Borinium cations as sigma-B-H ligands in osmium complexes.
The complex OsH(2)Cl(2)(P(i)Pr(3))(2) reacts with pinacolborane, Me(2)NH-BH(3), and (t)BuNH(2)-BH(3) to give the complexes OsH(2)Cl{eta(2)-HBOC(CH(3))(2)C(CH(3))(2)OBpin}(P(i)Pr(3))(2) and OsH(2)Cl(eta(2)-HBNR(1)R(2))(P(i)Pr(3))(2) (R(1) = R(2) = Me; R(1) = H, R(2) = (t)Bu) containing monosubstituted alkoxy- and amidoborinium cations coordinated as sigma-B-H ligands. The process is proposed to take place via the electrophilic 14-valence-electron fragment OsHCl(P(i)Pr(3))(2), which promotes hydride transfer from the corresponding borane to the osmium atom.


Inhibition of peptide aggregation by lipids: insights from coarse-grained molecular simulations.
The amyloidogenic peptide apolipoprotein C-II(60-70) is known to exhibit lipid-dependent aggregation behaviour. While the peptide rapidly forms amyloid fibrils in solution, fibrillization is completely inhibited in the presence of lipids. In order to obtain molecular-level insights into the mechanism of lipid-dependent fibril inhibition, we have employed molecular dynamics simulations in conjunction with a coarse-grained model to study the aggregation of an amyloidogenic peptide, apoC-II(60-70), in the absence and presence of a short-chained lipid, dihexanoylphosphatidylcholine (DHPC). Simulation of a solution of initially dispersed peptides predicts the rapid formation of an elongated aggregate with an internal hydrophobic core, while charged sidechains and termini are solvent-exposed. Inter-peptide interactions between aromatic residues serve as the principal driving force for aggregation. In contrast, simulation of a mixed peptide-DHPC solution predicts markedly reduced peptide aggregation kinetics, with subsequent formation of a suspension of aggregates composed of smaller peptide oligomers partially inserted into lipid micelles. Both effects are caused by strong interactions between the aromatic residues of the peptide with the lipid hydrophobic tails. This suggests that lipid-induced aggregate inhibition is partly due to the preferential binding of peptide aromatic sidechains with lipid hydrophobic tails, reducing inter-peptide hydrophobic interactions. Furthermore, our simulations suggest that the morphology of peptide aggregates is strongly dependent on their local lipid environment, with greater contacts with lipids resulting in the formation of more elongated aggregates. Finally, we find that peptides disrupt lipid self-assembly, which has possible implications for explaining the cytotoxicity of peptide oligomers.


Short communication: Nitazoxanide inhibits HIV viral replication in monocyte-derived macrophages.
We document the anti-HIV activity of nitazoxanide (NTZ), the first member of the thiazolide class of antiinfective drugs, originally effective against enteritis caused by Cryptosporidium parvum and Giardia lamblia. NTZ has been administered extensively worldwide, with no severe toxicities associated with its use. Here, we show for the first time that NTZ decreases HIV-1 replication in monocyte-derived macrophages (MDM) if present before or during HIV-1 infection. This NTZ effect is associated with downregulation of HIV-1 receptors CD4 and CCR5, and increasing gene expression of host cell anti-HIV resistance factors APOBEC3A/3G and tetherin. As NTZ is already in clinical use for other conditions, this newly described anti-HIV activity in MDM may facilitate innovative intensification strategies against HIV-1 when combined with current antiretroviral drug regimens.


Purification of LAT-Containing Membranes from Resting and Activated T Lymphocytes.
In T lymphocytes, the immune synapse is an active zone of vesicular traffic. Directional transport of vesicular receptors and signaling molecules from or to the immune synapse has been shown to play an important role in T-cell receptor (TCR) signal transduction. However, how vesicular trafficking is regulating the activation of T cells is still a burning question, and the characterization of these intracellular compartments remains the first step to understand this process. We describe herein a protocol, which combines a separation of membranes on flotation gradient with an affinity purification of Strep-tagged fusion transmembrane proteins with Strep-Tactin® resin, allowing the purification of membranes containing the Strep-tagged molecule of interest. By keeping the membranes intact, this protocol leads to the purification of molecules physically associated with the Strep-tagged protein as well as of molecules present in the same membrane compartment: transmembrane proteins, proteins strongly associated with the membranes, and luminal proteins. The example shown herein is the purification of membrane compartment prepared from T lymphocytes expressing LAT fused to a Strep-tag.


Biomedical and psychosocial factors influencing transtibial prosthesis fit: a Delphi survey among health care professionals.
We aimed to reach consensus among professionals caring for prosthesis users, on definitions of biomedical and psychosocial factors, to assess their influence on fit of transtibial prosthesis and to identify new factors. A three-round, internet-based, Delphi survey was conducted among experts recruited via the Dutch National Amputee and Prosthesis Work Group. The main outcome measure was consensus among care professionals on statements concerning new and presented biomechanical and psychosocial factors that influence transtibial prosthesis fit. Fifty-four experts participated in the survey, and consensus was reached on 67% (46/69) of all statements. Consensus on statements relevant for good prosthesis fit was reached in most of the statements concerning psychosocial factors and on statements concerning the biomedical factors "prosthesis support and suspension". Least consensus was reached on statements concerning the biomedical factor "skin problems and pain in the residual limb". Biomedical and psychosocial factors influence transtibial prosthesis fit. Consensus was reached among care professionals in a majority of the presented statements concerning these factors. Implications for Rehabilitation Prosthesis fit and comfort is suboptimal in many prosthesis users. Both biomedical and psychosocial factors influence fit. Biomedical and psychosocial factors should be checked during transtibial prosthesis prescription to achieve and maintain an optimal fit. Consensus on many factors influencing prosthesis fit is achieved among care professionals. Consensus was largest regarding prosthesis support and suspension and least regarding skin problems and pain in the residual limb. This consensus contributes to systematic assessment of prosthesis fit.


Maternal infections. Problems and prevention.
Prenatal care; proper aseptic technique in labor, delivery, and postpartum areas; and general postpartum hygiene are important factors in preventing nosocomial infections. However, if these infections do occur, they must be promptly recognized and early signs and symptoms reported in order that proper therapy may be instituted.


Generation of aberrant forms of DFF40 concurrent with caspase-3 activation during acute and chronic liver injury in rats.
DNA fragmentation factors (DFF) form protein complexes consisting of nuclease DFF40/CAD and inhibitory chaperon DFF45/ICAD. Although activated caspase-3 has been shown to cleave DFF complexes with the release of active DFF40 and DNA fragmentation, the organ-specific mechanisms of DFF turnover during liver injury accompanied by massive apoptosis are unclear. In this study, we investigated hepatic profile of DFF40-immunopositive proteins in two models of liver injury in rats: acute ischemia/reperfusion (I/R) and chronic alcohol administration. We show that DFF40-like proteins occur in intact rat liver mainly as a 52kDa protein. Hepatic I/R-induced caspase-3 activation and a time-dependent accumulation of DFF40-positive protein fragments (40 and 20kDa), most likely via specific caspase-3 cleavage as evidenced by in vitro digestion of intact liver tissue with recombinant caspase-3. In addition, immunoprecipitation with DFF40 followed by Western blot with active caspase-3 antibody revealed the presence of active caspase-3 in DFF40-immunopositive 20kDa proteins. Chronic alcohol administration in rats also resulted in a dose-dependent fragmentation of DFF40 proteins similar to I/R injury. Collectively, these data demonstrate that DFF40 immunopositive proteins exist in the liver as distinct, tissue-specific molecular forms that may be processed by caspase-3 during both acute and chronic liver injury.


Study on the relationship between SLCO1B1 and ApoE gene polymorphisms and the risk of coronary heart disease in the Mongolian population.
Objective This study aimed to analyze the influence of SLCO1B1 and APOE gene polymorphisms on coronary heart disease in Mongolian population who living in Ordos area. Methods From January 2019 to June 2020, 200 Mongolian patients with coronary heart disease admitted to our hospital and other banner hospitals were selected as the case group. At the same time, 150 randomly selected healthy Mongolian people from medical examination centers comprised the control group. The polymorphisms of SLCO1B1 (388A>G, 521 T > C) and ApoE (388 T > C, 526 C > t) were detected by real-time polymerase chain reaction. Combined with environmental data, the effect of gene polymorphism on coronary heart disease was explored. Results Both SLCO1B1 and ApoE polymorphisms satisfied Hardy-Weinberg equilibrium. The SLCO1B1 genotype *1a/*1b showed the highest frequency in the case group, accounting for 35.0%, while The SLCO1B1 genotype *1b/*1b showed the highest frequency in the control group, accounting for 32.0%. Allele *1b was the most commonly seen allele in both the case group and control group (57.8% and 53.7%, respectively). Meanwhile, The difference in the distribution of SLCO1B1 *1a/*15 genotype between the two groups was statistically significant (P < .05). Conclusion The results showed that the SLCO1B *1a/*15 genotype, ApoE ε3 /ε3 genotype, and ε3 allele reduced the risk of coronary disease in the Mongolian population, making them protective genes against this disease, while the ApoE ε4 allele increased the risk of coronary disease, making it a coronary disease risk factor.


Efficacy of screen-capture tutorials in literature search training: a pilot study of a research method.
This pilot study evaluated a research method for examining the efficacy of screen capture tutorials in teaching database search skills. This is not a results-oriented paper but rather describes the facets and testing of a mixed methods protocol. The lessons learned can be applied to a result-oriented study with a larger sample size and to the development of methods for similar studies. The protocol tried to balance control of variables with observing behavior in the natural setting. A combination of concept maps, an information stage questionnaire, and screen recordings provided rich information about health practitioners' research questions and search strategies.


Retrograde nailing of femoral fractures.
Retrograde nailing represents an established fixation method for fractures of the distal femur and offers in femoral shaft fractures an alternative to the existing technique of antegrade nailing. The aim of this study was to investigate in a retrospective analysis the results of retrograde nailing in distal femoral fractures and selected cases of femoral shaft fractures. Emphasis was posed on long- term functional outcome, especially in daily activities. Retrograde femoral nailing was used from 1999 until 2006 in two Level 1 trauma centers for the treatment of distal femoral (AO/ASIF-type 33) and femoral shaft fractures (AO/ASIF - type 32) in 40 patients with 41 fractures. The mean age of patients was 63,7 years (min: 21 / max.: 103) and 70, 7% presented with ipsilateral local pathologies or associated entities. A pre-existing reduced activity level was found in 12 /40 patients (30%) and was equally caused by neurologic conditions and geriatric entities. Indication for retrograde nailing was left in AO/ASIF fracture-type 33 to the individual estimation of the surgeon, while it was restricted in AO /ASIF fracture- type 32 to problematic cases. For fracture fixation the Distal Femoral Nail (28/41 68,3%) of Synthes Int.(R) and a spupracondylar /; retrograde modified sc - UFN (13 /41 31,7%) produced by Synthes(R) Austria were used. Patients were followed till fracture healing and invited to a functional follow-up using the Lysholm / Gilquist score and the Tegner /Lysholm score. Osseous healing occured in shaft fractures in 18,1 weeks on an average compared to 16,5 weeks in supracondylar fractures. Postoperative complications requiring re-intervention were seen in 6/41 (14,6%) fractures. 28/40 patients (70%) were evaluated with a mean follow-up period of 20,4 months using the functional score of Lysholm /Gilquist and the activity score of Tegner/ Lysholm. Both scores were balanced among shaft fractures and distal femoral fractures (Lysholm - mean: 87,7 pts shaft. vs. 80,1 pts. distal Tegner-mean: 5,2 pts. shaft vs. 3,9 pts. distal), while motion showed better results in shaft fractures (arc of motion - mean: 120 degrees ) than in distal femoral fractures (arc of motion - mean: 105). Despite a high age of patients (average 63,7 years) and a reduced activity level with many local co-morbitities, retrograde nailing resulted in the majority (95,1%) in reliable osseous healing. Thus, achievement of a painless fracture-site and a stable knee-joint provides early mobilization even in problematic cases. Impairment of functional outcome, mirrored in an over-all Lysholm /Gilquist score of 83,3 pts. and an over-all Tegner /Lysholm score of 4,4 pts. , was mainly related to preexisting restrictions of the loco-motor system. Retrograde nailing represents a reliable fixation method for extra-articular (33 - A1-3) and simple intra-articular (33 - C1-2) fractures of the supracondylar area. In femoral shaft fractures retrograde inserted nails offer a valuable alternative, especially when the proximal femoral approach is obstructed.


[The progress of therapeutic hypothermia for patients with comatose survivors of out-of-hospital cardiac arrest this century].
Two randomized clinical trials were reported using mild therapeutic hypothermia following cardiac arrest in the 2002. One is the multicenter randomized clinical trial projected by The Hypothermia after Cardiac Arrest Study Group. The other one was performed by four centers in Australia. Two trials significantly showed better outcome in the hypothermia group compared with the normothermia group. There were some differences between Europe study and Australia study, although their outcome was doing very well. We will discuss cooling techniques (blanket or ice pack or cold saline intravenously), selection of patients (ventricular fibrillation or pulseless electrical activity or asystole), timing of cooling (as possible as earlier or within 3 hours or 6 hours) and monitoring in the hypothermia group in future. In addition, clinicians including cardiologists, intensivists, emergency physicians and neurologists, should work together to practice protocols for mild hypothermia treatment.


Dopamine Agonists in the Management of Non-Functioning Pituitary Adenomas.
Non-functioning pituitary tumors (NFPA) are usually large at the time of diagnosis and present with symptoms caused by compression on the neighbouring structures. Transsphenoidal resection of the tumor is the first-line treatment but in many cases complete tumor resection cannot be attained. Close follow-up with repeated hormonal assessment and pituitary imaging is recommended after surgery. During follow-up of the tumor remnant sometimes radiotherapy is used to stop or prevent tumor progression. Medical treatment with dopamine agonists (DA) is the mainstay in the management of prolactinomas. For NFPA several small series or case reports suggested beneficial effects with tumor shrinkage in some cases. The aim of the current paper is to summarize the available evidence related to the potential efficacy of DA medical treatment in NFPA while underlining that in the absence of randomized, placebo-controlled studies, no final conclusion on the efficacy of these drugs in the treatment of NFPA can be drawn.


A super-infection in the cornea caused by Stemphylium, Acremonium, and α-Streptococcus.
Polymicrobial keratitis with fungus and bacteria can lead to blindness and is challenging to treat. Here, we introduce a case of fungal keratitis caused by two different strains in addition to definite bacterial super-infection caused by an α-Streptococcus sp., and describe the importance of microscopic examination. A 74-year-old woman, who had a past history of infection with leprosy, presented with conjunctival hyperaemia, pain, and corneal opacity in her right eye. Under the presumptive diagnosis of infectious keratitis, corneal scrapings were stained by various reagents and inoculated on several agar plates. Microscopic findings of the scrapings revealed fungi and a small number of Gram-positive cocci. Multiple anti-fungal therapies with levofloxacin ophthalmic solution were administered. Although empiric treatment was initially effective, keratitis recurred 10 days after its initiation. Repeated corneal scraping revealed an abundance of Gram-positive chain cocci and a small amount of fungi, resulting in the switching of an antibiotic medication from levofloxacin to moxifloxacin and cefmenoxime. Keratitis resolved gradually after the conversion. Stemphylium sp., Acremonium sp., and α-Streptococcus sp. were simultaneously isolated from the corneal scrapings. To the best of our knowledge, this is the first case of fungal keratitis caused by Stemphylium sp., and also the first case of super-infection in the cornea caused by two different fungi and one bacterium. Microscopic examination of the corneal scrapings was beneficial in rapid decision of changing to appropriate drug according to the dominancy of pathogenicity.


Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma.
Hodgkin's disease and non-Hodgkin's B-cell lymphoma occasionally occur in the same patient. The identification of a common precursor of the two types of lymphoma would show definitively that Reed-Sternberg cells originate from B cells. We studied lymphomas from two patients, one with a composite lymphoma (classic Hodgkin's disease and a follicular lymphoma in the same lymph node) and the other with a T-cell-rich B-cell lymphoma that was followed by classic Hodgkin's disease. Single Reed-Sternberg cells and non-Hodgkin's lymphoma cells from frozen sections were micromanipulated. The rearranged immunoglobulin variable-region genes (V genes) of the heavy and light chains were amplified by the polymerase chain reaction from genomic DNA and sequenced. In both patients, the Reed-Sternberg cells were related clonally to the non-Hodgkin's lymphoma B cells. The V genes carried somatic mutations (a hallmark of germinal-center B cells and their descendants). In both patients, some somatic mutations were shared by the Reed-Sternberg and non-Hodgkin's lymphoma cells, whereas other somatic mutations were found exclusively in one or the other cell type. In two patients with classic Hodgkin's disease and non-Hodgkin's B-cell lymphoma, we identified a common B-cell precursor, probably a germinal-center B-cell, for both lymphomas. This finding suggests that the two types of lymphoma underwent both shared and distinct transforming events and provides proof of the B-cell derivation of Reed-Sternberg cells in classic Hodgkin's disease.


Molecular characterization of Moniezia sichuanensis in captive musk deer (Moschus berezovskii).
The musk deer (Moschus berezovskii) is an economically important species from which musk is extracted and used in perfumes and medicines. Cestodes (parasitic flatworms) of the genus Moniezia are important parasites that infect this endangered species and can cause high mortality in young deer. In 1982, Moniezia (S.) sichuanensis sp. nov. was described from a specimen obtained from wild musk deer. The new species was distinct from the other described species of Moniezia by the sawtooth-shaped interproglottidal glands, the thick vagina and the absence of a cirrus spine. In the present study, 12 cestodes collected from musk deer were examined morphologically and confirmed to be M. sichuanensis. Molecular characterization was performed by amplifying and comparing the internal transcribed spacer 1 (ITS1) and 5.8S rRNA gene (ITS1-5.8S) of ribosomal DNA with available sequences from other Moniezia species. The amplified sequences ranged from 761 to 764 bp and similarity ranged from 98.7-100%, compared to 67.8-92.4% with other Moniezia spp. Construction of a phylogenetic tree using the neighbour-joining method indicated that all 12 ITS1-5.8S sequences formed a single clade, confirming M. sichuanensis as a separate species. This study provides novel molecular insight into M. sichuanensis that could prove useful for future diagnosis and control of monieziasis in musk deer.


Developing treatments for cognitive deficits in schizophrenia: the challenge of translation.
Schizophrenia is a life-long debilitating mental disorder affecting tens of millions of people worldwide. The serendipitous discovery of antipsychotics focused pharmaceutical research on developing a better antipsychotic. Our understanding of the disorder has advanced however, with the knowledge that cognitive enhancers are required for patients in order to improve their everyday lives. While antipsychotics treat psychosis, they do not enhance cognition and hence are not antischizophrenics. Developing pro-cognitive therapeutics has been extremely difficult, however, especially when no approved treatment exists. In lieu of stumbling on an efficacious treatment, developing targeted compounds can be facilitated by understanding the neural mechanisms underlying altered cognitive functioning in patients. Equally importantly, these cognitive domains will need to be measured similarly in animals and humans so that novel targets can be tested prior to conducting expensive clinical trials. To date, the limited similarity of testing across species has resulted in a translational bottleneck. In this review, we emphasize that schizophrenia is a disorder characterized by abnormal cognitive behavior. Quantifying these abnormalities using tasks having cross-species validity would enable the quantification of comparable processes in rodents. This approach would increase the likelihood that the neural substrates underlying relevant behaviors will be conserved across species. Hence, we detail cross-species tasks which can be used to test the effects of manipulations relevant to schizophrenia and putative therapeutics. Such tasks offer the hope of providing a bridge between non-clinical and clinical testing that will eventually lead to treatments developed specifically for patients with deficient cognition.


White blood cell transcriptome correlates with renal function in acute heart failure.
It is notoriously difficult to classify patients with acute heart failure (AHF) because of variations in clinical presentation, different etiologies, the impact of comorbidities, and variable prognoses. In this study, we used DNA whole-genome microarrays to classify 24 patients with AHF based on the transcriptome of their peripheral blood nuclear cells. The main purpose was to verify whether any transcriptomic sub-clusters had clinical correlations. We identified two distinct groups of transcriptomic profiles that correlated with normal (1.125 mg/dL) and increased (1.783 mg/dL) mean blood creatinine concentrations. These two subgroups of patients (n = 12) differed in the expression of more than 6000 genes and 108 signaling pathways. The most significant regulated signaling pathway was the aldosterone-regulated sodium reabsorption pathway and the most significant regulated genes included the angiotensin-converting enzyme gene. This suggests that kidney impairment in patients with AHF is related to dysregulation of the renin-angiotensin-aldosterone system. The interesting findings of our study were the significant differences in expression of genes belonging to the aldosterone-regulated signaling pathway: Na+/K+ transporting ATPase and NEDD4L (neuronal precursor cell expressed developmentally down-regulated 4-like) between patients with and without renal dysfunction. Future studies of blood-cell transcriptomic profiles in patients with AHF will provide further insights into the molecular pathogenesis of this cardiorenal disorder.


PT-symmetric solitons and parameter discovery in self-defocusing saturable nonlinear Schrödinger equation via LrD-PINN.
We propose a physical information neural network with learning rate decay strategy (LrD-PINN) to predict the dynamics of symmetric, asymmetric, and antisymmetric solitons of the self-defocusing saturable nonlinear Schrödinger equation with the PT-symmetric potential and boost the predicted evolutionary distance by an order of magnitude. Taking symmetric solitons as an example, we explore the advantages of the learning rate decay strategy, analyze the anti-interference performance of the model, and optimize the network structure. In addition, the coefficients of the saturable nonlinearity strength and the modulation strength in the PT-symmetric potential are reconstructed from the dataset of symmetric soliton solutions. The application of more advanced machine learning techniques in the field of nonlinear optics can provide more powerful tools and richer ideas for the study of optical soliton dynamics.


How Much Time Before Attempting Compulsory Licensing of Pharmaceuticals? A Non-parametric Event History Model With P-splines.
Compulsory licensing (CL), provided by the Agreement on Trade-Related Aspects of Intellectual Property Rights, enables countries, including high-income countries, to ensure the protection of public health in the context of stringent intellectual property regimes. This study investigated associations between the time to attempted CL and a series of factors at the drug and country level. We used a dataset of all attempted CL that occurred from 1995 to 2014, calculated the duration as the difference in years between the year of global marketing of a certain drug and the year of attempted CL in a certain country, and applied a nonparametric event history model. We found that the Doha Declaration was quite effective in shortening the time to attempted CL. Additionally, even though global justice movements have encouraged some countries to attempt CL for various medicines since 2012, the time to CL attempts in this period became significantly longer compared to those that occurred immediately after the Doha Declaration. Our findings show that the subject of CL has not successfully expanded to oncology medicines from HIV/AIDS medicines and that recently approved medicines are not yet subjects of CL. Furthermore, our duration model suggests a learning-by-doing effect in attempting CL: previous experience of CL not only triggers CL for the same drugs in other countries but also accelerates CL for other drugs within the country.


Diode dosimetry of 103Pd model 200 seed in water phantom.
The relative dose distribution around the 103Pd model 200 implant seed was measured with a computerized data acquisition system employing a p-n junction silicon diode immersed in a water phantom. Data are acquired in polar coordinates by computer control of (1) the diode distance from the seed center and (2) the rotation angle of seed about a transverse axis. Transverse axis data are compared with thermoluminescent dosimeter (TLD) measurements and a Monte Carlo calculation by others.


A risk score for predicting postoperative complications in non-intubated thoracic surgery.
The risk factors for postoperative complications in non-intubated video-assisted thoracoscopic surgery (VATS) have not been observed before. Here to develop a simple risk score to predict the risk of postoperative complications for patients who scheduling non-intubated VATS, which is beneficial to guide the clinical interventions. A total of 1,837 patients who underwent non-intubated VATS were included from January 2011 to December 2018. A development data set and a validation data set were allocated according to an approximate 3:2 ratio of total cases. The stepwise logistic regression was used to establish a risk score model, and the methods of bootstrap and split-sample were used for validation. Multivariable analysis revealed that the forced expiratory volume in the first second in percent of predicted, the anesthesia method, blood loss, surgical time, and preoperative neutrophil ratio were risk factors for postoperative complications. The risk score was established with these 5 factors, varied from 0 to 53, with the corresponding predicted probability of postoperative complications occurrence ranged from 1% to 92% and was calibrated (Hosmer-Lemeshow χ2 =6.261; P=0.618). Good discrimination was acquired in the development and validation data sets (C-statistic 0.705 and 0.700). A positive correlation was between the risk score and postoperative complications (P for trend <0.01). Three levels of low-risk (0-15 points], moderate-risk (15-30 points], and high-risk (>30 points] were established based on the score distribution of postoperative complications. This simple risk score model based on risk factors of postoperative complications can validly identify the high-risk patients with postoperative complications in the non-intubated VATS, and allow for early interventions.


[Analysis of cells in bronchoalveolar lavage and ultrastructure of lung tissues in experimental silicosis].
Sprague-Dawley rats received intratracheal instillation of 50 mg silica dissolved in 1 ml saline. Animals were killed by intraperitoneal injection of nembutal at periods between 0.5 hour and 4 months. Analysis of bronchoalveolar lavage (BAL) cells and histological and ultrastructural studies were performed on the right and left lungs, respectively. A large number of neutrophils was recovered in BAL fluid from 3 hours after silica infusion, and was maintained until 4 months as the silica stimulus remained in the lung tissues. The absolute number of lymphocytes gradually increased in BAL fluid from day 2. The recovery of macrophages was quite low 24 hours after silica instillation. In contrast, massive aggregates of macrophages were forming silica granulomata in the lung tissues. This discrepancy of results between cells obtained from BAL and those in the lung tissues was caused by an impaired capacity of migration of alveolar macrophages by the development of a junctional apparatus, the "subplasmalemmal linear densities (SPLD)". These structures consisting of hemidesmosome-like unpaired and desmosome-like paired ones infrequently appeared in the acute stages of granuloma formation and were quite common in macrophages and epithelioid-like cells in granulomata 2 weeks after instillation and thereafter. Silicotic granulomata grew in the alveolar ducts from the aggregates of macrophages superimposed on a various number of alveolar sacs. Regeneration of type II alveolar epithelial cells and bronchiolar cuboidal cells usually covered the outer border of the granuloma. Endothelial cells of alveolar capillaries regenerated following recurrent injuries, and only occasionally formed a fenestration structure in their cytoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)


Tumor necrosis factor-alpha decreases pulmonary artery endothelial nitrovasodilator via protein kinase C.
We postulated that tumor necrosis factor-alpha (TNF) decreases endothelium-derived nitrovasodilator(s) via a protein kinase C (PKC)-dependent pathway. Calf pulmonary artery endothelial monolayers (PAEM) were treated with TNF (10, 100, and 1,000 U/ml) for 15 min or 18 h during an 18-h incubation. At the end of the incubation, the cell lysate and supernatant were harvested. Compared with controls, an 18-h incubation with TNF (100 and 1,000 U/ml) resulted in a decrease in NO2- [the oxidation product of nitric oxide (NO)] in PAEM lysate and supernatant. TNF (100 U/ml) treatment for 15 min did not suppress NO2- levels. The decrease in NO2- and the increase in lipid peroxides in response to TNF were prevented by pretreatment (15 min prior to and throughout the incubation) with either calphostin C (1 microM; a specific PKC inhibitor) or the antioxidants N-acetylcysteine (1 mM), 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron) (10 mM), and superoxide dismutase (10 U/ml). Treatment with phorbol 12-myristate 13-acetate (PMA, 1 microM for 15 min), an activator of PKC, decreased NO2- similarly to TNF. Pretreatment with calphostin C or N-acetylcysteine prior to TNF (10 U/ml) revealed an increase in NO2- levels above control treatment. Treatment with the NO synthase antagonists NG-monomethyl-L-arginine (1 mM) and N-nitroso-L-arginine (1 mM) induced an L-arginine (1 mM)-dependent decrease in NO2- in control but not in TNF-treated PAEM. The induction of NO2- by calcium ionophore (A23187; 500 nM) was not affected by treatment with TNF.(ABSTRACT TRUNCATED AT 250 WORDS)


Probability of bivariate superiority: A non-parametric common-language statistic for detecting bivariate relationships.
Researchers often focus on bivariate normal correlation (r) to evaluate bivariate relationships. However, these techniques assume linearity and depend on parametric assumptions. We propose a new nonparametric statistical model that can be more intuitively understood than the conventional r: probability of bivariate superiority (PBS). Our development of Bp, the estimator of a PBS relationship, extends Dunlap's (1994) common-language transformation of r (CLr) by providing a method to directly estimate PBS-the probability that when x is above (or below) the mean of all X, its paired y score will also be above (or below) the mean of all Y. Probability of superiority is an important form of bivariate relationship that until now could only be accurately estimated when data met the parametric assumptions for r. We specify the copula that forms the theoretical basis for PBS, provide an algorithm for estimating PBS from a sample, and describe the results of a Monte Carlo experiment that evaluated our algorithm across 448 data conditions. The PBS estimate, Bp, is robust to violations of parametric assumptions and offers a useful method for evaluating the significance of probability-of-superiority relationships in bivariate data. It is critical to note that Bp estimates a different form of bivariate relationship than does r. Our working examples show that a PBS effect can be significant in the absence of a significant correlation, and vice versa. In addition to utilizing the PBS model in future research, we suggest that this new statistical procedure be used to find theoretically important but previously overlooked effects from past studies.


German Association of Endocrine Surgeons practice guideline for the surgical management of malignant thyroid tumors.
Over the past years, the incidence of thyroid cancer has surged not only in Germany but also in other countries of the Western hemisphere. This surge was first and foremost due to an increase of prognostically favorable ("low risk") papillary thyroid microcarcinomas, for which limited surgical procedures are often sufficient without loss of oncological benefit. These developments called for an update of the previous practice guideline to detail the surgical treatment options that are available for the various disease entities and tumor stages. The present German Association of Endocrine Surgeons practice guideline was developed on the basis of clinical evidence considering current national and international treatment recommendations through a formal expert consensus process in collaboration with the German Societies of General and Visceral Surgery, Endocrinology, Nuclear Medicine, Pathology, Radiooncology, Oncological Hematology, and a German thyroid cancer patient support organization. The practice guideline for the surgical management of malignant thyroid tumors includes recommendations regarding preoperative workup; classification of locoregional nodes and terminology of surgical procedures; frequency, clinical, and histopathological features of occult and clinically apparent papillary, follicular, poorly differentiated, undifferentiated, and sporadic and hereditary medullary thyroid cancers, thyroid lymphoma and thyroid metastases from primaries outside the thyroid gland; extent of thyroidectomy; extent of lymph node dissection; aerodigestive tract resection; postoperative follow-up and surgery for recurrence and distant metastases. These evidence-based recommendations for surgical therapy reflect various "treatment corridors" that are best discussed within multidisciplinary teams and the patient considering tumor type, stage, progression, and inherent surgical risk.


PSEUDO RESPONSE REGULATORs stabilize CONSTANS protein to promote flowering in response to day length.
Seasonal reproduction in many organisms requires detection of day length. This is achieved by integrating information on the light environment with an internal photoperiodic time-keeping mechanism. Arabidopsis thaliana promotes flowering in response to long days (LDs), and CONSTANS (CO) transcription factor represents a photoperiodic timer whose stability is higher when plants are exposed to light under LDs. Here, we show that PSEUDO RESPONSE REGULATOR (PRR) proteins directly mediate this stabilization. PRRs interact with and stabilize CO at specific times during the day, thereby mediating its accumulation under LDs. PRR-mediated stabilization increases binding of CO to the promoter of FLOWERING LOCUS T (FT), leading to enhanced FT transcription and early flowering under these conditions. PRRs were previously reported to contribute to timekeeping by regulating CO transcription through their roles in the circadian clock. We propose an additional role for PRRs in which they act upon CO protein to promote flowering, directly coupling information on light exposure to the timekeeper and allowing recognition of LDs.


TiO2 -coated fluoride nanoparticles for dental multimodal optical imaging.
Core-shell nanostructures associated with photonics techniques have found innumerous applications in diagnostics and therapy. In this work, we introduce a novel core-shell nanostructure design that serves as a multimodal optical imaging contrast agent for dental adhesion evaluation. This nanostructure consists of a rare-earth-doped (NaYF4 :Yb 60%, Tm 0.5%)/NaYF4 particle as the core (hexagonal prism, ~51 nm base side length) and the highly refractive TiO2 material as the shell (~thickness of 15 nm). We show that the TiO2 shell provides enhanced contrast for optical coherence tomography (OCT), while the rare-earth-doped core upconverts excitation light from 975 nm to an emission peaked at 800 nm for photoluminescence imaging. The OCT and the photoluminescence wide-field images of human tooth were demonstrated with this nanoparticle core-shell contrast agent. In addition, the described core-shell nanoparticles (CSNps) were dispersed in the primer of a commercially available dental bonding system, allowing clear identification of dental adhesive layers with OCT. We evaluated that the presence of the CSNp in the adhesive induced an enhancement of 67% scattering coefficient to significantly increase the OCT contrast. Moreover, our results highlight that the upconversion photoluminescence in the near-infrared spectrum region is suitable for image of deep dental tissue.


The viral theory of connective tissue diseases: a review.
For many years evidence for a viral aetiology of connective tissue diseases such as systemic lupus erythematosus and rheumatoid arthritis has been sought by a variety of methods, including attempts at direct isolation, the study of rheumatoid synovial cells, ultrastructural examination of pathological material and assays of anti-viral antibody. No convincing proof has yet been obtained. However, a better understanding of the mechanisms of viral persistence, and the ways in which host defences can be subverted by viral infections has prompted other ways of approaching this problem. A viral aetiology for this group of diseases remains an attractive but unsubstantiated hypothesis.


Multidrug-resistant bacterial isolates in infected wounds at Jimma University Specialized Hospital, Ethiopia.
The term 'Multidrug-resistant' (MDR) applies to a bacterium that is simultaneously resistant to a number of antimicrobials belonging to different chemical classes. The effectiveness of currently available antmicrobial drugs is decreasing due to the increasing number of resistant strains causing infections so that available therapeutic options for such organisms are severely limited. The aim of this study was to determine multidrug-resistance rate of bacterial isolates that caused wound infections. A Hospital based cross-sectional study was conducted on 322 wound samples taken from consecutive patients seen at inpatient and outpatient department of Jimma University Specialized Hospital from June to December 2011. Swabs from surgical incisions, burns, abscess and traumatic wounds were collected aseptically using Levine's technique. Bacteriological culture and examination was done following standard microbiological techniques. Multidrug-resistance test was performed by disk diffusion method against 10 classes of antimicrobials. The data was analyzed for descriptive statistics using SPSS version 16 and Microsoft Excel. The overall MDR among gram positive and gram negative bacterial isolates were (77%) and (59.3%) respectively. About, 86.2% S.aureus and 28.6% of Coagulase negative Staphylococci became MDR. Nearly 30.1% of S.aureus was resistant to six classes of antimicrobials. The average MDR rate of Proteus, Klebsiella, and Providencia species was 74.8%, 69.6% and 75% in that order. Nearly, 30.8% of Proteus sp, 32.6% of Klebsiella sp and 61% of Citrobacter sp were resistance to 4 classes each. Surprisingly, the average MDR rate for Citrobacter sp was 100%. About (76.7%) of S.aureus was Oxacillin/Methicillin resistant while (16.4%) were Vancomycin resistant. Proteus species was the predominant isolates (27.9%) followed by P.aeruginosa and S.aureus (19.3%) and (19%) respectively. This study indicated that, the overall rate of MDR bacterial pathogens that caused wound infection was very high and many of the isolates were also identified as resistant to three or more classes of antimicrobials. Such widespread resistance to antimicrobial classes is something serious because a few treatment options remain for patients with wound infections. Periodic monitoring of etiology and antimicrobial susceptibility in areas where there is no culture facility is essential to assists physician in selection of chemotherapy.


The improper use of the term "normal" in atherosclerosis research.
The improper use of the term "normal" was frequently detected in the available literature, in studies dealing with coronary artery anatomy, pathology and angiography, as well as in epidemiological investigations. Many examples are presented which try to demonstrate that without a clear understanding of the normal, it is a very difficult task to explore the abnormal during coronary atherogenesis and the successive stages which form the natural history of coronary atherosclerosis.


Waste must not be 'swept under carpet'.
New waste management legislation comes into force later this year which will change the way all organisations deal with waste generated on their premises. The issue of employee recycling participation and the right choice of waste and recycling systems should be high on the agenda for the healthcare sector according to Dr David Gillett, sales and marketing director at Taylor, the UK based waste containment provider.


Measuring the importance of influencing factor for COVID-19 vaccination intention in China.
Vaccination is considered an effective approach to deter the spread of coronavirus disease (COVID-19). However, vaccine hesitancy is a common issue that makes immunization programs more challenging. To promote vaccination in a targeted and efficient way, this study aims to develop and validate a measurement tool for evaluating the importance of influencing factors related to COVID-19 vaccination intention in China, and to examine the demographic differences. In study 1, we developed a Factor Importance Evaluation Questionnaire (FIEQ) based on semi-structured interview results and used exploratory factor analysis (EFA) to explore its factor structure. In study 2, we verified the four-factor structure of FIEQ by confirmatory factor analysis (CFA). We then administered FIEQ to Chinese participants and conducted a student t-test and analysis of variance to examine the differences in the importance evaluation of factors based on gender and educational level. In study 1, we developed a four-factor construct and retained 20 items after EFA (N = 577), with acceptable reliability (alpha = 0.87) and validity. In study 2, we found that the model fit was good (χ2 = 748.03 (162), p < 0.001, GFI = 0.949, RMSEA = 0.049, SRMR = 0.048, AGFI = 0.934), and reliability was acceptable (alpha = 0.730) (N = 1,496). No gender difference was found in factor importance. However, individuals with different educational levels reported significantly different importance evaluations of three factors, including perceived benefits and social norms (F = 3.786, p = 0.005), perceived influences from reference groups (F = 17.449, p < 0.001), and perceived risks (F = 2.508, p = 0.04). This study developed and validated FIEQ for measuring the importance of influencing factors related to the COVID-19 vaccination intention in Chinese participants. Moreover, our findings suggest that the educational level may play a role in how individuals evaluate the importance of factors. This study provides insights into the concerns that individuals have regarding vaccination and offers potentially effective and targeted strategies for promoting COVID-19 vaccination.


Child-directed speech is optimized for syntax-free semantic inference.
The way infants learn language is a highly complex adaptive behavior. This behavior chiefly relies on the ability to extract information from the speech they hear and combine it with information from the external environment. Most theories assume that this ability critically hinges on the recognition of at least some syntactic structure. Here, we show that child-directed speech allows for semantic inference without relying on explicit structural information. We simulate the process of semantic inference with machine learning applied to large text collections of two different types of speech, child-directed speech versus adult-directed speech. Taking the core meaning of causality as a test case, we find that in child-directed speech causal meaning can be successfully inferred from simple co-occurrences of neighboring words. By contrast, semantic inference in adult-directed speech fundamentally requires additional access to syntactic structure. These results suggest that child-directed speech is ideally shaped for a learner who has not yet mastered syntactic structure.


Effects of timber harvests and silvicultural edges on terrestrial salamanders.
Balancing timber production and conservation in forest management requires an understanding of how timber harvests affect wildlife species. Terrestrial salamanders are useful indicators of mature forest ecosystem health due to their importance to ecosystem processes and sensitivity to environmental change. However, the effects of timber harvests on salamanders, though often researched, are still not well understood. To further this understanding, we used artificial cover objects to monitor the relative abundance of terrestrial salamanders for two seasons (fall and spring) pre-harvest and five seasons post-harvest in six forest management treatments, and for three seasons post-harvest across the edge gradients of six recent clearcuts. In total, we recorded 19,048 encounters representing nine species of salamanders. We observed declines in mean encounters of eastern red-backed salamanders (Plethodon cinereus) and northern slimy salamanders (P. glutinosus) from pre- to post-harvest in group selection cuts and in clearcuts. However, we found no evidence of salamander declines at shelterwoods and forested sites adjacent to harvests. Edge effects induced by recent clearcuts influenced salamanders for approximately 20 m into the forest, but edge influence varied by slope orientation. Temperature, soil moisture, and canopy cover were all correlated with salamander counts. Our results suggest silvicultural techniques that remove the forest canopy negatively affect salamander relative abundance on the local scale during the years immediately following harvest, and that the depth of edge influence of clearcuts on terrestrial salamanders is relatively shallow (<20 m). Small harvests (<4 ha) and techniques that leave the forest canopy intact may be compatible with maintaining terrestrial salamander populations across a forested landscape. Our results demonstrate the importance of examining species-specific responses and monitoring salamanders across multiple seasons and years. Long-term monitoring will be necessary to understand the full impacts of forest management on terrestrial salamanders.


Perception of the Sports Social Environment After the Development and Implementation of an Identification Tool for Contagious Risk Situations in Sports During the COVID-19 Pandemic.
This study details the methodological process for creating a tool for the identification of COVID-19 potential contagion situations in sports and physical education before, during, and after practice and competition. It is a tool that implies an educational and methodological process with all the agents of the sports system. This tool identifies the large number of interactions occurring through sports action and everything that surrounds it in training, competition, and organization. The aim is to prepare contingency protocols based on an exhaustive analysis, risk detection, and proposal of contingency measures trying to reduce the residual risk to a minimum. In the second part, the results of the implementation of this tool in the sports system of Galicia (Spain) are shown. The technicians have changed their perceptions about the coronavirus transmission in sports. They highlight the problem for returning to sports participation for athletes under 18 years in the pandemic context.


OPTIMAL COLLIMATION SIGNIFICANTLY IMPROVES LUMBAR SPINE RADIOGRAPHY.
To determine the influence of optimal collimation during lumbar spine radiography on radiation dose and image quality. 110 lumbar spine patients were split into two groups-the first imaged with standard collimation and the second with optimal collimation. Body mass index, image field size, exposure conditions and dose area product were measured. Effective and absorbed organ doses were calculated. Image quality was assessed. Optimal collimation reduced the primary field by up to 40%. The effective dose was reduced by 48% for the AP projection, while no differences were found for the LAT projection due to incorrect positioning of the central beam with standard collimation. The absorbed dose to selected radiosensitive organs decreased by 41 and 10% in the AP and LAT projections, respectively. Image quality for the LAT projection improved by 24% and maintained for the AP projection. Optimal collimation in lumbar spine imaging significantly influences patient exposure to radiation.


[Evaluation of parathyroid function in presternal subcutaneous grafting after total parathyroidectomy for renal hyperparathyroidism].
In the setting of total parathyroidectomy (TPT) and parathyroid transplantation (PTx) for renal hyperparathyroidism (RHP), we evaluated long-term parathyroid graft function after subcutaneous presternal transplantation (SCPTx). Parathyroid glands are surrounded by fatty tissue. Therefore, we postulated that subcutaneous implantation of parathyroid tissue after TPT for RHP could be at least as effective as intramuscular grafting and would avoid the complications of the latter technique. We performed a study in a university hospital and its dialysis unit. Prospective open efficacy study of a postoperative diagnostic monitoring method of intact parathyroid hormone (iPTH) in a cohort of surgical patients without loss to follow-up. Thirty-five patients (19 women and 16 men) underwent TPT and SCPTx for RHP at the Department of General Surgery and Department of Nephrology, Donostia Hospital, San Sebastián, Gipuzkoa, Spain, from January 2002 to December 2005. Follow-up ranged from 6 to 42 months (mean, 15.4 months). Graft function was evaluated by measurement of plasma iPTH levels before surgery and 24 hours and 1, 3, 5, 15, 30, 60, 100 and 150 weeks after surgery. Reference values for PTH in our laboratory were 20-65 pg/mL. The mean preoperative iPTH values were 1245 +/- 367.9 pg/mL (mean +/- SD) (range, 493-2160). After TPT and SCPTx, iPTH levels became undetectable in all patients at 24 hours. A value of 50 pg/mL was established as the criterion for adequate parathyroid graft function. The following values were obtained: 15.54 +/- 10.61 pg/mL (mean +/- SD) (range, 6-44) after 1 week, 57.2 +/- 1.9 pg/mL (mean +/- SD) (range, 43-74) after 5 weeks, 64.21 +/- 9.73 pg/mL (mean +/- SD) (range, 11.3-89) after 15 weeks, 75.12 +/- 9.05 pg/mL (mean +/- SD) (range, 24.6-104.2) after 30 weeks, 101.63 +/- 19.85 pg/mL (mean +/- SD) (range, 65-143) after 60 weeks, 121.63 +/- 27.85 pg/mL (mean +/- SD) (range, 62-179) after 100 weeks, 63 +/- 19.85 pg/mL (mean +/- SD) (range, 68-723) after 150 weeks and 102 +/- 18.65 pg/mL (mean +/- SD) (range, 68-113) after 200 weeks. The prevalence of hypoparathyroidism (serum iPTH level of < 20 pg/mL with a normal or low serum calcium concentration) was 2 out of 35 patients (5.71%) by week 60, with recovery of normal values by week 100. Graft-related recurrence occurred in one out of 35 patients (2.85%). SCPTx after TPT and PTx for secondary RHP is an adequate method to replace muscular forearm parathyroid transplantation and avoid its complications. The functional results of TPT and SCPTx compare favorably with published data on other surgical techniques proposed for the treatment of RHP. Long-term follow-up of this series is currently being performed.


An unknown autoinflammatory syndrome associated with short stature and dysmorphic features in a young boy.
A young boy from nonconsanguineous Palestinian parents presented with short stature, motor developmental delay, wide nasal bridge, bilateral periorbital edema, everted lower lip, brachydactyly, large interphalangeal articulations, drumstick extremities of the fingers, bilateral simian crease, clinodactyly of the 5th fingers, painful joints, subcutaneous nodules all over his body and recurrent episodes of fever of unknown origin. Differential diagnoses such as the hyperimmunoglobulinemia D syndrome, tumor necrosis factor receptor associated periodic syndrome (TRAPS), the chronic infantile neurological cutaneous and articular (CINCA) syndrome, and the newly recognized nodulosis, arthropathy, and osteolysis (NAO) syndrome are discussed. This syndrome may not have been previously reported.


Kinetics of carrot somatic embryo development in suspension culture.
Somatic embryos in liquid culture can serve as a mass cloning system in a plant propagation program. A quantitative formulation of embryo development obtained from cell suspension cultures is used to develop a segregated kinetic model. The model is based on standard classification schemes as previously developed by plant physiologists. Dependent variables include carbohydrate concentrations (sucrose, fructose, and glucose) and biomass apportioned among the inoculum (free single cells, cell clusters), normal developmental stages, and aberrant cell and embryo types. Good agreement between the model and experimental results is indicated and allows for a rigorous approach to media optimization and reactor scaleup for embryo formation.


Chiari I malformation in children with transverse myelitis.
Transverse myelitis (TM) is an acute inflammatory spinal cord injury. Asymptomatic Chiari I malformation (CMI) management is highly controversial, particularly when associated with a spinal syrinx. Here, we assess the occurrence of CMI in the pediatric TM population and management outcomes. We performed a retrospective cohort study based on 61 consecutively identified pediatric TM cases over an -8-year period. We reviewed demographic characteristics, radiographic findings, presenting symptoms, and long-term outcomes. Eight CMI cases were identified within the TM cohort; all presented with TM by 16 months of age and affecting the cervical spinal cord. In three cases, CMI developed 15 months to 6 years after the onset of TM. One in 10 children with TM had CMI. These findings demonstrate a high prevalence of CMI in patients with TM. Large prospective clinical studies are needed to further investigate the natural history and recovery strategies of CMI involved with neuroinflammatory disorders.


A simplified assay for O6-methylguanine-DNA methyltransferase activity and its application to human neoplastic and non-neoplastic tissues.
A rapid assay of O6-MeG-DNA methyltransferase activity is described. Following incubation of cell extracts with O6-[3H]MeG-containing DNA, remaining radioactive DNA was hydrolyzed in trichloroacetic acid and separated from methylated radioactive protein by filtration or centrifugation. Transfer of radioactive methyl from DNA to protein was proportional to the amount of protein added, and was not linear with time. More than 90% of the radioactivity precipitated after acid hydrolyses was in S-methyl cysteine residues. The method was used to measure O6-MeG-DNA methyltransferase activity in extracts of 24 neoplastic tissues from human organs. Although five tumor tissues had 28-84% lower activity of O6-MeG-DNA methyltransferase than the corresponding normal tissue from the same patient, higher or similar levels of activity were found more frequently. Thus, a lack of O6-MeG-DNA methyltransferase activity in human tumours appears not to be a frequent event. The DNA repair enzyme uracil-DNA glycosylase was also measured in the same extracts. Most frequently the level of uracil-DNA glycosylase activity was essentially similar in tumors and normal tissues but significantly higher or lower levels were also observed.


Immune dysfunction in primary biliary cirrhosis. II. Increased production of prostaglandin E.
In a previous study we observed that after in vitro treatment with indomethacin, lymphocyte response to phytohaemagglutinin (PHA) in primary biliary cirrhosis (PBC) patients was higher than that of controls. We know that indomethacin also inhibits prostanoid production, and thus in the present work we directly measured prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) production by mononuclear cells and monocytes from 12 PBC patients, 11 control subjects, and three control disease patients (alcoholic cirrhosis, AC). PHA-stimulated enriched monocytes from PBC patients produced approximately threefold more PGE2 (after 48 h of culture) than did normal and AC monocytes (P less than 0.05). TXB2 production was similar in all groups studied. We also made cultures in which PBC-purified lymphocytes proliferated better than PBC mononuclear cells (i.e. lymphocytes plus monocytes). Thus, a monocyte population producing PGE2 could be responsible, at least in part, for the hyporesponsiveness to PHA observed in PBC patients.


Aspects of metabolic changes in first-episode drug-naïve schizophrenic patients.
Aim The aim of the study was to investigate the state of parameters characterising different sites of metabolism and the degree of endogenous intoxication in first-episode drug-naïve schizophrenic [first episode of schizophrenia (FES)] patients. It is hypothesised that the FES is the initial step in the development of pathologically disturbed biochemical status that is characteristic of chronic schizophrenia. Platelet monoamine oxidase (MAO) and serum semicarbazide-sensitive amine oxidase (SSAO) activities, serum concentrations of middle-mass endotoxic molecules (MMEM) and malondialdehyde and parameters of the serum albumin functional state were measured in 26 FES patients and 15 age-matched healthy controls. Severity of disorder before the treatment was 75.5 ± 2.2, according to Positive and Negative Syndrome Scale score. FES patients were characterised by significant increase in MAO activity (99%) and MMEM concentration (124%) and significant decrease in SSAO activity (26%) as compared with controls. Changes of all other parameters were insignificant. Regression analysis has showed a significant relationship of three parameters - MAO, SSAO and MMEM, with values of PANNS score. Two methods of extraction of factor analysis revealed that MAO and SSAO belonged to Factor 1, whereas MMEM and albumin functional parameters belonged to Factor 2. Comparing our earlier data on chronic schizophrenic patients with present data, we hypothesise that FES patients are at the stage that leads to a stable, pathological state of metabolism.


EVOLUTIONARILY STABLE MORPHOLOGIES IN PEA POPULATIONS.
We investigated the hypothesis that plant form can dramatically affect plant competitive ability, and that forms with dense canopies can invade populations of plants with more open canopies regardless of initial relative frequencies. Under controlled field conditions, we examined the effects of plant form on growth rate, size variation, mortality, and reproduction in high-density monocultures and mixtures of two morphologically distinct varieties of peas. These two varieties differ genetically at only the afila locus. In high-density monocultures and mixtures, peas with finely dissected, minute leaflets (af/af) grew more slowly and produced fewer seeds than Af/-individuals with large leaflets that cast more shade on neighbors. After as few as four generations, mixtures begun with 10% Af/- peas would be expected to evolve to Af/- monocultures. We conclude that an increase in morphological complexity (e.g., virtually leafless to leafy) can have dramatic ecological and evolutionary impacts on plant population dynamics.


What is the evidence for environmental causes of challenging behaviors in persons with intellectual disabilities and autism spectrum disorders?
An extensive literature on the causes of challenging behaviors has been developed, primarily in the applied behavior analysis literature. One hundred and seventy-three empirical studies were reviewed where functional assessment serves as the primary method of identifying these causes. Most of the studies were able to identify a clear function or functions. Most commonly established causes were attention, the efforts to acquire tangibles, negative reinforcement in the form of escape from tasks or environments, and sensory stimulation, also described as an alone condition. Examples are provided regarding how these conditions are investigated across studies. Biological and cognitive causes have also been demonstrated. However, to date the empirical literature is limited with the bulk of studies being correlational. Considerably more research is needed, but some causes and methods to identify them are beginning to emerge.


Oscillations of potential in the electroretinogram of the lobster.
The electroretinogram (ERG) evoked in the lobster by a short flash of light consists of a highly damped, slow oscillation of potential, triggered apparently by a single excitatory process. Near the threshold, only one wave may be evident; but as the intensity of stimulus rises, a prior wave appears, and grows so much more rapidly as to become dominant. Simultaneously third and later waves appear, so that at high intensities the response may include five to seven waves. Dark adaptation favors the second and later waves relative to the first; light adaptation tends to suppress them. On turning on a steady light the oscillations are superimposed on the early stages of development of a maintained, steady-state potential (on-response). Turning off the light causes a rapid fluctuation of potential followed by a similarly damped slow oscillation (off-response). These phenomena resemble in part oscillations recently observed in the b wave of the ERG of many vertebrates including man.


DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional α-thalassaemia.
Haemoglobin (Hb) Adana (HBA2:c.179>A) interacts with deletional and nondeletional α-thalassaemia mutations to produce HbH disorders with varying clinical manifestations from asymptomatic to severe anaemia with significant hepatosplenomegaly. Hb Adana carriers are generally asymptomatic and haemoglobin subtyping is unable to detect this highly unstable α-haemoglobin variant. This study identified 13 patients with compound heterozygosity for Hb Adana with either the 3.7 kb gene deletion (-α(3.7)), Hb Constant Spring (HbCS) (HBA2:c.427T>C) or Hb Paksé (HBA2:429A>T). Multiplex Amplification Refractory Mutation System was used for the detection of five deletional and six nondeletional α-thalassaemia mutations. Duplex-PCR was used to confirm Hb Paksé and HbCS. Results showed 84.6% of the Hb Adana patients were Malays. Using DNA studies, compound heterozygosity for Hb Adana and HbCS (α(codon 59)α/α(CS)α) was confirmed in 11 patients. A novel point in this investigation was that DNA studies confirmed Hb Paksé for the first time in a Malaysian patient (α(codon 59)α/α(Paksé)α) after nine years of being misdiagnosis with Hb Adana and HbCS (α(codon 59)α/α(CS)α). Thus, the reliance on haematology studies and Hb subtyping to detect Hb variants is inadequate in countries where thalassaemia is prevalent and caused by a wide spectrum of mutations.


Correction: Conceptual design of tetraazaporphyrin- and subtetraazaporphyrin-based functional nanocarbon materials: electronic structures, topologies, optical properties, and methane storage capacities.
Correction for 'Conceptual design of tetraazaporphyrin- and subtetraazaporphyrin-based functional nanocarbon materials: electronic structures, topologies, optical properties, and methane storage capacities' by Rodion V. Belosludov et al., Phys. Chem. Chem. Phys., 2016, 18, 13503-13518.


In-Fiber Collimator-Based Fabry-Perot Interferometer with Enhanced Vibration Sensitivity.
A simple vibration sensor is proposed and demonstrated based on an optical fiber Fabry-Perot interferometer (FPI) with an in-fiber collimator. The device was fabricated by splicing a quarter-pitch graded index fiber (GIF) with a section of a hollow-core fiber (HCF) interposed between single mode fibers (SMFs). The static displacement sensitivity of the FPI with an in-fiber collimator was 5.17 × 10-4 μm-1, whereas the maximum static displacement sensitivity of the device without collimator was 1.73 × 10-4 μm-1. Moreover, the vibration sensitivity of the FPI with the collimator was 60.22 mV/g at 100 Hz, which was significantly higher than the sensitivity of the FPI without collimator (11.09 mV/g at 100 Hz). The proposed FPI with an in-fiber collimator also exhibited a vibration sensitivity nearly one order of magnitude higher than the device without the collimator at frequencies ranging from 40 to 200 Hz. This low-cost FPI sensor is highly-sensitive, robust and easy to fabricate. It could potentially be used for vibration monitoring in remote and harsh environments.


Beyond Anderson localization in 1D: anomalous localization of microwaves in random waveguides.
Experimental evidence demonstrating that anomalous localization of waves can be induced in a controllable manner is reported. A microwave waveguide with dielectric slabs randomly placed is used to confirm the presence of anomalous localization. If the random spacing between slabs follows a distribution with a power-law tail (Lévy-type distribution), unconventional properties in the microwave-transmission fluctuations take place revealing the presence of anomalous localization. We study both theoretically and experimentally the complete distribution of the transmission through random waveguides characterized by α=1/2 ("Lévy waveguides") and α=3/4, α being the exponent of the power-law tail of the Lévy-type distribution. As we show, the transmission distributions are determined by only two parameters, both of them experimentally accessible. Effects of anomalous localization on the transmission are compared with those from the standard Anderson localization.


High incidence of vaproate-induced coagulation disorders in children receiving valproic acid: a prospective study.
Reports have been published on blood coagulation disturbances by valproate therapy. In the present prospective trial, blood samples were drawn before valproate therapy, after 6 weeks of therapy, after more than 6 weeks and after longer than 6 months of valproate therapy from 23 children newly treated with valproate. Two children developed thrombocytopenia, and six children with initial normal von Willebrand factor showed acquired von Willebrand's disease. Fibrinogen levels dropped below the lower limit in 12 patients and subnormal factor XIII plasma levels were observed in 17% of patients. No patient developed signs of hemorrhage. Eight percent of patients developed valproate-induced thrombocytopenia. Reduction in platelets did not reach statistic significance. Thrombelastography showed a 47% incidence of altered platelet function. We found a statistically significant, positive correlation between clotting time of collagen extrinsic pathway inhibitor and, accordingly, adenosindiphosphate and valproate level. Plasmatic coagulation investigations showed a significant decrease of prothrombin time. Activated partial thromboplastin time measurements also showed significant prolongation with valproate. Activity of von Willebrand factor antigen and von Willebrand factor ristocetin cofactor significantly decreased. Factor XIII activity significantly decreased after valproate therapy for longer than 6 months (17% of children). Fibrinogen was significantly reduced. In the coagulatory system a decrease in the main antiprotease antithrombin III activity was observed. Blood coagulation disturbances are common in patients with valproate, but rarely become clinically symptomatic. Acquired von Willebrand's disease and hypofibrinogenemia may become relevant in patients with surgery or trauma. Particular attention should be paid to factor-XIII deficiency, which is especially seen with valproate therapy.


Production of wild-type and peptide fusion cutinases by recombinant Saccharomyces cerevisiae MM01 strains.
This study focused on the growth of Saccha-romyces cerevisiae MM01 recombinant strains and the respective production of three extracellular heterologous cutinases: a wild-type cutinase and two cutinases in which the primary structure was fused with the peptides (WP)(2) and (WP)(4), respectively. Different cultivation and strategies were tested in a 2-L shake flask and a 5-L bioreactor, and the respective cell growth and cutinase production were analyzed and compared for the three yeast strains. The highest cutinase productions and productivities were obtained in the fed-batch culture, where wild-type cutinase was secreted up to a level of cutinase activity per dry cell weight (specific cell activity) of 4.1 Umg(-1) with activity per protein broth (specific activity) of 266 Umg(-1), whereas cutinase-(WP)(2) was secreted with a specific cell activity of 2.1 Umg(-1) with a specific activity of 200 Umg(-1), and cutinase-(WP)(4) with a specific cell activity of 0.7 Umg(-1) with a specific activity of 15 Umg(-1). The results indicate that the fusion of hydrophobic peptides to cutinase that changes the physical properties of the fused protein limits cutinase secretion and subsequently leads to a lower plasmid stability and lower yeast cell growth. These effects were observed under different cultivation conditions (shake flask and bioreactor) and cultivation strategies (batch culture versus fed-batch culture).


Preliminary clinical outcomes from the Peruvian National Cataract Elimination Plan.
to evaluate the clinical outcomes of a publicly funded cataract elimination program. outcomes of all patients (186) who received extracapsular cataract extraction (ECCE) surgery free of charge at the Instituto Regional de Oftalmología in northern Peru in the first year (August 2008 to July 2009) of the Peruvian National Cataract Elimination Plan were compared retrospectively with the outcomes of all patients (68) who paid in the highest charge tier for ECCE surgery during the same period. Preoperatively, the median uncorrected visual acuity (UCVA) of National Plan patients was Hand Motion; the UCVA of paying patients was Counting Fingers (P = 0.09). Complication frequency and visual acuity (uncorrected visual acuity, pinhole visual acuity, and best correct visual acuity) were the primary outcome measures. The World Health Organization (WHO) Vision 2020 goal is for 85% of operated eyes to achieve 20/60 vision; the Ministerio de Salud del Perú goal is for 75% of eyes to achieve 20/50. one month postoperatively, only 24% of National Plan patients achieved a UCVA of 20/60. The median UCVA for both groups was 20/100 (P = 0.23). Intraoperative complications occurred in 27% of all patients; postoperative complications occurred in 39%. Patients more likely to have a poor outcome (UCVA < 20/200) were those who experienced a postoperative complication (odds ratio [OR] 3.3, P = 0.002), who experienced an intraoperative complication (OR 2.5, P = 0.01), and who were 75 years or older (OR 2.7, P = 0.008). National Plan patients were more likely to have an OCTET Grade II intraoperative complication (OR 4.2, P = 0.03) and were less likely to receive refractive services (OR 1.5, P = 0.002). neither WHO nor Peruvian benchmarks for surgical outcome were achieved in the first year of the Peruvian National Cataract Elimination Plan. Providing more comprehensive services to patients and addressing variables correlated with poor outcomes may improve interventions and help achieve Vision 2020 goals.


Cross-cultural adaptation of the German Pain Solutions Questionnaire: an instrument to measure assimilative and accommodative coping in response to chronic pain.
According to the dual process model of coping, assimilative or accommodative strategies can be applied to deal with aversive life situations. In people with chronic pain, the tenacious focus on achieving analgesia is often referred to as assimilative coping and associated with more disability and catastrophic thinking. In contrast, accommodative coping (accepting one's pain and setting new goals) appears to have beneficial effects. To assess how people with chronic pain use these different coping strategies, questionnaires measuring these concepts are needed. Following international guidelines, a German version of the Pain Solutions Questionnaire (PaSol) was prepared. A sample of 165 participants with chronic low back pain (CLBP; 60% women; age 53 ± 8.4 years) filled in the questionnaire and measures for pain-related disability, affective distress, catastrophic thinking, and attention to pain. Item analyses, an exploratory factor analysis, and correlations with pain-related measures were calculated. In addition, data from 98 participants who received psychological treatment were examined to investigate the PaSol's sensitivity to change. The exploratory factor analysis reproduced the original questionnaire's four-factor structure. Internal consistencies for the subscales ranged from Cronbach's α=0.72 to α =0.84. Mean item difficulties for the subscales ranged from pi=0.62 to pi=0.79. The highest correlations were found for Meaningfulness with catastrophic thinking (r=-0.58) and affective distress (r=-0.36). The PaSol subscale Meaningfulness predicted pain-related disability; the subscales Meaningfulness and Solving Pain predicted affective distress. Furthermore, the PaSol was found to be sensitive to detect changes over time. The German version of the PaSol is a reliable and valid instrument in the measurement of assimilative and accommodative coping strategies in people suffering from CLBP. It may provide a useful tool when examining temporal dynamics of the changing coping strategies in the transition from acute to chronic pain as well as during pain treatments.


Aortic emergencies.
This article discusses the anatomy and pathobiology of the aorta, common aortic emergencies and their diagnosis, and the roles and limitations of diagnostic imaging in assessment, medical intervention and monitoring.


Marginal bone loss and resorption of second molars related to maxillary third molars in panoramic images compared with CBCT.
Compare findings among observers in panoramic images (PAN) and cone beam CT (CBCT); and assess findings in PAN as indicators for marginal bone loss and resorption observed in CBCT. 120 impacted maxillary third molars with PAN and CBCT were included. Four observers assessed morphological features: (1) tooth angulation; (2) number of roots; (3) bony impaction (yes/no) and pathology; (4) marginal bone level at the second molar (normal/>3 mm = bone loss); (5) resorption in the second molar (no/superficial/< half way through the dentin/≥ half way through the dentin/involving the pulp); (6) size of follicular space (normal/> 4 mm(cyst)). Percentage accordance and κ statistics described observer variation in PAN and CBCT. Logistic regression analyses tested findings in PAN as indicators for marginal bone loss or resorption observed in CBCT. κ values were fair and interobserver accordance was marginally higher in CBCT than PAN. Agreement between PAN and CBCT was 81-88% for marginal bone loss and 68-81% for resorption. Severe resorption was more often observed in CBCT. Mesio-angulated third molars and marginal bone loss interpreted in PAN significantly indicated marginal bone loss observed in CBCT (odds ration 17-34; p < 0.012; 8.8-52.8; p < 0.02). In contrast, findings in PAN were not significant indicators for resorption observed in CBCT (p > 0.05). In general, there was a fair agreement for marginal bone loss between PAN and CBCT, and PAN could significantly predict bone loss observed in CBCT. However, presence of resorption observed in CBCT could not be determined from PAN, and more severe resorption was observed in CBCT. CBCT is indicated if resorption in the second molar needs to be assessed.


Identification of candidate proteomic markers in the serum of medication overuse headache patients: An exploratory study.
The pathophysiological mechanism of medication overuse headache is uncertain; no distinctive markers have been described right now. The aim of this study was to conduct proteomic analyses on serum samples from patients with medication overuse headache and healthy individuals. Specifically, mono- (SDS-PAGE) and two-dimensional gel electrophoresis (2-DE) followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to evaluate changes in serum proteins. By SDS-PAGE, four over-expressed bands were revealed in patients, compared to controls. 2-DE combined with LC-MS/MS analysis allowed confirmation of some proteins preliminarily detected by SDS-PAGE: Hemopexin, alpha-1-acid glycoprotein 1, apolipoprotein A4 and haptoglobin. Moreover, other differential proteins were isolated, mostly increased in MOH patients: Alpha-1-antitrypsin, immunoglobulin heavy constant alpha 1, retinol binding protein and transthyretin. Only one protein, immunoglobulin kappa constant, was decreased in the patients' group. The investigation of the serum proteome can offer a better understanding about biological mechanisms underlying medication overuse headache. Specifically, medication overuse headache shares some serum biochemical markers with chronic pain conditions. Further studies might uncover the relevance of these proteins in medication overuse headache.


Total Force Fitness Summit 2021: Maximizing the Health and Well-being of Service Members and Their Families.
Total Force Fitness (TFF) is a multidomain, holistic framework that provides the Department of Defense (DoD) with the capability to assess, promote, and sustain human performance optimization across the full spectrum of components key to meeting mission requirements. On September 14 and 15, 2021, in Bethesda, MD, The Consortium for Health and Military Performance convened a second TFF Summit with the goal of promoting the mission of optimizing the health and well-being of our service members across their careers. Participants included scientists, clinicians, educators, public health professionals, and military leaders from all the services. The current operating picture of TFF within the DoD was described, and then working groups were convened to address issues related to (1) delivering full spectrum health and performance services; (2) advocacy, awareness, and empowerment; (3) research; (4) education; and (5) standardization, branding, and metrics. The outcomes of the summit included recommendations that operational leadership and a consolidated and joint approach are required for TFF to be successful, and TFF must be regarded as an integral part of the National Defense, Security, and Military Strategy. To that end, TFF should be aligned within OUSD(P&R), not the Military Health System, so it extends beyond the medical setting and fully supports mission readiness and performance. Importantly, we must be proactive and teach new recruits about the TFF holistic approach to sustain optimal performance across their careers.


Mechanisms of toxicity in C9FTLD/ALS.
A hexanucleotide repeat expansion within a non-coding region of the C9ORF72 gene is the most common mutation causative of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Elucidating how this bidirectionally transcribed G4C2·C4G2 expanded repeat causes "C9FTLD/ALS" has since become an important goal of the field. Likely pathogenic mechanisms include toxicity induced by repeat-containing RNAs, and loss of C9orf72 function due to epigenetic changes resulting in decreased C9ORF72 mRNA expression. With regards to the former, sense and antisense transcripts of the expanded repeat aberrantly interact with various RNA-binding proteins and form discrete nuclear structures, termed RNA foci. These foci have the capacity to sequester select RNA-binding proteins, thereby impairing their function. (G4C2)exp and (C4G2)exp transcripts also succumb to an alternative fate: repeat-associated non-ATG (RAN) translation. This unconventional mode of translation, which occurs in the absence of an initiating codon, results in the abnormal production of poly(GA), poly(GP), poly(GR), poly(PR) and poly(PA) peptides, collectively referred to as C9RAN proteins. C9RAN proteins form neuronal inclusions throughout the central nervous system of C9FTLD/ALS patients and may contribute to disease pathogenesis. This review aims to summarize the important findings from studies examining mechanisms of disease in C9FTLD/ALS, and will also highlight some of the many questions in need of further investigation.


Comparison of the Cobas 4800 HPV test and the Seeplex HPV4A ACE with the hybrid capture 2 test.
It is well-known that persistent cervical infections with high-risk human papillomavirus (HPV) are related to the development of high-grade cervical intraepithelial neoplasia and invasive cervical cancer and that infection with HPV 16 and HPV 18 accounts for approximately 70% of all cases of invasive cervical cancer. We performed 3 HPV molecular tests-the Cobas 4800 HPV test, the Seeplex HPV4A ACE, and the hybrid capture 2 (HC2) test-in 146 cervical swab samples to compare between these three tests. There was a concordance rate of 82.8% between the results of the Cobas 4800 HPV and the HC2 test and a concordance rate of 84.9% between the results of the Seeplex HPV4A ACE and the HC2 test. Between the Cobas 4800 HPV test and the Seeplex HPV4A ACE, there was a concordance rate of 89.6% in the detection of high-risk HPV between the results and a concordance rate of 98.7% in the detection of HPV 16 or 18. When an abnormal Pap test was defined as ≥ low grade squamous intraepithelial lesion (LSIL), the sensitivity of the Cobas 4800 HPV test, the Seeplex HPV4A ACE and the HC2 test were 71.1%, 80.0%, and 88.9%, respectively, while their specificities were 76.4%, 74.5%, and 67.9%, respectively. The results of this study suggest that the Cobas 4800 HPV test and the Seeplex HPV4A ACE may be as effective as the HC2 test in detecting HR HPV and that the concordance between the results of the Cobas 4800 HPV test and the Seeplex HDV4A ACE may be higher in the detection of HPV 16 and HPV18 than concerning high-risk HPV.


Gulf of Maine Harmful Algal Bloom in summer 2005 - Part 1: In Situ Observations of Coastal Hydrography and Circulation.
An extensive Alexandrium fundyense bloom occurred along the coast of the Gulf of Maine in late spring and early summer, 2005. To understand the physical aspects of bloom's initiation and development, in-situ observations from both a gulf-wide ship survey and the coastal observing network were used to characterize coastal circulation and hydrography during that time period. Comparisons between these in-situ observations and their respective long term means revealed anomalous ocean conditions during May 2005: waters were warmer and fresher gulf-wide due to more surface heating and river runoff; coastal currents were at least two times stronger than their climatological means. Surface winds were also anomalous in the form of both episodic burst of northeaster storms and downwelling favorable mean condition. These factors may have favored more vigorous along-shore transport and near shore aggregation of toxic A. fundyense cells (a red tide) in 2005.


Aging, health and women in West New Britain.
Modernization has not significantly improved the lives of elderly women in an isolated Melanesian community. While demographic changes may deprive the elderly of the care of co-resident children, modern medical technology has not greatly bettered their health. People who suffer from the degenerative diseases of old age do not travel to the hospital because they believe that Western medicine cannot cure them and because they fear dying far from home, kin and friends. Modernization has, however, eroded the healing role and prestige of elderly female healers, and their skills and medical knowledge are being lost.


Test-Retest Reliability and Convergent Validity of Two Brief Fruit and Vegetable Intake Questionnaires among School-Aged Children.
Reliable, valid, and easy-to-implement tools are required to assess children's fruit and vegetable intake as part of behavior change-focused nutrition education programs; however, the availability of such instruments is limited. The purpose of this study was to examine the reproducibility and accuracy of two brief fruit and vegetable intake questionnaires among 8- to 12-year-old children. A total of 109 participants from diverse racial/ethnic groups were recruited from urban afterschool programs. The results of two short questionnaires (food web and plate activity) were reproducible between two repeated measures conducted one week apart. Compared to a reference 24-h dietary recall, the food web questionnaire had acceptable convergent validity for assessing children's fruit intake (kappa: 0.51; r = 0.53, p < 0.001), but limited validity for assessing children's vegetable intake (kappa: 0.43; r = 0.33, p < 0.003). Children tended to overestimate intake when visualizing fruit and vegetable consumption via the plate activity questionnaire, indicating that this questionnaire was not a valid tool to assess children's fruit and vegetable consumption at dinner meals. Children's report of fruit intake via the food web questionnaire may be a useful indicator of program success in improving fruit intake.


Variability in Prevalence of Helicobacter pylori Strains Resistant to Clarithromycin and Levofloxacin in Southern Poland.
Background. An increasing resistance of Helicobacter pylori strains to antimicrobial agents is the serious therapeutic problem. The aim of this study was to compare the primary and secondary resistance of H. pylori strains isolated between 2006-2008 (data published) and 2009-2011 to clarithromycin and levofloxacin. Material and Methods. 220 dyspeptic patients (153 before treatment, 67 after), were enrolled in the study. 51 H. pylori strains were isolated. MIC values of clarithromycin and levofloxacin were determined by the E-test method. The statistical analysis was conducted with the χ(2) test with Yates correction at the 0.05 significance level (P ≤ 0.05). Results. Between 2006 and 2008, 34% (39/115) of H. pylori strains were resistant to clarithromycin (primary 21% (19/90), secondary 80% (20/25)). 5% (6/115) of strains were resistant to levofloxacin (primary 2% (2/90), secondary 16% ((4/25); data published) Between 2009-2011, 22% (11/51) of H. pylori strains were resistant to clarithromycin (primary 19% (8/43), secondary 38% (3/8)). 16% (8/51) of strains were resistant to levofloxacin (primary 12% (5/43), secondary 38% (3/8)). Conclusion. The present study has shown the increasing amount of resistant H. pylori strains isolated from patients in Southern Poland to levofloxacin and decreasing number of resistant strains to clarithromycin.


Frizzled-7 mediates TGF-β-induced pulmonary fibrosis by transmitting non-canonical Wnt signaling.
Pulmonary fibrosis is a progressive and often fatal lung disease characterized by fibroblast proliferation and excessive deposition of extracellular matrix. Both TGF-β and Wnt signaling have been implicated in the regulation of organ fibrosis. However little is known about whether TGF-β-induced gene expression changes in Wnt signaling pathway could predict disease progression. In the study, we investigated the interaction between TGF-β and Wnt signaling in mediating pulmonary fibrosis by big data analysis, in vitro and in vivo experimental studies and clinical data analysis. We found that TGF-β1 treatment induces a marked upregulation of Frizzled-7 (FZD7) in human lung fibroblasts. FZD7 expression is also increased in animal models of TGF-β1-induced pulmonary fibrosis. TGF-β1 upregulated FZD7 expression in a Smad3-dependent manner. Functionally, knockdown of FZD7 inhibits TGF-β1-induced expression of α-smooth muscle actin (α-SMA), collagen I (Col I), fibronectin and connective tissue growth factor (CTGF). FZD7 inhibition further attenuates TGF-β1-induced pulmonary fibrosis in vivo. Finally our data demonstrated that FZD7 transmits non-canonical Wnt signaling by interacting Wnt5A in the regulation of ECM expression. These results suggest that FZD7-targeted therapeutic strategies may be applicable for treating an array of fibrotic diseases.


Factors associated with the positive well-being of grandparents caring for their grandchildren.
Prior research on grandparent caregivers has focused on stress, depression, and other negative outcomes. This paper describes research on factors that are associated with grandparents' positive well-being. In particular, it investigated the extent to which the perception of grandparental stress and grandparents' resources are associated with grandparents' well-being, after controlling for sociodemographic and health factors. A sample of 129 grandparents had individual interviews. Using a hierarchical block multiple regression analysis, the authors found that a low perception of stress related to caring for grandchildren and resources were responsible for a high level of wellbeing. The findings of this study suggest that social workers can best help grandparent caregivers by lowering their perception of stress and enhancing their informal supports and community resources. This can be incorporated into supportive, strengths-based individual or family counseling.


The essential role of the clinical research nurse (CRN).
In an age of increasing focus on expanding the opportunity of clinical research trial participation to broader patient populations, the clinical research nurse (CRN) has become an essential member of the clinical research team. The CRN is responsible for many roles and aspects of clinical trial management. Clarification of these roles and responsibilities will be provided in this article.


N-glycome of the Lysosomal Glycocalyx is Altered in Niemann-Pick Type C Disease (NPC) Model Cells.
Increasing evidence implicates lysosomal dysfunction in the pathogenesis of neurodegenerative diseases, including the rare inherited lysosomal storage disorders (LSDs) and the most common neurodegenerative diseases, such as Alzheimer's and Parkinson's disease (AD and PD). Although the triggers of the lysosomal impairment may involve the accumulated macromolecules or dysfunction of the lysosomal enzymes, the role of the lysosomal glycocalyx in the lysosomal (dys)function has not been studied. The goal of this work was to analyze whether there are changes in the lysosomal glycocalyx in a cellular model of a LSD Niemann-Pick type C disease (NPC). Using the ferrofluid nanoparticles we isolated lysosomal organelles from NPC1-null and CHOwt cells. The magnetically isolated lysosomal fractions were enriched with the lysosomal marker protein LAMP1 and showed the key features of NPC disease: 3-fold higher cholesterol content and 4-5 fold enlarged size of the particles compared with the lysosomal fractions of wt cells. These lysosomal fractions were further processed to isolate lysosomal membrane proteins using Triton X-114 and their N-glycome was analyzed by HILIC-UPLC. N-glycans presented in each chromatographic peak were elucidated using MALDI-TOF/TOF-MS. We detected changes in the N-glycosylation pattern of the lysosomal glycocalyx of NPC1-null versus wt cells which involved high-mannose and sialylated N-glycans. To the best of our knowledge this study is the first to report N-glycome profiling of the lysosomal glycocalyx in NPC disease cellular model and the first to report the specific changes in the lysosomal glycocalyx in NPC1-null cells. We speculate that changes in the lysosomal glycocalyx may contribute to lysosomal (dys)function. Further glycome profiling of the lysosomal glycocalyx in other LSDs as well as the most common neurodegenerative diseases, such as AD and PD, is necessary to better understand the role of the lysosomal glycocalyx and to reveal its potential contribution in lysosomal dysfunction leading to neurodegeneration.


Factors Associated With Discrepancy in Parent-Teacher Reporting of Symptoms of ADHD in a Large Clinic-Referred Sample of Children.
Objective: To identify factors associated with discrepancy in parent-teacher reporting of symptoms of ADHD. Method: Parents and teachers rated 1,364 children using an ADHD rating scale. Data were analyzed using multiple regressions and ANOVA. Results: Demographic variables predicted greater parent-teacher discrepancy for ethnic minority families than for Caucasian families. Comorbidity variables predicted greater discrepancy for children who had a comorbid externalizing disorder. Academic performance variables predicted discrepancy for children who showed more homework problems. When all significant predictors were entered together, externalizing disorders and homework problems emerged as significant predictors. Participants whose parents reported higher levels of symptoms were of significantly higher socioeconomic status. Participants whose teachers reported higher levels of symptoms were significantly less likely to have a comorbid externalizing disorder and parent-reported homework problems. Conclusion: Parent-teacher discrepancies are likely to occur when the child has significant homework and externalizing behavior problems.


Synonymize Arma chinensis as Arma custos based on morphological, molecular and geographical data.
Arma custos and A. chinensis have a very conspicuous difference in the shape of the pronotal humeral angle, but the genitalic morphological characters are ambiguous and difficult to recognize. The aim of this study was to analyze the taxonomic status of A. chinensis and A. custos based on morphological, molecular, and geographical evidence, and to determine whether DNA barcoding could be a useful additional tool for differentiating similar species. The results clearly demonstrate that A. custos and A. chinensis have not diverged into separate species. So, the following new synonym is proposed: Arma chinensis Fallou, 1881 = Arma custos (Fabricius, 1794) syn. nov.. The results also showed that DNA barcoding using the marker COI can resolve insect taxonomic problems.


Employing Tip-Edge brackets on canines to simplify straight-wire mechanics.
The straight-wire appliance was developed in part to reduce wire bending and therefore make treatment results more predictable. Because tip prescription is built into the bracket slots, teeth are held at their final crown angulations throughout treatment. Straight-wire brackets are used in an attempt to produce bodily tooth movement. However, teeth tend to tip when a force is applied. This tipping, especially when canines are retracted, can deflect the arch wire causing supereruption of the incisors with a resultant increase in anterior overbite and an open bite in the canine/premolar area. Placing Tip-Edge brackets (TP Orthodontics, Inc., LaPorte, Ind.) on canines and employing tipping and uprighting mechanics on these teeth can overcome these problems. Two cases are presented to illustrate this approach to treatment.