating agent, extraction solvent, and disperser solvent, respectively. The effective variables of developed method have been optimized and studied in detail. The limit of detection of Cr(VI) and Pb(II) were 0.037 and 0.054 µg/L, respectively. The enrichment factors in both cases were 400 with 40 mL of initial volumes. The relative standard deviations (RSDs, n = 6) were <4%. The applicability and the accuracy of DLLME were estimated by the analysis of Cr(VI) and Pb(II) in industrial effluent wastewater by standard addition method (recoveries >96%). The proposed method was successfully applied to the determination of Cr(VI) and Pb(II) at ultratrace levels in natural drinking water and industrial effluents wastewater of Denizli. Moreover, the proposed method was compared with the literature reported method.


Cut-off values for waist circumference in Turkish population: Is there a threshold to predict insulin resistance?
To identify the cut-off values for waist circumference (WC) that may best predict cardiometabolic risk associated with insulin resistance in adult Turkish men and women. A total of 1,039 non-diabetic subjects (592 females, 447 males; mean age 40.2+/-12.8 years) aged = or >18 years were enrolled. Insulin resistance was assessed with homeostasis model assessment of insulin resistance (HOMA-IR). The subjects were classified into quantiles based on the WC values and quantiles were compared with respect to the HOMA-IR levels. Receiver operating characteristic (ROC) analysis was used to identify the WC cut-off value that would best predict insulin resistance. HOMA-IR values increased in parallel with increasing WC quantiles for both genders (p=0.001). The cut-off values for WC that showed the highest sensitivity and specificity to predict insulin resistance were 93 cm for men (91.6% and 51%, respectively) and 83 cm for women (91.1% and 34.8%, respectively). Our results demonstrate that the cut-off values for WC that would best predict cardiometabolic risk associated with insulin resistance are 93 cm for men and 83 cm for women in Turkish adults. However, our findings also raise the question as to whether it is indeed necessary to define a WC cut-off value for the prediction of insulin resistance, because, regardless of the cut-off WC value taken into account, insulin resistance will be overlooked in a significant number of individuals with a WC below this cut-off value.


The influence of environmental temperature on the response of the skin to local pressure: the impact of aging and diabetes.
To protect against ischemia, pressure-induced vasodilation (PIV) causes an increase in skin blood flow. Endothelial dysfunction, which is commonly found in older patients and those with diabetes, and global temperatures can affect the resting blood flow in skin, which may reduce the blood flow during and after the application of local pressure. The present study investigated the PIV of the skin with exposure to three global temperatures in younger and older populations and those with diabetes. Older subjects (n = 15, mean age 64.2 +/- 14.0 years), subjects with diabetes (n = 15, mean age 62 +/- 5.9 years, mean duration 13.2 +/- 9.1 years), or younger subjects (n = 15, mean age 25.7 +/- 2.9 years) participated. An infrared laser Dopler flow meter was used to measure skin blood flow on the bottom of the foot, lower back, and hand during and after applications of pressure at 7.5, 15, 30, 45, and 60 kPa at 16 degrees C, 24 degrees C, and 32 degrees C global temperatures. The resting blood flow for all subjects was significantly lower in the 16 degrees C environment (P < 0.05). Blood flow in the group with diabetes was significantly lower at rest, during the application of all pressure, and after the release of pressure in all global temperatures (P < 0.05). The younger group showed a significant increase in blood flow after every pressure application, except 7.5 kPa, in all global conditions (P < 0.001). Older subjects and patients with diabetes did not have a significant reactive hyperemia, especially in the 16 degrees C environment. The protective mechanism of PIV is severely reduced in older populations and those with diabetes, especially in colder environments where skin blood flow is already diminished.


Appendiceal disease in hematopoietic cell transplantation.
Appendiceal diseases are rare reported complications during hematopoietic stem cell transplantation with no guidance on management in the published literature. Medical therapy may be considered in selected patients prior to surgical solutions.


Synthesis of N-terminally linked protein and peptide dimers by native chemical ligation.
Dimerization can be utilized to double the molecular weight of proteins and peptides and potentially increase their avidity of binding to target receptors. These dimerization effects may be utilized to increase in vivo half-lives in a manner similar to PEGylation and may also improve biological activity. In this paper, we report a new strategy for the synthesis of N-terminally linked protein and peptide homodimers utilizing native chemical ligation to conjugate a short dithioester linker to the N-terminal cysteines of protein and peptide monomers to form dimers in a single step. This strategy is general and has been applied to the production of dimers from three recombinantly expressed polypeptides, the IgG binding domain Protein G, an HIV entry inhibitor peptide C37H6, and human interleukin-1 receptor antagonist (IL-1ra). The biological activities of the C37H6 and IL-1ra dimers produced by these methods were retained or even slightly increased when compared to their corresponding monomers.


Differential Regulation of Maize Homoserine Dehydrogenase under Physiological Conditions.
Homoserine dehydrogenase is associated with the multibranched pathway of amino acid biosynthesis originating with aspartic acid. Like most of the related pathway enzymes, this enzyme is localized in chloroplasts. The activity and regulatory properties of the threonine-sensitive isozyme of homoserine dehydrogenase isolated from Zea mays var earliking were examined under variable conditions that could exist within chloroplasts. Catalytic activity is not significantly altered within the range of pHs that occur within these organelles, but inhibition of the enzyme by the pathway product, l-threonine, is markedly diminished at the alkaline pHs characteristic of illuminated chloroplasts. Inhibition by threonine is also subject to modulation by physiological levels of NADPH. Under conditions considered to represent the environment within unilluminated chloroplasts, the enzyme is severely inhibited by micromolar concentrations of threonine, but significant enzyme activity is retained under conditions that are likely to occur during illumination, even in the presence of millimolar levels of threonine. These results indicate that homoserine dehydrogenase may be subject to environmentally mediated regulation in vivo. Other observations support this concept and suggest that the intrinsic catalytic and regulatory properties of key enzymes could facilitate a direct link between light-dependent carbon and nitrogen assimilation and amino acid biosynthesis in chloroplasts of higher plants.


Fabrication of microfluidic systems in poly(dimethylsiloxane).
Microfluidic devices are finding increasing application as analytical systems, biomedical devices, tools for chemistry and biochemistry, and systems for fundamental research. Conventional methods of fabricating microfluidic devices have centered on etching in glass and silicon. Fabrication of microfluidic devices in poly(dimethylsiloxane) (PDMS) by soft lithography provides faster, less expensive routes than these conventional methods to devices that handle aqueous solutions. These soft-lithographic methods are based on rapid prototyping and replica molding and are more accessible to chemists and biologists working under benchtop conditions than are the microelectronics-derived methods because, in soft lithography, devices do not need to be fabricated in a cleanroom. This paper describes devices fabricated in PDMS for separations, patterning of biological and nonbiological material, and components for integrated systems.


Novel human PDCD4 (H731) gene expressed in proliferative cells is expressed in the small duct epithelial cells of the breast as revealed by an anti-H731 antibody.
The novel gene H731 (approved name: PDCD4 (programmed cell death 4)) has been isolated as an antigen gene of the monoclonal antibody Pr-28 which recognized a nuclear antigen in proliferating cells. The gene is homologous to the mouse gene (MA-3/Pdcd4/A7-1) which was associated with apoptosis and was shown to suppress tumor promoter-induced neoplastic transformation. A polyclonal antibody against H731-protein derived from an extract of Escherichia coli transformed with an H731 expression plasmid was prepared, and the H731-protein expression in human normal and tumor cells using the antibody was studied. The staining patterns of asynchronous cultures of human normal fibroblasts (MRC-5) were heterogeneous but the antigen was accumulated in the nuclei at the G0 phase. On the contrary, the antigen was overproduced and localized in the cytoplasm during the cell cycle in tumor cell lines. Immunohistological studies revealed that the H731-protein was highly expressed in bladder carcinoma and breast carcinoma tissues compared with the normal tissues so far tested. These results indicated that expression of the H731-protein was up-regulated or induced in the proliferative cells. Immunohistological studies also revealed that the protein was abundantly expressed in the small duct epithelial cells of the normal mammary gland.


Comparative study of the effect of serum containing granulocyte-stimulating activity and colony-stimulating activity on hematopoiesis in triple-set diffusion chambers.
Serum obtained from rats with polyvinylpyrrolidone-induced sterile inflammation contains granulopoiesis-stimulating activity (GSA). In triple-set diffusion chambers (DC) with GSA in the middle chamber a stimulation of morphologically recognizable granulocytic cells (MRG) was found in mouse bone marrow cells cultivated in side chambers for 6 and 24 h. GSA also induced an increase in the number of CFU-GM when DC were inplanted into the peritoneum of normal rats. Under the same experimental conditions, colony-stimulating factor (CSA) from mouse-lung-conditioned medium did not cause such changes either in MRG or in CFU-GM compartments. The data obtained indicate the different stimulating action of GSA and CSA on granulopoiesis.


Dynamic mechanical loading facilitated chondrogenic differentiation of rabbit BMSCs in collagen scaffolds.
Mechanical signals have been played close attention to regulate chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In this study, dynamic mechanical loading simulation with natural frequencies and intensities were applied to the 3D cultured BMSCs-collagen scaffold constructs. We investigated the effects of dynamic mechanical loading on cell adhesion, uniform distribution, proliferation, secretion of extracellular matrix (ECM) and chondrogenic differentiation of BMSCs-collagen scaffold constructs. The results indicated that dynamic mechanical loading facilitated the BMSCs adhesion, uniform distribution, proliferation and secretion of ECM with a slight contraction, which significantly improved the mechanical strength of the BMSCs-collagen scaffold constructs for better mimicking the structure and function of a native cartilage. Gene expression results indicated that dynamic mechanical loading contributed to the chondrogenic differentiation of BMSCs with higher levels of AGG, COL2A1 and SOX9 genes, and prevented of hypertrophic process with lower levels of COL10A1, and reduced the possibility of fibrocartilage formation due to down-regulated COL1A2. In conclusion, this study emphasized the important role of dynamic mechanical loading on promoting BMSCs chondrogenic differentiation and maintaining the cartilage phenotype for in vitro reconstruction of tissue-engineered cartilage, which provided an attractive prospect and a feasibility strategy for cartilage repair.


Spatial and temporal genetic homogeneity of orf viruses infecting Japanese serows (Capricornis crispus).
This study genetically characterized orf viruses (ORFVs) isolated from recent outbreaks in Japanese serows (Capricornis crispus) in 2007 and 2008, and from earlier outbreaks from 1985 to 2001. Nucleotide sequences of genes for the viral envelope, vascular endothelial growth factor (VEGF), and virus interferon resistance (VIR) were determined in two ORFVs isolated from recent outbreaks and in eight from earlier outbreaks. No deletions or insertions were observed in these genes. Surprisingly, the amino acid sequences of the envelope and VIR genes were identical among the 10 ORFVs, and only one amino acid substitution in the VEGF gene was found in one of the two recent ORFVs (2007). Genotyping by differential PCR for the A32L gene, which encodes an ATPase, classified all of the 10 ORFVs into the same genotype. In an ORFV isolated from a sheep in 1970, the three sequenced genes were almost the same as in the ORFVs isolated from Japanese serows, and the ORFV in 1970 was classified into the same genotype as the ORFVs from Japanese serows. These results suggest that recent outbreaks in Japanese serows are caused by ORFVs genetically closely related to the viruses in earlier outbreaks and that these genetically stable ORFVs have circulated among Japanese serows over a long period of time.


Measurements of tortuosity in stereolithographical bone replicas using audiofrequency pulses.
The tortuosity of five air-filled stereolithographical cancellous bone replicas has been obtained from measurements using audiofrequency pulses in a rectangular waveguide. The data obtained from the replicas yields information about anisotropy with respect to orthogonal axes of the passages that would be marrow filled in vivo. A strong relationship has been found between the acoustically measured tortuosity and the independently measured porosity. Use of stereolithographical bone replicas has the potential to simulate perforation and thinning of cancellous bone and hence evaluate the dependence of acoustic properties on cancellous bone microstructure. As an "extreme" illustration of such use, "inverses" of the original replicas have been manufactured and acoustic measurements have been made on them. The data reveal significantly greater tortuosity of the passages that are geometrically equivalent to the original solid bone structures.


Quantitative proteomics identifies TUBB6 as a biomarker of muscle-invasion and poor prognosis in bladder cancer.
Muscle-invasive urothelial carcinoma (MIUC) of the bladder shows highly aggressive tumor behavior, which has prompted the quest for robust biomarkers predicting invasion. To discover such biomarkers, we first employed high-throughput proteomic method and analyzed tissue biopsy cohorts from patients with bladder urothelial carcinoma (BUC), stratifying them according to their pT stage. Candidate biomarkers were selected through bioinformatic analysis, followed by validation. The latter comprised 2D and 3D invasion and migration assays, also a selection of external public datasets to evaluate mRNA expression and an in-house patient-derived tissue microarray (TMA) cohort to evaluate protein expression with immunohistochemistry (IHC). Our multilayered platform-based analysis identified tubulin beta 6 class V (TUBB6) as a promising prognostic biomarker predicting MIUC of the bladder. The in vitro 2D and 3D migration and invasion assays consistently showed that inhibition of TUBB6 mRNA significantly reduced cell migration and invasion ability in two BUC cell lines with aggressive phenotype (TUBB6 migration, P = .0509 and P < .0001; invasion, P = .0002 and P = .0044; TGFBI migration, P = .0214 and P = .0026; invasion, P < .0001 and P = .0001; T24 and J82, respectively). Validation through multiple public datasets, including The Cancer Genome Atlas (TCGA) and selected GSE (Genomic Spatial Event) databases, confirmed TUBB6 as a potential biomarker predicting MIUC. Further protein-based validation with our TMA cohort revealed concordant results, highlighting the clinical implication of TUBB6 expression in BUC patients (overall survival: P < .001). We propose TUBB6 as a novel IHC biomarker to predict invasion and poor prognosis, also select the optimal treatment in BUC patients.


Effectiveness of HIV prevention social marketing with injecting drug users.
Social marketing involves applying marketing principles to promote social goods. In the context of health behavior, it has been used successfully to reduce alcohol-related car crashes, smoking among youths, and malaria transmission, among other goals. Features of social marketing, such as audience segmentation and repeated exposure to prevention messages, distinguish it from traditional health promotion programs. A recent review found 8 of 10 rigorously evaluated social marketing interventions responsible for changes in HIV-related behavior or behavioral intentions. We studied 479 injection drug users to evaluate a community-based social marketing campaign to reduce injection risk behavior among drug users in Sacramento, California. Injecting drugs is associated with HIV infection in more than 130 countries worldwide.


GM-CSF regulates human eosinophil responses to F-Met peptide and platelet activating factor.
Evidence is accumulating that suggests that granulocyte macrophage CSF (GM-CSF) may have inflammatory actions in addition to its effects as a hematopoietic growth factor. In these studies, the effects of culture of purified human eosinophils with GM-CSF on cellular responses, including intracellular calcium responses, the expression of adherence molecules, and adhesion, were examined. In freshly isolated eosinophils expression of the adhesion molecule CD11b was only weakly increased by a 10-min incubation with platelet-activating factor (PAF) (118 +/- 3, 121 +/- 4, 117 +/- 2, n = 8) and FMLP (100 +/- 1, 106 +/- 6, and 105 +/- 4% of control for 10(-8), 10(-7), and 10(-6) M, respectively, n = 4). Lyso PAF never increased CD11b expression. Exposure of eosinophils to GM-CSF (0.5 ng/ml for 2 days) induced an increase in CD11b responses to PAF (132 +/- 3, 144 +/- 4, and 140 +/- 7) and FMLP (123 +/- 8, 145 +/- 10, and 137 +/- 4% of control for 10(-8), 10(-7), and 10(-6) M concentrations, respectively, n = 4). In 3-day culture studies, responses were greatest on days 2 and 3. The half-maximal GM-CSF concentration for the increase in the response to FMLP (10(-7) M, day 2) was approximately 100 pg/ml. GM-CSF (0.5 ng/ml) induced an increase in basal CD11b expression by day 1, which declined toward the initial baseline on days 2 and 3. Dexamethasone (10(-7) M) hastened the decline in baseline CD11b expression but did not inhibit the increase in the response to either PAF or FMLP. After 3 days of culture with GM-CSF (0.08 ng/ml), FMLP (10(-6) M)-induced elevations of intracellular calcium were increased (277 +/- 27% of day 0 control, n = 4, p < 0.01), whereas the response induced by PAF was not (70 +/- 36% of day 0 control, p = NS). A 30-min exposure to GM-CSF caused a potentiation of both PAF- and FMLP-induced adherence of eosinophils to gelatin-coated plastic. Longer incubation with GM-CSF (3 days) potentiated only FMLP-induced adherence. We conclude that expression of adherence molecules, transmembrane signaling, and adherence responses of eosinophils are enhanced by exposure to GM-CSF. These effects of GM-CSF could potentiate the adherence to endothelium and subsequent migration of eosinophils to inflammatory sites in vivo.


Realtime three-dimensional remote medical skills acquisition.
Three-dimensional techniques are gaining widespread use in a number of disciplines, including medicine, where the visualization of depth information is not only useful but important. Both computer-generated 3-D imaging and 3-D video are set to become increasingly important tools for both diagnosis and teaching. In this paper we will present some of the work that we are currently undertaking using 3-D techniques for remote surgical skills acquisition. This work is based on the use of a small headset with twin miniature video cameras, video codecs, two different 3-D visualization systems and BT's ISDN telecommunications network.


Marked reduction in antibiotic usage following intensive malaria control in a cohort of Ugandan children.
Intensive malaria control may have additional benefits beyond reducing the incidence of symptomatic malaria. We compared antibiotic treatment of children before and after the implementation of highly effective malaria control interventions in Tororo, a historically high transmission area of Uganda. Two successive cohorts of children, aged 0.5 to 10 years, were followed from September 2011 to October 2019 in a dedicated study clinic. Universal distribution of long-lasting insecticidal nets was conducted in 2013 and 2017. Sustained indoor residual spraying of insecticide (IRS) was initiated in December 2014. Generalized linear mixed-effects models were used to compare the incidence of antimalarial and antibiotic treatments before and after vector control measures were implemented. Comparing the period prior to the implementation of IRS to the period after IRS had been sustained for 4-5 years, the adjusted incidence of malaria treatments decreased from 2.68 to 0.05 per person-year (incidence rate ratio [IRR] = 0.02, 95% CI 0.01-0.03, p < 0.001), and the adjusted incidence of antibiotic treatments decreased from 4.14 to 1.26 per person-year (IRR = 0.30, 95% CI 0.27-0.34, p < 0.001). The reduction in antibiotic usage was primarily associated with fewer episodes of symptomatic malaria and fewer episodes of fever with sub-microscopic parasitemia, both of which were frequently treated with antibiotics. In a historically high transmission setting, the implementation of highly effective vector control interventions was followed by a marked reduction in antibiotic treatment of children. This added benefit of malaria control could have important implications for antibiotic prescribing practices, efforts to curtail antimicrobial resistance, and health system costs.


How OHC lesions can lead to neural cochlear hypersensitivity.
Several laboratories, including ours, have found that damage to OHCs--but not to IHCs--can produce hypersensitivity of cochlear nerve afferents to low-frequency sound in the presence of hyposensitivity at the characteristic frequency (CF). It is possible to explain the paradox by a mechanical coupling of the OHCs and IHCs through the tectorial membrane, for which there is accumulating experimental evidence. No direct contact between the IHC stereocilia and the tectorial membrane is required.


[Use of preventive strategies by surgeons and HIV exposure].
The objective of this study was to estimate how often surgeons use surgical gowns, masks, gloves and eyewear in the context of occupational exposure to HIV. The authors also wanted to determine what factors were associated with the use of these strategies. Generally surgeons reported infrequent use of preventive strategies. Regular use of double gloving was reported only by 8.5% of respondents, eye protection by 23%. About three-quarters of surgeons reported they always used masks and gowns, 86%--single gloves. Doctors who used eye protection regularly had less blood contacts via conjunctiva per year than surgeons who used such protection seldom or never (mean = 17.6 SD 52.2 vs mean = 21.5 SD 73.6; p<0.003). The older surgeons were more likely than the other respondents to use preventive strategies (p<0.01). Also, the orthopaedic surgeons more than the others adopted such strategies (p<0.0007). To improve the situation, efforts will need to be done to motivate the surgeons to adopt preventive strategies through adequate education system. Improving the comfort of barrier precautions and making them available may also increase the compliance with protection against HIV in the operation room.


Antrodia camphorata induces apoptosis and enhances the cytotoxic effect of paclitaxel in human ovarian cancer cells.
Antrodia camphorata is a Chinese herb. Recently, several reports demonstrated that it had growth-inhibiting effects on some cancer cells. In this study, we investigated whether the crude extract of A. camphorata could inhibit the growth of ovarian cancer cells and examined the possible mechanisms involved. We also examined whether the cytotoxic effect of paclitaxel on ovarian cancer cells would be affected by A. camphorata. Two human ovarian cancer cell lines, SKOV-3 and TOV-21G, were treated with A. camphorata (3-300 μg/mL). An MTT assay was used to test its cytotoxic effect. The apoptosis-related factors including the activity of caspase-3, -8, and -9 and the cytochrome c level released from mitochondria were analyzed. The expression of Bcl-2 family proteins (Bcl-2, Bcl-xL, Bax, Bim, Bad, and Bak) was examined by Western blot analysis. Cell lines were further treated with paclitaxel or paclitaxel plus A. camphorata to examine the cytotoxic efficiency. The MTT assay revealed that A. camphorata was cytotoxic to both the ovarian cancer cells in a dose- and time-dependent manner. Activities of caspase-3, -8, and -9 and release of mitochondrial cytochrome c increased in both ovarian cancer cell lines with increased dose of A. camphorata. Western blot analysis of Bcl-2 family proteins revealed an increased expression of Bad in SKOV-3 cells, whereas increased expression of Bim and Bak and decreased expression of Bcl-xL were noted in TOV-21G cells. In addition, the cytotoxic effect of paclitaxel on SKOV-3 and TOV-21G cells was increased significantly with the addition of A. camphorata (P < 0.01) by MTT assay. These in vitro results suggest that A. camphorata causes a cytotoxic effect on ovarian cancer cells through the induction of apoptosis. It may also enhance the antitumor effect of paclitaxel. Further studies with the ultimate goal of conducting clinical trials are warranted.


Thermal-induced unfolding domains in aldolase identified by amide hydrogen exchange and mass spectrometry.
Amide hydrogen exchange has been measured in short segments of intact rabbit muscle aldolase at temperatures of 14-50 degrees C by the protein fragmentation/mass spectrometry method (Zhang Z, Smith DL, 1993, Protein Sci 2:522-531). Deuterium levels in some segments did not change over the temperature range of the measurements, whereas deuterium levels in other segments increased rapidly with temperature. These results demonstrate that the equilibrium constant for local unfolding, Kunf, of some segments increases with temperature in the low temperature range (14-30 degrees C) of this study. Aldolase begins to lose activity at temperatures above 40 degrees C. In the 40-50 degrees C temperature range, Kunf is greater than 10(-4) in some regions and less than 10(-6) in other regions. This wide range of regional stability in the temperature range where aldolase begins to denature is interpreted in terms of cooperative unfolding/folding domains. Regions of highest stability were located along the hydrophobic subunit binding surface. It is proposed that hydrogen exchange might be used to identify unfolding domains in multidomain proteins whose thermodynamic properties have been determined by differential scanning calorimetry.


Periocular neurofibrosarcoma in a horse.
A periocular neurofibrosarcoma was debulked and treated with intralesional cisplatin in a 5-year-old Thoroughbred mare. The horse presented with a 1-year history of a large slowly progressing subcutaneous mass over the right supraorbital process. The mass was surgically debulked, and intralesional cisplatin (1.0 mg/cm3) was injected in 3 doses at 2 weeks, 5 weeks, and 8 weeks postoperatively. No recurrence was noted over a 15-month follow-up period. Histopathology of the mass indicated neurofibrosarcoma.


Genotyping of noroviruses from patients of the Pilsen University Hospital in the Czech Republic, 2017-2020.
Noroviruses are members of the Caliciviridae family and are currently segregated into at least 10 genogroups. The distribution of these viruses in the Czech Republic has not yet been investigated in detail. A pilot study was performed to contribute to the overall knowledge and understanding of norovirus circulation in the population. Clinical specimens from patients diagnosed with norovirus infection during their hospitalization at the Pilsen University Hospital were genotyped. A total of 118 patients were diagnosed with norovirus infection between July 2017 and March 2020. Stool samples from patients presenting with gastroenteritis were routinely screened by the RIDA®QUICK Norovirus Test (R-Biopharm AG), a rapid chromatographic immunoassay for the qualitative detection of Norovirus genogroups I and II, according to the manufacturers instructions. Norovirus positive samples were subsequently analysed by molecular biological methods. Stool suspensions (10%) were prepared with phosphate-buffered saline, and nucleic acid was extracted using the QIAamp Viral RNA kit (Qiagen) according to the manufacturers instructions. To investigate the genotype distribution, RT-PCR targeting specific sections of the norovirus genome (region C) was employed, followed by purification of PCR products using the QIAquick PCR Purification Kit (Qiagen) and sequencing (Eurofins Genomics). The sequences obtained were analysed by the MEGA X software, and the results of phylogenetic analyses were confirmed by Norovirus Typing Tool Version 2.0 (https://www.rivm.nl/mpf/typingtool/ norovirus/. During the study period, 14 norovirus genotypes or genogroup variants NoV GI, NoV GII and NoV GIX (previously NoV GII.15) were identified. The major genotype NoV GII.4 Sydney-2012 accounted for a total of 70.3% of norovirus gastroenteritis cases. This norovirus variant was detected in 24 months out of 34 months of the study period. In general, the number of norovirus infections increased during autumn and winter months (October to March) when 68 (57.6%) cases were diagnosed. Although norovirus infection was confirmed in all age categories (age range 0-96 years, median 8, mean 27.9), the statistical analysis revealed a significant difference in the incidence of NoV GII.4 infection between the age group 0-4 years and older patients (χ2 = 3.95, P = 0.047). Many patients (51) were residents of the Pilsen-city district. The case history data showed that 35 of them (29.7%) had another family member who developed symptoms of gastroenteritis at the time of the onset of their infection. The pilot study is the first attempt to map the molecular epidemiology of noroviruses, not only in the Pilsen Region but also in the whole Czech Republic. Despite the relatively low number of officially reported cases, noroviruses are undoubtedly one of the most important causes of gastroenteritis in this country. Further studies are therefore necessary to expand the body of knowledge of their ecology and circulation.


[Functionality determinants of the integrated systems dedicated to health care institutions].
The Authors of the hereby dissertation aimed at presenting the functionality concept of the integrated e-service platform dedicated to health care institutions. In the form of a problem repository the research results allowing the identification of the functionality determinants were presented. Finally, the study presents the system's structure as well as analyzing the needs for e-services in terms of society and their usefulness evaluated by branch experts.


In vivo deleterious effects of a right shift of the HbO2 curve during hypoxemia.
We investigated the influence of a right shift of the oxyhemoglobin dissociation curve on tissue oxygenation in two groups of anesthetized rabbits subjected to short periods of graded hypoxia: Group 1 (n = 5) with elevated P50 due to increased RBC 2,3-diphosphoglycerate and adenosine triphosphate and Group 2 (n = 5) with normal P50. Hemoglobin fell progressively in all animals due to blood letting for necessary measurements. During 16% inspired O2 (FIO2), both groups remained stable. During 13% FIO2, arterial pO2 was the same in both groups, but only in Group I did it fall below the crossover point (C.O.P.), which was raised by the high P50. Arterial pH and arterial-venous O2 content difference remained within the normal range in both groups throughout the experiment. During 13% FIO2, animals with high P50 showed a fall in cardiac output and oxygen consumption while animals with normal P50 remained stable. We postulate that when systemic O2 content is sufficiently reduced and tissue O2 extraction is maximal, the O2 needs of the myocardium perfused with a pO2 below the C.O.P. cannot be met: under these conditions cardiac output and systemic O2 consumption fall, presumably due to a reduction in coronary blood flow.


Role of the SDF-1/CXCR4 system in myocardial infarction.
Myocardial infarction (MI) is accompanied by an inflammatory response, leading to the recruitment of leukocytes and subsequent myocardial injury and healing. Chemokines are potent chemoattractant cytokines that regulate leukocyte trafficking in inflammatory processes. Recent evidence indicates that chemokines play a role not only in leukocyte trafficking but also in angiogenesis and cardioprotection. In particular, stromal cell-derived factor-1alpha (SDF-1alpha) has generated considerable interest for its role in the pathophysiology of MI. This review will focus on the role of SDF-1 and its receptor CXC chemokine receptor 4 (CXCR4; ie, the SDF-1/CXCR4 system) in the pathophysiology of MI and discuss their potential as therapeutic targets for MI.


Analysis of the features of 45 identified CRISPR loci in 32 Staphylococcus aureus.
Staphylococcus aureus (S. aureus) is a common pathogen that can cause serious infections, even death. Because of the horizontal gene transfer (HGT) of antibiotic resistance genes, the drug resistant condition is becoming increasingly prevalent. Recently, an adaptive immunity system, named clustered regularly interspaced short palindromic repeats (CRISPR), was discovered and demonstrated to confer a defense against foreign invading elements that may carry the antibiotic resistance genes. In this study, we reveal the features of 45 identified CRISPR loci and the CRISPR associated gene (Cas) in 32 S. aureus strains from CRISPR database. Five spacers of S. aureus 08BA02176 and MSHR1132 were homologous with foreign genetic sequences from phages or plasmids, even containing a spacer sequence identical to part of some phages' genomes containing lukPV gene that encodes the PVL toxin. Many S. aureus strains with the same CRISPR type shared the same MLST type. CRISPR loci that had 3 or more similar protein loci mostly belonged to the same CRISPR type. We came to the conclusion that the CRISPR/Cas of strains 08BA02176 and MSHR1132 were inherited from a common ancestor or recombined from Staphylococcus lugdunensis. CRISPR loci can be mobilized and can transfer among different but closely related species, and the same types of MLST strains exhibit a higher affinity to the same types of CRISPR loci. Bacteriophages may be the predominant challenge facing S. aureus. The CRISPR/Cas structure may limit the transmission of bacterial virulence among S. aureus.


Interaction of TPPP3 with VDAC1 Promotes Endothelial Injury through Activation of Reactive Oxygen Species.
Endothelial injury plays a critical role in the pathogenesis of cardiovascular disorders and metabolic-associated vascular complications which are the leading cause of death worldwide. However, the mechanism underlying endothelial dysfunction is not completely understood. The study is aimed at investigating the role of tubulin polymerization-promoting protein family member 3 (TPPP3) in palmitic acid- (PA-) induced endothelial injury. The effect of TPPP3 on human umbilical vein endothelial cells (HUVECs) was determined by evaluating apoptosis, tube formation, and reactive oxygen species (ROS) production. TPPP3 silencing inhibited PA overload-induced apoptosis and production of ROS, along with the alteration of apoptosis-related key proteins such as BCL-2 and Bax. Mechanically, voltage-dependent anion channel 1 (VDAC1) was identified as a novel functional binding partner of TPPP3, and TPPP3 promoted VDAC1 protein stability and its activity. Further studies indicated that TPPP3 could promote apoptosis, ROS production, tube formation, and proapoptotic protein expression and reduce antiapoptotic protein expression through increasing VDAC1 expression under mildly elevated levels of PA. Collectively, these results demonstrated that TPPP3 could promote PA-induced oxidative damage in HUVECs via a VDAC1-dependent pathway, suggesting that TPPP3 might be considered as a potential therapeutic target in vascular disease.


The crosstalk of RAS with the TGF-β family during carcinoma progression and its implications for targeted cancer therapy.
Both RAS and transforming growth factor (TGF)-β signaling cascades are central in tumorigenesis and show synergisms depending on tumor stage and tissue context. In this review we focus on the interaction of RAS subeffector proteins with signaling components of the TGF-β family including those of TGF-βs, activins and bone morphogenic proteins. Compelling evidence indicates that RAS signaling is essentially involved in the switch from tumor-suppressive to tumor-promoting functions of the TGF-β family leading to enhanced cancer growth and metastatic dissemination of primary tumors. Thus, the interface of these signaling cascades is considered as a promising target for the development of novel cancer therapeutics. The current pharmacological anti-cancer concepts combating the molecular cooperation between RAS and TGF-β family signaling during carcinoma progression are critically discussed.


New horizons in fracture risk assessment.
Fracture is the clinical outcome of concern in osteoporosis, a disease variably defined over the last 30 years, mostly in terms of bone mineral density (BMD). However, an 'osseocentric' view of the condition may have hampered our understanding of how best to identify patients at the greatest risk of fragility fracture. More recently, the identification of a number of clinical risk factors for fragility fracture and the creation of fracture risk assessment tools, such as FRAX®, QFracture and Garvan have helped in a move towards clinically useful definitions, using the common currency of 10-year major osteoporotic and 10-year hip fracture risks. However, there are a large number of available fracture risk assessment tools and there remain few validation studies comparing their performance. The National Institute for Health and Clinical Excellence has recently advocated the use of these methods in case finding and studies are underway in their clinical application. It seems likely that the operational definition of osteoporosis must now include fracture risk, which will never replace fracture incidence as a measure of clinical efficacy but may be used in future studies to define patient groups likely to benefit from intervention. We still need to understand more about the performance of these tools, particularly in the context of specific patient groups, such as those with vertebral osteoporosis, the frail, those who fall and patients with secondary osteoporosis.


Integrin targeting of glyphosate and its cell adhesion modulation effects on osteoblastic MC3T3-E1 cells revealed by label-free optical biosensing.
This study is a discovery of interesting and far reaching properties of the world leading herbicide active ingredient glyphosate. Here we demonstrate the cell adhesion-modifying characteristics of glyphosate affecting cellular interactions via Arg-Gly-Asp (RGD)-dependent integrins. This conclusion was supported by the observations that a glyphosate surface coating induced integrin-specific cell adhesion, while glyphosate in solution inhibited cell adhesion on an RGD-displaying surface. A sensitive, real-time, label-free, whole cell approach was used to monitor the cell adhesion kinetic processes with excellent data quality. The half maximal inhibitory concentration (IC50) for glyphosate was determined to be 0.47 ± 0.07% (20.6 mM) in serum-free conditions. A three-dimensional dissociation constant of 0.352 mM was calculated for the binding between RGD-specific integrins in intact MC3T3-E1 cells and soluble glyphosate by measuring its competition for RGD-motifs binding, while the affinity of those RGD-specific integrins to the RGD-motifs was 5.97 µM. The integrin-targeted affinity of glyphosate was proven using competitive binding assays to recombinant receptor αvβ3. The present study shows not only ligand-binding properties of glyphosate, but also illustrates its remarkable biomimetic power in the case of cell adhesion.


Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families.
Genetic variants in a gene on 6p22.3, dysbindin, have been shown recently to be associated with schizophrenia (Straub et al. 2002a). There is no doubt that replication in other independent samples would enhance the significance of this finding considerably. Since the gene is located in the center of the linkage peak on chromosome 6p that we reported earlier, we decided to test six of the most positive DNA polymorphisms in a sib-pair sample and in an independently ascertained sample of triads comprising 203 families, including the families for which we detected linkage on chromosome 6p. Evidence for association was observed in the two samples separately as well as in the combined sample (P=.00068 for SNP rs760761). Multilocus haplotype analysis increased the significance further to .00002 for a two-locus haplotype and to .00001 for a three-locus haplotype. Estimation of frequencies for six-locus haplotypes revealed one common haplotype with a frequency of 73.4% in transmitted, and only 57.6% in nontransmitted, parental haplotypes. All other six-locus haplotypes occurring at a frequency of >1% were less often transmitted than nontransmitted. Our results represent a first successful replication of linkage disequilibrium in psychiatric genetics detected in a region with previous evidence of linkage and will encourage the search for causes of schizophrenia by the genetic approach.


Characterization of haze-active proteins in apple juice.
The nature of the haze-active protein (HAP) in apple juice was investigated. Heat treatment removed protein indiscriminately while polyvinylpolypyrrolidone (PVPP) treatment was fairly specific for proteins of 15 and 28 kDa. Presumably, the PVPP bound to polyphenols, which in turn were complexed with protein. Three candidate apple HAPs were isolated. Two were extracted from juice with acetone and fractionated by hydrophobic interaction chromatography and solid phase extraction with C18 (HAP I) or SAX (HAP II) material. Hydroxyproline-rich protein was extracted from apple tissue (HAP III). The order of haze formation with tannic acid was gliadin > HAP III > HAP II > HAP I > bovine serum albumin, which shows increasing haze formation with increasing proline content. The sizes of HAP I, II, and III were 28, 15, and 12 kDa; the first two corresponded to the sizes of proteins removed by PVPP treatment and are involved in juice haze formation.


Mechanical strain induces pp60src activation and translocation to cytoskeleton in fetal rat lung cells.
We have previously shown that mechanical strain-induced fetal rat lung cell proliferation is transduced via the phospholipase C-gamma-protein kinase C pathway. In the present study, we found that protein-tyrosine kinase activity of fetal lung cells increased after a short period of strain, which was accompanied by tyrosine phosphorylation of proteins of approximately 110-130 kDa. Several components of this complex were identified as pp60srcsubstrates. Strain increased pp60src activity in the cytoskeletal fraction, which coincided with a shift in subcellular distribution of pp60src from the Triton-soluble to the cytoskeletal fraction. Strain-induced pp60src translocation did not appear to be mediated via the focal adhesion kinase-paxillin pathway. In contrast, strain increased the association between pp60src and the actin filament-associated protein of 110 kDa. Preincubation of cells with herbimycin A, a tyrosine kinase inhibitor, abolished strain-induced phospholipase C-gamma1 tyrosine phosphorylation and its coimmunoprecipitation with pp60src. It also inhibited strain-induced DNA synthesis. These results suggest that activation of pp60src is an upstream event of the phospholipase C-gamma-protein kinase C pathway that may represent an important mechanism by which mechanical perturbations are converted to biological reactions in fetal lung cells.


Callosal function in multiple sclerosis: bimanual motor coordination.
Evidence of callosal dysfunction in patients with multiple sclerosis (MS) was examined using a test of bimanual coordination. MS patients were slower than non-patients on the Bimanual Coordination Test (BCT) on both unimanual trials (simple motor speed) and bimanual trials (intermanual coordination). Further, when compared to normals, MS patients exhibited a substantially greater difference between bimanual and unimanual response time, suggesting a deficit in interhemispheric motor interactions. A subgroup of MS subjects who showed markedly inefficient callosal transmission had previously been identified on the basis of abnormal evoked potentials (low amplitude cross-callosal evoked potentials). In comparisons of MS subgroups, the deficit in bimanual motor coordination was found only in MS patients with EP evidence of inefficient callosal transmission. These data support the conclusion that deficits in bimanual motor coordination occur in MS and that these deficits are related to callosal dysfunction.


Inhibition of monoADP-ribosylation prevents long-term memory consolidation of a single-trial passive avoidance task in the day-old chick.
The cytosolic posttranslational protein-modifying mechanism of monoADP-ribosylation has been implicated in long-term potentiation, a synaptic model of memory formation. The current study investigated the effect of inhibiting mono(ADP-ribosyl) transferase on memory for the passive avoidance task in day-old chicks (white Leghorn-black Australorp). Various doses of novobiocin or menadione sodium bisulfite were administered intracranially at different times before or after training. Control chicks were administered saline at matched times. Novobiocin (650 microM) or menadione sodium bisulfite (250 microM) administered between 5.0 min pretraining and 2.5 min posttraining was found to cause a persistent loss of retention from 120 min posttraining. These data provide the first demonstration that monoADP-ribosylation is required for the maintenance of long-term memory. Furthermore, the temporal characteristics of the memory loss caused by monoADP-ribosylation inhibition appears to exclude this mechanism as a downstream effect of the well-established nitric oxide activity previously shown to occur within 40 min of passive avoidance training.


Synergistic interaction between highly specific cyclooxygenase-2 inhibitor, MF-tricyclic and lovastatin in murine colorectal cancer cell lines.
Statins, anti-hypercholesterolemic agents, have previously been reported to induce apoptosis and exert antitumor activity when combined with other antitumor agents. The potential of lovastatin in combination with highly specific COX-2 inhibitor (MF-tricyclic) to induce anti-proliferative activity against tumour cells was evaluated using the combination index (CI) method. Murine colorectal cancer (colon-26, CMT-93), melanoma (B16F10) and human bladder carcinoma cells (T24) were tested. Exposure of colon-26 and CMT-93 cells resulted in synergistic interactions in both cell lines with CI<1 for 20-80% inhibition of cell growth in both cell lines. This synergy was not observed in the B16F10 melanoma and T24 bladder carcinoma cells. MF-tricyclic (40 microg/ml), augmented lovastatin-induced apoptosis up to 2.5-fold in colon-26 cancer cells. Combination of a specific COX-2 inhibitor, MF-tricyclic, may increase antiproliferative effects of lovastatin in colon cancer cells and this effect was due to an augmented apoptosis.


Momentum transmission of a diaphragmed magnetic spectrometer: I. Analysis and definitions.
An experimental device consisting of a plane source of charged particles and of a magnetic spectrometer equipped with horizontal and vertical diaphragms is considered. An analysis intended to achieve an exact analytical expression to connect the observed particle flux to the source emission and spectrometer transmission characteristics is developed. An analytical expression for the average value of the source brightness that is actually obtained from corpuscular flux measurements is also given. The effectiveness of the diaphragms in defining the domains of the initial conditions of the particles is also emphasized and general definitions of these domains are introduced. These definitions are stated for exact optical transformations, i.e., accounting for geometric and chromatic aberrations, and for general positions of the diaphragms along the optical axis as well as for symmetrical or asymmetrical apertures of the same. The results obtained and the introduced definitions will be used in Part II of this work. The important case of a thick source is considered in Appendix A.


Two Cases of Rectal Cancer with Retzius Shunt Treated with Robot-Assisted Surgery.
The retroperitoneal intestinal vein-general circulation anastomotic pathway is referred to as a Retzius shunt; however, it is not a well-recognized condition. Here, we describe two patients with a Retzius shunt who underwent robot-assisted surgery for rectal cancer. The first case was an 81-year-old woman who had tested positive for fecal occult blood. A type 0-Is tumor was found in the middle rectum, and we used robot-assisted surgery for resection. Intraoperative findings included a dilated vein between the inferior mesenteric artery (IMA) and inferior mesenteric vein (IMV); further, computed tomography (CT) revealed flow into the inferior vena cava (IVC). We clipped the vein without major bleeding and the tumor-specific mesorectal excision was completed. Thereafter, we reviewed relevant literature and identified the structure to be a Retzius shunt. The second case was 77-year-old man with type 1 advanced cancer in the middle rectum who underwent robot-assisted surgery. In this case, we recognized the Retzius shunt on preoperative CT due to our experience with the first case and surgery was completed without any problems. Preoperative recognition of vascular malformations, such as the Retzius shunt by CT is critical to ensure the safety of robot-assisted surgery.


Early experience treating thoracic disc herniations using a modified transfacet pedicle-sparing decompression and fusion.
Symptomatic thoracic disc herniations (TDHs) are relatively uncommon and are typically treated with an anterior approach. Various posterior surgical approaches have been developed to treat TDH, but the gold standard remains transthoracic decompression. Certain patients have comorbidities and herniation aspects that are not optimally treated with an anterior approach. A transfacet pedicle-sparing approach was first described in 1995, but outcomes and complications have not been well described. The objective of this study was to assess outcomes and complications in a consecutive series of patients with TDH undergoing posterior transfacet decompression and discectomy with posterior instrumentation and fusion. Eighteen consecutive patients undergoing operative management of TDH were identified from a tertiary care referral database. All patients underwent a transfacet pedicle-sparing decompression and segmental instrumentation with interbody fusion. Outcomes and complications were retrospectively assessed in this patient series. Clinical records were scrutinized to assess levels and types of disc herniation; blood loss; pre- and postoperative motor scores, Nurick grades, and visual analog pain scale scores; and complications such as wrong-level surgery, infection, seroma, and neurological changes. Pre- and postoperative imaging studies were reviewed to assess levels and types of herniation, alignment, and accuracy of instrumentation. Of the 18 patients, 9 had TDHs at multiple levels. The patients presented with symptoms including myelopathy, axial back pain, urinary symptoms, and radiculopathy and radiological evidence of 29 compressive TDHs ranging from T1-2 to T12-L1. Discs were classified as central (10) or paracentral (19). All discs were successfully removed with no incidence of wrong-level surgery or CSF leak. The mean estimated blood loss was 870 ml with no dural tears. Nurick grades improved on average from 2.5 to 1.9. All patients reported improvement in symptoms compared with preoperative status. The mean visual analog scale score improved from 59 to 21. Sixteen of the 18 patients spent an average of 4.2 days in the hospital; the 2 other patients spent 58 and 69 days. The average duration of follow-up was 12.2 months in 14 patients; 4 patients were lost to follow-up. Twelve patients had no complications. Five patients developed postoperative wound infections or seromas requiring additional operative debridement. One patient had a misplaced screw and suboptimally positioned interbody graft requiring revision. One transient neurological deterioration (American Spinal Injury Association [ASIA] D to ASIA B) occurred postoperatively associated with an inferior segment fracture 20 days after surgery. This necessitated extending the fusion caudally; the patient subsequently experienced a full return to better-than-baseline neurological status. A modified transfacetal pedicle-sparing approach combined with short segmental fusion offers a safe means of achieving concurrent decompression and segmental stabilization and is an option for certain subtypes of TDH. Although 6 patients required additional surgery for postoperative complications, all patients experienced improvement relative to their preoperative status.


Airway hyperresponsiveness and risk of chest symptoms in an occupational model.
The clinical outcome of asymptomatic airway hyperresponsiveness (AHR) remains unclear. A study was undertaken to evaluate the incidence of respiratory symptoms in a cohort of asymptomatic subjects with AHR at baseline. A 3 year prospective study involving methacholine challenge tests and serially administered questionnaires was undertaken in 769 apprentices exposed to high molecular weight allergens. Analyses were performed on 428 initially asymptomatic subjects. Thirty eight subjects (8.9%) were airway hyperresponsive (PC(20) < or =8 mg/ml) and asymptomatic at the start of the study. Forty four apprentices (10.3%) developed two or more respiratory symptoms unrelated to work, 13 (34.2%) in the AHR group and 31 (7.9%) in the non-AHR group (risk ratio (RR) 7.88 (95% CI 2.53 to 24.55) among subjects with AHR). The RR of developing two or more respiratory symptoms increased as the degree of PC(20) decreased with a significant trend (p<0.001). In a multivariate analysis, AHR (RR 8.33, 95% CI 2.65 to 26.16) and self-reported rhinitis on exposure to pollen through an interaction with a family history of asthma (RR 6.3, 95% CI 1.29 to 31.89) were associated with the incidence of two or more respiratory symptoms; atopy was not a significant covariate. AHR in asymptomatic subjects is an important determinant for the development of respiratory symptoms outside the workplace among apprentices exposed to high molecular weight allergens in their training environment.


The Effect of Video Education on Skin-to-Skin Contact at the Time of Delivery: A Randomized Controlled Trial.
Objective The objective of this study was to measure the impact of video education at the time of admission for delivery on intent and participation in skin-to-skin contact (SSC) immediately after birth. Methods This study was a randomized controlled trial of educational intervention in women ( N = 240) of 18 years or older admitted in anticipation of normal spontaneous term delivery. Alternate patients were randomized into video ( N = 120) and no video ( N = 120) groups. Both groups received a survey about SSC. The video group watched an educational DVD and completed a postsurvey about SSC. Results During the preintervention survey, 89.2% of those in the video group compared with 83.3% of those in the no video group indicated that they planned to use SSC ( p = 0.396). After the video, 98.3% planned to do SSC after delivery ( p < 0.001). However, only 59.8% started SSC within 5 minutes of delivery in the video group and only 49.4% started SSC within 5 minutes of delivery in the no video group ( p = 0.17). Conclusion Video education alters the intention and trends toward participation in SSC within 5 minutes of delivery. Despite the plans for SSC, however, there was no significant difference in rates between the two groups. These findings support that obstacles, other than prenatal education, may affect early SSC. Key Points Significant obstacles impact skin-to-skin rate.Video education alters skin-to-skin intent.Video education can improve skin-to-skin rate.Education can happen at the time of delivery.Video education can impact mothers and infants.


A possible role of divalent manganese ions in the photoinduction of phenylalanine ammonia-lyase.
Divalent Mn ions cause an increase in the level of phenylalanine ammonia-lyase in gherkin hypocotyls. With the exception of Mg ions, which had a small effect, no other metal ion has so far been found which could replace the Mn ion in this respect. Invertase and peroxidase were not significantly affected by the Mn treatment. The increase in phenylalanine ammonialyase activity is explained by the removal, under the influence of Mn ions, of hydroxycinnamic acids, which cause repression of phenylalanine ammonia-lyase synthesis and/or inactivation of phenylalanine ammonia-lyase. Arguments are advanced for the hypothesis that photochemical transformations of Mn complexes are involved in the photoinduction of phenylalanine ammonia-lyase in dark-grown gherkin seedlings.


[Small-for-size graft problems in adult-to-adult living donor liver transplantation].
A major concern regarding adult living donor liver transplantation is graft-size disparity. The right liver graft is now commonly used, which might impose a risk on the donors. In selected cases, the left liver with caudate lobe and right lateral sector graft might alleviate the problem without increasing the risk to donors.


Activation of the mTOR pathway by low levels of xenoestrogens in breast epithelial cells from high-risk women.
Breast cancer is an estrogen-driven disease. Consequently, hormone replacement therapy correlates with disease incidence. However, increasing male breast cancer rates over the past three decades implicate additional sources of estrogenic exposure including wide spread estrogen-mimicking chemicals or xenoestrogens (XEs), such as bisphenol-A (BPA). By exposing renewable, human, high-risk donor breast epithelial cells (HRBECs) to BPA at concentrations that are detectable in human blood, placenta and milk, we previously identified gene expression profile changes associated with activation of mammalian target of rapamycin (mTOR) pathway genesets likely to trigger prosurvival changes in human breast cells. We now provide functional validation of mTOR activation using pairwise comparisons of 16 independent HRBEC samples with and without BPA exposure. We demonstrate induction of key genes and proteins in the PI3K-mTOR pathway--AKT1, RPS6 and 4EBP1 and a concurrent reduction in the tumor suppressor, phosphatase and tensin homolog gene protein. Altered regulation of mTOR pathway proteins in BPA-treated HRBECs led to marked resistance to rapamycin, the defining mTOR inhibitor. Moreover, HRBECs pretreated with BPA, or the XE, methylparaben (MP), surmounted antiestrogenic effects of tamoxifen showing dose-dependent apoptosis evasion and induction of cell cycling. Overall, XEs, when tested in benign breast cells from multiple human subjects, consistently initiated specific functional changes of the kind that are attributed to malignant onset in breast tissue. Our observations demonstrate the feasibility of studying renewable human samples as surrogates and reinforce the concern that BPA and MP, at low concentrations detected in humans, can have adverse health consequences.