The gene of the N-acetylglucosaminidase, a Bacillus subtilis 168 cell wall hydrolase not involved in vegetative cell autolysis.
lytD, the structural gene of the Bacillus subtilis 168 N-acetylglucosaminidase was localized at 310 degrees, next to the tagABC operon. Sequence analysis revealed a monocistronic operon encoding a 95.6 kDa protein endowed with an export signal, the cleavage of which yields the monomer polypeptide (92.8 kDa) of the dimeric active form of the enzyme. Transcription is initiated at a sigma-D (sigma D)-dependent promoter and ends at a terminator common to lytD and the divergently transcribed tagABC operon. In addition, we report the sequence of the adjacent upstream ORF, transcribed in the same direction as lytD, which shows significant homology to phosphomannose isomerase-encoding genes. Cell separation, motility, autolysis, cell wall turnover and growth were not affected in strains devoid of the N-acetylglucosaminidase. A mutant deficient in the two most abundant autolysins, i.e. the LytC amidase and the glucosaminidase, exhibited the phenotype of the amidase-deficient strains, revealing their non-requirement for growth. This conclusion raises two fundamental questions: how does the cell undo the highly cross-linked peptidoglycan so as to be able to grow, and what is the role of the considerable amount of autolysin normally present? Possible answers to these questions are discussed.


Assessment of molybdenum application on soybean physiological characteristics in maize-soybean intercropping.
Soybean is a leguminous crop known for its efficient nitrogen utilization and ease of cultivation. However, its intercropping with maize may lead to severe reduction in its growth and yield due to shading effect of maize. This issue can be resolved by the appropriate application of essential plant nutrient such as molybdenum (Mo). Aim of this study was to assess the effect of Mo application on the morphological and physiological characteristics of soybean intercropped with maize. A two-year field experiment was conducted for this purpose, and Mo was applied in the form of sodium molybdate (Na2MoO4), and four different levels were maintained i.e., 0, 60, 120 and 180 g ha-1. Soybean exhibited varying responses to different levels of molybdenum (Mo) application. Notably, in both sole and intercropped cropping systems, the application of Mo at a rate of 120 g ha-1 demonstrated the highest level of promise compared to other application levels. However, most significant outcomes were pragmatic in soybean-maize intercropping, as application of Mo @ 120 g ha-1 significantly improved soybean growth and yield attributes, including leaf area index (LAI; 434 and 441%), total plant biomass (430 and 461%), transpiration rate (15 and 18%), stomatal conductance (9 and 11%), and yield (15 and 20%) during year 2020 and 2021 respectively, as compared to control treatment. Similarly, Mo @ 120 g ha-1 application resulted in highest total grain yield (626.0 and 725.3 kg ha-1) during 2020 and 2021 respectively, which exceeded the grain yields of other Mo levels under intercropping. Moreover, under Mo application level (120 g ha-1), grain NPK and Mo contents during years 2020 and 2021 were found to be 1.15, 0.22, 0.83 and 68.94 mg kg-1, and 1.27, 0.25, 0.90 and 72.18 mg kg-1 under intercropping system increased the value as compared to control treatment. Findings of current study highlighted the significance of Mo in enhancing soybean growth, yield, and nutrient uptake efficiency in maize-soybean intercropping systems.


Green synthesis, characterisation and antibacterial activities of Strobilanthes crispus-mediated silver nanoparticles (SC-AGNPS) against selected bacteria.
This study aims to characterize and determine the antibacterial activities of synthesized Strobilanthes crispus-mediated AgNPs (SC-AgNPs) against Streptococcus mutans, Escherichia coli and Pseudomonas aeruginosa. S. crispus water extract acts as a reducing and capping agent in the synthesis of AgNPs. The synthesized AgNPs were characterized by using UV-Vis spectrophotometer, dynamic light scattering (DLS), field emission scanning electron microscope (FESEM), X-ray diffractometer (XRD) and Fourier transform infra-red (FTIR). FESEM images showed a rough surface with a spherical shape. The average size distribution of 75.25 nm with a polydispersity index (PDI) of 0.373. XRD analysis matched the face-centred cubic structure of silver. FTIR analysis revealed a shifted peak from 1404.99 to 1345.00 cm-1. MIC and MBC values of SC-AgNPs were 1.25 mg/mL and 2.5 mg/mL against E. coli, P. aeruginosa and S. mutans, respectively. Time-kill assay showed that SC-AgNPs significantly reduced bacterial growth as compared to non-treated bacteria. Morphologies of bacteria treated with SC-AgNPs were shrunk, lysed, irregular and smaller as compared to control. SC-AgNPs significantly disrupted the gene expression of eae A, gtf B and Pel A (p < 0.05). This study indicated that the synthesized SC-AgNPs were stable with enhanced antibacterial activities.


"Composite" tumor--mixed squamous cell and small-cell anaplastic carcinoma of the larynx.
Mixed squamous and oat cell carcinomas (composite neoplasms) of the larynx behave aggressively with a propensity toward early dissemination. Diagnosis may not be made until definitive surgery is performed. The extent of surgery must be determined by the size and site of the primary neoplasm and the physiologic status of the patient. In our experience, surgery has adequately controlled the primary disease. A metastatic work-up is essential. Entry into a comprehensive program employing adjunctive radiotherapy and chemotherapy are strongly recommended. Theories concerning histogenesis remain controversial and include two separate colliding tumors, differentiation from a single cell line, or divergent differentiation of a single cell line.


Factors affecting the accuracy and safety of computed tomography-guided biopsy of intrapulmonary solitary nodules ≤30 mm in a retrospective study of 155 patients.
Computed tomography (CT)-guided percutaneous fine needle biopsy is a common method for lung biopsy. The objective of this study was to investigate factors affecting the accuracy and safety of CT-guided percutaneous lung biopsy of nodules ≤30 mm in diameter. Between January 2013 and March 2014, 155 patients underwent a CT-guided percutaneous biopsy procedure on an intrapulmonary solitary nodule measuring ≤30 mm in diameter. Prospectively collected data were retrospectively reviewed and examined for the influence of clinical and pathological characteristics (age, gender, smoking status, adhesion of nodule to the pleura, puncture depth, nodule size and time of biopsy) on the accuracy of biopsy and incidence of pneumothorax and hemorrhage. The accuracy of CT-guided biopsy was 90.3% (140/155). Biopsies predominantly contained lung adenocarcinoma (114/140; 81.4%) or squamous cell carcinoma of the lung (10/140; 7.1%). Accuracy was significantly dependent on nodule size, ranging in accuracy from 85 to 97% for patients with nodule diameters of ≤20 or 21-30 mm, respectively (P<0.05). Pleural adherence of the nodule significantly increased the accuracy of the biopsy (P<0.05). Patients with a nodule of 11-20 mm in diameter had a significantly higher incidence of pneumothorax compared with patients with a smaller nodule (P=0.013). In conclusion, the nodule size and adhesion to the pleura influenced the accuracy of CT-guided biopsy of intrapulmonary nodules that were ≤30 mm in diameter. Nodule size may also affect the incidence of severe complications. CT-guided percutaneous lung biopsy has a high accuracy and is easy and safe to conduct for intrapulmonary solitary nodules of ≤30 mm in diameter.


Hsp70-nucleotide exchange factor (NEF) Fes1 has non-NEF roles in degradation of gluconeogenic enzymes and cell wall integrity.
Fes1 is a conserved armadillo repeat-containing Hsp70 nucleotide exchange factor important for growth at high temperature, proteasomal protein degradation and prion propagation. Depleting or mutating Fes1 induces a stress response and causes defects in these processes that are ascribed solely to disruption of Fes1 regulation of Hsp70. Here, we find Fes1 was essential for degradation of gluconeogenic enzymes by the vacuole import and degradation (Vid) pathway and for cell wall integrity (CWI), which is crucial for growth at high temperature. Unexpectedly, Fes1 mutants defective in physical or functional interaction with Hsp70 retained activities that support Vid and CWI. Fes1 and the Fes1 mutants bound to the Vid substrate Fbp1 in vitro and captured Slt2, a signaling kinase that regulates CWI, from cell lysates. Our data show that the armadillo domain of Fes1 binds proteins other than Hsp70, that Fes1 has important Hsp70-independent roles in the cell, and that major growth defects caused by depleting Fes1 are due to loss of these functions rather than to loss of Hsp70 regulation. We uncovered diverse functions of Fes1 beyond its defined role in regulating Hsp70, which points to possible multi-functionality among its conserved counterparts in other organisms or organelles.


Severe Life-Threatening Sepsis Complicating Infected Thumb Carpometacarpal Arthroplasty.
Thumb Carpometacarpal (CMC) total joint arthroplasty is commonly performed with increasing numbers worldwide. We present a case of Prosthetic Joint Infection (PJI) leading to severe septic shock and disseminated septic emboli 8 months following uneventful thumb CMC arthroplasty. Such extensive and life-threatening infection following thumb CMC arthroplasty has not been reported. Level of Evidence: Level V (Therapeutic).


Determination of lysozyme activity by a fluorescence technique in comparison with the classical turbidity assay.
The aim of this comparable study was to evaluate two different methods for the assay of lysozyme activity. Lysozyme activity was assayed by turbidimetric and fluorescence-based methods with hen egg white lysozyme as standard. The standard activity of each assay was calibrated in units of activity per mg under the experimental conditions (37 degrees C) so that direct comparison between these two assays could be made. The turbidimetric assay was performed using a 0.36 mg/ml Micrococcus lysodeikticus suspension and a microtiter plate reader capable of analyzing enzyme kinetics at 450 nm, and the linearity, in the range of 2.3-23.8 units/ml, presented a correlation coefficient (R2) as high as 0.9967. The fluorescence-based assay was performed with EnzChek kit using a suspension of Micrococcus lysodeikticus labeled with fluorescein and a fluorescence microplate reader. The linearity in the range of 0.47-5.28 units/ml, presented a correlation coefficient (R2) as high as 0.9881. Thus, the turbidimetric assay provides a simple rapid accurate and specific method for the determination of lysozyme activity but with relatively low sensitivity in comparison with the fluorescence-based method which was demonstrated to be a high sensitivity assay, and hence a reliable applicable technique to determine lysozyme activity at low levels e.g. in cell culture systems.


Perceived psychological stress among high school basketball officials.
The purpose of this study was to survey certified high school basketball officials during midseason to assess whether the sources and magnitude of perceived psychological stress would be consistent with previous studies of officials in other sports. The sources and magnitude of perceived psychological stress were measured among 324 high school basketball officials (N=324; 312 men, 12 women) using a revised version of the Ontario Soccer Officials Survey. The mean age was 37.6 yr. (SD= 9.4), and the mean years of basketball refereeing experience was 11.7 yr. (SD=8.3). A random sample (N=498) of all basketball officials in a midwestern state (N=1,011) was used, and 324 of the surveys were returned (65%). The overall variance accounted for with the four factors was 84.7%. The magnitude of stress for these factors ranged from below mild to moderate.


Public attitudes regarding a pilot study of newborn screening for spinal muscular atrophy.
A population-based pilot study of newborns screening for a rare genetic condition, spinal muscular atrophy (SMA), is being conducted with funding from the National Institutes of Health. The first component of the study is to assess the ethical, legal, and social implications of population-based pilot studies with a focus on public engagement and parental decision-making for the proposed opt-out approach in this research. We conducted focus groups with members of the general public to ascertain attitudes about the pilot study and acceptability of an opt-out approach in two states, Colorado and Utah, where the pilot screening is being proposed (N = 70). We developed an informational video for the project and showed it to the groups prior to the discussion in order to inform participants about population-based research, newborn screening (NBS), permission/consent models, and SMA. Results indicated support for the conduct of pilot studies that is consistent with the current standard of practice for similar population-based programs. There was support for an opt-out approach for parental decision-making; however there was limited parental knowledge about population-based research, NBS and SMA. In general, our participants considered this pilot study to be low risk and of potential benefit to infants and families. The majority of participants were supportive of an opt-out approach with information delivered through various avenues


Localization-based super-resolution imaging of cellular structures.
Fluorescence microscopy allows direct visualization of fluorescently tagged proteins within cells. However, the spatial resolution of conventional fluorescence microscopes is limited by diffraction to ~250 nm, prompting the development of super-resolution microscopy which offers resolution approaching the scale of single proteins, i.e., ~20 nm. Here, we describe protocols for single molecule localization-based super-resolution imaging, using focal adhesion proteins as an example and employing either photoswitchable fluorophores or photoactivatable fluorescent proteins. These protocols should also be easily adaptable to imaging a broad array of macromolecular assemblies in cells whose components can be fluorescently tagged and assemble into high density structures.


Environmental health in the health care setting.
The health care industry is a major contributor to environmental pollution. Through the processes of waste disposal, including incineration, the health care industry is one of the largest contributors to environmental dioxin and mercury. Mercury contamination of our waterways has created the conditions by which a significant number of fish are sufficiently mercury-laden so as to pose a human health threat. Additionally, there are products and processes within the hospital that create health risks for the patients and health care staff. There are a number of positive actions that nurses can take to address the health threats posed by these exposures. These actions include: purchasing environmentally preferable products, implementing pollution prevention actions within the health care setting, and learning more about environmental health.


Teaching effectiveness of the trauma evaluation and management module for senior medical students.
The Trauma Evaluation and Management (TEAM) module was devised by the American College of Surgeons for teaching senior medical students trauma management principles. This article reports on the teaching effectiveness of this module. Cognitive skills (by 20 item multiple-choice question examination on trauma topics) and clinical trauma management skills performance, using the Objective Structured Clinical Examination, were compared between two groups of 16 randomly selected final year medical students who had completed the standard curriculum including trauma topics. One group had the TEAM (TEAM group) and the other did not (no-TEAM group). Objective Structured Clinical Examination score (percentage), Priority score (range, 1-7), Organized Approach score (range, 1-5), and Global Pass status were assigned at each station. The students also completed a five-part questionnaire. Results of the questionnaire showed that on a scale of 1 to 5, with 5 being excellent, 96.8% assigned a score of 4 or greater, indicating the objectives were met, 83.8% that trauma knowledge was improved, 51.6% that clinical skills were improved, 90.3% that the module should be mandatory, and 83.9% overall satisfaction with the program. The TEAM module is very effective in teaching trauma management principles to senior medical students, by whom the program was very well received. Consideration should be given to adopting this program more widely in our medical undergraduate curriculum.


Fasciola antigens as vaccines against fascioliasis and schistosomiasis.
Fascioliasis is an important trematode infection of herbivores worldwide with increasing evidence of prevalence as a disease of humans. Vaccination studies with purified native and recombinant Fasciola antigens suggest that this approach to diminished morbidity and mortality and reduced transmission is a realistic goal. Among the major potential vaccine candidates are fatty acid binding protein (FABP), cysteine (cathepsin) proteases, haemoglobulin, leucine aminopeptidase, and a saposin-like protein. In the case of Fasciola hepatica FABP, cross-reaction and cross-protection against Schistosoma mansoni is an important feature. In addition to protective effects with significant worm burden reductions, some vaccine candidates also have anti-fecundity (smaller flukes), anti-pathology (less liver lesions), and anti-embryonation effects. Optimism is tempered by the fact that fascioliasis in humans is an orphan disease and in need of governmental and foundation support.


Variable air temperature response of gas-phase atmospheric polychlorinated biphenyls near a former manufacturing facility.
Many investigations of gas-phase atmospheric PCB show a strong relationship between concentration and air temperature, especially near PCB sources. Comparative gas-phase atmospheric PCB trends during an annual temperature regime at two sites near a former PCB manufacturing plant and nearby PCB landfills in Anniston, AL, indicate a departure from this trend. The Mars Hill sampling site, located closest to the plant and landfills, shows an annual average sigmaPCB concentration of 27 ng m(-3) (ranging from 8.7 to 82 ng m(-3)) three times the average at Carter, 1.5 km away (9 ng m(-3), ranging from 1.1 to 39). However, total PCB and congener concentrations vary more with air temperature at Carter where PCB are evaporating from surfaces during warmer weather. The slopes of the Clausius-Clapeyron plots of 18 of the most concentrated congeners representing dichloro- through heptachlorobiphenyl homologues are significantly higher at the Carter site. While some of the atmospheric PCB at Mars Hill is derived from ground surface evaporation, the source of much of it apparently is the material buried in the landfills, which has different thermal properties than surface materials and is not in equilibrium with air temperature.


Beck's Depression Inventory as a screening instrument for adolescent depression in Sweden: gender differences.
Beck's Depression Inventory was administered in a study of all students aged 16-17 years in the first year of high school in a Swedish town, and was completed by 93% of them (n = 2270). Cronbach's reliability coefficient alpha was 0.89, and there were strong correlations between item scores and total scores. A diagnostic interview focused on depressive diagnosis during the last year was conducted with 88% (n = 199) of all students with high scores (> or = 16), and with the same number of controls with low scores. A depressive diagnosis was confirmed in 73% of high scorers and 13% of low scorers. The questionnaire performed better with girls than with boys. The mean score was significantly higher for girls, and the proposed limit for moderate depression (a score of 16) was reached by 14.2% of girls and 4.8% of boys. All symptoms were significantly more frequent and more severe in girls. It was found that 20% of girls and 6% of boys reported suicidal ideation. In a factor analysis the strongest factor that emerged differed between the sexes. For boys it included sadness, crying and suicidal ideation, and for girls it included failure, guilt, self-dislike and feeling unattractive, combined with suicidal ideation. The gender differences are discussed.


Structure of polydopamine: a never-ending story?
Polydopamine (PDA) formed by the oxidation of dopamine is an important polymer, in particular, for coating various surfaces. It is composed of dihydroxyindole, indoledione, and dopamine units, which are assumed to be covalently linked. Although PDA has been applied in a manifold way, its structure is still under discussion. Similarities have been observed in melanins/eumelanins as naturally occurring, deeply colored polymer pigments derived from L-DOPA. Recently, an alternative structure was proposed for PDA wherein dihydroxyindoline, indolinedione, and eventually dopamine units are not covalently linked to each other but are held together by hydrogen bonding between oxygen atoms or π stacking. In this study, we show that this structural proposal is very unlikely to occur taking into account unambiguous results obtained by different analytical methods, among them (13)C CPPI MAS NMR (cross-polarization polarization-inversion magic angle spinning NMR), (1)H MAS NMR (magic angle spinning NMR), and ES-HRMS (electrospray ionization high-resolution mass spectrometry) for the first time in addition to XPS (X-ray photoelectron spectroscopy) and FTIR spectroscopy. The results give rise to a verified structural assignment of PDA wherein dihydroxyindole and indoledione units with different degrees of (un)saturation are covalently linked by C-C bonds between their benzene rings. Furthermore, proof of open-chain (dopamine) monomer units in PDA is provided. Advanced DFT calculations imply the arrangements of several PDA chains preferably by quinone-hydroquinone-type interactions in a parallel or antiparallel manner. From all of these results, a number of hypotheses published before could be experimentally supported or were found to be contradictory, thus leading to a better understanding of the PDA structure.


Adsorption of platinum (IV), palladium (II) and gold (III) from aqueous solutions onto L-lysine modified crosslinked chitosan resin.
Crosslinked chitosan resin chemically modified with L-lysine has been used to investigate the adsorption of Pt(IV), Pd(II) and Au(III) from aqueous solutions. Batch adsorption studies were carried out with various parameters, such as initial metal ion concentration, contact time, pH and temperature. The maximum adsorption capacity was found at pH 1.0 for Pt(IV), at pH 2.0 for Au(III) and Pd(II). Langmuir and Freundlich isotherm models were applied to analyze the experimental data. The best interpretation for the experimental data was given by the Langmuir isotherm and the maximum adsorption capacity was found to be 129.26 mg/g for Pt(IV), 109.47 mg/g for Pd(II) and 70.34 mg/g for Au(III). The kinetic data was tested using pseudo-first-order and pseudo-second-order kinetic models. Kinetic data correlated well with the pseudo-second-order kinetic model, indicating that the chemical sorption was the rate-limiting step. Thermodynamic parameters like Gibbs free energy (DeltaG degrees), enthalpy (DeltaH degrees) and entropy (DeltaS degrees) were evaluated by applying the Van't Hoff equation. The thermodynamic study indicated that the adsorption process is spontaneous and exothermic in nature. The desorption studies were carried out using various reagents. The maximum percent desorption of precious metal ions were obtained when the reagent 0.7 M thiourea-2 M HCl was used.


Ordered hierarchically porous carbon codoped with iron and nitrogen as electrocatalyst for the oxygen reduction reaction.
N-doped carbon catalysts have attracted great attention as potential alternatives to expensive Pt-based catalysts used in fuel cells. Herein, an ordered hierarchically porous carbon codoped with N and Fe (Fe-NOHPC) is prepared by an evaporation-induced self-assembly process followed by carbonization under ammonia. The soft template and Fe species promote the formation of the porous structure and facilitate the oxygen reduction reaction (ORR).The catalyst possesses an ordered hierarchically porous structure with a large surface area (1172.5 m(2) g(-1) ) and pore volume of 1.03 cm(3) g(-1) . Compared to commercial 20% Pt/C, it exhibits better ORR catalytic activity and higher stability as well as higher methanol tolerance in an alkaline electrolyte, which demonstrates its potential use in fuel cells as a nonprecious cathode catalyst. The N configuration, Fe species, and pore structure of the catalysts are believed to correlate with its high catalytic activity.


Fifty-Patient Study Evaluating the Efficacy of Modified Collagen With Glycerin in Periwound Skin Management.
The management of chronic nonhealing ulcers pose a great challenge because they are associated with morbidity and increased costs. This report presents the observations of standard management along with application of modified collagen with glycerin (MCG) in the periwound area for management of nonhealing wounds. This observational report included 50 patients (33 male, 17 female) aged 24 to 94 years having nonhealing wounds. All wounds were treated using standard treatment protocols (TIME concept), whereas the periwound severity was assessed using the Harikrishna Periwound Skin Classification (HPSC). All patients received once-daily application of MCG lotion directly in the periwound areas and compression bandaging until there was complete wound healing. Patient compliance was ensured by regular follow-up and counseling. All diabetic patients were counseled to ensure glycemic control during the entire follow-up period. The criteria used for wound healing were based on clinical observation, and proper epithelialization of the wound was the end point. The median age of the wounds was 12.0 weeks (95% CI = 8.00 - 58.08). Majority of the non-healing wounds were diabetic foot ulcers with age of wound between 4 weeks to 15 years. The median time to complete wound healing was 12.71 (95% CI = 10.00-16.67) weeks. Standard treatment protocol of TIME principle with periwound area assessment based on HPSC 2015 and treatment accordingly with topical application of MCG along with additional measures has shown complete healing of nonhealing wounds. However, further large-scale comparative studies are needed to substantiate these effects on a larger population.


Petroclival meningioma: a rare cause of serous otitis media.
A 22 years man presented with aural fullness and hearing impairment in his right ear for one year. Otoscopy showed middle ear effusion in the right ear and nasopharyngoscopy revealed a protruding mass on the right side of the nasopharynx. Computed tomography of the nasopharynx showed a large intracranial tumor extending to the infratemporal region via foramen ovale. The patient received staged surgeries and final pathology was diagnosed as meningioma. Approximately 20% of all intracranial tumors are meningiomas and only about 2% of these occur in the petroclival region. Although most meningiomas are benign and asymptomatic, they can cause head and neck manifestations as extending through a skull foramen, across a cranial suture or through a tumor-induced bone defect. Radiographic evaluation is required to rule out this rare clinical entity.


[Confidential enquiries and medical expert committees: a method for evaluating healthcare. The case of Obstetrics].
Confidential inquiries into dramatic events are a specific type of audit used to measure quality of care. Confidential inquiries have been conducted on maternal deaths in some European countries since 1920-30. In France, the first one was carried out in 1996. The number of these surveys is increasing, including in developing countries. Initially implemented in perinatology, they are also being carried out in other surgical or medical areas. The aim of this work was to describe the methods used and demonstrate their contribution to evaluating healthcare services. We reviewed the literature and studied several confidential inquiries. These inquiries were in-depth examinations conducted by peers of medical events leading to critical outcomes. They were based on scientific reasoning in an attempt to explain what happened. Strict confidentiality, for patients and healthcare providers, was assured. The different steps and rules of investigation were clearly defined. About twenty confidential inquiries concerning perinatal events have been published worldwide. Other inquiries concerning anesthetic accidents, stroke with hypertension, or surgical complications have also been reported. Their principal contribution lies in the capacity to identify weaknesses in the healthcare service and care organization. Suboptimal care and avoidable factors of death were found in all cases. Most of the reports led to recommendations. These inquiries provide essential information for reorganizing current healthcare practices. Confidential inquiries are needed to complete standard epidemiology surveys in evaluating healthcare and healthcare organization.


Stomatal and mesophyll conductances to CO2 are the main limitations to photosynthesis in sugar beet (Beta vulgaris) plants grown with excess zinc.
*The effects of zinc (Zn) toxicity on photosynthesis and respiration were investigated in sugar beet (Beta vulgaris) plants grown hydroponically with 1.2, 100 and 300 microM Zn. *A photosynthesis limitation analysis was used to assess the stomatal, mesophyll, photochemical and biochemical contributions to the reduced photosynthesis observed under Zn toxicity. *The main limitation to photosynthesis was attributable to stomata, with stomatal conductances decreasing by 76% under Zn excess and stomata being unable to respond to physiological and chemical stimuli. The effects of excess Zn on photochemistry were minor. Scanning electron microscopy showed morphological changes in stomata and mesophyll tissue. Stomatal size and density were smaller, and stomatal slits were sealed in plants grown under high Zn. Moreover, the mesophyll conductance to CO(2) decreased by 48% under Zn excess, despite a marked increase in carbonic anhydrase activity. Respiration, including that through both cytochrome and alternative pathways, was doubled by high Zn. *It can be concluded that, in sugar beet plants grown in the presence of excess Zn, photosynthesis is impaired due to a depletion of CO(2) at the Rubisco carboxylation site, as a consequence of major decreases in stomatal and mesophyll conductances to CO(2).


[Usefulness of protein/creatinine ratio in spot urine using test strips].
The influence of concentration and dilution has been the major issue of urinalysis. This study is to evaluate the usefulness of protein (P)/creatinine (C) ratio (P/C ratio) in spot urine by test strips method. For this purpose, the basic performance of creatinine test strips is evaluated and judging criteria for the urine P/C ratio is defined. Our evaluation revealed that the creatinine test strips were basically not affected by substances which have similar composition to creatinine, such as creatine, but by some medical agents and disinfectant. Its minimum detective sensitivity was 6.0 mg/dl, while that of protein test strips was 1.3 mg/dl. We determined judging criteria for the P/C ratio as follows: Below 80 mg/gCr, Normal; 80 to 500mg/gCr, 1 +; over 500 mg/gCr, 2+. The P/C ratio based on the quantitative and test strips methods provided good consistency of 82.2%. In low-creatinine urine samples (11 to 99mg/dl), 181 of 216 samples (83.8%) were tested negative on single-protein tests; while the P/C ratio provided fewer negative results, 134 of 216(62.0%). Moreover, in high-creatinine urine samples (200 to 600 mg/dl), 70 of 122 samples (57.4%) were tested negative on single protein tests; while the P/C ratio provided negative results in almost all the samples, 120 of 122 (98.4%). These urine samples were mostly collected at a medical examination. The results above showed that the P/C ratio obtained by easy and quick test strip method is equivalent to the quantitative method in performance and useful for spot urine testing.


[Current surgical strategy of locally recurrent rectal cancer].
The incidence of locally recurrent rectal cancer (LRRC) is less than 10% following treatment for primary rectal cancer, while LRRC usually has serious symptoms and a very low survival rate when lack of treatment. For further efficacy improvement of LRRC operation, recent research topics include preoperative precise evaluation, correct decision, reasonable individual treatment by multidisciplinary collaboration. Surgery remains the only option for potential cure. Studies show R0 resection is the most important prognostic factor. Peking University First Hospital proposes a new classification of LRRC: Pelvic cavity is divided into right pelvic wall, left pelvic wall and posterior sacrococcyx. LRRC is classified as F0 to F3 according to invasion quantity in pelvic wall or sacrococcyx. This classification is more suitable for clinical practice. Though determining the LRRC location by CT, MRI and PET, scientific classification evaluation and correct choice of proper patients using F classification to fix the extent of pelvic wall can effectively elevate the R0 resection rate, and at the same time, can avoid ineffectual high-risk re-operation. This article also investigates the efficacy of comprehensive treatment based on preoperative neoadjuvant therapy, intra-operative radiotherapy and re-radiotherapy, in order to provide the guidance for the institution of reasonable and scientific treatment strategy in clinic.


Evaluating the effectiveness of therapies for urinary incontinence.
Subjective criteria, behavioral/emotional factors, and quality-of-life assessments are necessary components in evaluating incontinence therapies. Behavioral regimens often yield a response that lasts beyond the end of therapy and, when combined with pharmacologic therapy, are likely to extend duration of response. In addition to objective efficacy criteria, a number of instruments evaluate quality-of-life issues. Shortened forms of these will likely overcome limitations on patient compliance and completion. New instruments continue to be developed, but until one or more are universally accepted, variations in reported outcomes can be expected.


The inner laryngeal lymphatics. A lymphangioscopical and electron microscopical study.
Lymphangioscopical and ultrastructural studies of the larynx reveal a lymphatic capillary and a collecting vessel system. Collecting vessels show luminal valves and elastic structural components within the wall. Lymphangioscopy reveals that a strict compartmentation of different laryngeal areas is unjustifiable with the exception made for the capillaries of the free margin of the true vocal cords. Multiple anastomoses of capillaries and collecting vessels enhance midline- and vertical plane-crossing lymphatic drainage. These collaterals are gaining importance in case of impediment of the physiologic drainage pathway.


Tamoxifen enhances the Hsp90 molecular chaperone ATPase activity.
Hsp90 is an essential molecular chaperone that is also a novel anti-cancer drug target. There is growing interest in developing new drugs that modulate Hsp90 activity. Using a virtual screening approach, 4-hydroxytamoxifen, the active metabolite of the anti-estrogen drug tamoxifen, was identified as a putative Hsp90 ligand. Surprisingly, while all drugs targeting Hsp90 inhibit the chaperone ATPase activity, it was found experimentally that 4-hydroxytamoxifen and tamoxifen enhance rather than inhibit Hsp90 ATPase. Hence, tamoxifen and its metabolite are the first members of a new pharmacological class of Hsp90 activators.


The reliability and transparency bases of trust in human-swarm interaction: principles and implications.
Automation reliability and transparency are key factors for trust calibration and as such can have distinct effects on human reliance behaviour and mission performance. One question that remains unexplored is: what are the implications of reliability and transparency on trust calibration for human-swarm interaction? We investigate this research question in the context of human-swarm interaction, as swarm systems are becoming more popular for their robustness and versatility. Thirty-two participants performed swarm-based tasks under different reliability and transparency conditions. The results indicate that trust, whether it is reliability- or transparency-based, indicates high reliance rates and shorter response times. Reliability-based trust is negatively correlated with correct rejection rates while transparency-based trust is positively correlated with these rates. We conclude that reliability and transparency have distinct effects on trust calibration. Practitioner Summary: Reliability and transparency have distinct effects on trust calibration. Findings from our human experiments suggest that transparency is a necessary design requirement if and when humans need to be involved in the decision-loop of human-swarm systems, especially when swarm reliability is high. Abbreviations: HRI: human-robot interaction; IOS: inter-organisational systems; LMM: liner mixed models; MANOVA: multivariate analysis of variance; UxV: heterogeneous unmanned vehicles; UAV: unmanned aerial vehicle.


Long-term outcomes for patients with post-liver transplant anastomotic biliary strictures treated by endoscopic stent placement.
Biliary stricture is one of the most common complications of liver transplantation. A number of treatment options are available, but a standard approach has not been established. A total of 25 patients with post-liver transplantation anastomotic strictures were treated endoscopically by stent placement. Long-term outcomes (bile duct patency, morbidity, and mortality) were reviewed retrospectively. Placement of a stent was attempted in 25 patients with anastomotic stricture. Successful stent placement with stricture resolution at the time of stent removal was noted in 22 patients (technical success 88%). In those 22 patients, long-term success (mean follow-up after all stents removed, 54 months) was observed in 20 patients (90%) and partial success in two (10%). Long term, failure did not occur in any patient. There was no procedure- or disease-related mortally. Three mild episodes of cholangitis occurred during the period while the stents were in place, in relation to 79 endoscopic interventions for a procedure-related complication rate of 3.7%. The long-term outcome for patients with post-liver transplantation biliary anastomotic strictures treated with endoscopic stent placement is excellent, with no therapy- or disease-associated mortality and minimal morbidity.


Impaired fasting glucose and impaired glucose tolerance have distinct lipoprotein and apolipoprotein changes: the insulin resistance atherosclerosis study.
Cardiovascular risk is increased in individuals with impaired glucose tolerance (IGT) and impaired fasting glucose (IFG); however, those with IGT appear to be at greater risk. Lipoprotein abnormalities occur also in the prediabetic state. The authors examined lipoprotein composition in IGT and IFG. Cross-sectional analysis of a large epidemiological study was done. The Insulin Resistance Atherosclerosis Study had a total of 1107 participants. Lipoproteins and apolipoproteins were measured by conventional methods and lipoprotein composition by nuclear magnetic resonance spectroscopy. Compared with normal glucose tolerance, apolipoprotein B (105.2 vs 99.8 mg/dL, P < .05) was high in isolated IFG, triglyceride (1.48 vs 1.16 mmol/L, P < .001) was high in isolated IGT, and high-density lipoprotein cholesterol was low in combined IFG/IGT (1.12 vs 1.26 mmol/L, P < .001). Nuclear magnetic resonance spectroscopy revealed additional changes: increased total low-density lipoprotein (LDL) particles (1190 vs 1096 nmol/L, P < .01) in isolated IFG; increased large very-low-density lipoprotein (3.61 vs 2.47 nmol/L, P < .01) and small LDL subclass particles (665 vs 541 nmol/L, P < .05) and decreased large LDL subclass particles (447 vs 513 nmol/L, P < .01) in isolated IGT; and decreased large high-density lipoprotein subclass particles in combined IFG/IGT (4.24 vs 5.39 μmol/L, P < .001). Isolated IFG is characterized by increased apolipoprotein B and total LDL particles, whereas isolated IGT is associated with increased triglycerides, large very-low-density lipoprotein subclass particles, and structural remodeling of LDL particles. These results may help to explain differences in cardiovascular disease risk in the prediabetic state.


Infected fractures of the hand and wrist.
Infected fractures of the hand and wrist are uncommon, occurring most often after open crushing injury in a contaminated environment. Fundamental principles of treatment include thorough debridement of necrotic material, appropriate antibiotic selection, and adequate stabilization of bone. Delayed reconstruction of bone and soft tissue is at times aided by the use of free tissue transfer.


Regulatory effects of novel neurotrophin-1/b cell-stimulating factor-3 (cardiotrophin-like cytokine) on B cell function.
We describe regulatory effects that a novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3; also reported as cardiotrophin-like cytokine) has on B cell function. NNT-1/BSF-3 stimulates B cell proliferation and Ig production in vitro. NNT-1/BSF-3-transgenic mice, engineered to express NNT-1/BSF-3 in the liver under control of the apolipoprotein E promoter, show B cell hyperplasia with particular expansion of the mature follicular B cell subset in the spleen and the prominent presence of plasma cells. NNT-1/BSF-3-transgenic mice show high serum levels of IgM, IgE, IgG2b, IgG3, anti-dsDNA Abs, and serum amyloid A. NNT-1/BSF-3-transgenic mice also show non-amyloid mesangial deposits that contain IgM, IgG, and C3 and are characterized by a distinctive ultrastructure similar to that of immunotactoid glomerulopathy. NNT-1/BSF-3-transgenic mice produce high amounts of Ag-specific IgM, IgA, and IgE and low amounts of IgG2a and IgG3. Normal mice treated with NNT-1/BSF-3 also produce high amounts of Ag-specific IgE. NNT-1/BSF-3 regulates immunity by stimulating B cell function and Ab production, with preference for Th2 over Th1 Ig types.


The effects of a cyclo-oxygenase II inhibitor on placental artery production of thromboxane and prostacyclin.
The study was undertaken to determine the effects of a cyclo-oxygenase II inhibitor on fetoplacental artery production of prostacyclin and thromboxane A(2). Eight placentas were obtained from normal parturients at delivery and four chorionic plate arteries were dissected from each placenta. Arteries were incubated in media alone, media plus angiotensin II (1x10(-10) mol), media plus rofecoxib (300 ng/mL), or media plus angiotensin II and rofecoxib. Serial samples were assayed for metabolites of thromboxane B(2) and prostacyclin by enzyme-linked immunosorbent assay. Results were compared by analysis of variance, and P<.05 was considered significant. At 24 hours, 6-keto-prostaglandin F(1alpha) levels in the rofecoxib group (1.74+/-1.39 ng/mg tissue, P<.01) and the rofecoxib plus angiotensin II group (2.15+/-1.85 ng/mg tissue, P<.01) were significantly lower than levels in the control group (4.25+/-2.03 ng/mg tissue). Thromboxane B(2) levels were lower in the angiotensin II group (0.65+/-0.33 ng/mg tissue) than the control group (1.22+/-0.70 ng/mg tissue, P<.05). Cyclo-oxygenase II inhibition decreases the production of prostacyclin in fetoplacental arteries and alters the normal ratio of thromboxane A(2) to prostacyclin.


Visual pigment renewal in the mature frog retina.
It has been demonstrated by autoradiography that radioactive amino acids serve as precursors for proteins which are subsequently incorporated into retinal rod outer segment discs in mature animals. By the isolation and purification of visual pigment from retinas of adult frogs after injection of tritiated leucine and phenylalanine, it has been shown that at least part of this labeled protein consists of visual pigment (rhodopsin).


NIH Budget Makes Up Ground.
Since 2015, 4 consecutive years of substantial increases have expanded the NIH budget by a total of $9 billion, or 30%-a boost that has helped the agency close the gap on medical inflation. Most recently, Congress approved a $2 billion increase for fiscal year 2019, bringing the agency's total budget to $39.1 million.


Postoperative Shivering Among Cannabis Users at a Public Hospital in Trinidad, West Indies.
Postoperative shivering has been anecdotally observed to be frequent and severe in Cannabis smokers following general anesthesia in the Caribbean. The aim of this study was to compare the frequency and intensity of postoperative shivering in Cannabis users versus non-users. A prospective, cross-sectional, observational design was used. Demographic data were obtained. Patients were grouped into Cannabis users and non-users. All patients received standardized general anesthesia and were administered warmed fluids intraoperatively. Ambient room temperatures and clinical data were recorded. Patients' core body temperature was recorded at 10-minute intervals both in the operating room and the post-anesthesia care unit (PACU). Postoperatively an independent observer assessed the patients who had shivering using a scoring system ranging from 0 to 3. Treatment for shivering and post-treatment shivering scores were also recorded. Fifty-five patients were studied, of which 71% were male. There were 25 (45%) Cannabis users, of which 50% smoked < 5 joints per week, and 35% smoked >10 joints per week; 30 (55%) patients were non-users. The overall incidence of postoperative shivering was 36%; 16% had a shivering score of '3', 13% had '2' and 7% had a score of '1'. The incidence of postoperative shivering among Cannabis users was 40% while it was 33.3% in non-users. Also, 90% of Cannabis users had shivering scores of 2 and 3, compared to 70% of non-users. There was a higher incidence and intensity of shivering in Cannabis smokers, although the study could not establish a statistically significant difference in the frequency and severity of shivering between Cannabis users and non-users.


Severe immune thrombocytopenia induced by a single dose of nivolumab in a patient with advanced non-small cell lung cancer.
Nivolumab-induced immune thrombocytopenia (ITP) is a rare process with few reported cases. We present a 67-year-old man with advanced non-small cell lung cancer who was hospitalized with severe thrombocytopenia. Physical exam was notable for petechiae across his chest and extremities as well as bullae in his oral cavity. The patient initially received high-dose glucocorticoids and intravenous immuno - globulin, but did not respond to treatment. He was then started on weekly rituximab and after three doses, there was complete resolution of his thrombocytopenia. Altogether, his presentation was an extreme case and rare side effect of immune checkpoint therapy, known as nivolumab-induced ITP. Diagnosis of nivolumab-induced ITP is challenging given the lack of specific testing and a wide differential diagnosis. There are few cases reporting severe ITP following nivolumab treatment. We highlight the importance of recognizing and treating this rare complication of immunotherapy.


Transfer of human nasal papilloma into nude mice.
We transferred tumor tissue from two inverted schneiderian nasal papillomas to hypothymic nude mice. Tissue from one tumor, which later underwent malignant change, was transferred three times. Forty days lapsed before growth was evident, with a subsequent period of rapid growth. Histologic appearances of the primary tumor and xenografts were similar. Although the data are derived from only two cases, our findings suggest that the capacity of these tumors to grow in nude mice may be an index of their malignant potential.


To Evaluate the Correlation between the ABO Blood Group, Lip, and Fingerprint Pattern.
This research set out to see whether there was a connection between the ABO blood type and the unique patterns found on people's lips and fingerprints.As many as a hundred people were surveyed for this study. Red lip gloss, cellophane tape, white A3 paper, a stamp pad with blue ink, and a magnifying glass were also used.O+ blood type, a full vertical lip print, and a loopy fingerprint pattern were the most common types of individuals.Lip patterns, fingerprints, and blood types are just a few of the personally identifiable characteristics that have been shown to be useful in forensic identification. We found no evidence of a link between these three variables in our analysis.


In vitro study of hydroxyapatite/polycaprolactone (HA/PCL) nanocomposite synthesized by an in situ sol-gel process.
Hydroxyapatite (HA) is the most substantial mineral constituent of a bone which has been extensively used in medicine as implantable materials, owing to its good biocompatibility, bioactivity high osteoconductive, and/or osteoinductive properties. Nevertheless, its mechanical property is not utmost appropriate for a bone substitution. Therefore, a composite consist of HA and a biodegradable polymer is usually prepared to generate an apt bone scaffold. In the present work polycaprolactone (PCL), a newly remarkable biocompatible and biodegradable polymer, was employed as a matrix and hydroxyapatite nanoparticles were used as a reinforcement element of the composite. HA/PCL nanocomposites were synthesized by a new in situ sol-gel process using calcium hydroxide and phosphoric acid precursors in the presence of Tetrahydrofuran (THF) as a solvent. Chemical and physical characteristics of the nanocomposite were studied by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and Fourier transform infrared (FTIR) analyses. The results indicated that pure HA nanoparticles were well-incorporated and homogenously dispersed in the PCL matrix. It was found that the mechanical property of PCL was improved by addition of 20wt.% HA nanoparticles. Furthermore, the biological property of nanocomposites was investigated under in vitro condition. For this purpose, HA/PCL scaffolds were prepared through a salt leaching process and immersed in a saturated simulated body fluid (SBF) after 3 and 7days. It was found that a uniform layer of biomimetic HA could be deposited on the surface of HA/PCL scaffolds. Therefore, the prepared HA/PCL scaffolds showed good potential for bone tissue engineering and could be used for many clinical applications in orthopedic and maxillofacial surgery.


Novel Phospholipid-Protein Conjugates Allow Improved Detection of Antibodies in Patients with Autoimmune Diseases.
Reliable measurement of clinically relevant autoimmune antibodies toward phospholipid-protein conjugates is highly desirable in research and clinical assays. To date, the development in this field has been limited to the use of natural heterogeneous antigens. However, this approach does not take structural features of biologically active antigens into account and leads to low reliability and poor scientific test value. Here we describe novel phospholipid-protein conjugates for specific detection of human autoimmune antibodies. Our synthetic approach includes mild oxidation of synthetic phospholipid cardiolipin, and as the last step, coupling of the product with azide-containing linker and copper-catalyzed click chemistry with β2-glycoprotein I and prothrombin. To prove utility of the product antigens, we used enzyme-linked immunosorbent assay and three cohorts of samples obtained from patients in Denmark (n = 34) and the USA (n = 27 and n = 14). Afterwards we analyzed correlation of the obtained autoantibody titers with clinical parameters for each patient. Our results prove that using novel antigens clinically relevant autoantibodies can be detected with high repeatability, sensitivity and specificity. Unlike previously used antigens the obtained autoantibody titers strongly correlate with high disease activity and in particular, with arthritis, renal involvement, anti-Smith antibodies and high lymphocyte count. Importantly, chemical composition of antigens has a strong influence on the correlation of detected autoantibodies with disease activity and manifestations. This confirms the crucial importance of antigens' composition on research and diagnostic assays, and opens up exciting perspectives for synthetic antigens in future studies of autoimmunity.


Perforated Ileal GIST Associated with Meckel Diverticulum - A Rare Pathological Entity of Surgical Acute Abdomen.
Introduction: The GIST tumors are very rare entities ( 1% of all tumors). They originate in the Cajal interstitial cells, which are part of the autonomic nervous system of the intestine. Their most common location is the stomach, followed by the small intestine. The aim of this paper is to present a very rare case of perforated ileal GIST, associated with Meckel diverticulum. Case report: A 71 years old patient with comorbidities is admitted in emergency for symptoms and signs of acute surgical abdomen. The exploratory laparotomy reveals generalized acute peritonitis due to perforated ileal tumor and Meckel's diverticulum. A segmental enterectomy is performed, with favorable postoperative evolution. The histological examination of the resection piece shows the appearance of GIST, confirmed immunohistochemically. Conclusions: The GIST tumors of the small intestine are unusual tumors and the spontaneous perforation and life-threatening hemorrhage are a rarity. The main treatment for this form of GIST is the resection, with a favorable clinical outcome.


Surgical and Immunohistochemical Outcomes of Scleral Reconstruction with Autogenic, Allogenic and Xenogenic Grafts: An Experimental Rabbit Model.
Purpose: Choukroun's platelet-rich fibrin (PRF), a second-generation platelet concentrate, has unique morphological and chemical features and may be considered as a scaffold for scleral reinforcement and regeneration. The purpose of this study was to compare the use of xenogenic human-derived amniotic membrane (HAM), allogenic sclera, and autogenic PRF in rabbit lamellar scleral defect model with respect to both anatomical and immunohistochemical improvement. Methods: A total of 45 adult New Zealand rabbits were randomized into five groups: normal control; without surgical procedure, negative control; scleral defect model (SDM), xenogenic HAM; SDM+HAM graft, allogenic sclera; SDM+allogenic sclera graft, autogenic PRF; SDM+autogenic PRF graft. Clinical findings, Hematoxylin&Eozin (HE), Masson Trichrome, Verhoeff Acid Fuchsin, Transforming Growth Factor β Receptor 1, Fibroblast Growth Factor, Bone Morphogenetic Protein 2, collagen type 1, aggrecan, and Matrix Metalloproteinase 2 were evaluated. Results: Ocular surface inflammation was significantly lower in normal control and autogenic PRF groups (p < .001). Graft was avascular and not integrated to scleral wound area in 25% rabbits of allogenic sclera group (p = .02), was out of the scleral wound in 33.3% rabbits of xenogenic HAM group (p > .05), all the grafts were at the normal location and viable in autogenic PRF group. The inflammation and vascularization in autogenic PRF group was significantly lower than negative control and xenogenic HAM groups in HE (p < .001). The collagen score of negative control and xenogenic HAM groups were significantly lower than normal control (p < .001) and autogenic PRF (p < .001) groups. There were insignificant differences between allogenic sclera and autogenic PRF groups (p > .05). For immunohistochemistry, the closest values to normal control group were detected in autogenic PRF group for all immunomarkers. Conclusion: Autogenic PRF showed superior features via its excellent anatomical and chemical composition for scleral regeneration when compared to single-layered xenogenic HAM and allogenic sclera grafts.


The repressive effect of NF-kappaB on p53 by mot-2 is involved in human keratinocyte transformation induced by low levels of arsenite.
Inorganic arsenic is a ubiquitous environmental contaminant associated with an increased risk of skin hyperkeratosis and cancer. Although several hypotheses that relate to arsenic-induced carcinogenesis have been suggested, the mechanism of action remains obscure. In the present study, molecular mechanisms underlying the inactivation of p53 function and the genomic instability in malignant transformation of the human keratinocyte cell line, HaCaT, induced by low levels of arsenic were investigated. Our results show that long-term exposure of HaCaT cells to sodium arsenite (1.0 microM) increases their proliferation, causes DNA double-strand breaks, and induce anchorage-independent growth. In arsenite-exposed cells, the levels of phospho-p53, p21, and mdm2 increase at early times after exposure. The levels, however, decrease with longer times. Interaction of the promoter of mot-2 (a p53 inhibitor) with nuclear factor kappaB (NF-kappaB) was established by Southwestern and Western blot assays. Blockage of NF-kappaB prevents the increases of arsenite-induced mot-2 levels, and knockdown of mot-2 facilitates the nuclear translocation of p53, indicating that, in HaCaT cells exposed to arsenite, NF-kappaB inhibits p53 function by mot-2. Moreover, inactivation of NF-kappaB facilitated p53-mediated DNA repair and prevented arsenite-induced malignant transformation. Together, the results suggest that the repressive effect of NF-kappaB on p53 by mot-2 leads to genomic instability, which is involved in arsenite-induced malignant transformation of human keratinocytes.


New C37 skeletal carotenoid from the clam, Paphia amabillis.
Carotenoids in the muscle of Paphia amabillis (Veneridae) were investigated. Amarouciaxanthin 3-ester (1a) was found to be a major carotenoid along with amarouciaxanthin A (1b), fucoxanthinol 3-ester (2), peridininol 3'-ester (3), and a new C(37) skeletal carotenoid, named hydratopyrrhoxanthinol 3'-ester. This structure was determined to be 3'-acyloxy-3,5,6-trihydroxy-7',8'-didehydro-5,6-dihydro-12',13',20'-trinor-beta,beta-caroten-19,11-olide (4) by UV-vis, NMR, and FAB-MS spectral data. The absolute configuration of 4 was postulated to be (3S,5R,6R,3'R) on the bases of CD and ROESY data. The fatty acids esterified with hydratopyrrhoxanthinol were assigned as C22:6, C20:1, C20:4, C20:5, C18:0, C18:1, C17:0, C16:0, C16:1, and C14:0 on the basis of FAB-MS data.


Association of passive and active smoking with incident type 2 diabetes mellitus in the elderly population: the KORA S4/F4 cohort study.
Active smoking is a risk factor for type 2 diabetes (T2DM), but it is unclear whether exposure to environmental tobacco smoke (ETS) is also associated with T2DM. The effect of passive and active smoking on the 7-year T2DM incidence was investigated in a population-based cohort in Southern Germany (KORA S4/F4; 1,223 subjects aged 55-74 years at baseline in 1999-2001, 887 subjects at follow-up). Incident diabetes was identified by oral glucose tolerance tests or by validated physician diagnoses. Among never smokers, subjects exposed to ETS had an increased diabetes risk in the total sample (odds ratio (OR) = 2.5; 95% confidence interval (CI): 1.1, 5.6) and in a subgroup of subjects having prediabetes at baseline (OR = 4.4; 95% CI: 1.5, 13.4) after adjusting for age, sex, parental diabetes, socioeconomic status, and lifestyle factors. Active smoking also had a statistically significant effect on diabetes incidence in the total sample (OR = 2.8; 95% CI: 1.3, 6.1) and in prediabetic subjects (OR = 7.8; 95% CI: 2.4, 25.7). Additional adjustment for components of the metabolic syndrome including waist circumference did not attenuate any of these associations. This study provides evidence that both passive and active smoking is associated with T2DM.


Superoxide, hydrogen peroxide and nitric oxide as signalling molecules: their production and role in disease.
All cells rely on a complex interplay of both extracellular and intracellular signals to control their metabolism, growth and differentiation. Recent evidence shows that several free radicals and their derivatives are able to act as signalling molecules. However, these molecules are inherently reactive towards biological materials such as proteins, lipids and DNA. In fact, the destructive power of these compounds appears to be harnessed and used by organisms to destroy both invading pathogens and tumour cells. Therefore, their use as signals seems to be a puzzle. Here, their production, role in signalling, and involvement in some diseases are discussed.


Large electrical currents traverse growing pollen tubes.
Using a newly developed vibrating electrode, we have explored the electric fields around lily pollen germinating in vitro. From these field measurements, we infer that each weeted pollen drives a steady current of a few hundred picoamperes through itself. Considered as a flow of positive ions, this current enters an ungerminated grain's prospective growth site and leaves it opposite end. After a grain germinates and forms a tube, this current enters most of the growing tube and leaves the whole grain. The current densities over both of these extended surface regions are relatively uniform, and the boundary zone, near the tube's base, is relatively narrow. This current continues as long as the tube grows, and even continues when elongation, as well as cytoplasmic streaming, are blocked by 1 mug/ml of cytochalasin B. After a otherwise indistinguishable minority of tubes have grown to lengths of a millimeter or more, their current comes to include an endless train of discrete and characteristic current pulses as well as a steady component. These pulses are about 30s long, never overlap, recur every 60-100s, and seem to enter a region more restricted to be growing tip than the steady current's sink. In most ways, the current through growing lily pollen resembles that known to flow through focoid eggs.


Behavioral family therapy for Vietnam combat veterans with posttraumatic stress disorder.
Severe interpersonal problems are common in veterans with combat-related posttraumatic stress disorder (PTSD) and their families. The authors first detail the rationale and use of behaviorally based family therapy to help reduce avoidance and withdrawal symptoms of PTSD and improve the active coping capacities of both veterans and their loved ones, then present a case example of the model, and finally discuss the clinical application of behavioral family therapy to the unique concerns of veterans with combat-related PTSD.


Impaired energy metabolism of the taurine‑deficient heart.
Taurine is a β-amino acid found in high concentrations in excitable tissues, including the heart. A significant reduction in myocardial taurine content leads to the development of a unique dilated, atrophic cardiomyopathy. One of the major functions of taurine in the heart is the regulation of the respiratory chain. Hence, we tested the hypothesis that taurine deficiency-mediated defects in respiratory chain function lead to impaired energy metabolism and reduced ATP generation. We found that while the rate of glycolysis was significantly enhanced in the taurine-deficient heart, glucose oxidation was diminished. The major site of reduced glucose oxidation was pyruvate dehydrogenase, an enzyme whose activity is reduced by the increase in the NADH/NAD+ ratio and by decreased availability of pyruvate for oxidation to acetyl CoA and changes in [Mg2+]i. Also diminished in the taurine-deficient heart was the oxidation of two other precursors of acetyl CoA, endogenous fatty acids and exogenous acetate. In the taurine-deficient heart, impaired citric acid cycle activity decreased both acetate oxidation and endogenous fatty acid oxidation, but reductions in the activity of the mitochondrial transporter, carnitine palmitoyl transferase, appeared to also contribute to the reduction in fatty acid oxidation. These changes diminished the rate of ATP production, causing a decline in the phosphocreatine/ATP ratio, a sign of reduced energy status. The findings support the hypothesis that the taurine-deficient heart is energy starved primarily because of impaired respiratory chain function, an increase in the NADH/NAD+ ratio and diminished long chain fatty acid uptake by the mitochondria. The results suggest that improved energy metabolism contributes to the beneficial effect of taurine therapy in patients suffering from heart failure.


Shear wave elastography of the common fibular nerve at the fibular head.
The aim of this work is to study the sonoelastographic features of the common fibular nerve in healthy adult subjects.This is an observational cross-sectional study. Shear wave elastography was used to evaluate the common fibular nerve. Crosssectional area and stiffness were measured in kilopascal (kPa) and meters/second (m/s).The study included 82 common fibular nerves in 41 healthy adult subjects. The mean cross-sectional area of the common fibular nerve at the fibular head was 8.7 mm2. Positive correlation was noted between stiffness measurements between short and long axes by both methods. The mean stiffness of the common fibular nerve in the short axis was 22.5 kPa, and in the long axis (LA) was 35.4 kPa. Positive correlation was noted between height and stiffness measured by both methods in both axes by kPa. In m/s, the mean stiffness of the common fibular in the short axis was 2.6 m/s, and while in the LA was 3.4 m/s. Height showed positive correlation with both axes for stiff measurements in m\s. Weight showed positive correlation with stiffness measurements by m/s in the LA.The results obtained in our study could be a reference point for evaluating stiffness of the common fibular nerve in research involving different pathologies.


Aberrant expression of shared master-key genes contributes to the immunopathogenesis in patients with juvenile spondyloarthritis.
Association of juvenile spondyloarthritis (jSpA) with the HLA-B27 genotype is well established, but there is little knowledge of other genetic factors with a role in the development of the disease. To date, only a few studies have tried to find those associated genes by obtaining expression profiles, but with inconsistent results due to various patient selection criteria and methodology. The aim of the present study was to identify and confirm gene signatures and novel biomarkers in highly homogeneous cohorts of untreated and treated patients diagnosed with jSpA and other forms of juvenile idiopathic arthritis (JIA) according to ILAR criteria. For the purposes of the research, total RNA was isolated from whole blood of 45 children with jSpA and known HLA genotype, 11 children with oligo- and polyarticular forms of JIA, as well as 12 age and sex matched control participants without diagnosis of inflammatory disease. DNA microarray gene expression was performed in 11 patients with jSpA and in four healthy controls, along with bioinformatical analysis of retrieved data. Carefully selected differentially expressed genes where analyzed by qRT-PCR in all participants of the study. Microarray results and bioinformatical analysis revealed 745 differentially expressed genes involved in various inflammatory processes, while qRT-PCR analysis of selected genes confirmed data universality and specificity of expression profiles in jSpA patients. The present study indicates that jSpA could be a polygenic disease with a possible malfunction in antigen recognition and activation of immunological response, migration of inflammatory cells and regulation of the immune system. Among genes involved in these processes TLR4, NLRP3, CXCR4 and PTPN12 showed almost consistent expression in study patients diagnosed with jSpA. Those genes and their products could therefore potentially be used as novel biomarkers, possibly predictive of disease prognosis and response to therapy, or even as a target for new therapeutic approaches.


KRIBB11: A Promising Drug that Promotes Microglial Process Elongation and Suppresses Neuroinflammation.
Microglia are key components of the central innate immune system. The over-activation of microglia, which occurs in nervous system disorders, is usually accompanied with retractions of their ramified processes. Reversing of microglial process retraction is a potential strategy for the prevention of neuroinflammation. Our previous studies have reported some endogenous molecules and drugs that can promote microglial process elongation at conditions in vitro and in vivo, such as butyrate and β-hydroxybutyrate, sulforaphane, and diallyl disulfide. Here, reported another compound that can promote microglial process elongation. We found that KRIBB11, a compound which has been reported to suppress nitric oxide production in microglia, induced significant elongations of the processes in microglia in cultured and in vivo conditions in a reversible manner. KRIBB11 pretreatment also prevented lipopolysaccharide (LPS)-induced shortenings of microglial process in cultured conditions and in vivo conditions, inflammatory responses in primary cultured microglia and the prefrontal cortex, and depression-like behaviors in mice. Mechanistic studies revealed that KRIBB11 incubation up-regulated phospho-Akt in cultured microglia and Akt inhibition blocked the pro-elongation effect of KRIBB11 on microglial process in cultured conditions and in vivo conditions, suggesting that the regulatory effect of KRIBB11 is Akt-dependent. Akt inhibition was also found to abrogate the preventive effect of KRIBB11 on LPS-induced inflammatory responses in primary cultured microglia and prefrontal cortexes as well as LPS-induced depression-like behaviors in mice. Collectively, our findings demonstrated that KRIBB11 is a novel compound that can prevent microglial activation and neuroinflammation-associated behavioral deficits possibly through inducing the Akt-mediated elongation of microglial process.


Multicenter Surveillance of Capsular Serotypes, Virulence Genes, and Antimicrobial Susceptibilities of Klebsiella pneumoniae Causing Bacteremia in Taiwan, 2017-2019.
We conducted a longitudinal epidemiological surveillance of hypervirulent Klebsiella pneumoniae (hvKP) in Taiwan. Bacteremic KP isolates collected from 16 hospitals in Taiwan between 2017 and 2019 were collected, and the virulent serotypes (K1, K2, K20, K54, and K57), antimicrobial susceptibilities, and virulence genes of these isolates were investigated. During the 3-year period, 1,310 bacteremic KP isolates were collected, of which 27.5% belonged to virulent serotypes, including K1 (n = 162), K2 (n = 74), K57 (n = 56), K54 (n = 41), and K20 (n = 27). K1 was the most prevalent capsular serotype, with an annual prevalence of 11-15%, and was equally distributed across the four geographic areas. The prevalence of K2 declined significantly in 2019. According to wzi-K typing results, 87% of K1 isolates were classified as wzi-1. Among K2 isolates, wzi-72 (55.4%) and wzi-2 (41.9%) were the most common, whereas wzi-206 was the most prevalent (48.2%) among K57 isolates, followed by wzi-77 (25.0%). Wzi-115 accounted for 85.4% of the K54 isolates, whereas wzi-95 accounted for 92.6% of K20 isolates. rmpA was present in 99.4% of K1, 98.6% of K2, 89.3% of K57, 78.0% of K54, and 84.0% of K20 isolates. rmpA2 was present in 100% of K1 and 98.6% of K2 isolates but was only present in 64.3% of K57, 58.5% of K54, and 74.1% of K20 isolates. K1 remains the dominant hvKP serotype and is associated with most virulence genes in Taiwan. Further studies are required to elucidate the significance of other virulent serotypes.


Genome-wide search for loss of heterozygosity in transgenic mouse tumors reveals candidate tumor suppressor genes on chromosomes 9 and 16.
A genome-wide scan for loss of heterozygosity (LOH) in tumors provides a powerful route to the identification of genes involved in tumorigenesis. This approach has not previously been applied to transgenic mice, despite the considerable advantages they afford for genetic dissection. Here, we report a genome-wide LOH analysis of insulinomas and carcinoid tumors in transgenic mice expressing the simian virus 40 large tumor oncogene. Although the overall genome-wide rate of LOH was quite low, chromosomes 9 and 16 showed high rates of allelic loss. About one-third of tumors showed partial LOH, allowing localization of the likely tumor suppressor genes to intervals of approximately 11 centimorgans. The locus on chromosome 9, named Loh-1, lies in a region with synteny conservation to human chromosomes 3q, 6q12, 15q24, and 3p21, while the locus on chromosome 16, named Loh-2, lies in a region corresponding to human chromosomes 3q and 22q. Of particular note is the synteny conservation with human 3p21, which shows frequent loss in human cancers. These regions do not encode two tumor suppressors, pRB and p53, known to interact with large tumor oncoprotein, suggesting the presence of new genes whose loss of function contributes to multistage tumorigenesis.


The use of LPNs in Ohio home care agencies.
A rapid rate of change in the home care arena has been widely documented and many more changes are likely to continue. This article presents the results of a descriptive study to characterize the use of licensed practical nurses (LPNs) within Ohio home care agencies. Among the findings were that that agencies use LPNs primarily in medical-surgical cases and that the use of LPNs is expected to increase.


On leadership. The new millennium and leadership: evolution or entropy?
Health care in the new millennium will be different. We have a wonderful opportunity to live in a new paradigm of leadership and management that opens up myriad possibilities for innovations in health care and leadership. If leaders stand still and don't quickly adapt to the new demands, they will be killed as leaders in this new millennium. The next 20 years are only for those who can act and adapt quickly.


Using Titer and Titer Normalized to Confluence Are Complementary Strategies for Obtaining Chinese Hamster Ovary Cell Lines with High Volumetric Productivity of Etanercept.
The selection of clonally derived Chinese hamster ovary (CHO) cell lines with the highest production rate of recombinant glycoproteins remains a big challenge during early stages of cell line development. Different strategies using either product titer or product titer normalized to cell number are being used to assess suspension-adapted clones when grown statically in microtiter plates. However, no reported study so far has performed a direct head-to-head comparison of these two early reporters for predicting clone performance. Therefore, a screening platform for high-throughput analysis of titer and confluence of etanercept-producing clones is developed. Then an unbiased comparison of clone ranking based on either titer or titer normalized to confluence (TTC) is performed. Using two different suspension cultivation vessels, the authors demonstrate that titer- or TTC-based ranking gives rise to the selection of clones with similar volumetric productivity in batch cultures. Therefore, using both titer- and TTC-based ranking is proposed, allowing for selection of distinct clones with both high integral of viable cell density (IVCD) and high specific productivity features, respectively. This contributes to selection of a versatile panel of clones that can be further characterized and from which the final producer clone can be selected that best fits the production requirements.


Polycyclic Aromatic Hydrocarbon Affects Acetic Acid Production during Anaerobic Fermentation of Waste Activated Sludge by Altering Activity and Viability of Acetogen.
Till now, almost all the studies on anaerobic fermentation of waste activated sludge (WAS) for bioproducts generation focused on the influences of operating conditions, pretreatment methods and sludge characteristics, and few considered those of widespread persistent organic pollutants (POPs) in sludge, for example, polycyclic aromatic hydrocarbons (PAHs). Herein, phenanthrene, which was a typical PAH and widespread in WAS, was selected as a model compound to investigate its effect on WAS anaerobic fermentation for short-chain fatty acids (SCFAs) accumulation. Experimental results showed that the concentration of SCFAs derived from WAS was increased in the presence of phenanthrene during anaerobic fermentation. The yield of acetic acid which was the predominant SCFA in the fermentation reactor with the concentration of 100 mg/kg dry sludge was 1.8 fold of that in the control. Mechanism exploration revealed that the present phenanthrene mainly affected the acidification process of anaerobic fermentation and caused the shift of the microbial community to benefit the accumulation of acetic acid. Further investigation showed that both the activities of key enzymes (phosphotransacetylase and acetate kinase) involved in acetic acid production and the quantities of their corresponding encoding genes were enhanced in the presence of phenanthrene. Viability tests by determining the adenosine 5'-triphosphate content and membrane potential confirmed that the acetogens were more viable in anaerobic fermentation systems with phenanthrene, which resulted in the increased production of acetic acid.


Mast cells in the synovium and synovial fluid in osteoarthritis.
SF and synovium from normal individuals and patients with OA, RA and traumatic arthritis (TA) were studied for the presence of mast cells (MC). When compared with normals, patients with OA had large numbers of intact and degranulated MC in the synovium and SF of diseased joints. The numbers of MC are comparable with those in RA where they have been implicated in the pathogenesis of joint damage. These data raise the possibility that in OA too MC may participate in the pathological processes in articular and periarticular tissues.


Decreased density of vascular receptors for atrial natriuretic peptide in DOCA-salt hypertensive rats.
We have previously found that vascular receptors for atrial natriuretic peptide (ANP) in the rat are down-regulated by volume expansion. For this reason vascular ANP receptor density and affinity were examined in a model of volume-expanded hypertension, the deoxycorticosterone acetate (DOCA)-salt hypertensive rat. The density of mesenteric vascular ANP binding sites was decreased in DOCA-salt hypertensive rats from a control value in uninephrectomized rats of 203 +/- 25 fmol/mg protein to 60 +/- 13 fmol/mg protein (p less than 0.01). The sensitivity of norepinephrine-precontracted aorta to ANP was significantly reduced in DOCA-salt hypertensive rats (p less than 0.001). DOCA-salt hypertensive rats infused intravenously for 4 days with ANP, 100 to 300 ng/hr, did not experience a lowering of blood pressure, in contrast to the significant reduction in blood pressure seen in two-kidney, one clip Goldblatt hypertensive rats similarly infused. In the latter there was no natriuretic response to ANP, while in the DOCA-salt hypertensive rats natriuresis occurred without lowering of blood pressure. In the DOCA-salt hypertensive rats plasma ANP concentration was increased to 68 +/- 8 fmol/ml from 10 +/- 1 fmol/ml in uninephrectomized rats. In conclusion, raised ANP concentration in plasma of volume-expanded hypertensive rats (DOCA-salt hypertension) may result in decreased density of ANP vascular receptors. These results suggest that a decrement in the number of ANP receptors may be a cause of decreased sensitivity of vascular responses to ANP in vitro and resistance to the blood pressure-lowering action of ANP in vivo.


Weldable and closed-loop recyclable monolithic dynamic covalent polymer aerogels.
Owing to their low density, high porosity and unique micro-nanostructures, aerogels are attractive for application in various fields; however, they suffer from shrinkage and/or cracking during preparation, mechanical brittleness, low production efficiency and non-degradation. Herein, we introduce the concept of dynamic covalent polymer chemistry to produce a new class of aerogels-referred to as DCPAs. The resulting lightweight DCPAs have the potential to be prepared on a large scale and feature high porosity (90.7%-91.3%), large degrees of compression (80% strain) and bending (diametral deflection of 30 mm) without any cracks, as well as considerable tensile properties (an elongation with a break at 32.7%). In addition, the DCPAs showcase the emergent characteristics of weldability, repairability, degradability and closed-loop recyclability that are highly desirable for providing versatile material platforms, though hardly achieved by traditional aerogels. Taking advantage of their robust porous structures, we demonstrate the potential of DCPAs for applications in thermal insulation and emulsion separation. These findings reveal that the dynamic covalent bond strategy would be generalized for the production of a new generation of aerogels with customized features for functioning in the field of intelligent and sustainable materials.


[Repetitive movement of the upper limbs: results of exposure evaluation and clinical investigation during jar packaging of preserved vegetables].
In order to assess the prevalence of work-related musculo-skeletal disorders of the upper limbs, a total population of 29 female workers in an industrial vegetable preserving plant were examined. The average age of the workers was 41.3 years (SD = 9.2), and their average length of service was 16.7 years (SD = 7.2). Only 20% of the workers were anamnestically negative, whilst 80% had one or more disorders attributable to repetitive trauma of the upper limbs. The disorders showed no prevalence for the right side, a finding in line with the risk analysis which indicated that both limbs were equally used. The results of the risk analysis and clinical assessment confirm that high-frequency actions, combined with improper posture and a shortage of suitable recovery times, play a causal role in determining the onset of the disorders studied.


[Surgical treatment of congenital transverse septum below the cervix of the vagina].
Transverse septa underneath the cervix are thick and have above them a funnel-shaped vault covered by pathological mucous membranes. The surgical procedures that are normally used to try to treat the condition and to avoid soft tissue dystocia by carrying out V-Y plasties using Garcia's technique or Z-plasties, or even radial incisions followed by the insertion of a pack, are all somewhat unsatisfactory. The authors, confronted with a similar case, decided to cut out the dome of the vagina and the diaphragm and followed that by a small amputation of the cervix, with anastomosis of the uterus and the remaining vagina.


High-EPA Biomass from Nannochloropsis salina Cultivated in a Flat-Panel Photo-Bioreactor on a Process Water-Enriched Growth Medium.
Nannochloropsis salina was grown on a mixture of standard growth media and pre-gasified industrial process water representing effluent from a local biogas plant. The study aimed to investigate the effects of enriched growth media and cultivation time on nutritional composition of Nannochloropsis salina biomass, with a focus on eicosapentaenoic acid (EPA). Variations in fatty acid composition, lipids, protein, amino acids, tocopherols and pigments were studied and results compared to algae cultivated on F/2 media as reference. Mixed growth media and process water enhanced the nutritional quality of Nannochloropsis salina in laboratory scale when compared to algae cultivated in standard F/2 medium. Data from laboratory scale translated to the large scale using a 4000 L flat panel photo-bioreactor system. The algae growth rate in winter conditions in Denmark was slow, but results revealed that large-scale cultivation of Nannochloropsis salina at these conditions could improve the nutritional properties such as EPA, tocopherol, protein and carotenoids compared to laboratory-scale cultivated microalgae. EPA reached 44.2% ± 2.30% of total fatty acids, and α-tocopherol reached 431 ± 28 µg/g of biomass dry weight after 21 days of cultivation. Variations in chemical compositions of Nannochloropsis salina were studied during the course of cultivation. Nannochloropsis salina can be presented as a good candidate for winter time cultivation in Denmark. The resulting biomass is a rich source of EPA and also a good source of protein (amino acids), tocopherols and carotenoids for potential use in aquaculture feed industry.


Bacteria-Responsive Nanoliposomes as Smart Sonotheranostics for Multidrug Resistant Bacterial Infections.
Rapid emergence of multidrug resistant (MDR) "superbugs" poses a severe threat to global health. Notably, undeveloped diagnosis and concomitant treatment failure remain highly challenging. Herein, we report a sonotheranostic strategy to achieve bacteria-specific labeling and visualized sonodynamic therapy (SDT). Using maltohexaose-decorated cholesterol and bacteria-responsive lipid compositions, a smart nanoliposomes platform (MLP18) was developed for precise delivery of purpurin 18, a potent sonosensitizer proved in this study. Taking advantage of the bacteria-specific maltodextrin transport pathway, the prepared MLP18 can specifically target the bacterial infection site and accurately distinguish the foci from sterile inflammation or cancer with a highly selective fluorescence/photoacoustic signal on the bacteria-infected site of mice. Moreover, the bacteria-responsive feature of MLP18 activated an efficient release and internalization of high concentration sonosensitizer into bacterial cells, resulting in effective sonodynamic elimination of MDR bacteria. In situ MRI monitoring visualized such potent sonodynamic activity and indicated that MLP18-mediated SDT could successfully eradicate inflammation and abscess from mice with bacterial myositis. In view of the above advantages, the developed nanoliposomes may serve as a promising sonotheranostic platform against MDR bacteria in the areas of healthcare.


Solitary intramammary schwannoma mimicking phylloides tumor: Cytological clues in the diagnosis.
A 30-year-old woman presented with a huge exophytic lobulated mass in the right breast, clinically and radiologically resembling phylloides tumor. Fine needle aspiration cytology smears showed clusters and singly scattered spindle cells along with structures reminiscent of verocay bodies. However, the epithelial elements were absent. A cytological diagnosis of benign mesenchymal spindle cell lesion, suggestive of schwannoma was rendered. Subsequent histopathological examination and strong S-100 positivity of tumor cells on immunohistochemistry confirmed the diagnosis.Breast is an uncommon location for benign schwannoma. The present case describes the unusual clinical picture, highlights cytological features and discusses the differential diagnoses of schwannoma from other benign spindle cells lesions of the breast on cytology smears.


Galileo and the embryos: religion and science in parliamentary debate over research on human embryos.
Confrontation between science and religion was a significant feature of the lengthy public appraisal of research on human embryos in Britain during the 1880s. The series of formal debates over embryo research in the House of Lords is chosen as a particularly appropriate setting to study this confrontation. It is shown that religious opposition to embryo research was repeatedly attacked in these debates by means of a stereotyped contrast between religious and scientific styles of thought. Leading figures in the movement for embryo research attempted to discredit their opponents by claiming that, whereas their own case was built upon reasoned assessment of the facts, the other side relied on religious dogma, clerical authority and faith. It is shown that, although there were genuine differences between those critical of embryo research on religious grounds and those supporting such research on grounds furnished by scientists, this account of the differences is inaccurate: dogma, reliance on authority and faith were as characteristic of the discourse associated with science as they were of that associated with religion. It is argued that these features were not generated by the presence of religious or scientific beliefs as such, but by the struggle between advocates of science and religion for intellectual and moral dominance.


Immunosuppressive and anticancer effect of a mammalian ribonuclease that targets high-affinity interleukin-2-receptors.
To target high-affinity interleukin (IL)-2 receptors involved in lymphocyte proliferation processes such as allograft rejection, autoimmune disorders, and certain haematological malignancies, using a minimally immunogenic mammalian-derived enzyme, bovine RNaseA, which becomes cytotoxic on entering cytoplasm. Laboratory study. Teaching hospital, Japan. Human lymphocytes isolated from healthy histoincompatible donors in mixed lymphocyte cultures or stimulated with phytohemagglutinin (PHA) to promote IL-2Ralpha expression. MJ, an HTLV-1-infected malignant T-cell line that overexpresses IL-2Ralpha, and the IL-2Ralpha-negative cell lines MOLT-4F and MT-1, were used as controls. Bovine RNaseA was chemically conjugated to 7G7B6, a monoclonal antibody to the alpha-chain of human IL-2 receptors, and several concentrations of the conjugates were added to the lymphocyte cultures. Inhibition of cell proliferation as a percentage of 3H-thymidine incorporation in 24 hours. 7G7B6-RNaseA dose-dependently inhibited cell proliferation in PHA-stimulated human lymphocytes at a 50% inhibitory concentration (IC50) of 2 x 10(-7) M. whereas RNase alone and RNase plus antibody had no inhibitory effect. 7G7B6-RNaseA also dose-dependently inhibited the human mixed lymphocyte reaction at an IC50 of 2 x 10(-6) M, whereas RNase alone did not. The conjugate also inhibited cell proliferation in MJ cells, a cell line that is infected with HTLV-I and overexpresses the high-affinity IL-2 receptor, at an IC50 of 5 x 10(-7) M. However the conjugate had no inhibitory effect on the IL-2 receptor non-expressing human T-cell lymphoblastic leukaemia cell lines MOLT-4F or MT-1. 7G7B6-RNaseA can inhibit cell proliferation in antigen- or mitogen-stimulated lymphocytes that overexpress high-affinity IL-2 receptors, and it may be safer than conventional chemotherapy or immunotoxins in the treatment of transplant rejection, certain lymphocytic malignancies, and other IL-2R-associated diseases, because it contains a mammalian cytotoxic enzyme.


Interactome analysis of myeloid-derived suppressor cells in murine models of colon and breast cancer.
In solid cancers, myeloid derived suppressor cells (MDSC) infiltrate (peri)tumoral tissues to induce immune tolerance and hence to establish a microenvironment permissive to tumor growth. Importantly, the mechanisms that facilitate such infiltration or a subsequent immune suppression are not fully understood. Hence, in this study, we aimed to delineate disparate molecular pathways which MDSC utilize in murine models of colon or breast cancer. Using pathways enrichment analysis, we completed interactome maps of multiple signaling pathways in CD11b+/Gr1(high/low) MDSC from spleens and tumor infiltrates of mice with c26GM colon cancer and tumor infiltrates of MDSC in 4T1 breast cancer. In both cancer models, infiltrating MDSC, but not CD11b+ splenic cells, have been found to be enriched in multiple signaling molecules suggestive of their enhanced proliferative and invasive phenotypes. The interactome data has been subsequently used to reconstruct a previously unexplored regulation of MDSC cell cycle by the c-myc transcription factor which was predicted by the analysis. Thus, this study represents a first interactome mapping of distinct multiple molecular pathways whereby MDSC sustain cancer progression.


Amphetamine-type stimulant use and conditional paths of consumption: data from the Second Brazilian National Alcohol and Drugs Survey.
The aim of this study was to estimate nationally representative prevalence rates of amphetamine-type stimulant (ATS) use and to identify consumption-associated factors, proposing a conditional model of direct and indirect consumption paths. Using data from the Second Brazilian National Alcohol and Drugs Survey, this cross-sectional study analyzed a subsample of 3,828 participants between 15 and 64 years old, gathering information on the use of psychoactive substances in a probabilistic sample of the Brazilian household population. Rates of lifetime and last-year ATS use were, respectively, 4.1 and 1.6%. Economically privileged individuals and users of other substances were more at risk for using ATS. The results suggest that higher education decreases the chances of ATS consumption. The conditional model showed that higher income increased ATS use, higher education lowered the odds of such an increase, and cocaine use cancelled that associative effect. Brazil presents high rates of ATS use. Prevention and treatment strategies should focus on the protective effect of higher education levels and should target polydrug use. Knowledge of ATS-associated factors and user profiles is the starting point for developing effective treatments and tailored prevention strategies.


Evidence that enteric neurons may derive from the sympathoadrenal lineage.
The first neurons that differentiate in the embryonic foregut of mammals transiently express catecholamine biosynthetic enzymes and accumulate catecholamine. Since this transmitter is found predominantly in cells of the sympatho-adrenal (SA) lineage, it has been suggested that enteric and sympathetic neurons may derive from the same progenitor. Enteric neurons would then lose the catecholamine phenotype during further development, as the two lineages diverge. We have further investigated this possibility using the SA1 monoclonal antibody that binds selectively to SA progenitor cells in the embryonic rat. We find that SA1 binds to the tyrosine hydroxylase+, neurofilament+, and SCG10+ cells of the Embryonic Day 14.5 (E14.5) rat foregut. We also find that a marker for later neuronal differentiation in the SA lineage, B2, also appears in the myenteric plexus concomitant with the loss of SA1 staining. Thus, at least some enteric neuronal precursors may exhibit the SA1----B2 antigenic switch previously observed in developing sympathetic neurons at E14.5. SA1 staining in the foregut partially overlaps with staining for neuropeptide Y, vasoactive intestinal polypeptide, and serotonin. These results support the hypothesis that enteric and sympathetic neurons derive from a common progenitor and that as the markers for the SA lineage are down-regulated, the many types of enteric neurons begin to differentiate.


Sublethal insecticide exposure of an herbivore alters the response of its predator.
Sublethal insecticide exposure poses risks for many non-target organisms and is a challenge for successful implementation of integrated pest management (IPM) programs. Next to detrimental effects of short-term insecticide exposure on fitness-related traits of organisms, also properties such as chemical signaling traits can be altered, which mediate intra- and interspecific communication. We investigated the effects of different durations of larval sublethal exposure to the pyrethroid lambda-cyhalothrin on performance traits of larvae and adults of the herbivorous mustard leaf beetle, Phaedon cochleariae. Moreover, by applying a direct contact and olfactometer bioassays, we determined the reaction of a generalist predator, the ant Myrmica rubra, towards insecticide-exposed and unexposed herbivore larvae and their secretions. Already short-term sublethal insecticide exposure of a few days caused a prolonged larval development and a reduced adult body mass of males. These effects may result from an insecticide-induced reduction in energy reserves. Furthermore, ants responded more frequently to insecticide-exposed than to unexposed larvae of P. cochleariae and their secretions. This increased responsiveness of ants towards insecticide-exposed larvae may be due to an insecticide-induced change in synthesis of chrysomelidial and epichrysomelidial, the dominant compounds of the larval secretion, which act defensive against various generalist predators. In conclusion, the results highlight that short-term insecticide exposure can impair the fitness of an herbivorous species due to both direct toxic effects and an increased responsiveness of predators. Consequently, exposure of single non-target species can have consequences for ecological communities in both natural habitats and IPM programs.


Oxidative Inactivation of Liver Mitochondria in High Fructose Diet-Induced Metabolic Syndrome in Rats: Effect of Glycyrrhizin Treatment.
Metabolic syndrome is a serious health problem in the present world. Glycyrrhizin, a triterpenoid saponin of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate the primary complications and hepatocellular damage in rats with the syndrome. In this study, we have explored metabolic syndrome-induced changes in liver mitochondrial function and effect of glycyrrhizin against the changes. Metabolic syndrome was induced in rats by high fructose (60%) diet for 6 weeks. The rats were then treated with glycyrrhizin (50 mg/kg body weight) by single intra-peritoneal injection. After 2 weeks of the treatment, the rats were sacrificed to collect liver tissue. Elevated mitochondrial ROS, lipid peroxidation and protein carbonyl, and decreased reduced glutathione content indicated oxidative stress in metabolic syndrome. Loss of mitochondrial inner membrane cardiolipin was observed. Mitochondrial complex I activity did not change but complex IV activity decreased significantly. Mitochondrial MTT reduction ability, membrane potential, phosphate utilisation and oxygen consumption decreased in metabolic syndrome. Reduced mitochondrial aconitase activity and increased aconitase carbonyl content suggested oxidative damage of the enzyme. Elevated Fe(2+) ion level in mitochondria might be associated with increased ROS generation in metabolic syndrome. Glycyrrhizin effectively attenuated mitochondrial oxidative stress and aconitase degradation, and improved electron transport chain activity. Copyright © 2016 John Wiley & Sons, Ltd.