Nitromethane as solvent in capillary electrophoresis.
Nitromethane has several properties that make it an interesting solvent for capillary electrophoresis especially for lipophilic analytes that are not sufficiently soluble in water: freezing and boiling points are suitable for laboratory conditions, low viscosity leads to favourable electrophoretic mobilities, or an intermediate dielectric constant enables dissolution of electrolytes. In the present work we investigate the change of electrophoretically relevant analyte properties - mobilities and pKa values - in nitromethane in dependence on the most important experimental conditions determined by the background electrolyte: the ionic strength, I, and the pH. It was found that the mobility decreases with increasing ionic strength (by, e.g. up to 30% from I = 0 to 50 mmol/L) according to theory. An appropriate pH scale is established by the aid of applying different concentration ratios of a buffer acid with known pKa and its conjugate base. The mobility of the anionic analytes (from weak neutral acids) depends on the pH with the typical sigmoidal curve in accordance with theory. The pKa of neutral acids derived from these curves is shifted by as much as 14 pK units in nitromethane compared to water. Both findings confirm the agreement of the electrophoretic behaviour of the analytes with theories of electrolyte solutions. Separation of several neutral analytes was demonstrated upon formation of charged complexes due to heteroconjugation with chloride as ionic constituent of the background electrolyte.


Benign paroxysmal positional vertigo.
Benign paroxysmal positional vertigo (BPPV) is characterized by positional vertigo (brief attacks of rotatory vertigo triggered by head position changes in the direction of gravity) and is the most common peripheral cause of vertigo. There are two types of BPPV pathophysiology: canalolithiasis and cupulolithiasis. In canalolithiasis, otoconial debris is detached from the otolithic membrane and floats freely within the endolymph of the canal. In cupulolithiasis, the otoconial debris released from the otolithic membrane settles on the cupula of the semicircular canal and the specific gravity of the cupula is increased. Consensus has been reached regarding three subtypes of BPPV: posterior-canal-type BPPV (canalolithiasis), lateral-canal-type BPPV (canalolithiasis) and lateral-canal-type BPPV (cupulolithiasis). In the interview-based medical examination of BPPV, questions regarding the characteristics of vertigo, triggered movement of vertigo, duration of vertigo and cochlear symptoms during vertigo attacks are important for the diagnosis of BPPV. The Dix-Hallpike test is a positioning nystagmus test used for diagnosis of posterior-canal-type BPPV. The head roll test is a positional nystagmus test used for diagnosis of lateral-canal-type BPPV. When the Dix-Hallpike test is repeated, positional nystagmus and the feeling of vertigo typically become weaker. This phenomenon is called BPPV fatigue. The effect of BPPV fatigue typically disappears within 30 min, at which point the Dix-Hallpike test again induces clear positional nystagmus even though BPPV fatigue had previously caused the positional nystagmus to disappear. For the treatment of BPPV, sequential head movements of patients can cause the otoconial debris in the semicircular canal to move to the utricle. This series of head movements is called the canalith repositioning procedure (CRP). The appropriate type of CRP depends on the semicircular canal in which the otoconial debris is located. The CRP for posterior-canal-type BPPV is called the Epley maneuver, and the CRP for lateral-canal-type BPPV is called the Gufoni maneuver. Including a time interval between each head position in the Epley maneuver reduces the immediate effect of the maneuver. This finding can inform the development of methods for reducing the effort exerted by doctors and the discomfort experienced by patients with posterior-canal-type BPPV during the Epley maneuver.


Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity.
Genetic alterations and epigenetic dysregulation in cancer cells create a vast array of neoepitopes potentially recognizable by the immune system. Immune checkpoint blockade has the capacity to enhance and sustain endogenous immunity against non-mutated tumor-associated antigens as well as uniquely mutant antigens, establishing durable tumor control. Recent evidence from preclinical models highlights the pivotal role of the Programmed Death-1 (PD-1) T cell co-receptor and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, in maintaining an immunosuppressive tumor microenvironment. Encouraging early clinical results using blocking agents against components of the PD-1 pathway have validated its importance as a target for cancer immunotherapy.


Oxysterols in Metabolic Syndrome: From Bystander Molecules to Bioactive Lipids.
Oxysterols are cholesterol metabolites now considered bona fide bioactive lipids. Recent studies have identified new receptors for oxysterols involved in immune and inflammatory processes, hence reviving their appeal. Through multiple receptors, oxysterols are involved in numerous metabolic and inflammatory processes, thus emerging as key mediators in metabolic syndrome. This syndrome is characterized by complex interactions between inflammation and a dysregulated metabolism. Presently, the use of synthetic ligands and genetic models has facilitated a better understanding of the roles of oxysterols in metabolism, but also raised interesting questions. We discuss recent findings on the absolute levels of oxysterols in tissues, their newly identified targets, and the mechanistic studies emphasizing their importance in metabolic disease, as there is a pressing need to further comprehend these intriguing bioactive lipids.


Characteristics of older adults admitted to the emergency department (ED) and their risk factors for ED readmission based on comprehensive geriatric assessment: a prospective cohort study.
Patients aged 75 years and older represent 12% of the overall emergency department (ED) population, and this proportion will increase over the next decades. Many of the discharged patients suffer an unplanned readmission in the immediate and midterm post-discharge period, suggesting under recognition of psychosocial, cognitive and medical problems. The aim of this study was to compare the characteristics of older patients admitted and discharged from the ED and to determine independent predictors for ED readmission 1 month and 3 months after ED discharge based on comprehensive geriatric assessment (CGA). Cohort study in a Belgian university hospital. A CGA, including demographic and medical data (e.g. reason for admission, comorbidity, number of medications), functional (e.g. activities of daily living, falls), mental (i.e. cognition, dementia, delirium), and nutritional status, and pain, was performed in 442 ED patients aged 75 years or older. Patients discharged from the ED (n = 117, 26.5%) were significantly less dependent for ADL, mobility, shopping and finances compared with hospitalised patients. Hospitalised patients (n = 325, 73.5%) were significantly more at risk for having nutritional problems, had a higher comorbidity index, and a lower cognitive status compared with those discharged. Ninety-seven patients (82.9%) were discharged home from the ED. Of the latter, 18 (18.6%) and 28 patients (28.9%) suffered an ED readmission within 1 and 3 months, respectively. At one month post-discharge, nursing care at home, meals on wheels, and risk for depression; and at 3 months post-discharge previous hospitalisation in the last 3 months, physiotherapy and meals on wheels were found to be independent predictors for ED readmission, respectively. This study observed a geriatric risk profile in older adults at the ED and a high readmission rate of those discharged, and suggests the potential value of CGA in identifying older patients at high risk for ED readmission.


[Seasonal primary production cycle in Lake Onega].
A long-term average curve of seasonal changes in the primary production of phytoplankton in the pelagial zone of Lake Onega has been plotted on the basis of experimental data approximated by a specified function. Long-term average values of primary production for each day of the growing season and its integrated and daily average values for different growing seasons have been calculated. Interannual variation of the seasonal process of primary production has been analyzed, and its quantitative estimations are given. The influence of basic environmental factors on the seasonal dynamics of primary production is discussed.


Namibia: refusal to enlist HIV-positive in army ruled discriminatory.
On 10 May 2000, in N v Minister of Defence, the Labour Court in Windhoek delivered a mixed ruling on HIV-based discrimination in employment that could have significant positive implications for armies throughout the region of southern Africa.


Falls in older persons with type 2 diabetes in the Malaysian Elders Longitudinal Research (MELoR) study.
Older persons with diabetes are at an increased risk of falls leading to fractures, head injuries and disability. To evaluate the potential relationship between falls and diabetes in older persons and identify differences in risk factors of falls among older persons with and without diabetes using the first wave dataset of the Malaysian Elders Longitudinal Research (MELoR) study. Community dwelling adults aged ≥ 55 years were selected through stratified random sampling from three parliamentary constituencies in greater Kuala Lumpur. Baseline data was obtained through computer-assisted, home-based interviews. The presence of falls was established by enquiring about falls in the preceding 12 months. Diabetes was defined as self-reported, physician-diagnosed diabetes, diabetes medication use and an HbA1c of ≥ 6.3%. Diabetes was present in 44.4% of the overall 1610 participants. The prevalence for fall among older diabetics was 25.6%. Recurrent falls (odds ratio (OR) 1.65; 95% confidence interval (CI) 1.06-2.57) was more common among diabetics. Following adjustment for potential confounders, osteoporosis (OR 2.58; 95% CI 1.31-5.08) and dizziness (OR 1.50; 95% CI 1.01-2.23) were independent risk factors for falls. Better instrumental activities of daily living scores were protective against falls (OR 0.75; 95% CI 0.58-0.97). The presence of osteoporosis and dizziness was associated with an increased risk of falls among older diabetics. These findings will need to be confirmed in future prospective follow-up of this cohort.


Driving the polar spin reorientation transition of ultrathin ferromagnets with antiferromagnetic-ferromagnetic phase transition of nearby FeRh alloy film.
We show that in-plane to out-of-plane magnetization switching of a ferromagnetic layer can be driven by antiferromagnetic-ferromagnetic phase transition in a nearby FeRh system. For FeRh/Au/FeAu trilayers, the impact of the magnetic phase transition of FeRh onto the perpendicular magnetization of monoatomic FeAu superlattices is transferred across the Au spacer layer via interlayer magnetic coupling. The polar spin reorientation process of the FeAu spins driven by the magnetic phase transition in the FeRh reveals its major features; namely it is reversible and displays hysteresis.


Stable isotope labeling assisted liquid chromatography-electrospray tandem mass spectrometry for quantitative analysis of endogenous gibberellins.
In the current study, we developed a stable isotope labeling strategy for the absolute quantification of gibberellins (GAs) by high performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS/MS). N,N-dimethyl ethylenediamine (DMED) and its deuterated counterpart d(4)-DMED were used to derivatize GAs extracted from plant tissue samples and GA standards respectively. The both derivatives of GAs were mixed and then subjected to HPLC-ESI-MS/MS analysis. The absolute quantification of GAs in plant tissues could be achieved by calculating the peak area ratios of DMED labeled GAs/d(4)-DMED labeled GAs. In the proposed strategy, the derivatization reaction of the labeling reagents with GAs could be completed rapidly (within 5 min) with high efficiency (>99%) under mild conditions. The resulting derivatives could produce specific fragments in collision induced dissociation (CID), leading to high selectivity in multiple-reaction monitoring (MRM) mode, thus enhanced the reliability of the LC-MS/MS method. Furthermore, the limits of quantitation (LOQs) of GAs were considerably decreased (2-32 folds) due to incorporating easily ionized moieties into GAs, and the quantification of GAs in plant tissue could be achieved without isotopically labeled GA standards. Good linearity was obtained with correlation coefficients R(2) values of >0.99. The limits of detection (LODs) and quantitation (LOQs) ranged from 0.02 to 0.74 pg and 0.07 to 2.45 pg, respectively. Eleven GAs could be successfully determined in spiked sample with 72-128% recoveries and the relative standard deviations (RSDs) were between 1.0% and 13.9%. Finally, the developed method was successfully applied for the detection of GAs in 50mg (fresh weight) Oryza sativa leaves.


Monoamine concentrations in the human brain. A comparison between two methods of tissue handling.
The brains of five neurologically healthy humans were analyzed for their content of various monoamines and metabolites using two different dissection methods. The left hemisphere was frozen immediately and subsequently dissected in the frozen state. The right hemisphere was dissected fresh in the autopsy room whereupon the brain parts were put in a freezer. Few significant differences were noted with respect to the monoamine content, indicating that the methods could be considered to be equivalent for the purpose of monoamine analysis.


Expanding hematopoietic stem cell ex vivo: recent advances and technical considerations.
Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic hierarchy, which are responsible for sustaining the lifelong production of mature blood and immune cells. Due to their superior long-term regenerative capacity, HSC therapies such as stem cell transplantation have been used in a broad range of hematologic disorders. However, the rarity of this population in vivo considerably limits its clinical applications and large-scale analyses such as screening and safety studies. Therefore, ex vivo culture methods that allow long-term expansion and maintenance of functional HSCs are instrumental in overcoming the difficulties in studying HSC biology and improving HSC therapies. In this perspective, we discuss recent advances and technical considerations for three ex vivo HSC expansion methods including 1) polyvinyl alcohol-based HSC expansion, 2) mesenchymal stromal cell-HSC co-culture, and 3) two-/three-dimensional hydrogel HSC culture. This review summarizes the presentations and discussions from the 2022 International Society for Experimental Hematology (ISEH) Annual Meeting New Investigator Technology Session.


An hypothesis on information, memory and perception.
It is generally held that a sensory receptor serves, in some way to "map" an external event (such as a light or sound signal) onto some internal or neural event (such as a volley of impulses moving along an axon toward the brain). Or schematically (external event leads to neural event). It is postulated in this paper that it is not the external event, but rather uncertainty about the nature of the external event, which produces the neural activity. In place of the traditional map it is hypothesized that we should substitute (rate of change of uncertainty about an external event leads to neural event). It follows from this revised mapping process that one perceives only those external events about which he was initially uncertain. One cannot perceive something about which he is perfectly certain. It is seen that various observed sensory phenomena, such as the process of adaptation and the fading of a fixed retinal image, issue directly from this new hypothesis.


Phase II evaluation of thioTEPA for treatment of central nervous system tumors.
Nineteen patients with primary malignant gliomas were treated with thioTEPA. It was found to be ineffective in 13 evaluable patients.


Effects of aging on pituitary and testicular luteinizing hormone-releasing hormone receptors in the rat.
Aging exerts profound influences on the function of the hypothalamic-pituitary-testicular-axis. This work has been performed in order to verify whether, in male rats, the decreased secretion of LH and testosterone (T) occurring in old animals is reflected by modifications of luteinizing hormone-releasing hormone (LHRH) receptors at the level of the anterior pituitary and of the testes. To this purpose, the affinity constant (Ka) and the maximal binding capacity (Bmax) for the LHRH analog [D-Ser(tBu)6]des-Gly10-LHRH-N-ethylamide were evaluated, by means of a receptor binding assay, in membrane preparations derived from the anterior pituitary and testicular Leydig cells of male rats of 3 and 19 months of age. Serum levels of LH and T were measured by specific RIAs. The results obtained show that, in aged male rats, the concentration of pituitary LHRH receptors is significantly lower than that found in young animals. On the other hand, the concentration of LHRH binding sites is significantly increased on the membranes of Leydig cells of old rats. In no instance the Ka for the LHRH analog is significantly affected. Serum levels of LH and T are significantly lower in old than in young male rats. In conclusion, these results suggest that the reduced secretion of LH in old male rats may be linked, at least partially, to a decrease of the number of pituitary LHRH receptors. The impaired production of testosterone occurring in aged rats is accompanied by a significant increase of the number of testicular LHRH receptors, indicating that also the intratesticular mechanisms controlling testosterone release undergo significant alterations with aging.


Diversity-Oriented Synthesis of Thiazolidine-2-imines via Microwave-Assisted One-Pot, Telescopic Approach and Its Interaction with Biomacromolecules.
In this work, a one-pot, telescopic approach is described for the combinatorial library of thiazolidine-2-imines. The synthetic manipulation proceeds smoothly via the reaction of 2-aminopyridine/pyrazine/pyrimidine with substituted isothiocyanates followed by base catalyzed ring closure with 1,2-dibromoethane to obtain thiazolidine-2-imines with broad substrate scope and high functional group tolerance. The synthetic strategy merges well with the thiourea formation followed by base catalyzed ring closure reaction for the thiazolidine-2-imine synthesis in a more modular and straightforward approach. The synthetic procedure reported herein represents a cleaner route toward thiazolidine-2-imines as compared to traditional methodologies. Moreover, the biological significance of combinatorially synthesized thiazolidin-2-imines has been investigated for their use as possible inhibitors for acetyl cholinesterase through molecular docking studies.


Linear subcutaneous fat atrophy after corticosteroid injection of periocular hemangiomas.
Two children developed evidence of subcutaneous fat atrophy after corticosteroid injection of periocular hemangiomas. The atrophy appeared at the site of injection and followed the expected course of lymphatic channels to the vicinity of regional lymph nodes.


Mitomycin, ifosfamide, and mesna in the treatment of lung cancer.
Observations have been made of the multiple-drug resistance phenomenon in mitomycin-exposed cells in vitro. Collateral resistance to anthracyclines and Vinca alkaloids was demonstrated in mitomycin carbon-treated 1-1210 cells in vitro. However, because it has also been found that this resistance can be reversed with agents such as verapamil and progestogens, it may be possible to effect a similar reversal in vivo. A study is currently being performed in patients with colorectal cancer, in which the potential for reversal is being tested. The pharmacokinetics of ifosfamide result in high cytotoxic specificity which, along with its therapeutic range, makes it a particularly active agent in the treatment of non-small cell lung cancer. Its urotoxicity is effectively controlled by the coadministration of mesna, a uroprotective agent.


Reduction of severe lumbosacral spondylolisthesis. A report of 22 cases with a ten-year follow-up period.
Severe spondylolisthesis produces a kyphos at the lumbosacral junction. Reduction can be complicated by injury to the cauda equina. To prevent this, a posterior decompression and fusion is carried out before a slow reduction in extension. An anterior fusion with internal fixation then locks the reduction. Using these principles, a good reduction was achieved in 20 of 22 patients. Only two patients suffered a permanent neurologic deficit consisting of slight loss of ankle dorsiflexion. Severe spondylolisthesis can be safely reduced by this method.


Loperamide, an FDA-approved antidiarrhea drug, effectively reverses the resistance of multidrug resistant MCF-7/MDR1 human breast cancer cells to doxorubicin-induced cytotoxicity.
Loperamide is an FDA-approved antidiarrhea drug which acts on the μ-opioid receptors in the mesenteric plexus of large intestine and exhibits limited side effects. We hypothesized that loperamide might reverse the multidrug resistance (MDR) of human cancer cells to chemotherapeutic agents. MCF-7/MDR1 cells express high level of MDR1 and are resistant to doxorubicin. We found that loperamide significantly enhanced the cytotoxicity of doxorubicin to MCF-7/MDR1 cells in a dose-dependent manner. In conclusion, loperamide reversed the resistance of MCF-7/MDR1 cells to doxorubicin, suggesting that chemotherapy in combination with loperamide may benefit patients with MDR tumors once applied in clinic.


The neutralization sensitivity of viruses representing human immunodeficiency virus type 1 variants of diverse subtypes from early in infection is dependent on producer cell, as well as characteristics of the specific antibody and envelope variant.
Neutralization properties of human immunodeficiency virus (HIV-1) are often defined using pseudoviruses grown in transformed cells, which are not biologically relevant HIV-1 producer cells. Little information exists on how these viruses compare to viruses produced in primary lymphocytes, particularly for globally relevant HIV-1 strains. Therefore, replication-competent chimeras encoding envelope variants from the dominant HIV-1 subtypes (A, C, and D) obtained early after infection were generated and the neutralization properties explored. Pseudoviruses generated in 293T cells were the most sensitive to antibody neutralization. Replicating viruses generated in primary lymphocytes were most resistant to neutralization by plasma antibodies and most monoclonal antibodies (b12, 4E10, 2F5, VRC01). These differences were not associated with differences in envelope content. Surprisingly, the virus source did not impact neutralization sensitivity of most viruses to PG9. These findings suggest that producer cell type has a major effect on neutralization sensitivity, but in an antibody dependent manner.


Professional attitudes and behaviors acquired during undergraduate education in the College of Dentistry, King Saud University.
The purpose of the study was to investigate and evaluate the professional attitudes and behaviors acquired by students and recently graduated dentists during undergraduate education at King Saud University. This cross-sectional survey used a 27-item questionnaire covering four cumulative theoretical dimensions of professionalism. Questionnaires were distributed to fifth-year students, interns, and demonstrators in the College of Dentistry during the academic year 2010-2011, and 203 completed questionnaires were used in analyses. Descriptive statistics were used to summarize responses. Crosstab and chi-squared tests were used, with statistical significance set at P < 0.05. The response rate was 79.3% (43.6% of males, 94% of females). Eighty-seven questionnaires were collected from fifth-year students, 92 from interns, and 24 from demonstrators. Many (59%) participants demonstrated high levels of professional attitudes and behaviors, whereas 40% did not comply with the elements of professionalism. Analyses revealed highly significant differences in certain responses with regard to gender, academic level, and grade point average. Although some participants did not possess all professional qualities, all participants possessed at least some elements of professionalism measured in this study. We thus recommend a strategic effort to develop targeted plans emphasizing professionalism at all levels of the dental school curriculum. High-profile role modeling, lectures, seminars, and academic ceremonies are ways of achieving professional development among dental students in parallel with their acquisition of basic scientific knowledge and clinical skills. This approach will formally and informally communicate that professionalism is a core value.


Gelatin blending and sonication of chitosan nanofiber mats produce synergistic effects on hemostatic functions.
To improve the hemostatic function of chitosan nanofiber mats, we studied the synergetic effects of gelatin blending and porosity control. Gelatin-blended-chitosan (Chi-Gel) nanofiber mats were evaluated with respect to surface morphology, mechanical properties and wettability, and functionally tested in a blood clotting study. The blood clotting efficiency of Chi-Gel nanofiber mats using rabbit whole blood in vitro was superior to that of chitosan nanofibers. Moreover, Chi-Gel nanofiber mats with enlarged porosity, produced by ultra-sonication, showed improved blood clotting efficiency, cell viability and cell infiltration compared with non-sonicated Chi-Gel nanofiber mats. Field-emission scanning electron microscopy revealed a richer density of platelets on sonicated nanofiber mats than on non-sonicated nanofiber mats after 3 min of blood clotting. The proliferation of human dermal fibroblast cells on sonicated Chi-Gel nanofiber mats using the DNA assay was higher than that on non-sonicated chitosan nanofiber mats after 7 days of culture. Confocal z-stack images showed that sonicated Chi-Gel nanofiber mats with high porosity supported active cell migration and infiltration into the 3-dimensional nanofiber mats. These results suggest that hydrophilic gelatin blending and sonication of chitosan nanofiber mats yields synergistic effects that not only improve hemostatic function but also promote wound repair.


Reflections on Aboriginal perinatal mental health, mothers, babies, families and community: A South Australian trainee's experience.
This paper explores novel training opportunities that the Expanded Setting Training Program (ESTP) provides for advanced psychiatry trainees. It is a reflection of a trainee's learning experiences during a year-long posting in Aboriginal Perinatal Mental Health, working alongside the Aboriginal Family Birthing Program, coupled with reflection and supervision. ESTP provided a fertile area to hone an advanced trainee's skills in the niche areas of Aboriginal mental health, perinatal mental health, culture and psychiatry. In addition, it provided skills in the area of leadership, health advocacy and the establishment and maintenance of successful programs in disadvantaged, culturally and linguistically diverse communities. The ESTP Aboriginal Mental Health rotation provides a unique experience for training, and the learning opportunities are limited only by the creativity of the trainee and supervisor.


Evaluation of the rescaled complementary principle in the estimation of evaporation on the Tibetan Plateau.
Accurate quantification of the terrestrial water balance can improve our knowledge of regional water cycle changes, and deepen our understanding of evaporation in hydrological cycle and under climate change. However, sparse observation networks on the Tibetan Plateau (TP) prevent the reliable estimates of actual evaporation. Based on the China regional surface Meteorological Feature Dataset (CMFD) and the Global Land Surface Satellite (GLASS) product, we adopted the latest rescaled nonlinear complementary relationship (CR) to calculate the monthly actual evaporation (E) from 1982 to 2015. We analyzed the spatio-temporal variability of the annual E on the entire TP, and explored the main meteorological factors controlling the annual E and the regulation of multiyear average annual E in different vegetation zones from southeast to northwest. Our results indicated that the net radiation (Rn) and E exhibited a favorable agreement with monthly changes of the observed values; and E estimated by the CR explained 79-96% variation of the eddy covariance flux measurements. The multiyear average E was 373.12 mm yr-1 and displayed similar spatial patterns of decreasing from southeast to northwest with two remote sensing products (GLDAS_VIC, GLEAM_v3.3) and one hydrological model (Budyko). Additionally, based on the Mann-Kendall trend test, there were 21.56% of the TP with significant upward trend of annual E which mainly distributed in the area with dense glaciers. The Nyenchen Tanglha Mountains and Pamirs Plateau area had the most obvious upward trend, with up to over 6 mm yr-1. In a relative sense, the key meteorological elements which affected annual E on the TP were relative humidity (RH) (r = 0.63) and Rn (r = 0.56).


Laparoscopic prostatectomy: a promising option in the treatment of prostate cancer.
It is still too soon to know if a laparoscopic approach is as good or even better than open surgical radical prostatectomy, the gold standard. Early data seem to suggest lower intraoperative bleeding rates, less postoperative pain, shorter hospital stay, and similar rates of oncologic cure, return to potency, and urinary continence.


Women Living with Familial Hypercholesterolemia: Challenges and Considerations Surrounding Their Care.
To highlight the gender-based differences in presentation and disparities in care for women with familial hypercholesterolemia (FH). Women with FH experience specific barriers to care including underrepresentation in research, significant underappreciation of risk, and interrupted therapy during childbearing. National and international registry and clinical trial data show significant healthcare disparities for women with FH. Women with FH are less likely to be on guideline-recommended high-intensity statin medications and those placed on statins are more likely to discontinue them within their first year. Women with FH are also less likely to be on regimens including non-statin agents such as PCSK9 inhibitors. As a result, women with FH are less likely to achieve target low-density lipoprotein cholesterol (LDL-C) targets, even those with prior atherosclerotic cardiovascular disease (ASCVD). FH is common, under-diagnosed, and under-treated. Disparities of care are more pronounced in women than men. Additionally, FH weighs differently on women throughout the course of their lives starting from choosing contraceptives as young girls along with lipid-lowering therapy, timing pregnancy, choosing breastfeeding or resumption of therapy, and finally deciding goals of care during menopause. Early identification and appropriate treatment prior to interruptions of therapy for childbearing can lead to marked reduction in morbidity and mortality. Women access care differently than men and increasing awareness among all providers, especially cardio-obstetricians, may improve diagnostic rates. Understanding the unique challenges women with FH face is crucial to close the gaps in care they experience.


Going beyond established model systems of Alzheimer's disease: companion animals provide novel insights into the neurobiology of aging.
Alzheimer's disease (AD) is characterized by brain plaques, tangles, and cognitive impairment. AD is one of the most common age-related dementias in humans. Progress in characterizing AD and other age-related disorders is hindered by a perceived dearth of animal models that naturally reproduce diseases observed in humans. Mice and nonhuman primates are model systems used to understand human diseases. Still, these model systems lack many of the biological characteristics of Alzheimer-like diseases (e.g., plaques, tangles) as they grow older. In contrast, companion animal models (cats and dogs) age in ways that resemble humans. Both companion animal models and humans show evidence of brain atrophy, plaques, and tangles, as well as cognitive decline with age. We embrace a One Health perspective, which recognizes that the health of humans is connected to those of animals, and we illustrate how such a perspective can work synergistically to enhance human and animal health. A comparative biology perspective is ideally suited to integrate insights across veterinary and human medical disciplines and solve long-standing problems in aging.


Computerised tomography of intracranial tuberculomata.
The CT appearances of 14 tuberculomata are described. In 10 of these there is a similarity of appearance which may permit a definitive or high probability diagnosis. The features are: a mass lesion approximately isodense with brain substance surrounded by an intense unbroken ring of contrast enhancement. Calcification may be present within the ring giving a 'target sign'. Two of the other cases were 'tuberculomata en plaque' which had features similar to each other.


Unifocal Invasive Lobular Carcinoma: Tumor Size Concordance Between Preoperative Ultrasound Imaging and Postoperative Pathology.
We systematically analyzed the extent of disease in unifocal invasive lobular carcinoma (ILC) using ultrasonography, with the histopathologic findings as the reference standard. In the present single-institution retrospective study, 128 cases of ILC were identified during a 5-year period. After exclusions, the analyzed cohort included 66 cases. Ultrasound measurements of the tumor extent along 3 axes were obtained. The tumor size was determined as the largest extent among the 3 axes and the tumor volume by ellipsoidal approximation. Pathology review provided the tumor size and volume. Correlation and regression analyses of tumor size and volume from the ultrasound and pathologic examinations were performed. The tumor stage from the ultrasound and pathologic examinations were used for the concordance analyses. The median and quartiles (Q1, Q3) of tumor size from ultrasonography and pathology were 12.5 mm (Q1, 9 mm; Q3, 19 mm) and 17 mm (Q1, 12 mm; Q3, 25 mm), respectively. The corresponding data for tumor volume were 0.52 cm3 (Q1, 0.18 cm3; Q3, 1.92 cm3) and 1.04 cm3 (Q1, 0.45 cm3; Q3, 2.49 cm3). The ultrasound measurements correlated with the pathology-reported tumor size (Spearman ρ = 0.678; P < .0001) and volume (Spearman ρ = 0.699; P < .0001). The ultrasound-measured size and volume differed from the pathology-reported size and volume (P < .0001; Wilcoxon signed ranks test). Concordance between the clinical tumor size stage from ultrasound (cT) and pathology tumor size stage (pT) varied with the pT stage (P = .0003, Fisher's exact test), with the greatest concordance rate of 95.7% (95% confidence limit, 85.2%-99.5%) observed for pT1 tumors. Ultrasonography underestimates the tumor size and volume, with the underestimation increasing for larger tumors. Hence, the concordance rate in tumor size stage between ultrasonography and pathology is tumor size dependent, with the greatest concordance rate observed for pT1 tumors.


Pre- and postoperative evaluation of renal function with five different tests in patients with primary hyperparathyroidism.
Renal function was investigated immediately before and 1 year following parathyroidectomy in 19 patients with moderate hypercalcaemia. On both occasions, all patients underwent five different tests of glomerular and tubular function: plasma creatinine, creatinine clearance, 51Cr-EDTA-clearance, beta 2-microglobulin excretion and the desmopressin test. Glomerular filtration rate, as assessed by plasma creatinine and clearance of both creatinine and 51Cr-EDTA, was normal in most patients, and was little affected by restoration of normocalcaemia. Renal concentrating capacity, as determined by the desmopressin test, was abnormally low in 14 of 19 patients, but increased significantly after surgery. It is concluded that serious renal damage is seldom encountered in present-day HPT patients, but that a treatable decrease in renal concentrating capacity often exists.


Propensity for biofilm formation by aerobic mesophilic and thermophilic spore forming bacteria isolated from Chinese milk powders.
Biofilms on the surface of dairy manufacturing plants are potential reservoirs of microbial contamination. These microbial aggregates may harbour pathogenic and spoilage organisms which contaminate dairy products. The biofilm forming capacity of many spore forming isolates of dairy origin has not been given much attention. The present study explored the biofilm forming potential of 148 isolates, comprising mesophilic and thermophilic bacteria, with particular emphasis on Bacillus licheniformis on polystyrene and stainless steel (SS) surfaces. We concluded that only four species are of significance for biofilm development on the surface of SS in the presence of skimmed milk, namely, B. licheniformis, Geobacillus stearothermophilus, Geobacillus thermoleovorans group and Anoxybacillus flavithermus. The maximum number of cells recovered from the biofilms developed on SS coupons in the presence of skimmed milk for these four species was as follows: 4.8, 5.2, 4.5 and 5.3logCFU/cm2, respectively. Number of cells recovered from biofilms on 1cm2 SS coupons increased in the presence of tryptic soy broth (TSB) for all mesophiles including B. licheniformis, while decreased for G. stearothermophilus, G. thermoleovorans group and A. flavithermus. The crystal violet staining assay on polystyrene proved to be inadequate to predict cell counts on SS for the bacteria tested in our trial in the presence of either TSB or skimmed milk. The results support the idea that biofilm formation is an important part of bacterial survival strategy as only the most prevalent isolates from milk powders formed good biofilms on SS in the presence of skimmed milk. Biofilm formation also proved to be a strain-dependent characteristic and interestingly significant variation in biofilm formation was observed within the same RAPD groups of B. licheniformis which supports the previously reported genetic and phenotypic heterogeneity within the same RAPD based groups. The work reported in this manuscript will broaden our knowledge on biofilm formation of a large number of dairy isolates and emphasize strain and substrate dependence.


How long is antibiotic therapy necessary after urgent cholecystectomy for acute cholecystitis?
The objective of the study was to analyze surgical site infection (SSI) frequency with different duration antibiotic courses to establish the minimum necessary duration. This is an observational study of prospective surveillance of 287 consecutive patients (mean age 67.8 years) operated on for acute cholecystitis of grade II severity in the first 72 h. Postoperative antibiotics had been withdrawn before diagnosis of any infection as an inclusion criterion. Patients were classified into three groups, according to therapy duration: group 1 (0-4 days, n = 45, 15.7 %); group 2 (5-7 days, n = 75, 26.1 %); and group 3 (>7 days, n = 167, 58.2 %). A multivariable analysis of risk infection was performed. Overall SSI frequency in groups 1, 2, and 3 was 2.2, 10.7, and 9 %, respectively. Risk analysis showed an increase in both crude and adjusted relative risks of overall infection in group 2 (crude relative risk (RR): 4.80 (0.62-37.13); adjusted RR, 2.03 (0.20-20.91)) and in group 3 (crude RR, 4.04 (0.55-29.79); adjusted RR, 2.35 (0.28-20.05)) by comparison with group 1, although without statistical significance. As a result, treatment lasting 4 days or less was not associated with overall surgical site infection incidence higher than longer treatment. Antibiotic treatment over 4 days after early cholecystectomy provides no advantage in decreasing surgical site infection incidence.


Direct detection of blood nitric oxide reveals a burn-dependent decrease of nitric oxide in response to Pseudomonas aeruginosa infection.
Burn is associated with severe immune dysfunction, including an anti-inflammatory state that occurs late after burn. While increased nitric oxide (NO) production is associated with severe infection and sepsis, the effect of burn trauma on these levels during a non-lethal infection remains unknown. We hypothesized that in a mouse model, (1) NO levels would be increased after infection without trauma and (2) burn would lead to decreased NO production even during infection. Mice were infected via intra-tracheal inoculation with Pseudomonas aeruginosa 14 d following a 20% total body surface area contact burn. At 48h following infection, blood was drawn to quantify NO concentrations using a microfluidic electrochemical sensor. In uninjured mice, infection caused a significant increase in blood NO levels. Increases in NO occurred in a dose-dependent response to the bacterial inoculum. Following burn, an identical infection did not elicit increases in NO. While increases in NO are expected over the course of an infection without prior trauma, burn and subsequent immune suppression decreases NO levels even in the presence of infection.


Analysis of cilia structure and function in zebrafish.
Cilia are microtubule-based protrusions on the surface of most eukaryotic cells. They are found in most, if not all, vertebrate organs. Prominent cilia form in sensory structures, the eye, the ear, and the nose, where they are crucial for the detection of environmental stimuli, such as light and odors. Cilia are also involved in developmental processes, including left-right asymmetry formation, limb morphogenesis, and the patterning of neurons in the neural tube. Some cilia, such as those found in nephric ducts, are thought to have mechanosensory roles. Zebrafish proved very useful in genetic analysis and imaging of cilia-related processes, and in the modeling of mechanisms behind human cilia abnormalities, known as ciliopathies. A number of zebrafish defects resemble those seen in human ciliopathies. Forward and reverse genetic strategies generated a wide range of cilia mutants in zebrafish, which can be studied using sophisticated genetic and imaging approaches. In this chapter, we provide a set of protocols to examine cilia morphology, motility, and cilia-related defects in a variety of organs, focusing on the embryo and early postembryonic development.


REIN: a tool for the benefit of renal transplantation
On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of access to renal transplantation for ESKD patients, the following key messages were retained. The registry of the REIN includes data about kidney transplant and dialysis. It thus allows evaluating the access to kidney transplant in France based on the needs of the population with stage 5 CKD treated by renal replacement therapy. The data produced by the registry is complementary to the data in the report of the Agence de la biomédecine (Agency of Biomedicine) based on the activity of the transplant centres and the population of registered patients waiting for a transplant. The proportion of preemptive transplant (transplant without prior recourse to dialysis) as well as that of preemptive registration (before starting dialysis) have increased since 2012 but remain low. The proportion of preemptive transplant as the first replacement therapy remains low and stable over time at around 3 to 4%. The access to the waiting list and the transplant varies depending on the age and co-morbidities of the patients (diabetes, obesity) as well as on the region. The rates of registration on the kidney transplant waiting list at the time of initiation of dialysis and at 1 year from the start have been increasing since 2012, irrespective of the patients' characteristics, though it remains low in elderly, diabetic and severely obese patients. This is partly the result related to the publication of the HAS (French National Authority for Health) recommendations in 2015 and the publications on the disparities in access to transplants established thanks to the REIN registry. The causes of non-registration at the time of initiation of dialysis have changed over time with some patients not registering for contraindication steadily decreasing since 2012. Thanks to several studies conducted using data from the registry, the variations in access to the list could be explained, partly, by the health condition of the dialysis population as well as by the socio-economic context and differences in practices according to dialysis networks. The median waiting time for a kidney transplant has been gradually increasing since 2012, with a delta of about 8 months between 2012 and 2020. However, the waiting time between the initiation of dialysis and the transplant has increased less significantly. The probability of receiving a first kidney transplant depends on the age, diabetic status and obesity of the patient, and has remained stable over time.


Research on fatigue optimization simulation of polymeric heart valve based on the iterative sub-regional thickened method.
Prosthetic polymeric heart valves (PHVs) have the potential to overcome the inherent material and design limitations of traditional valves in the treatment of valvular heart disease; however, their durability remains limited. Optimal design of the valve structure is necessary to improve their durability. This study aimed to enhance the fatigue resistance of PHVs by improving the stress distribution. Iterative subregional thickening of the leaflets was used, and the mechanical stress distribution and hemodynamics of these polymeric tri-leaflet valves were characterized using a fluid-structure interaction approach. Subregional thickening led to a reduction in stress concentration on the leaflet, with the effective orifice area still meeting ISO 5840-3 and the regurgitant volume achieving a similar value to those in previous studies. The maximum stress in the final iteration was reduced by 28% compared with that of the prototype. The proposed method shows potential for analyzing the stress distribution and hemodynamic performance of subregional thickened valves and can further improve the durability of PHVs.


Angiotensin II promotes differentiation of mouse embryonic stem cells to smooth muscle cells through PI3-kinase signaling pathway and NF-κB.
Embryonic stem cells (ES cells), the pluripotent derivatives of the inner cell mass from blastocysts, have the capacity for unlimited growth, self-renewal and differentiation toward all types of somatic cells. Angiotensin II (Ang II), the most important effector peptide of the renin-angiotensin system, is also an angiogenesis factor. However, the potential impact of Ang II on ES cell differentiation is still unknown. In the present study, we have successfully induced the differentiation of ES cells into smooth muscle cells (SMCs) on collagen IV. Interestingly, incubation of ES cells with Ang II further promoted SMC differentiation from ES cells, which was abolished by prior treatment with Ang II type 1 (AT1) receptor antagonist losartan, but not Ang II type 2 (AT2) receptor antagonist PD123319. Moreover, we found that, in parallel with SMC specific-marker induction, the expression levels of phosphoAkt and NF-Kappa B (NF-κB) p50 were up-regulated by Ang II. Importantly, addition of phosphoinositide-3 kinase (PI3K) inhibitor LY294002 led to a marked inhibition of Ang II induced SMC specific markers, phosphoAkt and NF-κB p50 expression. Furthermore, NF-κB inhibitor BAY11-7082 can inhibit Ang II induced expression of SMC specific markers. Thus, we demonstrate for the first time that Ang II plays a promotive role in the stage of ES cell differentiation to SMCs through AT1 receptor. We further confirmed that PI3K/Akt signaling pathway and NF-κB play key roles in this process.


Venous thromboembolism after spontaneous intracerebral hemorrhage and the status quo of anticoagulation in this population: A retrospective casecontrol study from a tertiary hospital in China.
Patients with spontaneous intracerebral hemorrhage (sICH) are susceptible to venous thromboembolism (VTE) including pulmonary embolism (PE) and deep venous thrombosis (DVT) due to a variety of risk factors. There are few studies regarding the predictive value of D-dimer for VTE in patients with sICH, and the anticoagulation therapy for these patients are still controversial. The objective of this study is to study the independent predictors of VTE in sICH patients. The rates of anticoagulation therapy and hemorrhagic evens were also investigated. Retrospective review of patients with sICH admitted to the First Affiliated Hospital of Dalian Medical University from 2012 to 2022 and who developed VTE (PE and/or DVT) during hospitalization. A similar number of sICH patients without VTE were randomly selected into the control group. A variety of clinical characteristics were compared between groups. Univariate and multivariate analyses were performed to identify independent predictors of VTE in patients with sICH. A total of 270 sICH patients were enrolled in this study, including 132 patients with VTE and 138 patients without VTE. After adjusting for other confounders, the maximum level of D-dimer during hospitalization (odds ratio [OR] 1.061, 95 % confidence interval (CI) 1.014-1.110), Glasgow coma scale (GCS) on admission (OR 1.347, 95 % CI 1.110-1.634), modified Rankin Scale (mRS) at discharge (OR 2.578, 95 % CI 1.546-4.298), neutrophil count (OR 1.056, 95 % CI 1.025-1.088) and hospitalization time (OR 1.089, 95 % CI 1.018-1.164) were independently associated with the sICH patients who developed VTE. The maximum D-dimer plasma level of 5.655 mg/L during hospitalization was the optimal threshold to indicate sICH patients developing VTE with a sensitivity of 83.3 % and a specificity of 67.4 %. No patients with sICH received prophylactic anticoagulation therapy against VTE in the present study. A total of 57.6 % (76/132) of the sICH patients with VTE were administered anticoagulant therapy and the rate of hemorrhagic complication was 9.2 %. sICH patients with increased levels of D-dimer, higher GCS scores, higher mRS scores, increased neutrophil counts and longer hospitalization time are more likely to develop VTE complications. Routine and serial monitoring of the D-dimer values may be useful in patients with sICH, and VTE should be considered when the plasma level of D-dimer increases to 5.655 mg/L during hospitalization. In tertiary hospitals in China, the rate of sICH patients with VTE receiving anticoagulation treatment is low. Further studies are necessary to explore the safety and efficacy of VTE therapeutic anticoagulation in patients with sICH.


[Determination of the quality of injuries of potato tubers due to damage and rot].
A new method is presented for determining damage to potato tuber tissue. It is based on the fact that starch can be leached with water from the damaged tissue. The starch content of the washing water informs about the extent of tissue damage. Damage assessments of the same samples yielded correlation coefficients ranging from r = 0.8 to r = 0.9 between the determinations and the assessments. The method considers both the mechanical tissue damage and the rot.


The effect of a predatory leech, Nephelopsis obscura, on mortality, growth, and production of chironomid larvae in a small pond.
The effect of a predatory leech, Nephelopsis obscura, on survivorship, growth, and production of chronomid larvae was studied by enclosure experiments carried out in a small pond. The prey population was composed almost entirely of the tubiculous, microphagous chironomid larvae, Chironomus riparius and Glyptotendipes paripes. Nephelopsis significantly reduced chironomid survivorship within the enclosures, and accounted for most of the measured mortality of fourth instar larvae. The cropping by Nephelopsis was not significantly biased toward either prey species. In long-term experiments (66 d) chironomid biomass in enclosures without leeches reached much higher levels than in enclosures containing Nephelopsis. This increase in biomass was due to growth of surviving larvae, rather than recruitment, since emergence and oviposition were not going on during the course of the experiments. The enhanced survivorship of larvae within leech-free enclosures was eventually accompanied by reduced growth and specific production (daily production/biomass) for C. riparius, which made up about 90% of the larval population. Growth and specific production of G. paripes (10% of larval population) was not affected. Short-term experiments (25 d) involving manipulation of densities and species ratio (9:1 CR:GP and 1:9 CR:GP) of larvae revealed that growth of the majority species was strongly influenced by larval density, whereas growth of the minority species was not. The same pattern was observed both in the presence and in the absence of Nephelopsis and was a result of differences in resource utilization between the two species. In the shortterm experiments, growth rates estimated for larvae exposed to leeches were significantly less than those for larvae in leech-free enclosures. This could be due either to size-biased consumption of larvae by Nephelopsis, or possibly a disturbance factor leading to reduced larval food intake and/or increased metabolic costs.


The Variation of Withdrawal of Life Sustaining Therapy in Older Adults With Traumatic Brain Injury.
The decision to withdraw life sustaining treatment (WDLST) in older adults with traumatic brain injury is subject to wide variability leading to nonbeneficial interventions and unnecessary use of hospital resources. We hypothesized that patient and hospital factors are associated with WDLST and WDLST timing. All traumatic brain injury patients ≥65 with Glasgow coma scores (GCS) of 4-11 from 2018 to 2019 at level I and II centers were selected from the National Trauma Data Bank. Patients with head abbreviated injury scores 5-6 or death within 24 h were excluded. Bayesian additive regression tree analysis was performed to identify the cumulative incidence function (CIF) and the relative risks (RR) over time for withdrawal of care, discharge to hospice (DH), and death. Death alone (no WDLST or DH) served as the comparator group for all analyses. A subanalysis of the composite outcome WDLST/DH (defined as end-of-life-care), with death (no WDLST or DH) as a comparator cohort was performed. We included 2126 patients, of whom 1957 (57%) underwent WDLST, 402 (19%) died, and 469 (22%) were DH. 60% of patients were male, and the mean age was 80 y. The majority of patients were injured by fall (76%, n = 1644). Patients who were DH were more often female (51% DH versus 39% WDLST), had a past medical history of dementia (45% DH versus 18% WDLST), and had lower admission injury severity score (14 DH versus 18.6 WDLST) (P < 0.001). Compared to those who DH, those who underwent WDLST had a lower GCS (9.8 versus 8.4, P < 0.001). CIF of WDSLT and DH increased with age, stabilizing by day 3. At day 3, patients ≥90 y had an increased RR of DH compared to WDLST (RR 2.5 versus 1.4). As GCS increased, CIF and RR of WDLST decreased, while CIF and RR of DH increased (RR on day 3 for GCS 12: WDLST 0.42 versus DH 1.31).Patients at nonprofit institutions were more likely to undergo WDLST (RR 1.15) compared to DH (0.68). Compared to patients of White race, patients of Black race had a lower RR of WDLST at all timepoints. Patient and hospital factors influence the practice of end-of-life-care (WDLST, DH, and death), highlighting the need to better understand variability to target palliative care interventions and standardize care across populations and trauma centers.


Measurements of the Total and Differential Higgs Boson Production Cross Sections Combining the H→γγ and H→ZZ^{*}→4ℓ Decay Channels at sqrt[s]=8 TeV with the ATLAS Detector.
Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3 fb^{-1} of pp collisions produced by the Large Hadron Collider at a center-of-mass energy of sqrt[s]=8 TeV and recorded by the ATLAS detector. Cross sections are obtained from measured H→γγ and H→ZZ^{*}→4ℓ event yields, which are combined accounting for detector efficiencies, fiducial acceptances, and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be σ_{pp→H}=33.0±5.3 (stat)±1.6 (syst) pb. The measurements are compared to state-of-the-art predictions.


Abrogation of the tumor promoting effect of allogeneic blood transfusion by polyadenylic-polyuridylic acid (poly A-poly U).
Studies from several centers have shown an immunosuppressive effect of surgical procedures, whilst others have shown blood transfusion in association with cancer surgery to have an adverse effect on ultimate prognosis. We have previously demonstrated enhanced growth of tumor metastases, in rats following allogeneic blood transfusion and surgery. Polyadenylic-polyuridylic acid (poly A-poly U) has been reported to stimulate immune responses. In this report, we have investigated the effectiveness of poly A-poly U as an adjuvant to blood transfusion and surgical procedures in BN rats bearing artificial lung metastases. Significantly reduced tumor growth was observed, following poly A-poly U adjuvant treatment. These results lead to serious contemplation of the use of this drug as adjuvant therapy in blood transfused and surgically treated patients.


Optimization of enhancement of therapeutic efficacy of ultrasound: Frequency-dependent effects on iodine formation from KI-starch solutions and ultrasound-induced killing of rat thymocytes.
We investigated liberation of iodine from solutions of KI-starch and cell lysis of rat thymocytes in argon-and nitrous oxide-saturated aqueous solutions induced by ultrasound at frequencies of 38 and 500 kHz and 1 and 2 MHz. Iodine was liberated in argon-saturated solutions exposed to ultrasound at 38 kHz, 500 kHz, and 1 MHz but not at 2 MHz. Lysis occurred in argon-saturated solutions at all four frequencies, but only at 38 kHz in nitrous oxide-saturated cell suspensions. No iodine was liberated in the other nitrous oxide-saturated samples. Relative ratio of the chemical effect versus 70-percent cell survival (an example of the physical effect) was, in order of frequency, 500 kHz>1.0 MHz>38 kHz>2.0 MHz. Partial protection was observed for cell lysis and cell viability after sonication with 500 kHz in argon-saturated solution containing cysteamine, a free radical scavenger. These results suggest that the chemical effects of ultrasound are prominent at specific frequencies, and that free radicals induced by ultrasonic cavitation partially affect lysis and the loss of viability of rat thymocytes.


The development of human benign prostatic hyperplasia with age.
In this study we report the prevalence and growth rate of human benign prostatic hyperplasia with age by combining and analyzing data from 10 independent studies containing more than 1,000 prostates. The normal prostate reaches 20 plus or minus 6 gm. in men between 21 and 30 years old, and this weight remains essentially constant with increasing age unless benign prostatic hyperplasia develops. The prevalence of pathological benign prostatic hyperplasia is only 8 per cent at the fourth decade; however, 50 per cent of the male population has pathological benign prostatic hyperplasia when they are 51 to 60 years old. The average weight of a prostate that is recognized at autopsy to contain benign prostatic hyperplasia is 33 plus or minus 16 gm. Only 4 per cent of the prostates in men more than 70 years old reach sizes greater than 100 gm. An analysis of a logistic growth curve of benign prostatic hyperplasia lesions removed at prostatectomy indicates that the growth of benign prostatic hyperplasia is initiated probably before the patient is 30 years old. The early phase of benign prostatic hyperplasia growth (men between 31 and 50 years old) is characterized by a doubling time for the tumor weight of 4.5 years. In the mid phase of benign prostatic hyperplasia growth (men between 51 and 70 years old) the doubling time is 10 years, and increases to more than 100 years in patients beyond 70 years old.


Projecting mechanics into morphospace: disparity in the feeding system of labrid fishes.
In no group of organisms has the link between species richness, morphological disparity, disparity in mechanics and functional or ecological diversification been made explicit. As a step towards integrating these measures of diversity, we examine how the mechanics of the anterior-jaw four-bar linkages of 104 species of Great Barrier Reef (GBR) labrid fishes maps into a scale-independent morphospace. As predicted from theory, no relationship exists between overall size and the mechanics of velocity and force transmission in labrid anterior-jaw linkages. Nonetheless, mechanics associated with the anterior jaw appear to have constrained diversification of labrid anterior-jaw morphology. Furthermore, simulations depict a generally nonlinear relationship between the length of individual links and transmission of motion. In addition, no relationship was found between morphological disparity and mechanical disparity among the most species-rich labrid groups from the GBR. It is also established that regions of morphospace equivalent in morphological disparity differ over nearly an order of magnitude in mechanical disparity. These results illustrate that without an explicit interpretation of the consequences of per unit change in morphology, conclusions about diversification drawn only from morphological disparity may be misleading.


Highly efficient carbon assimilation and nitrogen/phosphorus removal facilitated by photosynthetic O2 from algal-bacterial aerobic granular sludge under controlled DO/pH operation.
Reducing CO2 emission and energy consumption is crucial for the sustainable management of wastewater treatment plants (WWTPs). In this study, an algal-bacterial aerobic granular sludge (AGS) system was developed for efficient carbon (C) assimilation and nitrogen (N)/phosphorus (P) removal without the need for mechanical aeration. The photosynthetic O2 production by phototrophic organisms maintained the dissolved oxygen (DO) level at 3-4 mg/L in the bulk liquid, and an LED light control system reduced 10-30% of light energy consumption. Results showed that the biomass assimilated 52% of input dissolved total carbon (DTC), and the produced O2 simultaneously facilitated aerobic nitrification and P uptake with the coexisting phototrophs serving as a C fixer and O2 supplier. This resulted in a stably high total N removal of 81 ± 7% and an N assimilation rate of 7.55 mg/(g-MLVSS∙d) with enhanced microbial assimilation and simultaneous nitrification/denitrification. Good P removal of 92-98% was maintained during the test period at a molar ∆P/∆C ratio of 0.36 ± 0.03 and high P release and uptake rates of 10.84 ± 0.41 and 7.18 ± 0.24 mg/(g- MLVSS∙h), respectively. Photosynthetic O2 was more advantageous for N and P removal than mechanical aeration. This proposed system can contribute to a better design and sustainable operation of WWTPs using algal-bacterial AGS.


First Case of Meningoencephalitis and Bacteraemia with Flavobacterium Lindanitolerans.
Flavobacterium lindanitolerans is an environmental Gram-negative, non-spore-forming rod which is usually not considered to be a human pathogen. Isolation from human clinical samples has been described only once. We report the first case of meningoencephalitis and bacteraemia with Flavobacterium lindanitolerans. A 76-year-old female presented with fever, headache, alteration of mental status, marked meningism and dysarthria. A lumbar puncture demonstrated cerebrospinal fluid findings consistent with bacterial meningitis, and a broad-spectrum antibiotic therapy was initiated. Blood and cerebrospinal fluid cultures revealed a growth of Flavobacterium lindanitolerans. Based on antimicrobial susceptibilities testing, antibiotic treatment was changed to levofloxacin, resulting in a remission of the clinical symptoms after 21 days of treatment. Flavobacterium species are extremely rare human pathogens. However, some of them have been reported to cause opportunistic infections. We describe the first case of meningoencephalitis and bacteraemia caused by Flavobacterium lindanitolerans which was effectively treated with levofloxacin for 21 days. This is the first case of a meningoencephalitis and bacteraemia with Flavobacterium lindanitolerans.Levofloxacin can be given for 21 days as a treatment of F. lindanitolerans.


Hepatitis B in chronic kidney disease: moving toward effective prevention.
Control of hepatitis B virus (HBV) infection has been a continuous challenge in the management of patients with advanced kidney disease. HBV infections are still difficult to treat, so the main objective is disease prevention by timely immunization with hepatitis B surface antigen vaccines. In the general population, a simple two- or three-standard-dose vaccination strategy has been proven to be highly successful. In contrast, an intensified and more tailored approach is evolving in patients with advanced renal failure.


Prefabricated ankle-foot orthoses for children with cerebral palsy to overcome spastic drop-foot: does orthotic ankle stiffness matter?
Spastic drop-foot is a common problem in children with cerebral palsy that may lead to tripping and falling. To improve ankle dorsiflexion in swing phase, prefabricated carbon-composite ankle-foot orthoses are commonly prescribed; by increasing ankle stiffness, these orthoses may also improve knee extension in stance. To compare the effect of a stiff vs. flexible prefabricated ankle-foot orthosis on sagittal plane ankle and knee kinematics and kinetics during walking. Cross-sectional, repeated-measures, interventional study. Twenty-seven children and adolescents with cerebral palsy who had drop-foot in swing were included. Gait analysis was conducted under four conditions: barefoot, shod, with a stiff, and with a flexible orthosis. Participants were divided into two groups including children and adolescents who have a flexed knee during stance (KF, N = 12) and without flexed knee during stance (KE, N = 15). Ankle dorsiflexion in swing phase was significantly improved compared with the shod condition by 6.3 degrees (SD = 3.3 degrees) only in the KE group when using the flexible orthosis. For the stiff orthosis, knee extension in stance was significantly increased by 2.4 degrees (SD = 3.3 degrees) in the KE group compared with the shod condition. No significant improvements were observed for the KF group. Further analysis indicated that only seven patients in the KF group with weak ankle plantarflexors improved knee extension while using the stiff orthosis. Our results suggested that in the KE group, the flexible orthosis was best suited for patients with drop-foot without a knee extension deficit. The stiff orthosis was not suitable in this group as it caused a hyperextended knee without improving dorsiflexion in swing phase. Therefore, stiffness should be considered when prefabricated orthoses are prescribed.


Cytotoxic effects of Pd(II) complexes on cancer and normal cells: Their DNA & BSA adduct formation and theoretical approaches.
Herein, we report the synthesis and characterisation of a series of Pd(II) complexes: Pd(TEEDA)Cl2, C-1; [Pd(TEEDA)(OH2)2](NO3)2, C-2; [Pd(TEEDA)(l-cys)](NO3)2, C-3; [Pd(TEEDA)(NALC)], C-4; [Pd(TEEDA)(Meth)](NO3)2, C-5; and [Pd(TEEDA)(GSH)], C-6 (where TEEDA = N,N,N'-Triethylenediamine, l-cys = l-cysteine, NALC = N-acetyl-l-cysteine, Meth = dl-methionine and GSH = glutathione). UV-Vis spectroscopic characterisation was supported by TD-DFT theoretical simulation using Gaussian09 software. Different reactivity parameters were calculated from the energy difference between HOMO and LUMO of the complexes by DFT. The bonding mode of the labile ligands was confirmed by NBO analysis. Interaction of the complexes with DNA has been observed by gel electrophoresis experiment. DNA binding nature as well as binding constants of the complexes were measured with UV-Vis and fluorescence spectroscopic method. The binding nature of the complexes with DNA was confirmed by viscometric titration. Interaction of the complexes with BSA was investigated by UV-Vis and fluorescence titration method. Cytotoxic activity of the Pd(II) complexes was evaluated on A549 (lung carcinoma epithelial cells), HCT116(Colorectal Carcinoma) and HEK293 (Human embryonic kidney cells) cell lines. The ROS generation in the presence of the complexes was tested both on cancer cell lines A549 and HCT116 as well as human normal cell HEK293.


Androgen receptor genomic alterations and treatment resistance in metastatic prostate cancer.
Genomic alterations to the androgen receptor (AR) are common in metastatic castration-resistant prostate cancer (mCRPC). AR copy number amplifications, ligand-binding domain missense mutations, and intronic structural rearrangements can all drive resistance to approved AR pathway inhibitors and their detection via tissue or liquid biopsy is linked to clinical outcomes. With an increasingly crowded treatment landscape, there is hope that AR genomic alterations can act as prognostic and/or predictive biomarkers to guide patient management. In this review, we evaluate the current evidence for AR genomic alterations as clinical biomarkers in mCRPC, focusing on correlative studies that have used plasma circulating tumor DNA to characterize AR genotype. We highlight data that demonstrates the complexity of AR genotype within individual patients, and suggest that future studies should account for cancer clonal heterogeneity and variable tumor content in liquid biopsy samples. Given the potential for cooccurrence of multiple AR genomic alterations in the same or competing subclones of a patient, it is distinctly challenging to attribute blanket clinical significance to any individual alteration. This challenge is further complicated by the varied treatment exposures in contemporary patients, and the fact that AR genotype continues to evolve in the mCRPC setting across sequential lines of systemic therapy. As treatment access and liquid biopsy technology continues to improve, we posit that real-time measures of AR biology are likely to play a key role in emerging precision oncology strategies for metastatic prostate cancer.


Temperature dependence of the electronic spin-lattice relaxation time in a 2-iron-2-sulfur protein.
The ferredoxins are characterized by a strong temperature dependence of the electronic spin-lattice relaxation time T1. The measurement of this dependence above the liquid nitrogen temperature has been presented in earlier work [1] for the 2-iron-2-sulfur ferredoxin of the blue green alga Spirulina maxima. The different relaxation mechanisms which could be efficient in this range were briefly discussed. In the present paper, we extend the measurement of the temperature dependence of T1 to the low temperature range 1.25 to 30 K. From 1.25 K to 13 K, T1 is obtained by the saturating pulse method, whereas the continuous saturation method is used from 8 K to 30 K. The experimental conditions concerning these methods are discussed. The analysis of the temperature dependence curve over the whole range 1.25 K to 133 K shows clearly that different regions must be distinguished. For each region the possible relaxation processes and the corresponding vibrational modes are discussed.


Benign partial epilepsy in childhood: selective cognitive deficits are related to the location of focal spikes determined by combined EEG/MEG.
Benign partial epilepsy (BPE) in childhood is characterized by the occurrence of interictal stereotyped focal spikes with variable localization in the EEG. Children with BPE often exhibit neuropsychological deficits. It is unclear whether a correlation exists between these deficits and the localization of spikes, several EEG studies giving inconsistent results. Magnetoencephalography (MEG) improves the accuracy of spike localization. Therefore by using combined MEG/EEG, we investigated the topographic relation between focal spikes and neuropsychological findings in children with BPE. Twenty-seven children diagnosed consecutively with BPE were enrolled in the study. All were examined by combined MEG/EEG and magnetic resonance imaging (MRI). Location of spikes was determined by dipole source estimation. A standardized neuropsychological assessment was conducted, including Kaufman ABC battery, language tests, and motor performance series. All children with sufficient MEG data were included in the correlation analysis (N = 20). Focal spikes were located in the perisylvian region in 13 children, in the occipital region in seven, and in the frontal region in one. Five children had bilateral or multiple foci. Children with left perisylvian spikes did not differ from the others in global IQ, but performed significantly lower in language tests (p = 0.01). Children with occipital spikes performed significantly lower in simultaneous information processing (p = 0.01), especially in visual transformation tasks. Combined MEG/EEG investigation is a useful tool to examine interictal focal spikes. Our results show a correlation between the location of spikes and selective cognitive deficits in children with BPE. These findings indicate that focal interictal spikes may interfere with complex cognitive functions.


High-Dimensional Analysis of Circulating and Tissue-Derived Myeloid-Derived Suppressor Cells from Patients with Glioblastoma.
We will first describe analysis of MDSC subsets from patient tumors with multicolor flow cytometry. The key components of this methodology are to obtain viable single cell suspensions and eliminate red blood cell contamination.


Contiguity and covariation in human causal inference.
Nearly every theory of causal induction assumes that the existence and strength of causal relations needs to be inferred from observational data in the form of covariations. The last few decades have seen much controversy over exactly how covariations license causal conjectures. One consequence of this debate is that causal induction research has taken for granted that covariation information is readily available to reasoners. This perspective is reflected in typical experimental designs, which either employ covariation information in summary format or present participants with clearly marked discrete learning trials. I argue that such experimental designs oversimplify the problem of causal induction. Real-world contexts rarely are structured so neatly; rather, the decision about whether a cause and effect co-occurred on a given occasion constitutes a key element of the inductive process. This article will review how the event-parsing aspect of causal induction has been and could be addressed in associative learning and causal power theories.


Weaning and extubation from neonatal mechanical ventilation: an evidenced-based review.
Mechanical ventilation is a lifesaving treatment used to treat critical neonatal patients. It facilitates gas exchange, oxygenation, and CO2 removal. Despite advances in non-invasive ventilatory support methods in neonates, invasive ventilation (i.e., ventilation via an endotracheal tube) is still a standard treatment in NICUs. This ventilation approach may cause injury despite its advantages, especially in preterm neonates. Therefore, it is recommended that neonatologists consider weaning neonates from invasive mechanical ventilation as soon as possible. This review examines the steps required for the neonate's appropriate weaning and safe extubation from mechanical ventilation.


First-line panitumumab plus irinotecan/5-fluorouracil/leucovorin treatment in patients with metastatic colorectal cancer.
Panitumumab monotherapy is approved for KRAS wild-type (WT) metastatic colorectal cancer (mCRC) progressing after standard chemotherapy. This study evaluated first-line panitumumab plus FOLFIRI in patients with mCRC. In this phase II, single-arm study, panitumumab (6 mg/kg) and FOLFIRI [irinotecan (180 mg/m(2)) and leucovorin (400 mg/m(2)) followed by a 5-fluorouracil 400 mg/m(2) bolus and a 2,400-3,000 mg/m(2) continuous infusion] were administered every 14 days until progression. Data were analysed descriptively overall and by tumour KRAS status. KRAS data were available for 145/154 (94%) patients: 59% KRAS WT and 41% mutant (MT); mean follow-up was 39.5 versus 35.8 weeks, respectively. Objective responses occurred in 49% of patients: 56% versus 38% in the KRAS WT versus MT groups [(18% difference (95% CI 1-35%); odds ratio 2.1 (95% CI 1.0-4.4)]; median duration of response was 13.0 versus 7.4 months. More patients in the WT group underwent R0 resection (8% vs. 5%); median progression-free survival also favoured this group (8.9 vs. 7.2 months). The most common adverse events (any grade) were integument toxicities (98%), diarrhoea (79%) and stomatitis/oral mucositis (51%). As expected, consistently favourable efficacy was observed in patients with KRAS WT versus MT tumours receiving first-line panitumumab plus FOLFIRI treatment.


Erratum: WHO Grade IV Gliofibroma: A Grading Label Denoting Malignancy for an Otherwise Commonly Misinterpreted Neoplasm.
[This corrects the article on p. 325 in vol. 49, PMID: 26081826.].


Hypoxia-inducible factor-1-independent regulation of vascular endothelial growth factor by hypoxia in colon cancer.
The induction of vascular endothelial growth factor (VEGF) is an essential feature of tumor angiogenesis, and the hypoxia-inducible factor-1 (HIF-1) transcription factor is known to be a key mediator of this process. In colon cancer, the frequently mutated K-ras oncogene also can regulate VEGF expression, but the role that K-ras may play in hypoxia is unknown. Hypoxia induced VEGF promoter activity, mRNA, and protein levels in colon cancer cells. Although HIF-1alpha was induced by hypoxia, VEGF reporter constructs with selectively mutated hypoxia-response elements remained responsive to hypoxia. In addition, "knockdown" of HIF-1alpha by RNA interference only minimally inhibited the hypoxic induction of VEGF. A region of the VEGF promoter between -420 and -90 bp mediated this HIF-independent induction by hypoxia. The introduction of K-ras(Val12) augmented the hypoxic induction of VEGF, and this was observed in wild-type and HIF-1alpha knockdown colon cancer cells. Thus, VEGF may be induced by hypoxia through HIF-dependent and HIF-independent pathways, and K-ras also can induce VEGF in hypoxia independent of HIF-1. These findings suggest the existence of multiple mechanisms regulating the hypoxic induction of VEGF in colon cancer.


Pathomorphological and immunohistochemical analysis of proliferative activity of the buccal mucosal epithelium in lichen planus.
Structural reorganization of the buccal mucosa and changes in proliferative activity of epitheliocytes in typical and erosive ulcerative lichen planus were studied. The most manifest diagnostically significant pathomorphological signs of lichen planus of the buccal mucosa are described: acanthosis, granulosis, parakeratosis, lymphocytic infiltration of the lamina propria, and edema. The most pronounced morphological changes and higher index of epitheliocyte proliferative activity (by expression of Ki-67) are characteristic of the erosive ulcerative form of the disease.


An investigation of endoparasites and the determinants of parasite infection in European hedgehogs (Erinaceus europaeus) from Denmark.
The European hedgehog population is declining in Europe. It is therefore important to investigate the causes for the decline and monitor the general health of the species. We investigated the endoparasite occurrence in 299 dead European hedgehogs. Of these, endoparasites were detected in 69% of the individuals tested. We identified Crenosoma striatum, Capillaria aerophila (syn. Eucoleus aerophilus), Capillaria spp., coccidia, Cryptosporidium spp., Brachylaemus spp. and Capillaria hepatica. We also examined the hedgehogs for Giardia spp. and Echinococcus multilocularis but all were negative. Coccidia (n = 7, 2.5%) and Cryptosporidium spp. (n = 14, 5.2%) were only detected in individuals from Zealand, Lolland and Jutland south of the Limfjord. Single cases of Brachylaemus spp. (n = 1, 0.4%) and Capillaria hepatica (n = 1, 1.1%) were exclusively discovered in Jutland south and north of the Limfjord, respectively. These results indicate a regional difference in endoparasite species carried by European hedgehogs in Denmark. This stresses the need for hedgehogs to be cared for locally when admitted to wildlife rehabilitation centres, and to be released within their area of origin, to prevent spread of endoparasite infections among hedgehogs. Additionally, we explored the following possible determinants of parasite infection in the hedgehogs: sex, age, mortality category (in-care, natural and roadkill), infection with MRSA, genetic heterozygosity, month of death, geographical location and habitat type, and found that only age had a statistically significant effect on endoparasite prevalence, as we detected a lower occurrence of endoparasites in juvenile hedgehogs (<1 year) compared to the other age classes. However, pairwise comparisons of geographical regions did show significant differences in endoparasite occurrence: Zealand vs. Jutland south of the Limfjord and Zealand vs. Falster. We conclude that, in line with previous studies of European hedgehogs throughout their range in Western Europe, endoparasite infections are common and a natural part of their ecology.


Refractory serositis in Gorham-Stout syndrome.
Gorham-Stout syndrome (GSS) is a rare disorder with various presentations and unpredictable prognoses. Previous understandings of GSS mainly focused on progressive bone destruction, while we identified a group of GSS patients with serous effusion as the first symptom. This study aimed to investigate the clinical characteristics of patients with GSS having serous effusion as the first symptom. Patients diagnosed with GSS were identified through the Peking Union Medical College Hospital Medical Record System. The demographic, clinical, laboratory, and imaging data were collected. Patients who first presented with serous effusion were recruited into the serous group, while those with bone destruction were recruited into the bone group. Of the 23 patients with GSS enrolled, 13 were in the bone group and 10 in the serous group. The median disease duration was shorter and exercise tolerance was lower in the serous group. Despite less frequent bone pain in the serous group, the frequency of bone involvement was similar to that in the bone group. Patients in the serous group had higher rates of bilateral pleural effusion and multiple serous effusion. However, serous effusion also developed with disease progression in the bone group. Of the 17 patients treated with bisphosphonates, 14 reached bone-stable state. However, 5 out of 10 patients with serous effusion still had refractory effusions after bisphosphonates treatment. Three patients received sirolimus treatment, with an improvement in serous effusion. Seventeen patients were followed up; three patients died, two in the bone group and one in the serous group. This study discovered that GSS could first be presented with serous effusion. We believe that this may be a new phenotype of the disease. Sirolimus might help in controlling serous effusion and improving prognosis.


The fate of Fusarium mycotoxins (deoxynivalenol and zearalenone) through wort fermenting by Saccharomyces yeasts (S. cerevisiae and S. pastorianus).
The aim of this study was to evaluate the effect of 15 commercial yeasts in the mitigation of the Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN) during the brewing process. Saccharomyces strains (10 strains of S. cerevisiae and 5 of S. pastorianus) were used to ferment DON and ZEN contaminated wort. Wort samples were taken every 24 h during fermentation, while mycotoxin analysis in yeast was performed at the end of fermentation (96 h); additionally, pH and ethanol content were measured daily. For mycotoxin analysis, after immunoaffinity purification of sample extracts, analysis was performed using an Ultra-High-Pressure Liquid Chromatograph coupled with a diode array or fluorescence detector (UHPLC-DAD/FLD). Mycotoxin presence had no significant effect on the ethanol production during brewing. At the end of fermentation, 10-17% of DON and 30-70% of ZEN had been removed, 6% of the initial concentration of DON and 31% of the ZEN being adsorbed by the yeast. Beermakers must pay careful attention to the raw material since a high percentage of DON could be present at the end of the beer fermentation process. Future studies should focus on the quantification of "masked" mycotoxins that are relevant to food security.


[Functional diagnosis as a principle of therapy and rehabilitation--from nosological to comprehensive psychiatric diagnosis].
The current predominantly one-side orientation on nosological and syndromatological diagnosis as a basis for one-side somato-therapy in psychiatric practice is a result of the biological basic assumptions of medicine arising from the consideration of illness as an organismic phenomenon. No conclusions regarding suitable forms of psychotherapy or sociotherapy can be derived from a nosological diagnosis. The functional diagnosis method developed in the Soviet Union and presented here is a necessary enlargement of the diagnostic approach, provides the basis required for selecting appropriate forms of psychotherapy and sociotherapy and is in line with illness model customarily used in human medicine.


The effects of axotomy on electrophysiological properties of B cells of bullfrog sympathetic ganglia conditioned by a previous lesion.
In bullfrog sympathetic B cells, axotomy decreases the amplitude and decay time of membrane afterhyperpolarization (AHP) and increases action potential (AP) duration. A second (test) axotomy, 7 days after an initial (conditioning) axotomy, did not amplify these changes. No recovery of AHP amplitude or AP duration occurred by 56 days post-axotomy, but AHP decay time recovered 21 days earlier than after test axotomy alone. Conditioning, previously shown to accelerate regeneration, speeds the return to normal of those membrane properties previously shown to recover after axotomy.


Characterization and regional distribution of individual gangliosides in goldfish central nervous system.
Gangliosides were partially purified from goldfish brain and fractionated by DEAE Fractogel column chromatography. Each fraction was then analyzed by HPTLC and also by HPLC after conversion of the gangliosides to 2,4-dinitrophenylhydrazides. The tetrasialoganglioside GQ1c was found to constitute more than 50% of the total gangliosides. Gangliosides in smaller quantities were also tentatively identified. These included GT1b, GT1c, GT2, GT3, GD1a, and several others. By using this information, the amounts of individual gangliosides in various regions of goldfish central nervous system were compared. Although all areas of brain examined contained similar concentrations of gangliosides, with GQ1c as the predominant component, retina and optic nerve contained significantly lower concentrations of GQ1c, and GM3 was the major component.


Timing of Doppler examination for the detection of arteriovenous fistula after percutaneous renal biopsy.
Percutaneous renal biopsy is frequently performed, and postbiopsy arteriovenous fistula (AVF) formation is not uncommon. In most cases, it is asymptomatic and remains undiagnosed, because Doppler examination is not performed routinely. We describe 2 cases of postbiopsy AVF of the kidney that were detected 61 and 17 months after renal biopsy, respectively. The subsequent superselective transcatheter arterial embolization was successful in both cases. An undetected AVF of the kidney can progress and lead to serious consequences. A follow-up Doppler examination of the kidney soon after renal biopsy and 6 months later is recommended for early detection of nonresolving AVFs to prevent further complications.


Suppression of DNA synthesis in normal, but not neoplastic, nuclei by cytoplasmic extracts from resting cells.
We have previously shown that a heat-stable protein in cytoplasmic extracts from human quiescent peripheral blood lymphocytes (PBL) is capable of inhibiting the induction of DNA synthesis in isolated resting nuclei. We now report that these cytoplasmic extracts are also capable of suppressing DNA synthetic activity in replicative nuclei isolated from mitogen-activated PBL. PBL extracts had little or no inhibitory effect, however, on replicative nuclei derived from several transformed lymphoblastoid cell lines. These results suggest that the growth of normal lymphocytes may be negatively controlled by cytoplasmic inhibitory factors. Furthermore, the relative resistance of tumor cell nuclei to these inhibitory signals provides a possible explanation for the loss of growth control in neoplastic cells.


Predictors of hospital readmission in United States adults with psoriasis.
Previous studies showed a large inpatient burden of psoriasis in the United States. Less is known about the hospital readmission for psoriasis. To determine the patterns and predictors of hospital readmission rates for psoriasis. We analyzed data from the 2012-2014 Nationwide Readmissions Database, a representative sample of hospital readmissions in the United States. Among 2606 admissions for psoriasis, 216 had ≥1 readmissions for psoriasis (prevalence [95% confidence interval]: 8.3% [6.6%-10.0%]) and 918 for all-causes (35.2% [32.2%-38.3%]). The mean annual cost of first readmission for any reason was $3,500,141, with $8,357,961 for subsequent readmissions. In multivariable regression models, readmission for psoriasis was associated with ≥6 day-long index hospitalization (adjusted hazard ratio [95% confidence interval]: 1.82 [1.06-3.12]), teaching hospital (1.93 [1.13-3.31]), comorbid skin infection (2.13 [1.11-4.08]), and hospitalization in the autumn (4.51 [2.54-8.00]), but inversely associated with other infections (0.49 [0.26-0.92]). Readmissions for psoriasis increased from 2012 to 2014 (1.93 [1.26-2.93]). No data on psoriasis characteristics. Inpatients with psoriasis had high rates of readmission overall but low rates of readmission for psoriasis per se. A subset of psoriasis patients was hospitalized repeatedly and responsible for most inpatients costs. Future interventions are needed to lower readmission rates among psoriasis patients.


Targeting Glutamine Metabolism and PD-L1: A Novel Anti-tumor Pas de Deux.
In this issue of Molecular Cell, Byun et al. (2020) find that the dual targeting of glutamine metabolism and the PD-L1 checkpoint inhibitor augments anti-tumor immunity. Mechanistically, decreased glutamine availability attenuated S-glutathionylation of SERCA, resulting in an increase in cytosolic calcium, enhanced NF-κB activity, and upregulation of programmed death-ligand 1.


Three-year clinical evaluation of zirconia and zirconia-reinforced lithium silicate crowns with minimally invasive vertical preparation technique.
Large part of the tooth is required to be removed during crown preparation. A minimally invasive method for preparing single crowns is required to increase the durability of teeth. The aim of this study was to evaluate the clinical performance of two ceramic systems fabricated with minimally invasive vertical preparation. Forty endodontically treated maxillary premolars were prepared with vertical preparation and received temporary crowns for a period of 21 days. Twenty zirconia-reinforced lithium silicate (Celtra Duo HT, Dentsply Sirona, Germany) and 20 monolithic high translucency zirconia (Katana HT, Kuarary Noritake, Japan) crowns were fabricated by CAD/CAM and cemented with dual-polymerizing luting resin. The crowns were evaluated clinically and radiographically for 36 months following modified FDI criteria. Statistical analysis was conducted with t Student test (Cochran Q). Over the follow-up period, there was no need to replace any of the study's crowns. The overall survival rate of the 40 crowns was 100% according to the Kaplan-Meier survival method. The clinical quality of all crowns and the patient's satisfaction were high. No caries was detected and no adverse soft tissue reactions around the crowns were observed. Periodontal probing depth was reported to be increased at mesial and distal sites more than the facial one in the 36-month follow-up with no statistically significant difference between both materials (P = 0.186). Zirconia and zirconia-reinforced lithium silicate could be used as a material for restoration of teeth prepared with vertical preparation technique. Both ceramic materials achieved good esthetic results, promotes healthy and stable soft tissues with no mechanical complications after 3 years of clinical evaluation. Monolithic high translucency zirconia and zirconia-reinforced lithium silicate ceramics can be used for the restorations of minimal invasive vertical preparation in premolar area with 0.5 mm margin thickness.


Hydrothermally grown TiO2-nanorods on surface mechanical attrition treated Ti: Improved corrosion fatigue and osteogenesis.
Current bioactive modifications of Ti-based materials for promoting osteogenesis often decrease corrosion fatigue strength (σcf) of the resultant implants, thereby shortening their service lifespan. To solve this issue and accelerate the osteogenesis process, in the present study, a TiO2 nanorods (TNR)-arrayed coating was hydrothermally grown on optimal surface mechanical attrition treated (SMATed) titanium (S-Ti). The microstructure, bond integrity, residual stress distribution, and corrosion fatigue of TNR-coated S-Ti (TNR/S-Ti) and the response of macrophages and bone marrow-derived mesenchymal stem cells (BMSCs) to TNR/S-Ti were investigated and compared with those of mechanically polished Ti (P-Ti), S-Ti, and TNR-coated P-Ti (TNR/P-Ti). S-Ti showed a nanograined layer and an underlying grain-deformed region with residual compressive stress, which was sustained even when it was hydrothermally coated with TNR. TNR on S-Ti showed nanotopography, composition, and bond strength almost identical to those of P-Ti. While TNR/P-Ti showed a considerable decrease in σcf compared to P-Ti, TNR/S-Ti exhibited an improved σcf which was even higher than that of P-Ti. Biologically, TNR/S-Ti enhanced adhesion, differentiation, and mineralization of BMSCs, and it also promoted adhesion and M1-to-M2 transition of macrophages as compared to S-Ti and P-Ti. With rapid phenotype switch of macrophages, the level of proinflammatory cytokines decreased, while anti-inflammatory cytokines were upregulated. In co-culture conditions, the migration, differentiation, and mineralization of BMSCs were enhanced by increased level of secretion factors of macrophages on TNR/S-Ti. The modified structure accelerated bone apposition in rabbit femur and is expected to induce a favorable immune microenvironment to facilitate osseointegration earlier; it can also simultaneously improve corrosion fatigue resistance of Ti-based implants and thereby enhance their service life.


Mediastinal myelolipoma showing gradual enlargement over 9 years: a case report.
Myelolipoma is a rare benign tumor composed of mature adipose tissue and normal hematopoietic tissue. Although surgical resection has been recommended due to the potential of progressive enlargement, the natural history of mediastinal myelolipoma has not yet been described. Herein we report a surgically resected mediastinal myelolipoma showing gradual enlargement over a period of 9 years. A 70-year-old woman presented with a posterior mediastinal mass shadow detected by computed tomography (CT) examination. She had a medical history of sigmoidectomy for colon cancer 13 years previously. A CT scan showed a smooth, well-demarcated 2.8 × 2.1-cm paravertebral mass shadow, composed of a fat density area and a soft tissue density area, which showed gradual enlargement from a 1.6 × 1.0-cm nodule 9 years previously. This was not accompanied by chronic anemia or hematologic disease including thalassemia, and no abnormal accumulation was observed on bone marrow scintigraphy or fluoro-2-deoxyglucose positron emission tomography. With a clinical diagnosis of mediastinal myelolipoma, surgical resection was performed, and pathological examination confirmed the diagnosis. We experienced a rare case with mediastinal myelolipoma showing gradual enlargement, with a tumor doubling time of 1,212 days.