Development of a Highly Sensitive and Rapid Liquid Chromatography-Tandem Mass Spectrometric Method Using a Basic Mobile Phase Additive to Determine the Characteristics of the Urinary Metabolites for Niemann-Pick Disease Type C.
As Niemann-Pick disease type C (NPC) is difficult to diagnose owing to its various clinical symptoms; biomarker tests have been developed. Previously, we revealed urinary sulfated cholesterol metabolites as noninvasive biomarkers for NPC. However, LC/tandem mass spectrometry (LC/MS/MS) requires long separation time and large urine volumes. Recently, a basic mobile phase was reported to increase the MS intensity. Thus, we developed a highly sensitive and rapid LC/MS/MS method for analyzing urinary cholesterol metabolites using a basic mobile phase additive. 3β-Sulfooxy-7β-N-acetylglucosaminyl-5-cholenic acid, its glycine and taurine conjugates, 3β-sulfooxy-7β-hydroxy-5-cholenic acid, and 7-oxo form were measured, with selected reaction monitoring in negative ion mode. Oasis HLB and L-column 3 were used for column-switching LC/MS/MS and urine diluted 10-fold was employed as the sample. After trapping, gradient separation was performed using solutions containing 1% (v/v) ammonium solution. On average, a 16-fold increase in peak areas was observed compared to that obtained at pH 5.5 with the mobile phases. Although the previous method needed 60 min for separation from interference peaks, we succeeded to separate them in 7 min with optimized LC condition. Further, all compounds showed good linearity from 0.3-1000 ng/mL, with satisfactory intra- and inter-day reproducibility. The developed method was applied to the urinalysis of healthy participants and NPC patients. Overall, the concentrations of metabolites correlated with those obtained using the previous method. Therefore, we succeeded to increasing MS intensity and shorten LC running time; and the method is useful for the noninvasive diagnostic screening of patients with NPC.


Effect of organic acids on numbers of yeasts and mould fungi and aerobic stability in the silage of corn.
The aim of these studies was to assess the effect of chemical conservants (FA = formic acid, PA = propionic acid, FPA+i = formic acid, propionic acid and ammonium ions) on the cell counts of yeasts and mould fungi in silage. The silage was prepared from corn (Zea mays L), cultivar Buran FAO (240). The effect of the applied conservants on silage aerobic stability was also assessed. The performed chemical analyses comprised the determination of: the content of dry matter (DM), lactic acid (LA), acetic acid (AA), ethanol, water soluble sugars (WSC), crude protein (CP) and pH. The applied preparations were found to reduce the number of yeast and mould fungi cells in all the examined silages. The growth of fungi was inhibited most strongly by the FPA+i preparation (containing a mixture of formic and propionic acids and ammonium ions). The yeast cell counts dropped (P<<0.05) from 8.50 107 CFU g(-1) silage in the control (CCS = control corn silage) to 2.60 107 CFU g(-1) in silage treated with FPA+i, whereas counts of the mould fungi cells - from 15.20 104 CFU g(-1) silage in the control to 4.60 104 CFU g(-1) in silage treated with FPA+i. The applied conservants increased (P<<0.05) the content of DM from 255.00 g kg(-1) in control to 266.60 g kg(-1) with PA, WSC from 27.10 g kg(-1) DM to 30.50 g kg(-1) DM with FPA+i and ethanol from 9.10 g kg(-1) DM to 11.21 g kg(-1) DM with FPA+i in the silage. The additives decreased concentrations of lactic acid, acetic acid and crude protein concentration after opening the barrels. The diversifying factors decreased the pH value in the examined silage. The experimental conservants were found to improve the aerobic stability of silages after 7 days of air exposure.


Organizational justice and Black applicants' reactions to affirmative action.
Using organizational justice as a guiding framework, the authors studied perceptions of affirmative action programs by presumed beneficiaries. Three conceptual issues were addressed: (a) the content of different affirmative action plans; (b) the 3-way interaction among distributive, procedural, and interactional justice; and (c) the distinction between outcome favorability and distributive justice. These ideas were tested with a sample of Black engineering students who responded to 1 of 6 plans. Participants distinguished among the various plans, with some policies being viewed as more fair than others. In addition, a 3-way interaction among the 3 types of organizational justice was observed. Specifically, the 2-way interaction between distributive and interactional fairness was only significant when procedural justice was low. Implications for organizational justice and for the design of affirmative action programs are discussed.


Brigham Eyebrow Tool for Alopecia: A Reliable Assessment of Eyebrow Alopecia Areata.
There are no tools to evaluate eyebrow involvement in patients with alopecia areata. We developed and assessed the reliability of the Brigham Eyebrow Tool for Alopecia (BETA) as a quantitative evaluation of eyebrow alopecia areata. BETA uses facial landmarks of eyebrow anatomy and is calculated using surface area and density. A total of 50 eyebrow images with varying levels of hair loss were distributed to six board-certified dermatologists at three academic medical centers with standardized instructions and examples. Interrater and intrarater reliability were calculated using intraclass correlation coefficients (ICCs). BETA demonstrated high interrater (ICC = 0.88, confidence interval = 0.83-0.92 right eyebrow scores and ICC = 0.90, confidence interval = 0.85-0.94 left eyebrow scores) and intrarater (ICC = 0.90, confidence interval = 0.85-0.93 right eyebrow scores and ICC = 0.91, confidence interval = 0.87-0.94 left eyebrow scores) reliability. When measured in the same patient with varying degrees of hair loss over time, BETA demonstrated sensitivity to change. BETA is a simple and reliable objective assessment of eyebrow alopecia areata. BETA is easy-to-use and quick to calculate, making it feasible for a variety of clinical and research settings. Although developed for alopecia areata, we hope that BETA will be investigated in other etiologies of eyebrow alopecia to serve as a universal tool for monitoring disease progression, improvement, and response to treatment.


The influence of cytosolic phosphoglucomutase on photosynthetic carbohydrate metabolism.
The aim of this work was to examine the role of cytosolic phosphoglucomutase (cPGM; EC 18.104.22.168) in photosynthetic carbon partitioning. We have previously described the generation and characterisation of the tuber metabolism of transgenic potato ( Solanum tuberosum cv. Desiree) lines expressing the StcPGM gene in the antisense orientation under the control of the 35S promoter. Here we extend the characterisation of leaf metabolism within these lines, examining properties of gas exchange, carbon partitioning, and the effect of the genetic manipulation on a wide range of metabolites including metabolites of the sucrose-starch transition, glycolysis, the Krebs cycle and amino acid metabolism. The data acquired in the present study surprisingly reveal that the photosynthetic sucrose synthetic capacity of the leaves is largely unaltered but that these plants display a reduced rate of photosynthesis, a dramatic reduction in nucleotide levels, and a general decline of biosynthesis. We conclude that these lines exhibit only moderate changes in sucrose synthesis but more complex changes on a range of diverse metabolic pathways.


Psoriatic arthritis.
Psoriatic arthritis is a common form of arthritis. It is recognized that there is a subset of patients who have a severe, disabling form of the disease, and that patients need to be treated earlier if a good outcome is to occur. The pathogenesis of psoriatic arthritis is still unclear, but the "experiment of nature" provided by the HIV infection may help further outline the causative mechanisms. Newer modalities of therapy are being investigated.


Photomultiplying Visible Light Detection by Halide Perovskite Nanoparticles Hybridized with an Organo Eu Complex.
A molecular layer of an organo europium (Eu) complex was hybridized with the surface of halide perovskite (MAPbI3) nanocrystals to control charge transport between photoexcited perovskites and a metal electrode. A thin hybridized nanocrystalline film was found to cause an efficient photomultiplication reaction based on hole accumulation at photoexcited perovskite nanoparticles and charge tunneling across the Eu complex molecules under application of a low external bias (-0.5 V). A photodetecting device based on the Eu complex and perovskite absorber demonstrated photoinduced current generation at extremely high quantum conversion efficiency of 290 000% for weak monochromatic light (<1 mW cm-2), yielding a power responsivity value up to 1289 A W-1. High sensitivity of photodetection was enabled by using nanosized particles (<5 nm) of perovskite having a high surface area in contact with the Eu complex, while sensitivity was reduced by use of thick and large particle perovskite layers.


[A preliminary study of pharmacokinetics of evodiamine hydroxypropyl-β-cyclodextrin inclusion complex].
To compare the pharmacokinetic parameters of evodiamine hydroxypropyl-β-cyclodextrin inclusion complex and free evodiamine suspension in rats, and investigate the pharmacokinetic characteristics of evodiamine inclusion complex. Both water solubility and cumulative release percentage of EHD were tested with evodiamine as the control. Blood samples were collected from the venous plexus of SD rats after intravenous administration with evodiamine inclusion complex and free evodiamine at 100 mg/kg (equivalent evodiamine dose). Plasma concentrations of evodiamine were determined by high-performance liquid chromatography (HPLC), and the pharmacokinetic parameters were calculated using DAS 2.1.1. The evodiamine inclusion complex showed a better water solubility (18.46±0.36 µg/mL) and a higher cumulative release percentage [(76.8±4.9)%] than free evodiamine. The pharmacokinetic parameters of evodiamine inclusion complex and free evodiamine in rats were as follows: Cmax, 252.5±12.43 vs 161.3±3.45 µg/L; T(max), 4.00±0 vs 4.07±0 h; MRT(0-∞), 8.46±0.91 vs 4.43±0.74 h; AUC(0-t), 2266.40±28.64 vs 911.92±8.53 µg·L(-1)·h(-1); AUC(0-∞), 2359.76±31.58 vs 919.16±9.73 µg·L(-1)·h(-1). The relative bioavailability of evodiamine inclusion complex was 256.73%. Compared with free evodiamine, evodiamine inclusion complex has a higher bioavailability.


Probable warfarin and dapsone interaction.
We describe a case of a 41-year-old woman who was stable for over a year on 22.5 mg/week of warfarin. At a follow-up visit, her international normalized ratio (INR) was found to be supratherapeutic at 3.9. Her only significant change was acyclovir initiation for shingles, and clindamycin and dapsone for infection on her right foot. An interaction report was run using Micromedex with no interactions reported. Sixteen percent of the weekly dose was held and maintenance dose was continued. Two weeks later, the INR remained supratherapeutic at 4.3, with discontinuation of clindamycin and dapsone, 5 days earlier, as the only change. This time an interaction report was run using Lexi-Comp, which identified an interaction between warfarin and dapsone. The INR has been therapeutic and stable since discontinuation of transient factors. It is hypothesized that warfarin and dapsone compete for binding on the CYP2C9 and CYP3A4 isoenzymes and therefore serum concentration of warfarin was elevated.


Distribution of Marine Lipophilic Toxins in Shellfish Products Collected from the Chinese Market.
To investigate the prevalence of lipophilic marine biotoxins in shellfish from the Chinese market, we used hydrophilic interaction liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure levels of okadaic acid (OA), azaspiracid (AZA1), pectenotoxin (PTX2), gymnodimine (GYM), and spirolide (SPX1). We collected and analyzed 291 shellfish samples from main production sites along a wide latitudinal transect along the Chinese coastline from December 2008 to December 2009. Results revealed a patchy distribution of the five toxins and highlighted the specific geographical distribution and seasonal and species variation of the putative toxigenic organisms. All five lipophilic marine biotoxins were found in shellfish samples. The highest concentrations of OA, AZA1, PTX2, GYM, and SPX1 were 37.3, 5.90, 16.4, 14.4, and 8.97 μg/kg, respectively. These values were much lower than the legislation limits for lipophilic shellfish toxins. However, the value might be significantly underestimated for the limited detection toxins. Also, these toxins were found in most coastal areas of China and were present in almost all seasons of the year. Thus, these five toxins represent a potential threat to human health. Consequently, studies should be conducted and measures should be taken to ensure the safety of the harvested product.


A Cautionary Tale: Exploring Stakeholder Emotions During Curricular Change Using Group Concept Mapping.
PhenomenonCurricular change is essential but challenging. Change efforts often struggle and some fail due to well-articulated challenges as well as other barriers less understood. The curricular change literature characterizes the organizational and operational features of successful change yet virtually ignores stakeholder emotions. A deeper understanding of these emotional responses during the change process could enhance participant and organizational well-being and support change success. Approach In 2019, data were collected at one large North American medical school using group concept mapping methodology, an asynchronous mixed methods approach. We sought to generate themes characterizing the emotional responses of faculty, administrative staff, and students across multiple stakeholder groups participating in the new and traditional (legacy) curricula 27 months after curricular change initiation. Participants brainstormed, sorted, and rated statements on emotional responses. Rating participants rated each statement using a Likert scale from 1 (does not resonate) to 4 (very strongly resonates) according to this prompt: "This emotional response resonates with my emotional experience during the curricular change." Multidimensional scaling and hierarchical cluster analyses were used to generate emotional profiles and compare them across stakeholders. Findings Of 335 stakeholders invited, 123 contributed to brainstorming (36.7%), 153 completed rating (45.7%) and 33 completed sorting (9.9%). Participants generated six themes of emotional responses to curricular change: enthusiastic, apprehensive, overwhelmed, missed opportunities, uncertain, and abandoned. The enthusiastic theme overall had the highest mean statement ratings while the abandoned theme had the lowest. Demographic subgroup analysis revealed new curriculum students (Class of 2021) were most enthusiastic while legacy curriculum students (Class of 2020) were more likely to feel abandoned. Overall, faculty and administrative staff were more enthusiastic than students whereas students rated the five other themes higher than faculty and administrative staff. InsightsCurricular change is emotionally taxing. Students in both curricula experienced greater uncertainty, apprehension, sense of missed opportunities, and feeling overwhelmed than did faculty and administrative staff. Legacy curriculum students rated statements in the abandoned cluster highest while new curriculum students rated statements in the enthusiastic cluster highest. Given the ubiquity of curricular change which often includes a legacy cohort, medical schools embarking on this journey must carefully attend to the varied emotional responses of their different stakeholder groups. The very activities recommended by organizational change models used in medical education, such as communicating wins early and often, could alienate legacy students, creating emotional polarization. These findings suggest that tailored communication strategies are necessary during change implementation to optimize success.


Locoregional and radioisotopic targeted treatment of neuroendocrine tumours.
Gastro-entero-pancreatic neuroendocrine tumours (GEP NET) are a heterogeneous group of proliferative disorders whose management dramatically relies on tumour biology. For well-differentiated, low-proliferative index tumours, locoregional treatment and targeted radioisotopic therapies offer an attractive and seemingly efficient alternative to palliative surgical resections. Lack of well-designed, prospective, randomized multicentric studies hinders a balanced evaluation of available locoregional treatment methods: embolization, chemo-embolization, radio-embolization. According to available datas, all techniques achieve a 50-60% radiological response rate and almost 80% of symptomatic relieve for the patients, while their impact on progression-free and overall survival remains not assessable. Same conclusions can be drawn for radiolabeled targeted therapies like MetaiodoBenzylGuanidine (MIBG) and Peptide Receptor Radionuclide Therapy (PRRT), which, provided that their target is expressed by tumour cells, can deliver therapeutic doses of radiation to neoplastic tissues. 131I-MIBG has been associated with a 50% symptomatic response rate and mainly haematological toxicities. PRRT with 111In-DiethyleneTriamineentaacetic Acid-Octreotide, [90Y-DOTA0-Tyr3]-Octreotide, or [177Lu-DOTA0-Tyr3]-Octreotate seem to alleviate symptoms in 50% of patients and obtain a radiological response in 30-38%. Renal toxicity, partially preventable, is more frequent than previously thought and result in an annual decrease in glomerular function by 4 to 8% per year. Forthcoming research in GEP NET should by a majority be designed in randomized, prospective and multicentric fashion. Locoregional disease trials must focus on clinical outcome differences between embolization techniques (embolization, chemoembolization and radioembolization) and surgery. In disseminated disease, studies should assess radiolabeled targeted therapies efficiency when administered along with and compared to new biological and older chemotherapeutic agents.


Vulnerable elderly patients and overactive bladder syndrome.
Overactive bladder (OAB) prevalence increases with age, and the elderly population is rapidly increasing worldwide, particularly those aged >or=75 years. OAB symptoms may be associated with co-morbid conditions, particularly bowel symptoms and falls related to nighttime lavatory trips, as well as with higher rates of mortality in elderly persons. Physical changes associated with age that result in altered bladder function and altered drug solubility, metabolism and clearance, as well as increased polypharmacy, may impact disease management in elderly patients. Clinical trial data indicate that current treatments for OAB are generally effective and well tolerated in elderly patients. However, clinical trial participants have generally been relatively healthy persons aged >or=65 years, which may not reflect the true elderly population. Limited data exist that are specific to the vulnerable elderly, who have been defined as patients aged >or=65 years who are at increased risk of functional decline or death over a 2-year period. Identification and treatment of vulnerable elderly patients with OAB is important, because intervention may limit functional deterioration. Antimuscarinics are associated with improvement in OAB symptoms and health-related quality of life in older patients, although adverse effects such as constipation may be of particular concern in vulnerable elderly patients. Additional research is needed on the potential impact of antimuscarinics on cognition in vulnerable elderly persons. Behavioural interventions, including biofeedback, prompted voiding and pelvic floor muscle exercises, may be effective in some elderly patients without risk of adverse events, and they may enhance the efficacy of antimuscarinic treatment. The International Consultation on Incontinence has recommended behavioural interventions with the cautious addition and trial of antimuscarinic drugs for the treatment of urinary incontinence in frail elderly individuals or those already in a state of decline; these recommendations may also be useful for vulnerable individuals. Greater representation of vulnerable elderly individuals in clinical trials, the development and inclusion of outcomes relevant to this population, and the creation and testing of validated, evidence-based models to guide treatment decisions in vulnerable elderly individuals are needed.


The next meta-challenge for Bioinformatics.
The direct sequencing of uncultivable organisms present in complex biological and environmental samples has opportunities to discover new life forms and metabolic processes. This transformational field, known as metagenomics, is generating massive amounts of molecular information that can overwhelm the performance of conventional analysis and visualization algorithms. Here, I briefly highlight some of the emerging challenges this new discipline presents to the computational biology community and point some of the opportunities to develop applications that can translate metagenomic information into biomedical, agricultural, environmental, and industrial applications.


Small GTPase RBJ promotes cancer progression by mobilizing MDSCs via IL-6.
RBJ has been identified to be dysregulated in gastrointestinal cancer and promotes tumorigenesis and progression by mediating nuclear accumulation of active MEK1/2 and sustained activation of ERK1/2. Considering that nuclear accumulation and constitutive activation of MEK/ERK not only promotes tumor progression directly, but also induces chronic inflammation, we wonder whether and how RBJ impairs host immune-surveillance via chronic inflammation and consequently supports tumor progression. Here, we report that higher expression of RBJ in human breast cancer tissue has been significantly correlated with poorer prognosis in breast cancer patients. The forced expression of RBJ promotes tumor growth and metastasis both in vitro and in vivo. In addition, more accumulation of immune suppressive cells but less antitumor immune cell subpopulations were found in spleen and tumor tissue derived from RBJ force-expressed tumor-bearing mice. Furthermore, forced RBJ expression significantly promotes tumor cell production of pro-inflammatory cytokine IL-6 by constitutive activating MEK/ERK signaling pathway. Accordingly, RBJ knockdown significantly decreases tumor growth and metastasis in vitro and in vivo, with markedly reduced production of IL-6. Administration of anti-IL-6 neutralizing antibody could reduce MDSCs accumulation in tumor tissue in vivo. Therefore, our results demonstrate that RBJ-mediated nuclear constitutive activation of ERK1/2 leads to persistent production of IL-6 and increase of MDSCs recruitment, contributing to promotion of tumor growth and metastasis. These results suggest that RBJ contributes to tumor immune escape, maybe serving a potential target for design of antitumor drug.


Lump on back: a rare case of parosteal lipoma of scapula.
Lipomas are benign tumors of mature adipose tissue which can occur in subcutaneous, intramuscular, intermuscular, parosteal, and intraosseous compartments. Parosteal lipoma is a rare type of lipoma, accounting for less than 0.1% of primary bone neoplasms and 0.3% of all lipomas. Parosteal lipomas commonly arise in the femur and extremities. Around 150 cases have been reported in English literature with scapula being a rare site of involvement. They are known to be associated with underlying bony changes like focal cortical hyperostosis, pressure erosion of the underlying bone, and bowing deformity or with underlying osteochondroma. We report a rare case of a parosteal lipoma arising in the scapula with a bony excrescence in a 38-year-old male.


[Efficacy of induction chemotherapy for patients with high-risk myelodysplastic syndrome (MDS) or MDS-transformed acute myeloid leukemia with CHG regimen and its comparison with regimen GAG and HA].
This study was aimed to investigate the efficacy of moderate intensity regimen, CHG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor (G-CSF)) on the patients with high-risk MDS or MDS-transformed acute myeloid leukemia. 30 newly diagnosed adult patients with high-risk MDS or MDS-transformed AML were enrolled in this clinical trial to evaluate the efficacy of sequential low-dose homoharringtonine/cytarabine chemotherapy combined with G-CSF priming. Homoharringtonine and Ara-C were injected intravenously at doses of 1 mg and 25 mg daily for 14 consecutive days respectively, G-CSF was injected subcutaneously once daily at a dose of 300 microg on 12 hours prior to chemotherapy and continued given until the end of chemotherapy or when the peripheral WBC count reached > 20 x 10(9)/L. This regimen was given only for one course, and followed by conventional chemotherapy as maintenance or consolidation therapy when CR achieved. 33 patients with high- risk MDS and MDS-transformed AML were injected aclarubicin/Ara-C intravenously at doses of 10 mg and 25 mg for 8 and 14 consecutive days respectively, G-CSF was used at the same dose and the same way as the CHG regimen. 33 patients with high-risk MDS and MDS-transformed AML were treated with HHT/Ara-C intravenously at doses of 2 - 3 mg and 100 - 150 mg daily for 7 consecutive days respectively, G-CSF was injected when WBC count was below 4 x 10(9)/L, and it was stopped to be used when WBC count was > 4 x 10(9)/L. The results showed that (1) 14 patients achieved complete remission (CR) (46.67 %) and 7 patients achieved partial remission (PR) (23.33 %) with one course of CHG regimen, total effective rate was 70%; 14 patient achieved CR (42.4%) and 9 patients achieved PR (27.3%) with one course of CAG regimen, total effective rate was 69.7%; 7 patient achieved CR (33.3%) and 3 patients achieved PR (9.1%) with one course of HA regimen, total effective rate was 42.4%. There was no statistical difference between the effective rate of CHG and CAG, but difference was significant between CHG and HA. (2) Agranulocytosis (neutrophil < 0.5 x 10(9)/L) occurred in 12 cases (40%) of CHG-treated patients with a mean 8 days of agranulocytic period, so the infectious complications were less serious and tolerable without treatment-related death. (3) Among 14 out of 30 patients with CR, 9 relapsed, the mean duration from CR to replace was 8.2 months. All relapsed patients reusing CHG regimen did not achieved CR again. (4) Among 13 cases with CR, 6 patients just received HA or DA regimens as consolidatory and intensive chemotherapy after CR have relapsed, the mean CR time was only 6.1 months. Otherwise, the mean CR time of 7 CR patients received alternative succeeded chemotherapy containing mitoxantrone/idarubicin/THP/homoharringtonine/daunorubicin/aclarubicin after CR was 10.6 months; and among them 4 are still in continuous CR. It is concluded that the CHG chemotherapy regimen has a similar effect with CAG but better than HA, and in a saft chemotherapy regimen with slight myelosuppression in clinical application, strong and alternative succeeded chemotherapy is necessary for CR patients to keep longer CR and survival.


Towards targeted MRI: new MRI contrast agents for sialic acid detection.
The detection of sialic acid in living systems is of importance for the diagnosis of several types of malignancy. We have designed and synthesized two new lanthanide ion ligands (L1 and L2) that are capable of molecular recognition of sialic acid residues. The basic structure of these ligands consists of a DTPA-bisamide (DTPA, diethylenetriamine pentaacetic acid) whose amide moieties each bear both a boronic function for interaction with the diol groups in the side chain of sialic acid, and a functional group that is positively charged at physiologic pH values and is designed to interact with the carboxylate anion of sialic acid. The relaxometric properties of the Gd3+ complexes of these two ligands were evaluated. The relaxivity of the GdL1 complex has a significant second-sphere contribution at pH values above the pKa of its phenylboronic acid moiety. The interaction of the Gd3+ complexes of L1 and L2 with each of several saccharides was investigated by means of a competitive fluorescent assay. The results show that both complexes recognize sialic acid with good selectivity in the presence of other sugars. The adduct formed by GdL2 with sialic acid has the higher conditional formation constant (50.43+/-4.61 M(-1) at pH 7.4). The ability of such complexes to recognize sialic acid was confirmed by the results of a study on the interaction of corresponding radiolabeled complexes (153SmL1 and 153SmL2) with C6 glioma rat cells. 153SmL2 in particular is retained on the cell surface in significant amounts.


High prevalence of CD3, NK, and NKT cells in the graft predicts adverse outcome after matched-related and unrelated transplantations with post transplantation cyclophosphamide.
The predictive value of graft composition and plasma biomarkers on the outcome of allogeneic HSCT is well known for conventional GVHD prophylaxis based on calcineurin inhibitors with or without antithymocyte globulin. Currently, there is limited data whether these results could be translated to post transplantation cyclophosphamide (PTCy). The prospective extension cohort of NCT02294552 trial enrolled 79 adult patients with acute leukemia in CR. Twenty-six received matched-related bone marrow (BM) grafts with single-agent PTCy and 53 received unrelated peripheral blood stem cell graft (PBSC) with PTCy, tacrolimus, and MMF. The grafts were studied by the flow cytometry, and plasma samples were analyzed by ELISA. In the cluster and major component analysis, we determined that transplantation from donors with high content of CD3, NKT, and CD16-CD56 + subpopulations in the PBSC grafts was associated with poor immunological recovery and compromised event-free survival (50% vs. 80%, HR 2.93, p = 0.015) both due to increased relapse incidence and non-relapse mortality. The significant independent predictor of moderate and severe chronic GVHD was the high prevalence of and iNKT, Vβ11, and double-positive cells in the PBSC grafts from young donors (HR 2.75, p = 0.0483). No patterns could be identified for BM grafts and for plasma biomarkers.


Gossypol induced apoptosis in the human promyelocytic leukemia cell line HL 60.
In human promyelocytic leukemia cell line HL60, apoptosis was induced by treatment with gossypol that is an inhibitor of protein kinase C. Gossypol acetic acid was added to HL 60 cells at 50, 100, 150 and 200 microM concentrations for six hours. Morphological features of apoptosis as well as internucleosomal DNA fragmentation were evaluated by light microscope, agarose gel electrophoresis and spectrofluorometric quantitation. Our results indicated that with the effective concentrations of gossypol (50 and 100 microM), apoptosis was induced in HL 60 cells.


What makes community health worker models for tuberculosis active case finding work? A cross-sectional study of TB REACH projects to identify success factors for increasing case notifications.
In the field of tuberculosis (TB), Community Healthcare Workers (CHWs) have been engaged for advocacy, case detection, and patient support in a wide range of settings. Estimates predict large-scale shortfalls of healthcare workers in low- and middle-income settings by 2030 and strategies are needed to optimize the health workforce to achieve universal availability and accessibility of healthcare. In 2018, the World Health Organization (WHO) published guidelines on best practices for CHW engagement, and identified remaining knowledge gaps. Stop TB Partnership's TB REACH initiative has supported interventions using CHWs to deliver TB care in over 30 countries, and utilized the same primary indicator to measure project impact at the population-level for all TB active case finding projects, which makes the results comparable across multiple settings. This study compiled 10 years of implementation data from the initiative's grantee network to begin to address key knowledge gaps in CHW networks. We conducted a cross-sectional study analyzing the TB REACH data repository (n = 123) and primary survey responses (n = 50) of project implementers. We designed a survey based on WHO guidelines to understand projects' practices on CHW recruitment, training, activities, supervision, compensation, and sustainability. We segmented projects by TB notification impact and fitted linear random-effect regression models to identify practices associated with higher changes in notifications. Most projects employed CHWs for advocacy alongside case finding and holding activities. Model characteristics associated with higher project impact included incorporating e-learning in training and having the prospect of CHWs continuing their responsibilities at the close of a project. Factors that trended towards being associated with higher impact were community-based training, differentiated contracts, and non-monetary incentives. In line with WHO guidelines, our findings emphasize that successful implementation approaches provide CHWs with comprehensive training, continuous supervision, fair compensation, and are integrated within the existing primary healthcare system. However, we encountered a great degree of heterogeneity in CHW engagement models, resulting in few practices clearly associated with higher notifications.


The importance of the cosolvent propylene glycol on the antimicrobial preservative efficacy of a pharmaceutical formulation by DOE-ruggedness testing.
The aim of this study was to statistically evaluate the influence of the concentration of the co-solvent propylene glycol on the preservative efficacy of a complex pharmaceutical suspension-emulsion formulation containing methyl- and propylparaben. Preservative Efficacy Tests (PETs) were performed using the validated pharmacopoeial methodology with five test organisms over 1 month on lab-scale test formulations. These were independently prepared according to a Box-Behnken experimental design with a triplicate central point at 0.22% m/m methylparaben, 0.22% m/m propylparaben, and 2.75% m/m propylene glycol, and with an additional corner point of the Box-Behnken cube. We evaluated the preservative efficacies against the criteria of the United States Pharmacopeia (USP) and European Pharmacopoeias (PhEur) for formulations for oral use, as well as by the statistical comparison of the slopes obtained by linear regression of log (CFU/g) vs. time. With an initial bacterial challenge of 10(6) CFU/g for each of the three bacterial strains, no survivals were detected after 7 days. For the two fungal strains, box plots and analysis of variance showed significant, concentration-dependent, main effects: the three variables significantly influenced the kill-rate of C. albicans, while A. niger was predominantly influenced by the cosolvent propylene glycol, and only to a minor extent by methylparaben and not at all by propylparaben. These findings were confirmed by taking the pharmacopoeial criteria as the evaluation basis, where the dominant influence of propylene glycol concentration is apparent. It was concluded that the cosolvent propylene glycol is at least of equal preservative importance than both parabens.


Ambulatory polysomnography for the assessment of sleep bruxism.
Ambulatory polysomnography (PSG) is introduced as a new method for assessing sleep bruxism. Nocturnal recordings of masseter electromyography (EMG), electro-encephalography, electro-oculography, electrocardiography, thoracic effort and body position allow for the detection of typical nocturnal masseter activity as well as the determination of sleep stages. Twelve patients with a clinical diagnosis of bruxism were assessed with the ambulatory PSG, all of them fulfilled diagnostic PSG criteria according to Kato et al. (Dent Clin North Am. 2001; 45: 657-684). Per hour of sleep patients showed 34.2 (+/-10.6) EMG bursts and 5.6 (+/-1.3) sleep bruxism episodes. Because of the ability to determine sleep stages and the application in the home environment the ambulatory PSG represents a cost-saving alternative to sleep laboratory investigations that might be especially useful in field studies and clinical application.


Predictive and Prognostic Assessment Models for Tumor Deposit in Colorectal Cancer Patients With No Distant Metastasis.
More and more evidence indicated that tumor deposit (TD) was significantly associated with local recurrence, distant metastasis (DM), and poor prognosis for patients with colorectal cancer (CRC). This study aims to explore the main clinical risk factors for the presence of TD in CRC patients with no DM (CRC-NDM) and the prognostic factors for TD-positive patients after surgery. The data of patients with CRC-NDM between 2010 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. A logistic regression model was used to identify risk factors for TD presence. Fine and Gray's competing-risk model was performed to analyze prognostic factors for TD-positive CRC-NDM patients. A predictive nomogram was constructed using the multivariate logistic regression model. The concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and the calibration were used to evaluate the predictive nomogram. Also, a prognostic nomogram was built based on multivariate competing-risk regression. C-index, the calibration, and decision-curve analysis (DCA) were performed to validate the prognostic model. The predictive nomogram to predict the presence of TD had a C-index of 0.785 and AUC of 0.787 and 0.782 in the training and validation sets, respectively. From the competing-risk analysis, chemotherapy (subdistribution hazard ratio (SHR) = 0.542, p < 0.001) can significantly reduce CRC-specific death (CCSD). The prognostic nomogram for the outcome prediction in postoperative CRC-NDM patients with TD had a C-index of 0.727. The 5-year survival of CCSD was 17.16%, 36.20%, and 63.19% in low-, medium-, and high-risk subgroups, respectively (Gray's test, p < 0.001). We constructed an easily predictive nomogram in identifying the high-risk TD-positive CRC-NDM patients. Besides, a prognostic nomogram was built to help clinicians identify poor-outcome individuals in postoperative CRC-NDM patients with TD. For the high-risk or medium-risk subgroup, additional chemotherapy may be more advantageous for the TD-positive patients rather than radiotherapy.


Insomnia symptoms during pregnancy: A meta-analysis.
Reports of sleep disturbances are common during pregnancy, yet estimates of prevalence of insomnia symptoms during pregnancy vary widely. The goals of the current review were to summarize the existing data on prevalence of insomnia symptoms during pregnancy and to explore potential moderators, including trimester, gestational age, maternal age, symptoms of anxiety and symptoms of depression. A systematic search of PubMed, PsycInfo and Web of Science was conducted for articles published from inception up to June 2020. In total, 24 studies with a total of 15,564 participants were included in the analysis. The overall prevalence of insomnia symptoms during pregnancy was 38.2%. Trimester was a significant moderator, such that prevalence of insomnia symptoms was higher in the third trimester (39.7%) compared to first (25.3%) and second (27.2%) trimesters. No other variables significantly moderated the prevalence of insomnia symptoms. The results of the current meta-analysis suggest that the prevalence of insomnia symptoms is higher during pregnancy, particularly in the third trimester. Future research should examine the efficacy and safety of insomnia treatments with this population.


[Therapy control of perphenazine in paranoid conditions. 1. Organizational aspects].
A prospective investigation was carried out in the Department of Psychiatry, Odense University Hospital, on therapy control by serum monitoring of the neuroleptic, perphenazine for a period of one year. Newly admitted patients requiring treatment for paranoid symptoms, excluding mania, were offered medication with perphenazine (fixed dosage, oral or parenteral (depot)) which would be serum-monitored. A global record was made of the therapeutic effect and the side-effects by the physicians in the department. In the investigation period, 605 admissions were registered in the department, of them 363 were prospectively registered in the investigation. In all 199 were found to satisfy the inclusion criteria. Either one or two blood tests were carried out on each of 141 patients in the treatment period, i.e. six weeks. The gap in registration is consistent with the result from other investigations. Participation in the investigation varied from ward to ward (33%-87%). The reason for the variation is mainly due to different treatment procedures and traditions. The main conclusion drawn from the investigation is that it is possible to set up a stable treatment/serum-monitored system. In the majority of cases, the team of physicians in the department succeeded in finding the dosage most appropriate on the basis of the serum concentration level. Laboratory recommendations were followed in 93% of the cases.


Nonrenal drug clearance in CKD: Searching for the path less traveled.
Patients with chronic kidney disease (CKD) represent a significant and growing segment of the US population. A mounting body of experimental and clinical evidence indicates that nonrenal drug clearance is altered in patients with CKD. Specific nonrenal clearance (CL(NR)) pathways that are affected have been identified in experimental models, and include cytochrome P450 enzymes, P-glycoprotein, and organic anion-transporting polypeptides. Altered CL(NR) of several drugs has been described in clinical pharmacokinetics studies, but to date the specific CL(NR) pathways that are affected in CKD patients and result in clinically significant changes in drug exposure have not been definitively established, and the mechanism has not been elucidated. Accumulated uremic toxins may downregulate or directly inhibit drug metabolism and transport pathways, and may do so in a reversible manner. Future Food and Drug Administration recommendations pertaining to the conduct of pharmacokinetic studies in CKD will undoubtedly facilitate the search for the CL(NR) path less traveled, clarify the mechanisms involved, improve our understanding of the clinical significance of altered CL(NR) of individual drugs, and lead to more comprehensive drug dosing recommendations for patients with CKD. This review summarizes our current understanding of this field, focusing on recent developments in the search for the CL(NR) "path less traveled" in CKD.


An image-guided transcranial direct current stimulation system: a pilot phantom study.
In this study, an image-guided transcranial direct current stimulation (IG-tDCS) system that can deliver an increased stimulation current to a target brain area without the need to adjust the location of an active electrode was implemented. This IG-tDCS system was based on the array-type tDCS concept, which was validated through computer simulations in a previous study. Unlike a previous study, the present IG-tDCS system adopts a single reference electrode and an active electrode array consisting of 16 (4 × 4) sub-electrodes. The proposed IG-tDCS system is capable of shaping current flow inside the human head by controlling the input currents of the arrayed electrodes. Once a target brain area has been selected, the optimal injection current of each arrayed sub-electrode is evaluated automatically using a genetic algorithm in order to deliver the maximum available current to the target area. The operation of our pilot system was confirmed through a simple phantom experiment.


Ectopic production of beta-subunit of human chorionic gonadotropin in malignant lymphoma.
Ectopic production of human chorionic gonadotropin (HCG) in tumor cells is an uncommon phenomenon that has rarely been documented. The immunoperoxidase method was used to demonstrate the presence of beta-subunit of HCG in malignant lymphoma cases, using paraffin-embedded sections of lymph nodes. 3 of 11 cases of malignant lymphoma (27%) were positively stained with beta-subunit of HCG. All positive cases were T-cell type malignant lymphomas, but all adult T-cell leukemia lymphoma cases did not react with HCG. All B-cell type malignant lymphoma cases were not stained by HCG. Hence, this evidence suggested that beta-subunit of HCG may be useful as a tumor marker in certain malignant lymphoma patients. To the best of our knowledge, production of beta-subunit of HCG in the cytoplasm of malignant lymphoma cells has not been reported.


Magnetic resonance imaging of NMDA-induced lesion of the medial preoptic area and changes in sleep, temperature and sex behaviour.
Destruction of the medial preoptic area (mPOA) neurons of rat brain, induced by intracerebral injection of N-methyl D-aspartic acid (NMDA), has been studied by employing the non-invasive Magnetic Resonance Imaging (MRI) technique. Changes in the MRI images are compared and correlated with the functional changes after the mPOA lesion. The progress of the lesion at the injected site has been monitored (using MRI) from 15 min to 1 month after the stereotaxic microinfusion of NMDA (5 micrograms in 0.2 microliter). This study shows that the localised hyperintense (bright) area starts appearing at the mPOA from 3 h after NMDA injection, and the brightness increases progressively for about 2 days. The size and brightness of hyperintense area decrease thereafter. It has not been possible to locate the lesion site after 3 days, using MRI, except in one rat where a vacuole-like area was seen at the NMDA injected site on postmortem histological examination. The reduction in sleep after the mPOA lesion does not show any correlation with the changes in MRI, as it persists throughout the 3 weeks of recording. On the other hand, the initial drastic reduction in male sex behaviour and the increase in body temperature correlated to some extent with the increased brightness in MRI at the site of lesion. The size and location of the hyperintense area, observed during the first 2 days, match with the lesioned area which was histologically identified after 1 month of NMDA administration. Control administration of normal saline into the mPOA did not produce any alteration in the brightness of the MRI image and practically no loss of neurons at the injected site. Though some functional changes have correlation with the alteration in MRI, this cannot be used to interpret the changes in all the physiological parameters. This study also demonstrates that the disappearance of the brightness in MRI should not be taken to indicate a positive prognosis. Though the lesion could not be seen in MRI within 2 hours, its detection after 3-4 h (but within 3 days) after NMDA lesion would give very valuable information for long term studies.


An update on bimatoprost in glaucoma therapy.
Bimatoprost, a prostamide, effectively lowers intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension. In clinical trials, bimatoprost has demonstrated superiority to the beta-adrenergic antagonist timolol and has consistently provided approximately 1-2 mmHg greater mean IOP lowering than the prostaglandin latanoprost. Bimatoprost is more effective than either timolol or latanoprost in allowing patients to reach the low target pressures that best protect the visual field. Patients on bimatoprost therapy achieve low pressures throughout the day and night. Moreover, 1-year trials have shown that the efficacy of bimatoprost is sustained with long-term use. The most common side effects have been conjunctival hyperaemia, graded as trace or mild, and eyelash growth. No safety concerns have arisen in postmarketing surveillance. Bimatoprost appears to be a valuable new agent for glaucoma therapy.


Characterization of archaeal community in contaminated and uncontaminated surface stream sediments.
Archaeal communities from mercury and uranium-contaminated freshwater stream sediments were characterized and compared to archaeal communities present in an uncontaminated stream located in the vicinity of Oak Ridge, TN, USA. The distribution of the Archaea was determined by pyrosequencing analysis of the V4 region of 16S rRNA amplified from 12 streambed surface sediments. Crenarchaeota comprised 76% of the 1,670 archaeal sequences and the remaining 24% were from Euryarchaeota. Phylogenetic analysis further classified the Crenarchaeota as a Freshwater Group, Miscellaneous Crenarchaeota group, Group I3, Rice Cluster VI and IV, Marine Group I and Marine Benthic Group B; and the Euryarchaeota into Methanomicrobiales, Methanosarcinales, Methanobacteriales, Rice Cluster III, Marine Benthic Group D, Deep Sea Hydrothermal Vent Euryarchaeota 1 and Eury 5. All groups were previously described. Both hydrogen- and acetate-dependent methanogens were found in all samples. Most of the groups (with 60% of the sequences) described in this study were not similar to any cultivated isolates, making it difficult to discern their function in the freshwater microbial community. A significant decrease in the number of sequences, as well as in the diversity of archaeal communities was found in the contaminated sites. The Marine Group I, including the ammonia oxidizer Nitrosopumilus maritimus, was the dominant group in both mercury and uranium/nitrate-contaminated sites. The uranium-contaminated site also contained a high concentration of nitrate, thus Marine Group I may play a role in nitrogen cycle.


[Heart rate variability].
In 1981 a study on heart rate variability (HRV) and on the neural control of the heart was published in Science. Since then, the number of papers concerning this topic has increased exponentially. Some aspects of the relationship between HRV and the neural control of the cardiovascular system are now clear, for example: a decreased SDNN (a measure of variance) during a period of 24 hours is a well established independent negative prognostic factor after acute myocardial infarction and in chronic heart failure patients. Moreover, an increased sympathetic modulation elicited by standard laboratory maneuvers determines an increased power of the low frequency (LF) spectral component (0.03-0.15 Hz), expressed in normalized units. Nevertheless, the interpretation of the oscillatory components present in HRV, particularly in pathophysiological conditions, is far from being clear. The influence of several neurohumoral circuits can induce various changes in HRV according to different physiological or pathological conditions. A new approach to the study of HRV called "information domain" might help to obtain some more information about HRV. Furthermore, in the future, HRV analysis might be useful when deciding on the best pharmacological combination for the individual patient and for the probabilistic prediction of acute cardiac events.


[A REVIEW ABOUT SPONTANEOUS MOVEMENTS DISORDERS IN SCHIZOPHRENIA].
Spontaneous movements disorders are frequently observed in schizophrenia. Together with the negative and cognitive symptoms, they comprise manifestations more linked to the damage of this complex condition, although they are insufficient to make the diagnosis. When the psychotic symptoms express these phenomena, they have probably been causing deleterious effects for years. Within these intrinsic components, motor disorders are the most delayed, paradoxically, as a consequence of the progress of phar-macotherapy. Treatment with antipsychotics modified the clinical symptoms of schizophrenia by developing improvements in positive symptoms, disorganization and agitation, but also produced a change of another order, with the side effects that, many times, had difficulty in being distinguished from the pathology itself. Above all, the specific neuroleptics share to a greater or lesser extent of the production of extrapyramidal symptoms, classically expressed in motor alterations. Therefore, these abnormal movements are often mistakenly associated with antipsychotic medication in an exclusive manner, overshadowing primary motor manifestations.The objective of this work is to highlight the characteristics, importance and relationship with the conventional therapy of spon-taneous movements disorders in schizophrenia.


A consensus view on the technique of ambulatory blood pressure monitoring. The Fourth International Consensus Conference on 24-Hour Ambulatory Blood Pressure Monitoring.
This review, based on the Fourth International Consensus Conference on Ambulatory Blood Pressure Monitoring (Leuven, Belgium, 1994), deals with the technical aspects of ambulatory blood pressure monitoring. Ambulatory blood pressure monitoring by noninvasive intermittent techniques is widely used despite artifacts due to cuff size, movement, body position, short-term blood pressure variability, and interference with sleep. The performance of the currently available monitors under truly ambulatory conditions and during exercise remains a matter of debate, as are the procedures required to validate portable monitors under these circumstances. There is general agreement that whenever a monitor is to be used in special populations, such as older subjects or pregnant women, or in special conditions, such as exercise, a specific demonstration of its accuracy in these defined subgroups or conditions is warranted. Whether the auscultatory or oscillometric method is preferred remains controversial because each technique has specific advantages and disadvantages and because both can provide accurate results. Most experts in the field strongly believe that manufacturers should disclose the algorithms of their devices and that they should specify all changes made to the hardware and software of a previously validated monitor. Finally, the development of the volume-clamp method, which makes continuous noninvasive registration of blood pressure at the finger possible in both stationary and ambulatory conditions, opens new perspectives in research, in particular in relation to short-term blood pressure variability.


Spectral Control of an X-Ray L-Edge Transition via a Thin-Film Cavity.
By embedding a thin layer of tantalum in an x-ray cavity, we observe a change in the spectral characteristics of an inner-shell transition of the metal. The interaction between the cavity mode vacuum and the L_{III}-edge transition is enhanced, permitting the observation of the collective Lamb shift, superradiance, and a Fano-like cavity-resonance interference effect. This experiment demonstrates the feasibility of cavity quantum electrodynamics with electronic resonances in the x-ray range with applications to manipulating and probing the electronic structure of condensed matter with high-resolution x-ray spectroscopy in an x-ray cavity setting.


Regulation of the type-II gonadotrophin alpha and beta subunit mRNAs by oestradiol and testosterone in the European eel.
The gonadotrophic function of the European eel (Anguilla anguilla L.) at the silver stage is very weak: gonadotrophin-releasing hormone (GnRH) secretion is deficient and, moreover, dopamine inhibition overrides GnRH action. At the silver stage, oestradiol stimulates the biosynthesis of the type-II gonadotrophin (GTH-II). To study the molecular mechanism of this activation further, we examined the effect of testosterone and oestradiol administration on pituitary levels of mRNA encoding GTH-II alpha and beta subunits. Corresponding eel cDNA probes and Northern blot analysis were used. After 2 weeks, testosterone and oestradiol implantation resulted in a strong increase in mRNA encoding the GTH-II beta subunit (7-fold and 25-fold, respectively) and in a slight, but non-significant, rise in the a subunit mRNA level (1.8-fold and 1.5-fold, respectively). Co-implantation of these two steroids suggested a potentiation of their effects on the beta subunit (104-fold) while an additive effect was indicated on the alpha mRNA level (2.9-fold). Effects were detectable within 4 days and were maximal 4 weeks after implantation. These results indicate that in the European eel at the silver stage, gonadal steroids stimulate differentially the expression of GTH-II subunit genes at a pretranslational level.


Temporal changes in core body temperature in anesthetized adult horses.
To examine temporal patterns of core body temperatures in adult horses during general anesthesia and to determine the efficacy of forced-air warming blankets in attenuating decreases in core body temperatures. 5 clinically normal adult horses. Horses were assigned to each of 2 trials, warmer and no-warmer, in a randomized crossover design. Horses were instrumented with a thermistor-tipped pulmonary arterial catheter to measure core body temperature. Induction and maintenance of and recovery from general anesthesia were performed in an air-conditioned surgical suite where room temperature and relative humidity were maintained at approximately 21 C and 40%, respectively. Core body temperature measurements were recorded every 5 minutes during 2.5 hours of anesthesia and during recovery until horses could stand. Data were analyzed, using ANOVA for repeated measures. Without warming, mean core body temperature decreased steadily (0.37+/-0.18 C/h). Forced-air warming significantly decreased that rate to 0.19+/-0.09 C/h. In both trials, there was an additional, rapid, significant decrease in core body temperature when horses were moved to the recovery area, which was apparently the result of conductive heat loss to the cold floor. Recovery time and time required for core body temperature to return to baseline were unaffected by forced-air warming during anesthesia and recovery. Core body temperature decreases steadily in adult horses anesthetized in a cool, dry environment. Forced-air warming devices can attenuate this decrease. Additional body heat can be lost rapidly when anesthetized horses are positioned on cold surfaces during recovery.


Evaluation of the efficacy of Hypericum perforatum (St. John's wort) oil in the prevention of stricture due to esophageal corrosive burns.
The inflammatory response that follows the caustic burns results in fibrosis on the esophageal wall leading to esophageal stricture, dysphagia, and malnutrition. The controversy over the use of corticosteroids warrants alternative therapeutic interventions. We investigated the effect of extracts from St. John's wort (SJW) with known wound-healing activity on stricture formation in rat esophageal injury models. Five experimental groups were involved: sham group with no injury, control group with injury without treatment, and three different treatment groups (methylprednisolone, SJW extract, and combination of the two). Histopathological examination of esophageal damage and collagen accumulation, stenosis index, and tissue hydroxyproline levels were used to assess stricture and the effect of treatments. There was a significant weight loss in all groups except for those without injury and those treated with SJW extract, the latter gained weight albeit not significant. Stenosis index was increased in all groups compared to sham but not significantly in those treated with SJW extract. Histopathological and biochemical analyses produced mixed results. Some of the experimental indicators such as weight gain and stenosis index suggested the treatment of esophageal injury models using extracts of St. John's wort effective while other histopathological indicators show no significant benefit.


Combined geospatial, geophysical and hydrochemical studies on coastal aquifer at Muttom-Mandaikadu area, Tamilnadu, India.
A study was conducted in the Muttom-Mandaikadu coastal region, which is among the profitable coastal sectors in Tamil Nadu, to find the groundwater potential as well as its quality by an integrated geospatial, geophysical and geochemical approach. The GIS-based weighted overlay analysis was used to merge five thematic layers to create the groundwater potential zone map. The geophysical resistivity survey was performed in the study area at 26 stations by applying Schlumberger vertical electrical sounding technique. The observed data were inverted to develop a subsurface lithology model and its electrical properties using one-dimensional software AGI Earth Imager. The combined vertical electrical sounding result and remote sensing thematic maps have exposed the potential zone of groundwater in the study area. From the inferred results, it was observed that 20.8% of the area has ample groundwater potential and 7.7% of the area has scanty groundwater potential. The saltwater intrusion zone had been predicted by validating aquifer resistivity with Dar-Zarrouck (D-Z) parameter. From the geophysical and geochemical interpreted results, it was found that aquifers in 34.6% of the study area are vulnerable to saline contamination. The 4-D model with integrated groundwater quantity and quality suggests that the study area's Western part falls under excellent-to-good groundwater potential zone and excellent water quality.


Integrative biology and the developing limb bud.
The identification or selective construction of mutations within genes has allowed researchers to explore the downstream effects of gene disruption. Although these approaches have been successful, a limitation in our assessment of the consequences of conditional changes, and thereby our understanding of roles or function of genes, limits the degree to which we examine the effects of our manipulations. It is also clear that linear associations are incorrect models for describing development, and newer methods now give us an opportunity to practice an integrative biology. In our attempts to explore the consequences of Hoxa13 disruption in mice and humans, it has become clear that a better understanding of the consequences of gene alteration may be achievable by taking a broader approach with a long-term view. Fundamental questions regarding Hox gene function in vertebrates, including those related to the number of target genes; the degree of overlap of target gene regulation among paralogs; the magnitude of modulation exerted; and the identity of genes that are activated versus repressed need to be explored if a more thorough mechanistic understanding is to be achieved. To begin to address these questions, we undertook a comprehensive analysis of the expression of genes within developing limb buds of mice, and here we present some of our preliminary results. Our efforts will further (1) the exploration of the broader genetic relationships of expressed genes, (2) the determination of parallels or variations in target usage for a given gene in different tissues and between different organisms, (3) the evaluation of limb patterning mechanisms in other animal model systems, and (4) the exploration of gene expression hierarchies regulated by HOX proteins in developmental systems.


Effect of gastric acid-reducing agents on the pharmacokinetics and efficacy of lemborexant.
Lemborexant is a dual orexin receptor antagonist approved for treating insomnia. As the solubility of lemborexant is pH-sensitive, the impact of the gastric acid-reducing agent (ARA), famotidine, on lemborexant pharmacokinetics was evaluated in a Phase 1 study. Additionally, post hoc analysis of data from Phase 3 studies examined the potential effect of concomitant ARAs on patient-reported/subjective sleep onset latency (sSOL) in subjects with insomnia. Coadministration of lemborexant 10 mg with famotidine decreased the maximum observed concentration by 27% and delayed time of maximum observed concentration by 0.5 hours. Famotidine did not affect overall lemborexant exposure based on comparison of area under the concentration curves. Concomitant ARA use in the Phase 3 studies did not impact the effect of lemborexant on sSOL; the change from baseline during the last 7 nights of 1 month of treatment with lemborexant 10 mg was -17.1 minutes with vs -17.9 minutes without ARAs. Collectively, these results indicate that lemborexant can be coadministered with ARAs.


Vulnerability, health and health care.
The concept of vulnerability is an important one for nurses because of its implications for health. The experience of vulnerability creates stress and anxiety which affects physiological, psychological and social functioning. Although everyone is vulnerable at different times in his or her life, some individuals are more likely to develop health problems than others. Vulnerability is affected by personal factors as well as factors within the environment. Trends in society indicate that increasing numbers of vulnerable people will create additional demands on an already over-burdened health care system. Vulnerability is an area that requires much further research and application.


Changes in the T-lymphocyte subpopulation (CD+/CD8+) in the blood of patients following kidney transplant and during the acute rejection episode.
A study was made of changes in the ratio of CD4+/CD8+ in patients who had received cadaverous kidneys and who were under treatment with a combination of cyclosporin A + azathioprine + cor ticosteroids. The results showed that one month after the transparent there was a significant drop (P less than 0.05) in the immunoregulation index compared with the pretransplantation values. Throughout the whole period a correlation (r = -0.65, P less than 0.05) was found between the CD4+/CD8+ ratio and serum, creatinine. In recipients with acute rejection episode no significant difference was found between the CD4+/CD8+ values before the rejection episode (7 +/- 1 days and 3 +/- 1 days) and after it was diagnosed. The introduction of monoclonal antibodies specific for determinants in T-lymphocyte transplantation. Many authors have investigated changes in the CD4+ (helper inducer) to subpopulations (1) made possible immunological monitoring following the organ CDB+ (cytotoxic suppressor) ratio following the organ transplant (2, 3, 4, 5). Some reports (6, 7) have indicated that during rejection of a transplanted kidney there is a rise in the immunoregulation index (CD4+/CD8+), while other works (8, 9) failed to confirm this. Our work presents the dynamics of changes in the CD4+/CD8+ ratio in peripheral blood of recipients of cadaverous kidney transplants, and points to changes in the immunoregulation index before and during acute rejection episodes.


Selection rules for the nonlinear interaction of internal gravity waves.
Two intersecting beams of internal gravity waves will generically create two wave packets by nonlinear interaction. The frequency of one packet will be the sum and that of the other packet will be the difference of the frequencies of the intersecting beams. In principle, each packet should form an "X" pattern, or "St. Andrew's cross" consisting of four beams outgoing from the point of intersection. Here we derive selection rules and show that most of the expected nonlinear beams are forbidden. These rules can also be applied to the reflection of a beam from a boundary.


A Metabolomic Investigation of Eugenol on Colorectal Cancer Cell Line HT-29 by Modifying the Expression of APC, p53, and KRAS Genes.
Colorectal cancer is one of the most lethal cancers with a high mortality rate. Chemotherapy results in drug resistance in some cases; hence, herbal medicines are sometimes used in adjunct with it. Eugenol has been reported to have anti-inflammatory, antioxidant, and anticancer properties. Metabolomics is a study of metabolic changes within an organism using high-throughput technology. The purpose of this research was to investigate the anticancer effects of eugenol and variations in p53, KRAS, and APC gene expression and metabolic changes associated with the abovementioned gene expressions using 1HNMR spectroscopy. The MTT method was used to determine cell viability and its IC50 detected. After treating HT-29 cells with IC50 concentration of eugenol, RNA was extracted and cDNA was obtained from them and the expression of p53, KRAS, and APC genes was measured using the qRT-PCR technique. Metabolites were extracted using the chloroform-ethanol method, lyophilized, and sent for 1HNMR spectroscopy using the 1D-NOESY protocol. Chemometrics analysis such as PLS-DA was performed, and differentiated metabolites were identified using the Human Metabolome Database. Integrated metabolic analysis using the metabolites and gene expression was performed by the MetaboAnalyst website. The observed IC50 for eugenol was 500 μM, and the relative expression of APC and p53 genes in the treated cells increased compared to the control group, and the expression of KRAS oncogene gene decreased significantly. The crucial changes in convergent metabolic phenotype with genes were identified. The results indicate that eugenol exhibits its antitumor properties by targeting a specific biochemical pathway in the cell's metabolome profile due to changes in genes involved in colon cancer.


DNA Damage Repair in Brain Tumor Immunotherapy.
With the gradual understanding of tumor development, many tumor therapies have been invented and applied in clinical work, and immunotherapy has been widely concerned as an emerging hot topic in the last decade. It is worth noting that immunotherapy is nowadays applied under too harsh conditions, and many tumors are defined as "cold tumors" that are not sensitive to immunotherapy, and brain tumors are typical of them. However, there is much evidence that suggests a link between DNA damage repair mechanisms and immunotherapy. This may be a breakthrough for the application of immunotherapy in brain tumors. Therefore, in this review, first, we will describe the common pathways of DNA damage repair. Second, we will focus on immunotherapy and analyze the mechanisms of DNA damage repair involved in the immune process. Third, we will review biomarkers that have been or may be used to evaluate immunotherapy for brain tumors, such as TAMs, RPA, and other molecules that may provide a precursor assessment for the rational implementation of immunotherapy for brain tumors. Finally, we will discuss the rational combination of immunotherapy with other therapeutic approaches that have an impact on the DNA damage repair process in order to open new pathways for the application of immunotherapy in brain tumors, to maximize the effect of immunotherapy on DNA damage repair mechanisms, and to provide ideas and guidance for immunotherapy in brain tumors.


Issues in understanding pediatric asthma: epidemiology and genetics.
Asthma is a heterogeneous disease characterized by varying phenotypes. Ongoing research is focused on identifying which children who have wheezing early will progress to childhood asthma. Genetic factors, predominantly atopy and a parental history of asthma as well as environmental stimuli, are key components in the development of asthma. Investigation into immunologic processes indicates that atopic children may have a cytokine imbalance or dysregulation in which the transition from T helper 2 (T(H)2)-type to T(H)1-type immunity is delayed. Several risk factors have been identified in the pathophysiology of asthma, including sensitization and exposure to cockroaches, house dust mites, and the mold Alternaria alternata, among other aeroallergens. Viral respiratory infections, primarily those caused by respiratory syncytial virus, are a significant risk factor for the development of childhood wheezing in the first decade of life. A number of prospective epidemiologic studies are investigating, among other issues, the relations among cytokine dysregulation, respiratory tract infections, and allergen exposure and sensitization in the development of asthma. Identifying the pathogenic mechanisms should enable clinicians to identify children at high risk and thereby to treat childhood asthma more effectively.


An ecological microsystem to treat waste oil contaminated soil: Using phytoremediation assisted by fungi and local compost, on a mixed-contaminant site, in a cold climate.
As a result of anthropization and industrialization, northern remote communities face issues of soil contamination by mixtures of organic and inorganic contaminants. Soil bioremediation in cold environments is particularly challenging because of slower degradation rates, slower production of biomass for phytoextraction of trace elements (TEs), and remoteness, which can complicate logistics and inflate costs. This study evaluated a decontamination approach integrating indigenous willows, fungi and compost in a northern community. The site was a waste oil pit and its soil was initially contaminated with petroleum hydrocarbons (PHC) exceeding 200 g kg-1 and TEs including As, Cd, Co, Cr, Cu, Pb and Zn. In under five years, 65 and 75% of PHC (C6-C50 and >C50) were degraded, compared to 27 and 13% for the untreated control soil. We found contrasting TE translocation patterns to the aboveground biomass for the willow species used (Salix planifolia and Salix alaxensis), as well as distinctive rooting strategies. Hazard quotients were calculated to assess the risk plant material could pose to local wildlife. The highest TE concentration measured was Zn in S. planifolia, which exceeded Canadian soil guidelines. Results indicate toxicity risks to animals linked to TEs in Salix spp. leaves is generally unlikely. The fungus Trametes versicolor inoculated into the soil did not fruit, however fruiting bodies of Psathyrella sp. were observed consistently (four out of five years). Biological tests indicated that in five growing seasons soil toxicity significantly decreased compared to the untreated soil used as control. This was demonstrated by vegetation cover (137 vs 11% cover), toxicity assays on earthworms (Eisenia andrei) (0 vs 33% mortality) and barley seed germination (Hordeum vulgare) (86 vs 62% germination). The proposed decontamination approach, without the use of synthetic fertilizers, is promising for the PHC remediation of mixed-contaminants on cold climate sites.


Mycosporine-like amino acid content in four species of sea anemones in the genus Anthopleura reflects phylogenetic but not environmental or symbiotic relationships.
We examine the occurrence of UV-absorbing, mycosporine-like amino acids (MAAs) in four sympatric species of sea anemones in the genus Anthopleura, all collected from intertidal habitats on the Pacific Coast of temperate North America. We compare patterns of MAAs in A. elegantissima of several types: specimens having predominately zooxanthellae (dinoflagellates comprising at least two species) or zoochlorellae as symbionts; those containing algal endosymbionts of both kinds, and naturally occurring aposymbiotic specimens that lack the endosymbionts typically found in most specimens. We also compare MAAs in zooxanthellate specimens of A. sola and A. xanthogrammica, and specimens from the asymbiotic species A. artemisia. Our findings indicate that the complements of the four major MAAs in these species of Anthopleura (mycosporine-taurine, shinorine, porphyra-334, and mycosporine-2 glycine) broadly reflect phylogenetic differences among the anemones rather than the taxon of endosymbionts, presence or absence of symbionts, or environmental factors. An exception, however, occurs in A. elegantissima, where mycosporine-2 glycine increases in concentration with the density of zooxanthellae. Our evidence also shows that A. elegantissima can accumulate MAAs from its food, which may explain the occasional occurrence of minor MAAs in some individuals.


Quantification of microglial late reaction to stereotactic irradiation of the rat brain using computer-aided image analysis.
The role of microglial cells in the late delayed reaction following radiotherapy of brain tumors has not been elucidated. To investigate the late delayed response of microglial cells to radiation, we stereotactically irradiated spherical treatment volumes in the right frontal lobe of rat brains. Doses of 20, 30, 40, and 50 Gy were used in combination with two different collimators. The response of microglial cells at 10 and 19 months after irradiation was determined with Anti-CD 11 b/c (Ox 42) as an immunohistochemical marker. For evaluation of immunostaining, we developed a method using computer-aided image analysis in which the ratio of the area of stained cells to that of nonstained brain tissue is calculated. In addition, quantification of Ox-42+ cells per microscopic field was performed. Animals treated with 30 Gy or more had significantly increased total areas of staining at both time points studied. In contrast, the number of stained cells at 10 months increased significantly only in animals treated with 30 or 40 Gy. Likewise, at 19 months, this number increased significantly only in animals treated with 40 Gy or more. These results indicate that computer-aided determination of the area of stained cells is more sensitive than the counting of stained cells. We have demonstrated that microglial cells respond to stereotactic irradiation in a dose-dependent fashion. The image analysis we employed for this purpose is a systematic method to evaluate immunohistochemical staining.


Identification of genes differentially expressed in V79 cells grown as multicell spheroids.
Growth of Chinese hamster V79 cells as multicell spheroids leads to an increase in resistance to killing by ionizing radiation and etoposide. Differential display was used to identify changes in gene expression that occur when cells are grown as spheroids. Differential display was performed using exponentially growing Chinese hamster V79 cells and the outer cell layer of V79 spheroids. Using six different pairs of primers, 20 altered bands were selected. Eight genes, confirmed using reverse Northerns, showed a match in a GenBank search. Antibodies against a calcium-binding protein, mts1, confirmed differential expression of this protein. Intracellular free calcium levels were measured using fluo-3 fluorescence, and the effect of a calcium-binding agent on etoposide resistance was examined using the comet assay. Genes upregulated in the outer cell layer of spheroids relative to monolayers included: (1) mts1 (S100A4), a calcium binding protein implicated in proliferation, metastasis, cell adhesion, and angiogenesis; (2) cytochrome c oxidase II; (3) B-ind1, a mediator of Rac-1 signaling; (4) TRAM, an endoplasmic reticulum protein. Genes downregulated in spheroids were: (5) phosphoglycerate kinase; (6) ARL-3, a ras-related GTP binding protein; (7) MHC class III complement 4A; and (8) 2,4-dienoyl-CoA. Immunohistochemistry confirmed overexpression of mts1 and another calcium-binding protein, calreticulin, in V79 outer spheroid cells relative to monolayers. C6 rat glioma and SiHa human cervical carcinoma cells that demonstrate a contact effect also showed upregulation of mts1 or calreticulin, while WiDr colon carcinoma cells that lack contact resistance showed no change in expression of either calcium binding protein. Intracellular free calcium levels were found to be almost two times lower in the outer cells of V79 spheroids compared to monolayers. V79 monolayer and outer spheroid cells treated with the calcium chelating agent BAPTA-AM showed a similar level of DNA damage by etoposide. Expression of genes involved in calcium binding, signaling and metabolism are differentially expressed when V79 cells are grown as spheroids. Differences in the levels of intracellular calcium may underlie the contact effect.


Comparison of intensive care unit medication errors reported to the United States' MedMarx and the United Kingdom's National Reporting and Learning System: a cross-sectional study.
The objective was to compare the characteristics of medication errors reported to 2 national error reporting systems by conducting a cross-sectional analysis of errors reported from adult intensive care units to the UK National Reporting and Learning System and the US MedMarx system. Outcome measures were error types, severity of patient harm, stage of medication process, and involved medications. The authors analyzed 2837 UK error reports and 56 368 US reports. Differences were observed between UK and US errors for wrong dose (44% vs 29%), omitted dose (8.6% vs 27%), and stage of medication process (prescribing: 14% vs 49%; administration: 71% vs 42%). Moderate/severe harm or death was reported in 4.9% of UK versus 3.4% of US errors. Gentamicin was cited in 7.4% of the UK versus 0.7% of the US reports (odds ratio = 9.25). There were differences in the types of errors reported and the medications most often involved. These differences warrant further examination.


2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.
Tolerance development caused by dopamine replacement with l-DOPA and therapeutic drawbacks upon activation of dopaminergic receptors with orthosteric agonists reveal a significant unmet need for safe and effective treatment of Parkinson's disease. In search for selective modulators of the D1 receptor, the screening of a chemical library and subsequent medicinal chemistry program around an identified hit resulted in new synthetic compound 26 [UCM-1306, 2-(fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl] that increases the dopamine maximal effect in a dose-dependent manner in human and mouse D1 receptors, is inactive in the absence of dopamine, modulates dopamine affinity for the receptor, exhibits subtype selectivity, and displays low binding competition with orthosteric ligands. The new allosteric modulator potentiates cocaine-induced locomotion and enhances l-DOPA recovery of decreased locomotor activity in reserpinized mice after oral administration. The behavior of compound 26 supports the interest of a positive allosteric modulator of the D1 receptor as a promising therapeutic approach for Parkinson's disease.


Effect of food on enoxacin absorption.
Fifteen subjects received a single 400-mg oral dose of enoxacin in the fasting state and after carbohydrate and high-fat meals. The carbohydrate meal delayed the time to peak enoxacin concentration in plasma by an average of 0.92 h. The extent of enoxacin absorption was not altered by food.


Noroviruses: The leading cause of gastroenteritis worldwide.
Noroviruses are the leading cause of foodborne disease outbreaks worldwide, and may soon eclipse rotaviruses as the most common cause of severe pediatric gastroenteritis, as the use of rotavirus vaccines becomes more widespread. Genetic mutations and recombinations contribute to the broad heterogeneity of noroviruses and the emergence of new epidemic strains. Although typically a self-limited disease, norovirus gastroenteritis can cause significant morbidity and mortality among children, the elderly, and the immunocompromised. The lack of a cell culture or small animal model has hindered norovirus research and the development of novel therapeutic and preventative interventions. However, vaccines based on norovirus capsid protein virus-like particles are promising and may one day become widely available through transgenic expression in plants.


[Arab-Islamic medicine in the 12th century from the Persian ancient book Chahar Maghaleh].
The book named Chahar Maghaleh(Four Discourses) is written by Nizami Aruzi Samarqandi, a Persian writer in twelfth century. The book records 12 stories that can be regarded as medical records. Through the analysis of the 12 cases, we can get a lot of Arabia-Islamic medical information before and after 12th century, including basic concepts, medical academic origin, diagnostic methods, treatment methods and other content.That reflects the medieval Arabia-Persian society medical level.Compared with traditional Chinese medicine, ancient Arabia-Persian society had distinct features in medicine, food therapy, external therapy, psychotherapy and other fields; in the treatment of ideas and methods of diagnosis, they share some similarity with traditional Chinese medicine.


Modified Korean MIND Diet: A Nutritional Intervention for Improved Cognitive Function in Elderly Women through Mitochondrial Respiration, Inflammation Suppression, and Amino Acid Metabolism Regulation.
Mild cognitive impairment is associated with a high prevalence of dementia. The study examines the benefits of a modified Korean MIND (K-MIND) diet and explores biomarkers using multi-omics analysis. The K-MIND diet, tailored to the elderly Korean population, includes perilla oil, milk, or fermented milk, and avoids alcohol consumption. As a result, the K-MIND diet significantly improves subjects "orientation to place" in the Korean version of the Mini-Mental State Examination, 2nd edition test. According to multi-omics analysis, the K-MIND diet upregulates genes associated with mitochondrial respiration, including ubiquinone oxidoreductase, cytochrome C oxidase, and ATP synthase, and immune system processes, and downregulates genes related to nuclear factor kappa B activity and inflammatory responses. In addition, K-MIND affects the metabolic pathways of glycine, serine, threonine, tryptophan, and sphingolipids, which are closely linked to cognitive function through synthesis of neurotransmitters and structures of brain cell membranes. The findings imply that the K-MIND diet improves cognitive function by upregulating key genes involved in oxidative phosphorylation and downregulating pro-inflammatory cytokines.


Efficient decoy-state quantum key distribution with quantified security.
We analyse the finite-size security of the efficient Bennett-Brassard 1984 protocol implemented with decoy states and apply the results to a gigahertz-clocked quantum key distribution system. Despite the enhanced security level, the obtained secure key rates are the highest reported so far at all fibre distances.


Stability of tenzaloy aluminum mirrors.
We have tested several cast Tenzaloy aluminum mirrors, using standard optical test procedures. Although our tests are not extensive, we have established that Tenzaloy mirrors stable within one or two waves (5000 A), or less, can and have been made. This result is in contrast to that which has been obtained for mirrors cast from 356-T6 alloy, which are not satisfactorily stable.


Eigenvector alignment: Assessing functional network changes in amnestic mild cognitive impairment and Alzheimer's disease.
Eigenvector alignment, introduced herein to investigate human brain functional networks, is adapted from methods developed to detect influential nodes and communities in networked systems. It is used to identify differences in the brain networks of subjects with Alzheimer's disease (AD), amnestic Mild Cognitive Impairment (aMCI) and healthy controls (HC). Well-established methods exist for analysing connectivity networks composed of brain regions, including the widespread use of centrality metrics such as eigenvector centrality. However, these metrics provide only limited information on the relationship between regions, with this understanding often sought by comparing the strength of pairwise functional connectivity. Our holistic approach, eigenvector alignment, considers the impact of all functional connectivity changes before assessing the strength of the functional relationship, i.e. alignment, between any two regions. This is achieved by comparing the placement of regions in a Euclidean space defined by the network's dominant eigenvectors. Eigenvector alignment recognises the strength of bilateral connectivity in cortical areas of healthy control subjects, but also reveals degradation of this commissural system in those with AD. Surprisingly little structural change is detected for key regions in the Default Mode Network, despite significant declines in the functional connectivity of these regions. In contrast, regions in the auditory cortex display significant alignment changes that begin in aMCI and are the most prominent structural changes for those with AD. Alignment differences between aMCI and AD subjects are detected, including notable changes to the hippocampal regions. These findings suggest eigenvector alignment can play a complementary role, alongside established network analytic approaches, to capture how the brain's functional networks develop and adapt when challenged by disease processes such as AD.


Changes in cystathionine gamma-lyase in various regions of rat brain during development.
Developmental changes in the activities of cystathionine beta-synthase and cystathionine gamma-lyase were measured in six regions of rat brain. On day-1, no differences were observed in the activities of cystathionine beta-synthase and cystathionine gamma-lyase among these regions, the values being about 40 nmol/h/mg protein, and 3 nmol/h/mg protein, respectively. Cystathionine beta-synthase activity increased gradually during development at almost the same rate in each region, reaching the adult level at week-4 (about 4-fold). Cystathionine gamma-lyase activity also increased during development, reaching adult level at week-2. But, the increase of enzyme activity in the cerebellum (about 1.8-fold) was clearly lower than that in the other regions (about 4-fold). Cystathionine gamma-lyase content in the various regions of week-3 rat brain estimated by immunoblotting was consistent with the enzyme activity, and the enzyme level in the cerebellum was lower than that in the other regions. Cystathionine content of cerebellum in week-3 increased rapidly during development, and was about five-fold more than that on day-1. However, cystathionine content in the other regions did not change during development. These findings indicated that at least one reason of the high content of cystathionine in the 3 weeks rat cerebellum was due to the low level of cystathionine gamma-lyase.


Occupant Injury and Response on Oblique-Facing Aircraft Seats: A Computational Study.
Increased interest in the airline industry to enhance occupant comfort and maximize seating density has prompted the design and installation of obliquely mounted seats in aircraft. Previous oblique whole-body sled tests demonstrated multiple failures, chiefly distraction-associated spinal injuries under oblique impacts. The present computational study was performed with the rationale to examine how oblique loading induces component level responses and associated injury occurrence. The age-specific human body model (HBM) was simulated for two oblique seating conditions (with and without an armrest). The boundary conditions consisted of a 16 g standard aviation crash pulse, 45 deg seat orientation, and with restrained pelvis and lower extremities. The overall biofidelity rating for both conditions ranged from 0.5 to 0.7. The validated models were then used to investigate the influence of pulse intensity and seat orientation by varying the pulse from 16 g to 8 g and seat orientation from 0 deg to 90 deg. A total of 12 parametric simulations were performed. The pulse intensity simulations suggest that the HBM could tolerate 11.2 g without lumbar spine failure, while the possibility of cervical spine failure reduced with the pulse magnitude <9.6 g pulse. The seat orientation study demonstrated that for all seat angles the HBM predicted failure in the cervical and lumbar regions at 16 g; however, the contribution of the tensile load and lateral and flexion moments varied with respect to the change in seat angle. These preliminary outcomes are anticipated to assist in formulating safety standards and in designing countermeasures for oblique seating configurations.


Spatial expression and autoregulation of hetR, a gene involved in the control of heterocyst development in Anabaena.
The spatially patterned differentiation of heterocysts in the filamentous cyanobacterium Anabaena requires a functional hetR gene. Transcriptional fusions to luxAB show that hetR is transcribed at a low level throughout the filament when Anabaena is grown with combined nitrogen, and that induction of the gene begins within 2 h following nitrogen deprivation. By 3.5 h, induction is localized to spaced foci. By 6 h, there is an overall induction of at least threefold in whole cultures, reflecting at least a 20-fold increase within spatially separated cells. The induction requires the presence of a functional hetR gene, indicating that hetR is autoregulatory. Full induction of a heterocyst structural gene, hepA, also requires a functional hetR locus.


Effects of dyslexia on postural control in adults.
Dyslexia has been shown to affect postural control. The aim of the present study was to investigate the difference in postural stability measured as torque variance in an adult dyslexic group (n=14, determined using the Adult Dyslexia Checklist (ADCL) and nonsense word repetition test) and an adult non-dyslexic group (n=39) on a firm surface and on a foam block and with eyes open and eyes closed. Another aim was to investigate the correlation between ADCL scores and postural stability. Findings showed that ADCL scores correlated with torque variance in the anteroposterior direction on foam with eyes closed (p=0.001) and in the lateral direction on the foam surface with eyes closed (p=0.040) and open (p=0.010). General Linear Model analysis showed that high dyslexia scores were associated with increased torque variance (p<0.001). However, we found no significant difference between dyslexics and non-dyslexics, though there were indications of larger torque variance in the dyslexics. The findings suggest that adults with high dyslexic ADCL scores may experience sub-clinical balance deficits. Hence, assessing motor ability and postural control in those with high ADCL scores is motivated.


The nerve supply of the trapeziometacarpal joint.
Ten forearm and hand specimens from fresh cadavers were dissected and examined under magnification for articular branches to the trapeziometacarpal joint arising from the thenar and palmar cutaneous branches of the median nerve, the superficial branch of the radial nerve and the lateral cutaneous nerve of forearm. In all but one specimen the thenar branch of the median nerve sent an articular branch to the trapeziometacarpal joint. Multiple branches from the palmar cutaneous branch of the median nerve, the superficial branch of the radial nerve and the lateral cutaneous nerve of forearm were also found. All these branches need to be divided during a "complete" denervation of the trapeziometacarpal joint.


An iron-regulated gene, magA, encoding an iron transport protein of Magnetospirillum sp. strain AMB-1.
Magnetospirillum sp. AMB-1 is a freshwater magnetic bacterium which synthesizes intracellular particles of magnetite (Fe3O4). A genomic DNA fragment required for synthesis of magnetic particles was previously isolated from a nonmagnetic transposon Tn5 mutant. We have determined the complete nucleotide sequence of this fragment. The 2975-base pair region contains two putative open reading frames. One open reading frame, designated magA, encodes a polypeptide which is homologous to the cation efflux proteins, the Escherichia coli potassium ion-translocating protein, KefC, and the putative Na+/H(+)-antiporter, NapA, from Enterococcus hirae. Northern hybridization demonstrated that the magA mRNA transcript is 1.3 kilobases in size, corresponding to the size of the magA gene. A functional promoter was located upstream from the magA gene, and the transcription in AMB-1 was regulated by environmental iron concentration. Vesicles isolated from E. coli in which the MagA protein was expressed exhibited iron accumulation ability. We consider that the MagA protein is an iron transport involved in the synthesis of magnetic particles in AMB-1.


Ultratrace determination of lead in whole blood using electrothermal atomization laser-excited atomic fluorescence spectrometry.
Laser-excited atomic fluorescence has been used to detect lead that was electrothermally atomized from whole blood in a graphite furnace. A 9 kHz repetition rate copper vapor laser pumped dye laser was used to excite the lead at 283.3 nm, and the resulting atomic fluorescence was detected at 405.8 nm. No matrix modification was used other than a 1:21 dilution of the whole blood with high-purity water. Using the atomic fluorescence peak area as the analytical measure and a background correction technique based upon a simultaneous measurement of the transmitted laser intensity, excellent agreement for NIST and CDC certified whole blood reference samples was obtained with aqueous standards. A limit of detection in blood of 10 fg/mL (100 ag absolute) was achieved.


Comparison of foodservice management performance level between dietitians and non-dietitians in senior centers using IPA.
This study investigated the management importance and performance level of foodservice managers at senior centers. Using the survey, perceived importance and performance levels of seven foodservice management areas were evaluated and analyzed. Data showed the foodservice facilities were being managed by dietitians (61.6%) or non-dietitians (38.9%). The result indicated that overall importance level (3.43) was higher than performance level (3.02) (p<.01). As of the IPA result, dietitians and non-dietitians had different perspectives in terms of managing the eight categories of foodservice areas. The differences in the IPA results between the two groups may reflect bias attributable to the respondents' degrees of knowledge and professional preparation. The research findings could enhance our understanding of importance of hiring professional dietitians to operate foodservice at senior centers and find out which management area should be concentrated for more effective foodservice management.