Online control of rapid target-directed aiming using blurred visual feedback.
The accuracy and precision of target-directed aiming is contingent upon the availability of online visual feedback. The present study aimed to examine the visual regulation of aiming with blurred vision. The aiming task was executed using a stylus on a graphics digitizing board, which was translated onto a screen in the form of a cursor (representing the moving limb) and target. The vision conditions involved the complete disappearance or blur of the cursor alone, target alone, and cursor+target. These conditions involved leaving the screen uncovered or covering with a diffusing sheet to induce blur. The distance between the screen and sheet was increased to make the blur progressively more severe (0 cm, 3 cm). Results showed significantly less radial and variable error under blurred compared to no vision of the cursor and cursor+target. These findings were corroborated by the movement kinematics including a shorter proportion of time to peak velocity, more negative within-participant correlation between the distances travelled to and after peak velocity, and lower spatial variability from peak velocity to the end of the movement under blurred vision. The superior accuracy and precision under the blurred compared to no vision conditions is consistent with functioning visual regulation of aiming, which is primarily contingent upon the online visual feedback of the moving limb. This outcome may be attributed to the processing of low spatial-high temporal frequencies. Potential implications for low vision diagnostics are discussed.


Correction: Development of a Tailored Mobile Phone-Based Intervention to Facilitate Parent-Child Communication and Build Human Papillomavirus Vaccine Confidence: Formative Qualitative Study.
[This corrects the article DOI: 10.2196/43041.].


Increase of pro-oxidants with no evidence of lipid peroxidation in exhaled breath condensate after a 10-km race in non-athletes.
It is a well-established fact that exercise increases pro-oxidants and favors oxidative stress; however, this phenomenon has been poorly studied in human lungs. Pro-oxidative generation (H(2)O(2), NO(2) (-)), lipid peroxidation markers (MDA), and inflammation (pH) in exhaled breath condensate (EBC) have been determined through data from 10 active subjects who ran 10 km; samples were obtained immediately before, at 20, and at 80 min post-exertion. In EBC, the concentration of H(2)O(2) at 80 min post-exertion was increased. NO(2) (-) concentration showed a tendency to increase at 80 min post-exertion, with no variations in MDA and pH. No variations of NO(2) (-) were found in plasma, while there was an increase of NO(2) (-) at 80 min post-exertion in the relation between EBC and plasma. NO(2) (-) in EBC did not correlate to plasmatic NO(2) (-), while it did correlate directly with H(2)O(2) in EBC, suggesting a localized origin for the exercise-related NO(2) (-) increase in EBC. MDA in plasma did not increase nor correlate with MDA in EBC. In conclusion, high-intensity exercise increases lung-originated pro-oxidants in non-athlete subjects with no evidence of early lipid peroxidation and changes in the pH value in EBC.


Col3a1 delivered via extracellular vesicles of Sertoli cells is essential for mice Sertoli cell proliferation.
It is generally believed that Sertoli cells can proliferate only before sexual maturity. In this study, we found that extracellular vesicles of Sertoli cells derived from prepubertal mice (SEVs) have the ability to promote the proliferation of Sertoli cell population. In addition, via proteomic analysis, we compared the functional components of extracellular vesicles derived from Sertoli cells of mice at 12-14 days and 8 weeks. The functional profiling of SEVs suggested important developmental roles, and this was confirmed by analysis comparing the transcriptomic changes in Sertoli cells treated with DMSO and GW4869. The following analysis pointed to Col3a1 as a key factor in SEVs, which was further validated using primary Sertoli cells and TM4 cell line. The present study suggests a possible role for Col3a1 in promoting the proliferation of cultured Sertoli cells and provides a new perspective on the function of extracellular vesicles in Sertoli cell development.


What causes extended lows in microtine cycles? : Analysis of fluctuations in sympatric shrew and microtine populations in Fennoscandia.
Synchronous declines of sympatric shrew and microtine populations in boreal regions of Fennoscandia have been claimed as evidence that predation deepens and extends the low phase of the microtine population cycles. Assuming that shrews and microtines have the same maximum intrinsic rate of increase, and that the predators kill the shrews and microtines that they encounter unselectively, this hypothesis predicts that sympatric shrew and microtine populations will decline and increase simultaneously. In this study conducted at 60°56'N in southeast Norway, as well as in 13 of 15 other studies at sites in Fennoscandia, the shrew populations declined simultaneously with the sympatric microtine populations, but recovered sooner. The shrew-microtine ratio among animals trapped peaked about 2 years after the peak in the microtine population. The same pattern was found in the diet of raptors in Fennoscandia. Since the maximum intrinsic rate of increase does not seem to be higher in shrews than in microtines, the pattern suggests that either predation is not causing the extended lows in the microtine populations, or that the proportion of predators that selectively kill microtines fluctuates during the microtine cycle. The most likely candidates for selective killers are weasels.


Increasing incidence of anogenital warts with an urban-rural divide among males in Manitoba, Canada, 1990-2011.
Anogenital warts (AGW) are caused by the most common sexually transmitted infection, human papillomavirus. The objective of this study was to examine AGW incidence from 1990 to 2011 by sex, age, income quintile, and residential area category (urban/rural). The study period included the initiation of school-based HPV vaccination for girls in the sixth grade, which began in 2008. The data presented in this paper may also be useful for establishing baseline rates of AGW incidence which may be used to evaluate the success of the school-based HPV immunization program. Cases of anogenital warts were identified using Manitoba's administrative databases of Physician Claims and Hospital Discharge Abstracts. Annual age-standardized incidence in Manitoba from 1990 to 2011 was calculated. Incident AGW rates were compared by sex, age group, residential area category (urban/rural), and household income quintile using logistic regression. Joinpoint regression analyses were used to evaluate the time trends of AGW. Prior to 2000, AGW incidence was higher among females than males. However, from 2000 to 2011 the incidence was higher among males and increased steadily over time. AGW incidence tended to peak in younger age groups among females compared to males. Females and males living in urban areas had nearly twice the odds of AGW occurrence compared to those in rural areas. There is a need for education about AGW in male population. The upcoming initiation of HPV vaccination among boys may reduce the incidence and should be evaluated.


Thiocyanate-degrading microflora alleviates thiocyanate stress on tomato seedlings by improving plant and rhizosphere microenvironment.
Thiocyanate in irrigation water can adversely affect plant growth and development. A previously constructed microflora with effective thiocyanate-degrading ability was used to investigate the potential of bacterial degradation for thiocyanate bioremediation. The root and aboveground part dry weight of plants inoculated with the degrading microflora increased by 66.67% and 88.45%, respectively, compared to those plants without the microflora. The supplementation of thiocyanate-degrading microflora (TDM) significantly alleviated the interference of thiocyanate in mineral nutrition metabolism. Moreover, the supplementation of TDM significantly reduced the activities of antioxidant enzymes, lipid peroxidation, and DNA damage and it protected plants from excessive thiocyanate, while the crucial antioxidant enzyme (peroxidase) decreased by 22.59%. Compared with the control without TDM supplementation, the soil sucrase content increased by 29.58%. The abundances of Methylophilus, Acinetobacter, unclassified Saccharimonadales, and Rhodanobacter changed from 19.92%, 6.63%, 0.79%, and 3.90%-13.19%, 0.27%, 3.06%, and 5.14%, respectively, with TDM supplementation. Caprolactam, 5,6-dimethyldecane, and pentadecanoic acid seem to have an effect on the structure of the microbial community in the rhizosphere soil. The above results indicated TDM supplementation can significantly reduce the toxic effects of thiocyanate on the tomato-soil microenvironment.


[Synthesis of multifunctional surfactants for elaboration of micellar model systems of enzymes].
In order to provide a closer analogy between micelles and enzymes, the design of functionalized micellar systems have been undertaken. This paper presents the synthesis of surfactant cationic molecules which contains either a free or a protected aldehyde group. An ammonium quaternary surfactant with two functional groups, aldehyde dimethyl acetal and imidazole, has also been synthesized.


Treatment of Recurrent Refractory Pediatric Pre-B Acute Lymphoblastic Leukemia Using Inotuzumab Ozogamicin Monotherapy Resulting in CD22 Antigen Expression Loss as a Mechanism of Therapy Resistance.
Inotuzumab ozogamicin is a novel antibody-drug conjugate that targets CD22, a common antigen on pre-B acute lymphoblastic leukemia cells. A 7-year-old boy with pre-B acute lymphoblastic leukemia in his second relapse was given 2 cycles of inotuzumab ozogamicin. He responded morphologically with a negative bone marrow evaluation. However, he relapsed in cycle 3 of therapy with a loss of CD22 expression on his lymphoblast population. To our knowledge, this is the first published case of CD22 expression loss as a mechanism of therapy resistance for inotuzumab ozogamicin.


Rett syndrome: a case report and overview.
A 3-year-old girl with Rett syndrome is reported in this case report. The aim of this report is to highlight the clinical features of this rare neurodegenerative disorder that mainly affects young girls. A brief review of literature of this disorder is included.


Integrative analysis of relative abundance data and presence-absence data of the microbiome using the LDM.
We previously developed the LDM for testing hypotheses about the microbiome that performs the test at both the community level and the individual taxon level. The LDM can be applied to relative abundance data and presence-absence data separately, which work well when associated taxa are abundant and rare, respectively. Here, we propose LDM-omni3 that combines LDM analyses at the relative abundance and presence-absence data scales, thereby offering optimal power across scenarios with different association mechanisms. The new LDM-omni3 test is available for the wide range of data types and analyses that are supported by the LDM. The LDM-omni3 test has been added to the R package LDM, which is available on GitHub at https://github.com/yijuanhu/LDM. Supplementary data are available at Bioinformatics online.


Resectoscopic surgery in 10 women with abnormal uterine bleeding and atypical endometrial hyperplasia.
To evaluate the role of the resectoscope in the diagnosis and treatment of women with abnormal uterine bleeding (AUB) and atypical endometrial hyperplasia. Retrospective case series (Canadian Task Force classification III-3). University-affiliated teaching hospital. Ten women. Intervention. Hysteroscopic evaluation after preoperative endometrial biopsy indicated simple hyperplasia without atypia, complex hyperplasia with atypia, or inadequate specimen. Atypical hyperplasia was confirmed in eight patients after total endomyometrial resection. Hysterectomy was offered to all patients but accepted by only two: one for bilateral ovarian serous cystadenomas and the second for a granulosa cell ovarian tumor. No residual endometrium was found in hysterectomy specimens. Seven women were amenorrheic and well 1 to 9 years after resection. An additional patient with amenorrhea died from colon cancer 2 years after resection. Resectoscopic surgery confirmed or detected atypical endometrial hyperplasia in eight women and excluded it in two patients with AUB and a previous diagnosis of simple hyperplasia, atypical hyperplasia, or inadequate specimen. Skillful resectoscopic surgery may be an alternative to hysterectomy in selected patients with atypical hyperplasia who are compliant with regular and long-term follow-up.


A plant tethering system for the functional study of protein-RNA interactions in vivo.
The sorting of RNA transcripts dictates their ultimate post-transcriptional fates, such as translation, decay or degradation by RNA interference (RNAi). This sorting of RNAs into distinct fates is mediated by their interaction with RNA-binding proteins. While hundreds of RNA binding proteins have been identified, which act to sort RNAs into different pathways is largely unknown. Particularly in plants, this is due to the lack of reliable protein-RNA artificial tethering tools necessary to determine the mechanism of protein action on an RNA in vivo. Here we generated a protein-RNA tethering system which functions on an endogenous Arabidopsis RNA that is tracked by the quantitative flowering time phenotype. Unlike other protein-RNA tethering systems that have been attempted in plants, our system circumvents the inadvertent triggering of RNAi. We successfully in vivo tethered a protein epitope, deadenylase protein and translation factor to the target RNA, which function to tag, decay and boost protein production, respectively. We demonstrated that our tethering system (1) is sufficient to engineer the downstream fate of an RNA, (2) enables the determination of any protein's function upon recruitment to an RNA, and (3) can be used to discover new interactions with RNA-binding proteins.


Lipidomics of human brain aging and Alzheimer's disease pathology.
Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context.


Ventricular uptake during brain scanning. A case report of ventricular lymphomatosis.
Visualization of the cerebral ventricles during radionuclide brain scanning is rarely reported. A case demonstrating the lateral ventricles by brain scanning with 99mCc-stannous glucoheptonate in a patient with lymphoma is presented.


Surgical resection of carotid body tumors: long-term survival, recurrence, and metastasis.
We retrospectively reviewed a 20-year experience with 59 carotid body tumors in 55 patients examined at our institution in order to determine the long-term results of surgical resection, including the rates of distant metastasis, local recurrence, and long-term survival. Complete surgical excision was possible in 52 of the 55 patients (95%). Perioperative mortality was only 2% (1 of 59 procedures), and no operative deaths occurred during the last 10 years of the study. Survival of patients after resection of a carotid body tumor was equivalent to that for sex- and age-matched control subjects. Only one patient (2%) had development of metastatic disease during long-term follow-up. Three patients (6%) had recurrence of the carotid body tumor after complete excision. All recurrent tumors were observed in patients with multiple paragangliomas or a family history of cervical paragangliomas. Therefore, we advocate early surgical resection of all carotid body tumors in low-risk patients. Such early resection maximizes the possibility of cure and minimizes the risks of neurovascular complications associated with large and neglected tumors.


Diameter of the common bile duct in the elderly patient: measurement by ultrasound.
We wanted to assess the width of the common bile duct (CBD) in an asymptomatic elderly (> 75 years) population, since no previous report has particularly considered the important age-related increase in CBD diameter for this patient group. CBD width of 92 asymptomatic people over 75 years of age (mean 84.7 years, range 75-96 years) without clinical or laboratory evidence for biliary, hepatocellular or pancreatic disease was measured by real-time high-resolution ultrasound of the upper abdomen. All examinations were performed by one experienced radiologist. Mean values were calculated for three groups: patients with and without cholecystolithiasis and after cholecystectomy. Statistical analysis was carried out by analysis of variance. Considering the measurements of all patients, the mean width (+/- SD) of the CBD was calculated as 6.5 +/- 2.5 mm. The difference between patients without cholecystolithiasis (6.2 +/- 2.3 mm) and patients after cholecystectomy (8.7 +/- 2.9 mm) was statistically significant (P < 0.0001). Cholecystolithiasis (6.0 +/- 1.6 mm) proves not to be an additional factor for CBD widening in comparison with patients without stone disease. The CBD of these very elderly subjects shows a considerable increase in comparison with the recommended borderline values in the ultrasound literature. An upper limit of 10 mm seems reasonable for patients with and without cholecystolithiasis. A significant increase in CBD width after cholecystectomy was found and measurements up to 14 mm may occur. Measurements have to be correlated with clinical and laboratory findings.


Anti-human CD99 antibody exerts potent antitumor effects in mantle cell lymphoma.
CD99 is a surface molecule expressed on various cell types including cancer cells. Expression of CD99 on multiple myeloma is associated with CCND1-IGH fusion/t(11;14). This translocation has been reported to be a genetic hallmark of mantle cell lymphoma (MCL). MCL is characterized by overexpression of cyclin D1 and high tumor proliferation. In this study, high expression of CD99 on MCL cell lines was confirmed. Our generated anti-CD99 monoclonal antibody (mAb), termed MT99/3, exerted potent antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities against mantle B-cell lymphoma without direct cytotoxic effects. The anti-tumor activities of mAb MT99/3 were more effective in MCL than in other B-cell lymphomas. Moreover, in a mouse xenograft model using Z138 MCL cell line, treatment of mAb MT99/3 reduced tumor development and growth. Our study indicated that mAb MT99/3 is a promising immunotherapeutic candidate for mantle cell lymphoma therapy.


A plane layered model to estimate in situ ultrasound exposures.
Determination of in situ ultrasound exposures in experimental animals and patients is necessary to assess any potential hazard of ultrasound implied by reported biological effects in animals. A layered model was used to calculate total attenuation of ultrasound pulses as they passed through tissue layers to an organ site, thus enabling calculation of in situ intensities from free-field transducer emissions. The model assumes plane homogeneous layers of tissue of known thickness, attenuation and acoustic impedance. Calculations based on the model, compared with in situ measurements in a human cadaver specimen, were accurate to within approximately +/- 3 dB. We then calculated in situ clinical exposures using published obstetric B-scans. Total attenuation to the fetus averaged approximately 11 dB at 3.5 MHz.


Feasibility and safety of papermaking wastewater in using as ecological water supplement after advanced treatment by fluidized-bed Fenton coupled with large-scale constructed wetland.
Reuse of pulp-and-paper industry wastewater as reclaimed water is an effective way to mitigate water resource shortage. In this study, the feasibility and safety of papermaking wastewater for the use as ecological water supplement after the treatment by fluidized-bed Fenton (FBF) coupled with constructed wetland (CW), were investigated from laboratory-scale to large-scale field. The optimum pH, H2O2, H2O2/Fe2+ ratio and hydraulic retention time (HRT) of FBF were 3.5, 0.93 mL/L, 4 and 60 min, respectively, based on reduction of both total organic carbon (TOC) and genotoxicity. Furthermore, the safety of effluent was evaluated using SOS/umu assay and 8-hydroxy-2-deoxyguanosine (8-OHdG) in zebrafish. Results showed FBF followed by CW improved the conventional water quality indicators and reduced the toxicity. Average removal rates of chemical oxygen demand (COD), ammonia nitrogen (NH3-N), total nitrogen (TN), total phosphorus (TP) and colority were 87.3%, 93.59%, 51.73%, 84.75% and 95.86%, respectively. The equivalent concentration of 4-nitroquinoline 1-oxide (4-NQO-EQ) decreased from 30.6 ± 1.6 μg/L in influent to 12.4 ± 1.0 μg/L after treated by FBF, then decreased to 5.9 ± 0.4 μg/L after treated by CW and to 3.2 ± 0.3 μg/L after 12-km downstream self-purification. The chronic survival rates of 21-d zebrafish significantly increased from 0.0% in influent to 58.8 ± 4.0% in effluent of CW and gradually increased to 68.8 ± 2.6% after 12-km downstream self-purification. Similarly, 8-OHdG level in zebrafish decreased from 120.0 ± 19.3 ng/L in effluent of ecological oxidation pond to 94.0 ± 7.5 ng/L in effluent of CW and gradually decreased to 42.0 ± 3.0 ng/L after 12-km downstream self-purification. The study concluded that FBF-CW is an efficient detoxication and water quality improvement technology for papermaking wastewater to be used as an ecological water supplement.


The role of endothelial cell reactive antibodies in peripheral vascular disease.
The mechanism by which a small but significant proportion of patients with peripheral vascular disease (PVD) rapidly progress to critical ischaemia is unclear. Both experimental and clinical data suggest a role for autoantibodies in the pathogenesis of atherosclerotic disease, particularly in the accelerated atherosclerosis seen in patients with systemic lupus erythematosus and the anti-phospholipid syndrome. This review examines the evidence for a role for endothelial cell reactive autoantibodies in PVD and the potential mechanisms by which these autoantibodies could contribute to the acceleration of atherosclerosis in a proportion of patients. The identification of such markers could lead to the identification of patients with PVD who are at risk of developing critical ischaemia and may warrant early and aggressive intervention.


Parental age and offspring leukocyte telomere length and attrition in midlife: Evidence from the 1946 British birth cohort.
There is evidence that paternal age may influence offspring telomere length, but the joint effects of father's and mother's age are unclear. We evaluated whether parental ages, individually and jointly, were associated with offspring telomere length and shortening. We included 2305 British birth cohort participants with measured leukocyte telomere length (LTL) at age 53, among whom 941 had a second measurement at age 60-64. Linear regressions were performed to assess the associations of father's and mother's age at birth and the parental age gap, i.e. the difference between maternal and paternal age with LTL and LTL change. A one year increase in father's age corresponded to a 0.26% (95% CI: 0.04-0.47%) increase in offspring LTL at age 53 in the sex-adjusted model. No association was observed for mother's age. Associations of father's or mother's age with offspring LTL at age 53 went to opposite directions when both parental ages were included together. For the difference in parental age, every year that fathers were older than mothers corresponded to a 0.94% (95% CI, 0.38-1.50%) increase in LTL at age 53 after adjustment for potential confounders. Neither parental ages nor the difference in parental ages were correlated with LTL change. There was a joint effect of parental ages on offspring telomere length, further denoting a complex role of reproductive age in offspring health and ageing.


Prediction of Caco-2 cell permeability using a combination of MO-calculation and neural network.
In the present study, we developed an approach involving a combination of molecular orbital (MO) calculation and neural network to predict Caco-2 cell permeability (logP(app)) from the molecular structure of compounds. For a total of 87 compounds with logP(app) values obtained from the literature, three-dimensional molecular structures were determined by MO-calculation, and then five molecular descriptors were obtained, namely, the dipole moment, polarizability, sum of charges of nitrogen atoms (sum(N)), oxygen atoms (sum(O)), and hydrogen atoms bonding to nitrogen or oxygen atoms (sum(H)). The correlation between these five molecular descriptors and logP(app) was analyzed using a feed-forward back-propagation neural network with a configuration of 5-4-1 for input, hidden, and output layers found suitable for predicting Caco-2 cell permeability. A leave-one-out cross-validation procedure revealed that the neural network model possesses a fairly good predictability as far as Caco-2 cell permeability is concerned (predictive root mean square error (RMSE)=0.507), and better than the simple and quadratic regression model (predictive RMSE=0.584 and 0.568, respectively).


Therapeutic Potential of Amniotic Fluid Derived Mesenchymal Stem Cells Based on their Differentiation Capacity and Immunomodulatory Properties.
Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: "amniotic fluid derived mesenchymal stem cells", "cell-therapy", "degenerative diseases", "inflammatory diseases", "regeneration", "immunosuppression". Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.


Effect of acid blockade on gastric histamine in mice.
Vagotomy and omeprazole effectively inhibited 2-deoxy-D-glucose (-91%) and pentagastrin (-72%) stimulated acid production in mice, respectively. Both vagotomy and omeprazole treatment were accompanied by massive increases in histamine secretion (8-fold or more, during both basal and stimulated states). Mucosal stores of histamine, however, were not depleted. Similar rises in luminal histamine have been observed in patients treated in these ways. The mouse model may thus be suitable to elucidate the kinetics of histamine release in patients.


Gene products of the hupGHIJ operon are involved in maturation of the iron-sulfur subunit of the [NiFe] hydrogenase from Rhizobium leguminosarum bv. viciae.
In the present study, we investigate the functions of the hupGHIJ operon in the synthesis of an active [NiFe] hydrogenase in the legume endosymbiont Rhizobium leguminosarum bv. viciae. These genes are clustered with 14 other genes including the hydrogenase structural genes hupSL. A set of isogenic mutants with in-frame deletions (deltahupG, deltahupH, deltahupI, and deltahupJ) was generated and tested for hydrogenase activity in cultures grown at different oxygen concentrations (0.2 to 2.0%) and in symbiosis with peas. In free-living cultures, deletions in these genes severely reduced hydrogenase activity. The deltahupH mutant was totally devoid of hydrogenase activity at any of the O2 concentration tested, whereas the requirement of hupGIJ for hydrogenase activity varied with the O2 concentration, being more crucial at higher pO2. Pea bacteroids from the mutant strains affected in hupH, hupI, and hupJ exhibited reduced (20 to 50%) rates of hydrogenase activity compared to the wild type, whereas rates were not affected in the deltahupG mutant. Immunoblot experiments with HupL- and HupS-specific antisera showed that free-living cultures from deltahupH, deltahupI, and deltahupJ mutants synthesized a fully processed mature HupL protein and accumulated an unprocessed form of HupS (pre-HupS). Both the mature HupL and the pre-HupS forms were located in the cytoplasmic fraction of cultures from the deltahupH mutant. Affinity chromatography experiments revealed that cytoplasmic pre-HupS binds to the HupH protein before the pre-HupS-HupL complex is formed. From these results we propose that hupGHIJ gene products are involved in the maturation of the HupS hydrogenase subunit.


Adjuvant systemic therapy for intermediate and large gastric gastrointestinal stromal tumors (GISTs): Is there a survival benefit following margin negative surgical resection?
The value of adjuvant systemic therapy after margin-negative resection for gastric gastrointestinal stromal tumors (GISTs) remains unclear. The National Cancer Data Base was queried to identify patients undergoing margin negative resections for gastric GISTs >2 cm between 2010 and 2015. Patients were stratified by tumor size (small: 2.1-5 cm, intermediate: 5.1-10 cm, large: >10 cm), histologic grade (low: ≤5 mitoses/50 HPF and high: >5 mitoses/50 HPF), and use of adjuvant therapy. Multivariable cox proportional hazard methods were used to compare overall survival (OS). 3520 patients met inclusion criteria. Adjuvant therapy was associated with a statistical improvement in OS (86% vs. 76%, p = 0.014) for those with large tumors but had no measurable effect in patients with small or intermediate sized tumors. On multivariable analysis, this association was independent of grade. Adjuvant therapy is associated with improved OS for patients with gastric GISTs >10 cm but provides no statistically significant benefit in OS for those with GISTs 2-10 cm.


Testing CREATE at Community Colleges: An Examination of Faculty Perspectives and Diverse Student Gains.
CREATE (Consider, Read, Elucidate the hypotheses, Analyze and interpret the data, and Think of the next Experiment) is an innovative pedagogy for teaching science through the intensive analysis of scientific literature. Initiated at the City College of New York, a minority-serving institution, and regionally expanded in the New York/New Jersey/Pennsylvania area, this methodology has had multiple positive impacts on faculty and students in science, technology, engineering, and mathematics courses. To determine whether the CREATE strategy is effective at the community college (2-yr) level, we prepared 2-yr faculty to use CREATE methodologies and investigated CREATE implementation at community colleges in seven regions of the United States. We used outside evaluation combined with pre/postcourse assessments of students to test related hypotheses: 1) workshop-trained 2-yr faculty teach effectively with the CREATE strategy in their first attempt, and 2) 2-yr students in CREATE courses make cognitive and affective gains during their CREATE quarter or semester. Community college students demonstrated positive shifts in experimental design and critical-thinking ability concurrent with gains in attitudes/self-rated learning and maturation of epistemological beliefs about science.


Increased plasma levels of stromal-derived factor-1 (SDF-1/CXCL12) enhance human thrombopoiesis and mobilize human colony-forming cells (CFC) in NOD/SCID mice.
Stromal-derived factor-1 (SDF-1/CXCL12) is chemotactic for lympho/hematopoietic stem cells. We have previously shown that increasing peripheral blood (PB) levels of SDF-1 with adenovectors expressing human SDF-1 complementary DNA (ad-SDF-1) leads to hematopoietic stem cell mobilization as well as migration of megakaryocytes and thrombocytosis in mice. Herein, we studied the in vivo effects of ad-SDF-1 and of an analogue peptide of SDF-1 (CTCE-0214) on human hematopoiesis in a xenotransplant model. Sublethally irradiated (300 cGY) NOD/SCID mice transplanted with human cord blood mononuclear cells (CB MNC) were injected with ad-SDF-1 (10(9) plaque forming units, i.v., x 1) or CTCE-0214 (10 mg/kg/dose, i.v. q 24 hours x 7). Effects on megakaryocytopoiesis (CD41+ cells and platelets) as well as stem cell mobilization were monitored. CB MNC in NOD/SCID mice are able to differentiate into CD41+ cells and platelets, peaking at week 9 at a mean of 3.7 x 10(3)/microL. i.v. injection of ad-SDF-1 increased human CD41+ cells by day 4 in PB and was followed by an increase in human platelet production by day 5, with return to baseline by day 30. Human colony-forming cells (CFC) were mobilized from bone marrow to spleen (by day 6-13) and to PB (by day 13). Human CD34+ and CD33+ cells were mobilized by this treatment as well. A novel SDF-1 peptide agonist (CTCE-0214) also mobilized human CFC and enhanced human thrombopoiesis. SDF-1 and its analogue may be of clinical value in stimulating platelet recovery after chemo/radiation treatment as well as in stem cell mobilization.


Propranolol Off-Target: A New Therapeutic Option in Neutrophil-Dependent Dermatoses?
Epidermolysis bullosa acquisita (EBA) is a rare subepidermal blistering dermatosis characterized by autoantibodies targeting collagen VII (COL7), an essential component of the anchoring fibrils, located in the sublamina densa of the dermal‒epidermal junction. In EBA, tissue-bound autoantibodies cause the recruitment and subsequent activation of neutrophils, which eventually lead to subepidermal blistering through the release of proteases and ROS. Thus, targeting either pathogenic IgG autoantibodies or neutrophil recruitment or activation has shown efficacy in experimental murine EBA models and patients with EBA. In this issue, Stüssel et al. demonstrate that propranolol, a nonselective β-adrenoreceptor blocker, markedly inhibits the neutrophil release of ROS induced by complexes of COL7 and/or anti-COL7 IgG in vitro and ameliorates the formation of blisters and erosions in an antibody passive-transfer model of murine EBA. These findings warrant further investigations aimed at characterizing the therapeutic efficacy of propranolol in EBA and possibly beyond.


[An experimental study of recombinant adenovirus microsphere carrying antisense multidrug resistance-associated protein gene for reversing MRP of hepatocellular carcinoma in vitro].
To conduct an in vitro study on the effect of recombinant adenovirus microsphere encapusulated antisense MRP (as-mrp) for use in the gene therapy to overcome drug resistance in hepatocellular carcinoma. Recombinant adenovirus microsphere encapusulated as-mrp was transfected into hepatocellular carcinoma multidrug resistance cells HepG2/ADM, the fluorescence intensity of transfected cells were observed at 48 hours and 120 hours after transfection. in vitro drug sensitivity was measured by MTT assay; the resistant index of andromycin resistant variants was determined by drawing the cell dosage reaction curves. The levels of MRP mRNA expression were detected by RT-PCR and the ratio of MRP mRNA/beta-actin was detected. Intracelluar rubidomycin (DNR) concertration was examined by flow cytometry (FCM). More than 90% of the HepG2/ADM cells could be transfected when microspheres being 10 mg. Adv microsphere inhibited the expression of mRNA in HepG2/ADM and enhanced the sensitivity of HepG2/ADM to chemotherapeutic drug. Recombinant adenovirus microsphere encapusulated as-mrp could effectively reverse HepG2/ADM cells, which would provide an experimental basis for the methods of reversing the multidrug resistance in human hepatocellular carcinoma.


Physical-chemical basis of the protection of slowly frozen human erythrocytes by glycerol.
One theory of freezing damage suggests that slowly cooled cells are killed by being exposed to increasing concentrations of electrolytes as the suspending medium freezes. A corollary to this view is that protective additives such as glycerol protect cells by acting colligatively to reduce the electrolyte concentration at any subzero temperature. Recently published phase-diagram data for the ternary system glycerol-NaCl-water by M. L. Shepard et al. (Cryobiology,13:9-23, 1976), in combination with the data on human red cell survival vs. subzero temperature presented here and in the companion study of Souzu and Mazur (Biophys. J.,23:89-100), permit a precise test of this theory. Appropriate liquidus phase-diagram information for the solutions used in the red cell freezing experiments was obtained by interpolation of the liquidus data of Shepard and his co-workers. The results of phase-diagram analysis of red cell survival indicate that the correlation between the temperature that yields 50% hemolysis (LT(50)) and the electrolyte concentration attained at that temperature in various concentrations of glycerol is poor. With increasing concentrations of glycerol, the cells were killed at progressively lower concentrations of NaCl. For example, the LT(50) for cells frozen in the absence of glycerol corresponds to a NaCl concentration of 12 weight percent (2.4 molal), while for cells frozen in 1.75 M glycerol in buffered saline the LT(50) corresponds to 3.0 weight percent NaCl (1.3 molal). The data, in combination with other findings, lead to two conclusions: (a) The protection from glycerol is due to its colligative ability to reduce the concentration of sodium chloride in the external medium, but (b) the protection is less than that expected from colligative effects; apparently glycerol itself can also be a source of damage, probably because it renders the red cells susceptible to osmotic shock during thawing.


Loss of muscle mass during preoperative chemotherapy as a prognosticator for poor survival in patients with colorectal liver metastases.
The survival impact of specific body composition changes during preoperative chemotherapy in patients with colorectal liver metastases undergoing curative-intent surgery remains unclear. This study aimed to determine the impact of changes in body weight and muscle mass during preoperative chemotherapy on survival after hepatectomy in patients with colorectal liver metastases. Consecutive patients with colorectal liver metastases undergoing preoperative chemotherapy and curative hepatectomy during 2009-2013 were retrospectively analyzed. Recurrence-free and overall survival were examined according to body compositions, including muscle mass, as measured by skeletal muscle index (area of muscle [cm2]/square of height [m2]), and body weight before and after preoperative chemotherapy. The median follow-up duration in overall 169 patients was 47 months. Skeletal muscle index and body weight changed significantly during chemotherapy (skeletal muscle index: -0.52 cm2/m2, P = .03; body weight: +1.1 kg, P = .002). Patients with major muscle mass loss (≥7%) had significantly shorter median RFS than patients with no or minor muscle mass loss (<7%) (9.6 months vs 15.9 months; P = .02). Although major muscle mass loss was associated with poor outcome, skeletal muscle index before or after preoperative chemotherapy was not associated with recurrence-free or overall survival. On multivariate analysis, major muscle mass loss was independently associated with poorer recurrence-free survival (hazard ratio, 1.76; P = .045). Major loss of muscle mass but not body weight loss during preoperative chemotherapy is significantly associated with poor recurrence-free survival after hepatectomy in patients with colorectal liver metastases. The mechanisms mediating this association may inform future trials on maintaining muscle mass with dedicated nutrition and exercise programs to improve outcomes.


Development and Validation of a Prediction Model for Atrial Fibrillation Using Electronic Health Records.
This study sought to determine whether the risk of atrial fibrillation AF can be estimated accurately by using routinely ascertained features in the electronic health record (EHR) and whether AF risk is associated with stroke. Early diagnosis of AF and treatment with anticoagulation may prevent strokes. Using a multi-institutional EHR, this study identified 412,085 individuals 45 to 95 years of age without prevalent AF between 2000 and 2014. A prediction model was derived and validated for 5-year AF risk by using split-sample validation and model performance was compared with other methods of AF risk assessment. Within 5 years, 14,334 individuals developed AF. In the derivation sample (7,216 AF events of 206,042 total), the optimal risk model included sex, age, race, smoking, height, weight, diastolic blood pressure, hypertension, hyperlipidemia, heart failure, coronary heart disease, valvular disease, prior stroke, peripheral arterial disease, chronic kidney disease, hypothyroidism, and quadratic terms for height, weight, and age. In the validation sample (7,118 AF events of 206,043 total) the AF risk model demonstrated good discrimination (C-statistic: 0.777; 95% confidence interval [CI:] 0.771 to 0.783) and calibration (0.99; 95% CI: 0.96 to 1.01). Model discrimination and calibration were superior to CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology AF) (C-statistic: 0.753; 95% CI: 0.747 to 0.759; calibration slope: 0.72; 95% CI: 0.71 to 0.74), C2HEST (Coronary artery disease / chronic obstructive pulmonary disease; Hypertension; Elderly [age ≥75 years]; Systolic heart failure; Thyroid disease [hyperthyroidism]) (C-statistic: 0.754; 95% CI: 0.747 to 0.762; calibration slope: 0.44; 95% CI: 0.43 to 0.45), and CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Prior stroke, transient ischemic attack [TIA], or thromboembolism, Vascular disease, Age 65-74 years, Sex category [female]) scores (C-statistic: 0.702; 95% CI: 0.693 to 0.710; calibration slope: 0.37; 95% CI: 0.36 to 0.38). AF risk discriminated incident stroke (n = 4,814; C-statistic: 0.684; 95% CI: 0.677 to 0.692) and stroke within 90 days of incident AF (n = 327; C-statistic: 0.789; 95% CI: 0.764 to 0.814). A model developed from a real-world EHR database predicted AF accurately and stratified stroke risk. Incorporating AF prediction into EHRs may enable risk-guided screening for AF.


Elective nutritional support after major surgery: a prospective randomised trial.
We investigated the possibility that morbidity and mortality might be reduced by giving seven days elective intravenous nutrition after major thoraco-abdominal procedures and total cystectomy. In a prospective parallel randomised double-blind comparison with a standard post-operative fluid regimen, intravenous nutrition had no effect on morbidity, mortality or duration of hospital stay in a group of 122 sequentially recruited patients. This was not due to poor comparability of the patient groups or to failure to give the prescribed treatment. A policy to give post-operative intravenous nutrition routinely to such patients is not likely to prove cost effective. There may be certain patients who might benefit, but we were unable to identify them with a simple pre-operative assessment.


Hybrid elastomer-plastic microfluidic device as a convenient model for mimicking the blood-brain barrier in vitro.
In this study, we fabricated a hybrid elastomer-plastic microdevice using the silicone elastomer poly(dimethylsiloxane) (PDMS) and the plastic polycarbonate (PC), to mimic the human blood-brain barrier (BBB) in vitro. Specifically, the microchannel-imprinted elastomer was first coated with 3-aminopropyltriethoxysilane to produce amine-terminated PDMS. Then, simply by conformal contact at room temperature, the amine-functionalized PDMS was bonded to pristine PC through the formation of urethane linkages. Aside from realizing device bonding, the amine functionalization also assisted in subsequent dopamine coating to form polydopamine and provide a stable surface for culturing human endothelial cells and central nervous system-related cells (e.g., astrocytes) inside the microchannels. Successful mimicking of the BBB-like microenvironment was assessed by 3D co-culturing of human endothelial cells and astrocytes, where the microdevice was verified as an acceptable in vitro BBB model according to the following four criteria: the formation of tight junctions at the cell-cell boundaries of the endothelial cells, evaluated by the expression of the tight junction marker ZO-1; the formation of actin filaments, evaluated using rhodamine phalloidin dye; low permeability, tested using the fluorescent tracer 40-kDa FITC-dextran; and good transendothelial electrical resistance (a measure of the tight junction integrity formed between the endothelial cells). The fabricated PDMS-PC microfluidic device ensured simple yet stable device sealing, and simultaneously enhanced BBB-mimicking cell attachment, thus fulfilling all major criteria for its application as a convenient in vitro BBB model.


Risk assessment of disease recurrence in early breast cancer: A serum metabolomic study focused on elderly patients.
We previously showed that metabolomics predicts relapse in early breast cancer (eBC) patients, unselected by age. This study aims to identify a "metabolic signature" that differentiates eBC from advanced breast cancer (aBC) patients, and to investigate its potential prognostic role in an elderly population. Serum samples from elderly breast cancer (BC) patients enrolled in 3 onco-geriatric trials, were retrospectively analyzed via proton nuclear magnetic resonance (1H NMR) spectroscopy. Three nuclear magnetic resonance (NMR) spectra were acquired for each serum sample: NOESY1D, CPMG, Diffusion-edited. Random Forest (RF) models to predict BC relapse were built on NMR spectra, and resulting RF risk scores were evaluated by Kaplan-Meier curves. Serum samples from 140 eBC patients and 27 aBC were retrieved. In the eBC cohort, median age was 76 years; 77% of patients had luminal, 10% HER2-positive and 13% triple negative (TN) BC. Forty-two percent of patients had tumors >2 cm, 43% had positive axillary nodes. Using NOESY1D spectra, the RF classifier discriminated free-from-recurrence eBC from aBC with sensitivity, specificity and accuracy of 81%, 67% and 70% respectively. We tested the NOESY1D spectra of each eBC patient on the RF models already calculated. We found that patients classified as "high risk" had higher risk of disease recurrence (hazard ratio (HR) 3.42, 95% confidence interval (CI) 1.58-7.37) than patients at low-risk. This analysis suggests that a "metabolic signature", identified employing NMR fingerprinting, is able to predict the risk of disease recurrence in elderly patients with eBC independently from standard clinicopathological features.


Assessment of health risk behaviors. A tool to inform consumers, providers, health care organizations, and purchasers.
Tobacco use, diet and physical activity patterns, and alcohol use are the leading causes of death in the United States. To make major improvements in the health status of the population, behavioral risk factors for disease must be addressed. We propose a brief survey of behavioral risk factors for enrollees of health care organizations, employer groups, or other adult populations that can be used to profile the health risk behaviors of a population, assess performance of prevention and risk reduction programs, or make comparisons with other populations. The survey contains questions about tobacco, diet, physical activity, alcohol, firearms, motor vehicle safety, sexual behavior, and drugs. Recommendations for survey items, implementation, and calculation of performance measures are given. Widespread adoption of this type of survey would be a major step forward in acknowledging the impact that behavior has on health and in furthering individual and organizational accountability for improving health risk behaviors.


Low-carbon electricity generation-based dynamic equilibrium strategy for carbon dioxide emissions reduction in the coal-fired power enterprise.
Climate change is already resulting in extreme devastation in the earth, with carbon dioxide emissions produced by coal-fired power plants being the largest contributor. Therefore, integrated coal purchasing, blending, and distribution strategies are playing a more important role in large-scale coal-fired power enterprises due to the need to reduce carbon dioxide emissions and operational costs. In this study, a dynamic equilibrium strategy for integrated coal purchasing, blending, and distribution under an uncertain environment is proposed to reduce carbon dioxide emissions in large-scale coal-fired powered enterprises; the practicality and efficiency of which are verified using a real-world case. Sensitivity analyses under different carbon dioxide emissions levels and satisfactory degrees were also conducted to give insights into the conflict between economic development and environmental protection for large-scale coal-fired power enterprises, and balance short-term and long-term production plans. The results indicated that the proposed method was able to achieve economic-environmental coordination and sustainable development. Compared to previous studies, the developed model was found to be able to reduce carbon emissions by about 30% compared with the maximum carbon emissions and improve carbon emissions reduction performance to assist in mitigating climate change.


Increased total volume and dopamine β-hydroxylase immunoreactivity of carotid body in spontaneously hypertensive rats.
Under hypertension, it has been reported that the carotid body (CB) is enlarged and noradrenaline (NA) content in CB is increased. Therefore, it is hypothesized that morphological and neurochemical changes in CB are induced in hypertensive animal models. In the present study, we examined the morphological features and dopamine β-hydroxylase (DBH) immunoreactivity in CB of spontaneously hypertensive rats (SHR/Izm) and Wistar Kyoto rats (WKY/Izm). The CB of SHR/Izm was elongated in terms of the cross section of center and was enlarged in the reconstructed images compared with that of WKY/Izm, and the total volume of CB in SHR/Izm (0.048 ± 0.004 mm³) was significantly (p<0.05) increased compared with the value in WKY/Izm (0.032 ± 0.006 mm³). By immunohistochemistry, immunoreactivity for tyrosine hydroxylase in CB was mainly observed in glomus cells and the immunostaining properties were similar between WKY/Izm and SHR/Izm. On the other hand, DBH immunoreactivity was mainly observed in nerve fibers around blood vessels and observed in a few glomus cells in CB of WKY/Izm. The number of glomus cells with strong DBH immunoreactivity was increased in SHR/Izm compared with that in WKY/Izm. In conclusion, the present study exhibited the enlargement of CB as three-dimensional image and revealed the enhanced immunoreactivity for DBH of glomus cells in SHR/Izm. These results suggest that the morphology of CB is affected by the effect of sympathetic nerve and that the signal transduction from CB is regulated by NA in glomus cells under hypertensive conditions.


Profiling posttransplant circulating antibodies in kidney transplantation using donor endothelial cells.
Pathogenesis of antibody (Ab) responses to transplant are yet not well defined. This study aimed to detect and to analyze posttransplant circulating allo-Abs reacting toward graft endothelial cells (ECs) using primary EC cultures prospectively isolated from the transplant donor at the time of transplantation. This study shows a retrospective analysis performed using a dedicated EC crossmatch (ECXM) assay that we developed for the experimental assessment of donor-specific EC-reactive Abs. Donor-specific ECXM was performed by flow cytometry on posttransplant sera (n=256) from an historical cohort of 22 kidney allograft recipients. In this study, we show that 27.3% (6/22) of recipients have a positive ECXM that strictly correlates (100%, 6/6) with the presence of anti-human leukocyte antigen (HLA) Abs posttransplantation. ECXM identifies both donor-specific Abs (DSA; 50%) and non-DSA (50%) reactive to EC. DSA and non-DSA are mostly IgG1 and exhibit peak titers ranging from 1/8 to 1/1024. ECXM indicates that DSA correspond to anti-HLA class II Abs; this immunization is late (M3-M60) but persistent (still detected at M60). In contrast, non-DSA are non-HLA-type Abs reacting with third-party EC and reflecting an early but transient immunization (ended at M3-M12). Our findings demonstrate selective regulatory pathways initiated by anti-HLA class II and non-DSA in graft EC reflected by CCR4 and interleukin 1β up-regulation, respectively. We provide evidence that circulating Abs in HLA-sensitized transplant recipients include both DSA and non-HLA/non-DSA able to bind to graft EC and induce specific gene transcription.


Study of tear film optics and its impact on quality of vision.
To evaluate the relation of the tear film on the quality of vision comparing parameters in normal patients to those having dry eye disease. 50 normal and 50 eyes with dry eye disease (DED) were included in the study. Patients were screened for dry eye with Schirmer's test, tear break up time, ocular surface staining, and assessment of meibomian gland disease. Their quality of vision was assessed using the Optical quality analysis system (OQAS). The results of dry eye evaluation were correlated with the parameters on the OQAS especially the mean objective scatter index (OSI). Patients with dry eye and unstable tear film were found to have a significantly worse quality of vision and optical scatter (P < 0.05). They were also noted to have fluctuation of vision between blinks. Tear film optics can have an important bearing on the quality of vision and quality of life. A detailed assessment preoperatively will help improve surgical outcomes and patient satisfaction.


Exposition of visual stimuli in an aversive situation and self-exposure to light in rats.
The aim of the work presented was to test the effect of associating visual stimuli with an aversive situation on later self-exposure to these stimuli. Forty-five male albino rats (Wistar) aged approximately 90 days were divided into three groups; visual trained in avoidance response to visual stimuli; auditory trained in avoidance response to auditory stimuli; and neutral untrained in avoidance response. In part two of the experiment all the rats were tested in a chamber for self-exposure to light. A statistically significant increase in the rewarding value of visual stimulation was found in the visual group in comparison with the remaining groups. This effect is interpreted as a result of extinction of anxiety response to visual stimuli as a result of which relaxation begins to positively reinforce the response leading to switching on the light.


Apomorphine-induced disruption of prepulse inhibition that can be normalised by systemic haloperidol is insensitive to clozapine pretreatment.
Prepulse inhibition (PPI) of startle refers to the phenomenon in which a weak prepulse attenuates the startle response to a succeeding intense stimulus. PPI can be disrupted by systemic apomorphine in animals, and reduced PPI has been consistently reported in schizophrenia patients. The ability of the atypical antipsychotic clozapine to reverse apomorphine-induced PPI deficit has been demonstrated in the rat, but has not yet been tested in the mouse. The present study was designed to fill this gap. We investigated the efficacy of clozapine in reversing apomorphine-induced (2.0 or 2.5 mg/kg, s.c.) PPI deficit in C57BL6 mice. Clozapine failed to restore PPI disruption in apomorphine-treated mice in two independent laboratories across two dose ranges (1-3 mg/kg, i.p., or 3-30 mg/kg, p.o.), whereas the typical antipsychotic haloperidol (1 mg/kg, i.p.) completely normalised PPI performance. Unlike the rat, apomorphine-induced PPI disruption in mice might be instrumental in distinguishing between typical and atypical antipsychotic drugs. This also lends further support to the suggestion that the neuropharmacology of PPI is not identical in the two rodent species.


Microbial communities in different soil types do not converge after diesel contamination.
To study the comparative effect of diesel addition and simulated bioremediation on the microbial community in three different soil types. Three different soils were amended with diesel and bioremediation treatment simulated by addition of nutrients. The progress of bioremediation, and the effect on the indigenous microbial communities, was monitored using microbiological techniques. These included basal respiration, sole carbon source utilization patterns using both a commercially-available substrate set and a set designed to highlight changes in hydrocarbon-utilizing bacteria, and phospholipid fatty acid (PLFA) profiling. The development of active hydrocarbon-degrading communities was indicated by the disappearance of diesel, increases in soil respiration and biomass, and large changes in the sole carbon source utilization patterns and PLFA profiles compared with control soils. However, comparison of the relative community structure of the three soils using PLFA profiling showed that there was no tendency for the community structure of the three different soil types to converge as a result of contamination. In fact, they became more dissimilar as a result. Changes in the sole carbon source utilization patterns using the commercially-available set of carbon sources indicated the same result as shown by PLFA profiling. The specially selected set of carbon sources yielded no additional information compared with the commercially-available set. Diesel contamination does not result in the development of similar community profiles in different soil types. The results suggest that different soils have different inherent microbial potential to degrade hydrocarbons, a finding that should be taken into account in impact and risk assessments. Following the development of the microbial community and its recovery is a useful and sensitive way of monitoring the impact and recovery of oil-contaminated soils.


Silencing ECHS1 attenuates the proliferation and induces the autophagy of hepatocellular carcinoma via impairing cell metabolism and activating AMPK.
Hepatocellular carcinoma (HCC) is among the most common cancers in the world with a low survival rate. Our previous study showed Short chain enoyl-CoA hydratase (ECHS1) could bind to HBsAg (HBs) and that ECHS1's localization in mitochondria induced HepG2 cell apoptosis. However, the role of the ECHS1 in energy metabolism and autophagy during hepatocellular carcinoma development remains undefined. We aimed to determine what ECHS1 does to energy metabolism and its effects on HCC progression. We performed CCK-8, EdU assays in hepatocellular carcinoma cell lines (HepG2 and HuH7) with stable ECHS1 knock-down. ATP and NADP+/NADPH levels were measured using an colorimetric assay. Our data demonstrated that ECHS1 silencing inhibited cell proliferation and induced autophagy. ECHS1 knockdown did not increase fatty acid synthesis, but decreased cellular ATP. This resulted in AMP-activated protein kinase (AMPK) activation and induced HCC cell autophagy. Our results showed that silencing ECHS1 to attenuate proliferation and induce autophagy may make it a novel cancer therapy target.


Indirect ELISA for the detection of HSV-2 specific IgG and IgM antibodies with glycoprotein G (gG-2).
The glycoprotein G (gG-2) purified from HSV-2 infected cells has been reported to be useful for determination of HSV-2 type-specific antibodies using conventional ELISA formats. This study further confirmed the specificity of gG-2 and demonstrated the feasibility of a specific IgM assay. The gG-2 ELISA was developed to detect HSV-2 specific IgG and IgM antibodies in human sera with high levels of sensitivity and specificity. Of 45 patients with culture-proven recurrent HSV-2 genital infection 44 were reactive for gG-2 IgG. Of 30 sera from patients with culture-proven recent initial HSV-2 genital infection 29 were positive for gG-2 IgM. Three patients with primary HSV-2 genital infection showed gG-2 IgM in the convalescent but not in the acute sera. The IgG- and IgM-gG-2 ELISA showed high specificity. None of 40 sera from children were reactive by either assay. Only one of 94 sera from patients with antibody to herpesviruses other than HSV reacted in the IgG assay but none reacted in the IgM assay. There was no cross-reaction with sera from patients with proven HSV-1 infection with the gG-2 antigen. The results suggest that the IgG assay can be used for demonstration of past HSV-2 infection and the IgM assay for the diagnosis of HSV-2 in neonatal herpes and primary genital herpes, when cultures or rapid diagnostic techniques are unavailable.


Overexpression of an aquaporin gene EsPIP1;4 enhances abiotic stress tolerance and promotes flowering in Arabidopsis thaliana.
Aquaporins are water channel proteins that play an essential role in plant growth and development. Despite extensive functional characterization of aquaporins in model plants such as Arabidopsis, their contributions to abiotic stress tolerance in non-model plants are still poorly understood. As a close relative of Arabidopsis thaliana, Eutrema salsugineum is an excellent model for studying salt tolerance. Here, we identified and functionally characterized EsPIP1;4, a gene encoding a plasma membrane intrinsic protein (PIP) aquaporin in E. salsugineum. Overexpression of EsPIP1;4 in Arabidopsis improved seed germination and root growth of transgenic plants under abiotic stress, which was accompanied by an increase in proline accumulation, reduction in MDA, and decrease in the rate of ion leakage. Under abiotic stress, transgenic plants overexpressing EsPIP1;4 also showed increased antioxidant enzyme activity, and enhanced K+/Na+ ratio compared to control plants. Furthermore, overexpression of EsPIP1;4 promoted flowering by regulating genes in multiple flowering pathways. Together, our results demonstrated that an aquaporin from E. salsugineum improves abiotic stress tolerance and promotes flowering.


Assignment of the gene for glyoxalase I to region p21 leads to pter of human chromosome 6.
Using somatic cell hybrids between TK-deficient mouse cells and white blood cells derived from a patient with a translocation of the region p21 leads to pter of chromosome 17, we have assigned the gene for human GLO, to region p21 leads to pter of chromosome 6. Since the HLA region is only 10 cM distant from GLO, these results also confirm that the HLA region is located on the short arm of human chromosome 6.


Serial changes of CT findings in patients with chronic hypersensitivity pneumonitis: imaging trajectories and predictors of fibrotic progression and acute exacerbation.
To evaluate the longitudinal changes of chest CT findings in patients with chronic hypersensitivity pneumonitis (HP) and identify risk factors for fibrotic progression and acute exacerbation (AE). This retrospective study included patients with chronic HP with follow-up CT. Baseline and serial follow-up CT were evaluated semi-quantitatively. Fibrosis score was defined as the sum of the area with reticulation and honeycombing. The modified CT pattern of Fleischner Society idiopathic pulmonary fibrosis diagnostic guidelines was evaluated. Cox proportional hazards regression was performed to determine significant variables associated with fibrotic progression and AEs. Of 91 patients, mean age was 59.1 years and 61.5% were women. The median follow-up period was 4.9 years. Seventy-nine patients (86.8%) showed fibrotic progression with persistent areas of mosaic attenuation, finally replaced by fibrosis, and 20 (22.0%) developed AE. Baseline fibrosis score and CT pattern of usual interstitial pneumonia (UIP)/probable UIP were independent risk factors for predicting fibrotic progression (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 1.02-1.09, p < 0.001, for fibrosis score; HR = 2.50, CI = 1.50-4.16, p < 0.001, for CT pattern) and AEs (HR = 1.07, CI = 1.01-1.13, p = 0.019, for fibrosis score; HR = 5.47, CI = 1.23-24.45, p = 0.026, for CT pattern) after adjusting clinical covariables. Fibrotic progression and AE were identified in 86.8% and 22.0% of patients with chronic HP. Fibrosis score and CT pattern of UIP/probable UIP on baseline chest CT may predict fibrotic progression and AE. • Most patients (87%) showed fibrotic progression on long-term follow-up with persistent areas of mosaic attenuation that were finally replaced by fibrosis at a later stage. • One-fifth of patients (22%) experienced acute exacerbation associated with worse prognosis. • Fibrosis score (sum of reticulation and honeycombing) and CT pattern of UIP/probable UIP on baseline CT were independent predictors for predicting fibrotic progression and acute exacerbation.


Some relationships between membrane phospholipid domains, conformational order, and cell shape in intact human erythrocytes.
A novel method developed in this laboratory [D.J. Moore et al., Biochemistry 35 (1996) 229-235; D.J. Moore et al., Biochemistry 36 (1997) 660-664] to study the conformational order and the propensity for domain formation of specific phospholipids in intact human erythrocytes is extended to two additional species. Acyl chain perdeuterated 1,2-dilauroylphosphatidylethanolamine (diC12PE-d46) was incorporated preferentially (in separate experiments) into the inner leaflet of stomatocytic erythrocytes and into the outer leaflet of echinocytic erythrocytes, while acyl chain perdeuterated 1,2-dipentadecanoylphosphatidylcholine (diC15PC-d58) was incorporated into the outer leaflet of echinocytic erythrocytes. The conformational order and phase behavior of the incorporated molecules were monitored through FT-IR studies of the temperature dependence of the CD2 stretching vibrations. For both diC12PE-d46 and diC15PC-d58, the gel-->liquid crystal phase transition persisted when these lipids were located in the outer leaflet of echinocytic cells, a result indicative of the persistence of phospholipid domains. In each case, the transition widths were broadened compared to the pure lipids, suggestive of either small domains or the presence of additional molecular components within the domains. The conformational order of diC12PE-d46 differed markedly depending on its location and the morphology of the cells. When located predominantly in the inner membrane of stomatocytes, the phase transition of this species was abolished and the conformational order compared with pure lipid vesicles at the same temperature was much lower. The current results along with our previous studies provide a sufficient experimental basis to deduce some general principles of phospholipid conformational order and organization in both normal and shape-altered erythrocytes.


Course of Plasmodium infection studied using 2D-COS on human erythrocytes.
The threat of malaria is still present in the world. Recognizing the type of parasite is important in determining a treatment plan. The golden routine involves microscopic diagnostics of Giemsa-stained thin blood smears, however, alternative methods are also constantly being sought, in order to gain an additional insight into the course of the disease. Spectroscopic methods, e.g., Raman spectroscopy, are becoming increasingly popular, due to the non-destructive nature of these techniques. The study included patients hospitalized for malaria caused by Plasmodium falciparum or Plasmodium vivax, in the Department of Infectious Diseases at the University Hospital in Krakow, Poland, as well as healthy volunteers. The aim of this study was to assess the possibility of using Raman spectroscopy and 2D correlation (2D-COS) spectroscopy in understanding the structural changes in erythrocytes depending on the type of attacking parasite. EPR spectroscopy and two-trace two-dimensional (2T2D) correlation was also used to examine the specificity of paramagnetic centres found in the infected human blood. Two-dimensional (2D) correlation spectroscopy facilitates the identification of the hidden relationship, allowing for the discrimination of Raman spectra obtained during the course of disease in human red blood cells, infected by P. falciparum or P. vivax. Synchronous cross-peaks indicate the processes taking place inside the erythrocyte during the export of the parasite protein towards the cell membrane. In contrast, moieties that generate asynchronous 2D cross-peaks are characteristic of the respective ligand-receptor domains. These changes observed during the course of the infection, have different dynamics for P. falciparum and P. vivax, as indicated by the asynchronous correlation cross-peaks. Two-trace two-dimensional (2T2D) spectroscopy, applied to EPR spectra of blood at the beginning of the infection, showed differences between P. falciparum and P. vivax. A unique feature of 2D-COS is the ability to discriminate the collected Raman and EPR spectra. The changes observed during the course of a malaria infection have different dynamics for P. falciparum and P. vivax, indicated by the reverse sequence of events. For each type of parasite, a specific recycling process for iron was observed in the infected blood.


Do infants have the horizontal bias?
A robust set of studies show that adults make more horizontal than vertical and oblique saccades, while scanning real-world scenes. In this paper we study the horizontal bias in infants. The directions of eye movements were calculated for 41 infants (M=8.40 months, SD=3.74, range=3.48-15.47) and 47 adults (M=21.74 years, SD=4.54, range=17.89-39.84) while viewing 28 real-world scenes. Saccade directions were binned to study the proportion of saccades in the horizontal, vertical and oblique directions. In addition, saccade directions were also modeled using a mixture of Von Mises distributions, to account for the relatively large amount of variance in infants data. Horizontal bias was replicated in adults and also found in infants, using both the binning and Von Mises approach. Moreover, a developmental pattern was observed in which older infants are more precise in targeting their saccades than younger infants. That infants have a horizontal bias is important in understanding infants' eye movements. Future studies should account for the horizontal bias in their designs and analyses.


Intestinal permeability in small children during and after rotavirus diarrhoea assessed with different-size polyethyleneglycols (PEG 400 and PEG 1000).
The permeability properties of the small intestinal mucosa was investigated in nine previously healthy children with acute diarrhoea due to rotavirus. The investigation was performed after intake of a mixture in water of polyethyleneglycol molecules (PEG 400 and 1000) ranging from 282 to 1250 dalton in molecular weight. The 6-h urinary recovery of the PEGs was determined with high performance liquid chromatography and used to assess the permeability characteristics of the intestine. The patients served as their own controls and were investigated in the same manner after recovery 3-5 weeks later. A significantly lower urinary recovery of PEG was noted for all molecular sizes (326-1206 dalton) during acute diarrhoea in comparison with the results obtained after recovery (p less than 0.001-0.1). There was also a relatively lesser change in the urinary recovery of larger PEG molecules during infection, as reflected by a higher recovery ratio between 1074 and 370 dalton PEGs. The results indicate profound changes in the permeability characteristics of the intestine during acute rotavirus diarrhoea.


The immune modulatory role of marjoram extract on imidacloprid induced toxic effects in thymus and spleen of adult rats.
Imidacloprid (IMID), one of environmental persistent neonicotinoid insecticides, has been used a long time ago and categorized from insecticide induced moderate toxicity by World Health Organization (WHO). Marjoram, is one of the most worldwide used herbs in Egypt due to its antioxidant, anti-inflammatory, anti-genotoxic, anti-mutagenic, anticoagulant, and beneficial effects. This study aimed to evaluate the protective role of marjoram extract on the immunotoxic response and oxidative stress induced by IMID in the immune lymphoid organs (thymus and spleen) of rats. Fifty adult male albino rats were divided randomly into five groups; negative and positive (distilled water) control, marjoram extract (200 mg/kg/day), IMID (22.5 mg/kg/day), marjoram extract + IMID (200 mg/kg +22.5 mg/kg) orally for 8 weeks. Marjoram pretreatment reversed reduced animals body, thymus and spleen weights attributed to IMID. It amended the significantly elevated total leukocytes, neutrophils percentage, increased immunoglobulin G and the significantly reduction of lymphocytes percentage, phagocytic activity, phagocytic index and lysozyme activity induced by IMID. Moreover, marjoram administration significantly reduced thymic and splenic gene expression of interleukin-1β, interleukin-6, tumor necrosis factor-α and increased interleukin-10, in addition, it decreased thymic and splenic contents of malondialdehyde and restored the reduced antioxidant enzymes' activities following IMID exposure. Marjoram ameliorated IMID induced histopathological alterations in thymus and spleen and adjusted IMID immunomodulatory effects by increased the downregulation of CD4 and CD8 immune reactive cell expression. Conclusion, Marjoram has a protective role to reverse IMID immune toxic effects in thymus and spleen tissues of rats by its antioxidant, anti-inflammatory and immunomodulatory defense mechanisms.


Apropos of menstrual changes and abnormal uterine bleeding after COVID-19 vaccination.
It is news of 28 October 2022 that the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency has recommended to add heavy menstrual bleeding among the side effects of unknown frequency inside the package insert of nucleoside-modified messenger ribonucleic acid vaccines to prevent coronavirus disease 2019 (COVID-19). The decision has been made in the light of the numerous reports of unexpected menstrual changes or abnormal uterine bleeding following COVID-19 vaccination. Here we advance a possible involvement of the particular adenohypophyseal microcirculation in these strange and still unexplained events.


Effects of C5a on guinea pig lung: histamine release and mechanism of contraction.
C5a, a product of complement system activation, causes a significant contraction of the isolated guinea pig trachea, and the antihistamine diphenhydramine does not alter the rate, amplitude, or duration of the contraction (Regal et al., 1980). The present study demonstrates that over the range of C5a concentrations investigated, the C5a-induced contractile response of the trachea maximized, whereas the contraction of lung parenchymal strips and the release of histamine from chopped lung did not. In addition, the antihistamines, diphenhydramine and pyrilamine, caused a significant delay in the onset of the C5a-induced contraction of lung parenchymal strips. When parenchymal strips from nonperfused lung were used, the maximum of the contraction was also reduced by pyrilamine. Aspirin and indomethacin effectively inhibited the C5a-induced contraction of lung parenchymal strips, and inhibition by a combination of aspirin and pyrilamine was the sum of the inhibition by aspirin and the inhibition by pyrilamine. The SRS-A antagonist, FPL 55712, caused a more rapid relaxation of the C5a-induced response over control. These studies suggest that products of the cyclo-oxygenase pathway are mediators involved in the C5a-induced contraction of lung parenchyma, with histamine and leukotrienes contributing as well.


Expression of the drug transporters MDR1/ABCB1, MRP1/ABCC1, MRP2/ABCC2, BCRP/ABCG2, and PXR in peripheral blood mononuclear cells and their relationship with the expression in intestine and liver.
ATP binding cassette (ABC)-transporters like P-glycoprotein (multidrug resistance (MDR)1/ABCB1), the multidrug resistance associated proteins 1 and 2 (MRP1/ABCC1 and MRP2/ABCC2), and the breast cancer resistance protein (BCRP/ABCG2) have a large impact on the pharmacokinetics of numerous drugs and may also modulate the effectiveness of drug therapy. Prediction of a patient's susceptibility to xenobiotics and individualization of drug therapy would become possible, if a simple test were available for an easy screening of transporter expression. This study quantified the mRNA expression of the four ABC-transporters and of the pregnane X receptor (PXR), a key regulator in drug metabolism and efflux, in peripheral blood mononuclear cells (PBMCs), and corresponding liver or small intestine samples of humans by real-time reverse transcription-polymerase chain reaction (RT-PCR). The results obtained prove the absence of a correlation between the expression of four major ABC-transporters in PBMCs and in the intestine or liver. For all transporters (except MRP1/ABCC1 in the intestine), mRNA amount of the ABC-transporters was positively correlated with PXR expression in PBMCs and intestine. In conclusion, the study suggests that basal expression levels of the transporters are directly influenced by PXR expression in liver and PBMCs and demonstrates that PBMCs do not qualify as surrogate tissue for the expression of the four ABC-transporters in small intestine and liver. However, the transporter status in PBMCs remains important for drugs, whose primary site of therapeutic action is the lymphocyte and which are known substrates of the transporters.


Muscle disease, HIV and zidovudine: the spectrum of muscle disease in HIV-infected individuals treated with zidovudine.
Eleven patients with AIDS or AIDS-related complex who developed muscle-related symptoms whilst taking zidovudine were investigated. The clinical details of a further ten patients who did not undergo muscle biopsy are also outlined. The clinical features, quantitative muscle strength testing, electromyographic findings, serial creatine kinase levels, muscle biopsy appearance on light microscopy and the effects of zidovudine withdrawal and rechallenge are described. The spectrum of muscle disease encountered included four cases of frank myopathy diagnosed using clinical, electrophysiological and histological criteria, four patients with mild weakness and myalgia in whom muscle biopsies were normal, three patients with myalgia only and a mild increase in the interstitial cell infiltrate shown by biopsy. The patients presenting with myopathy showed no improvement on withdrawal of zidovudine but responded to immunosuppressive therapy with steroids and, in one case, thalidomide prescribed incidentally. At present, it is not yet possible to clinically define a specific zidovudine-induced myopathy that is distinct from the other effects of HIV infection on muscle structure and function. Our experience suggests that zidovudine may be implicated as a myotoxin in some patients, particularly those with myalgia and mild weakness. In those patients with severe weakness, and with biopsy findings of necrosis and inflammation, the drug effects may be difficult to separate from the primary effects of HIV.


Management of severe fibrocystic disease of the breast with leuprolide acetate.
Symptoms of severe fibrocystic disease of the breast were successfully ameliorated in two patients as a result of treatment with daily subcutaneous LA without adverse effects. A state of drug-induced hypogonadotropic hypogonadism appears to be responsible for the clinical effect and is further suggestive of the hormonal dependence of this common disorder.


Risk-adjusted analysis of survival variability among hospitals treating biliary malignancy.
Biliary tract cancer's (BTC) treatment main stone for advanced stages is constituted by chemotherapy. Surgical centralization and physicians' confidence in the use of new technologies and molecular analysis turned out to be of interest and potentially influencing survival. After applying a random-effect model, the relationship between each clinical variable on the main outcome was investigated through multilevel mixed-effects logistic regression. The risk-standardized outcomes were calculated for each centre involved. In the unadjusted cohort the median survival was 8.6 months (95%C.I.: 7.8-9.3) with a 9-month survival rate of 48.3% (95%C.I.: 45.0-51.5). A substantial heterogeneity across hospitals was found (I2: 70.3%). In multilevel mixed effect logistic regression, male, being treated for gallbladder cancer, higher ECOG, increased NLR, CEA and Ca 19.9 and low value of haemoglobin showed to increase the odds for 9-month mortality. The model estimated that the residual variance observed in 9-month mortality was attributable for the 2.6% to the treating hospital. Through a multilevel mixed effect model, average risk-standardized mortality within 9 months was 50.1%. As noticeable, all hospital's risk-standardized mortality falls within 95%C.I., thus all participating centres provided similar outcomes when adjusted for patient case-mix. Heterogenicity between hospital did not affect the outcome in term of overall survival.


Accurate alignment and high function after kinematically aligned TKA performed with generic instruments.
Performing kinematically aligned total knee arthroplasty (TKA) with generic instruments is less costly than patient-specific instrumentation; however, the alignment and function with this new technique are unknown. One hundred and one consecutive patients (101 knees) treated with kinematically aligned TKA, implanted with use of generic instruments, were prospectively followed. The medial collateral ligament was not released. The lateral collateral ligament was released in the 17 % of patients with a fixed valgus deformity. Six measures of alignment were categorized from a scanogram of the extremity, an axial scan of the knee, and an intraoperative measurement. Both the Oxford Knee and WOMAC™ scores were assessed as function. High function was a mean Oxford Knee score >41. The frequency that patients were categorized as in-range was 93 % for the mechanical alignment of the limb (0° ± 3°), 94 % for the joint line (-3° ± 3°), 57 % for the anatomic axis of the knee (-2.5° ± -7.4° valgus), 4 % for the varus-valgus rotation of the tibial component (≤0° valgus), 98 % for the rotation of the tibial component with respect to the femoral component (0° ± 10°), and 94 % for the intraoperative change in the anterior-posterior distance of the tibia with respect to the femur at 90° of flexion (0 ± 2 mm). The mean OKS score was 42, and WOMAC™ score was 89. For each alignment, the function was the same for patients categorized as an outlier or in-range. The authors prefer the use of generic instruments to perform kinematically aligned TKA in place of mechanically aligned TKA because five of six alignments were accurate and because high function was restored regardless of whether patients had an alignment categorized as an outlier or in-range. IV.


A retino-pulvinar projection in the macaque monkey as visualized by the use of anterograde transport of horseradish peroxidase.
A direct retino-pulvinar connection was found in the Japanese monkey (Macaca fuscata) by the anterograde horseradish peroxidase (HRP) method. HRP injected into the vitreous cavity of one eye labeled a few small clusters of optic fiber terminals in the medial border regions of the inferior pulvinar nucleus bilaterally, with a contralateral predominance.


Application of family-centered empowerment model in primary caregivers of premature infants: A quasi-experimental study.
To explore the effect of the family-centered empowerment model (FECM) on reducing anxiety, improving care ability, and readiness for hospital discharge of main caregivers of preterm infants. The primary caregivers of preterm infants who were admitted to the Neonatal intensive care Unit (NICU) of our center from September 2021 to April 2022 were selected as the research objects. According to the wishes of the primary caregivers of preterm infants, they were divided into group A (FECM group) and group B (non-FECM group). The intervention effects were evaluated with the Anxiety Screening Scale (GAD-7), the Readiness for Hospital Discharge Scale-Parent Version (RHDS-Parent Form), and the Primary Caregivers of Premature Infants Assessment of Care Ability Questionnaire. Before the intervention, there was no statistically significant difference in the general information, anxiety screening, the scores of each dimension, and total score of the comprehensive ability of the main caregivers, and the score of caregiver preparedness between the two groups (P > 0.05). After the intervention, there were statistically significant differences in the anxiety screening, the total score and total score of each dimension of the care ability, and the score of caregiver preparedness between the two groups (P < 0.05). FECM can effectively reduce the anxiety of primary caregivers of premature infants and improve their readiness for hospital discharge and care ability. To improve the quality of life of premature infants by implementing personalized training, care guidance, and peer support.


Influence of low-molecular-weight aggregates on aggregate growth kinetics and physical properties of solid-state proteins during storage.
Low-molecular-weight (LMW) aggregate is a critical determinant of subsequent protein aggregation, but the aggregate growth kinetics of solid proteins have not been fully characterized. In this study, the high-molecular weight (HMW) aggregate formation process for solid-state proteins and the relationship between aggregation and physical properties of tablets were evaluated using proteins with various initial aggregate ratios. Quantitative changes in monomers, LMW aggregates, and HMW aggregates during storage were measured. The monomer amount decreased uniformly for all proteins. Proteins with low initial LMW aggregates showed remarkable increases in LMW aggregates but little increases in HMW aggregates during storage. Proteins with high initial LMW aggregates showed decreases in LMW aggregates but remarkable increases in HMW aggregates. A correlation analysis and logistic regression indicated that HMW aggregate formation depended on the initial quantity of LMW aggregates. Furthermore, the initial LMW aggregate ratio was related to the disintegratability of protein-containing tablets after storage. These results provide novel insight into solid-state protein aggregation and may guide the prediction of the long-term quality of solid protein-containing pharmaceuticals and foods without storage.


MR analysis of the substantia innominata in normal aging, Alzheimer disease, and other types of dementia.
The substantia innominata can be visualized on coronal thin-section T2-weighted MR images. The purpose of this study was to investigate the morphologic changes of the substantia innominata in normal aging by using MR imaging and to determine whether the changes in this structure on MR images were specific to Alzheimer disease (AD). The thickness of the substantia innominata was measured on the coronal T2-weighted image obtained through the anterior commissure in 39 healthy control subjects (age range, 25-86 y; mean age, 62 y); 39 patients with AD; and 36 patients with non-AD dementia, including vascular dementia, frontotemporal dementia, and Parkinson disease with dementia. In the control subjects, the thickness of the substantia innominata significantly decreased with age. Compared with age-matched control subjects, both patients with AD and patients with non-AD dementia had significant atrophy of the substantia innominata. The thickness of the substantia innominata significantly correlated with scores from the Mini-Mental State Examination in patients with AD but not in patients with non-AD dementia. MR analysis reveals age-related shrinkage of the substantia innominata. Atrophy of the substantia innominata, which reflects degeneration in the nucleus basalis of Meynert, is pronounced both in patients with AD and in those with non-AD dementia. MR imaging features in this structure may not be specific to AD.


Comparison of manufactured and black carbon nanoparticle concentrations in aquatic sediments.
In this paper, we show that concentrations of manufactured carbon-based nanoparticles (MCNPs) in aquatic sediments will be negligible compared to levels of black carbon nanoparticles (BCNPs). This is concluded from model calculations accounting for MCNP sedimentation fluxes, removal rates due to aggregation or degradation, and MCNP burial in deeper sediment layers. The resultant steady state MCNP levels are compared with BCNP levels calculated from soot levels in sediments and weight fractions of nanosized fractions of these soot particles. MCNP/BCNP ratios range from 10(-7) to 10(-4) (w:w). This suggests that the often acclaimed effect of MCNPs on organic pollutant binding and bioavailability will likely be below the level of detection if natural BCNPs are present, even if binding to MCNP is one to two orders of magnitude stronger than to BCNPs. Furthermore, exposure and toxic effects of MCNPs in sediments and soils will be negligible compared to that of BCNPs.


Skeletal muscle deoxygenation responses during treadmill exercise in children.
Muscle O₂ saturation (SmO₂) and blood volume response in activating muscles during treadmill exercise were compared between prepubertal boys (n = 9, age: 9 ± 1 years) and young men (n = 9, age: 22 ± 2 years). SmO₂ and blood volume responses were monitored continuously during the exercise at the gastrocnemius medialis muscle by near infrared spatial resolved spectroscopy. SmO₂ was significantly decreased only at peak exercise in the boys, even though a significant decrease in SmO₂ was observed at 60, 80, and 100 % of peak O₂ uptake in the men (p < 0.05). No significant increase in blood volume was observed in the boys, while blood volume was significantly increased in the men with increased exercise intensity (p < 0.05). These results suggest that both blood volume and deoxygenation response in activating muscle may be minor in prepubertal boys, compared to young men. The blunted deoxygenation response in prepubertal boys may be caused by undeveloped diffusive O₂ transport (i.e. mitochondrial respiration).


The link between seizures and prolactin: A study on the effects of anticonvulsant medications on hyperprolactinemia in rats.
Seizures are a common neurological disorder that affects people of all ages. These sudden, uncontrolled electrical disturbances in the brain can cause a variety of symptoms, including convulsions, loss of consciousness, and abnormal sensations. While seizures have long been recognized as a potential cause of hormonal imbalances, recent research has shed new light on the link between seizures and prolactin. The study involved 30 adult female Wistar rats, which were divided into a control group (treated with normal saline) and four treatment groups: chronic group (treated with 30 mg/kg pentylenetetrazol intraperitoneally three days a week for 10 weeks), chronic + Levetiracetam (50 mg/kg, gavage), chronic + Cabergoline (0.05 mg/kg, gavage), and chronic + Levetiracetam (25 mg/kg) + cabergoline (0.025). The drugs were administered three days a week for 10 weeks. Field action potentials were recorded from the CA1 area of the hippocampus using eLab after anesthetizing the animals with a ketamine-xylazine combination (70 +7 mg/kg). The prolactin levels were measured using the ELISA method after serum preparation. The findings indicate that the use of levetiracetam as an anticonvulsant drug resulted in a significant decrease in the amount of prolactin and spike number of convulsive activities compared to the chronic group. However, the amplitudes of convulsive activities did not show a significant difference between the control and other treatment groups. In conclusion, investigating the possibility of subclinical seizures and utilizing anticonvulsant medications in hyperprolactinemia that is resistant to treatment are crucial in treating infertility.


Spatiotemporal variation in the water quality of Vembanad Lake, Kerala, India: a remote sensing approach.
Water quality is one of the essential parameters of environmental monitoring; even a slight variation in its characteristics may significantly influence the ecosystem. The water quality of Vembanad Lake is affected by anthropogenic effects such as industrial effluents and tourism. The optical parameters representing water quality, such as diffuse attenuation (Kd), turbidity, suspended particulate matter (SPM), and chlorophyll-a (Chl-a), are considered in this study to evaluate the water quality of Vembanad Lake, Kerala, India. As this lake is regarded as of ecological importance by the Ramsar Convention and has faced severe concerns over recent years, there was a substantial change in the water quality during the lockdowns of the COVID-19 pandemic. This research is aimed at examining the change in water quality using optical data from Sentinel-2 satellites in the ACOLITE processing software from 2016 to 2021. The analyses showed a 2.5% decrease in the values of Kd, whereas SPM and turbidity show a reduction of about 4.3% from the year 2016 to 2021. The flood and the COVID lockdown had an impact on the improvement in the quality of water from 2018 to 2021. The findings indicated that the reduction in industrial activities and tourism had a more significant effect on the improvement in the water quality of the lake. There was no substantial change in the Chl-a until 2020, whereas an average decrease of 12% in Chl-a values was observed throughout 2021. This decrease can be attributed to the reduction in the lake's hydrological residence time (HRT). Thus, these findings will be a valuable reference to help the government and non-government organizations (NGO) during strategic planning.


Conservative management in an elderly woman with proximal humeral head fracture and massive rotator cuff tear who refused surgery: A case report.
Proximal humerus fractures (PHFs) account for between 4% and 10% of all fractures in the elderly people and osteoporosis is frequently related to PHF. Furthermore, rotator cuff (RC) tears are also extremely common, affecting at least 10% of people aged over 60 in the United States. Among shoulder pathologies, the periarticular soft tissue disorders, including the RC, this is considered to be the most common. The incidence of full thickness RC tears increases with age. An aggressive surgical approach is often required for patients with massive RC tear and PHFs to restore the patients' functional daily living activities. To the best of the authors' knowledge, this is the first case report describing a successful conservative management in an elderly patient with a full thickness RC tear and PHF that refused surgery. This report describes the case of a 90-year-old woman with a massive RC tear who fell over on the sidewalk and sustained a PHF. The patient refused surgery even though it was recommended and prescribed by an orthopaedic surgeon. After having her shoulder immobilized with a brace as prescribed by the orthopaedic physician, the patient began a shoulder rehabilitation program with progressive work load exposure, functional movements and a pain and kinesiophobia education program. After 3 and a half months, the patient achieved full recovery to her pre-injury level of function. Such outcome was assessed using the Numeric Pain Rating Scale (NPRS), the Disability of the Arm, Shoulder and Hand (DASH) scale, the Fear-Avoidance Beliefs Questionnaire (FABQ), the Pain Catastrophysing Scale (PCS), and the Global Rating of Change (GROC) scale. In an elderly patient with a massive RC tear and an undisplaced PHFs, patient education, pain reconceptualization and change of beliefs in combination with progressive work load exposure appeared to be an effective management strategy to achieve a return to the pre-injury level of function.