Comparison of suction above cuff and standard endotracheal tubes in neurological patients for the incidence of ventilator-associated pneumonia and in-hospital outcome: A randomized controlled pilot study.
Ventilator-associated pneumonia (VAP) is a common complication with endotracheal intubation. The occurrence of VAP results in significant mortality and morbidity. Earlier studies have shown reduction in the incidence of VAP with subglottic secretion drainage. The incidence of VAP in neurologically injured patients is higher and can impact the neurological outcome. This study aimed to compare the incidence of VAP with standard endotracheal tube (SETT) and suction above cuff endotracheal tube (SACETT) in neurologically ill patients and its impact on clinical outcome. Fifty-four patients with neurological illnesses aged ≥18 years and requiring intubation and/or ventilation and anticipated to remain on ETT for ≥48 h were randomized to receive either SETT or SACETT. All the VAP preventive measures were similar between two groups except for the difference in type of tube. The data of 50 patients were analyzed. The incidence of clinical VAP was 20% in SETT group and 12% in SACETT group; (P = 0.70). The incidence of microbiological VAP was higher in the SETT group (52%) as compared to SACETT group (44%) but not statistically significant; (P = 0.78). There was no difference between the two groups for measured outcomes such as duration of intubation, mechanical ventilation, and Intensive Care Unit stay. In this pilot study in neurological population, a there was no significant difference in incidence of clinical and microbiological VAP was seen between SETT and SACETT, when other strategies for VAP prevention were similar. Other outcomes were similar with use of either tube for intubation.


New aspects in the treatment of immunomediated diseases.
The following constitutes a summary of lectures delivered during the session "New aspects in the treatment of immunomediated diseases" which was held during the 25th Annual Scientific Meeting of the European Society for Clinical Investigation in Pisa, Italy on 6th April 1991. The aim of this session was to present and discuss some of the novel therapeutic modalities currently being employed either in experimental models or in phase I clinical studies.


The effects of A1 pulley release after flexor tendon repair in a cadaveric model.
Decreasing rupture rates after flexor tendon repair is accomplished by increasing the strength of the repair and by decreasing the forces across tendons during rehabilitation. The authors sought to determine whether A1 pulley release affects work of flexion after a zone 2 flexor tendon repair. Four fresh-frozen cadaveric hands were thawed to room temperature. The flexor digitorum profundus and flexor pollicis longus tendons were tested in a tensile testing machine. In hands 1 and 2, work of flexion of uninjured tendons was evaluated through the sequential division of the A1 pulley, starting with either the proximal 50 percent or the distal 50 percent of the pulley. In hands 3 and 4, zone 2 flexor digitorum profundus lacerations were created and repaired using a modified Kessler technique; then, sequential division of the A1 pulley was performed. Force-excursion curves were generated and used to calculate work of flexion. Analysis of variance was performed for multigroup comparisons, and t tests were performed for pairwise comparisons. Values of p < 0.05 were considered statistically significant. In uninjured tendons, work of flexion decreased with sequential division of the A1 pulley. After tendon repair, work of flexion increased significantly from baseline in all digits. A1 pulley release after flexor tendon repair produced significant decreases in work of flexion in all digits. A1 pulley release effectively decreases work of flexion after flexor tendon repair. Release performed at the time of tendon repair may decrease the forces across tendons in the postoperative period.


Bayesian inference for the lead time in periodic cancer screening.
This article develops a probability distribution for the lead time in periodic cancer screening examinations. The general aim is to allow statistical inference for a screening program's lead time, the length of time the diagnosis is advanced by screening. The program's lead time is distributed as a mixture of a point mass and a piecewise continuous distribution. Simulation studies using the HIP (Health Insurance Plan for Greater New York) study's data provide estimates of different characteristics of a screening program under different screening frequencies. The components of this mixture represent two aspects of screening's benefit, namely, a reduction in the number of interval cases and the extent by which screening advanced the age of diagnosis. We present estimates of these two measures for participants in a breast cancer screening program. We also provide the mean, mode, variance, and density curve of the program's lead time. The model can provide policy makers with important information regarding the screening period, frequency, and the endpoints that may serve as surrogates for the benefit to women who take part in a periodic screening program. Though the study focuses on breast cancer screening, it is also applicable to other kinds of chronic disease.


A catalogue of signal molecules that interact with sensor kinases, chemoreceptors and transcriptional regulators.
Bacteria have evolved many different signal transduction systems that sense signals and generate a variety of responses. Generally, most abundant are transcriptional regulators, sensor histidine kinases and chemoreceptors. Typically, these systems recognize their signal molecules with dedicated ligand-binding domains (LBDs), which, in turn, generate a molecular stimulus that modulates the activity of the output module. There are an enormous number of different LBDs that recognize a similarly diverse set of signals. To give a global perspective of the signals that interact with transcriptional regulators, sensor kinases and chemoreceptors, we manually retrieved information on the protein-ligand interaction from about 1,200 publications and 3D structures. The resulting 811 proteins were classified according to the Pfam family into 127 groups. These data permit a delineation of the signal profiles of individual LBD families as well as distinguishing between families that recognize signals in a promiscuous manner and those that possess a well-defined ligand range. A major bottleneck in the field is the fact that the signal input of many signaling systems is unknown. The signal repertoire reported here will help the scientific community design experimental strategies to identify the signaling molecules for uncharacterised sensor proteins.


Early bone grafting in complete cleft lip and palate cases following maxillofacial orthopedics. IV. A radiographic study of the incorporation of the bone grafts.
The development of bone grafts in complete alveolar clefts was studied with standard radiographic methods. The patients were divided into three groups: one unilateral group of 39 children operated on between 1960-1965 without preoperative orthopedics, another unilateral group of 46 children operated on between 1965-1972 after preoperative orthopedics ("T-traction") and one group of bilateral clefts with 19 children operated on 1960-1972 after premaxillary retropositioning pressure if necessary combined with outward rotation of the lateral segments. All children had bone grafts inserted with "a four-flap" technique. The results were compared with those operated on with early bone grafting by a different method. The results were similar with good healing and incorporation of the transplanted bone. The group bone grafted after preoperative "T-traction", which facilitates the surgical procedure, showed the highest alveolar bone level. The amount of bone seemed to increase with increasing age of the patient and migration of teeth into the grafted region.


A Retrospective Comparative Study of the Effect of Controlled-Release Dinoprostone Vaginal Delivery System (Propess®) and Mechanical Methods for Cervical Ripening in Nulliparous Women in Late-Term Pregnancy.
The effects of the controlled-release dinoprostone vaginal delivery system (Propess®) and mechanical methods for cervical ripening in nulliparous women in late-term pregnancy were compared retrospectively. This retrospective comparative study included 46 nulliparous pregnant women (24 in the Propess® group and 22 in the mechanical methods groups) with a low Bishop score (≤1) who needed labor induction at 41 weeks of gestation. The primary outcome was the success rate of cervical ripening (= Bishop score >6 or vaginal delivery) by the next day following the insertion of Propess® only or mechanical cervical dilation only. In the cases in which cervical ripening was unsuccessful, other methods were performed, and the success rate of cervical ripening the day after was compared as the secondary outcome. As the primary outcome, there was not a significant difference in the success rate of cervical ripening between the Propess® and mechanical methods groups (21 vs. 22%, p = 0.88). As for the secondary outcomes, there was not a significant difference in the total success rate of cervical ripening between the two groups (75 (5+13/24) vs. 73 (5+11/22)%, p = 0.86)). Of the unsuccessful cervical ripening cases as secondary outcomes, the Bishop score of all was ≤2 on the second day of hospitalization. The combined use of Propess® and mechanical methods was effective for cervical ripening in nulliparous women with a low Bishop score in late-term pregnancy, regardless of order.


Raman imaging with a fiber-coupled multichannel spectrograph.
Until now, spatially resolved Raman Spectroscopy has required to scan a sample under investigation in a time-consuming step-by-step procedure. Here, we present a technique that allows the capture of an entire Raman image with only one single exposure. The Raman scattering arising from the sample was collected with a fiber-coupled high-performance astronomy spectrograph. The probe head consisting of an array of 20 × 20 multimode fibers was linked to the camera port of a microscope. To demonstrate the high potential of this new concept, Raman images of reference samples were recorded. Entire chemical maps were received without the need for a scanning procedure.


Facile construction of lanthanide metallomacrocycles with the bridging imidazolate and triazolate ligands and their ring expansions.
Four novel tri- or tetranuclear organolanthanide metallomacrocycles [Cp2Ln(mu-Im)(THF)3 (Cp = C5H5, Ln = Yb (1), Er (2)], [Cp2Dy(mu-Im)]4(THF)]3 x 2THF (3), and [Cp'2Yb(mu-eta1:eta2-Tz)]4 x 2THF (Cp' = CH3C5H4) (4) have been synthesized through protolysis of Cp3Ln or Cp'3Yb with imidazole or triazole, indicating that both the bridge-ligand size and the lanthanide-ion radii can be applied in the modulation of the metallomacrocycles. Further investigations on the reactivity of complexes 1, 3, and 4 toward phenyl isocyanate reveal that PhNCO inserts readily into the simple bridge Ln-N bonds of 1 and 3 to yield the corresponding insertion products [Cp2Ln(mu-eta1:eta2-OC(Im)NPh)]3 (Ln = Yb (5), Dy (6)) but cannot insert into the Ln-N bond with a mu-eta1:eta2-bonding mode in 4. The novel bridge ligand [OC(Im)NPh] can expand the numbers of the ring members from 12 to 18 in 5 or 16 to 18 in 6. The number of metal atoms in the metallacycles with the ligand [OC(Im)NPh] is independent of the lanthanide-ion size; both trinuclear lanthanide macrocycles are observed in 5 and 6. All of these new complexes have been characterized by elemental analysis and spectroscopic properties, and their structures have also been determined through X-ray single-crystal diffraction analysis.


Two different Bacillus thuringiensis toxin genes confer resistance to beet armyworm (Spodoptera exigua Hübner) in transgenic Bt-shallots (Allium cepa L.).
Agrobacterium-mediated genetic transformation was applied to produce beet armyworm (Spodoptera exigua Hübner) resistant tropical shallots (Allium cepa L. group Aggregatum). A cry1Ca or a H04 hybrid gene from Bacillus thuringiensis, driven by the chrysanthemum ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit (Rubisco SSU) promoter, along with the hygromycin phosphotransferase gene (hpt) driven by the CaMV 35S promoter, was employed for genetic transformation. An average transformation frequency of 3.68% was obtained from two shallot cultivars, Tropix and Kuning. After transfer of the in vitro plants to the greenhouse 69% of the cry1Ca and 39% of the H04 transgenic shallots survived the first half year. After one year of cultivation in the greenhouse the remaining cry1Ca and H04 transgenic plants grew vigorously and had a normal bulb formation, although the cry1Ca transgenic plants (and controls) had darker green leaves compared to their H04 counterparts. Standard PCR, adaptor ligation PCR and Southern analyses confirmed the integration of T-DNA into the shallot genome. Northern blot and ELISA analyses revealed expression of the cry1Ca or H04 gene in the transgenic plants. The amount of Cry1Ca expressed in transgenic plants was higher than the expression levels of H04 (0.39 vs. 0.16% of the total soluble leaf proteins, respectively). There was a good correlation between protein expression and beet armyworm resistance. Cry1Ca or H04 gene expression of at least 0.22 or 0.08% of the total soluble protein in shallot leaves was sufficient to give a complete resistance against beet armyworm. This confirms earlier observations that the H04 toxin is more toxic to S. exigua than the Cry1Ca toxin. The results from this study suggest that the cry1Ca and H04 transgenic shallots developed could be used for introducing resistance to beet armyworm in (sub) tropical shallot.


Inhibitory effect of omega-3 fatty acids on alveolar bone resorption and osteoclast differentiation.
In this study, a Porphyromonas gingivalis (P.g.)-infected mouse periodontitis model was used to investigate the effect of omega-3 fatty acid intake on differentiation and maturation of cultured osteoclast. Four-week-old C57BL/6JJcl mice were divided into four groups according to the diets they were fed from the beginning of the experiment (i.e., food containing omega-3 or omega-6 fatty acids) and whether they were orally administered P.g. Thirty-three days after beginning the experiment, bone marrow cells were sampled from the femoral bone of mice from each group and differentiated into osteoclasts; the effects of the ingestion of different fatty acids were subsequently investigated. There was no statistical interaction between the different fatty acids and P.g. infection on the number of osteoclasts (P = 0.6). However, the fatty acid type affected the number of osteoclasts in mice (P = 0.0013), with the omega-3 groups demonstrating lower osteoclast numbers than the omega-6 groups. Furthermore, the addition of resolvin E1 (RvE1), which is an omega-3 fatty acid-derived lipid mediator, suppressed the differentiation of mouse cultured osteoclasts (P < 0.0001). Therefore, the ingestion of omega-3 fatty acids may suppress osteoclast differentiation while inhibiting bone resorption and tissue destruction due to periodontitis.


Photoluminescence properties of aeschynite-type LaNbTiO6:RE3+ (RE = Tb, Dy, Ho) down-converting phosphors.
In this study, a series of LaNbTiO6:RE(3+) (RE = Tb, Dy, Ho) down-converting phosphors were synthesized using a modified sol-gel combustion method, and their photoluminescence (PL) properties were investigated as a function of activator concentration and annealing temperature. The resultant particles were characterized using X-ray diffraction, transmission electron microscopy, scanning electron microscopy, UV/Vis diffuse reflectance spectroscopy and PL spectra. The highly crystalline LaNbTiO6:RE(3+) (RE = Tb, Dy, Ho) phosphors with an average size of 200-300 nm obtained at 1100°C have an orthorhombic aeschynite-type structure and exhibit the highest luminescent intensity in our study range. The emission spectra of LaNbTiO6:RE(3+) (RE = Tb, Dy, Ho) phosphors under excitations at UV/blue sources are mainly composed of characteristic peaks arising from the f-f transitions of RE(3+), including 489 nm ((5) D4 → (7) F6) and 545 nm ((5) D4 → (7) F5) for Tb(3+), 476 and 482 nm ((4) F9/2 → (6) H15/2) and 571 nm ((4) F9/2 → (6) H13/2) for Dy(3+), and 545 nm ((5) F4 + (5) S2 → (5) I8) for Ho(3+), respectively. The luminescent mechanisms were further investigated. It can be expected that these phosphors are of intense interest and potential importance for many optical applications.


Shannon entropy as an indicator of atomic avoided crossings in strong parallel magnetic and electric fields.
Avoided crossings are the most distinctive atomic spectroscopic features in the presence of magnetic and electric fields. We point out the role of Shannon's information entropy as an indicator or predictor of these phenomena by studying the dynamics of some excited states of hydrogen in the presence of parallel magnetic and electric fields. Moreover, in addition to the well-known energy level repulsion, it is found that Shannon's entropy manifests the informational exchange of the involved states as the magnetic field strength is varied across the narrow region where an avoided crossing occurs.


Scar sarcoidosis in childhood: case report and review of the literature.
Sarcoidosis is a rare disease among children, manifesting differently in children below and above 4-5 years of age. Although the exact incidence and prevalence of childhood sarcoidosis is not known, the cutaneous involvement is frequent in both children and adults. Infiltration of old cutaneous scars with sarcoid granuloma in the active phase of disease, known as scar sarcoidosis is one of the uncommon cutaneous manifestations of sarcoidosis. We report a case of scar sarcoidosis in an 11-year-old child along with a brief review of the literature.


Frequency of beryllium-specific, central memory CD4+ T cells in blood determines proliferative response.
Beryllium exposure can lead to the development of beryllium-specific CD4+ T cells and chronic beryllium disease (CBD), which is characterized by the presence of lung granulomas and a CD4+ T cell alveolitis. Studies have documented the presence of proliferating and cytokine-secreting CD4+ T cells in blood of CBD patients after beryllium stimulation. However, some patients were noted to have cytokine-secreting CD4 T cells in blood in the absence of beryllium-induced proliferation, and overall, the correlation between the 2 types of responses was poor. We hypothesized that the relative proportion of memory T cell subsets determined antigen-specific proliferation. In most CBD patients, the majority of beryllium-specific CD4+ T cells in blood expressed an effector memory T cell maturation phenotype. However, the ability of blood cells to proliferate in the presence of beryllium strongly correlated with the fraction expressing a central memory T cell phenotype. In addition, we found a direct correlation between the percentage of beryllium-specific CD4+ T(EM) cells in blood and T cell lymphocytosis in the lung. Together, these findings indicate that the functional capability of antigen-specific CD4+ T cells is determined by the relative proportion of memory T cell subsets, which may reflect internal organ involvement.


Graphene oxide as a nanocarrier for controlled release and targeted delivery of an anticancer active agent, chlorogenic acid.
We have synthesized graphene oxide using improved Hummer's method in order to explore the potential use of the resulting graphene oxide as a nanocarrier for an active anticancer agent, chlorogenic acid (CA). The synthesized graphene oxide and chlorogenic acid-graphene oxide nanocomposite (CAGO) were characterized using Fourier transform infrared (FTIR) spectroscopy, thermogravimetry and differential thermogravimetry analysis, Raman spectroscopy, powder X-ray diffraction (PXRD), UV-vis spectroscopy and high resolution transmission electron microscopy (HRTEM) techniques. The successful conjugation of chlorogenic acid onto graphene oxide through hydrogen bonding and π-π interaction was confirmed by Raman spectroscopy, FTIR analysis and X-ray diffraction patterns. The loading of CA in the nanohybrid was estimated to be around 13.1% by UV-vis spectroscopy. The release profiles showed favourable, sustained and pH-dependent release of CA from CAGO nanocomposite and conformed well to the pseudo-second order kinetic model. Furthermore, the designed anticancer nanohybrid was thermally more stable than its counterpart. The in vitro cytotoxicity results revealed insignificant toxicity effect towards normal cell line, with a viability of >80% even at higher concentration of 50μg/mL. Contrarily, CAGO nanocomposite revealed enhanced toxic effect towards evaluated cancer cell lines (HepG2 human liver hepatocellular carcinoma cell line, A549 human lung adenocarcinoma epithelial cell line, and HeLa human cervical cancer cell line) compared to its free form.


Nuclease activity and protein A release of Staphylococcus aureus clinical isolates determine the virulence in a murine model of acute lung infection.
Staphylococcus aureus is a common cause of hospital-acquired pneumonia associated with high mortality. Adequate clinical treatment is impeded by increasing occurrence of antibiotic resistances. Understanding the underlying mechanisms of its virulence during infections is a prerequisite to finding alternative treatments. Here, we demonstrated that an increased nuclease activity of a S. aureus isolate from a person with cystic fibrosis confers a growth advantage in a model of acute lung infection compared to the isogenic strain with low nuclease activity. Comparing these CF-isolates with a common MRSA-USA300 strain with similarly high nuclease activity but significantly elevated levels of Staphylococcal Protein A (SpA) revealed that infection with USA300 resulted in a significantly increased bacterial burden in a model of murine lung infection. Replenishment with the cell wall-bound SpA of S. aureus, which can also be secreted into the environment and binds to tumor necrosis factor receptor -1 (TNFR-1) to the CF-isolates abrogated these differences. In vitro experiments confirmed significant differences in spa-expression between USA300 compared to CF-isolates, thereby influencing TNFR-1 shedding, L-selectin shedding, and production of reactive oxygen species through activation of ADAM17.


Protecting and using patient information: the role of the Caldicott Guardian.
All patient information is confidential and must be protected and used appropriately by all members of the healthcare team. Caldicott Guardians have a strategic, advisory and facilitative role to ensure that the Caldicott Principles underpin the approach organizations develop to protect and use patient identifiable information. It is essential all staff and students receive appropriate training and are aware that the responsibility for protecting and using patient information lies with the organisation headed by the Chief Executive and with each individual.


A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?
Recently, we showed that homozygosity for the common 677(C-->T) mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, causing thermolability of the enzyme, is a risk factor for neural-tube defects (NTDs). We now report on another mutation in the same gene, the 1298(A-->C) mutation, which changes a glutamate into an alanine residue. This mutation destroys an MboII recognition site and has an allele frequency of .33. This 1298(A-->C) mutation results in decreased MTHFR activity (one-way analysis of variance [ANOVA] P < .0001), which is more pronounced in the homozygous than heterozygous state. Neither the homozygous nor the heterozygous state is associated with higher plasma homocysteine (Hcy) or a lower plasma folate concentration-phenomena that are evident with homozygosity for the 677(C-->T) mutation. However, there appears to be an interaction between these two common mutations. When compared with heterozygosity for either the 677(C-->T) or 1298(A-->C) mutations, the combined heterozygosity for the 1298(A-->C) and 677(C-->T) mutations was associated with reduced MTHFR specific activity (ANOVA P < .0001), higher Hcy, and decreased plasma folate levels (ANOVA P <.03). Thus, combined heterozygosity for both MTHFR mutations results in similar features as observed in homozygotes for the 677(C-->T) mutation. This combined heterozygosity was observed in 28% (n =86) of the NTD patients compared with 20% (n =403) among controls, resulting in an odds ratio of 2.04 (95% confidence interval: .9-4.7). These data suggest that the combined heterozygosity for the two MTHFR common mutations accounts for a proportion of folate-related NTDs, which is not explained by homozygosity for the 677(C-->T) mutation, and can be an additional genetic risk factor for NTDs.


Species composition and temporal distribution of mosquito populations in Ibadan, Southwestern Nigeria.
Nigeria has a high burden of vector borne diseases such as malaria and lymphatic filariasis (LF). This study aimed to determine the species composition of mosquitoes in Ibadan, Southwest Nigeria as well as determine their role in malaria and LF transmission. Adult mosquitoes were collected by Pyrethrum Spray Catch (PSC) and identified and graded according to their abdominal conditions. The mosquitoes were dissected to determine the parity status and to check for microfilariae of Wuchereria bancrofti. The presence of circumsporozoite protein of Plasmodium falciparum was examined using ELISA. A total of 1600 mosquitoes were collected of which 31 (1.9%) were Anopheles gambiae s.l. while 1756 (98%) were Culex sp. None of the mosquitoes examined was positive for Plasmodium falciparum and Wuchereria bancrofti. The lack of adequate sanitary conditions in the area could be responsible for the large number of mosquitoes collected. Health education could help in sensitizing the inhabitants.


The Sapienza University of Rome network of automated external defibrillators: a prototype webMap developed to speed access to community defibrillators and increase survival from out-of-hospital cardiac arrest.
In Italy, only around 10% of people who experience out-of-hospital cardiac arrest (OHCA) survive. A large portion of OHCA events in public settings are characterized by an initial shockable rhythm, which requires prompt defibrillation. We aimed to create a system to quickly locate nearby public access automated external defibrillators (AEDs) on the campus of Sapienza University of Rome, the largest public university in Europe. We developed the AED webMap through a 6-step process involving the: 1) collection of information and geographical coordinates for each AED from the university management system; 2) development of a new geolocation database; 3) integration of information contained in the new database with data provided by university departments; 4) geolocation of AEDs in the Google MyMaps environment; 5) graphic representation of all AEDs on digital map templates using specific symbols, with pop-ups containing additional information for each AED; and 6) publication of the webMap on the university website. The AED webMap was published on the university website (https://www.uniroma1.it/it/pagina/defibrillatori-sapienza-in-rete) and facilitates prompt identification of nearby AEDs by providing: 1) detailed AED geolocalization with interactive pop-up information for each AED, including whether the AED is located internally or externally; 2) the option to use different base maps (e.g., digital street map); 3) calculation and display of the route to reach the chosen AED; and 4) the possibility to migrate towards multiple platforms. The webMap can help bystanders quickly identify, locate, and reach nearby AEDs present on the campus of the largest public university in Europe, a measure that could help speed defibrillation and maximize the life-saving potential of AEDs in the event of OHCA.


Lateral critical Casimir force in two-dimensional inhomogeneous Ising strip. Exact results.
We consider two-dimensional Ising strip bounded by two planar, inhomogeneous walls. The inhomogeneity of each wall is modeled by a magnetic field acting on surface spins. It is equal to +h1 except for a group of N1 neighboring surface spins where it is equal to -h1. The inhomogeneities of the upper and lower wall are shifted with respect to each other by a lateral distance L. Using exact diagonalization of the transfer matrix, we study both the lateral and normal critical Casimir forces as well as magnetization profiles for different temperature regimes: below the wetting temperature, between the wetting and the critical temperature, and above the critical temperature. The lateral critical Casimir force acts in the direction opposite to the shift L, and the excess normal force is always attractive. Upon increasing the shift L we observe, depending on the temperature regime, three different scenarios of breaking of the capillary bridge of negative magnetization connecting the inhomogeneities of the walls across the strip. As long as there exists a capillary bridge in the system, the magnitude of the excess total critical Casimir force is almost constant, with its direction depending on L. By investigating the bridge morphologies we have found a relation between the point at which the bridge breaks and the inflection point of the force. We provide a simple argument that some of the properties reported here should also hold for different models of the strip with the same type of inhomogeneity.


A Plain Language Summary on the Effect of the Medication Vibegron on Blood Pressure and Heart Rate in People With Overactive Bladder.
This is a plain language summary of an article originally published in the journal Blood Pressure Monitoring. Vibegron is a medicine that was approved by the US Food and Drug Administration (also called FDA) in 2020 for treatment of overactive bladder, a condition that causes a frequent and urgent need to urinate. This study took place before the medicine was approved to look at whether vibegron affects blood pressure or heart rate. A total of 214 patients with overactive bladder took part in the study. 108 patients took vibegron for 28 days, and 106 took placebo for 28 days. A placebo is a pill with no medicine in it. Their blood pressure was measured on the first day and the last day. A meaningful increase in blood pressure is when a patient's average blood pressure measurements changed by 3.5 mmHg or more. Patients with overactive bladder who took a 75 mg dose of vibegron once daily had no meaningful increase in blood pressure or heart rate. This included people who were already taking medication for their high blood pressure. This study suggests that patients can use vibegron without concern that it may meaningfully raise blood pressure or heart rate.


Identification and analysis of the promoter region of the human methionine sulphoxide reductase A gene.
MsrA (methionine sulphoxide reductase A) is an antioxidant repair enzyme that reduces oxidized methionine to methionine. Moreover, the oxidation of methionine residues in proteins is considered to be an important consequence of oxidative damage to cells. To understand mechanisms of human msrA gene expression and regulation, we cloned and characterized the 5' promoter region of the human msrA gene. Using 5'-RACE (rapid amplification of cDNA ends) analysis of purified mRNA from human cells, we located the transcription initiation site 59 nt upstream of the reference MsrA mRNA sequence, GenBank accession number BC 054033. The 1.3 kb of sequence located upstream of the first exon of msrA gene was placed upstream of the luciferase reporter gene in a pGL3-Basic vector and transfected into different cell lines. Sequentially smaller fragments of the msrA promoter region were generated by PCR, and expression levels were monitored from these constructs within HEK-293 and MCF7 human cell lines. Analysis of deletion constructs revealed differences in promoter activity in these cell lines. In HEK-293 cells, the promoter activity was constant from the minimal promoter region to the longest fragment obtained. On the other hand, in MCF7 cells we detected a down-regulation in the longest fragment. Mutation of a putative negative regulatory region that is located between -209 and -212 bp (the CCAA box) restored promoter activity in MCF7 cells. The location of the msrA promoter will facilitate analysis of the transcriptional regulation of this gene in a variety of pathological contexts.


A Boosted Multi-Task Model for Pedestrian Detection With Occlusion Handling.
Pedestrian detection is a challenging problem in computer vision, and has achieved impressive progress in recent years. However, the current state-of-the-art methods suffer from significant performance decline with increasing occlusion level of pedestrians. A common approach for occlusion handling is to train a set of occlusion-specific detectors and merge their results directly, but these detectors are trained independently and the relationship among them is ignored. In this paper, we consider pedestrian detection in different occlusion levels as different but related problems, and propose a boosted multi-task model to jointly consider their relatedness and differences. The proposed model adopts multi-task learning algorithm to map pedestrians in different occlusion levels to a common space, where all models corresponding to different occlusion levels are constrained to share a common set of features, and a boosted detector is then constructed to distinguish pedestrians from background. The proposed approach is evaluated on three challenging pedestrian detection data sets, including Caltech, TUD-Brussels, and INRIA, and achieves superior performances against state of the art in the literature on different occlusion-specific test sets.


Surgery for external auditory canal exostoses: a report of 182 operations.
The pre-operative findings and operative outcome were evaluated from patient records in 136 patients (182 ears) who had surgery for external auditory canal (EAC) exostoses. Furthermore, 114 patients (84%) replied to a questionnaire inquiring about the symptoms and the operation's impact on their quality of life. The main symptoms prior to the surgery were recurrent external otitis, hearing loss and wax retention. Interestingly, 23 patients (21%) were operated without any symptoms. After the operation, 75 patients (66%) had relief of their symptoms. In 33 patients (29%) the symptoms remained the same, and in 5 patients (4%) they became worse. The quality of life improved in 77 patients (68%); 19 patients (14%) had a complication due to the surgery, and 8 patients (6%) needed a re-operation. The surgery for EAC exostoses should be reserved only for symptomatic cases and only for experienced specialists in order to minimize complications and unnecessary operations.


Homozygosity for the V37I GJB2 mutation in fifteen probands with mild to moderate sensorineural hearing impairment: further confirmation of pathogenicity and haplotype analysis in Asian populations.
Hearing impairment affects 1 in 650 newborns, making it the most common congenital sensory impairment. Autosomal recessive nonsyndromic sensorineural hearing impairment (ARNSHI) comprises 80% of familial hearing impairment cases. Mutations in GJB2 account for a significant number of ARNSHI (and up to 50% of documented recessive (e.g., more than 1 affected sibling) hearing impairment in some populations). Mutations in the GJB2 gene are amongst the most common causes of hearing impairment in populations of various ethnic backgrounds. Two mutations of this gene, 35delG and 167delT, account for the majority of reported mutations in Caucasian populations, especially those of Mediterranean and Ashkenazi Jewish background. The 235delC mutation is most prevalent in East Asian populations. Some mutations are of less well-characterized significance. The V37I missense mutation, common in Asian populations, was initially described as a polymorphism and later as a potentially pathogenic mutation. We report here on 15 unrelated individuals with ARNSHI and homozygosity for the V37I GJB2 missense mutation. Nine individuals are of Chinese ancestry, two are of unspecified Asian descent, one is of Japanese descent, one individual is of Vietnamese ancestry, one of Philippine background and one of Italian and Cuban/Caucasian background. Homozygosity for the V37I GJB2 mutation may be a more common pathogenic missense mutation in Asian populations, resulting in mild to moderate sensorineural hearing impairment. We report a presumed haplotype block specific to East Asian individuals with the V37I mutation encompassing the GJB2 gene that may account for the high prevalence in East Asian populations.


Intelligent Construction Technology Adoption Driving Strategy in China: A Tripartite Evolutionary Game Analysis.
The adoption of intelligent construction technology (ICT) is regarded as one of the important strategies for the transformation and upgrading of the Chinese construction industry and the achievement of high-quality development. In the ICT adoption process, the government is the driving subject, the owner is an important subject, and ICT is applied in practice by the general contractor. This study first analyses the evolutionary process and the impact of participants' strategy choices on the system equilibrium by establishing a tripartite evolutionary game framework which includes the government, the owner, and the general contractor as the main stakeholders; then tests the feasibility and rationality of the model by analysing the ESS corresponding to the three phases of ICT adoption. The results show that the conditions for each ESS to be established mainly depend on the relationship between the costs and benefits of each stakeholder, and that owners are more sensitive to government subsidies and penalties than general contractors, so the government should establish a dynamic reward and punishment mechanism based on the results of the model. High adoption costs are a key barrier to ICT adoption for both owners and general contractors. This paper provides a new framework for research related to ICT adoption and a reference for the strategic adjustment of stakeholders in ICT adoption.


Role of lactoferrin and its receptors on biliary epithelium.
Human lactoferrin is an iron-binding glycoprotein present at high concentrations in breast milk and colostrum. It is produced by many exocrine glands and widely distributed in a variety of body fluids. This protein has antimicrobial, immunomodulatory, antioxidant, and anticancer properties. Two important hLf receptors have been identified: LDL receptor related protein (LRP1), a low specificity receptor, and intelectin-1 (ITLN1), a high specificity receptor. No data are present on the role of hLf on the biliary epithelium. Our aims have been to evaluate the expression of Lf and its receptors in human and murine cholangiocytes and its effect on proliferation. Immunohistochemistry and immunofluorescence (IF) were conducted on human healthy and primary biliary cholangitis (PBC) liver samples as well as on liver samples obtained from normal and bile duct ligated (BDL) mice to evaluate the expression of Lf, LRP1 and ITLN1. Cell proliferation in vitro studies were performed on human cholangiocyte cell lines via 3-(4,5-dimetiltiazol-2-il)-2,5-diphenyltetrazolium assay as well as IF to evaluate proliferating cell nuclear antigen (PCNA) expression. Our results show that mouse and human cholangiocytes express Lf, LRP1 and ITLN1, at higher extent in cholangiocytes from BDL and PBC samples. Furthermore, the in vitro addition of bovine Lf (bLf) has a proliferative effect on human cholangiocyte cell line. The results support a proliferative role of hLf on the biliary epithelium; this pro-proliferative effect of hLf and bLf on cholangiocytes could be particularly relevant in human cholangiopathies such as PBC, characterized by cholangiocyte death and ductopenia.


[Bioavailability of 17 beta-estradiol after transdermal administration--dependence on the patch system].
The objective of this study was to compare the pharmacokinetics of serum estradiol concentrations after application of two different transdermal estradiol delivery systems. Ten postmenopausal women (E2 < or = 30 pg/ml; follicle-stimulating hormone > or = 30 mIE/ml) were prospectively randomized to a crossover treatment protocol separated by a 7-day wash out period. The absorption of estradiol was measured after application of a patch either containing 4.0 mg of E2 in a reservoir system or 1.8 mg of E2 in a specially designed matrix system. Although the increase of serum estradiol concentrations after application of the patches with the matrix system was slightly delayed, mean E2 levels over the whole observation period of 80 hours were significantly higher than those achieved with the reservoir system (difference of mean values: 5.1 pg/ml; p < 0.05). This observation was most striking at the end of the observation period and after removal of the patches. Yet, fluctuations of hormone concentrations were greater with the matrix system patches, and the areas under the E2 concentration-time curves were slightly but not significantly increased as compared to these of the patches with the reservoir system (3211 +/- 584 vs. 2556 +/- 249 pg/ml x h). In conclusion, both transdermal estradiol delivery systems are well suited for postmenopausal hormone substitution providing stable serum estradiol concentrations at about 50 pg/ml, with the matrix system possibly increasing the life span of the patch and thus the recommended application period.


Reversing glomerular hypertension stabilizes established glomerular injury in renal ablation.
Male Munich-Wistar rats were studied 18 weeks after 1 2/3 nephrectomy. One group received no therapy. A second group received the angiotensin converting enzyme (ACE) inhibitor enalapril, starting 1 week after ablation. Two additional groups received no therapy during the first 8 weeks, and then received ACE inhibitor or a low (12%) protein diet. Early ACE inhibitor therapy resulted in control of systemic and glomerular hypertension (HTN), and a striking limitation of proteinuria and glomerular sclerosis. During the first 8 weeks untreated rats developed severe systemic HTN and increasing proteinuria. After 8 weeks proteinuria increased further in untreated rats, and widespread sclerosis resulted. Late ACE inhibition reversed systemic HTN. Both late ACE inhibition and late protein restriction reversed glomerular HTN and prevented further increases in proteinuria and sclerosis. Thus, control of glomerular HTN can stabilize renal injury even when therapy is delayed until hypertension and glomerular injury are established.


Pathogenicity of anaerobic gram-negative rods: possible mechanisms.
The literature dealing with the pathogenicity of anaerobic gram-negative rods in humans is reviewed. Knowledge concerning definite pathogenic mechanisms is, at best, cursory. There is evidence that encapsulation plays a role in the pathogenicity of Bacteroides fragilis and some of the black-pigmented Bacteroides. A range of enzymes, among them collagenase and IgA protease, are produced by several Bacteroides species. Supernatants of Fusobacterium necrophorum cultures may be leukotoxic. Synergism between anaerobic gram-negative rods and other bacterial species has been demonstrated in experimental animals.


Effect of a monoclonal antibody to VLA-4 on lymphocyte adherence to microvascular and aortic endothelial cells.
Lymphocyte migration out of the blood to inflammatory sites is preceded by the adherence of lymphocytes to the vascular endothelium. This lymphocyte binding is enhanced by cytokine activation of the endothelial cells (EC). Small peritoneal exudate lymphocytes (sPEL) migrate preferentially into cutaneous inflammation and to skin injected with INF gamma, TNF alpha or LPS. These cells adhere also to rat microvascular EC and this adherence correlates well with migratory properties of sPEL. Lymphocyte EC adhesion is in part mediated by the VLA-4 molecule on the lymphocytes. Since differences between microvascular and large vessel EC have been described, we investigated whether sPEL adherence to both types of EC is governed by similar molecular mechanisms. Lymphocyte adhesion was low to unstimulated microvascular EC and augmented by pretreatment of EC with INF gamma, TNF alpha and LPS. In contrast, lymphocyte adhesion to unstimulated large vessel (aortic) EC was higher than to microvascular EC and could not be increased by cytokine or LPS treatment. Anti VLA-4 mAb inhibited the enhanced cytokine stimulated adhesion to microvascular EC without affecting adhesion of sPEL to unstimulated EC. Anti VLA-4 mAb inhibited the high spontaneous adhesion to aortic EC, suggesting that with both EC, adhesion is in part VLA-4 dependent.


Development of standards for orthopaedic implants.
This article reviews the need for standards for orthopaedic implants and illustrates the differences in approach of the European Standard Organization compared to National and International Standards. The areas where new work is being undertaken are outlined.


Why are essential genes essential? - The essentiality of Saccharomyces genes.
Essential genes are defined as required for the survival of an organism or a cell. They are of particular interests, not only for their essential biological functions, but also in practical applications, such as identifying effective drug targets to pathogenic bacteria and fungi. The budding yeast Saccharomyces cerevisiae has approximately 6,000 open reading frames, 15 to 20% of which are deemed as essential. Some of the essential genes, however, appear to perform non-essential functions, such as aging and cell death, while many of the non-essential genes play critical roles in cell survival. In this paper, we reviewed and analyzed the levels of essentiality of the Saccharomyces cerevisiae genes and have grouped the genes into four categories: (1) Conditional essential: essential only under certain circumstances or growth conditions; (2) Essential: required for survival under optimal growth conditions; (3) Redundant essential: synthetic lethal due to redundant pathways or gene duplication; and (4) Absolute essential: the minimal genes required for maintaining a cellular life under a stress-free environment. The essential and non-essential functions of the essential genes were further analyzed.


High-sensitivity cardiac troponin T and the risk of incident atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) study.
Structural changes in the heart are known risk factors for atrial fibrillation (AF). An association between high-sensitivity cardiac troponin T (hs-cTnT), a marker of myocardial cell damage measured with a high-sensitivity assay, and the risk of AF could have implications for AF risk stratification. To estimate the association between hs-cTnT and the risk of incident AF in the ARIC study, a prospective cohort of middle-aged adults from 4 US communities. Study included 10,584 participants (mean age 62.7 years) free of AF in 1996 to 1998 and followed through 2008. Atrial fibrillation was defined using International Classification of Diseases codes from hospitalizations and death certificates. Participants with undetectable hs-cTnT levels (58%) were assigned the lower limit of measurement (5 ng/L). Net reclassification improvement was used to examine the discriminative ability of hs-cTnT for 10-year AF risk prediction (categories: <5%, 5%-15%, and >15%). A total of 920 incident AF cases were observed for 109,227 person-years. After adjustment, a 1-SD difference in ln(hs-cTnT) was associated with a hazard ratio of 1.16 (95% CI 1.10-1.23). Compared with those with undetectable levels, participants with hs-cTnT ≥14 ng/L had a hazard ratio of 1.78 (95% CI 1.43-2.24). Addition of hs-cTnT to known AF predictors did not increase the c statistic appreciably (0.756 vs 0.758) or improve risk stratification (net reclassification improvement 0.4%, 95% CI -1.4% to 2.3%). High-sensitivity cTnT level is associated with an increased incidence rate of AF but did not improve risk stratification.


Clinical and microbiologic characteristics of pleuro-pulmonary infection due to Streptococcus intermedius.
The clinical and microbiological characteristics of pleuro-pulmonary infection (PPI) caused by Streptococcus intermedius is described, including 6 cases in the literature and 9 cases handled at the present centre. Out of the 15 patients, 12 were male; mean age at diagnosis was 62.06 ± 15 years. Twelve had risk factors for S. intermedius infection such as alcoholism in 5 (35.7%) patients, periodontal disease in 3 (24.6%) cases, chronic obstructive pulmonary disease in 3 (24.6%), and diabetes mellitus in 2 (14.2%). Cough was present in 12 (80%) patients and chest pain and dyspnea in 9 (60%). The mean diagnosis interval was 34 days. The diagnosis was obtained from pleural fluid aspirate in 13 (86.6%) cases and from biopsy/tissue samples in 2. The most frequently antimicrobials used for treatment were ceftriaxone + levofloxacin. Ten patients cured with a combination of medical and surgical treatment and 2 patients died as a consequence of infection. The incidence of PPI caused by S. intermedius is increasing in our health area; drainage along with antibiotic therapy is recommended for treatment.


Biocompatible Semi-Interpenetrating Materials Based on Poly(3-hydroxyalkanoate)s and Poly(ethyleneglycol) Diacrylate.
Biocompatible gels based on poly(3-hydroxyalkanoate)s (PHAs) were developed by radical polymerization in the presence of poly(ethylene glycol) diacrylate (PEGDA). In order to elaborate cross-linked networks based on PEGDA and PHAs, several PHAs were tested; saturated PHAs, such as poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) or poly(3-hydroxyoctanoate) (PHO), and an unsaturated PHA, poly(3-hydroxyoctanoate-co-3-hydroxyundecenoate) PHOU. The PHAxPEGDA1-x networks obtained in this work were studied by FTIR, Raman spectroscopy, DSC, TGA and NMR. The microscopic structure varied according to the mass proportions between the two polymers. Time Domain 1H DQ NMR measurements demonstrated that in the case of the unsaturated PHA, it was chemically crosslinked with PEGDA, due to the presence of double bonds in the lateral groups. The organogels were able to swell in organic solvents, such as THF, up to 2000% and in water up to 86%. It was observed by rheological analysis that the stiffness of the networks was dependent on the content of PHA and on the degree of cross-linking. The biocompatible characters of PHOU and PEGDA were not affected by the formation of the networks and these networks had the advantage of being non-cytotoxic to immortalized C2C12 myoblast cells.


Acute and long-term effects of saxagliptin on a set of cardiovascular targets measured at fasting and post-prandially in obese patients with impaired glucose tolerance: A placebo-controlled study.
Studies of dipeptidyl peptidase inhibitors (DPP4is) report heterogeneous effects on cardiovascular targets in type 2 diabetes. This study aimed to investigate, in patients with impaired glucose tolerance (IGT), whether saxagliptin, a DPP4i, had beneficial cardiovascular effects at fasting and during the post-prandial state. In this randomized, placebo-controlled, double-blind, single-center pilot exploratory study, we included obese individuals with IGT. Twenty-four individuals (BMI 36.8 ± 4.8 kg/m2) were randomized to receive for 12 weeks either saxagliptin 5 mg a day or placebo. They were explored before and after a standardized breakfast for biological markers; microcirculatory blood flow at baseline and after transcutaneous administration of acetylcholine (Periflux System 5000® PERIMED); post-occlusive digital reactive hyperhemia (Endopat2000®); pulse wave velocity, augmentation index, central pulse pressure and subendocardial viability ratio (Sphygmocor®); cardiac hemodynamic parameters and cardiovascular autonomic nervous system activity (Task force monitor®). The results of all the investigations were similar after breakfast in the two groups at Visit 1 (acute post-prandial effects, after the first tablet) and Visit 2 (long-term post-prandial effects), and at fasting at Visit 1 and 2 (long-term effects, after 12 weeks of treatment). Only at Visit 2 the decrease in cardiac vagal activity occurring after breakfast was more sustained in the saxagliptin group than in the placebo group (interaction between treatment and time effect: p = 0.016). In obese patients with IGT, the effects of saxagliptin on the large set of cardiovascular parameters measured are neutral, except for a more marked post-prandial depression of vagal activity. NCT01521312.


Neonatal transient pseudohypoparathyroidism: could it be included among inactivating parathyroid hormone (PTH)/PTH-related protein signalling disorders?
We report a case of transient pseudohypoparathyroidism in a full-term newborn that presented at 20 hours of life with hypocalcemic seizures, hyperphosphatemia and raised parathormone levels. The diagnosis of pseudohypoparathyroidism was made according to biochemical investigations. The infant was treated with calcium supplementation and vitamin D analog therapy, and he remained stable and symptom-free with normal serum biochemistries during follow-up. We suggest that transient pseudohypoparathyroidism of the newborn (ntPHP) might be included among inactivating parathyroid hormone (PTH)/PTH-related protein signaling disorders as defined by the classification schema recently proposed by the European Pseudohypoparathyroidism Network. To the best of our knowledge, this is the first report in which the new classification has been applied to a case of ntPHP.


Silver triangular nanoplates as an high efficiently FRET donor-acceptor of upconversion nanoparticles for ultrasensitive "Turn on-off" protamine and trypsin sensor.
Silver triangular nanoplates (STNPs) as a high efficient fluorescence quenching reagent of upconversion nanoparticles (UCNPs) was used to constract a novel label-free fluorescence nanosensor for ultrasensitive detection of protamine and trypsin based on fluorescence resonance energy transfer (FRET) between STNPs and UCNPs. In this assay, the negatively charged STNPs can bind with positively charged UCNPs through electrostatic interaction, and then quenched the fluorescence of UCNPs. When protamine was added to the mixture of UCNPs-STNPs, the STNPs interacted with protamine and then detached from the surface of UCNPs and aggregated, which result in the recovery of the fluorescence of UCNPs. Trypsin could catalyze the hydrolysis of protamine and effectively quench the fluorescence recovered by protamine. By measuring the changes of the fluorescence of UCNPs, the concentrations of protamine and trypsin were determined. Under the optimized conditions, the linear response range was obtained from 10 to 500ng/mL, 5-80ng/mL and with the low detection limit of 3.1ng/mL and 1.8ng/mL for protamine and trypsin, respectively. Meanwhile, the nanosensor shows good selectivity, sensitivity and can be successfully applied to detection of protamine and trypsin in serum samples.


Transuranic Hybrid Materials: Crystallographic and Computational Metrics of Supramolecular Assembly.
Assembly of a family of 12 supramolecular compounds containing [AnO2Cl4]2- (An = U, Np, Pu), via hydrogen and halogen bonds donated by substituted 4-X-pyridinium cations (X = H, Cl, Br, I), is reported. These materials were prepared from a room-temperature synthesis wherein crystallization of unhydrolyzed and valence-pure [An(VI)O2Cl4]2- (An = U, Np, Pu) tectons is the norm. We present a hierarchy of assembly criteria based on crystallographic observations and subsequently quantify the strengths of the non-covalent interactions using Kohn-Sham density functional calculations. We provide, for the first time, a detailed description of the electrostatic potentials of the actinyl tetrahalide dianions and reconcile crystallographically observed structural motifs and non-covalent interaction acceptor-donor pairings. Our findings indicate that the average electrostatic potential across the halogen ligands (the acceptors) changes by only ∼2 kJ mol-1 across the AnO22+ series, indicating that the magnitude of the potential is independent of the metal center. The role of the cation is therefore critical in directing structural motifs and dictating the resulting hydrogen and halogen bond strengths, the former being stronger due to the positive charge centralized on the pyridyl nitrogen, N-H+. Subsequent analyses using the quantum theory of atoms in molecules and natural bond orbital approaches support this conclusion and highlight the structure-directing role of the cations. Whereas one can infer that Columbic attraction is the driver for assembly, the contribution of the non-covalent interaction is to direct the molecular-level arrangement (or disposition) of the tectons.


Old wine into new wineskins? "Legacy data" in research on Roman Period East Germanic iron smelting.
This paper discusses the use of "legacy data" in research on Roman Period iron smelting in the territory of the Przeworsk Culture in Magna Germania. The dataset includes results of 240 analyses of smelting slag and iron ores chemistry. A majority of these analyses were conducted in the 1950s-1980s. The quality of these data is far below present-day standards. Only major elements were reported, analytical methods were often not specified (although optical emission spectroscopy and wet chemical analyses can be assumed in such cases) and information on detection limits, precision and accuracy of the results is missing. In spite of this, a Principal Component Analysis-Agglomerative Hierarchical Clustering treatment successfully isolated observations from the three main iron smelting regions of the Przeworsk Culture (the Holy Cross Mountains, Masovia and Silesia). These results to a degree confirm a theory proposed in the 1960s by J. Piaskowski, according to whom it was possible to distinguish iron produced in the Holy Cross Mountains from the iron produced elsewhere in the territory of what is now Poland on the basis of metal characteristics. These findings will pave the way to the ongoing research project on the Przeworsk Culture metallurgy. It is also argued that, apart from a search for new methods in iron provenance studies, more attention should be paid to results of earlier analyses and to a compilation of legacy databases. The other result is an open and flexible Agglomerative Hierarchical Clustering R code to examine discrimination between production areas and to propose artefact provenance patterns in a convenient interactive way using the R development environment.


Comparison of Current Staging Systems for Sinonasal Inverted Papilloma.
A staging system is essential for determining the optimal surgical approach and predicting postoperative outcomes for inverted papilloma (IP). Although staging systems based on the extent to which the location is occupied by an IP have been widely used, an origin site-based classification of IP using unsupervised machine learning algorithms has recently been reported. To determine the most appropriate of five staging systems for sinonasal IP by comparing recurrence rates for each stage according to each of those systems. Eighty-seven patients with sinonasal IP were enrolled in the study. Their tumors were retrospectively categorized according to the Krouse, Oikawa, Cannady, and Han staging systems, which are based on the extent of IP, and the Meng system, which is based on the site of origin. The rates of recurrence for each stage of the five systems were compared. Seven of the 87 patients (8.0%) had recurrences during an average 45.5 months (12-138 months) of follow-up. There were significant differences in disease-free survival between the stages specified by Han and Meng (p = 0.027 and p < 0.001, respectively), but not between the stages specified by Krouse, Oikawa, and Cannady (p = 0.236, 0.062, and 0.130, respectively). Cox proportional hazard models revealed that Meng system (adjusted hazard ratio [aHR] 4.32, 95% confidence interval [CI] 1.10-17.04) and presence of dysplasia (aHR 7.42, 95% CI 1.15-47.85) were significantly associated with recurrence. The staging systems proposed by Han and Meng were found to be accurate in terms of tumor recurrence. We recommend use of the Han staging system before surgery and the Meng system after intraoperative identification of the origin of the tumor.


Assistive stabilization based on the neurodevelopmental treatment approach for dental care in individuals with cerebral palsy.
To study the effects of positioning individuals with cerebral palsy (CP) on a dental chair according to the neurodevelopmental treatment (NDT) approach, to establish the best position to perform dental care in the safest and most efficient manner in such individuals. A group of 158 noninstitutionalized patients (78 males and 80 females) with CP (mean age 10.5 [SD +/- 4.6]) were enrolled in the study. The behavior management techniques used were tell-show-do, voice control, assistive stabilization, oral premedication, a combination of techniques, and general anesthesia. The tell-show-do and voice control techniques were effective for only 36 (22.8%) of the patients who were collaborators: 3 presenting spastic diplegic, 23 presenting spastic hemiplegic, 4 presenting spastic double hemiplegic, and 6 presenting ataxic CP. The totality of patients with spastic quadriplegic CP, dystonic CP with athetosis, and mixed CP required all the combined forms of assistive stabilization and postural maintenance. The majority of the individuals with spastic diplegic CP required head and upper member stabilization and a mouth prop. Among the dental care treatments performed, preventive care (dental prophylaxis, sealants, and fluoride application) was performed on 78 (50.0%) patients, restorative dentistry on 40 (25.6%), and oral surgery on 38 (24.4%). Present data suggest that the use of assistive stabilization was effective and permitted the dental care of individuals with CP at the outpatient clinic level, while reducing the number of patients referred for general anesthesia and ensuring better quality of life for this patient population regarding oral health.


LitCog Caregiver Cohort: a prospective, observational cohort study investigating US caregivers' health literacy, self-care skills and cognitive function.
Many older adults receive assistance in managing chronic conditions. Yet complicating the utility of caregiver support is whether caregivers have sufficient skills to aid in a patient's self-care. Health literacy and cognition are important determinants of older adults' health outcomes, but few studies have examined caregiver health literacy, cognition and self-care skills and their relations to patient outcomes. We will expand an ongoing cognitive ageing cohort study (LitCog) to enroll a parallel caregiver cohort. Caregivers are eligible if they are (1) ≥18 years of age, (2) provided care for ≥6 months and (3) assisted with at least one activity of daily living, instrumental activity of daily living or health management task. Caregivers will complete interviews at time points corresponding with the LitCog participant interviews. Caregivers will complete assessments of health literacy, self-care skills, cognitive function, caregiver healthcare task difficulty, caregiver burden, caregiver self-efficacy, activation, technology use, busyness and routine and relationship quality. Caregivers will self-report the nature and intensity of care provided, and their own health status. Associations between caregiver presence and caregiver capacity with patient outcomes will be examined in a series of regression models, and mediating and moderating factors will be tested. The Institutional Review Board at Northwestern University has approved the study protocol (STU00026255). Results will be published in peer-reviewed journals and summaries will be provided to the funders of the study as well as patients and caregivers.


Flavonoids Distinctly Stabilize Lymph Endothelial- or Blood Endothelial Disintegration Induced by Colon Cancer Spheroids SW620.
The health effects of plant phenolics in vegetables and other food and the increasing evidence of the preventive potential of flavonoids in "Western Diseases" such as cancer, neurodegenerative diseases and others, have gained enormous interest. This prompted us to investigate the effects of 20 different flavonoids of the groups of flavones, flavonols and flavanones in 3D in vitro systems to determine their ability to inhibit the formation of circular chemorepellent induced defects (CCIDs) in monolayers of lymph- or blood-endothelial cells (LECs, BECs; respectively) by 12(S)-HETE, which is secreted by SW620 colon cancer spheroids. Several compounds reduced the spheroid-induced defects of the endothelial barriers. In the SW620/LEC model, apigenin and luteolin were most active and acacetin, nepetin, wogonin, pinocembrin, chrysin and hispidulin showed weak effects. In the SW620/BEC model acacetin, apigenin, luteolin, wogonin, hispidulin and chrysin exhibited weak activity.


Detection of COVID-19 using deep learning on x-ray lung images.
COVID-19 is a widespread deadly virus that directly affects the human lungs. The spread of COVID-19 did not stop at humans but also reached animals, so it was necessary to limit it is spread and diagnose cases quickly by applying a quarantine to the infected people. Recently x-ray lung images are used to determine the infection and from here the idea of this research came to use deep learning techniques to analyze x-ray lung images publicly available on Kaggle to possibly detect COVID-19 infection. In this article, we have proposed a method to possibly detect the COVID-19 by analyzing the X-ray images and applying a number of deep learning pre-trained models such as InceptionV3, DenseNet121, ResNet50, and VGG16, and the results are compared to determine the best performance model and accuracy with the least loss for our dataset. Our evaluation results showed that the best performing model for our dataset is ResNet50 with accuracies of 99.99%, 99.50%, and 99.44% for training, validation, and testing respectively followed by DenseNet121, InceptionV3, and finally VGG16.


A rabbit model of Lyme neuroborreliosis: characterization by PCR, serology, and sequencing of the OspA gene from the brain.
To test whether rabbits can serve as a model for Lyme neuroborreliosis (LNB), we injected New Zealand white rabbits with Borrelia burgdorferi. We obtained samples of blood and CSF for culture, polymerase chain reaction/hybridization (PCR/H), serology, and Western blot. We then sacrificed the rabbits 2 to 3 months after infection and removed organs for culture and PCR/H analysis. The rabbits developed an antibody response, characterized by ELISA and Western blot analysis, consistent with a systemic infection. PCR/H and blood cultures were negative, but PCR/H analysis of CSF in one rabbit was positive. Positive PCR/H analysis of organs from the rabbits was consistent with widespread dissemination of the organism. The most consistently infected organ was the CNS. To determine whether antigenic variation occurred at the genetic level, we compared the sequences of the OspA gene of both the infecting strain and the brain PCR product. The differences between the two were minimal, indicating that variation in the OspA gene did not occur during in vivo infection in the rabbit. Thus, rabbits, after intradermal inoculation with B burgdorferi, develop a chronic systemic infection in which the CNS is a consistent target. These data indicate that rabbits may be an excellent model of LNB.


A diversity-oriented strategy for the construction of tetrasubstituted pyrroles via coupled domino processes.
A new microwave-assisted rearrangement of 1,3-oxazolidines scaffolds is the basis for a new, metal-free, direct, and modular construction of tetrasubstituted pyrroles from terminal-conjugated alkynes, aldehydes, and primary amines. This new reaction manifold entails two linked domino processes in a one-pot manner with both atom- and bond-efficiency and under very simple and environment-friendly experimental conditions.


Comparison between concurrent and sequential chemoradiation for non-small cell lung cancer in vitro.
Current practice guidelines recommend the combination of chemotherapy and thoracic radiation for locally advanced non-small cell lung cancer (NSCLC). Previous meta-analyses have shown that concurrent chemoradiation (CCRT) may be superior to sequential chemoradiation (SCRT). However, few previous in vitro studies have analyzed these two treatment schedules. In the current study, four lung cancer cell lines harboring wild-type epidermal growth factor receptor, comprising two squamous and two non-squamous cell lines, were used. The IC10 concentrations of three platinum-based regimens were combined with radiation treatment. Cells were irradiated at 0, 2, 4, 6 and 8 Gy using a 137Cs irradiator concurrently or sequentially. Surviving fractions (SFs) were plotted as a function of the radiation dose. In A549 cells, only the docetaxel (Doc) and carboplatin (Carbo) combination showed a significant radiosensitizing effect with CCRT treatment. For the other three cell lines, no difference was identified in the SFs between CCRT and SCRT. An in vitro method of comparing CCRT with SCRT was established using lung cancer cell lines. Overall, no significant difference was detected in the radiosensitizing effect of the two treatment schedules, with the exception of the A549 cell lines treated with Doc/Carbo.


Psychological toxicity in classical hematology.
Although considered "benign," mild blood count abnormalities, genetic factors imparting inconsequential thrombotic risk, and low-risk premalignant blood disorders can have significant psychological and financial impact on our patients. Several studies have demonstrated that patients with noncancerous conditions have increased levels of anxiety with distress similar to those with malignancy. Additionally, referral to a classical hematologist can be a daunting process for many patients due to uncertainties surrounding the reason for referral or misconstrued beliefs in a cancer diagnosis ascribed to the pairing of oncology and hematology in medical practice. If not properly triaged, incidental laboratory abnormalities can trigger extensive and costly evaluation. These challenges are compounded by a lack of consensus guidance and generalizability of modern reference ranges that do not adequately account for common influencing factors. Although often benign, incidental hematologic findings can lead to emotional suffering and careful consideration of the potential psychological and financial duress imparted to an individual must be considered. In this article, we will review the current literature describing the psychological effect of some commonly known hematologic conditions, identify benign causes for variations in hematologic laboratory values, and provide recommendations to reduce psychological toxicity as it pertains to hematologic testing.


The Mediating Role of Precepts and Meditation on Attachment and Depressive Symptoms in Adolescents.
Research shows that Buddhist precept adherence (i.e., abstaining from killing, stealing, sexual misconduct, lying, and intoxicant use) and meditation practice influence mental health outcomes. This study investigated how Buddhist precept adherence and meditation practice influenced the relationship between insecure attachment and depressive symptoms among Thai adolescents. A total of 453 Thai boarding-school students from 10th-12th grade were recruited from five boarding schools (two purposively selected Buddhist schools and three conveniently selected secular schools). They completed these tools: Experiences in Close Relationships Questionnaire-revised-18, Outcome-Inventory-21: Depression Subscale, Precept Practice Questionnaire, and Inner-Strength-Based Inventory: Meditation. A parallel mediation model analyzed the indirect effects of attachment anxiety and attachment avoidance on depression through precept adherence and meditation practice. The participants' demographics were 16.35 ± 0.96 years, 88% female, and 89.4% Buddhist. The mean scores for attachment anxiety were 2.7 ± 1.1; attachment avoidance, 2.78 ± 1.2; overall regular precept adherence, 20.1 ± 4.4; regular but not daily meditation, 2.94 ± 1.3; and low depressive symptoms, 3.75 ± 3.4. The standardized indirect effects for attachment anxiety (β = 0.042, 95% CI = 0.022, 0.070) and avoidance (β = 0.024, 95% CI = 0.009, 0.046) on depressive symptoms through meditation and precept adherence were significant. Meditation practice had a significantly higher indirect effect size than precept adherence.


Biosensor-Assisted Method for Abdominal Syndrome Classification Using Machine Learning Algorithm.
The digestive system is one of the essential systems in human physiology where the stomach has a significant part to play with its accessories like the esophagus, duodenum, small intestines, and large intestinal tract. Many individuals across the globe suffer from gastric dysrhythmia in combination with dyspepsia (improper digestion), unexplained nausea (feeling), vomiting, abdominal discomfort, ulcer of the stomach, and gastroesophageal reflux illnesses. Some of the techniques used to identify anomalies include clinical analysis, endoscopy, electrogastrogram, and imaging. Electrogastrogram is the registration of electrical impulses that pass through the stomach muscles and regulate the contraction of the muscle. The electrode senses the electrical impulses from the stomach muscles, and the electrogastrogram is recorded. A computer analyzes the captured electrogastrogram (EGG) signals. The usual electric rhythm produces an enhanced current in the typical stomach muscle after a meal. Postmeal electrical rhythm is abnormal in those with stomach muscles or nerve anomalies. This study considers EGG of ordinary individuals, bradycardia, dyspepsia, nausea, tachycardia, ulcer, and vomiting for analysis. Data are collected in collaboration with the doctor for preprandial and postprandial conditions for people with diseases and everyday individuals. In CWT with a genetic algorithm, db4 is utilized to obtain an EGG signal wave pattern in a 3D plot using MATLAB. The figure shows that the existence of the peak reflects the EGG signal cycle. The number of present peaks categorizes EGG. Adaptive Resonance Classifier Network (ARCN) is utilized to identify EGG signals as normal or abnormal subjects, depending on the parameter of alertness (μ). This study may be used as a medical tool to diagnose digestive system problems before proposing invasive treatments. Accuracy of the proposed work comes up with 95.45%, and sensitivity and specificity range is added as 92.45% and 87.12%.


Efficacy of exercise in reducing depressive symptoms across 5-HTTLPR genotypes.
Exercise is effective in the alleviation of depressive symptoms and may have physiological effects similar to those of selective serotonin reuptake inhibitors (SSRI). Recent research has identified the difference in treatment effects across genetic polymorphisms of the serotonin transporter polymorphic region (5-HTTLPR), in which the l allele has been associated with a better response to SSRI compared with the s allele. The purpose of the current research was to examine the antidepressant effects of exercise across 5-HTTLPR genotypes. Participants, ages 18–23 yr, were randomly assigned to a 5-wk exercise intervention or a no-treatment control group. Participants completed the Beck Depression Inventory before and after the intervention and provided a saliva sample for DNA analysis. Exercise resulted in a significant reduction in depressive symptoms compared with the control group. In addition, individuals with at least one l allele demonstrated greater reductions in depressive symptoms compared with ss individuals. The effects of exercise on depressive symptoms appear to be moderated by 5-HTTLPR genotype, suggesting that the mechanisms responsible for the alleviation of depressive symptoms are similar for exercise and SSRI treatment. Furthermore, these findings suggest that 5-HTTLPR genotype should be a factor in determining the proper line of treatment for depression.


Comparison of breath gases, including acetone, with blood glucose and blood ketones in children and adolescents with type 1 diabetes.
Previous studies have suggested that breath gases may be related to simultaneous blood glucose and blood ketone levels in adults with type 2 and type 1 diabetes. The aims of this study were to investigate these relationships in children and young people with type 1 diabetes in order to assess the efficacy of a simple breath test as a non-invasive means of diabetes management. Gases were collected in breath bags and measurements were compared with capillary blood glucose and ketone levels taken at the same time on a single visit to a routine hospital clinic in 113 subjects (59 male, age 7 years 11 months-18 years 3 months) with type 1 diabetes. The patients were well-controlled with relatively low concentrations of the blood ketone measured (β hydroxybutyrate, 0-0.4 mmol l(-1)). Breath acetone levels were found to increase with blood β hydroxybutyrate levels and a significant relationship was found between the two (Spearman's rank correlation ρ = 0.364, p < 10(-4)). A weak positive relationship was found between blood glucose and breath acetone (ρ = 0.16, p = 0.1), but led to the conclusion that single breath measurements of acetone do not provide a good measure of blood glucose levels in this cohort. This result suggests a potential to develop breath gas analysis to provide an alternative to blood testing for ketone measurement, for example to assist with the management of type 1 diabetes.


Purification, physicochemical properties, and subcellular location of alkaline inorganic pyrophosphatase from sesame (Sesamum indicum L.) cotyledons.
Abstract: Changes in the levels of inorganic pyrophosphatases (PPases) were monitored in germinating sesame seeds at regular intervals. Activities of acid and alkaline PPases increased markedly in cotyledons up to day 4, remained at the peak level up to day 7, and then showed a considerable decline thereafter. An alkaline PPase was isolated and purified from 5-day-old sesame cotyledons following acetone precipitation, ammonium sulfate fractionation, and chromatography on DEAE-Sephadex. Current protocol yielded about 20% recovery of total activity with a 6.4-fold purification. The enzyme was a monomer with a molecular mass of 20.8 kDa. Some of the properties of alkaline PPase including stability, substrate specificity, ion requirement, and amino acid composition were studied. Alkaline PPase showed maximum activity at pH 8.6 in the presence of Mg2+ and at 50 degrees C. However, the metal ion could not protect the enzyme against thermal denaturation. Alkaline PPase was highly specific for inorganic pyrophoaphate (PP) as substrate and the Km value was 0.7677 +/- 0.0528 mM. Full activation of the enzyme was achieved with a Mg2+/PPi ratio of 2. Divalent metal ions such as Ca2+, Cu2+, and Zn2+ inhibited PPase activity. Mg2+, partially relieved the inhibition caused by adenosine 5'-triphosphate. Studies related to the localization of alkaline PPase in microbodies revealed that the enzyme was distributed between glyoxysomes and mitochondria, with the former containing more of it.


Subsets of keratinocytes and Langerhans' cells express epitopes associated with suppressor-inducer capabilities in resting normal human epidermis.
In recent years two cell populations with down-regulatory immune capabilities have been identified in murine epidermis. The present report demonstrates that even in human epidermis at least two populations of cells expressing suppressor-inducer phenotypes (i.e. CD45R-positive) exist, namely small subsets of keratinocytes and Langerhans' cells, respectively. Highly specific and sensitive 5-nm colloidal gold-immunoelectronmicroscopic techniques were carried out using anti-CD45R monoclonal antibodies, on freshly isolated crude epidermal cell suspensions, and 4000 cells were scrutinized in the electron microscope. Over 2% of the total epidermal cell population was CD45R+. Subpopulation analysis revealed that approximately 2% of keratinocytes and about 5% of the total Langerhans' cell population showed strong gold-plasma membrane staining, whilst the remaining epidermal cells were absolutely negative. Heterogeneity of staining together with this somehow surprising distribution of CD45R positivity on non-lymphoid epidermal cells was confirmed by the negative controls. These CD45R+ Langerhans' cells and keratinocytes are clearly candidates for the cells which have been functionally demonstrated as being capable of inducing down-regulation responsiveness in the human epidermis. However, functional investigations are needed to clarify the roles of the CD45R+ keratinocyte and Langerhans' cell subsets in the modulation of cutaneous immune responses.


The hepatitis B virus receptor.
Hepatitis B virus (HBV) infection affects 240 million people worldwide. A liver-specific bile acid transporter named the sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for HBV and its satellite, the hepatitis D virus (HDV). NTCP likely acts as a major determinant for the liver tropism and species specificity of HBV and HDV at the entry level. NTCP-mediated HBV entry interferes with bile acid transport in cell cultures and has been linked with alterations in bile acid and cholesterol metabolism in vivo. The human liver carcinoma cell line HepG2, complemented with NTCP, now provides a valuable platform for studying the basic biology of the viruses and developing treatments for HBV infection. This review summarizes critical findings regarding NTCP's role as a viral receptor for HBV and HDV and discusses important questions that remain unanswered.


Using quality indicators in anaesthesia: feeding back data to improve care.
After recent UK policy developments, considerable attention has been focused upon how clinical specialties measure and report on the quality of care delivered to patients. Defining the right indicators alone is insufficient to close the feedback loop. This narrative review aims to describe and synthesize a diverse body of research relevant to the question of how information from quality indicators can be fed back and used effectively to improve care. Anaesthesia poses certain challenges in the identification of valid outcome indicators sensitive to variations in anaesthetic care. Metrics collected during the immediate post-anaesthetic recovery period, such as patient temperature, patient-reported quality of recovery, and pain and nausea, provide potentially useful information for the anaesthetist, yet this information is not routinely fed back. Reviews of the effects of feeding back performance data to healthcare providers suggest that this may result in small to moderate positive effects upon outcomes and professional practice, with stronger effects where feedback is integrated within a broader quality improvement strategy. The dominant model for use of data within quality improvement is based upon the industrial process control approach, in which care processes are monitored continuously for process changes which are rapidly detectable for corrective action. From this review and experience of implementing these principles in practice, effective feedback from quality indicators is timely, credible, confidential, tailored to the recipient, and continuous. Considerable further work is needed to understand how information from quality indicators can be fed back in an effective way to clinicians and clinical units, in order to support revalidation and continuous improvement.


Applicability of ribosome engineering to vitamin B12 production by Propionibacterium shermanii.
Ribosome engineering has been widely utilized for strain improvement, especially for the activation of bacterial secondary metabolism. This study assessed ribosome engineering technology to modulate primary metabolism, taking vitamin B12 production as a representative example. The introduction into Propionibacterium shermanii of mutations conferring resistance to rifampicin, gentamicin, and erythromycin, respectively, increased per cell production (μg/L/OD600) of vitamin B12 5.2-fold, although net production (μg/L) was unchanged, as the cell mass of the mutants was reduced. Real-time qPCR analysis demonstrated that the genes involved in vitamin B12 fermentation by P. shermanii were activated at the transcriptional level in the drug-resistant mutants, providing a mechanism for the higher yields of vitamin B12 by the mutants. These results demonstrate the efficacy of ribosome engineering for the production of not only secondary metabolites but of industrially important primary metabolites.


Prediction of the Mortality Risk in Peritoneal Dialysis Patients using Machine Learning Models: A Nation-wide Prospective Cohort in Korea.
Herein, we aim to assess mortality risk prediction in peritoneal dialysis patients using machine-learning algorithms for proper prognosis prediction. A total of 1,730 peritoneal dialysis patients in the CRC for ESRD prospective cohort from 2008 to 2014 were enrolled in this study. Classification algorithms were used for prediction of N-year mortality including neural network. The survival hazard ratio was presented by machine-learning algorithms using survival statistics and was compared to conventional algorithms. A survival-tree algorithm presented the most accurate prediction model and outperformed a conventional method such as Cox regression (concordance index 0.769 vs 0.745). Among various survival decision-tree models, the modified Charlson Comorbidity index (mCCI) was selected as the best predictor of mortality. If peritoneal dialysis patients with high mCCI (>4) were aged ≥70.5 years old, the survival hazard ratio was predicted as 4.61 compared to the overall study population. Among the various algorithm using longitudinal data, the AUC value of logistic regression was augmented at 0.804. In addition, the deep neural network significantly improved performance to 0.841. We propose machine learning-based final model, mCCI and age were interrelated as notable risk factors for mortality in Korean peritoneal dialysis patients.


Interferon enhances prostacyclin production by cultured vascular endothelial cells.
The effects of interferon (IFN) on the arachidonate metabolism and physiological functions of cultured endothelial cells and blood platelets have been examined. Cultured bovine aortic endothelial cells were found to be sensitive to the antiviral and antiproliferative activities of human leukocyte (alpha) IFN and to increase their capacity to synthesize prostacyclin (PGI2) upon exposure to IFN. Several observations indicate that IFN stimulates PGI2 synthesis at the level of the enzymes phospholipase A2 and cyclooxygenase: (a) PGI2 production was dependent upon the supply of exogenous arachidonic acid or the liberation of endogenous cellular arachidonate by ionophore A23187, but was not observed when IFN-treated cells were exposed to the endoperoxide prostaglandin H2. (b) IFN had no effect on the spontaneous release of PGI2 into the culture medium during the incubation period (24-72 h). (c) The stimulatory effect of IFN on PGI2 production was inhibited by both glucocorticoids and indomethacin. The effect of IFN on platelet prostaglandin metabolism was also investigated. Incubation of platelet-rich plasma with IFN had no effect on platelet aggregation and thromboxane A2 production. The biological significance of the findings presented in this paper may be considered in view of the protective role of PGI2 in the vessel wall and the fact that infection with certain viruses induces endothelial damage both in man and experimental animal models.


Kidney diseases associated with anti-vascular endothelial growth factor (VEGF): an 8-year observational study at a single center.
Expanded clinical experience with patients taking antiangiogenic compounds has come with increasing recognition of the renal adverse effects. Because renal histology is rarely sought in those patients, the renal consequences are underestimated. Antiangiogenic-treated-cancer patients, who had a renal biopsy for renal adverse effects from 2006 to 2013, were included in the current study. Clinical features and renal histologic findings were reviewed. Our cohort was 100 patients (58 women) with biopsy-proven kidney disease using anti-vascular endothelial growth factor (VEGF) therapy with a mean age of 59.8 years (range, 20-85 yr). Patients were referred for proteinuria, hypertension, and/or renal insufficiency. Kidney biopsy was performed 6.87 ± 7.18 months after the beginning of treatment. Seventy-three patients experienced renal thrombotic microangiopathy (TMA) and 27 patients had variable glomerulopathies, mainly minimal change disease and/or collapsing-like focal segmental glomerulosclerosis (MCN/cFSGS). MCN/cFSGS-like lesions developed mainly with tyrosine-kinase inhibitors, whereas TMA complicated anti-VEGF ligand. Thirty-one percent of TMA patients had proteinuria up to 1 g/24 h. Half of TMA cases are exclusively renal localized. Pathologic TMA features are intraglomerular exclusively. MCN/cFSGS glomeruli displayed a high abundance of KI-67, but synaptopodin was not detected. Conversely, TMA glomeruli exhibited a normal abundance of synaptopodin-like control, whereas KI-67 was absent. Median follow-up was 12 months (range, 1-80 mo). Fifty-four patients died due to cancer progression. Hypertension and proteinuria resolved following drug discontinuation and antihypertensive agents. No patient developed severe renal failure requiring dialysis. Drug continuation or reintroduction resulted in a more severe recurrence of TMA in 3 out of 4 patients requiring maintenance of anti-VEGF agents despite renal TMA. In conclusion, TMA and MCN/cFSGS are the most frequent forms of renal involvement under anti-VEGF therapy. Careful risk-benefit assessment for individual patients should take into account risk factors related to the host and the tumor.


Dysregulated TDP-43 proteostasis perturbs excitability of spinal motor neurons during brainstem-mediated fictive locomotion in zebrafish.
Spinal motor neurons (SMNs) are the primary target of degeneration in amyotrophic lateral sclerosis (ALS). Degenerating motor neurons accumulate cytoplasmic TAR DNA-binding protein 43 (TDP-43) aggregates in most ALS cases. This SMN pathology can occur without mutation in the coding sequence of the TDP-43-encoding gene, TARDBP. Whether and how wild-type TDP-43 drives pathological changes in SMNs in vivo remains largely unexplored. In this study, we develop a two-photon calcium imaging setup in which tactile-evoked neural responses of motor neurons in the brainstem and spinal cord can be monitored using the calcium indicator GCaMP. We devise a piezo-assisted tactile stimulator that reproducibly evokes a brainstem descending neuron upon tactile stimulation of the head. A direct comparison between caudal primary motor neurons (CaPs) with or without TDP-43 overexpression in contiguous spinal segments demonstrates that CaPs overexpressing TDP-43 display attenuated Ca2+ transients during fictive escape locomotion evoked by the tactile stimulation. These results show that excessive amounts of TDP-43 protein reduce the neuronal excitability of SMNs and potentially contribute to asymptomatic pathological lesions of SMNs and movement disorders in patients with ALS.


Substance use disorders and overweight/obesity in bipolar I disorder: preliminary evidence for competing addictions.
This investigation was undertaken to explore the relationship between alcohol/illicit drug dependence and overweight/obesity in individuals with bipolar I disorder. The data for this analysis were procured from the Canadian Community Health Survey-Mental Health and Well-Being (CCHS) conducted by Statistics Canada in 2002. Bipolar I disorder was defined as persons screening positive for a lifetime manic episode using the World Mental Health 2000 version of the Composite International Diagnostic Interview (WMH-CIDI). Substance abuse and illicit drug dependence were determined using criteria commensurate with the DSM-IV-TR. Overweight and obesity were defined as a body mass index of 25.0 to 29.9 and greater than or equal to 30.0 kg/m(2), respectively. The total sample comprised 36,984 individuals (>or= 15 years old) screening positive for a lifetime manic episode. Subgroup analysis indicated that overweight/obese bipolar individuals had a significantly lower rate of substance dependence than the normal weight sample (13% vs. 21%, p < .01). Conversely, bipolar individuals who screened positive for substance dependence had a lower rate of overweight/obesity when compared with non-substance-dependent bipolar respondents (39% vs. 54%, p< .01). The inverse association between the presence of these 2 co-morbid conditions in bipolar I disorder continued to be statistically significant in multivariate analysis (OR = 0.57, 95% CI = 0.34 to 0.95, p < .05). An inverse relationship between the presence of comorbid overweight/obesity and substance use disorders was observed in bipolar I disorder. These results suggest that comorbid addictive disorders (i.e., substance use and compulsive overeating) may compete for the same brain reward systems.


How does robot-assisted radical prostatectomy (RARP) compare with open surgery in men with high-risk prostate cancer?
What's known on the subject? and what does the study add?: Previous studies have shown that robot-assisted radical prostatectomy (RARP) can be performed in men with high-risk prostate cancer with similar outcomes to that of open surgery. However, most of the literature consists of small case series and compares RARP outcomes to open outcomes from the literature. This study compared a cohort of high-risk patients undergoing open RP and RARP at a single institution with good follow up. We found no difference in positive margin rates or likelihood of prostate cancer recurrence. This adds to the growing evidence that RARP is a safe option for men with high-risk disease. To compare oncological outcomes in high-risk patients who underwent open retropubic radical prostatectomy (RRP) and robot-assisted RP (RARP) at a single institution. Despite equivalent oncological outcomes between open RRP and RARP, the use of RARP in men with high-risk tumours has been debated. A retrospective analysis of high-risk patients treated with open RRP or RARP at UCSF from 2002 to 2011 was conducted. The relationship between surgical approach and positive margin rate was assessed by multivariate logistic regression Cox proportional hazards regression assessed the effect of surgical approach on time to tumour recurrence. In all, 177 open RRP and 233 RARP patients made up the final cohort for analyses. The mean (SD) age was 61.6 (6.6) years and the median (range) follow-up was 27 (2-112) months. RARP patients had less blood loss (median 200 vs 400 mL, P < 0.01) and underwent complete bilateral nerve sparing more often (54% vs 34%, P < 0.01) than those undergoing open RRP. There were no differences by approach in pathological grade, stage, or positive margin rates. However, there was a trend towards higher positive margin rates with RARP early on. Recurrence-free survival was similar at 2 years (84% and 79%) and 4 years (68% and 66%) after open RRP and RARP, respectively (log-rank P = 0.53). This study is novel in that it assesses outcomes of open RRP vs RARP in a cohort of high-risk men at a single institution. RARP appears to be a feasible option for men with high-risk prostate cancer and displayed equivalent oncological outcomes compared with open RRP.


Idiotypic specificity of a human monoclonal anti-Rhesus(D) antibody.
A human monoclonal IgG anti-Rhesus(D) (H2D5D2) obtained after transformation of lymphoid cells by Epstein-Barr virus was purified from culture supernatant by affinity chromatography. Rabbits were immunized with the monoclonal anti-D. The rabbit antisera, after appropriate absorption, reacted only against the immunizing monoclonal anti-D. The antiidiotypic antibodies (anti-id ab) were purified and gave a complete inhibition of the monoclonal anti-D, whereas no inhibition was observed with monoclonal or polyclonal IgG or with sera containing high titres of anti-D. Polyclonal anti-D obtained from 118 immunized blood donors were coated on Rh-positive red cells. Agglutination by anti-id ab was observed in 4 cases (3.4%), indicating a cross-reactivity between the monoclonal anti-D and the polyclonal anti-D present in the sera of some immunized donors.


Report on the monogenean Cyclocotyla bellones and three cymothoids parasitizing two fish species from the Aegean Sea coasts of Turkey.
In this paper, three separate instances of an association between an ectoparasite, Cyclocotyla bellones (Otto, 1821) (Monogenea: Diclidophoridae) and ectoparasitic isopods have been reported for the first time from the Aegean Sea coasts of Turkey. The isopods were all of the family Cymothoidae: Ceratothoa oestroides, C. parallela, Emetha audouini.


Beta-2-Adrenergic stimulation of ornithine decarboxylase activity in porcine granulosa cells in vitro.
Epinephrine, norepinephrine, and isoproterenol produced dose-dependent stimulation of ornithine decarboxylase (EC 126.96.36.199) activity in isolated porcine granulosa cells maintained under defined conditions in vitro. beta- but not alpha-receptor-blocking agents prevented enzyme stimulation by catecholamines. Application of preferential beta-1 and beta-2-receptor antagonists and agonists localized the epinephrine effect to beta-2-adrenergic mediation. Epinephrine action was enhanced by the phosphodiesterase inhibitor, 1-methyl-3-isobutyl-xanthine, but not by saturating concentrations of the cyclic AMP analogue, 8-bromocyclic AMP, of follicle-stimulating hormone, or of prostaglandin E2. However, stimulation by epinephrine was additive to that of luteinizing hormone. Follicular fluid obtained from immature Graafian follicles contained concentrations of norepinephrine and epinephrine active in vitro. Thus, catecholamines may participate in the regulation of ornithine decarboxylase activity in the ovary. Catecholamine effects may be mediated by beta-2-receptors linked to the adenylate cyclase system.