Spontaneous exudative retinal detachment in a patient with sturge-weber syndrome after taking arginine, a supplement for erectile dysfunction.
Patients with Sturge-Weber syndrome can have ipsilateral diffuse or circumscribed choroidal hemangiomas. These hemangiomas have been seen to undergo spontaneous exudative or hemorrhagic retinal detachments. There is no definitive treatment for these types of retinal detachments, but radiotherapy, photodynamic therapy, oral propranolol, pegaptinib and bevacizumab have been used. A 26-year-old male with Sturge-Weber Syndrome developed an exudative retinal detachment that occurred immediately after taking a supplement containing arginine. The patient was treated with intravitreal bevacizumab 1.25 mg in 0.05 ml solution. Resolution of the retinal detachment was seen after 4 treatments over a six-month period. Arginine and other medications that cause a release of nitric oxide may lead to intravascular leakage and exudative retinal detachments in patients who have a choroidal hemangioma.


The effect of foreign skin on feather pattern in the common fowl (Gallus domesticus).
Experiments with skin grafting in the fowl have shown that a large measure of success is obtainable by means of a very simple technique. When a graft is placed on the back of a newly hatched chick the feathers subsequently developed conform very strictly in color and pattern to the type characteristic of the breed from which the graft was derived, except that occasionally some abnormally colored feathers are produced. These feathers are found to belong to two classes, one of which can be duplicated in unoperated birds, while the other is distinctive and represents a combination of the characteristics of donor and host. The data at hand do not justify anything more than a tentative hypothesis as to the exact mode of interaction in this case, but the fact that such an interaction does occur places the bird in line with some of the lower forms, and opens a new field for the study of regulatory processes in warm blooded animals.


Vicia: a green bridge to clean up polluted environments.
Vicia species, commonly known as vetches, include legume plants which nowadays can be found in many countries around the world. Their use to improve soil health and productivity is crucial in management schemes that make sustainable agriculture possible, but they can also play a part in the phytoremediation of polluted environments. Furthermore, they harbor a large community of rhizospheric microorganisms, such as biodegradative bacteria and plant growth-promoting rhizobacteria, which can help to increase phytoremediation efficiency. Their mutualistic association with Rhizobium sp. has also been proposed as an attractive bioremediation tool. Thus, Vicia species could make a remarkable difference in the ecological restoration of polluted soils, thanks to their dual role as cover crops and phytoremediator plants. This mini-review discusses recent advances in the use of Vicia. Challenges and opportunities connect with the application of these species will also be revised, as well as aspects that remain to be explored.


Pretreatment of corn stover using low-moisture anhydrous ammonia (LMAA) process.
A simple pretreatment method using anhydrous ammonia was developed to minimize water and ammonia inputs for cellulosic ethanol production, termed the low moisture anhydrous ammonia (LMAA) pretreatment. In this method, corn stover with 30-70% moisture was contacted with anhydrous ammonia in a reactor under nearly ambient conditions. After the ammoniation step, biomass was subjected to a simple pretreatment step at moderate temperatures (40-120°C) for 48-144 h. Pretreated biomass was saccharified and fermented without an additional washing step. With 3% glucan loading of LMAA-treated corn stover under best treatment conditions (0.1g-ammonia+1.0 g-water per g biomass, 80°C, and 84 h), simultaneous saccharification and cofermentation test resulted in 24.9 g/l (89% of theoretical ethanol yield based on glucan+xylan in corn stover).


Interdependent development of blood vessels and organs.
The cardiovascular system is the first functional organ in the vertebrate embryo, and many organs start to develop adjacent to cells of the cardiovascular system. Endothelial cells (EC) form the inner cell lining of blood vessels and represent the major cell type that interacts with developing organs. On the one hand, EC provide organs with signals. These signals determine the location, differentiation and morphology of an organ. On the other hand, EC receive signals from the organ-specific cell types. Such signals give EC organ-specific features that the organ needs to interact with the circulatory system. This review provides the reader with specific examples of an interdependent development of organs and blood vessels.


No-touch isolation technique in colon cancer: a controlled prospective trial.
In order to assess the effect of the no-touch isolation technique, in the treatment of large bowel cancers, on the site of first recurrence and disease-free and overall survival, 236 patients were prospectively and randomly assigned to either the no-touch isolation technique (117 patients) or to a conventional resection technique (119 patients). No patient with distant metastases or unresectable disease entered the study. The two treatment groups were comparable with regard to patient characteristics. Pre- and postoperative complications (including mortality within 30 days) were similar in both groups. After a complete follow-up of 5 years, a tendency for reduction in the number of, and time to, occurrences of liver metastases was seen in the no-touch isolation group (P = 0.14). This effect was most obvious in the sigmoid colon with angio-invasive growth. Overall (P = 0.42) and corrected (P = 0.25) survival did not differ significantly among the treatment groups although in every analysis the survival data of the no-touch isolation group were superior. The data do suggest a limited benefit of the no-touch isolation technique. This observation is important since the morbidity and mortality of surgery were equal in both groups.


The promise of cancer therapeutics targeting the TNF-related apoptosis-inducing ligand and TRAIL receptor pathway.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily and has been shown to induce apoptosis in cancer cells but not normal cells. TRAIL triggers apoptosis through binding to its receptors DR4 and KILLER/DR5. Chemo or radiotherapy induces apoptosis through activation of p53 in response to cellular damage, whereas TRAIL induces apoptosis independent of p53. Mutations or deletions of p53 occurred in more than half of human tumors confer resistance to chemo-radiotherapy. Treatment of TRAIL-resistant tumors with agents targeting death receptors, intrinsic Bcl-2 family members, inhibitor of apoptosis proteins or PI3K/Akt pathway restores the sensitivity to TRAIL-induced apoptosis. Combination of rhTRAIL or the agonist antibody for TRAIL receptor with conventional chemotherapeutic agents results in enhanced efficacy in preventing tumor progression and metastasis. Therefore, the rational design of TRAIL-based therapy combining with other modality that either synergizes to apoptosis induction or overcomes the resistance represents a challenging strategy to achieve the systemic tumor targeting and augment the antitumor activity of cancer therapeutics.


Morphologic and allozymic variation between long-term grazed and non-grazed populations of the bunchgrass Schizachyrium scoparium var. frequens.
Plant populations of Schizachyrium scoparium var. frequens with a history of long-term grazing by domestic herbivores were characterized by shorter and narrower leaf blades and tillers of lower weight than plants from populations with a history of no grazing. Following four biweekly defoliation events plants from the grazed populations additionally displayed lower specific leaf weights, lower amounts of biomass removed per tiller upon defoliation and a greater number of new and regrowing tillers. Production values per plant remained similar between the two populations because of a greater number of tillers per plant in the grazed population.A large amount of allozymic polymorphism was observed in both the grazed and non-grazed populations. Results of the electrophoretic analyses indicated that a minimum of 66% of the plants sampled represented separate genotypes. No distinction could be made between grazed and non-grazed populations in terms of allozymic partitioning. The morphological variation observed between these two populations may represent a shift in the relative dominance of a series of genotypes variously adapted to herbivory.


Vaccines for tumour prevention.
Despite tremendous progress in basic and epidemiological research, effective prevention of most types of cancer is still lacking. Vaccine use in cancer therapy remains a promising but difficult prospect. However, new mouse models that recapitulate significant features of human cancer progression show that vaccines can keep precancerous lesions under control and might eventually be the spearhead of effective and reliable ways to prevent cancer.


Nattokinase crude extract enhances oral mucositis healing.
Nattokinase (NK) is a promising alternative in the prevention and treatment of cardiovascular diseases due to its potent fibrinolytic activity. In this study, we investigated the effect of crude nattokinase extract on the healing of acetic acid-induced oral mucositis in mice. Bacillus subtilis culture media (BSCM) was isolated into the supernatant, named nattokinase crude extract (NCE), and the pellet was named Bacillus subtilis mass (BSM). An oral mucositis model was established in mice by applying 50% glacial acetic acid to the buccal mucosa. According to the treatment conditions, the mice were divided into BSCM, NCE, BSM and phosphate buffered saline (PBS) groups. The weight of the mice, oral mucositis healing score and histopathological examination were used to evaluate the treatment. Fibrinolytic activities of BSCM, NCE and BSM were approximately 8069, 10,800 and 80 U/ml, respectively. The weight gain of mice in the NCE group was significantly different from the PBS group after three days' treatment (p < 0.05). The oral mucositis score of NCE group was significantly higher than other groups (p < 0.05). The differences in histopathology scores between the NCE and other groups were statistically significant (p < 0.01). NCE could possess remarkable potential to reduce pain and promote oral mucositis healing with minimal safety concerns. In this study, we first report that NCE from the supernatant of Bacillus subtilis can promote the healing of oral mucositis, which extends the application scope of NK.


Dental care with manual toothbrushes during fixed orthodontic treatment--a new testing procedure.
The aim of this investigation was to employ a new in-vitro testing system for manual toothbrushes in order to distinguish the more effective from those less so for dental care during fixed appliance treatment. The testing apparatus consisted of a sliding carriage able to execute a horizontal brushing movement, and a row of artificial teeth upon which the various toothbrushes were manipulated. The artificial row of teeth was fixed on a sensor that recorded in all three dimensions the forces and moments caused by the toothbrushes on the toothbrush field. All the tests were executed with a weight of 110 g on a tooth field with a multibracket appliance. Tests were also carried out with five toothbrushes having weights of 200 g, 250 g and 300 g. Here, the decisive target values were 1) the degree of exertion necessary in the brushing direction to move a brush over the artificial teeth, and 2) the maximum force occurring in the brushing direction. High target values indicated high interaction between toothbrush bristles and the surfaces being brushed. From testing five toothbrushes with four different weights, we have established profiles confirming the beneficial and less beneficial properties of certain toothbrushes involving various high contact forces.


Ineligibility for anticoagulation in patients with atrial fibrillation.
Although anticoagulation therapy markedly reduces the risk of stroke in patients with atrial fibrillation, up to 50% of these patients are deemed ineligible for anticoagulation. In this manuscript we provide a framework to assess the net clinical benefit of anticoagulation in patients with atrial fibrillation with an increased risk of bleeding. We also review recent data related to the novel oral anticoagulants targeting thrombin or factor Xa, and discuss how the introduction of these agents raises the distinction between eligibility for vitamin K antagonist therapy specifically, and eligibility for anticoagulation in general.


Preoperative intensity-modulated radiotherapy and chemotherapy for locally advanced vulvar carcinoma.
Intensity-modulated radiation therapy (IMRT) is a rapidly maturing technology that allows delivery of radiation dose in a more conformal manner by varying the radiation beams spatially or temporally. The purpose of the study was to assess the clinical outcome in patients with locally-advanced vulvar cancers treated using preoperative chemotherapy with IMRT. Eighteen patients with stage II-IVA cancer were treated with a modified GOG schema using 5-fluorouracil (5-FU) and cisplatin with twice-daily (BID) IMRT during the first and last weeks of treatment. Surgery was planned for 6-8 weeks post-treatment. The median follow-up time was 22 months (2-60 months). Fourteen patients had surgery performed with pathological complete response (pCR) in 9 (64%) patients and partial response (pPR) in 5 patients. There were no recurrences in the 9 patients who achieved pCR whereas 3/5 with pPR had local recurrence (p=0.027). Four patients did not have surgery: one patient died a week after treatment while 2 of the remaining 3 patients had local recurrences. Acute desquamative skin reactions in the vulva and perineum were seen in all patients. Three of the 14 patients who had surgery had prolonged wound complications requiring debridement. No patients had radiation-related acute or late toxicity of grade = 3. The 2-year cause specific and overall survivals were 75% and 70% respectively. Preoperative chemotherapy and IMRT were well tolerated with good clinical response and early clinical outcome. Pathological complete response predicts better outcomes. Prospective clinical trials with sufficient patient numbers and follow-up are needed to determine the true impact of IMRT in these patients.


Apoptotic effect of mtrix metalloproteinases 9 in the development of diabetic retinopathy.
To explore the potential regulatory mechanism of MMP9 in the development of DR. Plasmids pcDNA-MMP9 and pcDNA-Ang2 were transfected into primary rat retinal Müller cells (RMCs) using Lipofectamine 2000. Cell viability and apoptosis were respectively determined by MTT assay and flow cytometry. Moreover, the interaction between MMP9 and Ang2 was explored. Besides, RMCs were treated with MMP-9 under normal glucose and high glucose condition for 2d. Besides, the expression levels of apoptotic proteins, like MMP9, Ang2, Bax2, Bcl2, cleaved PARP and cleaved caspase3 were determined by Western blot. The cell viability of siRNA-MMP9 group was significantly increased while decreased in MMP9 overexpression group when compared to control group, respectively. The apoptotic cells in MMP9 overexpression group significantly increased while decreased in siRNA-MMP9 group when compared with control group. MMP9 expression was significantly regulated by Ang2 whereas no significant changes occurred in Ang2 expression when MMP9 expression changed. Moreover, MMP9 expression in HG group significantly increased while there were no significant differences between NG group and control group. Besides, the expression of Bax2, Bcl2, cleaved PARP and cleaved caspase3 in HG group increased while there were no significant differences between NG group and control group. Our findings indicate that MMP9 may play an important role via inducing cell apoptosis in the development of DR via regulating by Ang2 or targeting apoptotic proteins, such as Bax2, Bcl2, cleaved PARP and cleaved caspase3.


Muscle Strength Gain is Positively Associated with Functional Recovery in Patients with Sarcopenic Obesity After Stroke.
Evidence regarding the effect of sarcopenic obesity on recovery in stroke patients is scarce in rehabilitation medicine. The aim of this study was to examine the association between changes in muscle strength and functional outcomes in patients with sarcopenic obesity undergoing rehabilitation after stroke. This study was a retrospective cohort study of stroke patients, consecutively admitted to post-acute rehabilitation wards of a single hospital, of which, only those diagnosed with sarcopenic obesity at admission were included in the final analysis. Bioimpedance analysis was used to measure skeletal muscle mass and body fat mass. Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Sarcopenia was diagnosed using muscle mass index and handgrip strength. Obesity was diagnosed using body fat percentage (men ≥30%, women ≥35%). The evaluated outcomes were Functional Independence Measure (FIM)-motor score at discharge and its gain. Multiple regression analysis was used to verify whether changes in hand grip strength during hospitalization were associated with functional outcomes. Sixty-two patients (29 men) with a mean age of 78 years, were analyzed. The mean change in the hand grip strength was 3.9 kg. In multiple regression analysis, changes in the hand grip strength were significantly associated with FIM-motor at discharge (β = 0.34, P < 0.01) and FIM-motor gain (β = 0.58, P < 0.01). Muscle strength gain was associated with improved functional recovery in stroke patients with sarcopenic obesity.


Preferences regarding contemporary prenatal genetic tests among women desiring testing: implications for optimal testing strategies.
To compare utilities for prenatal testing outcomes among women inclined to continue their pregnancy despite abnormal results versus those inclined to terminate and to analyze how differences affect optimal prenatal testing strategies. Time tradeoff utilities for 23 outcomes were elicited from 281 women. We compared utilities based on termination inclination and applied them to a decision-analytic framework. Of participants, 46.6% indicated that they would 'definitely' or 'probably' continue their pregnancy despite results indicating an intellectual disability. These women assigned higher utilities to abnormal testing results and having a child with an intellectual disability than women who would probably or definitely terminate. Primary cell-free DNA screening had the most quality-adjusted life years for women inclined to continue their pregnancy but yielded an incremental cost-effectiveness ratio (ICER) of $1 685 449. Multiple marker screening with either cell-free DNA or diagnostic testing as follow-up had an ICER of $9037. Primary diagnostic testing resulted in the most quality-adjusted life years for women inclined to terminate, with an ICER of $111 776. Women seeking testing vary in prenatal testing outcome preferences and termination inclinations in the context of results indicating an intellectual disability. How they envision utilizing prenatal testing information impacts their optimal testing strategy. © 2016 John Wiley & Sons, Ltd.


Regulation of neurokinin-1 receptor messenger RNA expression in synovial fibroblasts of patients with rheumatoid arthritis.
We examined whether soluble mediators regulate the expression of tachykinin receptor mRNAs in synovial fibroblasts of patients with rheumatoid arthritis (RA). mRNAs encoding long and short isomers of neurokinin 1 receptor (NK1R), and neurokinin 2 receptor (NK2R) were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Level of long, but not the short, of NK1R mRNA was increased by treatment with 10-100 ng/ml basic fibroblast growth factor (bFGF) or 20 ng/ml tumor necrosis factor-alpha (TNF-alpha), but not with 1ng/ml interleukin 1beta (IL-1beta). TNF-alpha upregulated NK2R mRNA as well as long NK1R mRNA whereas bFGF had no effect on NK2R mRNA. Expression of neurokinin 3 receptor (NK3R) mRNA was not observed in RA fibroblasts, and its expression was not induced by bFGF and TNF-alpha. The basal and increased levels of long NK1R mRNA were inhibited by treatment with 20 microM SU5402, an inhibitor of the tyrosine kinase activity of FGF receptor 1 (FGFR1), or 10 ng/ml transforming growth factor-beta1 (TGF-beta1). SU5402 and TGF-beta1 had no effect on the basal level of short NK1R mRNA. Immunocytochemistry revealed the enhancement by bFGF of immunoreactive NK1Rs in the cells at 24 h after treatment. These results suggest that bFGF, TGF-beta1, and TNF-alpha in synovial tissue and fluid play a role in the regulation of long NK1R expression in synovial fibroblasts of RA patients. It appears that the pathway of downregulation by TGF-beta1 is more dominant in the long NK1R mRNA expression than that of upregulation by bFGF or TNF-alpha. Furthermore, the regulation of short NK1R mRNA expression seems to be performed via a different pathway from that of long isomer mRNA.


Detection and evaluation of normal and malignant cells using laser-induced fluorescence spectroscopy.
The aim of this research is to study the normalized fluorescence spectra (intensity variations and area under the fluorescence signal), relative quantum yield, extinction coefficient and intracellular properties of normal and malignant human bone cells. Using Laser-Induced Fluorescence Spectroscopy (LIFS) upon excitation of 405 nm, the comparison of emission spectra of bone cells revealed that fluorescence intensity and the area under the spectra of malignant bone cells was less than that of normal. In addition, the area ratio and shape factor were changed. We obtained two emission bands in spectra of normal cells centered at about 486 and 575 nm and for malignant cells about 482 and 586 nm respectively, which are most likely attributed to NADH and riboflavins. Using fluorescein sodium emission spectrum, the relative quantum yield of bone cells is numerically determined.


Feasibility of Long-term Proteasome Inhibition in Multiple Myeloma by in-class Transition From Bortezomib to Ixazomib.
The ongoing US MM-6 study is investigating in-class transition (iCT) from parenteral bortezomib-based induction to all-oral IRd (ixazomib-lenalidomide-dexamethasone) with the aim of increasing proteasome inhibitor (PI)-based treatment adherence and duration while maintaining patients' health-related quality of life (HRQoL) and improving outcomes. US community sites are enrolling non-transplant-eligible patients with newly diagnosed multiple myeloma (MM) with no evidence of progressive disease after 3 cycles of bortezomib-based therapy to receive IRd (up to 39 cycles or until progression or toxicity). The patients use mobile or wearable digital devices to collect actigraphy (activity and sleep) data and electronically complete HRQoL, treatment satisfaction and medication adherence questionnaires. The primary endpoint is progression-free survival. The key secondary endpoints include response rates and therapy duration. At the data cutoff, 84 patients had been treated (median age 73 years; 44% aged ≥ 75 years; 49% men; 15% Black or African American; and 10% Hispanic or Latino). Of the 84 patients, 62% were continuing therapy. The mean duration of total PI therapy was 10.1 months and for the IRd regimen was 7.3 months. With an 8-month median follow-up, the 12-month progression-free survival rate was 86% (95% confidence interval, 73%-93%) from both the start of bortezomib-based treatment and the start of IRd. The overall response rate was 62% (complete response, 4%; very good partial response, 25%; partial response, 33%) after bortezomib-based induction and 70% (complete response, 26%; very good partial response, 29%; partial response, 15%) after iCT. The IRd safety profile was consistent with previous clinical trial data, and HRQoL and treatment satisfaction were maintained. The patients included in the US MM-6 study are representative of the real-world US MM population. The use of iCT might permit prolonged PI-based therapy with promising efficacy, without impacting patients' HRQoL or treatment satisfaction.


Safety, tolerability, and preliminary efficacy of SYN120, a dual 5-HT6/5-HT2A antagonist, for the treatment of Parkinson disease dementia: A randomized, controlled, proof-of-concept trial.
SYN120 is a dual serotonin receptor (5-HT6/5-HT2A) antagonist hypothesized to improve cognition and psychiatric symptoms. We evaluated the safety, tolerability, and efficacy of SYN120 in patients with Parkinson disease dementia (PDD). In a multicenter, double-blind, parallel-group, 16-week phase 2a proof-of-concept trial in PDD with concomitant cholinesterase inhibitor use, eligible patients were randomized to oral SYN120 (100 mg/day) or placebo. Adverse events (AEs), Unified Parkinson's Disease Rating Scale (UPDRS) scores, and discontinuations assessed safety and tolerability. The primary and key secondary efficacy measures were the Cognitive Drug Research (CDR) computerized assessment system Continuity of Attention and Quality of Episodic Memory scores. Other efficacy measures were: Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC), Brief Penn Parkinson's Daily Activity Questionnaire-15 (PDAQ-15), Scales for Outcomes in Parkinson's Disease-Sleep Scale (SCOPA-Sleep), and Neuropsychiatric Inventory (NPI). Eighty-two patients were randomized to SYN120 (N = 38) or placebo (N = 44), AEs occurred in 74% and 77% of patients, and treatment discontinuation in both groups was 16%. Nausea and vomiting were more frequent, and motor symptoms (UPDRS) worsened in the SYN120 group. At week 16, the SYN120 and placebo groups did not differ significantly for any cognitive assessment. Cognitive activities of daily living (PDAQ-15) and the NPI-Apathy/Indifference scores improved nominally in the SYN120 group compared with placebo (unadjusted p = 0.029 and 0.028). SYN120 was adequately tolerated, mild worsening of motor symptoms was noted and it did not improve cognition in PDD patients. Its potential benefits for cognitive activities of daily living and apathy warrant further study. Clinicaltrials.gov as NCT02258152.


The gas phase retention volume behavior of organophosphate esters on polyurethane foam.
In this study, the gas-phase retention volume behavior of four highly volatile organophosphate esters (OPEs) on polyurethane foam (PUF) was studied using a frontal chromatogram. The breakthrough volumes (VB) of trimethyl phosphate (TMP), triethyl phosphate (TEP), tripropyl phosphate (TPrP), and tri-n-butyl phosphate (TnBP) were 0.33, 0.59, 10.5, and 32.4 m3, respectively. A significant negative correlation was found between the logarithm value of VB and the subcooled liquid vapor pressure (PL) with an r2 of 0.905, indicating that the vapor penetration depends on both the volatility and total air volume. The enthalpy of desorption and vaporization (ΔHS-ΔHV) showed a significant difference between the tested OPEs and polycyclic aromatic hydrocarbons (PAHs), revealing that the strength of the sorption interaction of the tested OPEs vapor on PUF should be different from that of PAHs. The PUF-air partition coefficients (KPUF-air) of the tested OPEs ranged from 4.3 to 8.1, which were lower than those of three-to four-ring PAHs (7.02-10.2) and organochlorines (8.01-9.72), revealing that the partition of highly volatile OPEs on PUF is lower than that of low-volatile compounds. The PUF/XAD cartridge improved the absorption efficiency of the tested OPEs; however, its sorptive capacity was still limited.


Fast Fourier infrared spectroscopy to characterize the biochemical composition in diatoms.
Diatoms are photosynthetic unicellular microalgae and are nature's hidden source of several biosynthetic metabolites with their use in biofuel, food and drug industries. They mainly contain various lipids, sterols, isoprenoids and toxins with their use in apoptotic, fertility controlling and cancer drugs. Chemical studies on diatoms are limited due to various limitations such as variation of nutrients, contaminants and change in seasonal factors in the environment. To overcome these limitations, we obtained axenic cultures of 12 fresh-water diatom strains on the 22nd day of inoculation having a dry weight of 1 mg each and performed their Fourier transform infrared (FTIR) study for the detection of functional groups responsible for their chemical moiety. The spectral mapping showed a varied level of polyunsaturated fatty acids, amides, amines, ketone bodies and esters for their applications in various pharmacological, food and biofuel industries in the exponential phase of their growth in f/2 media. The FTIR study of the 12 diatom strains showed various similarities in the form of some common peak patterns ranging from 3000 to 3600 cm-1 for vO-H absorption. The symmetric stretching vibration frequency of Diadesmis confervaceae (V2) type species showed different behaviour than others in the spectral region starting from 1600 to 1700 cm-1. The absorption between 1500 and 1575 cm-1 reflects the presence of the -N-H group. Infrared (IR) absorptions falling between 1600 and 1700 cm-1 reflect the presence of amide's vC=O in all species. Placoneis elginensis (V8) type species showed an additional absorption band which is centred around 1735-1750 cm-1 which perhaps reflects the presence of ester's vC=O. Diadesmis confervaceae (V2), Nitzschia palea (V4), Placoneis elginensis (V8), Nitzschia palea var. debilis (V6), Nitzschia inconspicua (V10), Gomphonema parvulum (V11) and Sellaphora (V12) showed distinct structural features with important key functionalities that can make them essential drug markers in the pharmaceutical industry.


Cloning and functional characterization of Arabidopsis thaliana D-amino acid aminotransferase--D-aspartate behavior during germination.
The understanding of D-amino acid metabolism in higher plants lags far behind that in mammals, for which the biological functions of these unique amino acids have already been elucidated. In this article, we report on the biochemical behavior of D-amino acids (particularly D-Asp) and relevant metabolic enzymes in Arabidopsis thaliana. During germination and growth of the plant, a transient increase in D-Asp levels was observed, suggesting that D-Asp is synthesized in the plant. Administration of D-Asp suppressed growth, although the inhibitory mechanism responsible for this remains to be clarified. Exogenous D-Asp was efficiently incorporated and metabolized, and was converted to other D-amino acids (D-Glu and D-Ala). We then studied the related metabolic enzymes, and consequently cloned and characterized A. thaliana D-amino acid aminotransferase, which is presumably involved in the metabolism of D-Asp in the plant by catalyzing transamination between D-amino acids. This is the first report of cDNA cloning and functional characterization of a D-amino acid aminotransferase in eukaryotes. The results presented here provide important information for understanding the significance of D-amino acids in the metabolism of higher plants.


Prevalence, awareness, treatment, and control of hypertension among Black Surinamese, South Asian Surinamese and White Dutch in Amsterdam, The Netherlands: the SUNSET study.
To assess ethnic differences in prevalence, levels of awareness, treatment and control of hypertension among Dutch ethnic groups and to determine whether these differences are consistent with the UK findings. Cross-sectional survey. South-east Amsterdam, The Netherlands. A random sample of 1383 non-institutional adults aged 35-60 years. Of these, 36.7% were White, 42% were Black and 21.3% were South Asian people. Prevalence of hypertension, rates of awareness, treatment, and control of hypertension. The Black and South Asian subjects had a higher prevalence of hypertension compared with White people. After adjustments for age, the odds ratios (95% confidence interval) for being hypertensive were 2.2 (1.4-3.4; P < 0.0001) and 3.8 (2.6-5.7; P < 0.0001) for Black men and women, respectively, and 1.7 (1.0-2.6; P = 0.039) and 2.8 (1.8-4.5; P < 0.0001) for South Asian men and women, compared with White people. There were no differences in awareness and pharmacological treatment of hypertension between the groups. However, Black hypertensive men 0.3 (0.1-0.7; P < 0.01) and women 0.5 (0.3-0.9; P < 0.05) were less likely to have their blood pressure adequately controlled compared with White people. The higher prevalence of hypertension found among Black and South Asian people in The Netherlands is consistent with the UK studies. However, the lower control rates and the similar levels of awareness and treatment of hypertension in Black Surinamese contrast with the higher rates reported in African Caribbeans in the UK. The rates for the South Asians in The Netherlands were relatively favourable compared to similar South Asian groups in the UK. These findings underscore the urgent need to develop strategies aimed at improving the prevention and control of hypertension, especially among Black people, in The Netherlands.


Electrical and mechanical effects of amrinone on isolated guinea pig ventricular muscle.
The electromechanical effects of amrinone on isolated guinea pig papillary muscle were studied at various driving frequencies and under the influence of several antagonists and a low calcium medium. Amrinone (3 X 10(-5)-2 X 10(-3)M) caused a positive inotropic effect on preparations driven at 1.0 Hz in a concentration-dependent manner. When the preparations were driven at a frequency lower than 0.5 Hz, the positive inotropic effect of the drug was markedly attenuated. Amrinone caused a significant prolongation in action potential duration at an early repolarization phase--but not at a late repolarization phase--without affecting any other parameters of action potential. These effects of amrinone were not blocked by a beta-adrenoceptor antagonist or tetrodotoxin, but were inhibited by treatment with verapamil (5 X 10(-6)M) or a low calcium medium (0.1 or 0.3 mM). In papillary muscles depolarized by 30 mM [K+]o, amrinone enhanced the slow action potentials. In voltage clamp experiments using a single sucrose-gap method, amrinone (6 X 10(-4)M) caused a marked increase in the peak amplitude of the slow inward current, while it did not affect the net outward current. The results suggest that the slow calcium inward current may play a predominant role in the positive inotropic effect of amrinone.


A targeting delivery system for effective genome editing in leukemia cells to reverse malignancy.
Therapy resistance associated with relapse is a main cause of death in acute myeloid leukemia (AML). To address this issue, a dual-targeting CRISPR-Cas9 genome editing nanosystem was constructed for CXCR4 knockout to reverse the malignancy of leukemia cells. The surface of the dual-targeting nanosystem is composed of MUC1 specific aptamer incorporated alginate (MUC1 aptamer-alginate) and T22-NLS peptide with T22 sequence targeting CXCR4; the core of the nanosystem consists of protamine complexed with CRISPR-Cas9 plasmid. The in vitro study shows that the nanosystem mediated genome editing induces cell apoptosis, cell cycle arrest, as well as inhibited cell migration and adhesion in edited THP-1 cells after CXCR4 knockout. Further, the unprocessed peripheral blood from acute myeloid leukemia (AML) patients was directly used to carry out ex vivo study. The results show the genome editing nanosystem can effectively knock out CXCR4 in leukemia cells, leading to attenuated CXCR4 protein as studied by antibody labeling and reduced CXCR4 mRNA as probed by a molecular beacon delivery system. In addition to developing a promising delivery vector for gene therapy on AML, this study also provides an effective strategy to evaluate the therapeutic efficiency of particular treatments by peripheral blood-based ex vivo studies.


Curcumin Inhibits Invasion and Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma Cells by Regulating TET1/Wnt/β-catenin Signal Axis.
The molecular mechanisms of flavonoid curcumin used in cancer treatment are not fully understood. The results of this study suggest that curcumin evidently inhibits epithelial-mesenchymal transition, cell growth, and invasion of hepatocellular carcinoma cell lines HepG2 and Huh-7, as well as the Wnt/β-catenin signal pathway. Curcumin might exert anti-tumor effect on hepatocellular carcinoma cells by regulating the TET1/Wnt/β-catenin signal pathway to inhibit the epithelial-mesenchymal transition progress.


First example of conformational exchange in a natural taxane enolate.
A detailed NMR study and full assignments of the (1)H- and (13)C-NMR spectral data for a novel enolate taxane isolated from Taxus canadensis needles is described. The structures of two stable conformers were established using a combination of 1D and 2D NMR techniques including (1)H, (1)H-COSY, gs-HMQC, gs-HMBC, NOESY and T-ROESY. Ab initio quantum mechanical calculations were performed on the B3LYP/6-31G* level of basis set to assist the NMR findings.


A comparison of nanosilver and silver ion effects on bioreactor landfill operations and methanogenic population dynamics.
Silver nanoparticles (AgNPs, nanosilver) and silver ions released from industry and various consumer products are eventually disposed in sanitary landfills. To compare the effects of these two forms of silver on landfill bioreactor operations with leachate recirculation, municipal solid waste (MSW) in six identical 9-L bioreactors was exposed to AgNPs (stabilized with 0.06% polyvinyl alcohol) or Ag(+) at a silver concentration of 10 mg/kg solids. The landfill anaerobic digestion was operated and monitored for more than 200 days. There was no significant difference in cumulative methane volume or methane production rate between the groups of control and 10 mg/kg Ag(+). However, MSW treated with 10 mg/kg AgNPs resulted in a reduced methane production (by up to 80%) and accumulation of volatile fatty acids in the leachates. This was accompanied by higher leachate Ag concentrations (an average of 3.7 ± 0.3 mg/L) after day 132 as compared to those in the groups of control and 10 mg/kg Ag(+) at 0.7 ± 0.4 and 1.1 ± 0.3 mg/L, respectively. Quantitative PCR targeting 16S rRNA genes of methanogens indicated reduced methanogenic growth in the bioreactors exposed to nanosilver. The peak values of total methanogens in leachates were (1.18 ± 0.09) × 10(10), (4.57 ± 2.67) × 10(10) and (7.72 ± 0.78) × 10(8) (cells/mL) for the groups of control, Ag(+) and AgNPs, respectively. The results suggest that silver ions have minimal impact on landfill methane production at the concentration of 10 mg/kg. However, nanosilver inhibits methanogenesis and is more toxic than its counterpart, likely due to slow and long-term Ag(+) release from nanosilver dissolution yielding more bioavailability in landfill leachates.


Quantitative evaluation of pallor-disc ratio and colour of the optic disc by a photographic method.
A photographic technique is described, which is based on simultaneous photography of the papilla with green and red filters by means of a stereoscopic fundus camera. Using black and white film, the negatives are photometrically measured and the pallor-disc ratio and colour of the papilla are calculated from the densitometric tracings. The latter parameter is quantitatively expressed by a numerical index. The method is demonstrated in a practical example.


A three-dimensional data visualization technique for reporting movement pattern deviations.
Relative motion plots are the most prevalent method for displaying interjoint coupling. The method, however, is limited when amplitude and timing comparisons of like data are of interest. Another limitation of relative motion plots is that the second parameter (e.g., angle) is included at the expense of a continuous time reference. In this paper, we present a novel method for displaying three-dimensional movement pattern deviations. Parameter-parameter-time data (e.g., knee and hip angle as a function of time) are color-coded based on the magnitude and direction of the deviation. The color-coded deviations are mapped to an individual's three-dimensional parameter-parameter-time trajectory, resulting in a multi-color, three-dimensional curve depicting how an individual's parameter-parameter-time pattern differs relative to a reference pattern. The algorithmic development of the color-coded parameter-parameter-time display is presented and comparative patient and normative data are reported.


Study of the in vitro activation of the complement alternative pathway by Echinococcus granulosus hydatid cyst fluid.
In the present study we have investigated the fluid phase activation of the complement (C) alternative pathway by Echinococcus granulosus sheep hydatid cyst fluid (SHCF) and its higher molecular weight fraction (SHCF-I) by quantitating the formation of both the terminal C intermediary C5b6 complex and the terminal C complex (TCC). Our results show that in vitro C activation progresses beyond the C5 step suggesting that potentially lytic complexes may be generated in vivo. In addition, SHCF and SHCF-I glucidic moieties are probably involved in C activation since 80% and 86% of SHCF and SHCF-I activity respectively was destroyed by periodate oxidation. Furthermore, partial deglycosylation with Peptide N-Glycosidase F of SHCF-I which had been digested with Pronase E, released an active fraction (MW < 14 KDa) which bound to Soybean agglutinin, suggesting that N-linked oligosaccharides containing alpha- or beta-linked N-acetyl galactosamine play a role in C activation by SHCF.


Ceramides Increase Fatty Acid Utilization in Intestinal Progenitors to Enhance Stemness and Increase Tumor Risk.
Cancers of the alimentary tract, including esophageal adenocarcinomas, colorectal cancers, and cancers of the gastric cardia, are common comorbidities of obesity. Prolonged, excessive delivery of macronutrients to the cells lining the gut can increase one's risk for these cancers by inducing imbalances in the rate of intestinal stem cell proliferation vs differentiation, which can produce polyps and other aberrant growths. We investigated whether ceramides, which are sphingolipids that serve as a signal of nutritional excess, alter stem cell behaviors to influence cancer risk. We profiled sphingolipids and sphingolipid-synthesizing enzymes in human adenomas and tumors. Thereafter, we manipulated expression of sphingolipid-producing enzymes, including serine palmitoyltransferase (SPT), in intestinal progenitors of mice, cultured organoids, and Drosophila to discern whether sphingolipids altered stem cell proliferation and metabolism. SPT, which diverts dietary fatty acids and amino acids into the biosynthetic pathway that produces ceramides and other sphingolipids, is a critical modulator of intestinal stem cell homeostasis. SPT and other enzymes in the sphingolipid biosynthesis pathway are up-regulated in human intestinal adenomas. They produce ceramides, which serve as prostemness signals that stimulate peroxisome-proliferator activated receptor-α and induce fatty acid binding protein-1. These actions lead to increased lipid utilization and enhanced proliferation of intestinal progenitors. Ceramides serve as critical links between dietary macronutrients, epithelial regeneration, and cancer risk.


Rapid Quantification of Oxidation and UV Induced DNA Damage by Repair Assisted Damage Detection-(Rapid RADD).
Knowing the amount and type of DNA damage is of great significance for a broad range of clinical and research applications. However, existing methods are either lacking in their ability to distinguish between types of DNA damage or limited in their sensitivity and reproducibility. The method described herein enables rapid and robust quantification of type-specific single-strand DNA damage. The method is based on repair-assisted damage detection (RADD) by which fluorescent nucleotides are incorporated into DNA damage sites using type-specific repair enzymes. Up to 90 DNA samples are then deposited on a multiwell glass slide, and analyzed by a conventional slide scanner for quantification of DNA damage levels. Accurate and sensitive measurements of oxidative or UV-induced DNA damage levels and repair kinetics are presented for both in vitro and in vivo models.


Nemo-like kinase induces apoptosis in DLD-1 human colon cancer cells.
Deregulation of Wnt/beta-catenin signaling is thought to play a critical role in human carcinogenesis. Nemo-like kinase (NLK) is an evolutionarily conserved serine/threonine kinase that suppresses beta-catenin/T-cell factor (TCF) complex transcriptional activity through phosphorylation of TCF. Since NLK may be a tumor suppressor as a negative regulator of Wnt/beta-catenin pathway, we established tetracycline-inducible NLK and its kinase-negative mutant expression in DLD-1 human colon cancer cells to analyze the effect of NLK on cell growth and viability. The induction of wild-type NLK in DLD-1 cells caused suppression of cell growth whereas the kinase-negative mutant did not. Flow cytometry indicated that NLK expression increased the number of apoptotic cells but did not induce obvious cell cycle arrest. Apoptosis induction by wild-type NLK was confirmed using TUNEL assays. Our results suggest that overexpression of NLK may have targets other than TCF for induction of apoptosis in human colon carcinoma cells.


STRIDE: Systematic Radar Intelligence Analysis for ADRD Risk Evaluation with Gait Signature Simulation and Deep Learning.
Abnormal gait is a significant non-cognitive biomarker for Alzheimer's disease (AD) and AD-related dementia (ADRD). Micro-Doppler radar, a non-wearable technology, can capture human gait movements for potential early ADRD risk assessment. In this research, we propose to design STRIDE integrating micro-Doppler radar sensors with advanced artificial intelligence (AI) technologies. STRIDE embeds a new deep learning (DL) classification framework. As a proof of concept, we develop a "digital-twin" of STRIDE, consisting of a human walking simulation model and a micro-Doppler radar simulation model, to generate a gait signature dataset. Taking established human walking parameters, the walking model simulates individuals with ADRD under various conditions. The radar model based on electromagnetic scattering and the Doppler frequency shift model is employed to generate micro-Doppler signatures from different moving body parts (e.g., foot, limb, joint, torso, shoulder, etc.). A band-dependent DL framework is developed to predict ADRD risks. The experimental results demonstrate the effectiveness and feasibility of STRIDE for evaluating ADRD risk.


Ficus-mediated green synthesis of manganese oxide nanoparticles for adsorptive removal of malachite green from surface water.
The extract of ficus leaves was used to prepare manganese (IV) oxide nanoparticles (MnO2 NPs) for the first time. Several different analytical techniques were used to characterize the prepared MnO2 NPs. MnO2 has spherical crystals that are ~ 7 nm on average in size and have 149.68 m2/g of surface area and 0.91 cm3/g of total pore volume. Malachite green (MG) dye was then taken out of the water by adsorption using MnO2 NPs. Optimization of various adsorption parameters resulted in 188.68-277.78 mg/g maximum adsorption capacities at 298-328 K tested temperatures and 99.6% removal of 50 mg/L MG within 90 min using MnO2 dose of 0.01 g at pH 10 and 298 K. The results were tested using pseudo-first order, pseudo-second order, intraparticle diffusion, Elovich, and Liquid film kinetic models as well as Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich isotherm models. The most likely models to describe the adsorption process at 298 K are pseudo-second-order kinetics (R2 = 0.997) with a rate constant of 4 × 10-4 g/(mg.min) and Langmuir isotherm (R2 = 0.973). Additionally, the positive values of enthalpy change (3.91-67.81 kJ/mol) and the negative values of Gibb's free energy (- 3.38 to - 19.7 kJ/mol) indicate that the process is endothermic, spontaneous, and thermodynamically feasible. MnO2 NPs sustained their adsorption efficiency at 90.4% after 5 sorption cycles. MnO2 appears to be more selective for MG in studies examining the adsorption of various cationic dyes. Lately, the biosynthesized MnO2 NPs can be utilized to remove MG from aqueous solutions effectively.


Reappraisal of Supraorbital Sensory Nerve Conduction Recordings: Orthodromic and Antidromic Techniques.
To establish a supraorbital nerve sensory conduction recording method and assess its usefulness. Thirty-one healthy subjects without a history of trauma or neurological disease were recruited. For the orthodromic procedure, the recording electrode was attached immediately superior to the supraorbital notch. The stimulation electrode was placed on points along the hairline which evoked the largest sensory nerve action potentials (SNAPs). The antidromic sensory response was recorded after switching the recording and stimulating electrodes. The measured parameters were onset latency, peak latency, and baseline to peak amplitude of the SNAPs. The electrophysiological parameters of the bilateral supraorbital nerves were compared. We also recruited two patients who had sensory deficits on one side of their foreheads because of laceration injuries. The parameters of orthodromically recorded SNAPs were as follows: onset latency 1.21±0.22 ms (range, 0.9-1.6 ms), peak latency 1.54±0.23 ms (range, 1.2-2.2 ms), and baseline to peak amplitude 4.16±1.92 µV (range, 1.4-10 µV). Those of antidromically recorded SNAPs were onset latency 1.31±0.27 ms (range, 0.8-1.7 ms), peak latency 1.62±0.29 ms (range, 1.3-2.2 ms), and baseline to peak amplitude 4.00±1.89 µV (range, 1.5-9.0 µV). There was no statistical difference in onset latency, peak latency, or baseline to peak amplitude between the responses obtained using the orthodromic and antidromic methods, and the parameters also revealed no statistical difference between the supraorbital nerves on both sides. We have successfully recorded supraorbital SNAPs. This conduction technique could be quite useful in evaluating patients with supraorbital nerve lesions.


Human and mouse granzyme A induce a proinflammatory cytokine response.
Granzyme A (GzmA) is considered a major proapoptotic protease. We have discovered that GzmA-induced cell death involves rapid membrane damage that depends on the synergy between micromolar concentrations of GzmA and sublytic perforin (PFN). Ironically, GzmA and GzmB, independent of their catalytic activity, both mediated this swift necrosis. Even without PFN, lower concentrations of human GzmA stimulated monocytic cells to secrete proinflammatory cytokines (interleukin-1beta [IL-1beta], TNFalpha, and IL-6) that were blocked by a caspase-1 inhibitor. Moreover, murine GzmA and GzmA(+) cytotoxic T lymphocytes (CTLs) induce IL-1beta from primary mouse macrophages, and GzmA(-/-) mice resist lipopolysaccharide-induced toxicity. Thus, the granule secretory pathway plays an unexpected role in inflammation, with GzmA acting as an endogenous modulator.


Neuroendocrine control of the gut during stress: corticotropin-releasing factor signaling pathways in the spotlight.
Stress affects the gastrointestinal tract as part of the visceral response. Various stressors induce similar profiles of gut motor function alterations, including inhibition of gastric emptying, stimulation of colonic propulsive motility, and hypersensitivity to colorectal distension. In recent years, substantial progress has been made in our understanding of the underlying mechanisms of stress's impact on gut function. Activation of corticotropin-releasing factor (CRF) signaling pathways mediates both the inhibition of upper gastrointestinal (GI) and the stimulation of lower GI motor function through interaction with different CRF receptor subtypes. Here, we review how various stressors affect the gut, with special emphasis on the central and peripheral CRF signaling systems.


Lack of molecular evidence of fecal-borne viruses in capybaras from São Paulo state, Brazil, 2018-2020: a minor public health issue.
Capybara (Hydrochoerus hydrochaeris) is the world's largest rodent species distributed throughout South America. These animals are incredibly tolerant to anthropogenic environments and are occupying large urban centers. Capybaras are known to carry potentially zoonotic agents, including R. rickettsia, Leishmania spp., Leptospira spp., Trypanosoma spp., Salmonella spp., Toxoplasma gondii, and rabies virus. Focusing on the importance of monitoring potential sources of emerging zoonotic viruses and new viral reservoirs, the aim of the present study was to assess the presence of fecal-borne viruses in the feces of capybaras living in urban parks in São Paulo state, Brazil. A total of 337 fecal samples were collected between 2018 and 2020 and screened for the following: (i) Rotavirus group A (RVA) by ELISA; (ii) non-RVA species and Picobirnavirus (PBV) using PAGE; (iii) Human Bocaparvovirus (HBoV), Bufavirus (BuV), Tusavirus (TuV), and Cutavirus (CuV) qPCR; (iv) Human Enterovirus (EV), Norovirus GII (NoV), and Hantavirus by in houses RT-qPCR; (v) SARS-CoV-2 via commercial RT-qPCR kit assay; and (vi) Astrovirus (AstV) and Adenovirus (AdV) using conventional nested (RT)-PCRs. All fecal samples tested were negative for fecal-borne viruses. This study adds further evidence that the fecal-borne viruses is a minor public health issue in Brazilian capybaras, at least during the surveillance period and surveyed areas. Continuous monitoring of sylvatic animals is essential to prevent and control the emergence or re-emergence of newly discovered virus as well as viruses with known zoonotic potential.


Accelerating action of tea on mouse skin carcinogenesis.
The effect of different tannin-containing aqueous solutions on the carcinogenic action of benzo(a)pyrene (BP) on the mouse skin was investigated. It was found that the appearance of tumours was accelerated in mice treated with either tea or an oak extract after a single application of BP. The time of appearance of tumours in mice treated with gallic acid or tannic acid after treatment with BP was similar to that in the group treated with BP alone. The overall incidence of tumours was similar in all five groups.


Toward Reference Intervals of ARSA Activity in the Cerebrospinal Fluid: Implication for the Clinical Practice of Metachromatic Leukodystrophy.
Cerebrospinal fluid (CSF) has emerged as a sensitive matrix for the screening of biomarkers for diagnosis and clinical follow-up of diseases with neurological manifestations, including some lysosomal storage disorders. In this study, we assessed the range of values of arylsulfatase A (ARSA) activity in the CSF of pediatric and adult donors, and in pediatric patients who underwent gene therapy for metachromatic leukodystrophy (MLD). A cohort of 56 CSF samples was included in the study: pediatric donors (n = 36), adult donors (n = 9), and MLD patients (n = 11) at different timepoints [pre-gene therapy (GT), post-GT + 1 Year, post-GT + 2 Years, post-GT + 3 Years]. We have used our fluorometric assay for the determination of ARSA activity. The total protein content in the samples was also evaluated. We discovered that ARSA activity was higher in pediatric donors (geometric mean: 1.039 nmol/mg/h; 95% range: 0.859-1.258 nmol/mg/h) compared to adults (geometric mean: 0.305 nmol/mg/h; 95% range: 0.214-0.435 nmol/mg/h). No ARSA activity was detected in the CSF of MLD patients pre-GT, whereas ARSA activity was stably expressed and almost restored to range of values of pediatric donors in MLD patients post-GT + 3 Years with a geometric mean of 0.822 nmol/mg/h (95% range: 0.580-1.165 nmol/mg/h). This study establishes range of values of ARSA activity in the CSF for MLD clinical practice. The observed ranges of ARSA activities in CSF exhibited an unpredicted age dependence and, in turn, revealed the need of using pediatric ARSA activity for evaluating the restoration of the enzyme activity during the therapy of MLD.


PET/CT imaging in gynecologic malignancies: a critical overview of its clinical impact and our retrospective single center analysis.
Gynecologic cancers represent a major global healthcare problem since they are associated with a significant mortality and morbidity. Over the last decade, considerable efforts have been spent in the development and optimization of novel diagnostic modalities to achieve an early diagnosis, aid in choosing appropriate treatment, improving long term surveillance, with the ultimate goal of increasing survival of gynecologic cancer patients. A growing body of evidence defines PET/CT as one of the most powerful tools for tumor, nodal and metastasis (TNM) cancer staging both in pre-treatment and in post treatment follow-up settings. At any phase of cancer evaluation, detection of metastasis represents one of the most critical impediments to the cure of tumor; traditional diagnostic imaging modalities, such as computed tomography (CT), are frequently found to inadequately stage the tumor, based on subsequent outcomes. As a consequence, patients may undergo pointless surgery for disease that could be treated with local medical therapies. In the setting of restaging, the ability to describe primary lesion, lymph nodes, possible metastases to peritoneum, bone, liver, lungs and brain renders PET/CT a potential alternative for a series of tests, including bone scanning, MRI or ultrasound, diagnostic CT, lymph node surgical sampling, that need to be used in combination in order to obtain a level of clinical confidence. In this review, we describe, the theoretical advantage and prognostic implications of PET/CT in the management of gynecologic cancer patients.


Intensity Modulated Proton Therapy Better Spares Non-Adjacent Organs and Reduces the Risk of Secondary Malignant Neoplasms in the Treatment of Sinonasal Cancers.
This study compare dosimetric parameters and secondary malignancy risk (SMN) using intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans for the treatment of sinonasal cancer (SC). After IRB-approval, 10 patients previously treated with IMPT for cancers of the ethmoid, sphenoid, maxillary, or frontal sinuses were identified. Dosimetrists blinded to the IMPT plans generated VMAT plans for comparison. Volume coverage and dose to organs at risk (OAR) were recorded and compared. Organ equivalent dose (OED) of tissues outside of the treatment volume was used to define the excess absolute and relative risk of SMNs. In all cases, both VMAT and IMPT provided acceptable target volume coverage and were able to meet OAR constraints. IMPT was superior for brain V10, V30, and mean, brainstem D0.01 ipsilateral cochlea V30, contralateral cochlea mean, contralateral lacrimal gland mean, contralateral parotid mean, spinal cord D0.01 and body outside of the CTV V10, V20, and V30. VMAT was superior for ipsilateral eye mean, ipsilateral lens mean, CTV V100 and maximum hotspot. The relative risk of SMNs with VMAT compared to IMPT is 3.35 (95% CI, 1.92-5.89). For the treatment of SC, IMPT spares OARs that are not immediately adjacent to the treatment volume and reduces the risk of SMNs when compared to VMAT. VMAT spares OARs abutting the target volume better than IMPT and has more homogenous target coverage. Tumors of the ethmoid sinus, benefit more from IMPT, while tumors located elsewhere require application of our findings on a case by case basis.


Point-of-care C-reactive protein test results in acute infections in children in primary care: an observational study.
Acute infections are a common reason for children to consult primary care. Serious infections are rare but differentiating them from self-limiting illnesses remains challenging. This can lead to inappropriate antibiotic prescribing. Point-of-care C-reactive protein testing is used to guide antibiotic prescribing in adults. However, in children its use remains unclear. The purpose of this study was to assess point-of-care CRP test levels with respect to patients' characteristics, care setting, preliminary diagnosis, and management. A prospective observational study was performed in children with an acute infection presenting to ambulatory care in Belgium. In this study 8280 cases were analysed, of which 6552 had a point-of-care CRP value available. A total of 276 physicians participated. The median patient age was 1.98 years (IQR 0.97 to 4.17), 37% of children presented to a general practitioner, 33% to a paediatric out-patient clinic, and 30% to the emergency department. A total of 131 different preliminary diagnoses were found, with acute upper airway infection as the most frequent. In 6% (n = 513) patients were diagnosed with a serious infection. The most common serious infection was pneumonia. Antibiotics were prescribed in 28% (n = 2030) of all episodes. The median CRP over all infectious episodes was 10 mg/L (IQR < 5-29). Children below 5 years of age and those presenting to a paediatrician had a higher median CRP. Median CRP in patients with serious infections was 21 mg/L (IQR 6 to 63.5). Pneumonia had a median CRP of 48 mg/L (IQR 13-113). In the episodes with antibiotics prescription, median CRP level was 29 mg/L (IQR 10-58) compared to 7 mg/L (IQR < 5-19) when they were not prescribed. A low POC CRP as a standalone tool did not seem to be sufficient to rule out serious infections, but its potential in assessing serious infections could increase when integrated in a clinical decision rule. ClinicalTrials.gov Identifier: NCT02024282 (registered on 31/12/2013).


Gender and online privacy among teens: risk perception, privacy concerns, and protection behaviors.
Survey data from 395 high school students revealed that girls perceive more privacy risks and have a higher level of privacy concerns than boys. Regarding privacy protection behaviors, boys tended to read unsolicited e-mail and register for Web sites while directly sending complaints in response to unsolicited e-mail. This study found girls to provide inaccurate information as their privacy concerns increased. Boys, however, refrained from registering to Web sites as their concerns increased.


Suspended lead suit and physician radiation doses during coronary angiography.
This study was performed to evaluate physician radiation doses with the use of a suspended lead suit. Interventional cardiologists face substantial occupational risks from chronic radiation exposure and wearing heavy lead aprons. Head-level physician radiation doses, collected using real-time dosimeters during consecutive coronary angiography procedures, were compared with the use of a suspended lead suit versus conventional lead aprons. Multiple linear regression analyses were completed using physician radiation doses as the response and testing patient variables (body mass index, age, sex), procedural variables (right heart catheterization, fractional flow reserve, percutaneous coronary intervention, radial access), and shielding variables (radiation-absorbing pad, accessory lead shield, suspended lead suit) as the predictors. Among 1054 coronary angiography procedures, 691 (65.6%) were performed with a suspended lead suit and 363 (34.4%) with lead aprons. There was no significant difference in dose area product between groups (61.7 [41.0, 94.9] mGy·cm2 vs. 64.6 [42.9, 96.9] mGy·cm2 , p = 0.20). Median head-level physician radiation doses were 10.2 [3.2, 35.5] μSv with lead aprons and 0.2 [0.1, 0.9] μSv with a suspended lead suit (p < 0.001), representing a 98.0% reduced dose with suspended lead. In the fully adjusted regression model, the use of a suspended lead suit was independently associated with a 93.8% reduction (95% confidence interval: -95.0, -92.3; p < 0.001) in physician radiation dose. Compared to conventional lead aprons, the use of a suspended lead suit during coronary angiography was associated with marked reductions in head-level physician radiation doses.


Optimising Golgi-Cox staining for use with perfusion-fixed brain tissue validated in the zQ175 mouse model of Huntington's disease.
The Golgi-Cox stain is an established method for characterising neuron cell morphology. The method highlights neurite processes of stained cells allowing the complexity of dendritic branching to be measured. Conventional rapid Golgi and Golgi-Cox methods all require fresh impregnation in unfixed brain blocks. Here, we describe a modified method that gives high quality staining on brain tissue blocks perfusion-fixed with 4% paraformaldehyde (PFA) and post-fixed by immersion for 24h. Tissue perfused with 4% PFA and post fixed for 24h remained viable for the modified Golgi-Cox silver impregnation staining of mouse striatum from perfused wild type and zQ175. It was not found necessary to impregnate tissue blocks with Golgi solutions prior to sectioning, as post-sectioned tissues yielded equally good impregnation. Impregnation for 14 days resulted in optimal visualisation of striatal neuron and dendritic morphology. Although no modifications applied to the rapid Golgi method were reliable, the modified Golgi-Cox method yielded consistently reliable high-quality staining. The current method used fixed tissues to reduce damage and preserve cell morphology. The revised method was found to be fast, reliable and cost effective without the need for expensive staining kits and could be performed in any neuroscience lab with limited specialist equipment. The present study introduces a robust reproducible and inexpensive staining method for identifying neuronal morphological changes in the post fixed mouse brain, and is suitable for assessing changes in cell morphology in models of neurodegeneration and in response to experimental treatment.


Capacity to produce interleukin 2 is impaired in haemophilia in the absence and presence of HIV 1 infection.
Capacity to produce interleukin-2 (IL-2) was measured in haemophiliacs from a well-defined treated cohort. Patients were selected on the basis of HIV-1 antibody status, mean annual dose of clotting factor and liver disease severity. T-cell subsets and peripheral blood mononuclear cell proliferation to Mycobacterium tuberculosis purified protein derivative (PPD) were also measured. Haemophiliacs had reduced IL-2 production, independent of HIV-1 antibody status, mean annual dose of clotting factor concentrate used and liver disease severity. In HIV-1 antibody positive patients reduced levels correlated with PPD proliferative responses (r = 0.6, P = 0.04) and CD8 + ve (r = 0.5, P = 0.05) but not CD4 + ve cell numbers (r = 0.3, P = 0.2). No such correlations were seen in HIV-1 antibody negative patients. Reduced IL-2 production in HIV-1 antibody negative haemophiliacs was due to a qualitative defect. In HIV-1 positive patients a qualitative defect in T lymphocytes that selectively proliferate in response to PPD was observed. CD4 + ve cell numbers were reduced in HIV-1 positive patients.


Genetic, Biochemical, and Structural Analyses of Bacterial Surface Polysaccharides.
Surface polysaccharides are an often essential component of the outer surface of bacteria. They may serve to protect organisms from harsh environmental conditions and to increase virulence. The focus of this review will be to introduce polysaccharide biosynthesis and export from the cell, and the associated techniques used to determine these glycostructures. Protein interactions and proteomics will then be discussed while introducing systems biology approaches used to determine protein-protein and protein-polysaccharide interactions. The final section will address related screening methods used to study gene regulation in bacteria relating to polysaccharide gene clusters and their associated regulators. The goal of this review will be to highlight key studies that have increased our knowledge of glycobiology and discuss novel methods that examine this field at the cellular level using systems biology.


Embryonic hippocampal grafts ameliorate the deficit in DRL acquisition produced by hippocampectomy.
Transplants of fetal neural tissue survive and develop in lesion cavities produced in adult rats. The present experiment tested the effect of grafting fetal hippocampal or brainstem tissue on the ability of rats with hippocampal lesions to perform on a differential reinforcement of low response rate (DRL) operant schedule. The DRL interval was 20s. Eighty-six percent of the hippocampal grafts and 69% of the brainstem grafts developed to maturity. Inspection of sections from rats in which the mature transplant had been injected with Fast blue, indicated that these grafts formed connections with the host brain. Consistent with previous reports, rats with hippocampal lesions were impaired in performance of the DRL task. Rats given fetal grafts of hippocampal tissue into the hippocampal lesion site on the day of lesion production were significantly better in performance of the DRL requirement than were lesion-only rats or rats receiving grafts of fetal brainstem tissue. The results of this study confirm that grafts of fetal brain tissue can both develop in a lesion site in an adult brain and ameliorate lesion-induced behavioral deficits.


Childbirth and pelvic floor trauma.
The issue of traumatic damage to the pelvic floor in childbirth is attracting more and more attention amongst obstetric caregivers and laypersons alike. This is partly due to the fact that elective caesarean section as a potentially preventative intervention is increasingly available and perceived as safe. As there is a multitude of emotive issues involved, including health economics and the relative roles of healthcare providers, the discussion surrounding pelvic floor trauma in childbirth has not always been completely rational. However, after 25 years of urogynaecological research in this field it should be possible to determine whether pelvic floor trauma in childbirth is myth or reality, and, if real, whether it matters for the pathogenesis of incontinence and prolapse. On reviewing the available evidence, it appears that there are sufficient grounds to assume that vaginal delivery (or even the attempt at vaginal delivery) can cause damage to the pudendal nerve, the inferior aspects of the levator ani muscle and fascial pelvic organ supports. Risk factors for such damage have been defined and variously include operative vaginal delivery, a long second stage, and macrosomia. It is much less clear, however, whether such trauma is clinically relevant, and how important it is in the aetiology of pelvic floor morbidity later in life.


Genetic homogeneity between childhood-onset and adult-onset autosomal recessive spinal muscular atrophy.
Molecular diagnosis of childhood proximal spinal muscular atrophy has been enhanced by the discovery of the survival motor neuron (SMN) gene, which is absent or truncated in 98.6% of patients. To determine whether deletion analysis of the SMN gene may also be diagnostic for adult-onset disease, we studied six patients and found deletions in all. This finding will facilitate the diagnosis of adult-onset spinal muscular atrophy, and provides evidence for genetic homogeneity between the clinically diverse adult and childhood forms of the disease.


Metatranscriptomics reveal differences in in situ energy and nitrogen metabolism among hydrothermal vent snail symbionts.
Despite the ubiquity of chemoautotrophic symbioses at hydrothermal vents, our understanding of the influence of environmental chemistry on symbiont metabolism is limited. Transcriptomic analyses are useful for linking physiological poise to environmental conditions, but recovering samples from the deep sea is challenging, as the long recovery times can change expression profiles before preservation. Here, we present a novel, in situ RNA sampling and preservation device, which we used to compare the symbiont metatranscriptomes associated with Alviniconcha, a genus of vent snail, in which specific host-symbiont combinations are predictably distributed across a regional geochemical gradient. Metatranscriptomes of these symbionts reveal key differences in energy and nitrogen metabolism relating to both environmental chemistry (that is, the relative expression of genes) and symbiont phylogeny (that is, the specific pathways employed). Unexpectedly, dramatic differences in expression of transposases and flagellar genes suggest that different symbiont types may also have distinct life histories. These data further our understanding of these symbionts' metabolic capabilities and their expression in situ, and suggest an important role for symbionts in mediating their hosts' interaction with regional-scale differences in geochemistry.


Preeclampsia and Severe Maternal Morbidity During the COVID-19 Pandemic: A Population-Based Cohort Study in Ontario, Canada.
Significant changes to the delivery of obstetrical care that occurred with the onset of the COVID-19 pandemic may be associated with higher risks of adverse maternal outcomes. We evaluated preeclampsia/HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome and composite severe maternal morbidity (SMM) among pregnant people who gave birth during the COVID-19 pandemic and compared these data with those of people who gave birth before the pandemic in Ontario, Canada. This was a population-based, retrospective cohort study using linked administrative data sets from ICES. Data on pregnant people at ≥20 weeks gestation who gave birth between March 15, 2020, and September 30, 2021, were compared with those of pregnant people who gave birth within the same date range for the years 2015-2019. We used multivariable logistic regression to assess the effect of the pandemic period on the odds of preeclampsia/HELLP syndrome and composite SMM, adjusting for maternal baseline characteristics and comorbidities. There were no differences between the study periods in the adjusted odds ratios (aORs) for preeclampsia/HELLP syndrome among primiparous (aOR 1.00; 95% CI 0.91-1.11) and multiparous (aOR 0.94; 95% CI 0.81-1.09) patients and no differences for composite SMM (primiparous, aOR 1.00; 95% CI 0.95-1.05; multiparous, aOR 1.01; 95% CI 0.95-1.08). Adverse maternal outcomes were not higher among pregnant people who gave birth during the first 18 months of the COVID-19 pandemic in Ontario, Canada, when compared with those who gave birth before the pandemic.


Restoration of the bone marrow pluripotent stem cells in AKR mice after arabinosylcytosine treatment.
The hypothesis of repression of multipotent stem cells (CFU) by leukemic cells to explain their depletion, previously demonstrated in AKR leukemic mice, was tested. Using arabinosylcytosine to destroy leukemic cells, it was shown that the bone marrow CFU pool was acutely depressed between 2 h and 12 h after treatment. However, 5 to 7 days later, this pool was restored, surpassing the value of the bone marrow pool in normal mice. This seems to indicate that the CFU pool in leukemic mice is potentially capable of proliferating but is repressed by leukemic cells.


Polyarthritis associated with testicular tumour.
Rarely rheumatological features may dominate and is the cause of missed or delayed diagnosis of a malignant lesion. A case is presented wherein the patient with embryonal type of testicular tumour masqueraded with symmetrical polyarthritis with small joint involvement. p53 antigen was detected in testicular tissue. Such an example is indeed unreported in literature to the best of our knowledge.


Rumen and fecal microbial profiles in cattle fed high lignin diets using metagenome analysis.
Coconut coir (a lignin-rich, organic material) is widely used for its commercial and economic benefits. In this study, crossbred (exotic) and Kankrej (indigenous) breeds of cattle were fed diets containing 7 or 14% coconut coir. Metagenomic analyses (16S rRNA gene amplicon and shotgun sequencing) were used to characterize the microbial community in the rumen and fecal samples along with their functional capabilities. Both amplicon and shotgun analyses revealed the predominance of bacterial phyla, Bacteroidetes, Firmicutes, Actinobacteria and Fibrobacter in ruminal liquid, ruminal solid and fecal samples. 16S rRNA gene amplicon sequencing revealed a total of 18 different bacterial taxa were found to be enriched exclusively in the animals fed with 14% coir. The shotgun analysis revealed abundance of bacterial genera, Fibrobacter, Clostridium, Prevotella, Butyrivibrio, and Ruminococcus in both liquid and solid fractions of ruminal contents, while in the fecal sample, Bacteroides, Alistipes, Plaudibacter, Parabacteroides, Porphyromonas, and Victivallis and archaeal genus, Methanocorpusculum were abundant. The functional analysis based on dbCAN database suggested that among the Glycoside hydrolase family, genes that encode oligosaccharide degrading enzymes, GH3, GH13 (p-value < 0.05), and GH43 were abundant in the feces. In ruminal solid, cellulase encoding the GH5 family was abundant. Also, lignocellulosic binding modules encoded by the CBM family, including cellulose (CBM3) and hemicellulose binding modules (CBM32 and CBM67) were abundant. Thus, the study indicated the enrichment of lignocellulosic enzymes in ruminal contents in response to feeding the coconut coir, which could be mined for potential biofuel production and other biotechnological applications.


Biochemical pharmacology and experimental chemotherapy studies with guanine-7-oxide, a novel purine antibiotic.
1. Guanine-7-oxide is a novel purine antibiotic produced by a Streptomyces species, ATCC 39364. 2. Guanine-7-oxide is cytotoxic to murine and human leukemia cells in vitro at sub-micromolar concentrations. Murine and human carcinoma cells are much less sensitive. 3. Guanine-7-oxide has significant in vivo antitumor activity, particularly against the intraperitoneal and subcutaneous L1210 leukemia systems. 4. Guanine-7-oxide, at highly cytotoxic concentrations, has little effect on biosynthesis of RNA and DNA. 5. There is preliminary evidence for an early effect of guanine-7-oxide on cellular protein synthesis. 6. Guanine, guanosine and hypoxanthine protect cells from the cytotoxicity of guanine-7-oxide. 7. Activation of guanine-7-oxide requires the presence of the enzyme hypoxanthine-guanine phosphoribosyltransferase in the target cells. 8. Cytotoxic concentrations of guanine-7-oxide do not cause depletion of cellular guanine nucleotides during a two hr incubation period. 9. Guanine-7-oxide is converted within mouse and human cells to a metabolite with chromatographic mobility corresponding to a ribonucleoside 5'-triphosphate.


Changing patterns of relapse in Hodgkin's disease.
The patterns of early and late relapses (those occurring later than 3 years after diagnosis) in 432 patients achieving complete remission after treatment for stage I and II Hodgkin's disease at the Royal Marsden Hospital between 1964 and 1983 were studied to identify factors predicting for late relapse. The incidence of early relapse has fallen progressively in recent treatment eras as staging procedures and management have improved but in contrast there has been no decrease in the risk of late relapse. The incidence of late relapse was greater in patients treated with radiotherapy rather than combined modality therapy (P less than 0.05). However, patients who were clinically staged and treated with combined modality therapy retained as high a risk of relapse between 3 and 6 years as in years 2 and 3. The risk of late relapse was also greater in patients with stage II disease and in those without B symptoms at presentation. Patients falling into the higher risk categories for late relapse require continued close follow-up beyond 3 years to monitor for possible relapse.


Comparative effect of horse gram and black gram on inflammatory mediators and antioxidant status.
A balanced diet is important for the overall wellbeing of an individual. Pulses are an important part of a nutritive diet. Pulses have been consumed for at least 10,000 years and are among the most extensively used foods in the world. They are a rich source of protein and fiber, as well as a significant source of vitamins and minerals, such as iron, zinc, and magnesium. The purpose of this study was to compare the effect of two pulses, horse gram and black gram, on inflammatory mediators and the antioxidant enzymes. Two sets of experiments were conducted in rats which were fed with boiled and unboiled horse gram and black gram, at a dose of 100 mg/100 g body weight, for 21 days and 60 days. The results showed that horse gram supplementation for 21 days and 60 days significantly increased the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase and showed no significant changes in the activities of the inflammatory mediators such as cyclooxygenase, lipoxygenase, myeloperoxidase, nitric oxide synthase, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), etc. However, the black gram (with skin and without skin) supplementation significantly increased activities of the inflammatory mediators and showed a significant decrease in the antioxidant enzymes in both the 21-day and 60-day experiments. Thus, these preliminary results demonstrate the anti-inflammatory and antioxidant potential of horse gram and the proinflammatory effects of black gram in rats. This is in accordance with the dietary regime advised by Ayurveda practitioners, where horse gram is to be included and black gram is to be excluded from the diet for conditions such as rheumatoid arthritis. Further studies are to be conducted to validate the same.


Using Facebook and text messaging to deliver a weight loss program to college students.
Between 31 and 35% of the college-aged population is overweight or obese, yet few weight loss trials for this population have been conducted. This study examined the feasibility, acceptability, and initial efficacy of a technology-based 8-week weight loss intervention among college students. Students (N = 52) were randomly assigned to one of the three arms: Facebook (n = 17); Facebook Plus text messaging and personalized feedback (n = 18); Waiting List control (n = 17), with assessments at 4 weeks and 8 weeks (post-treatment). Participants were 20.47 ± 2.19 years old, 86.45 ± 17.11 kg, with a body mass index of 31.36 ± 5.3 kg/m(2) . Participants were primarily female (86.5%), and the sample was racially diverse (57.7% Caucasian, 30.8% African American, 5.8% Hispanic, and 5.7% other races). The primary outcome was weight loss after 8 weeks (post-treatment); 96.0% of the participants completed this assessment. At 8 weeks, the Facebook Plus group had significantly greater weight loss (-2.4 ± 2.5 kg) than the Facebook (-0.63 ± 2.4 kg) and Waiting List (-0.24 ± 2.6 kg) (both Ps < 0.05). Weight change at 8 weeks was not significantly different between the Facebook and Waiting List groups. Results show preliminary efficacy and acceptability of the two active intervention arms (97.0% found the program helpful, 81.3% found the videos/handouts helpful, and 100% would recommend the program to others). Results indicate the potential for an innovative weight loss intervention that uses technology platforms (Facebook and text messaging) that are frequently used and already integrated into the cultural life of college students.


Frequently increased epidermal growth factor receptor (EGFR) copy numbers and decreased BRCA1 mRNA expression in Japanese triple-negative breast cancers.
Triple-negative breast cancer (estrogen receptor-, progesterone receptor-, and HER2-negative) (TNBC) is a high risk breast cancer that lacks specific therapy targeting these proteins. We studied 969 consecutive Japanese patients diagnosed with invasive breast cancer from January 1981 to December 2003, and selected TNBCs based on the immunohistochemical data. Analyses of epidermal growth factor receptor (EGFR) gene mutations and amplification, and BRCA1 mRNA expression were performed on these samples using TaqMan PCR assays. The prognostic significance of TNBCs was also explored. Median follow-up was 8.3 years. A total of 110 (11.3%) patients had TNBCs in our series. Genotyping of the EGFR gene was performed to detect 14 known EGFR mutations, but none was identified. However, EGFR gene copy number was increased in 21% of TNBCs, while only 2% of ER- and PgR-positive, HER2-negative tumors showed slightly increased EGFR gene copy numbers. Thirty-one percent of TNBCs stained positive for EGFR protein by immunohistochemistry. BRCA1 mRNA expression was also decreased in TNBCs compared with controls. Triple negativity was significantly associated with grade 3 tumors, TP53 protein accumulation, and high Ki67 expression. TNBC patients had shorter disease-free survival than non-TNBC in node-negative breast cancers. TNBCs have an aggressive clinical course, and EGFR and BRCA1 might be candidate therapeutic targets in this disease.


Vasoconstriction after adenosine and inosine in the rat isolated hindlimb abolished by blockade of tryptaminergic mechanisms.
The isolated right hindlimb of the rat was perfused at a fixed flow rate through the femoral artery with heparinized blood from the carotid artery of a donor. Single injections of adenosine (1--300 microgram) induced a biphasic response, a long-lasting vasoconstriction preceded by a transient vasodilatation. Inosine (1--300 microgram) produced only vasoconstriction. After repeated administration of 300 microgram of these substances, the vasoconstriction became less prominent, and finally reverted to vasodilatation. The vasoconstrictor response to these substances (300 microgram) was also diminished or reverted to vasodilatation after pretreatment with reserpine or methysergide. From these results, it is concluded that vasoconstriction after adenosine or inosine may be mediated by 5-hydroxytryptamine released from the peripheral stores and that the intrinsic direct action of these substances on the femoral vascular bed is vasodilator.


Why is there no interspecific host discrimination in the two coexisting larval parasitoids of Drosophila species; Lepyopilina heterotoma (Thomson) and Asobara tabida (Nees).
(1) The parasitic wasps Leptopilina heterotoma (Thomson) and Asobara tabida (Nees) usually refrain from laying eggs in hosts that have already been parasitized by themselves or by a conspecific (=intraspecific host discrimination). (2) In contrast to intraspecific host discrimination, interspecific host discrimination, in which females refrain from laying eggs in hosts that have already been parasitized by the other species, is not found in these sympatric parasitid species. (3) Because we expected that development of interspecific host discrimination would increase the fitness of the wasps, we wondered why this strategy had not evolved in L. heterotoma and A. tabida. (4) We therefore developed a simulation model of the parasitization process, in which interspecific host discrimination can be included. (5) By varying the time needed for host location, survival chances and the proportions of hosts parasitized, we obtained estimates for the number of offspring in situations with and without interspecific host discrimination. (6) The results imply that, assuming that female wasps carry an ample supply of eggs, the development of interspecific host discrimination by L. heterotoma or A. tabida will not lead to increased fitness, even under extreme circumstances. Hence, interspecific host discrimination will not evolve.


[Ecological and hygienic conditions in the use of sewage sediments in agriculture].
Exposure of humans to heavy metals and helminthic eggs during agricultural utilization of sewage sediments is discussed. Recommendations for reducing or completely eliminating the risk of human exposure to heavy metals are offered.


Lacosamide cardiac safety: a thorough QT/QTc trial in healthy volunteers.
To determine whether lacosamide prolongs the corrected QT interval (QTc). In this randomized, double-blind, positive- and placebo-controlled, parallel-design trial, healthy volunteers were randomized to lacosamide 400 mg/day (maximum-recommended daily dose, 6 days), lacosamide 800 mg/day (supratherapeutic dose, 6 days), placebo (6 days), or moxifloxacin 400 mg/day (3 days). Variables included maximum time-matched change from baseline in QT interval individually corrected for heart rate ([HR] QTcI), other ECG parameters, pharmacokinetics (PK), and safety/tolerability. The QTcI mean maximum difference from placebo was -4.3 ms and -6.3 ms for lacosamide 400 and 800 mg/day; upper limits of the 2-sided 90% confidence interval were below the 10 ms non-inferiority margin (-0.5 and -2.5 ms, respectively). Placebo-corrected QTcI for moxifloxacin was +10.4 ms (lower 90% confidence bound >0 [6.6 ms]), which established assay sensitivity for this trial. As lacosamide did not increase QTcI, the trial is considered a negative QTc trial. There was no dose-related or clinically relevant effect on QRS duration. HR increased from baseline by ~5 bpm with lacosamide 800 mg/day versus placebo. Placebo-subtracted mean increases in PR interval at tmax were 7.3 ms (400 mg/day) and 11.9 ms (800 mg/day). There were no findings of second-degree or higher atrioventricular block. Adverse events (AEs) were dose related and most commonly involved the nervous and gastrointestinal systems. Lacosamide (≤ 800 mg/day) did not prolong the QTc interval. Lacosamide caused a small, dose-related increase in mean PR interval that was not associated with AEs. Cardiac, overall safety, and PK profiles for lacosamide in healthy volunteers were consistent with those observed in patients with partial-onset seizures.


Treatment compliance to statins and health results during a year of follow-up after acute myocardial infarction with ST-segment elevation.
There is deficient control of dyslipidaemia after an acute myocardial infarction with ST-segment elevation (STEAMI) despite high rates of statin prescription. The aim of this study was to estimate the rate of statin treatment compliance after a first episode of type 1 STEAMI, the factors that determine the compliance and its impact on cardiovascular morbidity and mortality during the first year of progression. We conducted an observational retrospective study with a cohort of patients hospitalised between 2008 and 2013, with an active statin prescription during the first year of follow-up. We determined the compliance using the proportion of days covered. The relationship between compliance and the rest of the variables was determined with a binary logistic regression analysis. The relationship with cardiovascular morbidity and mortality was determined with a cumulative incidence analysis. The study included 552 patients (64.7 ± 13.7; 73.9% men) of the 613 analysed. There was less compliance among foreign nationals, smokers and individuals with hepatic impairment. Compliance was greater starting at 50 years of age, among pensioners and those with dyslipidaemia, obesity and kidney failure and in cases of compliance with the rest of the groups indicated in secondary prevention. Compliance reduced cardiovascular mortality (1.9% vs. 9.1%; HR 0.201; 95% CI 0.075-0.539; p = 0.001) but not the onset of a new cardiovascular event (5.5% vs. 6.5%; p = 0.834). Statin treatment compliance during the first year after a STEAMI is a key factor in mortality, a period in which its assessment is needed beyond the prescription.


IL-17 induces the production of IL-16 in rheumatoid arthritis.
The purpose of this study was to investigate the expression of IL-16 in the rheumatoid synovium and the role of inflammatory cytokines and Toll-like receptor (TLR) ligands in IL-16 production by fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) patients. Immunohistochemical staining was performed with a monoclonal antibody to IL-16 in synovial tissues from patients with RA and likewise in patients with osteoarthritis (OA). FLS were isolated from RA synovial tissues and stimulated with IL-15, IL-1beta, IFN-gamma, and IL-17. The IL-16 mRNA level was assessed by semiquantitative RT-PCR and real time (RT) PCR and a comparison was made between IL-16 mRNA levels produced by RA-FLS and OA-FLS. Production of IL-16 was identified by a western blot assay, and IL-16 production after stimulation by specific ligands of TLR2 and TLR4 was assessed by RT-PCR. While immunohistochemical staining demonstrated strong expression of IL-16 mRNA in synovial tissues from patients with RA, similar findings were not present in the OA group. Moreover, mRNA expression of IL-16 by RA-FLS increased after treatment with IL-17 but not with IL-15, IL-1beta, and IFN-gamma. Specifically, IL-17 increased IL-16 mRNA level by RA-FLS and peripheral blood mononuclear cells in a dose-dependent manner. However, IL-17 did not stimulate IL-16 production in OA-FLS. Peptidoglycan, a selective TLR2 ligand, also increased production of IL-16 by RA-FLS dose- dependently, whereas LPS, a selective TLR4 ligand, had no such stimulatory effect. The results from our data demonstrate that IL-17 and TLR2 ligands stimulate the production of IL-16 by RA-FLS.


[Unusual size and growth rate of a hypernephroma].
No reports have so far been published on hypernephroma sizes of more than 20 cm. We report on a histologically confirmed hypernephroma of an unusual size of almost 40 cm as identified both by CT and sonography that had developed within a period of three years.


Influence of soluble suture factors on in vitro macrophage function.
Suture materials may interact with immune competent cells and thereby affect localized immunity. Macrophages are central to the inflammatory response and coordinate wound healing. They are also involved in the clearance of foreign material, bacteria and malignant cells. We studied the influence of soluble factors associated with silk, steel, nylon, polyglactin, polydioxanone and chromic catgut sutures on macrophage adherence, phagocytosis and the production of lysozyme and tumour necrosis factor. Soluble factors from suture materials influenced macrophage behaviour in vitro causing cellular activation, functional impairment and alterations in secreted levels of the cytokine tumour necrosis factor and the bactericidal agent lysozyme. Of the six materials studied, polyglactin had the most extreme effect, causing significant inhibition of cell adherence and lysozyme production. Silk also exerted a considerable effect on macrophages, significantly inhibiting adherence. In contrast, steel and polydioxanone media caused minimal inhibition of macrophage function although, as with all materials, they did activate the cells. This study has demonstrated that sutures release immunotoxic factors which considerably influence macrophage behaviour in vitro. These effects may have important clinical implications.


[Dentists' opinion of their education. Results of a survey among dentists who graduated from dental school in Nijmegen in the years 1982-1990].
Five hundred and seventy-eight dental students from the Catholic University of Nijmegen (the Netherlands), graduated between 1982 and 1990, were asked by questionnaire to give their opinion on their undergraduate dental training. Most respondents thought the undergraduate dental education prepared them reasonably well for general practice. Yet imperfections in the education were noticed. These imperfections show resemblance and slight differences from a similar survey in ACTA, the Academic Centre for Dentistry Amsterdam, the Netherlands.


Phenylketonuria oxidative stress and energy dysregulation: Emerging pathophysiological elements provide interventional opportunity.
Phenylalanine hydroxylase (PAH) deficient phenylketonuria (PKU) is rightfully considered the paradigm treatable metabolic disease. Dietary substrate restriction (i.e. phenylalanine (Phe) restriction) was applied >60 years ago and remains the primary PKU management means. The traditional model of PKU neuropathophysiology dictates blood Phe over-representation directs asymmetric blood:brain barrier amino acid transport through the LAT1 transporter with subsequent increased cerebral Phe concentration and low concentrations of tyrosine (Tyr), tryptophan (Trp), leucine (Leu), valine (Val), and isoleucine (Ile). Low Tyr and Trp concentrations generate secondary serotonergic and dopaminergic neurotransmitter paucities, widely attributed as drivers of PKU neurologic phenotypes. White matter disease, a central PKU characteristic, is ascribed to Phe-mediated tissue toxicity. Impaired cerebral protein synthesis, by reduced concentrations of non-Phe large neutral amino acids, is another cited pathological mechanism. The PKU amino acid transport model suggests Phe management should be more efficacious than is realized, as even early identified, continuously treated patients that retain therapy compliance into adulthood, demonstrate neurologic disease elements. Reduced cerebral metabolism was an early-recognized element of PKU pathology. Legacy data (late 1960's to mid-1970's) determined the Phe catabolite phenylpyruvate inhibits mitochondrial pyruvate transport. Respirometry of Pahenu2 cerebral mitochondria have attenuated respiratory chain complex 1 induction in response to pyruvate substrate, indicating reduced energy metabolism. Oxidative stress is intrinsic to PKU and Pahenu2 brain tissue presents increased reactive oxygen species. Phenylpyruvate inhibits glucose-6-phosphate dehydrogenase that generates reduced niacinamide adenine dinucleotide phosphate the obligatory cofactor of glutathione reductase. Pahenu2 brain tissue metabolomics identified increased oxidized glutathione and glutathione disulfide. Over-represented glutathione disulfide argues for reduced glutathione reductase activity secondary to reduced NADPH. Herein, we review evidence of energy and oxidative stress involvement in PKU pathology. Data suggests energy deficit and oxidative stress are features of PKU pathophysiology, providing intervention-amenable therapeutic targets to ameliorate disease elements refractory to standard of care.