Characterisation of different nanoparticles with a potential use for drug delivery in neuropsychiatric disorders.
Nanoparticles are promising tools for targeted delivery of drugs in the treatment of different diseases, including neuropsychiatric disorders. However, they need to be carefully characterised for any adverse effects which may occur in their presence. In this study, we evaluated the applicability of nanoparticles that belong to three different groups: (i) aggregates from amphiphilic diblock copolymers composed of poly(2-ethyl-2-oxazoline) (PEtOx) and poly(2-phenyl-2-oxazoline) (PPhOx) in different ratios, (ii) stabilised polymeric micelles (SPM) based on poly(ethylene oxide)-b-poly(propylene oxide)-bpoly(ethylene oxide) (PEO-PPO-PEO) and (iii) star-like polymer with poly(acrylic acid) arms and branched polystyrene interior (PSPAA). Using cultured human neural progenitor cells, we characterised six nanoparticles (POx-9, POx-23 and POx-46 - the polyoxazoline group, SPM-F38 and SPMMS - the SPM group, and PSPAA - the star-like polymer) for neurotoxicity and effect on neurodevelopmental genes. Nanoparticles ability to activate complement system in blood was assessed by ELISA. None of the nanoparticles exhibited neurotoxicity. However, POx-9, POx-23, POx-46 and SPM-F38 activated complement system. POx-9 and SPM-F38 resulted in inhibition of expression of 19 and 26 out of 30 tested neurodevelopmental genes, respectively. Considering the properties of the studied nanoparticles, only PSPAA and SPMMS can be used at high concentrations for drug delivery without compromising neurogenesis and neurodevelopment, and activation of complement system.


Secondary structure determination by NMR spectroscopy of an immunoglobulin-like domain from the giant muscle protein titin.
We present the complete 15N and 1H NMR assignment and the secondary structure of an immunoglobulin-like domain from the giant muscle protein titin. The assignment was obtained using homonuclear and 15N heteronuclear 2D and 3D experiments. The complementarity of 3D TOCSY-NOESY and 3D 15N NOESY-HSQC experiments, using WATERGATE for water suppression, allowed an efficient assignment of otherwise ambiguous cross peaks and was helpful in overcoming poor TOCSY transfer for some amino acids. The secondary structure is derived from specific NOEs between backbone alpha- and amide protons, secondary chemical shifts of alpha-protons and chemical exchange for the backbone amide protons. It consists of eight beta-strands, forming two beta-sheets with four strands each, similar to the classical beta-sandwich of the immunoglobulin superfamily, as previously predicted by sequence analysis. Two of the beta-strands are connected by type II beta-turns; the first beta-strand forms a beta-bulge. The whole topology is very similar to the only intracellular immunoglobulin-like domain for which a structure has been determined so far, i.e., telokin.


TCR-mimic bispecific antibodies to target the HIV-1 reservoir.
HIV-1 infection is incurable due to the persistence of the virus in a latent reservoir of resting memory CD4+ T cells. "Shock-and-kill" approaches that seek to induce HIV-1 gene expression, protein production, and subsequent targeting by the host immune system have been unsuccessful due to a lack of effective latency-reversing agents (LRAs) and kill strategies. In an effort to develop reagents that could be used to promote killing of infected cells, we constructed T cell receptor (TCR)-mimic antibodies to HIV-1 peptide-major histocompatibility complexes (pMHC). Using phage display, we panned for phages expressing antibody-like variable sequences that bound HIV-1 pMHC generated using the common HLA-A*02:01 allele. We targeted three epitopes in Gag and reverse transcriptase identified and quantified via Poisson detection mass spectrometry from cells infected in vitro with a pseudotyped HIV-1 reporter virus (NL4.3 dEnv). Sequences isolated from phages that bound these pMHC were cloned into a single-chain diabody backbone (scDb) sequence, such that one fragment is specific for an HIV-1 pMHC and the other fragment binds to CD3ε, an essential signal transduction subunit of the TCR. Thus, these antibodies utilize the sensitivity of T cell signaling as readouts for antigen processing and as agents to promote killing of infected cells. Notably, these scDbs are exquisitely sensitive and specific for the peptide portion of the pMHC. Most importantly, one scDb caused killing of infected cells presenting a naturally processed target pMHC. This work lays the foundation for a novel therapeutic killing strategy toward elimination of the HIV-1 reservoir.


A risk-adapted strategy of adjuvant paclitaxel/carboplatin in early-stage ovarian cancer: time-dependent effect of 4 versus 6 cycles on outcome.
We investigated the efficacy of risk-adapted adjuvant paclitaxel/carboplatin chemotherapy in early-stage ovarian carcinoma. Fifty-three patients were treated according to the risk of relapse: patients with stages IA or IB or with grade 1 (low risk) received 4 cycles of paclitaxel and carboplatin; patients with IC/IIA and grade 2 or 3 (high risk) received 6 cycles of chemotherapy. The outcome was compared with that of 95 patients who were all treated with 4 cycles. Median follow-up was 88, 113 and 42 months for the whole cohort, non-risk-adapted and risk-adapted treatment, respectively. Five-year relapse-free and disease-specific survival was 86 and 93% for the whole population, 96 and 97% for low-risk and 81 and 91% for high-risk patients. Risk classification was the only significant prognostic factor for relapse-free (p = 0.011) and disease-specific survival (p = 0.039). Among high-risk patients, the administration of 6 cycles was associated with a significantly lower relapse rate after censoring events, which occurred beyond 2 years (3 vs. 18%; p = 0.013), but this difference was diminished at 5 years (23 vs. 25%; p = 0.797). Six cycles of chemotherapy reduced the risk of relapse within 2 years, but the benefit from two additional cycles beyond this time is questionable.


Alginate-based composite microspheres coated by berberine simultaneously improve hemostatic and antibacterial efficacy.
It is important to develop effective, biocompatible, easily stored and affordable hemostats for controlling bleeding and preventing infection in prehospital trauma. In this study, we synthesized a series of alginate-based composite microspheres coated by different amounts of berberine (SCC-1B, SCC-5B and SCC-10B), which were further characterized using scanning electron microscopy (SEM), viscometer, particle analyzer and Fourier transform infrared (FT-IR) spectroscopy. The in vitro and vivo results demonstrated that compared to control group (SCC, Composite polysaccharide microspheres without berberine, and CMPHP, Commercial hemostatic agent), SCC-10B with proper content berberine (7%), not only exhibited inherent excellent antibacterial activity, but also enhanced hemostatic effect by increasing adhesion and aggregation of blood cells, which could be considered as synergistic effects. More importantly, through inserting berberine into the cross-linked network, biodegradability and biocompatibility of SCC-10B were also improved. Taken together, SCC-10B could be a candidate for emergency hemostatic and antibacterial treatment in prehospital trauma.


Etiology of community-acquired pneumonia in hospitalized patients: a 3-year prospective study in Japan.
To compare the etiology of community-acquired pneumonia in Japan and Western countries, the causative pathogens were prospectively investigated in patients requiring hospitalization. Prospective study over a 3-year period. A community general hospital in Japan. Three hundred twenty-six episodes of community-acquired pneumonia in 318 patients admitted to the hospital between July 1994 and June 1997. The microbiological diagnosis was based on the results of quantitative sputum culture, blood culture, and other invasive procedures, including transthoracic needle aspiration or bronchoscopic examination. Serologic tests for Mycoplasma pneumoniae, Chlamydia spp, Legionella spp, and viruses were also routinely performed. Causative pathogens were identified in 199 episodes (61%). Streptococcus pneumoniae was the most common pathogen (23%), followed by Haemophilus influenzae (7.4%), M pneumoniae (4.9%), and Klebsiella pneumoniae (4.3%). The Streptococcus milleri group and Chlamydia pneumoniae were detected in 3.7 and 3.4% of the episodes, respectively. Pneumonia due to Legionella spp was recognized in only two patients. The etiology of community-acquired pneumonia in Japan did not differ markedly when compared with that of Western countries except for the low incidence of Legionella pneumonia. C pneumoniae and the S milleri group, which are emerging or newly recognized pathogens, were also significant causative microorganisms.


Structural and functional diversity in plant specialized metabolism signals and products: The case of oxylipins and triterpenes.
Metabolic enzymes tend to evolve towards catalytic efficacy, precision and speed. This seems particularly true for ancient and conserved enzymes involved in fundamental cellular processes that are present virtually in every cell and organism and converting and producing relatively limited metabolite numbers. Nevertheless, sessile organisms like plants have an astonishing repertoire of specific (specialized) metabolites that, by numbers and chemical complexity, by far exceed primary metabolites. Most theories agree that early gene duplication, subsequent positive selection and diversifying evolution have allowed relaxed selection of duplicated metabolic genes, thus facilitating the accumulation of mutations that could broaden substrate/product specificity and lower activation barriers and kinetics. Here, we use oxylipins, oxygenated fatty acids of plastidial origin to which the phytohormone jasmonate belongs, and triterpenes, a large group of specialized metabolites whose biosynthesis is often elicited by jasmonates, to showcase the structural and functional diversity of chemical signals and products in plant metabolism.


Non-Hodgkin's lymphomas of head and neck extranodal sites.
The initial staging, therapy and course of 156 patients with non-Hodgkin's lymphomas of head and neck extranodal sites were analyzed to determine whether they have a natural history which differs from primary nodal disease. The sites involved were: Waldeyer's ring-103 patients (tonsil-60, nasopharynx-25, base of tongue-18), and extralymphatic sites-53 patients (salivary gland-20, paranasal sinus-20, oral cavity-10, and larynx-3). Seventy-six percent had unfavorable histologies and 24% had favorable histologies. Fifty-three percent had pathologic Stages I-II and 47% had Stages III-IV. The 5-year survival was influenced by primary sites: salivary gland-61%, oral cavity-57%, tonsil-49%, base of tongue-47%, nasopharynx-36% and paranasal sinus-12%. The 5-year survival was also influenced by histology: unfavorable histologies-39%, favorable histologies-69%. The Ann Arbor staging system was more useful than TNM for determining outcome. For patients with Stage I-II unfavorable histologies treated with radiation alone, the 5-year survival was: involved field-24%, extended field-42%, total lymphoid irradiation-52%. The majority of patients who failed did so in extranodal sites. Forty-one patients with advanced disease received a variety of chemotherapy regimens as the sole treatment. There was a high percentage of CNS recurrence with paranasal sinus lymphoma, and CNS prophylaxis may be necessary. For head and neck extranodal lymphomas, limited radiation is inadequate, and combined modality programs should be considered.


Use of adhesive surgical tape with the absorbable continuous subcuticular suture.
The absorbable continuous subcuticular suture is frequently used to close surgical incisions where the aim is healing by primary intention. A form of adhesive surgical tape is commonly also placed over the wound but this combination closure seems to have its development based on anecdotal, rather than experimental evidence. The present study reviews the scientific literature on the development of sutureless wound closure and presents the current evidence for the use of combination wound closure. Review was undertaken of the medical literature using the PubMed Internet database and cross-referencing major -articles on the subject. The following combinations of key words were searched: skin closure, wound closure, suture technique, sutureless, adhesive tape, op-site, staples, subcuticular suture, complication, infection and scars. Taped closure alone has advantages of lower wound infection rates and greater wound tensile strength, but disadvantages of epidermal reaction, skin edge inversion, doubtful safety and time required for meticulous surgical technique. The use of the continuous absorbable subcuticular suture allows accurate skin edge approximation, which increases the safety margin. The combination closure has a slightly superior cosmetic result to sutureless techniques but no study has been performed to compare the results of combination subcuticular suture and tape, with tape or subcuticular suture alone. There is no evidence in the scientific literature to justify or support the practice of closing a surgical wound with both subcuticular suture and adhesive surgical tape.


Retrospective analysis of trauma incidence in patients with temporomandibular disorders.
The relationships between direct trauma, whiplash injuries, and temporomandibular disorders (TMD) have not been well established. The aim of this study was to evaluate the percentage of direct and/or whiplash trauma in patients with TMDs. The clinical records of 237 patients with temporomandibular disorders who had sought treatment at the Orofacial Pain Clinic were reviewed. Clinical data for age and gender of the patients, history of trauma, temporomandibular joint (TMJ) sounds, and TMD diagnosis were extracted from the medical records of all included patients. The presence of TMJ sounds and TMD diagnosis had been determined based on the Research Diagnostic Criteria for TMDs. The mean age of patients with osteoarthritis was significantly higher than that of patients with disk displacement with reduction (P = .001, P ˂ .05). There was no statistically significant gender-based difference in diagnosis, clicking, crepitus, and trauma frequency (P > .05). A history of direct and whiplash trauma was observed in 18.6% and 14.8% of patients, respectively. Statistical analysis for the relationship between clicking and crepitus, and trauma showed no significant correlation (P > .05). Direct and/or whiplash trauma in patients with temporomandibular disorders were not associated with the diagnostic records and temporomandibular joint sounds.


Quantification of proviral DNA load of human immunodeficiency virus type 2 subtypes A and B using real-time PCR.
HIV-2 infection is confined mostly to West Africa. Seven HIV-2 subtypes have so far been described; only HIV-2 subtypes A and B are prevalent, the others being considered self-limiting infections at the epidemiological level. The main limitation for the HIV-2 DNA proviral quantification is the lack of HIV-2 DNA standard. We designed and tested a new HIV-2 primer couple that amplifies both the HIV-2 ROD strain and HIV-1 LAV/BRU strain. These HIV-2 primers were used to quantified an HIV-2 standard comparatively to a standard widely used in proviral DNA HIV-1 quantification, i.e., the 8E5 cell line transfected by a single defective integrated provirus of HIV-1 BRU/LAV by cell. The primers and probe used to quantify HIV-2 DNA are located in a long terminal repeat (LTR) region with low variability. These primers amplify both HIV-2 subtypes A and B. The relevance of the follow-up of the infected patients by the quantification of the proviral DNA HIV-2 is currently studied.


Penta-acetyl-gitoxin: the prototype of a prodrug in the cardiac glycoside series.
Penta-acetyl-gitoxin is a suitable prodrug of gitoxin since it shows--side-effect latentiation, due to its inactive application form;--bioavailability, due to its improved solubility and thus good enteral absorption and--bioactivation, due to rapid de-acetylation in the body after absorption.


Artificial Stupidity: Data We Need to Make Machines Our Equals.
AI must understand human limitations to provide good service and safe interactions. Standardized data on human limits would be valuable in many domains but is not available. The data science community has to work on collecting and aggregating such data in a common and widely available format, so that any AI researcher can easily look up the applicable limit measurements for their latest project.


High and low density lipoprotein cholesterol in myocardial and cerebral infarction.
High density lipoprotein (HDL) and low density lipoprotein (LdL) cholesterol levels were measured in fasting blood samples from 950 healthy subjects and 188 aged patients by a new simple method. The HDL-cholesterol levels and HDL/LDL-cholesterol ratios are significantly higher in females than in males. In the healthy subjects, there are slight decreases in the levels of HDL-cholesterol and HDL/LDL-cholesterol ratio with aging in both sexes. The patients with myocardial infarction had significantly lower HDL-cholesterol levels and HDL/LDL-cholesterol ratios as compared to those of the group without infarction. On the contrary, no differences in total lipoprotein cholesterol levels were observed in the patients with cerebral infarction. The results, obtained in respect of electrocardiographic findings after the isoproterenol stress test, suggest that the HDL-cholesterol levels and HDL/LDL-cholesterol ratios may be related not only to the established myocardial infarction, but also to the presence of coronary atherosclerosis and stenosis.


Acute iron intoxication with intestinal infarction.
A fatal case of acute iron intoxication with intestinal infarction is reported, with emphasis on the acute gastrointestinal effects of iron ingestion. The patient demonstrated the progressive necrotizing effects of retained iron on the gastrointestinal tract. Although moderate amounts of iron may be irritating and may produce diarrhea, larger amounts may cause paralytic ileus. Localized concentrations of iron may then exert corrosive effects and cause segmental infarctions and perforations. Emphasis must be given to the purging of iron products from the bowel. Should surgery become necessary because of localized infarction or perforation, we believe that it is advisable to not only thoroughly irrigate the peritoneal cavity but also irrigate the lumen of the bowel so as to remove as much of the remaining iron as possible, lest further areas of necrosis and perforation develop because of continued corrosive effects.


The Irving-Scholander legacy in polar physiology.
The pioneer arctic and cold environment studies of Laurence Irving and Per Scholander, undertaken during the middle decades of the 20th century, have had a wide ranging and major influence on the direction and character of experimental research on polar species. Their investigations included comparative studies of metabolism, insulation, and acclimatization of mammals and birds in arctic Alaska and the tropics. Freezing, supercooling, and antifreeze research included fishes, insects, and plants. They examined the special problems of cooling in appendages of mammals and birds and the potential for acclimatization of these structures by repeated cold exposure. Studies of cold exposure in human populations considered possible adaptive reactions. Their research on diving mammals opened a vast new area for studies with attention to asphyxial tolerance and temperature regulation. A lesser-known accomplishment was an innovative approach to recovery of ancient atmospheric gases from polar ice fields, an approach that was stimulated by original investigations of frozen insect larvae and gas permeability through ice.


Mouse epidermal keratinocytes. Clonal proliferation and response to hormones and growth factors in serum-free medium.
A serum-free medium (LEP-1) has been developed for mouse epidermal keratinocytes. LEP-1 consists of "Ca2+-free" Eagle's MEM with non-essential amino acids and seven added supplements (transferrin, 5 micrograms/ml; epidermal growth factor (EGF), 5 ng/ml; hydrocortisone, 0.5 microM; insulin, 5 micrograms/ml; phosphoethanolamine and ethanolamine, each 50 microM; bovine pituitary extract, 180 micrograms of protein/ml). Although serum-free the culture system was dependent for growth on bovine pituitary extract as the only still undefined supplement. LEP-1 supports sustained multiplication of mouse keratinocytes for 25 or more population doublings. A clonal growth assay was developed to investigate the action of growth factors, hormones and other supplements on keratinocytes. Cells grown in LEP-1 (calcium concentration was 0.03 mM) maintained a high proliferative rate and presented the typical morphology of basal epidermal cells. When the calcium concentration of the medium was raised to 1.0 mM, the cells were triggered to differentiate terminally. The epithelial nature of the cells was demonstrated both by electron microscopy and by immunostaining with anti-keratin antibody. The maturation stage of the keratinocytes was defined by several morphological features during the proliferative phase and in terminally differentiating cultures. This serum-free system supported a useful number of cell divisions while keratinocytes retained the capacity to undergo terminal differentiation when given the appropriate stimulus. It provides, therefore, provides a useful model for investigations on growth, differentiation and malignant transformation of epidermal cells in culture.


Impact of Acute Self-Care Indicators and Social Factors on Medicare Inpatient Readmission Risk.
Readmissions are costly for Medicare and are associated with poor patient outcomes. To determine whether two domains relevant to acute occupational therapy practice-self-care status and social factors-were associated with readmissions for Medicare patients in the Medicare Hospital Readmissions Reduction Program (HRRP). Cross-sectional, retrospective study. Single academic medical center. Medicare inpatients with a diagnosis included in the HRRP (N = 17,618). Outcomes and Measures: Three logistic regression models were estimated to examine the associations among (1) self-care status and 30-day readmission, (2) social support and 30-day readmission, and (3) housing situation and 30-day readmission. Subgroup analyses were conducted for the individual HRRP diagnoses. No associations were found between acute self-care status, social support, or housing situation and 30-day readmission when all HRRP diagnoses were examined together. However, higher levels of independence with self-care were significantly associated with reduced odds of readmission for patients with pneumonia. The findings for patients with pneumonia are consistent with those of other studies done in the acute care setting. Deficiencies in acute occupational therapy documentation may have affected the findings for the other HRRP diagnoses. What This Article Adds: This study is the first to examine the association between acute self-care status (as documented by acute care occupational therapy practitioners) and readmission.


miR‑222-3p reduces neuronal cell apoptosis and alleviates spinal cord injury by inhibiting Bbc3 and Bim.
Spinal cord injury (SCI) is a severe traumatic event, but without any established effective treatment because of the irreversible neuronal death. Here, we investigated the role of miR-222-3p in neuronal apoptosis following SCI. Rat SCI models and neuron hypoxia models were accordingly established. The Bbc3, Bim, Bcl-2, Bax, cleaved-caspase 3, cleaved-caspase 9, Cytochrome c, and miR-222-3p expression levels were examined by Western blotting and real-time reverse transcription polymerase chain reaction (RT-qPCR). The possible association between miR-222-3p and Bbc3/Bim was analyzed by dual-luciferase assay. The neuron viability was assessed by Cell Counting Kit-8 assay and Nissl's staining. Live cell staining was performed to detect the mitochondrial membrane potential and neuronal apoptosis. Rat locomotor function was assessed using the Basso-Beattie-Bresnahan scores. Cytochrome c was outflowed from the mitochondria after SCI or hypoxia treatment, and Bbc3, Bim, Bax, cleaved-caspase 9, and cleaved-caspase 3 were significantly upregulated, while Bcl-2 and miR-222-3p were decreased remarkably. Meanwhile, neuronal cell viability was significantly inhibited. Treatment of miR-222-3p significantly suppressed the Cytochrome c efflux and neuronal apoptosis and improved neuronal cell viability and motor function in SCI rats. Moreover, we found that Bbc3 and Bim were the direct targets of miR-222-3p. Overall, our data suggest that miR-222-3p could alleviate the mitochondrial pathway-mediated apoptosis and motor dysfunction in rats after SCI by targeting Bbc3 and Bim.


Pseudoexfoliative material and oxytalan fibers.
Pseudoexfoliative material (PSX) was found to show oxytalan staining like the ocular zonular fibers. These two fibrous proteins also shared positive reactions for disulfide and sulhydryl groups and for acidic mucosubstances, both of which have been suggested as reactive groups in the oxytalan staining reaction. The deep striated zone in the pre-equatorial lens capsule and the lens capsular inclusions shared most of these reactions, indicating that they contain some similar components. PSX material showed histochemical differences from the zonule, including evidence of less PAS-positive glycoprotein and more acidic mucosubstance. Variations in staining within the PSX excrescences indicated that they are a composite of more than one substance. PSX material appears to be a product of local basement membrane-secreting cells, representing an abnormal polymerization of glycoconjugates similar to those in elastic microfibrils.


Isolated unguarded tricuspid valve: a rare cause of syncope and new-onset right cardiac failure in adult.
An unguarded tricuspid valve is a rare congenital anomaly. We describe the clinical and echocardiographic features of two young adult African patients with syncope, new-onset right cardiac failure, in whom the diagnosis of isolated unguarded tricuspid valve was established. One of the patients underwent tricuspid annuloplasty with good surgical results.


Adjustable V-Flap Epicanthoplasty Based on Desired Eyelid Morphology.
Eyelid shape is one key distinctive feature of the Asian eye. The presence of epicanthal folds is a common eyelid defect of Asians. Different surgical techniques have been developed to correct epicanthal folds. However, potential problems with these techniques are emerging, such as difficulty in design, recurrence and/or prominent scarring after surgery, and restricted application together with double eyelidplasty. An improved epicanthoplasty technique with high simplicity and flexibility is imperative. From October 2000 to March 2017, we performed V-flap epicanthoplasty procedures on 423 Asian patients. The whole procedure, including V-shaped skin incision, myotomy and pilication of the medial canthal ligament was performed layer by layer. A similar palpebral fissure distance and inner canthal distance were acquired with this surgical operation. Besides, this surgical technique will not cause limitations on double eyelid morphology when a double blepharoplasty is performed at the same period. The V-flap epicanthoplasty we described here is able to fully correct the epicanthal folds with a simple and flexible design, and the surgery can be adjusted according to patient needs for desired double eyelid shape. Satisfactory results were ideally achieved with no recurrence and finer scar.Level of evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors www.springer.com/00266 .


The mediating role of personality traits in the association between childhood trauma and depressive symptoms in young adulthood.
The aim of this study was to investigate the mediating role of the Big 5 personality traits (extraversion, neuroticism, openness, agreeableness, conscientiousness) in the association between early traumatization and depressive symptoms in early adulthood (20-25-year-olds) in a German population-based sample. A total of 3176 participants from the German National Cohort (NAKO) baseline with an age between 20 and 25 years were included in this investigation. The sum score of the 9-item-version of the Patient Health Questionnaire was used for assessment of depressive symptoms. A structural equation model was built to test the paths between childhood trauma, Big 5 personality traits and depressive symptoms. Overall, 10.7 % of the young adult sample had a PHQ-9 sum score of ten or higher. The final mediation model fitted well for young adults. We found evidence for a partial mediating effect of Big 5 personality traits. We only adjusted for age, sex, and year of data collection and did not include biological factors in the model. Young adults with early trauma experiences have a risk for developing depressive symptoms in young adulthood. Personality traits, especially neuroticism, partially mediated the association between early trauma and depressive symptoms for young adults and should be recognized in preventive strategies.


The non-homologous end-joining pathway is not involved in the radiosensitization of mammalian cells by heat shock.
A synergistic increase in cell killing is observed when a heat-shock is administered prior to, during, or immediately after exposure to ionizing radiation (IR). This phenomenon, known as heat-radiosensitization, is believed to be mediated by inhibition of repair of radiation-induced double strand breaks (DSB) when cells are exposed to temperatures above 42 degrees C. However, the mechanism by which heat inhibits DSB repair is unclear. The bulk of radiation-induced DSBs are repaired via the non-homologous end-joining pathway (NHEJ). Several reports indicate that the Ku70 and Ku80 subunits of the mammalian DNA-dependent protein kinase (DNA-PK), a complex involved in NHEJ, appear to be susceptible to a heat-induced loss of DNA-binding activity, with Ku80 representing the heat-sensitive component. Since the heat-induced loss and subsequent recovery of Ku-DNA binding activity correlates well with heat-radiosensitization, a role for Ku80 and NHEJ in heat-radiosensitization has been proposed. However, direct evidence implicating Ku80 (and NHEJ) in heat-radiosensitization has been indeterminate. In this study, we demonstrate that equitoxic heat treatments at 42.5-45.5 degrees C induce a similar amount of aggregation of Ku80 in human U-1 melanoma cells. These data suggest that the time-temperature-dependent relationship between heat lethality and Ku80 aggregation are similar. However, the aggregation/disaggregation of Ku80 and its transient or permanent inactivation is unrelated to heat-radiosensitization. When survival curves were obtained for irradiated or irradiated and heated Ku80(-/-) mouse embryo fibroblasts (MEFs) and compared with survival curves obtained for wild-type (WT) cells, we found that heat-radiosensitization was not reduced in the Ku80(-/-) cells, but actually increased. Thus, our findings indicate that Ku80 is not essential for heat-radiosensitization. Non-involvement of Ku-dependent or Ku-independent NHEJ pathways in heat-radiosensitization was confirmed by comparing clonogenic survival between DNA ligase IV-defective and WT human cells. Our data therefore implicate homologous recombination in inhibition of repair of radiation-induced DSBs and as a target for heat-radiosensitization.


Attenuation of Abeta deposition in the entorhinal cortex of normal elderly individuals associated with tobacco smoking.
Investigating correlates of tobacco smoking provides the only currently available opportunity of examining effects of long-term exposure of nicotinic receptors on a specific nicotinic agonist in human. Alzheimer-type pathology (Abeta and abnormally phosphorylated tau assessed on the basis of AT8 immunoreactivity) together with vascular markers has been compared in age-matched groups of normal elderly smokers and non-smokers in the entorhinal cortex, an area of noted age-related pathology. The density of total Abeta and diffuse Abeta immunoreactivity, together with formic acid-extractable Abeta42 but not Abeta40, was reduced in smokers (n = 10-18) compared with non-smokers (n = 10-20) (P < 0.05). There was also a reduced percentage of cortical and leptomeningeal vessels with associated Abeta immunoreactivity in smokers (n = 13) compared with non-smokers (n = 14) (P < 0.005 and 0.05, respectively). There was a significant inverse correlation between formic acid-extractable Abeta42 and pack years (n = 34, r = -0.389, P = 0.025), with a similar trend for total Abeta immunoreactivity which did not reach statistical significance (n = 30, r = -0.323, P = 0.082). In contrast, there were no significant group differences for vascular markers (collagen IV, alpha-actin or glucose transporter 1), AT8 immunoreactivity or phosphate-buffered saline-soluble Abeta peptides, and no significant associations with gender for any of the measured parameters. These findings are consistent with previously reported reductions in histologically assessed amyloid plaques in aged human brain associated with tobacco use and dramatic lessening of Abeta deposits in APPsw mice after nicotine treatment. Development of nicotinic drugs to protect against beta-amyloidosis as one of the principal pathological hallmarks of brain ageing and Alzheimer's disease is indicated.


Preference for sugars and nonnutritive sweeteners in young beagles.
Two-bowl choice tests were used to examined preference of puppies aged two to four months for compounds tasting sweet to humans. Puppies found many, but not all of the compounds highly palatable, and were sensitive to both type and amount of sugar or nonnutritive sweetener contained in a semi-moist dog food recipe. Lactose, fructose, and sucrose were well accepted, whereas maltose elicited indifference or rejection. Sodium cyclamate, but not sodium saccharin, was preferred at some concentrations to 15 percent sucrose sweetened semi-moist food used as the standard. Solutions of lactose, fructose, glucose and galactose were preferred to plain tap water.


[Ring chromosome 13 with. 13p. preserved. A case report and review of literature (author's transl].
A case with ring chromosome 13 is presented. The G and Q band analysis indicates that breakes are on long arms at region 3, band 4, and other on the short arms region 1, band 3. Short arms are nearly complete. The behaviour of the ring and of different cell lines obtained are interpreted. Authors also discuss the possible paternal origin of the abnormal chromosome.


Toward improved models for predicting bioconcentration of well-metabolized compounds by rainbow trout using measured rates of in vitro intrinsic clearance.
Models were developed to predict the bioconcentration of well-metabolized chemicals by rainbow trout. The models employ intrinsic clearance data from in vitro studies with liver S9 fractions or isolated hepatocytes to estimate a liver clearance rate, which is extrapolated to a whole-body biotransformation rate constant (kMET ). Estimated kMET values are then used as inputs to a mass-balance bioconcentration prediction model. An updated algorithm based on measured binding values in trout is used to predict unbound chemical fractions in blood, while other model parameters are designed to be representative of small fish typically used in whole-animal bioconcentration testing efforts. Overall model behavior was shown to be strongly dependent on the relative hydrophobicity of the test compound and assumed rate of in vitro activity. The results of a restricted sensitivity analysis highlight critical research needs and provide guidance on the use of in vitro biotransformation data in a tiered approach to bioaccumulation assessment.


Untargeted urinary metabolomics for bladder cancer biomarker screening with ultrahigh-resolution mass spectrometry.
Bladder cancer (BC) is a common urological malignancy with a high probability of death and recurrence. Cystoscopy is used as a routine examination for diagnosis and following patient monitoring for recurrence. Repeated costly and intrusive treatments may discourage patients from having frequent follow-up screenings. Hence, exploring novel non-invasive ways to help identify recurrent and/or primary BC is critical. In this work, 200 human urine samples were profiled using ultra-high-performance liquid chromatography and ultra-high-resolution mass spectrometry (UHPLC-UHRMS) to uncover molecular markers differentiating BC from non-cancer controls (NCs). Univariate and multivariate statistical analyses with external validation identified metabolites that distinguish BC patients from NCs disease. More detailed divisions for the stage, grade, age, and gender are also discussed. Findings indicate that monitoring urine metabolites may provide a non-invasive and more straightforward diagnostic method for identifying BC and treating recurrent diseases.


Establishment of a Novel Human Fetal Adrenal Culture Model that Supports de Novo and Manipulated Steroidogenesis.
Disorders affecting adrenal steroidogenesis promote an imbalance in the normally tightly controlled secretion of mineralocorticoids, glucocorticoids, and androgens. This may lead to differences/disorders of sex development in the fetus, as seen in virilized girls with congenital adrenal hyperplasia (CAH). Despite the important endocrine function of human fetal adrenals, neither normal nor dysregulated adrenal steroidogenesis is understood in detail. Due to significant differences in adrenal steroidogenesis between human and model species (except higher primates), we aimed to establish a human fetal adrenal model that enables examination of both de novo and manipulated adrenal steroidogenesis. Human adrenal tissue from 54 1st trimester fetuses were cultured ex vivo as intact tissue fragments for 7 or 14 days. Model validation included examination of postculture tissue morphology, viability, apoptosis, and quantification of steroid hormones secreted to the culture media measured by liquid chromatography-tandem mass spectrometry. The culture approach maintained cell viability, preserved cell populations of all fetal adrenal zones, and recapitulated de novo adrenal steroidogenesis based on continued secretion of steroidogenic intermediates, glucocorticoids, and androgens. Adrenocorticotropic hormone and ketoconazole treatment of ex vivo cultured human fetal adrenal tissue resulted in the stimulation of steroidogenesis and inhibition of androgen secretion, respectively, demonstrating a treatment-specific response. Together, these data indicate that ex vivo culture of human fetal adrenal tissue constitutes a novel approach to investigate local effects of pharmaceutical exposures or emerging therapeutic options targeting imbalanced steroidogenesis in adrenal disorders, including CAH.


An electrochemical fabrication process for the assembly of anisotropically oriented collagen bundles.
Controlled assembly of collagen molecules in vitro remains a major challenge for fabricating the next generation of engineered tissues. Here we present a novel electrochemical alignment technique to control the assembly of type-I collagen molecules into highly oriented and densely packed elongated bundles at the macroscale. The process involves application of electric currents to collagen solutions which in turn generate a pH gradient. Through an isoelectric focusing process, the molecules migrate and congregate within a plane. It was possible to fabricate collagen bundles with 50-400 microm diameter and several inches length via this process. The current study assessed the orientational order, and the presence of fibrillar assembly in such electrochemically oriented constructs by polarized optical microscopy, small angle X-ray scattering, second harmonic generation, and electron microscopy. The mechanical strength of the aligned crosslinked collagen bundles was 30-fold greater than its randomly oriented-crosslinked counterpart. Aligned crosslinked collagen bundles had about half the strength of the native tendon. Tendon-derived fibroblast cells were able to migrate and populate multiple macroscopic bundles at a rate of 0.5mm/day. The anisotropic order within biocompatible collagenous constructs was conferred upon the nuclear morphology of cells as well. These results indicate that the electrochemically oriented collagen scaffolds carry baseline characteristics to be considered for tendon/ligament repair.


Cooperation of myocardin and Smad2 in inducing differentiation of mesenchymal stem cells into smooth muscle cells.
Several reports demonstrated that mesenchymal stem cells (MSCs) might differentiate into smooth muscle cells (SMCs) in vitro and in vivo. It has been shown that myocardin protein is a strong inducer of smooth muscle genes and MSCs can differentiate into SMCs in response to transforming growth factor-β (TGF-β). However, the relationship or link between myocardin and TGF-β3-induced MSC differentiation has not been fully elucidated. Here, we demonstrated that both myocardin and TGF-β3 were able to induce differentiation of rat bone marrow-derived MSCs toward smooth-muscle-like cell types, as evidenced by increasing expression of SMC-specific genes. Of note, myocardin cooperated with Smad2 to synergistically activate SM22α promoter and significantly enhance the expression of SM22α. Report assays with site-direct mutation analysis of SM22α promoter demonstrated that myocardin and Smad2 coactivated SM22α promoter mainly depending on CArG box and less on smad binding elements (SBE) sites as well. These findings reveal the cooperation of myocardin and Smad2 in process of MSC differentiation into SMCs.


Assay of mixtures of phenylpropanolamine hydrochloride and caffeine in appetite suppressant formulations by high-performance liquid chromatography.
A simple assay method for the quality control of appetite suppressant products containing phenylpropanolamine hydrochloride and caffeine has been developed. A methanolic extract of the product was evaporated to dryness and the residue was treated with aqueous solutions of sodium metaperiodate and disodium phosphate. Following addition of methyl p-hydroxybenzoate as internal standard and subsequent filtration, an aliquot of the filtrate was subjected to high-performance liquid chromatography on a 10-microns Partisil ODS-2 column with acetonitrile-water (30:70) as mobile phase. The drug: internal standard peak height ratio at 254 nm was linear over the ranges 0.3-2.0 micrograms of phenylpropanolamine hydrochloride and 1.1-16.0 micrograms of caffeine injected. All peaks were well-resolved. The heights equivalent to a theoretical plate (+/- S.D.) for phenylpropanolamine (as benzaldehyde) and caffeine were (n = 10) 0.42 +/- 0.08 and 1.31 +/- 0.23 mm, respectively. Overall per cent recoveries (+/- S.D.) from simulated formulations (n = 6) were 100.7 +/- 1.6% phenylpropanolamine hydrochloride and 99.1 +/- 1.4% caffeine. The method was applied to marketed products and is also applicable for single dose analysis.


Glucose metabolism disorders and vestibular manifestations: evaluation through computerized dynamic posturography.
Global sugar consumption has increased in the past 50 years; its abusive intake is responsible for peripheral insulin resistance, which causes the metabolic syndrome - obesity, diabetes mellitus, hypertension, and coronary heart disease. To evaluate the effect of a fractionated diet without glucose as treatment for labyrinthine disorders associated with glucose-insulin index. The study design was a prospective randomized controlled trial. Fifty-one patients were divided into two groups: the diet group (DG), which comprised subjects treated with a fractionated diet with glucose restriction, and the control group (CG), in which individuals were not counseled regarding diet. Patients underwent computerized dynamic posturography (CDP) and visual analog scale (VAS) on the first and 30th days of the study. There was improvement in the assessed posturographic conditions and VAS self-assessment in the DG group after 30 days when compared to the control group. The fractionated diet with glucose restriction was effective for the treatment of vestibular dysfunction associated with glucose metabolism disorders.


Impulse control disorders in women with eating disorders.
We compared symptom patterns, severity of illness, and comorbidity in individuals with eating disorders with and without impulse control disorders (ICD), and documented the temporal pattern of illness onset. Lifetime ICD were present in 16.6% of 709 women with a history of eating disorders. The most common syndromes were compulsive buying disorder and kleptomania. ICD occurred more in individuals with binge eating subtypes, and were associated with significantly greater use of laxatives, diuretics, appetite suppressants and fasting, and with greater body image disturbance, higher harm avoidance, neuroticism, cognitive impulsivity, and lower self-directedness. In addition, individuals with ICD were more likely to have obsessive-compulsive disorder, any anxiety disorder, specific phobia, depression, cluster B personality disorder, avoidant personality disorder, and to use psychoactive substances. Among those with ICD, 62% reported the ICD predated the eating disorder and 45% reported the onset of both disorders within the same 3-year window. The presence of a lifetime ICD appears to be limited to eating disorders marked by binge eating and to be associated with worse eating-related psychopathology, more pathological personality traits, and more frequent comorbid Axis I and II conditions. Untreated ICD may complicate recovery from eating disorders.


Titanium dioxide nanoparticles: revealing the mechanisms underlying hepatotoxicity and effects in the gut microbiota.
Numerous studies in recent years have questioned the safety of oral exposure to titanium dioxide nanoparticles (TiO2 NPs). TiO2 NPs are not only likely to accumulate in the gastrointestinal tract, but they are also found to penetrate the body circulation and reach distant organs. The liver, which is considered to be a target organ for nanoparticles, is of particular concern. TiO2 NPs accumulate in the liver and cause oxidative stress and inflammatory reactions, resulting in pathological damage. The impact of TiO2 NPs on liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was studied using a meta-analysis. According to the findings, TiO2 NPs exposure can cause an elevation in AST and ALT levels in the blood. Furthermore, TiO2 NPs are eliminated mostly through feces, and their lengthy residence in the gut exposes them to microbiota. The gut microbiota is also dysbiotic due to titanium dioxide's antibacterial capabilities. This further leads to changes in the amount of microbiota metabolites, which can reach the liver with blood circulation and trigger hepatotoxicity through the gut-liver axis. This review examines the gut-liver axis to assess the effects of gut microbiota dysbiosis on the liver to provide suggestions for assessing the gut-hepatotoxicity of TiO2 NPs.


Impact of a primary care pharmacist consultations on pregnant women's medication use: the SafeStart intervention study linked to a national prescription database.
Prior studies show that pharmacist consultations are highly appreciated by pregnant women and feasible in community pharmacies. However, it is unknown whether such counseling has an impact on medication use during pregnancy. This study aimed to assess whether a pharmacist consultation in early pregnancy was associated with pregnant women's medication use, with a focus on antiemetic medications. The SafeStart study recruited Norwegian pregnant women in the first trimester between February 2018 and February 2019. Women in the intervention group received a pharmacist consultation in a community pharmacy or by phone. A follow-up questionnaire was completed 13 weeks after enrollment. Data from the SafeStart study were linked to the Norwegian Prescription Database. Logistic regression was used to assess the association between the pharmacist intervention and medication use in the second trimester. The study included 103 women in the intervention group and 126 in the control group. Overall prescription fills in the first and second trimesters were 55% and 45% (intervention group) and 49% and 52% (control group), respectively. In total, 16-20% of women in the first trimester and 21-27% of women in the second trimester had a prescription for antiemetics. The pharmacist intervention was not associated with women's medication use in the second trimester. This study did not detect an impact of a pharmacist consultation on pregnant women's use of medications. In the future, pharmacist consultations should focus on other outcome factors, such as risk perception, knowledge level, and the use of other health care services. Trial registration The SafeStart study is registered with ClinicalTrials.gov (identifier: NCT04182750, registration date: December 2, 2019).


Some comments on the article: 'The Structure of Human-Plasma Low-Density Lipoprotein B. An X-Ray Small-Angle Scattering Study' by K. Muller, P. Laggner, O. Glatter, and G. Kostner [Eur. J. Biochem. 82, 73--90 (1978)].
In their paper, K. Muller, P. Laggner, O. Glatter and G. Kostner report X-ray scattering and density experiments on human plasma low-density lipoprotein B, performed at different solvent densities (i.e. contrast variation method). The interpretation of the experimental data lead those authors to question the use of that method and particularly the use of the characteristic scattering functions in the study of serum lipoproteins. In the present paper it is shown that several aspects of their analysis are in fact highly questionable and that the objections raised are therefore unfounded.


Pathological changes of high-grade prostatic intraepithelial neoplasia and prostate cancer after monotherapy with bicalutamide 150 mg.
To evaluate the morphological changes induced by a 3-month course of neoadjuvant bicalutamide 150 mg/day before radical prostatectomy (RP) on prostatic adenocarcinoma and high-grade prostatic intraepithelial neoplasia (HGPIN). In all, 90 patients with cT1-T2 prostate cancer and HGPIN on prostatic biopsy were randomized to receive bicalutamide (150 mg/day for 3 months) before RP, or to have immediate surgery. Surgical specimens were assessed for the histopathological features of cancer, HGPIN and benign epithelium in a blinded manner. The volumes of prostate cancer and HGPIN were evaluated using a stereological (i.e. grid) method. Compared with the bicalutamide-treated group, the ratio of stroma to epithelium, evaluated by visual microscopic assessment in the normal epithelium of the three prostate zones, was significantly lower in the control group, at 2.27 (sd 1.13), than in the treated group, at 1.87 (sd 0.72) (P = 0.048). The mean (sd) tumour volume was significantly lower in the bicalutamide-treated than in the control group, at 0.914 (0.13) vs 1.47 (0.24) mL (P = 0.044). Similarly, the mean (sd) volume of HGPIN was significantly lower in the bicalutamide-treated than in the control group, at 0.34 (0.06) vs 0.62 (0.07) mL (P = 0.003). At RP, specimen Gleason scores in the bicalutamide-treated group were similar to those in the control group, and were no different from the biopsy Gleason scores. Involution and epithelial shrinkage of prostate cancer and HGPIN were evident after neoadjuvant treatment with bicalutamide 150 mg. There was no evidence of the emergence of higher-grade cancer after treatment.


Glenoid bone lesions: comparison between 3D VIBE images in MR arthrography and nonarthrographic MSCT.
To evaluate the feasibility of using a fat-suppressed 3D volumetric interpolated breath-hold examination (VIBE) sequence in magnetic resonance (MR) arthrography as a substitute for nonarthrographic multislice computed tomography (MSCT) in detecting glenoid bone lesions. Fat-suppressed 3D VIBE MR arthrography and MSCT were performed in 56 patients (46 male, 10 female; age range, 14-51 years; mean age, 26 years). Based on the results of MSCT, the sensitivity and specificity of fat-suppressed 3D VIBE images for detection of bony Bankart lesion and glenoid bone loss were determined. Statistical significance of the percentages of glenoid bone loss between these two methods was calculated. Bony Bankart lesions were noted in 23 (41.1%) of 56 glenohumeral joints, and glenoid bone loss was found in 40 (71.4%) of 56 patients at nonarthrographic MSCT. Compared with MSCT, the sensitivity and specificity of fat-suppressed 3D VIBE images in detecting bony Bankart lesions were 95.7%-100% and 93.9%-97.0%, respectively (kappa value = 0.926), and those in predicting glenoid bone loss were 95.0% and 93.8%, respectively. For quantification of glenoid bone loss, there was a high correlation between fat-suppressed 3D VIBE and MSCT (r = 0.921, P < 0.001). Fat-suppressed 3D VIBE MR arthrography is a promising substitute for MSCT as a reliable method for evaluating bony Bankart lesion and glenoid bone loss.


Experimental carcinoma of the biliary tract induced in dogs by N-ethyl-N'-nitro-N-nitrosoguanidine.
The present study was designed to produce the experimental carcinoma of the biliary tract in dogs. Tube cholecystostomy was constructed in 8 mongrel dogs and 5-10 ml of 0.7-1.0 mg/ml solution of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) was administered through the tube every day for the maximum period of 180 days. As the results: The experiment had to be cut off in 7 dogs (5 dogs: The tube was inadvertently pulled out. 2 dogs: died of general weakness). Pathological changes were observed in one dog given ENNG for 180 days and sacrificed at 372 days after the beginning of the experiment. Macroscopically, scattered foci of flat elevation of the mucosa were observed in the entire mucosal surface of common bile duct and a tiny polypoid lesion at the terminal protion. A tiny polypoid projection was adenocarcinoma confined to the mucosa, and areas of flat elevation showed marked hyperplasia of mucosa with partial atypical proliferation. No remarkable findings were noted in other organs.


Basement membrane thickness, insulin antibodies and HLA-antigens in long standing insulin dependent diabetics with and without severe retinopathy.
The study was designed to show whether there was any relation between muscle capillary basement membrane thickness, HLA-antigens, anti-insulin antibodies and proliferative retinopathy. Electron microscopic measurements of muscle capillary basement membrane thickness were performed on muscle biopsies from 15 insulin-dependent diabetics and severe proliferative retinopathy, 24 insulin-dependent diabetics with minimal retinopathy and 18 age- and sex matched non-diabetics. All the patients had had diabetes for 20 years or more. None had biochemical or clinical evidence of diabetic nephropathy. Basement membrane thickness was measured according to the methods of Siperstein and Williamson. Muscle capillary basement membrane thickening occurred in 32 of 39 diabetics, using the Siperstein method, but patients with proliferative retinopathy did not exhibit thicker basement membranes than patients with no or minimal changes in the retina. There were apparent differences in HLA-antigens between diabetics with and without proliferative retinopathy, but they did not reach statistical significance. There was no correlation between muscle capillary basement membrane thickness and the quantity of insulin antibodies. The results indicate that factors other than basement membrane thickening and genetic factors in the HLA-region, are responsible for the development of proliferative retinopathy.


An abattoir survey of contagious bovine pleuropneumonia lesions in slaughtered cattle in selected districts in Northern Tanzania.
To establish and estimate incidence of contagious bovine pleuropneumonia (CBPP), using abattoir survey as a diagnostic tool in slaughtered cattle in Northern Tanzania. A total of 4 460 cattle were slaughtered in five abattoirs in 3 northern zone regions (Arusha, Kilimanjaro and Tanga) during the period of January to May 2004. They were examined ante-mortem for 'pneumonia signs', and 'characteristic contagious bovine pleuropneumonia (CBPP) lung lesions'. Forty-one (0.91%) of the slaughtered cattle, the majority of which were Tanzania short horn zebu, had gross lung lesions suggestive of CBPP. The prevalence of lesions was significantly (P<0.05) higher in Karatu abattoir compared to others. No animal was detected to have lesion in Bomang' ombe abattoir. The most observed pneumonic signs included labored breathing (90%), dry cough (57%) and mucopurulent nasal discharge (47%). The gross characteristic CBPP pathological lesion, frequently encountered was left lung lesion (47%), pinkish lung (71%) and pleural adhesion (98%). Epidemiological reports show that the CBPP reported outbreaks increased from 19 in 2002, 65 in 2003 and 18 in 2004 (January-March). The corresponding number of reported deaths increased from 137 in 2002, 269 in 2003 and 77 in 2004 (January-March). It's concluded from this study that CBPP is a problem in spite of the extensive awareness and vaccination campaigns. Nevertheless, a continued surveillance programme including routine checks of all cattle carcasses at the abattoir and subsequent epidemiological investigation of suspected cases are recommended.


Behavioural flexibility in an Arctic seabird using two distinct marine habitats to survive the energetic constraints of winter.
Homeothermic marine animals in Polar Regions face an energetic bottleneck in winter. The challenges of short days and cold temperatures are exacerbated for flying seabirds with small body size and limited fat stores. We use biologging approaches to examine how habitat, weather, and moon illumination influence behaviour and energetics of a marine bird species, thick-billed murres (Uria lomvia). We used temperature-depth-light recorders to examine strategies murres use to survive winter in the Northwest Atlantic, where contrasting currents create two distinct marine habitats: cold (-0.1 ± 1.2 °C), shallower water along the Labrador Shelf and warmer (3.1 ± 0.3 °C), deep water in the Labrador Basin. In the cold shelf water, murres used a high-energy strategy, with more flying and less diving each day, resulting in high daily energy expenditure and also high apparent energy intake; this strategy was most evident in early winter when day lengths were shortest. By contrast, murres in warmer basin water employed a low-energy strategy, with less time flying and more time diving under low light conditions (nautical twilight and night). In warmer basin water, murres increased diving at night when the moon was more illuminated, likely taking advantage of diel vertically migrating prey. In warmer basin water, murres dove more at night and foraging efficiency increased under negative North Atlantic Oscillation (calmer ocean conditions). The proximity of two distinct marine habitats in this region allows individuals from a single species to use dual (low-energy/high-energy) strategies to overcome winter energy bottlenecks.


Post-traumatic stress disorder in young people with intellectual disability.
Post-traumatic stress disorder (PTSD) is common and treatable. There is extensive research on people of average intelligence yet little on individuals with developmental disabilities. We report two people with intellectual disability (ID) who experienced PTSD. The relevance of their developmental difficulties, social and communication profiles, attentional skills, and causes of these, to their presentations is discussed. Both individuals have fragile X syndrome and severe ID. One has Diagnostic and Statistical Manual - 4th Edition (DSM-IV) autistic disorder; the other DSM-IV attention deficit-hyperactivity disorder. They experienced developmental and psychological regressions, new challenging behaviours and exacerbations of existing ones coincident with emotional trauma. PTSD symptoms and phenomena were identifiable despite intellectual and communicatory impairments. Presentation of PTSD is influenced by degree and cause of ID, social circumstances, social and communicatory skills, nature and timing of traumatic experience and subsequent management. The paucity of literature suggests it is missed frequently in individuals with ID who risk having problems misattributed to other causes with potential for inappropriate interventions.


Ammonium ion transport-a cause of cell death.
Ammonium can be transported into the cell by ion pumps in the cytoplasmic membrane. Ammonia then diffuse out through the cell membrane. A futile cycle is created that results in cytoplasmic acidification and extracellular alkalinisation. Ammonium transport can be quantified by measuring the extracellular pH changes occurring in a cell suspension (in PBS) after addition of ammonium. By using this technique, in combination with specific inhibitors of various ion pumps, it was shown that ammonium ions are transported across the cytoplasmic membrane by the Na(+)K(+)2Cl(-)-cotransporter in both hybridoma and myeloma cells. Further, the Na(+)/H(+) exchanger, which regulates intracellular pH by pumping out protons, was shown to be active during ammonium exposure. The viability of hybridoma cells suspended in PBS and exposed to NH (inf4) (sup+) for only 90 min, was reduced by 11% (50% necrosis and 50% apoptosis). A control cell suspension did not loose viability during this time. Turning off the activity of the Na(+)/H(+) exchanger (by amiloride) during ammonium exposure decreased viability further, while inhibiting transport itself (by bumetanide) restored viability to the same level as for the control experiment with bumetanide alone. These results show that one effect of ammonia/ammonium on cell physiology is specifically related to the inward transport of ammonium ions by membrane bound ion pumps.


Bioaccumulation of heavy metals from wastewater through a Typha latifolia and Thelypteris palustris phytoremediation system.
Animal production is a source of heavy metals in livestock wastewater and also a key link in the food chain, with negative impacts on human and animal health. In intensive animal production systems, the most critical elements are zinc and copper. In order to development of innovative non-invasive strategies to reduce the environmental impact of livestock, this study assessed the ability of two plants, Typha latifolia and Thelypteris palustris, to bioaccumulate the heavy metals used in animal nutrition, from wastewater. Four mesocosms (width 2.0 m, length 2.0 m, 695 L of water, 210 kg of soil) were assembled outdoors at the Botanical Garden. Two of them were planted with T. latifolia (TL treated, n = 30; TL control, n = 30) and two with T. palustris (TP treated, n = 60; TP control, n = 60). In T0 a solution of a mineral additive premix (Zn 44.02 mg/L; Cu 8.63 mg/L) was dissolved in the treated mesocosms. At T0, d 15 (T1) and d 45 (T2) samples of roots, leaves, stems, soil and water were collected, dried, mineralized and analyzed using ICP-MS in order to obtain HMs content. We found that T. latifolia and T. palustris accumulate and translocate Zn, Cu from contaminated wastewater into plant tissues in a way that is directly related to the exposure time (T2 for Zn: 271.64 ± 17.70, 409.26 ± 17.70 for Cu: 47.54 ± 3.56, 105.58 ± 3.56 mg/kg of DM, respectively). No visual toxicity signs were observed during the experimental period. This phytoremediation approach could be used as an eco-sustainable approach to counteract the output of heavy metals.


Functional properties of chitosan-based films.
Chitosan-based films plasticized with glycerol were prepared by casting with the aim to obtain environmentally friendly materials for packaging applications. Different contents of glycerol were incorporated into chitosan solutions to improve mechanical properties and all films obtained were flexible and transparent. It was observed that the transparency and good behaviour of the films against UV radiation were not affected by chitosan molecular weight or glycerol content. Moreover, chitosan-based films exhibited excellent barrier properties against water vapour and oxygen, even with the addition of glycerol. The effect of the plasticizer on the properties has been explained using Fourier transform infrared (FTIR) spectroscopic analysis. The changes observed in the intensity of the bands showed that glycerol interacts with chitosan, which could be confirmed by total soluble matter (TSM).


Residual androgen binding in testicular feminization (TFM).
Most mutants with genetic androgen-resistance possess some level of androgen binding which exhibits properties of receptors. The present studies aim to determine whether the androgen binding activities in mutants are, or are related to, receptors. This binding portion is termed residual androgen receptors. We have examined several androgen-resistance mutants with testicular feminization (TFM). Putative androgen receptors from mice, rats, and humans with TFM have been compared, and at least three different types of residual receptors have been observed. They are discussed in relation to possible receptor defects and to differences in the nature of androgen-resistance associated with each of them.


Zinc uptake across the apical membrane of freshwater rainbow trout intestine is mediated by high affinity, low affinity, and histidine-facilitated pathways.
Zinc is both a vital nutrient and an important toxicant to aquatic biota. In order to understand the interplay between nutrition and toxicity, it will be important to determine the mechanisms and the factors that regulate zinc uptake. The mechanism of apical intestinal Zn(II) uptake in freshwater rainbow trout and its potential modification by the complexing amino acid histidine was investigated using brush-border membrane vesicles (BBMVs). Following characterisation of the BBMV preparation, zinc uptake in the absence of histidine was both time- and concentration-dependent and consisted of two components. A saturable phase of uptake was described by an affinity constant of 57+/-17 microM and a transport capacity of 1867+/-296 nmol mg membrane protein(-1) min(-1). At higher zinc levels (>500 microM) a linear, diffusive component of uptake was evident. Zinc transport was also temperature-dependent, with Q10 values suggesting zinc uptake was a carrier-mediated process. Zinc uptake by vesicles in the presence of histidine was correlated to a mono-histidine species (Zn(His)+) at all Zn(II) concentrations examined.


Flaming portal vein as a new color Doppler sign of portal gas: report of two cases.
Portal gas is relatively rare, and the majority of reported cases have shown it to have a close relation to bowel diseases. At present, portal exploration usually begins with color Doppler sonography, and clinicians now possess a good understanding of color Doppler findings of a wide spectrum of portal abnormalities. However, the color Doppler sign we present in this article has not been reported before. We report two cases of ischemic bowel disease in which B-mode ultrasound showed multiple hyperechoic spots moving in the portal vein; the color Doppler appearance was as if the portal vein was on fire (flaming portal vein sign). Knowledge of this simple color Doppler sign helps to improve the diagnostic strategies in patients with portal gas.


Platelet factor 4 (CXCL4/PF4) upregulates matrix metalloproteinase-2 (MMP-2) in gingival fibroblasts.
Periodontitis is a chronic inflammatory disease characterized by the release of matrix metalloproteinases (MMPs) from resident connective tissue cells in tooth-supporting tissues (periodontium). Platelet activation, and the attendant release of pro-inflammatory chemokines such as platelet factor 4 (CXCL4/PF4), are associated with periodontitis although the associated biochemical pathways remain undefined. Here we report that recombinant PF4 is internalized by cultured human gingival fibroblasts (hGFs), resulting in significant (p < 0.05) upregulation in both the production and release of MMP-2 (gelatinase A). This finding was corroborated by elevated circulating levels of MMP-2 (p < 0.05) in PF4-overexpressing transgenic mice, relative to controls. We also determined that PF4 induces the phosphorylation of NF-κB; notably, the suppression of NF-κB signaling by the inhibitor BAY 11-7082 abrogated PF4-induced MMP-2 upregulation. Moreover, the inhibition of surface glycosaminoglycans (GAGs) blocked both PF4 binding and NF-κB phosphorylation. Partial blockade of PF4 binding to the cells was achieved by treatment with either chondroitinase ABC or heparinase III, suggesting that both chondroitin sulfate and heparan sulfate mediate PF4 signaling. These results identify a novel pathway in which PF4 upregulates MMP-2 release from fibroblasts in an NF-κB- and GAG-dependent manner, and further our comprehension of the role of platelet signaling in periodontal tissue homeostasis.


Anisometropia and amblyopia in nasolacrimal duct obstruction.
To investigate an association of childhood nasolacrimal duct obstruction (NLDO) with anisometropia and amblyopia. The medical records of patients from newborn to 6 years of age with a diagnosis of NLDO seen from 2000 to 2010 were retrospectively reviewed. Data collected included age at onset of NLDO, laterality of NLDO, cycloplegic refractive error, determination of clinically significant anisometropia (defined as ≥1 D), and diagnosis of amblyopia with amblyopia subtype (anisometropic vs other). A total of 1,218 patients with NLDO were included. Of these, 887 cases (72.8%) were unilateral; 331 (27.2%), bilateral. Anisometropia was found in 67 (7.6%) unilateral cases and 12 (3.6 %) bilateral cases on initial examination (χ2=5.48, P < 0.01). Same-sided unilateral NLDO was significantly associated with greater hyperopia in the anisometropia patients (χ(2) = 33.01, P < 0.001). Follow-up data were available for 482 NLDO patients and revealed an additional 26 patients with anisometropia for a total of 105 of 1218 (8.6%). Of the 482 patients, 28 (5.8%) developed amblyopia, 16 cases of which were purely attributable to anisometropia. Of 41 patients with anisometropia who were in the follow-up, 9 (22%) developed amblyopia. Anisometropia occurred at a greater rate in unilateral NLDO patients compared with bilateral NLDO patients and occurred at a greater rate in this NLDO cohort than expected in the general pediatric population. Several patients with anisometropia developed clinical amblyopia. Measurement of cycloplegic refraction in all NLDO patients at initial examination should be considered. Periodic follow-up is appropriate for patients with NLDO and anisometropia.


[Sacral insufficiency, unexpected clinical entity as a cause of low back pain. Report of two cases].
sacral insufficiency fractures are a cause of debilitating pain in the elderly. These fractures were first described as a clinical entity in 1982. The bone in these patients is structurally weakened and often associated with diseases such as osteoporosis, cancer and immunological processes. This translates into back and pelvic pain unrelated to trauma. These fractures are usually caused by fatigue in most cases. Bone scans and MRI are the imaging studies with the most sensitivity for detecting sacral insufficiency. two patients with sacral insufficiency fractures who were studied by MRI and bone scan, in whom the diagnosis of sacral insufficiency was made, were treated by sacroplasty. sacral insufficiency is an underdiagnosed disease, caused by wide range of diseases, mainly osteoporosis. The studies of choice for diagnosis are MRI and bone scans. Techniques, such as percutaneous sacroplasty, produce significant improvements in pain scores and seem a suitable alternative for managing this disease.


Reduced synthesis and rapid esterification of cholesterol in the liver of hamsters with spontaneous hypercholesterolemia.
The rates of in vitro incorporation of [2-14C]mevalonate and of [2-14C]acetate were determined in the liver and in the ileum obtained from two groups of hamsters. The first (N-H) were conventional hamsters with normal cholesterolemia, the second (FEC-H) were hamsters which develop high levels of cholesterol in plasma and in the liver with age. In FEC-H, the levels of cholesterol reached 130 to 220 mg/100 ml in plasma and 600-2400 mg/100 g fresh tissue in the liver in contrast to about 100 mg and 350 mg respectively in the N-H group. The accumulation of cholesterol in the tissues of FEC-H was found to be associated with a strong decrease in the incorporation rate of the precursors into cholesterol, but above all, the distribution of the radioactivity derived from [2-14C]mevalonate between free cholesterol and esterified cholesterol was markedly different in the two groups of hamsters. In FEC-H, 78% of the radioactivity was found in the esters, as opposed to 10% found in the N-H group. Thus, the development of hypercholesterolemia with age in FEC-H might be related to alterations in the enzyme systems (ACAT, CEH) which modulate the level of cholesterol esters in the liver. No significant difference was observed between the two groups of hamsters either in the concentration of cholesterol or in the rate of cholesterogenesis in the ileum.


Pulmonary inflammatory myofibroblastic tumor invading the left atrium.
Inflammatory myofibroblastic tumor is a rare solid tumor that most often affects children and young adults. Although benign, the tumor may be very aggressive locally. We describe a 9-year-old boy with primary inflammatory myofibroblastic tumor of the left upper lobe involving the left atrium.


Nursing students' interprofessional socialisation and readiness for interprofessional learning: A cross-sectional research study.
Interprofessional education programs in university settings have facilitated the development of student attributes needed to become a team-player, understand roles and responsibilities of other health disciplines, and acquire knowledge to deliver patient-centred care. Although the benefits of interprofessional education are widely acknowledged, there is limited research on interprofessional socialisation within university contexts. To examine readiness of undergraduate nursing students for interprofessional learning and interprofessional socialisation. A cross-sectional design was used to examine the correlation between interprofessional learning and socialisation, and group differences between mode of study, year level, and prior healthcare experience. A large Australian regional university, across two campuses. A total of 103 undergraduate nursing students across year levels, including 58 enrolled on-campus, and 45 studying externally. Students completed an online survey using the Readiness for Interprofessional Learning Scale and the Interprofessional Socialisation and Valuing Scale. Data analyses included independent t-tests, and a one-way between subjects ANOVA. No significant differences in student readiness for interprofessional learning or interprofessional socialisation were found between on-campus and external modes of study and between healthcare experience and no prior healthcare experience. Participants with previous healthcare experience had significantly higher scores for interprofessional socialisation than those with no previous healthcare experience. Readiness for interprofessional learning and interprofessional socialisation and were not impacted by the students' mode of study; however, previous experience in the healthcare industry and duration of study significantly improved interprofessional socialisation skills. As nursing students advance through their study, they may experience interprofessional education opportunities that influence their perceived socialisation skills.


Mild hepatitis at recommended doses of acetaminophen in patients with evidence of constitutionally enhanced cytochrome P450 system activity.
Acetaminophen (paracetamol) is used throughout the world for pain relief and antipyresis in both children and adults. In many countries, it can be purchased without a medical prescription and it is also a common component of a number of over-the-counter remedies for colds, influenza and the like. Fasting, malnutrition and use of alcohol and/or other drugs are thought to play causal roles in hepatotoxicity associated with recommended doses of acetaminophen although liver injury provoked by therapeutic doses has also been observed in the absence of these factors. We describe two patients who experienced subclinical hepatotoxic reactions after taking acetaminophen at therapeutic doses. The results of an antipyrine metabolism test suggest the presence of constitutional hyperactivity of the cytochrome P450-dependent mixed function oxidative system in both patients. We hypothesize that the latter contributed to the hepatotoxicity and that it may play a role in idiosyncratic reactions to this drug.


Different effects of total flavonoids from Arachniodes exilis on human umbilical cord mesenchymal stem cells in vitro.
Traditional Chinese medicines are used in promotion of fractured bone healing and bone diseases. Some studies reported total flavonoids from plant can be used as an auxiliary source of exogenous.Use different methods to identify and verify effects of total flavonoids from Arachniodes exilis (TFAE) on human umbilical cord mesenchymal stem cells (HUCMSCs) in vitro.Concentrations of 1 and 5 μg/mL TFAE significantly increased ALPase activity in HUCMSCs compared to the other concentrations at days 3 and 7 (P < .05). RT-PCR showed that expression levels of osteogenic genes (Col1a1, OPN, Runx2 and Osx) were remarkably enhanced in HUCMSCs following treatment with different concentrations of TFAE for 9 days compared with 0 μg/mL TFAE group (control). The results showed that concentration < 5 μg/mL of TFAE induced osteogenic differentiation in HUCMSCs Alizarin red staining assays revealed that both TFAE and S1191 was significantly decreased (7.80 ± 0.66) compared with the TFAE group (16.00 ± 0.97) (P < .01). ALPase activity on days 3 and 7 was relatively lower in HUCMSCs grown in media supplemented with both S1191 and TFAE than that of in TFAE group only. The results indicated that osteogenic markers (Col1a1, OPN, Runx2 and Osx) were significantly downregulated in the TFAE + S1191 group in comparison to the control group. The expressions of Col1a and OPN in the TFAE + S1191 group decreased significantly (P < .01) by Western blotting.TFAE promotes the odonto/osteogenic differentiation of human UCMSCs via activation of ER.


Genome-wide association studies in Alzheimer's disease: a review.
Over the past decade, research aiming to disentangle the genetic underpinnings of late-onset Alzheimer's disease has mostly focused on the identification of common variants through genome-wide association studies. The identification of several new susceptibility genes through these efforts has reinforced the importance of amyloid precursor protein and tau metabolism in the cause of the disease and has implicated immune response, inflammation, lipid metabolism, endocytosis/intracellular trafficking, and cell migration in the cause of the disease. Ongoing and future large-scale genome-wide association studies, translational studies, and next-generation whole genome or whole exome sequencing efforts, hold the promise to map the specific causative variants in these genes, to identify several additional risk variants, including rare and structural variants, and to identify novel targets for genetic testing, prevention, and treatment.


Dynamic measurement of altered chemical messenger secretion after cellular uptake of nanoparticles using carbon-fiber microelectrode amperometry.
In this work, carbon-fiber microelectrode amperometry is used to characterize serotonin exocytosis from murine peritoneal mast cells cocultured with fibroblasts in the presence of Au nanoparticles. In the case of mast cell exposure to 1 nM 28 nm diameter spherical Au nanoparticles, there is a decrease of greater than 30% in the number of successful granule transport and fusion events, greater than 30% increase in the rate of intragranular matrix expansion, and greater than 20% increase in the number of secreted serotonin molecules per granule. These results suggest that nanoparticles interrupt the dense-core biopolymer intragranular matrix and present the potential for systematic studies showing how exocytotic function is influenced by nanoparticle size, shape, and composition.


Sex-specific effects of Cre expression in Syn1Cre mice.
The Cre-loxP system has been used to generate cell-type specific mutations in mice, allowing researchers to investigate the underlying biological mechanisms of disease. However, the Cre-recombinase alone can induce phenotypes that confound comparisons among genotypes if the appropriate Cre control is not included. In this study, we characterised behavioural, morphological and metabolic phenotypes of the pan-neuronal Syn1Cre line. We found that these mice possess intact neuromuscular parameters but have reduced exploratory activity and a male-specific increase in anxiety-like behaviour. Moreover, we observed a male-specific deficit in learning and long-term memory of Syn1Cre mice that could be a result of decreased visual acuity. Furthermore, we found that over-expression of human growth hormone (hGH) from Syn1Cre results in a male-specific reduction in body weight and femur length, potentially through decreased hepatic Igf1 expression. However, metabolic characteristics of Syn1Cre mice such as glucose metabolism, energy expenditure and feeding were unaffected by the presence of Syn1Cre. In conclusion, our data demonstrate that Syn1Cre expression has effects on behavioural and morphological traits. This finding highlights the importance of including the Cre control in all comparisons, while the male-specific effects on some phenotypes highlight the importance of including both sexes.


GeneScan analysis to detect clonality of T-cell receptor γ gene rearrangement in feline lymphoid neoplasms.
Lymphoid neoplasms are usually diagnosed on the basis of cytological and histopathological findings. However, in some cases, discrimination of lymphoid neoplasms from reactive lymphoid proliferation is difficult. Polymerase chain reaction (PCR) amplification of the complementarity-determining region (CDR) 3 of the T-cell receptor (TCR) γ gene can be used to assess clonality of T-cell populations as a supportive diagnostic tool for T-cell neoplasms. Because the length variation in the TCRγ CDR3 is relatively small, false positive results may occur in non-neoplastic T-cell populations in the absence of high-resolution analytical methods for PCR products. In the present study, a PCR assay system was developed to detect clonal TCRγ gene rearrangement in feline lymphoid cells using GeneScan analysis. Thirty T-cell neoplasms, 27 B-cell neoplasms, and 34 non-neoplastic tissues were subjected to the newly developed TCRγ gene rearrangement analysis. Clonal TCRγ gene rearrangement was detected in 26 of 30 (87%) T-cell neoplasms, 2 of 27 (7%) B-cell neoplasms, and 1 of 34 (3%) non-neoplastic tissues. To compare GeneScan analysis with conventional PAGE and heteroduplex analysis, 20 clonal and 20 polyclonal samples were subjected to both analyses. Most of the results were concordant between the 2 analyses; however, several clonal peaks (bands) appeared as a single band when analyzed via conventional PAGE with heteroduplex analysis in 4 of the 20 (20%) clonal samples as a result of the difference in resolution. The PCR assay system to detect clonal TCRγ gene rearrangement in feline lymphoid cells, using GeneScan analysis, would be a useful molecular diagnostic tool for feline T-cell neoplasms, with high fidelity.


Predictors of the decision to place developmentally disabled family members in residential care.
Critical circumstances that predict parents' requests for residential placements for developmentally disabled persons were described. The survey sample included 154 families who placed their disabled family member and 377 families who provided care at home. Empirical findings suggest that among families who place, the disabled persons are more impaired and have more severe behavior problems than do disabled persons being cared for at home. Families who place are more likely to be larger, headed by a single parent, suffer greater disruption of family life, and receive fewer direct client services. The policy implications of these findings were discussed.


Reduced specificity of the clonidine suppression test in patients with normal plasma catecholamine levels.
Although originally devised to discriminate between patients with pheochromocytoma and those with elevated plasma catecholamine levels for other reasons, the clonidine suppression test has recently been used in patients with normal resting catecholamine levels. Upon review of 49 patients evaluated for pheochromocytoma, 26 had elevated plasma norepinephrine levels and underwent clonidine suppression testing. Only one of 13 patients with sustained elevated norepinephrine levels before clonidine administration had a false-positive clonidine test result, in contrast to five of 13 patients whose pre-clonidine norepinephrine levels had decreased into the normal range. This difference was statistically significant (by chi-square) at p less than 0.05. Clonidine suppression testing for pheochromocytoma should be performed only in patients with elevated catecholamine levels, because it carries a higher false-positive rate in patients with normal resting norepinephrine levels; a more accurate diagnosis may be made in such patients using glucagon stimulation tests.


Clinical evaluation of prostate cancer gene 3 score in diagnosis among Chinese men with prostate cancer and benign prostatic hyperplasia.
Prostate cancer is the second most common diagnosed cancer in men. Due to the low specificity of current diagnosis methods for detecting prostate cancer, identification of new biomarkers is highly desirable. The study was conducted to determine the clinical utility of the prostate cancer gene 3 (PCA3) assay to predict biopsy-detected cancers in Chinese men. The study included men who had a biopsy at The Affiliated Sixth People's Hospital of Shanghai Jiao Tong University from January 2013 to December 2013. Formalin-fixed, paraffin-embedded tissue blocks were used to test PCA3 and prostate-specific antigen (PSA) mRNA. The diagnostic accuracy of the PCA3 score for predicting a positive biopsy outcome was studied using sensitivity and specificity, and it was compared with PSA. The probability of a positive biopsy increased with increasing PCA3 scores. The mean PCA3 score was significantly higher in men with prostate cancer (198.03, 95 % confidence interval [CI] 74.79-321.27) vs benign prostatic hyperplasia (BPH) (84.31, 95 % CI 6.47-162.15, P < 0.01). The PCA3 score (cutoff 35) had a sensitivity of 85.7 % and specificity of 62.5 %. Receiver operating characteristic analysis showed higher areas under the ROC curve for the PCA3 score vs PSA, but without statistical significance. Increased PCA3 in biopsy tissue correlated with prostate cancer and the PCA3 assay may improve the diagnosis efficacy as the PCA3 score being independent of PSA level. The diagnostic significance of urinary PCA3 testing should be explored in future study to determine the prediction value in guiding biopsy decision as the clinical relevance of current study was limited for PCA3 testing based on biopsy tissue in a limited number of Chinese men.


A linkage disequilibrium-based approach to position unmapped SNPs in crop species.
High-density SNP arrays are now available for a wide range of crop species. Despite the development of many tools for generating genetic maps, the genome position of many SNPs from these arrays is unknown. Here we propose a linkage disequilibrium (LD)-based algorithm to allocate unassigned SNPs to chromosome regions from sparse genetic maps. This algorithm was tested on sugarcane, wheat, and barley data sets. We calculated the algorithm's efficiency by masking SNPs with known locations, then assigning their position to the map with the algorithm, and finally comparing the assigned and true positions. In the 20-fold cross-validation, the mean proportion of masked mapped SNPs that were placed by the algorithm to a chromosome was 89.53, 94.25, and 97.23% for sugarcane, wheat, and barley, respectively. Of the markers that were placed in the genome, 98.73, 96.45 and 98.53% of the SNPs were positioned on the correct chromosome. The mean correlations between known and new estimated SNP positions were 0.97, 0.98, and 0.97 for sugarcane, wheat, and barley. The LD-based algorithm was used to assign 5920 out of 21,251 unpositioned markers to the current Q208 sugarcane genetic map, representing the highest density genetic map for this species to date. Our LD-based approach can be used to accurately assign unpositioned SNPs to existing genetic maps, improving genome-wide association studies and genomic prediction in crop species with fragmented and incomplete genome assemblies. This approach will facilitate genomic-assisted breeding for many orphan crops that lack genetic and genomic resources.


The effect of internal voids in membrane proteins: high-pressure study of two photochemical reaction centres from Rhodobacter sphaeroides.
The effect of application of high pressure on the carotenoid-containing bacterial reaction centre from Rhodobacter sphaeroides strain 2.4.1 was studied, and compared to recent experiments performed on its carotenoid-less counterpart, isolated from strain R26.1. Our results indicate that the cavity created by the absence of carotenoid contributes to localised differences in protein compressibility when using the intrinsic chromophores as molecular probes. Differential stability of the electronic transitions of the primary electron donor under high hydrostatic pressure is observed, dependent on the presence of the carotenoid cofactor. This suggests that the transition intensity loss is induced by a slight change of the primary electron donor structure, allowed by the void created by the absence of the carotenoid molecule.


The Interaction of Deworming, Improved Sanitation, and Household Flooring with Soil-Transmitted Helminth Infection in Rural Bangladesh.
The combination of deworming and improved sanitation or hygiene may result in greater reductions in soil-transmitted helminth (STH) infection than any single intervention on its own. We measured STH prevalence in rural Bangladesh and assessed potential interactions among deworming, hygienic latrines, and household finished floors. We conducted a cross-sectional survey (n = 1,630) in 100 villages in rural Bangladesh to measure three exposures: self-reported deworming consumption in the past 6 months, access to a hygienic latrine, and household flooring material. We collected stool samples from children 1-4 years, 5-12 years, and women 15-49 years. We performed mini-FLOTAC on preserved stool samples to detect Ascaris lumbricoides, Enterobius vermicularis, hookworm, and Trichuris trichiura ova. Approximately one-third (32%) of all individuals and 40% of school-aged children had an STH infection. Less than 2% of the sample had moderate/heavy intensity infections. Deworming was associated with lower Ascaris prevalence (adjusted prevalence ratio (PR) = 0.53; 95% CI 0.40, 0.71), but there was no significant association with hookworm (PR = 0.93, 95% CI 0.60, 1.44) or Trichuris (PR = 0.90, 95% CI 0.74, 1.08). PRs for hygienic latrine access were 0.91 (95% CI 0.67,1.24), 0.73 (95% CI 0.43,1.24), and 1.03 (95% CI 0.84,1.27) for Ascaris, hookworm, and Trichuris, respectively. Finished floors were associated with lower Ascaris prevalence (PR = 0.56, 95% CI 0.32, 0.97) but not associated with hookworm (PR = 0.48 95% CI 0.16,1.45) or Trichuris (PR = 0.98, 95% CI 0.72,1.33). Across helminths and combinations of exposures, adjusted prevalence ratios for joint exposures were consistently more protective than those for individual exposures. We found moderate STH prevalence in rural Bangladesh among children and women of childbearing age. This study is one of the first to examine independent and combined associations with deworming, sanitation, and hygiene. Our results suggest that coupling deworming with sanitation and flooring interventions may yield more sustained reductions in STH prevalence.


Survey of formaldehyde, acetaldehyde and oligomers in polyethylene terephthalate food-packaging materials.
Polyethylene terephthalate (PET) is frequently used as a packaging material for beverage bottles, fruit and vegetable trays, and egg crates in Japan. Levels of formaldehyde (FA), acetaldehyde (AA) and PET oligomers in various PET food packaging were determined. PET samples were initially dissolved in trifluoroacetic acid with 2,4-dinitrophenylhydrazine to derivatize formaldehyde and acetaldehyde to their dinitrophenylhydrazones. The stable derivatives along with the oligomers were analysed using HPLC with ultraviolet light detection at 360 and 254 nm, respectively. The PET pellets contained 3.5-12.4 microg g-1 AA and 4.0-7.2 mg g-1 oligomers, while FA was below the determination limit. FA, AA and oligomer levels in Japanese bottles were 0.6-3.0 microg g-1, 8.4-25.7 microg g-1 and 5.0-8.7 mg g-1, ND-1.6 microg g-1, 5.0-13.1 microg g-1 and 4.9-8.2 mg g-1 in French and Italian bottles, and ND-1.2 microg g-1, 9.1-18.7 microg g-1 and 5.6-8.0 mg g-1 in US and Canadian bottles, respectively. Compared with European bottles, Japanese bottles contain higher FA and AA levels. In sheet-moulding products, their contents were determined as ND-1.1 microg g-1, 11.5-43.1 microg g-1 and 4.6-9.2 mg g-1, respectively. The results show that sheet-moulding products contain lower FA and higher AA in comparison with bottles. FA and AA are considered to be generated from PET during the heating process for moulding the pellets to bottles or sheet-moulding articles and de-aeration during the sheet-moulding process is effective in removing FA. In contrast, the level of the oligomers remains unchanged during the moulding process from pellets to bottles or sheet products.


Multiple avascular necrosis of bone and polyarticular septic arthritis in patients with systemic lupus erythematosus.
Avascular necrosis of bone (AVN) and osteoarticular infection share similar risk factors in systemic lupus erythematosus (SLE) patients. However, their coincidental development in SLE has rarely been described. We describe four cases of AVN complicated by Staphylococcus aureus infection in SLE. Patients were identified by retrospectively reviewing an SLE cohort followed between 1979 and 2003. A review of the literature from 1960 until 2003 was also done. Among 315 SLE patients, four developed joint infection by S. aureus following or coincidentally with AVN. All presented multifocal disease with severe or relapsing course, resulting in severe incapacity. The clinical course suggests that AVN developed first in active SLE patients with positive antiphospholipid (aPL) antibodies treated with high-dose corticosteroids (CS), and subsequent bone infarcts favor infection. Our patients often required prolonged antibiotic therapy and surgical treatment. Active SLE patients with aPL antibodies on high-dose CS seem at high risk of developing multiple AVN complicated by infection. Avascular necrosis and bone or joint infection by S. aureus in these patients is a major complication that leads to severe joint destruction and disability.


Comparison of facemask therapy effects using skeletal and tooth-borne anchorage.
To investigate long-term outcomes of dentoskeletal changes induced by facemask therapy using skeletal anchorage in Class III patients and compare them to those of conventional tooth-borne anchorage. This retrospective study included 20 patients who received facemask (FM) therapy with miniplates as anchorage for maxillary protraction (Miniplate/FM group, 10.6 ± 1.1 years old [mean ± SD]) and 23 patients who were treated with facemask with rapid maxillary expander (RME/FM group, 10.0 ± 1.5 years old [mean ± SD]). Dentoskeletal changes were evaluated using lateral cephalograms at pretreatment (T1), after facemask therapy (T2), and at the post-pubertal stage (T3). Cephalometric changes were compared between groups and clinical success rates at T3 were evaluated. SNA and A to N perpendicular to FH increased significantly more in the Miniplate/FM group than in the RME/FM group when comparing short-term effects of facemask therapy (T1-T2). ANB, Wits appraisal, Angle of convexity, mandibular plane angle, and overjet decreased significantly more in the RME/FM group than in the Miniplate/FM group after facemask therapy (T2-T3). A more favorable intermaxillary relationship was observed in the Miniplate/FM group than in the RME/FM group in long-term observations (T1-T3). Clinical success rate at T3 was 95% in the Miniplate/FM group and 85% in the RME/FM group. Facemask therapy with skeletal anchorage showed a greater advancement of the maxilla and more favorable stability for correction of Class III malocclusion in the long-term than conventional facemask therapy with tooth-borne anchorage.