Morphophysiological and biochemical attributes influence intra-genotypic preference of shoot fly [Atherigona soccata (Rondani)] among sorghum genotypes.
Shoot fly [Atherigona soccata (Rondani)] is a destructive pest of sorghum at the seedling stage and causes huge losses to grain yield and green fodder. The host-plant resistance mechanism is the best approach to reduce the attack of insects in plants. The damage parameters, morphophysiological traits, and biochemical metabolites had been investigated in the leaves and stem of contrasting sorghum genotypes, viz., resistant (IS18551, ICSV705, ICSV700), moderately resistant (PSC-4), and susceptible (SWARNA and SL-44) at 15 and 21 days after emergence (DAE) against shoot fly infestation. The resistant genotypes recorded lowest shoot fly oviposition and incidence (0.3-0.7 eggs plant-1 and 10-15%) than the susceptible genotypes (2.4-3.0 eggs plant-1 and 70-80%), respectively. The susceptible genotype SWARNA recorded 50% and 80% higher deadheart formation than the resistant genotype IS18551 at 15 and 21 DAE, respectively. Resistant genotypes exhibited higher trichome density at adaxial and abaxial part of leaf (118-145 and 106-131) with pink colored leaf sheath (scale 1.50-3.25), glossy leaves (scale1.00-1.25), and lower leaf surface wetness (scale1.25-2.00) compared with susceptible genotype with 49.3-73.3 and 25.3-64.0, scale 2.50-4.00, scale 2.75-3.50, and scale 3.25-4.25 for the respective parameters. Another defense response of sorghum toward the insect attack was modulation of plant metabolism. The infested genotypes responded to insect attack by upregulation of total soluble sugar, total phenol, prussic acid, and chlorophyll content by 1.2-2.1-fold, 1.5-2.0-fold, 1.2-1.3-fold, and 1.2-3.9-fold with more induction in susceptible genotypes at 21 DAE. On the whole, the present study indicates that morphophysiological and biochemical attributes contribute toward the resistance mechanism in sorghum against shoot fly infestation.


Mitigation of pesticide-mediated ocular toxicity via nanotechnology-based contact lenses: a review.
The xenobiotic stress exerted by pesticides leads to the deterioration of human and animal health including ocular health. Acute or prolonged exposure to these agricultural toxicants has been implicated in a number of pathological conditions of the eye such as irritation, epiphora or hyper-lacrimation, abrasions on the ocular surface, and decreased visual acuity. The issue is compounded by the fact that tissues of the eye absorb pesticides faster than other organs of the body and are more susceptible to damage as well. However, there is a lacuna in our knowledge regarding the ways by which pesticide exposure-mediated ocular insult might be counteracted. Topical instillation of drugs known to combat the pesticide induced toxicity has been explored to mitigate the detrimental impact of pesticide exposure. However, topical eye drop solutions exhibit very low bioavailability and limited drug residence duration in the tear film decreasing their efficacy. Contact lenses have been explored in this respect to increase bioavailability of ocular drugs, while nanoparticles have lately been utilized to increase drug bioavailability and increase drug residence duration in different tissues. The current review focuses on drug delivery and futuristic aspects of corneal protection from ocular toxicity using contact lenses.


The type of behavior and the role of relationship length in mate choice for prosociality among physically attractive individuals.
Two further key aspects of prosociality as a sexual signal are explored here. First, the context in which it is used (in particular, relationship length) and, second, the different types of prosocial behaviors that exist in social interactions. Therefore, this commentary can show why prosocial behaviors are biased toward physically attractive individuals, as they can gain valuable information from them.


Gramicidin A-based peptide vector for intracellular protein delivery.
The development of the peptide-based vectors for the intracellular delivery of biologically active macromolecules has opened new prospects of their application in research and therapy. Earlier the amphipathic cell-penetrating peptide (CPP) Pep-1 was reported to mediate cellular uptake of proteins without covalent binding to them. In this work we studied the ability of a series of membrane-active amphipathic peptides, based on the gramicidin A sequence, to transport a model protein across the eukaryotic cell membrane. Among them the positively charged Cys-containing peptide P10C demonstrated the most effective beta-galactosidase intracellular delivery. Besides, this peptide was shown to form noncovalent associates with beta-galactosidase as judged from electrophoresis and enzymatic activity assays. In addition, a series of new gramicidin analogues were prepared and the effect of N-terminus modification of gramicidin on the protein transduction efficiency was studied.


Alpha-1 adrenergic receptor number and receptor density in isolated hepatocytes from foetal, juvenile and adult rats.
Alpha-1 adrenergic receptor number was defined by [3H]-prazosin binding in crude membrane preparations of hepatocytes and in intact hepatocytes isolated from foetal (day 22 of gestation), juvenile (12 days old), adult female and adult male (90-150 days old) rats and compared with the alpha-1 adrenergic response (measured by epinephrine stimulated glucose liberation in presence of the beta-antagonist propranolol). The alpha-1 receptor number (expressed as fmol bound [3H]-prazosin/mg membrane protein or as receptor number/cell) increases in an age-dependent fashion reaching the highest values in hepatocytes of adult female and male rats. Statistically significant differences could be found between foetal, juvenile and adult rat hepatocytes. No differences in [3H]-prazosin binding were observed between hepatocytes of adult female and adult male rats. The receptor density (expressed as receptor number/microns 2 cell surface), however, was found to be equal in juvenile and adult rats. There are no differences of alpha-1 adrenergic response in juvenile, adult female and adult male rat hepatocytes, whereas the values in foetal hepatocytes were significantly lower. So the biological response is closely correlated with the receptor density and not with the receptor number per cell.


Successful treatment of a renal arteriovenous fistula with a Fogarty catheter.
A large renal arteriovenous fistula developed in a 71-year-old patient after percutaneous needle biopsy. Attempts to control the fistula with autologous clot were unsuccessful. A Fogarty catheter placed fluoroscopically was used to obliterate the feeding vessel. This is the first case reported in which this technique was used to control a renal arteriovenous fistula. This method of treatment offers the advantage of avoiding major surgical intervention with precise control of the fistula.


Characterization of a factor(s) which synergizes with recombinant interleukin 2 in promoting allogeneic human cytolytic T-lymphocyte responses in vitro.
Supernatants from PHA-activated human peripheral blood mononuclear cells, depleted of virtually all IL-2 activity by an anti-rIL-2 immunoadsorbent column, contain a factor(s) which synergizes with rIL-2 in facilitating the generation of allogeneic human CTL responses in vitro. This factor, provisionally termed CTL maturation factor (TcMF), did not appear to promote CTL responses in the absence of rIL-2. Furthermore, it acted later than IL-2 in facilitating CTL responses and could not be replaced by recombinant IFN-gamma. In this report we show that rIFN-alpha, rIL-1 alpha, and rIL-1 beta likewise lack TcMF activity. The TcMF activity in lymphokine-containing culture supernatants could be eliminated by trypsin or pronase but not by neuraminidase or RNase. Gel filtration revealed two peaks of TcMF activity, one at 12,000 to 25,000 Da and the other at 45,000 to 65,000 Da. Isoelectrofocusing demonstrated substantial charge heterogeneity. The majority of TcMF activity was recovered between pI 4.0 and pI 5.5 with a minor component at pI 6.5, corresponding to the areas in which IL-1 activity was also found. However, TcMF activity could be separated from IL-1 by reverse-phase HPLC. Moreover, TcMF recovered following reverse-phase HPLC was also found to be depleted of IL-4 activity. These studies suggest that TcMF activity is mediated by a protein(s) distinct from IL-1, IL-2, IL-4, and interferon-alpha or-gamma.


[Obstructive hypopnea sleep apnea syndrome in the elderly].
obstructive sleep apnea hypopnea syndrome (OSAHS) is a common but often under diagnosed disease among elderly persons. The aim of our study was to determine the clinical and polygraphic characteristics of OSAHS in elderly by comparing them to younger patients. a retrospective study was performed at Pavillon D pneumology at Abderrahmen Mami Hospital in Ariana including 222 patients with OSAHS, divided into two groups: group 1 including 72 patients aged 18 to 45 years and Group 2 including 150 patients aged 65 and over. Clinical and polygraphic data was collected. elderly patients were more female, less exposed to tobacco but more exposed to biomass smoke. The average consultation time was significantly longer for elderly patients compared to young patients. Diurnal fatigue and memory impairment were more observed in elderly patients. Asthma, hypothyroidism, diabetes, dyslipidemia, hypertension and atrial fibrillation were most commonly observed in elderly patients. Pauses in airflow and tonsillary hypertrophy were less observed in this group. There was no significant difference in OSAHS severity between the 2 groups. Logistic regression analysis showed that elderly apneic patients were more likely to be female, to have more memory impairment and to have more comorbidities with HTA, atrial fibrillation, diabetes and hypothyroidism. the frequency of cardiovascular, metabolic and cognitive comorbidities requires sleep investigation in apneic elderly subject, whether the clinical presentation is typical or not.


Routine Laboratory Blood Tests Predict SARS-CoV-2 Infection Using Machine Learning.
Accurate diagnostic strategies to identify SARS-CoV-2 positive individuals rapidly for management of patient care and protection of health care personnel are urgently needed. The predominant diagnostic test is viral RNA detection by RT-PCR from nasopharyngeal swabs specimens, however the results are not promptly obtainable in all patient care locations. Routine laboratory testing, in contrast, is readily available with a turn-around time (TAT) usually within 1-2 hours. We developed a machine learning model incorporating patient demographic features (age, sex, race) with 27 routine laboratory tests to predict an individual's SARS-CoV-2 infection status. Laboratory testing results obtained within 2 days before the release of SARS-CoV-2 RT-PCR result were used to train a gradient boosting decision tree (GBDT) model from 3,356 SARS-CoV-2 RT-PCR tested patients (1,402 positive and 1,954 negative) evaluated at a metropolitan hospital. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.854 (95% CI: 0.829-0.878). Application of this model to an independent patient dataset from a separate hospital resulted in a comparable AUC (0.838), validating the generalization of its use. Moreover, our model predicted initial SARS-CoV-2 RT-PCR positivity in 66% individuals whose RT-PCR result changed from negative to positive within 2 days. This model employing routine laboratory test results offers opportunities for early and rapid identification of high-risk SARS-CoV-2 infected patients before their RT-PCR results are available. It may play an important role in assisting the identification of SARS-CoV-2 infected patients in areas where RT-PCR testing is not accessible due to financial or supply constraints.


[Typing of methicillin-resistant Staphylococcus aureus strains for epidemiological studies using the polymerase chain reaction].
To determine whether polymerase chain reaction (PCR) fingerprinting can be used to gain insight into the epidemiology of methicillin resistant Staphylococcus aureus (MRSA). Retrospective DNA analysis of MRSA strains. BACTERIAL STRAINS: MRSA strains were collected in two Dutch and one Belgian hospital (Reinier de Graaf Gasthuis, Delft; St. Antonius Ziekenhuis, Nieuwegein; St. Jan Ziekenhuis, Brugge). MRSA DNA was isolated by standard procedures. Differences in genomic organisation were detected with the aid of exponential enzymatic synthesis of intrinsically variable DNA domains. This so-called PCR fingerprinting, a relatively new technique, was performed in direct comparison with phage typing. The latter is the current golden standard for S. aureus typing. The results of both PCR fingerprinting and phage typing appeared to be useful for strain identification. All results were consistent with other epidemiological data. Genotyping MRSA with PCR fingerprinting is complementary to phage typing. In some instances PCR fingerprinting is even to be preferred to the other technique. PCR fingerprinting is well suited for the analysis of MRSA spreading.


Land use regression for spatial distribution of urban particulate matter (PM10) and sulfur dioxide (SO2) in a heavily polluted city in Northeast China.
Particulate material 10 μm (PM10) and sulfur dioxide (SO2) are representative air pollutants in Northeast China and may contribute more to the morbidity of respiratory and cardiovascular disease than may other pollutants. Up to now, there have been few studies on the relation between health effect and air pollution by PM10 and SO2 in Northeast China, which may be due to the lack of a model for determination of air pollution exposure. For the first time, we used daily concentration data and influencing factors (different type of land use, road length and population density, and weather conditions as well) to develop land use regression models for spatial distribution of PM10 and SO2 in a central city in Northeast China in both heating and non-heating months. The final models of SO2 and PM10 estimation showed good performance (heating months: R2 = 0.88 for SO2, R2 = 0.88 for PM10; non-heating months: R2 = 0.79 for SO2; R2 = 0.87 for PM10). Estimated concentrations of air pollutants were more affected by population density in heating seasons and land use area in non-heating seasons. We used the land use regression (LUR) models developed to predict pollutant levels in nine districts in Shenyang and conducted a correlation analysis between air pollutant levels and hospital admission rates for childhood asthma. There were high associations between asthma hospital admission rates and air pollution levels of SO2 and PM10, which indicated the usability of the LUR models and the need for more concern about the health effects of SO2 and PM10 in Northeast China. This study may contribute to epidemiological research on the relation between air pollutant exposure and typical chronic disease in Northeast China as well as providing the government with more scientific recommendations for air pollution prevention.


Conditioned changes of synaptic transmission in the motor cortex of the cat.
Intracellular recordings were made from 117 neurons in the motor cortex of anesthetized cats. The pyramidal tract (PT) and VL nucleus of thalamus were stimulated in order to activate the neurons from two directions. 1. PT cells were conditioned by antidromic trains (10--50 cps for 4--15 s) and by paired PT and VL stimuli with different intervals and sequences. The VL-EPSPs were examined before and after conditioning, to find differences in efficacy in giving rise to spikes. The conditioning procedures resulted in a remarkable facilitation of VL-EPSPs, manifesting itself as a significant rise of efficacy in generating spikes, a shortening of peak latency and in some cases, an enhancement of background firing. 2. In non-PT neurons the same conditioning procedures elicited heterosynaptic facilitation and a rise in firing activity. 3. Intracellularly injected square wave pulses also resulted in facilitation of VL-EPSPs. 4. Pairings of PT and VL stimuli were more effective than trains in evoking conditioned changes. 5. Plastic modifications were observed in the 13.7% of the neurons subjected to conditioning procedures. 6. The authors assume that synchronous activity of the pre- and postsynaptic neurons is a highly important condition for plastic changes in the efficacy of synaptic transmission.


Quantitative evaluation of ankle cartilage in asymptomatic adolescent football players after season by T2-mapping magnetic resonance imaging.
Ankle sprain affects the structure and function of ankle cartilage. However, it is not clear whether the daily training and competition affect the ankle cartilage without acute injury. Changes in ankle cartilage without injury may influence future strategies to protect ankle function in athletes. This study aimed to evaluate whether the composition of ankle cartilage significantly altered in asymptomatic adolescent football players after a whole season of training and competition using T2-mapping magnetic resonance imaging (MRI). 12 local club's U17 asymptomatic adolescent football players without abnormalities in routine MRI were included. Routine and T2-mapping MRI were performed to measure the cartilage thickness of tibiotalar joint (TT) and posterior subtalar joint (pST) and T2 values in pre- and post-seasons. All of them took the right side as dominant foot. In the pre- and post-seasons, cartilage T2 values in TT (talus side) and pST (calcaneus side) were higher than that of TT (tibial side) and pST (talus side) (all p < 0.05), which was caused by magic angle effect and gravity load. No statistically significant differences in thickness after season in the other cartilages of ankle were found compared with that before the season (all p > 0.05). However, T2 values of TT (tibial side and talus side) cartilage in the dominant foot were significantly reduced after season (p = 0.008; p = 0.034). These results indicate that the microstructure of articular cartilage changes in the joints with greater mobility, although no trauma occurred and the gross morphology of cartilage did not change. Changes in the T2 values of tibiotalar joint cartilage in the dominant foot of healthy young athletes before and after the season suggest that the microstructure of cartilage had changed during sports even without injury. This finding suggests that the dominant ankle joint should be protected during football to delay degeneration of the articular cartilage.


Automatic cardiac ventricle segmentation in MR images: a validation study.
Segmenting the cardiac ventricles in magnetic resonance (MR) images is required for cardiac function assessment. Numerous segmentation methods have been developed and applied to MR ventriculography. Quantitative validation of these segmentation methods with ground truth is needed prior to clinical use, but requires manual delineation of hundreds of images. We applied a well-established method to this problem and rigorously validated the results. An automatic method based on active contours without edges was used for left and the right ventricle cavity segmentation. A large database of 1,920 MR images obtained from 59 patients who gave informed consent was evaluated. Two standard metrics were used for quantitative error measurement. Segmentation results are comparable to previously reported values in the literature. Since different points in the cardiac cycle and different slice levels were used in this study, a detailed error analysis is possible. Better performance was obtained at end diastole than at end systole, and on mid-ventricular slices than apical slices. Localization of segmentation errors were highlighted through a study of their spatial distribution. Ventricular segmentation based on region-driven active contours provided satisfactory results in MRI, without the use of a priori knowledge. The study of error distribution allows identification of potential improvements in algorithm performance.


[Color Doppler imaging of the retrobulbar circulation in non-exudative and exudative age-related macular degeneration].
To study ocular perfusion in the ophthalmic artery, central retinal artery, nasal and temporal posterior ciliary : arteries in non-exudative and exudative age-related macular degeneration. Twenty five subjects with non-exudative age-related macular degeneration were compared to twenty five subjects with exudative age-related macular degeneration and to twenty five age-matched control subjects. Color Doppler imaging measured peak systolic velocity (PSV) and end diastolic velocity (EDV) in the ophthalmic artery, central retinal artery, nasal and temporal posterior ciliary arteries of one eye. The resistivity index (RI) and the pulsatility index (PI) were calculated. There were statistically significant differences between: subjects with non-exudative age-related macular degeneration and subjects with exudative age-related macular degeneration in EDV, RI and PI in the ophthalmic artery and PSV in the temporal posterior ciliary artery, subjects with non-exudative age-related macular degeneration and control subjects in RI in central retinal artery, subjects with non-exudative age-related macular degeneration and control subjects in RI and PI in nasal posterior ciliary artery, subjects with exudative age-related macular degeneration and control subjects in PI in nasal posterior ciliary artery. The study results showed reduced ocular blood flow in patients with non-exudative age-related macular degeneration compared to patients with exudative age-related macular degeneration and to control subjects. The higher RI in central retinal artery in non-exudative age-related macular degeneration compared to control subjects, suggest there may be a more generalized perfusion abnormality beyond the choroid.


Smoking-adjusted lung cancer incidence among Asian-Americans (United States).
Chinese women residing in Asia and Hawaii have low consumption of tobacco but a high incidence of lung cancer. To explore this question further, we conducted a study of lung cancer among Chinese women residing in mainland US. Using data from NCI's SEER program, we identified residents of Los Angeles County, the San Francisco Metropolitan Area, and the Seattle-Puget Sound Area who were 50 years or older, diagnosed with cancer of the lung or bronchus in 1999-2001, with race specified as non-Hispanic white (n = 18,493), Chinese (n = 853), Filipino (n = 615), or Japanese (n = 282). The sex-specific observed number of lung cancer cases among each Asian sub-group was compared to the expected number of lung cancer cases for each Asian sub-group. The expected number was determined by multiplying the age-, sex-, and geographic area-adjusted incidence rates for non-Hispanic whites by the age- and sex-specific ratio of percentage of current smokers in each Asian sub-group to whites in 1990, and then by the size of the respective Asian populations. Chinese women had a four-fold increased risk of lung cancer, and Filipino women a two-fold increased risk, compared to that expected based on rates in US non-Hispanic whites with a similar proportion of cigarette smokers. Lung cancer among Chinese, Filipino, and Japanese males, as well as Japanese females, did not deviate from expected risk. Among Chinese women, the increased risk was largely restricted to adenocarcinoma and large cell undifferentiated carcinoma. Chinese female residents of the western US mainland have a much higher risk of lung cancer than would be predicted from their tobacco use patterns, just as they do in Asia.


Recovery from alexia without agraphia: report of an autopsy.
The patient is a 58-year-old Japanese teacher of German literature who suffered twice from cerebrovascular accidents, showing alexia without agraphia. Pathological examination showed an old infarct in the posterior two-thirds of the fusiform and almost the whole lingual gyrus, involving the posterior border of the parahippocampal gyrus in the left hemisphere. The left cuneus and the calcarine cortex were preserved. There was degeneration of the lower third of the splenium of the corpus callosum, extending to its occipital radiation and tapetum on both sides. Comparing clinico-pathological findings of the 31 known autopsy cases, it was proposed that the lesion of the left spleno-lingual system produces alexia without agraphia but it may ameliorate. In addition, when spleno-cuneate system is also involved alexia becomes persistent and it may accompany object agnosia or optic aphasia.


The "little five": exploring the nomological network of the five-factor model of personality in adolescent boys.
The California Child Q-set (CCQ) was used to explore the structure of personality in early adolescence and to develop scales to measure the "Big Five" dimensions: Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness to Experience. Mothers provided Q-sorts of 350 ethnically diverse boys between 12 and 13 years old. Analyses of the construct validity of the scales provided a nomological network relating the Big Five to theoretically and socially important criterion variables, such as juvenile delinquency, Externalizing and Internalizing disorders of childhood psychopathology, school performance, IQ, SES, and race. These effects were obtained using diverse methods, including self-reports from the boys, ratings by their mothers and their teachers, and objective-test data. In addition to the Big Five, analyses also suggested 2 possibly age-specific dimensions of personality in early adolescence. Discussion is focused on the changing manifestations of personality traits throughout development.


A new HLA-B*08 allele, HLA-B*0828, found in two voluntary stem cell donors.
The novel allele HLA-B*0828 differs from HLA-B*080101 by three nucleotide exchanges at codon 113, 114, and 116 in exon 3.


IL-27 amplifies cytokine responses to Gram-negative bacterial products and Salmonella typhimurium infection.
Cytokine responses from monocytes and macrophages exposed to bacteria are of particular importance in innate immunity. Focusing on the impact of the immunoregulatory cytokine interleukin (IL)-27 on control of innate immune system responses, we examined human immune responses to bacterial products and bacterial infection by E. coli and S. typhimurium. Since the effect of IL-27 treatment in human myeloid cells infected with bacteria is understudied, we treated human monocytes and macrophages with IL-27 and either LPS, flagellin, or bacteria, to investigate the effect on inflammatory signaling and cytokine responses. We determined that simultaneous stimulation with IL-27 and LPS derived from E. coli or S. typhimurium resulted in enhanced IL-12p40, TNF-α, and IL-6 expression compared to that by LPS alone. To elucidate if IL-27 manipulated the cellular response to infection with bacteria, we infected IL-27 treated human macrophages with S. typhimurium. While IL-27 did not affect susceptibility to S. typhimurium infection or S. typhimurium-induced cell death, IL-27 significantly enhanced proinflammatory cytokine production in infected cells. Taken together, we highlight a role for IL-27 in modulating innate immune responses to bacterial infection.


Hepatocellular carcinoma (HCC) tumor microenvironment is more suppressive than colorectal cancer liver metastasis (CRLM) tumor microenvironment.
While HCC is an inflammation-associated cancer, CRLM develops on permissive healthy liver microenvironment. To evaluate the immune aspects of these two different environments, peripheral blood-(PB), peritumoral-(PT) and tumoral tissues-(TT) from HCC and CRLM patients were evaluated. 40 HCC and 34 CRLM were enrolled and freshly TT, PT and PB were collected at the surgery. PB-, PT- and TT-derived CD4+CD25+ Tregs, M/PMN-MDSC and PB-derived CD4+CD25- T-effector cells (Teffs) were isolated and characterized. Tregs' function was also evaluated in the presence of the CXCR4 inhibitor, peptide-R29, AMD3100 or anti-PD1. RNA was extracted from PB/PT/TT tissues and tested for FOXP3, CXCL12, CXCR4, CCL5, IL-15, CXCL5, Arg-1, N-cad, Vim, CXCL8, TGFβ and VEGF-A expression. In HCC/CRLM-PB, higher number of functional Tregs, CD4+CD25hiFOXP3+ was detected, although PB-HCC Tregs exert a more suppressive function as compared to CRLM Tregs. In HCC/CRLM-TT, Tregs were highly represented with activated/ENTPD-1+Tregs prevalent in HCC. As compared to CRLM, HCC overexpressed CXCR4 and N-cadherin/vimentin in a contest rich in arginase and CCL5. Monocytic MDSCs were highly represented in HCC/CRLM, while high polymorphonuclear MDSCs were detected only in HCC. Interestingly, the function of CXCR4-PB-Tregs was impaired in HCC/CRLM by the CXCR4 inhibitor R29. In HCC and CRLM, peripheral blood, peritumoral and tumoral tissues Tregs are highly represented and functional. Nevertheless, HCC displays a more immunosuppressive TME due to Tregs, MDSCs, intrinsic tumor features (CXCR4, CCL5, arginase) and the contest in which it develops. As CXCR4 is overexpressed in HCC/CRLM tumor/TME cells, CXCR4 inhibitors may be considered for double hit therapy in liver cancer patients.


The first crystal structure of a Mimosoideae lectin reveals a novel quaternary arrangement of a widespread domain.
The crystal structures of the apo and mannose-bound Parkia platycephala seed lectin represent the first structure of a Mimosoideae lectin and a novel circular arrangement of beta-prism domains, and highlight the adaptability of the beta-prism fold as a building block in the evolution of plant lectins. The P.platycephala lectin is a dimer both in solution and in the crystals. Mannose binding to each of the three homologous carbohydrate-recognition domains of the lectin occurs through different modes, and restrains the flexibility of surface-exposed loops and residues involved in carbohydrate recognition. The planar array of carbohydrate-binding sites on the rim of the toroid-shaped structure of the P.platycephala lectin dimer immediately suggests a mechanism to promote multivalent interactions leading to cross-linking of carbohydrate ligands as part of the host strategy against phytopredators and pathogens. The cyclic structure of the P.platycephala lectin points to the convergent evolution of a structural principle for the construction of lectins involved in host defense or in attacking other organisms.


Mutations in the Na(+)/citrate cotransporter NaCT (SLC13A5) in pediatric patients with epilepsy and developmental delay.
Mutations in the SLC13A5 gene that codes for the Na(+)/citrate cotransporter, NaCT, are associated with early onset epilepsy, developmental delay and tooth dysplasia in children. In the present study we identify additional SLC13A5 mutations in nine epilepsy patients from six families. To better characterize the syndrome, families with affected children answered questions about the scope of illness and treatment strategies. There are currently no effective treatments, but some anti-epileptic drugs targeting the GABA system reduce seizure frequency. Acetazolamide, a carbonic anhydrase inhibitor and atypical anti-seizure medication decreases seizures in 4 patients. In contrast to previous reports, the ketogenic diet and fasting produce worsening of symptoms. The effects of the mutations on NaCT transport function and protein expression were examined by transient transfections of COS-7 cells. There was no transport activity from any of the mutant transporters, although some of the mutant transporter proteins were present on the plasma membrane. The structural model of NaCT suggests that these mutations can affect helix packing or substrate binding. We tested various treatments, including chemical chaperones and low temperatures, but none improve transport function in the NaCT mutants. Interestingly, coexpression of NaCT and the mutants results in decreased protein expression and activity of the wild-type transporter, indicating functional interaction. In conclusion, our study has identified additional SLC13A5 mutations in patients with chronic epilepsy starting in the neonatal period, with the mutations producing inactive Na(+)/citrate transporters.


Mapping trait-like socio-affective phenotypes in rats through 50-kHz ultrasonic vocalizations.
Fifty-kilohertz ultrasonic vocalizations (USV) in rats are believed to express inter-individual differences in trait-like positive affective phenotypes. Emission of 50-kHz USV can be induced by amphetamine (AMPH) to model mania-like positive affect, raising the possibility that predispositions for high 50-kHz USV production confer susceptibility to mania-like states. Such 50-kHz USV presumably express the sender's motivation for social contact and elicit social approach behavior in receivers. We recently showed that AMPH-induced 50-kHz USV are paralleled by mania-like patterns of enhanced social approach behavior towards playback of 50-kHz USV. Here, we assessed whether these AMPH effects are dependent on trait-like inter-individual differences in 50-kHz USV production. To this aim, we subdivided juvenile rats into those emitting low (LC) and high (HC) rates of baseline 50-kHz USV and compared them across four AMPH dosage conditions: 0.0, 0.5, 1.0, and 2.5 mg/kg. HC rats were considerably more susceptible to AMPH in inducing 50-kHz USV than LC rats, consistently across all examined doses. They further appeared to attribute more incentive salience to signals of rewarding social contact, as evidenced by enhanced social approach behavior towards 50-kHz USV playback, a response pattern also seen in LC rats after receiving AMPH treatment. HC but not LC rats emitted aversive 22-kHz USV following 50-kHz USV playback, indicating increased proneness to experience negative affective states if no actual social consequence followed the incentive signal. Inter-individual differences in 50-kHz USV map onto a unique trait-like socio-affective phenotype associated with enhanced emotional reactivity towards social and non-social reward, possibly conferring risk to mania-like states.


Genetics of the human renin angiotensin system.
The genes coding for the renin angiotensin system have been extensively studied. During the last 15 years, informative markers and functional polymorphisms have been identified, and numerous linkage and association studies have been performed in cardiovascular diseases, especially human hypertension. This mini-review aims to summarize the main findings observed for each component of this enzymatic cascade taken alone or in combination, with an emphasis on the most recent or innovative studies.


Long term outcomes of lymphatic sparing laparoscopic varicocelectomy.
To assess the long-term occurrence of hydroceles and varicocele recurrence in patients receiving lymphatic sparing laparoscopic varicocelectomy (LSLV) compared to those receiving plain laparoscopic varicocelectomy (PLV), and also to assess the growth of testicular volume postoperatively. We employed a standard three-trocar configuration. The spermatic vessels were identified in the retroperitoneum above the internal inguinal ring. Lymphatics were dissected free from the spermatic artery and veins based on laparoscopic appearance. The spermatic artery and veins were divided between plastic locking clips. We performed a retrospective chart review of all pediatric patients who underwent laparoscopic varicocelectomy between June 2003 and January 2009. Of a total of 97 patients, 67 underwent LSLV with mean follow-up of 45.8 ± 20.7 months and 30 underwent PLV with mean follow-up of 40.8 ± 25.3 months (p = 15). There was a 4.5% hydrocele rate in the LSLV group compared to 43.3% in the PLV group. Of the patients who underwent a PLV and subsequently developed a hydrocele, 31% (n = 4) required a hydrocelectomy, vs none of those who developed a hydrocele after LSLV. Varicocele rate was 6% in the LSLV group vs 3.3% in the PLV group. However, when the artery was not preserved, the probability of recurrence in the LSLV group was 1.3%. Time to hydrocele formation was 16 months in the LSLV group vs 37 months in the PLV group. There was catch-up testicular growth in both groups. There appears to be increased risk of need for a hydrocelectomy after a PLV as compared to LSLV. Performing a lymphatic sparing, non-artery preserving, laparoscopic varicocelectomy has success and complication rates comparable with those of subinguinal microsurgical varicocelectomy. There appears to be excellent catch-up testicular growth with either laparoscopic varicocelectomy technique.


Ion Tunnel Matrix Initiated Oriented Attachment for Highly Utilized Zn Anodes.
Metallic zinc is an ideal anode for aqueous energy storage; however, Zn anodes suffer from nonhomogeneous deposition, low reversibility, and dendrite formation; these lead to an overprovision of zinc metal in full cells. Herein, oriented-attachment-regulated Zn stacking initiated through a trapping-then-planting process with a high zinc utilization rate (ZUR) is reported. Due to the isometric topology features of cubic-type Prussian blue analog (PBA), the initial Zn plating occurs at specific sites with equal spacing of ≈5 Å in the direction perpendicular to the substrate; the trace amount of zinc ions trapped in tunnel matrix provides nuclei for the oriented attachment of Zn (002) deposits. As a result, the PBA-decorated substrate delivers high reversibility of dendrite-free zinc plating/stripping for more than 6600 cycles (1320 h) and achieves an average Coulombic efficiency (CE) of 99.5% at 5 mA cm-2 with 100% ZUR. Moreover, the anode-limited full cell with a low negative-positive electrode ratio (N/P) of 1.2 can be operated stably for 360 cycles, displaying an energy density of 214 Wh kg-1 ; this greatly exceeds commercial aqueous batteries. This work provides a proof of concept design of metal anodes with a high utilization ratio and a practical method for developing high-energy-density batteries.


Deoxycholate bile acid directed synthesis of branched Au nanostructures for near infrared photothermal ablation.
We report an approach for simple, reproducible and high-yield synthesis of branched GNPs directed by deoxycholate bile acid supramolecular aggregates in Au solution. A growth process involving stepwise trapping of the GNP seeds and Au ions in the deoxycholate bile acid solution yields multiple-branched GNPs. Upon NIR laser irradiation strong NIR absorption for branched GNPs induced photothermal-heating to destroy tumor cells. Subsequently, these branched GNPs were biofunctionalized with cRGD cell penetrating-targeting peptides for photothermal cancer treatment applications. Branched GNPs conjugated with cRGD peptides enhanced internalization of the branched GNPs in BxPC3 human pancreatic adenocarcinoma cells and effectively ablated BxPC3 cells when irradiated with a NIR laser (808 nm). Their potential use as photothermal transducing agents was demonstrated in in vivo settings using a pancreatic cancer xenograft model. The tumors were effectively ablated with cRGD-branched GNPs injection and laser exposure without any observation of tumor recurrence. This firstly reported method for deoxycholate bile acid directed synthesis of branched GNPs opens new possibilities for the production of strong NIR absorbing nanostructures for selective nano-photothermolysis of cancer cells and the further design of novel materials with customized spectral and structural properties for broader applications.


Calcium-chlorotetracycline fluorescence and pancreatic exocrine secretion in the rat.
The fluorescence and secretory response of calcium-chlorotetracycline were simultaneously and continuously measured in isolated perfused rat pancreata. Continuous vascular perfusion with 10 microM chlorotetracycline increased the fluorescence intensity exponentially. Continuous stimulation with higher nonphysiological doses of CCK (20 mU/ml) or ACh (10(-6) M) induced a gradual decrease in the Ca-cholorotetracycline fluorescence which increased to control after cessation of the stimulation, and secretory response, consisting of an initial rapid ascent followed by a decline. On the other hand, continuous stimulation with a lower concentration of CCK (5 mU/ml) or ACh (5 X 10(-8) M), which seems to be rather physiological, did not change the time course of the Ca-chlorotetracycline fluorescence increase, but it evoked a definite secretory response, consisting of an initial rapid ascent to a maximum followed by a descent to a sustained plateau. In a Ca2+-deficient environment, stimulation with 5 mU CCK/ml evoked only a small secretory response and a gradual insignificant decrease in the Ca-chlorotetracycline fluorescence. The present results may support the view that continuous stimulation with secretagogues at physiological concentrations does not cause dissociation of stored Ca2+ from intracellular sites but does initiate secretion probably via the rise in [Ca2+]i induced by the influx of extracellular Ca2+.


Facilitating antidepressant-like actions of estrogens are mediated by 5-HT1A and estrogen receptors in the rat forced swimming test.
Previous studies have shown that 17beta-estradiol (E2) induces antidepressant-like actions per se and potentiates those produced by fluoxetine (FLX) in the forced swimming test (FST). The aim of the present work was to explore the participation of serotonin 1A receptors (5-HT1A) and estrogen receptors (ERs) in the antidepressant-like actions of E2, FLX or their combination in the FST. Although all antidepressants reduce behavioral immobility, antidepressants that modulate serotonergic neurotransmission increase swimming behavior whereas those that modulate the catecholaminergic neurotransmission increase climbing behavior. Thus, using this animal model, it is possible to infer which neurotransmitter system is modulating the action of an antidepressant compound. Ovariectomized female Wistar rats were used in all experiments. In the first experiment, an effective dose of E2 (10 microg/rat, -48 h) was combined with several doses (0.5, 1.0 and 2 mg/kg) of RU 58668 (a pure ER antagonist) 48 h previous to the FST. The second experiment evaluated the action of (1 mg/kg, -48 h or -23, -5 and -1 h) WAY 100635 (5-HT1A receptor antagonist) on the antidepressant-like action of FLX (10 mg/kg, -23, -5 and -1 h). In the third experiment, the effect of RU 58668 (2 mg/kg, -48) or WAY 100635 (1 mg/kg, -48 h) on the antidepressant-like action of the combination of a sub-optimal dose of E2 (2.5 microg/rat, -48 h) plus a non-effective dose of FLX (2.5 mg/kg, -23,-5 and -1 h) was evaluated. The results showed that RU 58668, the antagonist to the ER, canceled the antidepressant-like action of E2 in a dose-dependent manner. The antagonist to the 5-HT1A receptor blocked the antidepressant action of FLX only when administered simultaneously with FLX, i.e. -23, -5 and -1 h before the FST. Finally, the administration of both RU 58668, and WAY100635 canceled the antidepressant-like action of the combination of E2/FLX. These results imply that both 5-HT1A receptors and ERs participate in the facilitating actions of E2 on the antidepressant-like action of FLX in the FST.


Staff Training Interests, Barriers, and Preferences in Rural and Urban Child Care Programs in Minnesota.
To describe any rural-urban differences in child care providers' (1) past training on the facilitation of child healthy eating and physical activity and (2) views relevant to the design of trainings. Cross-sectional analysis of data from the 2016 Healthy Start, Healthy State survey of Minnesota child care providers (rural, n = 232; urban, n = 386). Licensed family home-based care providers and providers working at licensed centers responded online or by mail to measures of desired training content, barriers, and delivery mode preferences. Training barriers that were more often a concern for rural compared with urban providers included scheduling outside work hours, difficulties finding trainings, and travel (all P < .001). Rural and urban providers identified similar preferences with regard to training content and delivery. The findings suggest it would be worthwhile for future research to examine whether rural providers' training participation is affected by uniquely relevant participation barriers.


One-Step Method to Prepare PLLA Porous Microspheres in a High-Voltage Electrostatic Anti-Solvent Process.
A one-step method using a high-voltage electrostatic anti-solvent process was employed to fabricate poly-l-lactide (PLLA) porous microspheres (PMs). To address the simplification and control of the preparation process, a 2⁴ full factorial experiment was performed to optimize the operating process and analyze the effect of the factors on the morphology and aerodynamic properties of the PLLA PMs, and various characterization tests were also performed. The resulting PLLA PMs exhibited an even and porous morphology with a density less than 0.4 g/cm³, a geometric mean diameter (Dg) of 10-30 μm, an aerodynamic diameter (Da) of 1-5 μm, a fine particle fraction (FPF) of 56.3%, and a porosity of 76.2%, meeting the requirements for pulmonary drug delivery. The physicochemical characterizations reveal that no significant chemical change occurred in the PLLA during the process. An investigation of its in vitro cytotoxicity and pulmonary toxicity shows no obvious toxic response, indicating good biosafety. This study indicates that the one-step method using a high-voltage electrostatic anti-solvent process has great potential in developing an inhalable drug carrier for pulmonary drug delivery.


How to manage celiac disease and gluten-free diet during the COVID-19 era: proposals from a tertiary referral center in a high-incidence scenario.
The outbreak of COVID-19 and SARS-CoV-2 infection is spreading worldwide as the first coronavirus pandemic. The clinical picture is variable but flu-like symptoms are common with bilateral interstitial pneumonia being the most frightening presentation. No specific therapies nor vaccine have been developed to date and the only way to limit the virus diffusion is by modifying one's lifestyle limiting social life and following strict hygienic precautions. No data is available on the risk of COVID-19 and its outcomes in celiac disease (CeD). The restrictions applied to counter COVID-19 can impact on CeD treatment and gluten-free dieting, the only available therapy for CeD. With the present manuscript, we aim to support gastroenterologists and nutritionists in the management of CeD patients in the new pandemic scenario, being conscious that availability and local situations are extremely various.


LLDT-8 protects against cerebral ischemia/reperfusion injury by suppressing post-stroke inflammation.
(5R)-5-Hydroxytriptolide (LLDT-8), an analogue of triptolide, displays lower toxicity compared to triptolide and has comparable immunosuppressive effects. We investigated the anti-inflammatory and neuroprotective effects of LLDT-8 on cerebral ischemia/reperfusion injury. Nitric oxide production from microglia was assessed by measuring the nitrite concentration in the culture medium with Griess reagent. Microglial cells and ischemic brain tissues were examined for the expression of proinflammatory mediators by qPCR and western blot. Infarct volumes were assessed with TTC histology. The TLR4/NF-κB signaling pathway was analyzed with western blot and immunocytochemistry. LLDT-8 significantly reduced infarct sizes and expression of pro-inflammatory cytokines in the ischemic cortex. LLDT-8 inhibited NO release and expression of TNF-α, IL-1β and iNOS in BV-2 microglia and primary microglia treated with LPS. In addition, LLDT-8 suppressed expression of TLR4, degradation of IκBα and nuclear translocation of NF-κB. LLDT-8 exerted anti-inflammatory effects and protected against acute cerebral ischemia/reperfusion injury possibly by acting through the IκB/NF-κB cascade to suppress microglia-mediated neuroinflammation.


Geissoschizoline, a promising alkaloid for Alzheimer's disease: Inhibition of human cholinesterases, anti-inflammatory effects and molecular docking.
Due to the lack of effective pharmacotherapy options to treats Alzheimer's disease, new strategies have been approached in the search for multi-target molecules as therapeutic options. In this work, four indole alkaloids, geissoschizoline, geissoschizone, geissospermine, and 3',4',5',6'-tetradehydrogeissospermine were isolated from Geissospermum vellosii (Pao pereira) and evaluated for their anticholinesterase activities. While geissospermine inhibited only butyrylcholinesterase (BChE), the other alkaloids behaved as non-selective inhibitors of acetylcholinesterase (AChE) and BChE. In cell viability tests, only geissoschizoline was not cytotoxic. Therefore, geissoschizoline actions were also evaluated in human cholinesterases, where it was twice as potent inhibitor of hBChE (IC50 = 10.21 ± 0.01 µM) than hAChE (IC50 = 20.40 ± 0.93 µM). On enzyme kinetic studies, geissoschizoline presented a mixed-type inhibition mechanism for both enzymes. Molecular docking studies pointed interactions of geissoschizoline with active site and peripheral anionic site of hAChE and hBChE, indicating a dual site inhibitor profile. Moreover, geissoschizoline also played a promising anti-inflammatory role, reducing microglial release of NO and TNF-α at a concentration (1 μM) ten and twenty times lower than the IC50 values of hBChE and hAChE inhibition, respectively. These actions give geissoschizoline a strong neuroprotective character. In addition, the ability to inhibit hAChE and hBChE, with approximate inhibitory potencies, accredits this alkaloid for therapeutic use in the moderate to severe phase of AD. Thus, geissoschizoline emerges as a possible multi-target prototype that can be very useful in preventing neurodegeneration and restore neurotransmission.


Evidence-Based Leadership: A Study of Its Application to General Hospital of the Public Health System Through the Implementation Leadership Scale.
Evidence-based practice (EBP) is about integrating scientifically proven effective methods into clinical practice by healthcare professionals in the context of patient care. This approach is being studied extensively by the scientific community because of its positive effects on patients and on the health system. The aim of the study was to investigate the degree of implementation of evidence-based leadership in Greek public hospitals. This is a cross-sectional study. The sample of the study consisted of 213 nurses who worked to two large public hospitals of Athens, Greece. The Implementation Leadership Scale (ILS) used for data collection. The SPSS v. 24. was used to analyze the data. Most of participants were females (89.7%), aged 31-40 years (38.5%), married (74.8%), were RN (68.1%), and had more than 10 years of work experience (63.9%). About half of participants (40.4%) supported that the head nurse has taken in a great extent the necessary measures to facilitate evidence-based clinical care, thus positively affecting its implementation. About one third of participants (35.2%) considered that their head nurses are well informed. The more knowledge nurses have about evidence-based clinical care, the greater their prevention (r = 0.852, p < 0.05) and the more persistent they are in implementing it despite any difficulties (r = 0.796, p < 0.05). Knowledgeable, supportive, proactive, and persistent leadership positively influences the implementation of evidence-based practice. The hospital managers, and especially head nurses, are able to promote the implementation of evidence-based care.


A robust potency assay highlights significant donor variation of human mesenchymal stem/progenitor cell immune modulatory capacity and extended radio-resistance.
The inherent immunomodulatory capacity of mesenchymal stem/progenitor cells (MSPCs) encouraged initiation of multiple clinical trials. Release criteria for therapeutic MSPCs cover identity, purity and safety but appropriate potency assessment is often missing. Reports on functional heterogeneity of MSPCs created additional uncertainty regarding donor and organ/source selection. We established a robust immunomodulation potency assay based on pooling responder leukocytes to minimize individual immune response variability. Comparing various MSPCs revealed significant potency inconsistency and generally diminished allo-immunosuppression compared to dose-dependent inhibition of mitogenesis. Gamma-irradiation to block unintended MSPC proliferation did not prohibit chondrogenesis and osteogenesis in vivo, indicating the need for alternative safety strategies.


Quality care close to home: Objectives and early outcomes of a second paediatric heart transplant service in Australia.
We describe the experience of a new paediatric heart transplant (HT) centre in Australia. New South Wales offers quaternary paediatric cardiac services including comprehensive care pre- and post-HT; however, perioperative HT care has previously occurred at the national paediatric centre or in adult centres. Internationally, perioperative HT care is highly protocol-driven and a majority of HT occurs in low volume centres. Establishing a low volume paediatric HT centre in New South Wales offers potential for quality HT care close to home. Retrospective review of programme data for the first 12 months was undertaken. Patient selection was audited against the programme's intended initiation criteria. Longitudinal patient data on outcomes and complications were obtained from patient medical records. The programme's initial phase offered HT to children with non-congenital heart disease and no requirement for durable mechanical circulatory support. Eight patients met criteria for HT referral. Three underwent interstate transfer to the national paediatric centre. Five children (13-15 years, weight 36-85 kg) underwent HT in the new programme. Individual predicted 90-day mortality was 1.3-11.6%, with increased risk for recipients transplanted from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and with restrictive/hypertrophic cardiomyopathies. Survival at 90 days and for duration of follow-up is 100%. Observed programme benefits include mitigation of family dislocation and improved continuity of care within a family-centred programme. Audit of the first 12 months' activity of a second paediatric HT centre in Australia demonstrates adherence to proposed patient selection criteria and excellent 90-day patient outcomes. The programme demonstrates feasibility of care close to home, providing continuity for all patients including those requiring increased rehabilitation and psychosocial support post-transplantation.


Phenotypic Spectrum in a Family Sharing a Heterozygous KCNQ3 Variant.
Mutations in KCNQ3 have classically been associated with benign familial neonatal and infantile seizures and more recently identified in patients with neurodevelopmental disorders and abnormal electroencephalogram (EEG) findings. We present 4 affected patients from a family with a pathogenic mutation in KCNQ3 with a unique constellation of clinical findings. A family of 3 affected siblings and mother sharing a KCNQ3 pathogenic variant are described, including clinical history, genetic results, and EEG and magnetic resonance imaging (MRI) findings. This family shows a variety of clinical manifestations, including neonatal seizures, developmental delays, autism spectrum disorder, and anxiety. One child developed absence epilepsy, 2 children have infrequent convulsive seizures that have persisted into childhood, and their parent developed adult-onset epilepsy. An underlying c.1091G>A (R364H) variant in KCNQ3 was found in all affected individuals. The phenotypic variability of KCNQ3 channelopathies continues to expand as more individuals and families are described, and the variant identified in this family adds to the understanding of the manifestations of KCNQ3-related disorders.


The murine T-lymphocyte response to tyrosine-azobenzenearsonate. Characteristics of a low responder haplotype T-cell clone.
An I-Ab-restricted, L3T4+ Ly2- T-cell clone, 5R-4F3, specific for ABAtyr was established in culture from a B10.A(5R) mouse. Since b haplotype mice respond weakly to ABAtyr compared to other haplotypes, this is a candidate clone of low responder phenotype. In support of this contention, 5R-4F3 grew very poorly under conditions that supported the vigorous growth of E beta bE alpha k-restricted T-cell clones from the same mouse. The I-A (low responder) and I-E (high responder) restricted T-cell clones also differed in their responses to apc pre-pulsed with antigen, compared to apc with antigen present continuously during culture. The low and high responder clones responded comparably to IL-2. Attempts to elevate the response of C57BL/6 mice to ABAtyr in vivo by injecting them with human recombinant IL-2 and antigen together were only partially successful: C57BL/6 mice treated in this way showed a 3-5-fold increase in their proliferative responses to ABAtyr, which was at best only one quarter of the level of response shown by high responder A/J mice to the same antigen dose.


Characterization of maternal motivation in the lactating rat: Contrasts between early and late postpartum responses.
We previously assessed the motivational properties of pups relative to those of cocaine in parturient female rats (dams) across the postpartum period and demonstrated that the larger subset of dams in early postpartum (PPD8) preferred the pup-associated chamber, whereas the majority of dams tested in late postpartum (PPD16) preferred the cocaine-associated chamber [Mattson, B.J., Williams, S., Rosenblatt, J.S., Morrell, J.I. 2001. Comparison of two positive reinforcing stimuli: pups and cocaine throughout the postpartum period. Behav. Neurosci., 115, 683-694; Seip, K.M., Morrell, J.I. 2007. Increasing the incentive salience of cocaine challenges preference for pup- over cocaine-associated stimuli during early postpartum: place preference and locomotor analyses in the lactating female rat. Psychopharmacology 194, 309-319]. The present study uses a dual-choice conditioned place preference to ask how the progression of the postpartum period, including natural pup development, influences maternal motivation for pups. Preferences for cued chambers associated with pups that were age-matched to the postpartum stage of the dam in contrast to a stimulus with little incentive salience were higher during the early than the late postpartum, suggesting that the incentive salience of pups diminishes as the postpartum period progresses. Preferences of the early postpartum dams deprived of pups for 15 min, 2, 6, 12 or 22 hrs prior to conditioning and testing did not differ statistically but there was a trend of more pup preference after 22 hr deprivation; pup age was not an important factor in early postpartum. In marked contrast, late postpartum dams only exhibited robust pup-associated place preference when they were conditioned with young (4-7 day-old) pups or after a 22 hr period of deprivation from contemporaneous pups. Together these results suggest that both forces are at work in the mother-pup dyad, changes in the pups as they develop and changes in the physiological and endocrine state of the female as she progresses through the postpartum period.


The phenotypic suppression of a mutation in the gene rplX for ribosomal protein L24 by mutations affecting the lon gene product for protease LA in Escherichia coli K12.
A suppressor mutation of a temperature-sensitive mutant of ribosomal protein L24 (rplX19) was mapped close to the lon gene by genetic analysis and was shown to affect protease LA. The degradation and the synthesis rates of individual ribosomal proteins were determined. Proteins L24, L14, L15 and L27 were found to be degraded faster in the original rplX19 mutant than in the rplX19 mutant containing the suppressor mutation. Other ribosomal proteins were either weakly or not at all degraded in both mutants. Temperature-sensitive growth was also suppressed by the overproduction of mutant protein L24 from a plasmid. Our results suggest that (1) either free ribosomal proteins or proteins bound to abortive assembly precursors are highly susceptible to the lon gene product and (2) the mutationally altered protein L24 can still function at the nonpermissive growth temperature of the mutant, if it is present in sufficient amounts.


The Association of Untreated Mental Health Problems with Alcohol and Tobacco use Among New York City Taxi Drivers.
Mental disorders and substance use disorders are highly comorbid. The "self-medication hypothesis" posits that individuals may use substances such as tobacco and alcohol to cope with symptoms associated with untreated mental health problems. The present study examined the association between having a currently untreated mental health condition and tobacco and alcohol use among male taxi drivers in NYC, a population at risk for poor mental and physical health outcomes. The sample included 1105 male, ethnoracially diverse, primarily foreign-born NYC taxi drivers participating in a health fair program. This secondary cross-sectional analysis utilized logistic regression modeling to examine whether endorsement of a currently untreated mental health problem (i.e., depression, anxiety, or posttraumatic stress disorder) was associated with alcohol and/or tobacco use, controlling for potential confounders. 8.5% of drivers reported having mental health problems; among these, only 0.5% reported receiving treatment. Untreated mental health problems were associated with an increased risk of current tobacco/alcohol use after controlling for age, educational attainment, nativity, and pain history: drivers with untreated mental health problems had 1.9x the odds of reporting current tobacco use [95% CI: 1.10-3.19] and 1.6x the odds of reporting current alcohol use [95% CI: 1.01-2.46] than those without untreated mental health problems. Few drivers with mental health problems receive treatment. In line with the self-medication hypothesis, drivers with untreated mental health problems demonstrated significantly increased risk of tobacco and alcohol use. Efforts to encourage timely screening and treatment of mental health problems among taxi drivers are warranted.


Localization of rat striatal monoamine oxidase activities towards dopamine, serotonin and kynuramine by gradient centrifugation and nigro-striatal lesions.
Subfractionation of the crude synaptosomal-mitochondrial fraction of rat striatum in a continuous sucrose gradient in a zonal rotor led to the following results. The distribution pattern of monoamine oxidase (MAO) activity towards dopamine (DA) was very similar to the pattern of MAO activity towards serotonin (5HT), but differed from the pattern of MAO activity towards kynuramine (KYN). As 5HT is specifically deaminated by MAO-A while KYN is a common MAO substrate, this supports earlier suggestions that in rat striatal preparations DA is deaminated preferentially by MAO-A. The patterns of the MAO activities towards DA and 5HT were clearly dissimilar, despite considerable overlap, to the patterns of tyrosine hydroxylase (TH) and DOPA decarboxylase (DD) activity, both marking the presence of striatal dopaminergic synaptosomes. The peak activities were separated and all patterns were symmetrical without showing a shoulder. This indicates that rat striatal MAO activity towards DA and 5HT is not specifically or for the greater part localized in dopaminergic terminals. We also investigated the effects of electrolytic and 6-hydroxydopamine lesions of the substantia nigra, both causing extensive degeneration of striatal dopaminergic terminals as appeared from the large decrease of striatal TH and DD activity. However, neither type of lesion induced a reduction of the MAO activity towards any of the substrates used. It is concluded that the amount of MAO activity towards DA and 5HT (probably MAO-A activity) present in dopaminergic terminals is very low compared with the total activity of this enzyme in rat striatal tissue.


MicroRNAs signatures, bioinformatics analysis of miRNAs, miRNA mimics and antagonists, and miRNA therapeutics in osteosarcoma.
MicroRNAs (miRNAs) involved in key signaling pathways and aggressive phenotypes of osteosarcoma (OS) was discussed, including PI3K/AKT/MTOR, MTOR AND RAF-1 signaling, tumor suppressor P53- linked miRNAs, NOTCH- related miRNAs, miRNA -15/16 cluster, apoptosis related miRNAs, invasion-metastasis-related miRNAs, and 14Q32-associated miRNAs cluster. Herrin, we discussed insights into the targeted therapies including miRNAs (i.e., tumor-suppressive miRNAs and oncomiRNAs). Using bioinformatics tools, the interaction network of all OS-associated miRNAs and their targets was also depicted.


Sarcolemmal carbonic anhydrase in red and white rabbit skeletal muscle.
Sarcolemmal vesicles of white and red skeletal muscles of the rabbit were prepared by consecutive density gradient centrifugations in sucrose and dextran according to Seiler and Fleischer (1982, J. Biol. Chem. 257, 13,862-13,871). White and red muscle membrane fractions enriched in sarcolemma were characterized by high ouabain-sensitive Na+, K(+)-ATPase, by high Mg2(+)-ATPase activity, and by a high cholesterol content. Ca2(+)-ATPase activity, a marker enzyme for sarcoplasmic reticulum, was not detectable in the highly purified white and red muscle sarcolemmal fractions. White and red muscle sarcolemmal fractions exhibited no significant differences with regard to Na+, K(+)-ATPase, Mg2(+)-ATPase, and cholesterol. Specific activity of carbonic anhydrase in white muscle sarcolemmal fractions was 38 U.ml/mg and was 17.6 U.ml/mg in red muscle sarcolemma. Inhibition properties of sarcolemmal carbonic anhydrase were analyzed for acetazolamide, chlorzolamide, and cyanate. White muscle sarcolemmal carbonic anhydrase is characterized by inhibition constants, KI, toward acetazolamide of 4.6 X 10(-8) M, toward chlorzolamide of 0.75 X 10(-8) M, and toward cyanate of 1.3 X 10(-4) M. Red muscle sarcolemmal carbonic anhydrase is characterized by KI values toward acetazolamide of 8.1 X 10(-8) M, toward chlorzolamide of 6.3 X 10(-8) M, and toward cyanate of 0.81 X 10(-4) M. In contrast to the high specific carbonic anhydrase activities in sarcolemma, carbonic anhydrase activity in sarcoplasmic reticulum from white muscle varied between values of only 0.7 and 3.3 U.ml/mg. Carbonic anhydrase of red muscle sarcoplasmic reticulum ranged from 2.4 to 3.7 U.ml/mg.


Evaluation of preoperative testicular volume in Japanese children with unilateral cryptorchidism.
We measured the testis volume of patients with unilateral cryptorchidism preoperatively and compared with a unilateral hydrocele testis to assess testicular development in these patients. The present study included 129 children (ranging in age from 10 months to 5 years) with unilateral cryptorchidism who were treated from 2000 to 2006 at our institution. We evaluated the correlation between testicular volume and the location of testes or the age of these children. We also examined the testicular volume of 50 children with unilateral hydrocele testis (range, 8 months to 5 years). There was no difference in testicular volume among each position of the undescended testis. The volumes of both undescended testes and hydrocele testes did not change until 5 years of age. There was a significant difference in testicular volume between undescended and hydrocele testes. The average testicular volume of cryptorchidism is significantly smaller than that of hydrocele testes both under and over 2 years old. From the viewpoint of undescended testicular volume, cryptorchid children should be operated on as early as possible.


Incisional paresthesia following clavicle plate fixation: does it matter to patients?
Operative management of clavicle fractures is increasingly common. In the context of explaining the risks and benefits of surgery, understanding the impact of incisional numbness as it relates to the patient experience is key to shared decision making. This study aims to determine the prevalence, extent, and recovery of sensory changes associated with supraclavicular nerve injury after open reduction and plate internal fixation of middle or lateral clavicle shaft fractures. Eighty-six patients were identified retrospectively and completed a patient experience survey assessing sensory symptoms, perceived post-operative function, and satisfaction. Correlations between demographic factors and outcomes, as well as subgroup analyses were completed to identify factors impacting patient satisfaction. Ninety percent of patients experienced sensory changes post-operatively. Numbness was the most common symptom (64%) and complete resolution occurred in 32% of patients over an average of 19 months. Patients who experienced burning were less satisfied overall with the outcome of their surgery whereas those who were informed of the risk of sensory changes pre-operatively were more satisfied overall. Post-operative sensory disturbance is common. While most patients improve, some symptoms persist in the majority of patients without significant negative effects on satisfaction. Patients should always be advised of the risk of persistent sensory alterations around the surgical site to increase the likelihood of their satisfaction post-operatively.


Preserving the pterygoid plates in posterior repositioning of the LeFort I osteotomy.
The pterygoid plates have to be fractured and displaced to allow the maxilla to be repositioned posteriorly in the Le Fort I push-back osteotomy. A technique to reposition the maxilla posteriorly while preserving the pterygoid plates and the greater palatine neurovascular bundle is described. This technique reduces the risk of damaging the internal maxillary artery and the internal jugular vein which can lead to excessive haemorrhage. The disturbance to the Eustachian apparatus is also minimized.


SOS mutagenesis.
In Escherichia coli, UV and many chemicals appear to cause mutagenesis by a process of translesion synthesis that requires some form of DNA polymerase III and the SOS-regulated proteins UmuD, UmuC and RecA. An analysis of SOS mutagenesis offers insights into the molecular basis of induced mutagenesis and into mechanisms of DNA damage tolerance.


Robot-assisted laparoscopic abdominoperineal resection for anal canal cancer associated with Crohn's disease: A case report.
A 37-year-old man with Crohn's disease (CD) and a history of abdominal surgery was diagnosed with anal canal cancer. Robot-assisted laparoscopic abdominoperineal resection was performed and the patient was discharged without any postoperative complications. Recently, minimally invasive surgery for CD patients has grown in popularity. However, there have been few studies of robotic surgery for CD patients with anal canal cancer. To the best of our knowledge, we present the first report of a patient with CD-associated anal canal cancer who underwent robot-assisted laparoscopic abdominoperineal resection.


Quantitative assessment of DNA fragmentation and beta-amyloid deposition in insular cortex and midfrontal gyrus from patients with Alzheimer's disease.
It has been suggested that the neurodegeneration that occurs with Alzheimer's disease (AD) may result from apoptosis, a process of programmed cell death. Neuronal injury, induced by abnormal aggregates of beta-amyloid peptide, has been identified as an apoptotic trigger. In the present study, brain tissue samples were obtained from the insular cortex (INS) and midfrontal gyrus (MFG) of Alzheimer subjects and age-matched, nondemented controls. Tissue sections from all samples were alternately stained by an in situ TUNEL assay to identify 3' termini DNA strand breaks characteristic of apoptosis or immunohistochemically for beta-amyloid deposition in senile plaques. The incidence of DNA fragmentation detected in pyramidal neurons was relatively infrequent overall, but was significantly higher in AD compared to controls. AD subjects consistently exhibited a dense accumulation of plaques, with a twofold greater concentration in MFG as INS. There was no significant difference in pyramidal cell number regardless of subject or brain region. Taken together, our results indicate that the TUNEL assay may be revealing cell damage rather than cell loss. Our finding of a moderate correlation between the incidence of TUNEL-positive cells and plaque density implicates beta-amyloid as one of multiple factors provoking cell injury in AD. A notable contribution of this study is the identification of distinctive neuropathologies co-occurring in two brain regions interconnected with each other and with limbic and cortical areas typically damaged during AD.


In vivo determination of 31P spin relaxation times (T1, T2, T1 rho) in rat leg muscle. Use of an off-axis solenoid coil.
A probe using a solenoid coil tilted 45 degrees off-axis has been used to study the 31P NMR relaxation characteristics of the resonances arising from phosphorus metabolites in rats in vivo. T1, T1 rho and T2 values have been determined for phosphocreatine and ATP in leg muscle. The ratio of 31P T1(1700ms) to T2(12ms) for ATP was in excess of 200:1 compared with a ratio of 5:1 for 1H T1:T2. Of major significance was the observation that T2 values for phosphocreatine (230ms) were markedly longer than T2 values for ATP (12ms). Thus by use of appropriate delay times in spin echo sequences ATP signals can be nulled, and discrete 31P imaging of phosphocreatine in muscle may be possible provided the overall signal-to-noise is satisfactory.


Postoperative midline shift as secondary screening for the long-term outcomes of surgical decompression of malignant middle cerebral artery infarcts.
Decompressive hemicraniectomy (DC) can save the lives of patients with malignant middle cerebral artery (MCA) infarction. We proposed that postoperative midline shift is important for the long-term outcome of patients with MCA infarction. We conducted a retrospective study of DC in 38 patients with malignant MCA infarction. The long-term outcome was assessed one year after surgery using the modified Rankin Scale (mRS) score. Patients who had midline shift less than the optimal diagnostic cut-off point on the fourth postoperative day were classified as having a successful decompression and the remaining patients were classified in the failed decompression group. The successful decompression group mRS score was 4.20±0.89 one year after surgery and the failed decompression group mRS score was 5.11±0.76 (p<0.0001). Successful decompression, resulting in postoperative midline shift of less than 5mm, was a key factor for beneficial, long-term functional outcomes in patients with malignant MCA infarction.


A giant choledochal cyst in a 17 year old female managed in a resource limited setting: A case report.
Choledochal cysts are rare congenital bile duct anomalies that lead to cystic dilatations of the biliary tree. This condition is very rare in Africa. When these cysts exceed 10 cm in diameter, they are referred to as giant choledochal cysts, which are much rarer. Giant choledochal cysts present both a diagnostic and surgical challenge. We present a case of a giant Choledochal cyst surgically managed in a resource limited setting with excellent outcome. A 17-year-old female presented with 4 months history of progressive abdominal distension associated with abdominal pain, yellow discoloration of eyes, and occasional constipation. Abdominal CT-scan revealed a huge cystic mass in the right upper quadrant extending inferiorly to the right lumbar region. Complete excision of a type IA choledochal cyst was done plus cholecystectomy in addition to bilioenteric reconstruction. The patient recovered uneventfully. To the best of our knowledge, this is the largest giant Choledochal cyst reported in literature. Even in a resource limited settings, sonography and a CT scan may be all that is required to make a diagnosis. During surgical excision, the surgeon should take extra caution to carefully dissect the adhesions off the giant cyst for a successful complete excision.


Non-invasive and non-destructive micro-XRF and micro-Raman analysis of a decorative wallpaper from the beginning of the 19th century.
Non-destructive and non-invasive micro-Raman fibre optic and micro-XRF analyses were performed to study a wallpaper from the beginning of the 19th century. The complementarity of these two non-destructive techniques is shown in this work. The analysed artwork is considered one of the most beautiful wallpapers ever manufactured according to the catalogues and books; it is known as Chasse de Compiègne, manufactured by Jacquemart, Paris, in 1812. During the analysis, an unexpected pigment was detected by both analytical techniques: lead-tin yellow type II. This pigment was used until ca. 1750, when other yellow pigments replaced it, thus it is very difficult to find it in paintings afterwards. Together with this pigment, red lead, Prussian blue, brochantite, yellow iron oxide, calcium carbonate, vermilion, carbon black of animal origin (bone black), lead white, and raw and burnt sienna were also determined by combining the analytical information provided by both techniques. A possible degradation of brochantite to antlerite is also discussed.


Genetic regulation of osteoclast development and function.
Osteoclasts are the principal, if not exclusive, bone-resorbing cells, and their activity has a profound impact on skeletal health. So, disorders of skeletal insufficiency, such as osteoporosis, typically represent enhanced osteoclastic bone resorption relative to bone formation. Prevention of pathological bone loss therefore depends on an appreciation of the mechanisms by which osteoclasts differentiate from their precursors and degrade the skeleton. The past five years have witnessed important insights into osteoclast formation and function. Many of these discoveries have been made through genetic experiments that involved the rare hereditary disorder osteopetrosis.


Hepatoprotective role and antioxidant capacity of selenium on arsenic-induced liver injury in rats.
The present study was undertaken to evaluate the protective effect of selenium against arsenic-induced oxidative damage in experimental rats. Males were randomly divided into four groups where the first was served as a control, whereas the remaining groups were respectively treated with sodium selenite (3 mg/kg b.w.), sodium arsenite (5.55 mg/kg b.w.) and a combination of sodium arsenite and sodium selenite. Changes in liver enzyme activities, thiobarbituric acid reactive substances (TBARS) level, antioxidants and reduced glutathione (GSH) contents were determined after 3 weeks experimental period. Exposure of rats to As caused a significant increase in liver TBARS compared to control, but the co-administration of Se was effective in reducing its level. The activities of glutathione peroxidase (GPx) and glutathione-S-transferase (GST) of As-treated group were found lower compared to the control and the Se-treated group. The co-administration of Se had an additive protective effect on liver enzyme activities compared to As-treated animals. On the other hand, a significant increase in plasmatic activities of AST, ALT and ALP was observed in As-treated group. The latter was also exhibited a decrease in body weight and an increase in liver weight compared to the control. The co-administration of Se has decreased the activities of AST, AST and ALP and improved the antioxidant status as well. Liver histological studies have confirmed the changes observed in biochemical parameters and proved the beneficial role of Se. To conclude, results suggest that As exposure enhanced an oxidative stress by disturbing the tissue antioxidant defense system, but the Se co-administration protected liver tissues against As intoxication probably owing to its antioxidant properties.


Pigment epithelium-derived factor plays an inhibitory role in proliferation and migration of HaCaT cells.
The normal vasculature is maintained by a balance between angiogenic factors and anti-angiogenic factors. Recent studies have shown that pigment epithelium-derived factor (PEDF) can induce differentiation and inhibit angiogenesis of tumors. This study was designed to investigate the expression of PEDF and its roles in proliferation, adhesion and migration of HaCaT cells, a human keratinocyte cell line. Our results have shown that PEDF is expressed in HaCaT cells at both mRNA and protein levels determined by RT-PCR and Western blot, separately. PEDF signal mainly localizes in the cytoplasm of HaCaT cell, as determined by immunofluorescence. Furthermore, expression of PEDF is decreased by 50 ng/ml of VEGF(165). Proliferation and migration of HaCaT cells are decreased by PEDF, while adhesion of HaCaT cells is upregulated approximately by 29%. PEDF also induce the S phase accumulation of HaCaT cells. In addition, phosphorylation of ERK1/2, not JNK and p38, is decreased by PEDF. These results indicate that PEDF may play an inhibitory role on growth and migration of HaCaT cells through dephosphorylation of ERK1/2.


Bronchial Artery Embolization for Hemoptysis in Primary Lung Cancer: A Retrospective Review of 84 Patients.
To evaluate the safety and efficacy of bronchial artery embolization (BAE) in patients with primary lung cancer-related hemoptysis and to identify factors associated with hemoptysis-free survival. Data from 84 patients with primary lung cancer (non-small cell [n = 74] and small cell [n = 10]) who underwent BAE from 1997 to 2018 for the management of hemoptysis were retrospectively reviewed. Of these, 53 patients had stage IV lung cancer. The hemoptysis volume prior to initial BAE was trivial (blood-tinged sputum) in 21 patients, moderate (< 300 mL per 24 hours) in 34 patients, and massive (> 300 mL per 24 hours) in 29 patients. Technical success, defined as the ability to selectively embolize the abnormal vessel, was achieved in 83 patients (98.8%), and clinical success was achieved in 69 (82.1%) patients. Polyvinyl alcohol particles were used to embolize in 51 patients, gelfoam in 15 patients, and gelfoam plus microcoils in 17 patients. Hemoptysis recurred in 20 patients (23.8%) during follow-up. The median hemoptysis-free survival and overall survival periods were both 61 days. In the clinical-success and clinical-failure groups, the median overall survival period was 99 and 9 days, respectively (P < .001). In multivariable analysis, massive hemoptysis (P = .012) and cavitary lung mass (P = .019) were predictive factors for shortened hemoptysis-free survival. BAE is a safe and effective approach to control hemoptysis, although the prognosis in primary lung cancer patients presenting with hemoptysis is generally poor. Massive hemoptysis and cavitary lung mass are significant predictors of shortened hemoptysis-free survival.


Evaluation of Industry Payments to US Advanced Practice Clinicians in 2021.
Advanced practice clinicians (APCs) are a growing part of the US health care system, and their financial relationships with pharmaceutical and medical device companies have not been well studied. To examine the value, frequency, and types of payments made to APCs and the association of state scope-of-practice laws with these payments. This cross-sectional study used 2021 Open Payments Program data to analyze payments from pharmaceutical or medical device companies to physicians or APCs between January 1 and December 31, 2021. Doctors of medicine and osteopathy were categorized as physicians, and nurse practitioners, physician assistants, clinical nurse specialists, certified registered nurse anesthetists, certified nurse midwives, and anesthesiologist assistants as APCs. The total value and total number of payments were calculated in aggregate and per clinician for each type of APC, all APCs, and physicians. These calculations were repeated by submitting manufacturer, form of payment, nature of payment, and state scope-of-practice law for nurse practitioners, physician assistants, and physicians. A total of 412 000 physicians and 232 000 APCs collectively received $1.99 billion in payments from industry in 2021, of which APCs received $121 million (6.1%). The median total value of payments per clinician for physicians was $167 (IQR, $45-$712) and for APCs was $117 (IQR, $33-$357). The median total number of payments per clinician was equal for physicians and APCs (n = 4). The most common payments to APCs included food and beverage ($69 million [57.6%]), compensation for services other than consulting ($32 million [26.4%]), and consulting fees ($8 million [6.6%]). Advanced practice clinicians in states with the most restrictive scope-of-practice laws received 15.9% lower total value of payments than those in the least restrictive states (P = .002). Physician assistants received 7.6% (P = .005) higher value and 18.1% (P < .001) greater number of payments than nurse practitioners. In this cross-sectional study, 232 000 APCs collectively received $121 million in industry payments in 2021. The frequency of industry interactions with APCs was similar to that for physicians, but the average value was lower. The greater value of payments to APCs who practice in states with the least restrictive scope-of-practice laws suggests that industry payments may be related to clinician autonomy.


Analysis of clinical and laboratory characteristics in 42 patients with thrombotic thrombocytopenic purpura from a single center in China.
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by microvascular platelet deposition and thrombus formation with resulting microangiopathic hemolytic anemia. Deficiency of the von Willebrand factor cleavage protease, also known as ADAMTS 13, has been implicated as an important etiological factor in TTP. Little studies were obtained on Chinese patients with TTP until now. Our aim was to analyze the clinical features, outcome and laboratory characteristics of Chinese TTP patients, and determine whether plasma ADAMTS 13 activity is decreased in TTP and its diagnostic value for TTP. Forty-two TTP patients (29 females; 13 males) admitted to our hospital from 1998 to 2010 were analyzed. There were 34 patients (81%) with the triad of TTP, including hemolytic anemia, thrombocytopenia and neurologic abnormalities; 7 (16.7%) had the classical pentad of TTP. Major etiologic factors were acquired autoimmunological abnormalities (31%); no familial TTP was identified in this series. The schistocytes of peripheral blood smears were present in all cases with a mean frequency of 4.6% (range from 0.3% to 13.4%). Plasma ADAMTS 13 activity was determined in 22 patients with the FRET-vWF86 assay. Only 4 idiopathic TTP patients (18.2%) had severe ADAMTS 13 deficiency (activity<10%); 9 (40.9%) had moderate decrease of ADAMTS 13 activity (activity: 10-40%); another 9 (40.91%) had normal ADAMTS 13 activity (>40%). T lymphocyte subpopulation was measured in 23 TTP patients with FACS Calibur; 14 of the 23 (60.9%) had significantly decreased CD4 cells count and CD4/CD8 ratio, suggesting cellular immune dysfunction may be involved in the pathogenesis of TTP. In the studies, plasmapheresis is the main therapeutic method. 26 of 31 patients (83.9%) accepting plasmapheresis achieved complete remission; those patients who only underwent plasma infusion had low remission rate (18.2%) and high mortality (9/11; 81.8%). Four patients with packed RBC infusion manifested transient exacerbation of neurologic or psychiatric symptoms. In conclusion, the diagnosis of TTP in China is still based on clinical features including evidence of microangiopathic hemolysis. Severe ADAMTS 13 activity deficiency might be a valuable indicator for idiopathic TTP diagnosis. Further studies are needed to determine the real value of ADAMTS 13 activity for TTP diagnosis and whether T lymphocytes subset dysregulation plays important role in TTP pathogenesis.


TRIM28 prevents autoinflammatory T cell development in vivo.
TRIM28 is a component of heterochromatin complexes whose function in the immune system is unknown. By studying mice with conditional T cell-specific deletion of TRIM28 (CKO mice), we found that TRIM28 was phosphorylated after stimulation via the T cell antigen receptor (TCR) and was involved in the global regulation of CD4(+) T cells. The CKO mice had a spontaneous autoimmune phenotype that was due in part to early lymphopenia associated with a defect in the production of interleukin 2 (IL-2) as well as incomplete cell-cycle progression of their T cells. In addition, CKO T cells showed derepression of the cytokine TGF-β3, which resulted in an altered cytokine balance; this caused the accumulation of autoreactive cells of the T(H)17 subset of helper T cells and of Foxp3(+) T cells. Notably, CKO Foxp3(+) T cells were unable to prevent the autoimmune phenotype in vivo. Our results show critical roles for TRIM28 in both T cell activation and T cell tolerance.


Recovery trajectories of kelp forest animals are rapid yet spatially variable across a network of temperate marine protected areas.
Oceans currently face a variety of threats, requiring ecosystem-based approaches to management such as networks of marine protected areas (MPAs). We evaluated changes in fish biomass on temperate rocky reefs over the decade following implementation of a network of MPAs in the northern Channel Islands, California. We found that the biomass of targeted (i.e. fished) species has increased consistently inside all MPAs in the network, with an effect of geography on the strength of the response. More interesting, biomass of targeted fish species also increased outside MPAs, although only 27% as rapidly as in the protected areas, indicating that redistribution of fishing effort has not severely affected unprotected populations. Whether the increase outside of MPAs is due to changes in fishing pressure, fisheries management actions, adult spillover, favorable environmental conditions, or a combination of all four remains unknown. We evaluated methods of controlling for biogeographic or environmental variation across networks of protected areas and found similar performance of models incorporating empirical sea surface temperature versus a simple geographic blocking term based on assemblage structure. The patterns observed are promising indicators of the success of this network, but more work is needed to understand how ecological and physical contexts affect MPA performance.


Statistical methods for the Ames Salmonella assay: a review.
The Ames Salmonella assay remains the most widely used in vitro genotoxicity assay. Several statistical methods have been proposed for its analysis [B.H. Margolin, N. Kaplan, E. Zeiger, Statistical analysis of the Ames Salmonella/microsome test, Proc. Natl. Acad. Sci., 78 (1981) 3779-3783; L.E. Myers, N.H. Saxton, L.I. Southerland, T.J. Wolff, Regression analysis of Ames test data, Environ. Mol. Mutagen., 3 (1981) 575-586; A.G. Stead, V. Hasselblad, J.P. Creason, L. Claxton, Modelling the Ames test, Mutation Res., 85 (1981) 13-27; L. Bernstein, J. Kaldor, J. McCaan, M.C. Pike, An empirical approach to the statistical analysis of mutagenesis data from the Salmonella test, Mutation Res., 97 (1982) 267-281; N.E. Breslow, Extra-Poisson variation in log-linear models, Appl. Stat., 33 (1984) 38-44; J. Wahrendorf, G.A.T. Mahon, M. Schumacher, A nonparametric approach to the statistical analysis of mutagenicity data, Mutation Res., 147 (1985) 5-13; D.G. Simpson, B.H. Margolin, Recursive nonparametric testing for dose-response relationships subject to downturns at high doses, Biometrika, 73 (1986) 589-596; D.G. Simpson, B.H. Margolin, Nonparametric testing for dose-response curves subject to downturns: Asymptotic power considerations, Annals Stat., 18 (1990) 373-390.]. In this paper we review recent literature to see what statistical methods are in fact employed for the analysis of the Ames assay. We then note that these methods can be classified into a common category in the framework of Haynes and Eckardt's mutation induction kinetics model [R.H. Haynes, F. Eckardt, Mathematical analysis of mutation induction kinetics, in: F.J. de Serres, A. Hollaender (Eds. ), Chemical Mutagens, Principles and Methods for Their Detection, Vol. 6, Plenum, New York, 1980, pp. 271-307]. The value in knowing this is that most methods of analysis considered here will likely exhibit common statistical behavior. These analyses are computationally intensive, e.g., [B.H. Margolin, N. Kaplan, E. Zeiger, Statistical analysis of the Ames Salmonella/microsome test, Proc. Nat. Acad. Sci., 78 (1981) 3779-3783], hence the ready availability of computer programs is essential if biologists are to use these methods. We briefly review two statistical software programs that are available in the public domain, and describe in detail a third program, Salm, [B.H. Margolin, N. Kaplan, E. Zeiger, Statistical analysis of the Ames Salmonella/microsome test, Proc. Nat. Acad. Sci., 78 (1981) 3779-3783; B.H. Margolin, B.S. Kim, K. Risko, The Ames Salmonella/microsome assay: Issues of inference and validation, J. Amer. Stat. Assoc., 84 (1989) 651-661]. The Salm program is obtainable through the file transfer protocol (ftp) or using a WWW browser. Finally, we discuss two statistical consequences of naively applying the two-fold rule, a method of analysis employed by a number of researchers.


Role of heparan sulfate in immune system-blood vessel interactions.
Heparan sulfate proteoglycan, a component of endothelial cell membranes and extracellular matrices, is involved in a number of the critical functions of endothelium and of antigen-presenting cells. This review discusses how heparan sulfate is released from endothelial cells during inflammation, how the loss of heparan sulfate potentially alters endothelial cell physiology, and how the presence of heparan sulfate in a soluble form might regulate the functioning of lymphocytes at sites of inflammation.


Atrial level right to left intracardiac shunt associated with postoperative hypoxemia: demonstration with contrast two-dimensional echocardiography.
Transient hypoxemia is not uncommon after major cardiac or thoracic surgery. The differential diagnosis includes atelectasis, pulmonary embolus, pneumonitis, congestive heart failure and several other diverse cardiovascular and pulmonary problems. Less well recognized is transient right to left intracardiac shunting through a patient foramen ovale or previously unsuspected atrial septal defect. Three cases of clinically important hypoxemia associated with right to left shunting after aortocoronary bypass surgery are presented. The right to left shunting was documented with contrast-enhanced echocardiography, which is a simple, inexpensive and accurate means of screening patients for intracardiac right to left shunts and may play a valuable role in the postoperative management of patients.


Treatment of superficial venous insufficiency in a large patient cohort with retrograde administration of ultrasound-guided polidocanol endovenous microfoam versus endovenous laser ablation.
To evaluate outcomes among symptomatic patients with superficial chronic venous insufficiency treated with retrograde ultrasound-guided polidocanol endovenous microfoam 1% (PEM) or endovenous laser ablation (EVLA). This study is a retrospective chart review from a single vein center between October 2013 and June 2019. Procedures were performed on 1070 patients with Clinical, Etiologic, Anatomic, and Pathophysiologic class 2 to 6 disease and symptomatic superficial venous reflux of the great saphenous vein or anterior accessory saphenous vein. PEM was used for 550 procedures and patients were followed for 43 ± 13 months; EVLA was used for 520 procedures and patients were followed for 57 ± 18 months. After complete treatment, the elimination of reflux was documented in 93.5% (514/550) and 92.8% (482/520) of the PEM and EVLA procedures, respectively. During the follow-up period, 18% of patients treated with EVLA returned for additional treatment to address residual symptoms in the affected leg. In C6 patients treated with PEM, 69% of ulcers (11/16) healed in less than 1 month, compared with 5% of patients (1/21) treated with EVLA. In C4 patients with lesions, resolution of spontaneous bleeding was 100% in both groups. There were no neurological or cardiac adverse events in the PEM group. Minor complications included asymptomatic deep vein thrombosis (0.5%), one common femoral vein thrombus extension, and superficial venous thrombosis (4%) in the PEM group and asymptomatic deep vein thrombosis (0.8%) and two endovenous heat-induced thromboses in the EVLA group. PEM is comparable in safety and efficacy with EVLA for the treatment of saphenous reflux and associated symptoms. PEM was an effective intervention for most patients with C6 disease. Closure rates in both groups were maintained 36 months after treatment.


Comparison of Endothelial Barrier Functional Recovery After Implantation of a Novel Biodegradable-Polymer Sirolimus-Eluting Stent in Comparison to Durable- and Biodegradable-Polymer Everolimus-Eluting Stents.
The advantage of biodegradable-polymer drug-eluting stents (BP-DES) versus durable-polymer (DP) DES remains uncertain. We compared neointimal formation and endothelial barrier function of new BP sirolimus-eluting stents (BP-SES, BuMA Supreme®) to other contemporary BP-DES, DP-DES, and bare metal stents (BMS). Light microscopic assessment in swine coronary arteries showed comparable neointimal formation between BP-SES and DP everolimus-eluting stent (DP-EES). The performance of BP-SES was compared with DP-EES (Xience Xpedition®), BP-EES (Synergy®), and BMS (Multi-Link Vision®) at 45- and 90-days in rabbit ilio-femoral arteries using Evans blue dye (EBD) followed by immunostaining for endothelial barrier proteins (p120/vascular endothelial-cadherin [VE-cad]) to evaluate endothelial barrier function and scanning electron microscopy (SEM) to determine strut tissue coverage. BMS followed by BP-SES and BP-EES exhibited smaller EBD positive areas versus that of DP-EES at 45- and 90-days. p120/VE-cad immunostaining and SEM-determined strut coverage was greater at 45- and 90-days for BMS followed by all DESs. Regardless of stent type, the lack of p120/VE-cad co-localization showed greater leukocyte and platelet aggregation. Three types of DES showed different endothelial healing pattern regardless their equivalent suppression of neointimal formation.