Protective ability against oxidative stress of brewers' spent grain protein hydrolysates.
The protein fraction of Brewers' spent grain (BSG) was used as substrate to obtain hydrolysates with antioxidant activity. Three enzymatic approaches were applied: brewer's spent yeast (BSY) proteases, Neutrase® and Alcalase®, at the same proteolytic activity (1U/mL), using an enzyme/substrate ratio of 10:100 (v/v), at 50°C, 4h. Total Phenolic Content (TPC) and Ferric Ion Reducing Antioxidant Power (FRAP) of hydrolysates and fractions <10kDa and <3kDa were assayed. Additionally, the protective ability of <10kDa fractions against oxidative stress on Caco-2 and HepG2 cells was investigated. Alcalase® hydrolysate presented significantly (p<0.05) higher TPC and FRAP (0.083mgGAE/mgdw; 0.101mgTE/mgdw, respectively) than Neutrase® and BSY hydrolysates. The three BSG protein hydrolysates (fraction <10kDa) exerted protective effect against free-radical induced cytotoxicity in Caco-2 and HepG2 cell lines, but the strongest effect was observed for BSY hydrolysates, therefore, it presents greater potential as functional ingredient.


Subchronic toxicity and mutagenicity/genotoxicity studies of Irvingia gabonensis extract (IGOB131).
African Bush Mango from Irvingia gabonensis is a West African culinary fruit and the mucilage from this fruit seed is used to make traditional soups and sauces. Extract from the kernel (IGOB131) has been claimed for its health benefits. In the present investigations, potential adverse effects, if any, of IGOB131 were investigated in dose-response 90-day study and genotoxicity studies. In the subchronic study, Sprague Dawley rats (20/sex/group) were gavaged with I. gabonensis extract (IGOB131) at dose levels of 0, 100, 1000 and 2500 mg/kg body weight (bw)/day for 90-days. No treatment-related changes in clinical signs, functional observations, mortality, ophthalmologic observations, body weights, body weight gain or feed consumption were noted. Similarly, hematological, clinical chemistry, urine analysis parameters, and organ weights did not reveal any toxicologically significant treatment-related changes. No treatment-related macroscopic and microscopic abnormalities were noted at the end of treatment period. The mutagenicity as evaluated by Ames assay, in vitro and in vivo chromosomal aberration test and in vivo micronucleus assay did not reveal any genotoxicity of IGOB131. The results of subchronic toxicity study suggest the no-observed-adverse-effect level (NOAEL) for I. gabonensis extract (IGOB131) as ≥ 2500 mg/kg bw/day, the highest dose tested.


Inhibition of lactate dehydrogenase in cultured SIRC cells by cigarette smoke.
SIRC cell monolayer cultures were exposed to whole smoke from a mid tar and nicotine level research cigarette (ASFC, 72 puffs), or from a high tar and nicotine level reference cigarette (Kentucky 2RI, 48 puffs) over a period of 65 days. The activity and distribution of lactate dehydrogenase (LDH) in the cells were investigated, and the electrophoretic characteristics of its isozymes studied. Cell morphology was examined by light microscopy and by transmission- and scanning electron microscopy. LDH activity was reduced by exposure to smoke from both cigarette types, the greater inhibitory effect being produced by that of the Kentucky cigarette. In addition, cells exposed to this high tar and nicotine smoke displayed intramitochondrial granules which were larger and more numerous than those found in cells exposed to the mid tar and nicotine smoke, or in the control cells. It is speculated that cation accumulation in the mitochondria may be involved in the observed inhibition of LDH activity.


A review of the role of liposome-encapsulated phytochemicals targeting PPAR Ɣ and associated pathways to combat obesity.
A limited number of studies have directly examined the effects of liposomal encapsulated phytochemicals and their anti-obesity effects in adults. This study aimed to summarize the evidence on the effect of liposomal encapsulated phytochemicals and their role in regulating major pathways involved in the anti-obesity mechanism. A systematic search was performed using several search engines like Science Direct, Google Scholar, and other online journals, focusing on laboratory research, systematic reviews, clinical trials, and meta-analysis that focused on liposomal encapsulated phytochemicals with anti-obesity properties, and followed the preferred reporting terms for this systematic review. An initial search provided a result of 1810 articles, and 93 papers were selected after the inclusion and exclusion criteria. Very few studies have been conducted on the liposomal encapsulation of phytochemicals or its synergistic study to combat obesity; hence this review paves the way for future obesity research and is mainly helpful for the pediatric obesity population. Liposomal encapsulation of phytochemicals has improved the efficiency of freely administered phytochemicals. Targeted delivery improved drug utilization and regulated the anti-obesity pathways. PPARƔ is a major therapeutic target for obesity as it inhibits adipocyte differentiation and maintains energy homeostasis.


Positive association of adiponectin with soluble thrombomodulin, von Willebrand factor and soluble VCAM-1 in dyslipidemic subjects.
Both decreased and increased risk of cardiovascular events/mortality have been reported with high adiponectin levels. Only a few studies have reported an association of adiponectin with markers of hemostasis/endothelial dysfunction which might explain the reported discrepancies. We evaluated the association of total adiponectin with von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), soluble thrombomodulin (sTM), adhesion molecules sICAM-1 and sVCAM-1, lipids and markers of insulin resistance (IR) in 308 asymptomatic dyslipidemic subjects and healthy controls. Subjects were divided into 4 dyslipidemic phenotypes (DLP): DLP1 (TG < 1.5 mmol/L + ApoB < 1.2 g/L), DLP2 (TG ≥ 1.5 + ApoB < 1.2), DLP3 (TG < 1.5 + ApoB ≥ 1.2) and DLP4 (TG ≥ 1.5 + ApoB ≥ 1.2). The results were evaluated also according to the presence (+) and absence (-) of metabolic syndrome (MS). In hyperlipidemic subjects (DLP2-4), PAI-1, t-PA and sICAM-1 correlated with markers of IR but only t-PA correlated inversely with adiponectin. In contrast positive association of adiponectin with vWF, sTM and sVCAM-1 was found but none of these parameters correlated with markers of insulin resistance. In multiple regression analysis, adiponectin remained independently associated with vWF [in DLP3, DLP4, DLP2-4, MS(-)], with sTM [in DLP2, DLP4, DLP2-4, MS(+)] and with sVCAM-1 [in DLP2, DLP3, DLP4, DLP2-4, MS(+)]. In healthy controls (DLP1), no association between adiponectin and markers of hemostasis/endothelial dysfunction was found. The independent positive association of adiponectin with vWF, sTM and sVCAM-1 deserves further evaluation in connection with the risk of atherothrombotic cardiovascular events.


Cardiac transplantation after bridged therapy with continuous flow left ventricular assist devices.
Cardiac transplantation is an effective surgical therapy for end-stage heart failure. Patients (pts) may need to be bridged with a continuous flow left ventricular assist device (CF-LVAD) while on the transplant list as logistic factors like organ availability are unknown. Cardiac transplantation post-LVAD can be a surgically challenging procedure and outcome in these pts is perceived to be poorer based on experience with earlier generation pulsatile flow pumps. Data from a single institution comparing these pts with those undergoing direct transplantation in the present era of continuous flow device therapy are limited. Evaluate results of cardiac transplantation in pts bridged with a CF-LVAD (BTx) and compare outcomes with pts undergoing direct transplantation (Tx) in a single institution. From June 2007 till January 2012, 106 pts underwent cardiac transplantation. Among these, 37 (35%) pts (51±11 years; 85% male) were bridged with a CF-LVAD (BTx), while 70 (65%) comprised the Tx group (53±12 years; 72% males). The median duration of LVAD support was 227 (153,327) days. During the period of LVAD support, 10/37 (27%) pts were upgraded to status 1A and all were successfully transplanted. Median hospital stay in the BTx (14 days) was slightly longer than the Tx group (12 days) but not statistically significant (p=0.21). In-hospital mortality in the BTx (5%) and Tx (1%) were comparable (p=0.25). Estimated late survival in the BTx cohort was 94±7, 90±10 and 83±16% at the end of one, two and three years, respectively which was comparable to 97±4%, 93±6% and 89±9% for the Tx group (p=0.50). Cardiac transplantation after LVAD implant can be performed with excellent results. Patients can be supported on the left ventricular assist device even for periods close to a year with good outcome after cardiac transplantation.


Fusarium toxins in wheat from an area in Henan Province, PR China, with a previous human red mould intoxication episode.
Wheat samples of the 1998 and 1999 crops from Puyang, an area in Henan Province, PR China with a previous human red mould intoxication episode, were analysed for trichothecenes and zearalenone (ZEA). For the 1998 Puyang crop, deoxynivalenol (DON) was the predominant toxin detected abundantly and frequently at a level of up to 14,000 microg kg(-1) (mean 2850 microgkg(-1)) in 30 of 31 (97%) wheat samples. Among these were 21 (70%) with a DON level that exceeded the Chinese regulation of 1,000 microg kg(-1). Nivalenol (NIV) and 15-acetyl-DON (15-ADON) were also found at 578 microg kg(-1) (one sample) and 59-1,800 microg kg(-1) (mean 365 microg kg(-1), 20 samples), respectively. ZEA co-occurred in 21 samples at 9-1,400 microg kg(-1) (mean 209 microg kg(-1)). Twenty-five (89%) wheat samples from Zhumadian, a region without a history of human red mould intoxication in the same province, contained low levels of DON (53-1240, mean 223 microg kg(-1)) with seven (25%) co-contaminated with ZEA (10-217, mean 108 microg kg(-1)). All were free from 15-ADON and NIV. Significant differences in DON, 15-ADON and ZEA concentrations between both areas were found. DON (<1000 microg kg(-1)) and ZEA (5-111 microg kg(-1)) were also detected in the 1999 Puyang wheat. Proper environmental conditions for Fusarium species surviving winter combined with unusual high precipitation during wheat flowering were responsible for a high concentration of Fusarium mycotoxins in the 1998 Puyang wheat.


Quality assurance challenge 2.
We would like to invite you to participate in the Analytical Challenge, which is a series of puzzles designed to entertain and challenge our readers. The special ABC feature 'Analytical Challenge' has established itself as a truly unique quiz series, with a new scientific puzzle published every second month. Readers can access the complete collection of published problems with their solutions on the ABC homepage at www.springeronline.com/journal/00216. Test your knowledge and tease your wits in diverse areas of analytical and bioanalytical chemistry by viewing this collection. Quality assurance is the topic of the present challenge. And please note: there is a prize to be won (a Springer book from our catalogue up to a value of euros 75,-). Please read on...


Postnatal development of the cholecystokinin innervation of monkey prefrontal cortex.
Although the structure and function of primate prefrontal cortex undergo substantial modifications during postnatal development, relatively little is known about the maturation of neurotransmitter systems in these cortical regions. In the primate brain, cholecystokinin is present in the greatest concentrations in prefrontal regions. Thus, in this study, we used immunohistochemical techniques to investigate the postnatal development of the cholecystokinin innervation of monkey prefrontal cortex. In animals aged 4 days through adult, cholecystokinin immunoreactivity was present in nonpyramidal neurons that appeared to represent at least two distinct cell types. The most common type was a vertically oval bitufted neuron, located in layers II-superficial III, which typically had a radially descending axon that gave rise to short collaterals in layer IV. Another frequently observed cell type was a larger multipolar neuron located in the superficial half of layer III. The axon of these neurons branched locally in the vicinity of the cell body. The greatest density of cholecystokinin-containing neurons and processes was present in monkeys less than 1 month of age. The density of immunoreactive structures in every prefrontal region then progressively declined with increasing age, with the most marked changes occurring during the first postnatal year. As a result, the density of labeled neurons in adult monkeys was less than one-third of that in neonatal monkeys. However, labeled structures were significantly more dense in some ventromedial and orbital regions than in dorsal regions of the prefrontal cortex in neonatal, but not in older animals. In all animals, cholecystokinin-containing neurons were present in highest density in layers II-superficial III, and labeled terminal fields were observed in layers II, IV, and VI. In animals less than 1 month of age, fascicles of radial fibers traversed through layers III and V, whereas in animals 1 to 3 months of age, individual radial fibers rather than fiber bundles were present in layers III and V. In addition, immunoreactive pericellular arrays, which appeared to surround unlabeled nonpyramidal cells, were present in layers V and VI and the subcortical white matter in the youngest monkeys. Although many aspects of the cholecystokinin innervation of monkey prefrontal cortex remain constant during postnatal life, the distinct developmental changes in the cholecystokinin innervation of these regions suggest that it may play an important role in the maturation of the cortical circuitry that mediates the acquisition of certain cognitive abilities.


The promoter hypermethylation of SULT2B1 accelerates esophagus tumorigenesis via downregulated PER1.
Esophageal cancer is currently the eighth most common tumor in the world and a leading cause of cancer death. SULT2B1 plays crucial roles in tumorigenesis. The purpose of this study is to explore the role of SULT2B1 in esophageal squamous cell carcinoma (ESCC). The expression of SULT2B1 and its clinicopathological characteristics were evaluated in ESCC cohorts. Bisulfite genomic sequencing and methylation specific PCR were used to detect the promoter hypermethylation of the SULT2B1 gene. The effects of SULT2B1 on the biological characters of ESCC cells were identified on functional assays. Subcutaneous xenograft models revealed the role of SULT2B1 in vivo with tumor growth. RNA-Seq analysis and qRT-PCR were performed to recognize the targeted effect of SULT2B1 on PER1. SULT2B1 was not expressed or at a low level in most patients with ESCC or in ESCC cell lines, and this was accompanied by poor clinical prognosis. Furthermore, the downregulation of SULT2B1 occurred in promoter hypermethylation. According to the functional results, overexpression of SULT2B1 could inhibit tumoral proliferation in vitro and retard tumor growth in vivo, whereas SULT2B1 knockdown could accelerate ESCC progression. Mechanistically, SULT2B1 targeted PER1 at the mRNA level during post-transcriptional regulation. Finally, PER1 was verified as a suppressor and poor-prognosis factor in ESCC. SULT2B1 loss is a consequence owing to its ability to promote hypermethylation. In addition, it serves as a suppressor and poor-prognosis factor because of the post-transcriptional regulation of PER1 in ESCC.


Plasma levels of beta-thromboglobulin and factor VIII-related antigen in diabetic children and adults.
In order to investigate the relationship between the in vivo platelet activation in diabetes mellitus and the endothelial damage connected with the diabetic micro- and/or macroangiopathy, plasma levels of beta-thromboglobulin (B-TG) and of factor VIII-related antigen (VIII R:Ag) were studied (1) in juvenile-onset (Type I) diabetics without clinical signs of angiopathy (age under 12 years) and (2) in mostly maturity-onset (Type II) diabetics with and without overt angiopathy (age between 14 and 60 years). Normal controls and nondiabetics with atherosclerosis were also studied. Plasma levels of both proteins were found to be elevated in all the groups of diabetic and atherosclerotic patients in comparison with the controls. Highest levels were found in adult diabetics with angiopathy and in atherosclerotics even without diabetes, but values of the diabetic children were also elevated. The data suggest a causal relationship between the vascular damage and the enhanced platelet reactivity in which the former may play the primary role.


Continuous positive airway pressure by face mask in acute cardiogenic pulmonary edema.
The therapeutic efficacy of continuous positive airway pressure (CPAP) administered by face mask was studied in 40 patients with acute cardiogenic pulmonary edema and respiratory failure. Arterial blood gas values and pH, systemic arterial pressure, heart rate and respiratory rate were measured during administration of 30% oxygen with a high-flow face mask apparatus at ambient airway pressure. Twenty patients were then randomly chosen to continue ambient airway pressure breathing and 20 received 10 cm H2O of CPAP. The measurements were repeated 10, 60 and 180 minutes after therapy was initiated. During the first 10 minutes of CPAP treatment, arterial blood oxygen partial pressure increased 8 +/- 9 mm Hg (mean +/- 1 standard deviation), (p less than 0.01) and respiratory rate decreased 5 +/- 5 breaths/min (p less than 0.001). Systolic arterial pressure decreased 12 +/- 21 mm Hg (p less than 0.05), and heart rate by 10 +/- 11 beats/min (p less than 0.001). A decrease in respiratory rate by 2 +/- 5 breaths/min (p less than 0.05) was the only change that occurred in the control group. The improvement in arterial blood oxygenation persisted throughout the investigation period (p less than 0.05). Thirteen patients (65%) in the control group and 7 patients (35%) in the CPAP group met our criteria for treatment failure during the study (p = 0.068). Thus, CPAP administered by face mask improves gas exchange, decreases respiratory work, unloads circulatory stress, and may reduce the need for ventilator treatment in acute cardiogenic pulmonary edema.


Effect of the lipid environment on protein motion and enzymatic activity of sarcoplasmic reticulum calcium ATPase.
In order to investigate the roles of the physical states of phospholipid and protein in the enzymatic behavior of the Ca2+ -ATPase from sarcoplasmic reticulum, we have modified the lipid phase of the enzyme, observed the effects on the enzymatic activity at low temperatures, and correlated these effects with spectroscopic measurements of the rotational motions of both the lipid and protein components. Replacement of the native lipids with dipalmitoyl phosphatidylcholine inhibits ATPase activity and decreases both lipid fluidity, as monitored by EPR spectroscopy on a stearic acid spin label, and protein rotational mobility, as monitored by saturation transfer EPR spectroscopy on the covalently spin-labeled enzyme. Solubilization of the lipid-replaced enzyme with Triton X-100 reverses all three of these effects. Ten millimolar CaCl2 added either to the enzyme associated with the endogenous lipids or to the Triton X-100 soulbilized enzyme inhibits both ATPase activity and protein rotational mobility but has no detectable effect on the lipid mobility. These results are consistent with the proposal that both lipid fluidity and protein rotational mobility are essential for enzymatic activity.


Calculation of complication probability factors for non-uniform normal tissue irradiation: the effective volume method.
An estimation of normal tissue complication probability factors is important, particularly for evaluating 3-dimensional treatment plans. A method has been developed to calculate complication probability factors for non-uniformly irradiated normal organs using dose volume histograms and complication probabilities for uniform partial organ irradiation. In the effective volume method each volume element of the histogram is considered independently and subject to a power law dose volume relationship. Thus, a non-uniform dose volume histogram is reduced to a uniform one with an effective volume, and a dose equal to the maximum dose to the organ. The complication probability is then obtained from known complication probabilities for uniform partial organ irradiation. The effective volume histogram transformation method is shown to obey various boundary conditions, and is illustrated by comparing probability calculations for alternative 3-dimensional treatment plans for the pelvis. In addition, the limitations of this histogram reduction method are discussed and compared to other calculational techniques. The use of probability factor calculations in treatment plan evaluation, and their role in numerical scoring is explored.


HIV serostatus disclosure to sexual partner: a survey among women in Tehran, Iran.
Disclosure of HIV-positive status in women is associated with many factors. Consequently, status disclosure remains a challenge for Iranian women living with HIV. This study aimed to assess the prevalence, related factors, and reflections of HIV-positive status disclosure to a sexual partner(s) among Iranian women living with HIV. A cross-sectional study was conducted on 170 HIV-seropositive women. Participants were selected from patients registered in the largest HIV clinic and HIV-positive club of Iran. The "HIV disclosure" questionnaire had 38-items and all the interviews were administered by the researcher. Data were analyzed using SPSS version 21.0 software. We used a logistic regression method to calculate the crude odds ratio (COR) and the adjusted odds ratio (AOR) for self-disclosure as the independent predictor variable and the dependent variable, respectively. One hundred and seventy HIV-positive women were enrolled. Most of them had disclosed their HIV status to at least one person (94.1%) and their sexual partners (86.5%). In the univariate analysis, being married (COR = 18.66, 95% CI 5.63-61.87), living with a sexual partner (COR = 4.72, 95% CI 1.92-11.62), being aware of sexual partners' HIV status (COR = 6.20, 95% CI 1.79-21.49), and gaining the support of sexual partner (COR = 9.08, 95% CI 3.48-23.64) were associated with higher odds of HIV status disclosure. In the multivariate analysis, being aware of sexual partners' HIV status, and gaining the support of sexual partners remained associated with HIV status disclosure. Most women reported a positive reflection from their sexual partners after disclosure, however, negative reflections from society were more common compared to sexual partners and family members. This study shows high overall HIV disclosure proportions. It should be noted that a large number of women were infected by their sexual partners, especially by their spouses. The high rate of transmission in married people indicates an urgent need for more emphasis on appropriate prevention behaviors by infected partners.


Characterization of Lactococcus lactis subsp. lactis isolated from surface waters.
A group of nine presumptive enterococci was isolated on enterococcal selective media Slanetz-Bartley agar and/or kanamycin-esculin-azide agar during a screening of Enterococcus spp. in surface waters. All strains formed a homogeneous cluster separated from all enterococcal species using rep-PCR fingerprinting with the (GTG)5 primer but they matched fingerprints revealed by Lactococcus lactis subsp. lactis representatives. Further identification using extensive biotyping and automated ribotyping with EcoRI (RiboPrinter microbial characterization system) confirmed all strains as L. lactis subsp. lactis in full correspondence with the (GTG)5-PCR. We demonstrated that L. lactis subsp. lactis strains occur in different surface waters and can be confused with enterococci due to their positive growth on selective enterococcal media as well as positive results in tests commonly used for identification of the genus Enterococcus (esculin hydrolysis, acetoin and pyrrolidonyl arylamidase production, growth at 10 degrees C and in 6.5% NaCl). The (GTG)5-PCR fingerprinting was revealed as a reliable and fast method for the identification of L. lactis subsp lactis while automated ribotyping with EcoRI proved to be a good tool for intrasubspecies typing purposes.


Phasing DNA Methylation.
Haplotyping enables the study of allele-specific events. Heterozygous variants, primarily single nucleotide variants (SNVs), enable the assignment of the paternal and maternal origin of the chromosomes and are widely employed to phase sequencing reads to their haplotype of origin. Certain long-read technologies enable the detection of both the DNA sequence and DNA modifications. These long reads and their inherent methylation information are suitable for genome-wide haplotyping and allele-specific DNA methylation analysis. Here, we describe the workflow to phase reads and DNA methylation using nanopore sequencing.


Fusion after intradural spine tumor resection in adults: A review of evidence and practices.
There is ample evidence supporting concomitant fusion after intradural spinal tumor resection in select pediatric patients. Unfortunately, the data are scarcer in adults. The objective of this work is to review the published literature and analyze practice patterns for stabilization and fusion after intradural tumor resection in adults. We performed a literature review via PubMed for information available regarding fusion in adults with intradural spine tumors. Additionally, we manually searched the references of selected articles to add relevant articles. Finally, we retrieved the criteria for fusion (if any) in the selected studies. A total of 639 articles were found and 35 were finally selected for analysis. Of those, three were literature reviews and 32 were retrospective case series. There were a total of 1288 patients on the series with 104 of them requiring fusion (8.1%). The median follow up of all the series was 24 months (range 1.5-180).The criteria for fusion that were common in most cases series were: previous deformity (i.e. kyphosis in the cervical spine), 3 or more levels of laminectomy, laminectomy encompassing a spinal junction, "young adults" (33 ± 4.2 years), facetectomy ≥ 50% (unilateral or bilateral), persistence of deformity after 1 year of the surgery and, C2 laminectomy. There appears to be some consistent practices for fusion after intradural tumor resection in adults, but this is based on retrospective analyses of case series. Prospective or randomized trials will likely provide more evidence based support for this practice.


A survey of drug usage among patients admitted to a psychiatric hospital.
A six-month survey of the urinary concentrations of drugs and alcohol of 176 patients within one hour of their admission to the acute psychiatric wards of the Macquarie Hospital, Sydney, is reported. Non-prescribed drugs were detected in the urine specimens of 29.5% of patients and alcohol in the urine specimens of 13.6% of patients. The survey demonstrated inconsistencies between patients' reports of their recent drug or alcohol intake and the laboratory findings, and inadequacies in the information recorded and relayed to the laboratory at the time of patients' admission to the hospital.


Malaria and haemoglobin A2 levels in northern Liberia.
The influence of malaria on HbA2 levels was investigated in two groups of children aged two to nine years from the Mano tribe of northern Liberia. One group, 174 children living in a town where there is malaria control, had a parasite rate of 6.5%, only a few having palpable spleens, but 282 children living in an area of intense malaria transmission had a parasite rate of 92%. All but one child in this group had enlarged spleens. However, the difference in proportions of elevated HbA2 values within the limits for beta-thalassaemia, 8% and 10.3% respectively, was not statistically significant (0.5 greater than P greater than 0.1). It was concluded that the influence of malaria on HbA2 levels is not significant and that this parameter is valid for detecting beta-thalassaemia trait in this population. Further, iron deficiency may be a more important factor than malaria to consider when assessing the results of HbA2 estimations.


Prospective payment experience with DRGs in headache patients.
The new Diagnostic Related Group (DRG) Prospective Hospital Payment System pays a set fee to hospitals depending on the patient's diagnosis. Care of certain patients covered by Neurology DRGs has proven to be unprofitable. The purpose of this project was to study hospital resource consumption for hospitalized patients with a principal or secondary diagnosis of headache. We studied various resource parameters for patients in the three neurology DRGs for headache (#24-seizure and headache, age greater than 69 and/or complicating condition; #25 and #26-seizure and headache age 18-69 without complicating condition, and age 0-17, respectively) by whether or not the patients had a diagnosis of headache. As demonstrated in Table 1, patients with headache had (on average) lower hospital resource utilization than patients in these same DRGs without a headache diagnosis. Headache patients had lesser total hospital costs, a lower severity of illness, and generated profits under DRGs compared to non-headache patients. We found that our headache patients were adequately reimbursed by the DRG hospital payment system and suggest that this could be a financially attractive population to hospitals.


Distribution of potentially toxic elements in soils and sediments in Pearl River Delta, China: Natural versus anthropogenic source discrimination.
Although anthropogenic contamination has been regarded as the most important source of potentially toxic elements (PTEs) in soils of large river delta plains, the extent to which human activities affect PTEs in soils is worth exploring. This study used high density geochemical data to distinguish source patterns of PTEs in soils of the Pearl River Delta Economic Zone, a large industrialized and urbanized area in China. Enrichment factor, discriminant analysis, principal components analysis, cumulative distribution function, and positive matrix factorization were used to identify sources of PTEs in soils. The results indicated that parent material was the most significant factor affecting geochemical characteristics of PTEs in soils. Median concentrations of Cd, Cr, Cu, Hg, Pb, and Zn were 0.400, 88.5, 40.5, 0.143, 43.0, and 116.0 mg/kg for stream sediments, 0.333, 75.7, 39.0, 0.121, 42.6, and 98.5 mg/kg for deep soils, and 0.365, 74.0, 45.1, 0.143, 44.6, and 119.5 mg/kg for surface soils, respectively, all of which exceed relevant reference standards. Compared with stream sediments and deep soils, surface soils exhibit substantial concentrations of PTEs. Chemical weathering and erosion of parent materials distributed in the Pearl River Delta were the main sources of PTEs in soils. Diffuse contamination and many small local contamination sources distributed throughout the study area were the most significant anthropogenic sources of PTEs in surface soils. Intensive human activities failed to change the soil geochemical characteristics derived from the parent material at the regional scale. However, it could induce non-point source pollution and local severe PTEs pollution in surface soils.


Effects of isoniazid (INH) on the oogenesis of mice.
Mutagenic damages in female germ cells of mice have been tested with the dominant lethal assay and the cytogenetic analysis of unfertilized M II-oocytes. Concluding one can say that from the experimental data presented here do not show any mutagenic effect of INH on oogenesis of different strains of mice can be stated.


The improvement of the analytical performance of direct current atmospheric pressure glow discharge generated in contact with the small-sized liquid cathode after the addition of non-ionic surfactants to electrolyte solutions.
A low power direct current atmospheric glow discharge sustained in the open to air atmosphere in contact with a small-sized flowing liquid cathode was used as an excitation source in optical emission spectrometry. The composition of electrolyte solutions served as the liquid cathode was modified by the addition of non-ionic surfactants, namely Triton x-45, Triton x-100, Triton x-405 and Triton x-705. The effect of the concentration of each surfactant was thoroughly studied on the emission characteristic of molecular bands identified in spectra, atomic emission lines of 16 metals studied and the background level. It was found that the presence of both heavy surfactants results in a significant increase in the net intensity of analytical lines of metals and a notable reduction of the intensity of bands of diatomic molecules and the background. In conditions considered to be a compromise for all metals, selected figures of merit for this excitation source combined with the optical emission spectrometry detection were determined. Limits of detection for all metals were within the range of 0.0003-0.05 mg L(-1), the precision was better than 6%, while calibration curves were linear over 2 orders of the magnitude of the concentration or more, e.g., for K, Li, Mg, Na and Rb. The discharge system with the liquid cathode modified by the addition of the surfactant found its application in the determination of Ca, Cu, Fe, K, Mg, Mn, Na and Zn in selected environmental samples, i.e., waters, soils and spruce needles, with the quite good precision and the accuracy comparable to that for measurements with flame atomic absorption spectrometry (FAAS) and flame atomic emission spectrometry (FAES).


Chemerin aggravates DSS-induced colitis by suppressing M2 macrophage polarization.
Chemerin is present in various inflammatory sites and is closely involved in tissue inflammation. Recent studies have demonstrated that chemerin treatment can cause either anti-inflammatory or pro-inflammatory effects according to the disease model being investigated. Elevated circulating chemerin was recently found in patients with inflammatory bowel disease (IBD); however, the role of chemerin in intestinal inflammation remains unknown. In this study, we demonstrated that the administration of exogenous chemerin (aa17-156) aggravated the severity of dextran sulfate sodium (DSS)-induced colitis, which was characterized by higher clinical scores, extensive mucosal damage and significantly increased local and systemic production of pro-inflammatory cytokines, including IL-6, TNF-α and interferon (IFN-γ). Interestingly, chemerin did not appear to influence the magnitudes of inflammatory infiltrates in the colons, but did result in significantly decreased colonic expression of M2 macrophage-associated genes, including Arginase 1 (Arg-1), Ym1, FIZZ1 and IL-10, following DSS exposure, suggesting an impaired M2 macrophage skewing in vivo. Furthermore, an in vitro experiment showed that the addition of chemerin directly suppressed M2 macrophage-associated gene expression and STAT6 phosphorylation in IL-4-stimulated macrophages. Significantly elevated chemerin levels were found in colons from DSS-exposed mice and from ulcerative colitis (UC) patients and appeared to positively correlate with disease severity. Moreover, the in vivo administration of neutralizing anti-chemerin antibody significantly improved intestinal inflammation following DSS exposure. Taken together, our findings reveal a pro-inflammatory role for chemerin in DSS-induced colitis and the ability of chemerin to suppress the anti-inflammatory M2 macrophage response. Our study also suggests that upregulated chemerin in inflamed colons may contribute to the pathogenesis of IBD.


An image processing scheme to quantitatively extract and validate hyoid bone motion based on real-time ultrasound recordings of swallowing.
An image processing technique with associated hardware was developed to quantitatively extract hyoid bone motion from realtime submandibular ultrasound images recorded during the swallowing act. Videofluorographic imaging, the "gold standard" of swallowing studies, was recorded simultaneously and synchronized to the ultrasound. Hyoid position obtained from the ultrasound was validated based on the videofluorography using personal computer-based image processing methods.


Epidemiology and Factors Affecting Functional Outcome of Distal Radial Fracture in an Urban Tertiary Medical Centre in Malaysia.
Distal radial fracture is a commonly encountered fracture. This study aims to study the epidemiology of distal radial fracture and factors affecting the patients' functional outcome one to two years after the injury. This is a retrospective cohort study. The records of patients, fulfilling the radiographical diagnosis of distal radial fracture, and aged 18 and above, who presented to our Emergency Department from 1st January 2018 to 31st December 2018 were retrieved. According to AO classification, we grouped our patients into A (extra-articular), B (partial articular) and C (complete articular). Patients with congenital abnormalities were excluded. Epidemiological data and relevant medical history were obtained and tabulated. A Malaysian language translation of Disability of the Arm, Shoulder and Hand (DASH) questionnaire was used to assess the functional outcome. Out of 168 patients' data retrieved, only 110 patients' data were found complete for purposes of this study. The mean DASH score was 13.7 ± 7.87 approximately one to two years post-injury regardless of treatment method. Increasing age was associated with higher DASH score with r=0.407(p<0.001). Several variables had significantly better functional outcome: male gender (p=0.01), Type A fracture configuration (p=0.007) and non-operational treatment (p=0.03). There was no significant difference between treatment modalities in Type A fracture (p=0.094), but Type B (p=0.043) and Type C (p=0.007) had better outcome without surgery. There was no significant difference between different ethnic groups, open or closed fracture and mechanism of injury. Better functional outcome after sustaining distal radial fracture was associated with young age, male gender, type A fracture and treated non-operatively. Interestingly, more complex fracture pattern had better functionality were observed without surgery.


Sequence analysis of operator mutants of the phase-1 flagellin-encoding gene, fliC, in Salmonella typhimurium.
In phase-2 cells of diphasic Salmonella strains, expression of the phase-1 flagellin-encoding gene, fliC, is repressed by the repressor encoded by the fljA gene. Nine operator-constitutive (Oc) mutants of fliC were isolated from S. typhimurium by selecting those which could express fliC in the presence of the repressor. Among them, eight mutants could express fliC both in the presence and the absence of the repressor, whereas the ninth one could express only in the presence of the repressor. Nucleotide sequence analysis revealed that the Oc mutations of the former type were all located between bp 7 and 20 upstream from the coding region of fliC, which suggests that this region may correspond to the operator for fliC. The latter mutant was found to have a tandem duplication of 28 bp which contains a part of the operator sequence, and seems to require the repressor to activate fliC expression.


A Critical Review of Zebrafish Neurological Disease Models-2. Application: Functional and Neuroanatomical Phenotyping Strategies and Chemical Screens.
Extensive phylogenetic conservation of molecular pathways and neuroanatomical structures, associated with efficient methods for genetic modification, have been exploited increasingly to generate zebrafish models of human disease. A range of powerful approaches can be deployed to analyze these models with the ultimate goal of elucidating pathogenic mechanisms and accelerating efforts to find effective treatments. Unbiased neurobehavioral assays can provide readouts that parallel clinical abnormalities found in patients, although some of the most useful assays quantify responses that are not routinely evaluated clinically, and differences between zebrafish and human brains preclude expression of the full range of neurobehavioral abnormalities seen in disease. Imaging approaches that use fluorescent reporters and standardized brain atlases coupled with quantitative measurements of brain structure offer an unbiased means to link experimental manipulations to changes in neural architecture. Together, quantitative structural and functional analyses allow dissection of the cellular and physiological basis underlying neurological phenotypes. These approaches can be used as outputs in chemical modifier screens, which provide a major opportunity to exploit zebrafish models to identify small molecule modulators of pathophysiology that may be informative for understanding disease mechanisms and possible therapeutic approaches.


Consumer participation in early detection of the deteriorating patient and call activation to rapid response systems: a literature review.
This review investigated the impact of consumer participation in recognition of patient deterioration and response through call activation in rapid response systems. Nurses and doctors have taken the main role in recognition and response to patient deterioration through hospital rapid response systems. Yet patients and visitors (consumers) have appeared well placed to notice early signs of deterioration. In response, many hospitals have sought to partner health professionals with consumers in detection and response to early deterioration. However, to date, there have been no published research-based reviews to establish the impact of introducing consumer involvement into rapid response systems. A critical research-based review was undertaken. A comprehensive search of databases from 2006-2014 identified 11 studies. Critical appraisal of these studies was undertaken and thematic analysis of the findings revealed four major themes. Following implementation of the consumer activation programmes, the number of calls made by the consumers following detection of deterioration increased. Interestingly, the number of staff calls also increased. Importantly, mortality numbers were found to decrease in one major study following the introduction of consumer call activation. Consumer and staff knowledge and satisfaction with the new programmes indicated mixed results. Initial concerns of the staff over consumer involvement overwhelming the rapid response systems did not eventuate. Evaluation of successful consumer-activated programmes indicated the importance of: effective staff education and training; ongoing consumer education by nurses and clear educational materials. Findings indicated positive patient outcomes following introduction of consumer call activation programmes within rapid response systems. Effective consumer programmes included information that was readily accessible, easy-to-understand and available in a range of multimedia materials accompanied by the explanation and support of health professionals. Introduction of consumer-activated programmes within rapid response systems appears likely to improve outcomes for patients experiencing deterioration.


Late hypopharyngo-esophageal perforation after cervical spine surgery: proposal of a therapeutic strategy.
Hypopharynx and esophagus are occasionally at risk of perforation after cervical spine surgery. Although relatively rare--compared to the frequency of anterior instrumentation--hypopharyngo-esophageal perforation has to be considered as a late complication. An interdisciplinary surgical strategy is required for treatment. We herein propose a flow sheet for an interdisciplinary treatment strategy. The concept is based on the authors' personal experiences with this rare complication in a high-volume center for esophageal surgery. Our interdisciplinary surgical strategy is based on three central parameters that determine the course of treatment: (1) The patient's general condition and signs of systemic infection determine the requirement for critical care management. (2) The stability of the spine (to be addressed by the orthopedic surgeon) determines the requirement for dorsal stabilization, prior to the mandatory removal of the anterior osteosynthesis material that is damaging the hypopharyngo-esophageal structures. (3) The surgical strategy for treatment of the gastrointestinal perforation--the decision to undertake either primary repair or resection--is based on its morphological characteristics; whether it is covered or free, whether it is associated with severe local infection or not, whether the defect is small or large. Hypopharyngo-esophageal perforations after spine surgery are an interdisciplinary challenge, best treated by a concert of specialists (ICU, orthopedic surgeon, and gastrointestinal surgeon).


Influence of the built environment of Nanjing's Urban Community on the leisure physical activity of the elderly: an empirical study.
Urbanization and aging are global phenomena that offer unique challenges in different countries. A supportive environment plays an important role in addressing the issues of health behavioral change and health promotion (e.g., prevent chronic illnesses, promote mental health) among older adults. With the development of the socio-ecological theoretical model, studies on the impact of supportive environments on physical activity have become popular in the public health field in the EU and US. Meanwhile, very few Chinese studies have examined the relationship between built environment features and older adults' physical activity at the ecological level. The purpose of the study is to investigate how the factors part of the built environment of Nanjing's communities also influence leisure time physical activity among the elderly. Using a socio-ecological model as a theoretical framework, we conducted a cross-sectional study of 399 elderly people from 19 communities in Nanjing, China, using a one-on-one questionnaire to collect data, including participants' perceived built environment and self-reported physical activity. A multivariate linear regression method was used to analyze the factors influencing their recreational physical activity. This study found that compared to older people with low average monthly income, the recreational physical activity of the elderly with average monthly incomes between 1001 and 2000 ¥ (β = 23.31, p < 0.001) and 2001 ¥ or more (β = 21.15, p < 0.001) are significantly higher. After controlling for individual covariates, street connectivity (β = 7.34, p = 0.030) and street pavement slope (β = - 7.72, p = 0.020), we found that two out of ten built environment factors indicators influence their physical activity. The importance of each influencing factor ranked from highest to lowest are monthly average income, street pavement slope, and street connectivity. Other factors were not significantly related to recreational physical activity by the elderly. Older adults with a high income were more likely to participate in recreational physical activity than those with a low income. In order to positively impact physical activity in older adults and ultimately improve health, policymakers and urban planners need to ensure that street connectivity and street pavement slope are factored into the design and development of the urban environment.


Autotaxin signaling facilitates β cell dedifferentiation and dysfunction induced by Sirtuin 3 deficiency.
β cell dedifferentiation may underlie the reversible reduction in pancreatic β cell mass and function in type 2 diabetes (T2D). We previously reported that β cell-specific Sirt3 knockout (Sirt3f/f;Cre/+) mice developed impaired glucose tolerance and glucose-stimulated insulin secretion after feeding with high fat diet (HFD). RNA sequencing showed that Sirt3-deficient islets had enhanced expression of Enpp2 (Autotaxin, or ATX), a secreted lysophospholipase which produces lysophosphatidic acid (LPA). Here, we hypothesized that activation of the ATX/LPA pathway contributed to pancreatic β cell dedifferentiation in Sirt3-deficient β cells. We applied LPA, or lysophosphatidylcoline (LPC), the substrate of ATX for producing LPA, to MIN6 cell line and mouse islets with altered Sirt3 expression to investigate the effect of LPA on β cell dedifferentiation and its underlying mechanisms. To examine the pathological effects of ATX/LPA pathway, we injected the β cell selective adeno-associated virus (AAV-Atx-shRNA) or negative control AAV-scramble in Sirt3f/f and Sirt3f/f;Cre/+ mice followed by 6-week of HFD feeding. In Sirt3f/f;Cre/+ mouse islets and Sirt3 knockdown MIN6 cells, ATX upregulation led to increased LPC with increased production of LPA. The latter not only induced reversible dedifferentiation in MIN6 cells and mouse islets, but also reduced glucose-stimulated insulin secretion from islets. In MIN6 cells, LPA induced phosphorylation of JNK/p38 MAPK which was accompanied by β cell dedifferentiation. The latter was suppressed by inhibitors of LPA receptor, JNK, and p38 MAPK. Importantly, inhibiting ATX in vivo improved insulin secretion and reduced β cell dedifferentiation in HFD-fed Sirt3f/f;Cre/+ mice. Sirt3 prevents β cell dedifferentiation by inhibiting ATX expression and upregulation of LPA. These findings support a long-range signaling effect of Sirt3 which modulates the ATX-LPA pathway to reverse β cell dysfunction associated with glucolipotoxicity.


(1H-Benzimidazol-2-yl)methanaminium perchlorate-18-crown-6-water (1/1/1).
The crystal structure of the title compound C(8)H(10)N(3) (+)·ClO(4) (-)·C(12)H(24)O(6)·H(2)O, consists of an organic (1H-benzimidazol-2-yl)methanaminium cation, an inorganic ClO(4) (-) anion, one 18-crown-6 mol-ecule and one water mol-ecule. In the crystal, the cations and 18-crown-6 mol-ecules are linked by N-H⋯O hydrogen bonds. The crystal packing is stabilized by inter-molecular O-H⋯O, O-H⋯N and O-H⋯Cl hydrogen bonds between anions and the water mol-ecules. One 18-crown-6 C atom and a perchlorate O atom are disordered; both have an occupancy factor ratio of 0.60 (2) and 0.40 (2).


Effect Modification of Cortisol on the Associations Between Obsessive-Compulsive Symptoms on Suicidality in Patients With Acute Coronary Syndrome.
Obsessive-compulsive symptoms (OCS) and suicidal ideation (SI) are common in patients with acute coronary syndrome (ACS). This study investigated the associations of OCS and serum cortisol levels with SI, and further evaluated the possible modifying effects of cortisol on the associations between OCS and SI in acute and chronic phases of ACS. In total, 969 ACS patients were recruited from a tertiary university hospital in Korea within 2 weeks of disease onset and evaluated in terms of OCS (using the OCS dimension of the Symptom Checklist-90-Revised), serum cortisol levels, and SI (using the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale). Covariates included sociodemographics, depression, vascular risk factors, and disease severity. After 1 year, 711 patients were re-evaluated in terms of SI. Logistic regression analysis was performed with adjustment for covariates. Higher OCS was significantly associated with SI both at baseline and follow-up. Serum cortisol showed no such association, but modified the association between OCS and SI. That was the associations were significant only in the higher but not in the lower serum cortisol levels, with significant interaction terms after adjusted for relevant covariates. Evaluating OCS and serum cortisol levels at the acute phase could improve the accuracy of clinical predictions of SI both in the acute and chronic phases of ACS.


Process performance and modelling of anaerobic digestion using source-sorted organic household waste.
Three distinctive start-up strategies of biogas reactors fed with source-sorted organic fraction of municipal solid waste were investigated to reveal the most reliable procedure for rapid process stabilization. Moreover, the experimental results were compared with mathematical modeling outputs. The initial inoculations to start-up the reactors were 10, 50 and 100% of the final working volume. While a constant feeding rate of 7.8gVS/d was considered for the control reactor, the organic loading rate for fed-batch reactors with 10 and 50% inoculation was progressively increased during a period of 60 and 13days, respectively. The results clearly demonstrated that an exponentially feeding strategy, considering 50% inoculation relative to final volume, can significantly decrease the alternatively prolonged period to reach steady conditions, as observed by high biogas and methane production rates. The combination of both experimental and modelling/simulation succeeded in optimizing the start-up process for anaerobic digestion of biopulp under mesophilic conditions.


Classification of maize contaminated withFusarium Graminearum Using Mid-infrared Spectroscopy and Chemometrics.
Advances in the development of a novel method for the detection ofFusarium graminearum employing mid-infrared spectroscopy are described. The dried and ground sample was sieved and the fraction with particle sizes between 250 and 100 μm was used for spectroscopy. The sample was pressed against a diamond ATR-crystal, mounted in the sample chamber of an FT-IR spectrometer and the mid-infrared absorption spectrum was recorded. The most prominent features in the spectrum were identified as protein, lipid and carbohydrate bands, which are changed by fungal infection. Multivariate data analysis was employed to detect the spectral changes: Principal component analysis (PCA) of mean centred data proved to be the most efficient method for the separation of contaminated maize from uninfected samples using the first two principal components. Ergosterol and the toxin deoxynivalenol (DON) served as reference parameters and were obtained from each sample using conventional analytical techniques. Samples with a toxin content of as low as 309 μg/kg could be separated from blank samples, which is well in the range of natural contamination. Investigated concentration ranges were 0.73-4.5 mg/kg for ergosterol and 0-2.6 mg/kg for DON. The percentage of correctly classified samples was between 75 and 100%.


Butyrate effect on nuclear proteins of two Chinese hamster cell lines.
The effect of sodium butyrate on the nuclear proteins of two Chinese hamster cell lines (V79 and CHO) was studied. Butyrate treatment induces hyperacetylation of core histones in both cell lines, while H1 histone shows a different behavior. In CHO cells H1 is dephosphorylated following butyrate incubation; V79 do not show any change of H1 subtypes. It seems that H1 response to butyrate treatment is cell type dependent. Using silver staining a group of proteins that could be present in vivo in the nucleo-protein complex was also detected.


Demonstration of high monoaminoxidase-A levels in neuroendocrine gastroenteropancreatic tumors in vitro and in vivo-tumor visualization using positron emission tomography with 11C-harmine.
A majority of neuroendocrine gastroenteropancreatic (GEP) tumors can be detected by conventional radiological methods and scintigraphic techniques. Still there are problems to visualize small tumor lesions and non-functioning tumors. The aim of this study was to investigate some of the monoamine processing pathways of neuroendocrine GEP-tumors and try to find a new tracer substance for in vivo characterization and visualization by Positron Emission Tomography (PET). Autoradiography of tumor sections from 8 midgut carcinoids (MGC) and 8 endocrine pancreatic tumors (EPT) was performed with (11)C-labeled tracers for serotonin and dopamine transporters, serotonin HT2A-, dopamine D1- and muscarinic receptors and for monoamine oxidase A (MAO-A). The in vitro results initiated PET studies with (11)C-Harmine in 4 patients with MGC and 7 patients with EPT (one insulinoma, two glucagonomas and four non-functioning EPT). The MAO-A-ligand Harmine expressed specific in vitro binding of 87 +/-21% for MGC and 125 +/- 50% for EPT, compared to reference tissue (rat brain, 100%). All other substances showed relatively low specific binding. (11)C-harmine-PET could visualize tumors in all patients. The mean standardized uptake value (SUV) for MGC was 7.5 +/- 3.9 and for EPT 12.9 +/- 2.7, whereas the SUV of normal liver, intestine and pancreas were 3.1 +/- 0.5, 3.4 +/- 1.2 and 8.9 +/- 3.0 respectively. This study demonstrates in vitro and in vivo that neuroendocrine GEP-tumors are characterized by a high MAO-A-expression, thereby adding to the similarities of neuronal and neuroendocrine tissue. It also indicates a possible application for (11)C-harmine as a new PET-tracer for neuroendocrine GEP-tumors with the potential to visualize also non-functioning EPT's.


Use of microdialysis for the assessment of fluoroquinolone pharmacokinetics in the clinical practice.
Antibacterial drugs, including fluoroquinolones, can exert their therapeutic action only with adequate penetration at the infection site. Multiple factors, such as rate of protein binding, drug liposolubility and organ blood-flow all influence ability of antibiotics to penetrate target tissues. Microdialysis is an in vivo sampling technique that has been successfully applied to measure the distribution of fluoroquinolones in the interstitial fluid of different tissues both in animal studies and clinical setting. Tissue concentrations need to be interpreted within the context of the pathogenesis and causative agents implicated in infections. Integration of microdialysis -derived tissue pharmacokinetics with pharmacodynamic data offers crucial information for correlating exposure with antibacterial effect. This review explores these concepts and provides an overview of tissue concentrations of fluoroquinolones derived from microdialysis studies and explores the therapeutic implications of fluoroquinolone distribution at various target tissues.


Hibiscus rosa-sinensis as a potential hyperaccumulator in metal contaminated magnesite mine tailings.
Mining is one of the major contributors for land degradation and severe heavy metals based soil pollution. In this study, the physicochemical properties of magnesite mine soil was investigated and assess the optimistic and eco-friendly remediation approach with Hibiscus rosa-sinensis with the effect of pre-isolated Acidithiobacillus thiooxidans. The physicochemical properties analysis results revealed that most the parameter were either too less or beyond the permissible limits. The pre-isolated A. thiooxidans showed remarkable multi-metal tolerance up to 800 μg mL-1 concentration of Cr, Cd, Pb, and Mn. Heavy metal content in polluted soil was reduced to avoid more metal toxicity by diluting with fertile control soil as 80:20 and 60:40. The standard greenhouse experiment was performed to evaluate the phytoextraction potential of H. rosa-sinensis under the influence of A. thiooxidans in various treatment groups (G-I to G-V). The outcome of this investigation was declared that the multi-metal tolerant A. thiooxidans from G-III and G-II showed remarkable effect on growth and phytoextraction ability of H. rosa-sinensis on metal polluted magnesite mine soil in 180 d greenhouse study. These results suggested that the combination of H. rosa-sinensis and A. thiooxidans could be used as an excellent hyper-accumulator to extract metal pollution from polluted soil.


Raman spectroscopy of selected arsenates--implications for soil remediation.
The contamination of soils with heavy metals such as As, Cr and Cu is of great importance; the remediation of such soils even more so. Arsenic compounds are prevalent in soils either through leaching of mine tailings, the use of Cu/Cr/As as a wood preservative or through the use of arsenic in cattle dips. The arsenic compounds in soils and leachates can be highly reactive and mobile, resulting in the formation of metal arsenate compounds. Of these compounds, one such set of minerals that can be formed is the vivianite arsenate minerals. Raman spectroscopy has been used to characterise the vivianite arsenates and to identify arsenic contaminants in a soil.


Fecal excretion of intestinal glycosphingolipids by newborns and young children.
Glycosphingolipids were shown to persist in human fecal excretions from birth up 2 years of age. The pattern of glycosphingolipids was dependent on blood group and secretor status of the child and changed dramatically during the first months of life. Perinatally cerebroside, hematoside and blood group active fucolipids were dominating among fecal glycolipids. From the time of weaning lactosylceramide abruptly became and then persisted as a dominating glycolipid although cerebroside, complex gangliosides and blood group active fucolipids could still be detected in feces even at 2 years of age.


Intracellular metabolism of 4-hydroxynonenal.
4-hydroxynonenal (HNE) is a major aldehydic product of lipid peroxidation known to exert a multitude of biological, cytotoxic, and signal effects. Mammalian cells possess highly active pathways of HNE metabolism. The metabolic fate of HNE was investigated in various mammalian cells and organs such as hepatocytes, intestinal enterocytes, renal tubular cells, aortic and brain endothelial cells, synovial fibroblasts, neutrophils, thymocytes, heart, and tumor cells. The experiments were carried out at 37 degrees C at initial HNE concentrations between 1 microM--that means in the range of physiological and pathophysiologically relevant HNE levels--to 100 microM. In all cell types which were investigated, 90-95% of 100 microM HNE were degraded within 3 min of incubation. At 1 microM HNE the physiological blood serum level of about 0.1-0.2 microM was restored already after 10-30 s. As primary products of HNE in hepatocytes and other cell types the glutathione-HNE-1:1-conjugate, the hydroxynonenoic acid and the corresponding alcohol of HNE, the 1,4-dihydroxynonene, were identified. Furthermore, the beta-oxidation of hydroxynonenoic acid including the formation of water was demonstrated. The quantitative share of HNE binding to proteins was low with about 2-8% of total HNE consumption. The glycine-cysteine-HNE, cysteine-HNE adducts and the mercapturic acid from glutathione-HNE adduct were not formed in the most cell types, but in kidney cells and neutrophils. The rapid metabolism underlines the role of HNE degrading pathways in mammalian cells as important part of the secondary antioxidative defense mechanisms in order to protect proteins from modification by aldehydic lipid peroxidation products.


Virtual screening and molecular dynamics simulation for identification of natural antiviral agents targeting SARS-CoV-2 NSP10.
New variations of SARS-CoV-2 continue to emerge in the global pandemic, which may be resistant to at least some vaccines in COVID-19, indicating that drug and vaccine development must be continuously strengthened. NSP10 plays an essential role in SARS-CoV-2 viral life cycle. It stimulates the enzymatic activities of NSP14-ExoN and NSP16-O-MTase by the formation of NSP10/NSP14 and NSP10/NSP16 complexes. Inhibiting NSP10 can block the binding of NSP10 to NSP14 and NSP16. This study has identified potential natural NSP10 inhibitors from ZINC database. The protein druggable pocket was identified for screening candidates. Molecular docking of the selected compounds was performed and MM-GBSA binding energy was calculated. After ADMET assessment, 4 hits were obtained for favorable druggability. The analysis of site interactions suggested that the hits all had excellent binding. Molecular dynamics studies revealed that selected natural compounds stably bind to NSP10. These compounds were identified as potential leads against NSP10 for the development of strategies to combat SARS-CoV-2 replication and could serve as the basis for further studies.


Adverse effects and bioconcentration of chromium in two freshwater rotifer species.
Bioaccumulation of trivalent (CrIII) and hexavalent chromium (CrVI), and its adverse effects were studied in two rotifer species: Brachionus calyciflorus (two different strains), and Lecane quadridentata. Median Lethal Concentration (LC50) at 24 h of both species showed that CrVI is highly toxic: LC50 ranges from 4.7 × 10(-5) to 4 × 10(-6) mg L(-1)), compared with CrIII: LC50 ranges from 0.64 to 1.279 mg L(-1). Using the LC50 as an exposure concentration, and using atomic absorption, the bioconcentration factor (BCF) was obtained and BCFs of rotifers exposed to CrIII are four orders of magnitude lower than BCFs of rotifers exposed to CrVI. The effect of Cr on the elemental composition of the two species of rotifers in their structures by X-ray microanalysis by energy dispersion showed that Cr is found in intoxicated rotifers, but not in control rotifers. The basal immunoreactivity to metallothioneins is greater in B. calyciflorus than L. quadridentata. The immunoreactivity to metallothioneins decreases in B. calyciflorus when is exposed to CrIII, in contrast in L. quadridentata the immunoreactivity to metallothioneins increase when is exposed to CrIII, and the immunoreactivity to CrVI in L. quadridentata decrease. A mechanism is proposed in which the harder lorica of L. quadridentata acts as a barrier and accumulator of CrVI, and allows for attenuating responses like metallothionein production in L. quadridentata. Instead, in B. calyciflorus the lack of a harder lorica allows for deeper penetration of CrVI, and no time to produce attenuating measures.


Classification of glacier with supervised approaches using PolSAR data.
Glacier comprises distinct features (snow, ice, and debris cover) and their identification and classification using satellite imagery is still a challenging task. Classification of different glacier features (zones) using remote sensing data is useful for numerous environmental and societal applications. The purpose of this study is to develop the fully polarimetric SAR (PolSAR) deep neural networks classification approach for the extraction of different features of the alpine glaciers. The developed approach was tested and classification results were compared with the support vector machines-based classification over the part of two glaciers: Siachen glacier and Bara Shigri glacier. The overall accuracy (OA) of GF-DNN classification is relatively high (91.17% for Siachen and 89% for Bara Shigri) with a good kappa coefficient (0.88 for Siachen and 0.85 for Bara Shigri) as compared to SVM for both the selected glaciers. An improvement of more than 10% is achieved in the OA of GF-DNN classification as compared to SVM for both the glaciers. The obtained classified results and accuracy demonstrates the potential of deep neural networks-based glacier features classification approach for glaciated terrain features.


Dosimetric correlates for acute esophagitis in patients treated with radiotherapy for lung carcinoma.
Acute esophagitis is a common complication of radiotherapy (RT) for non-small-cell carcinoma of the lung. Previous reports have related esophagitis to dosimetric parameters such as the length of the irradiated esophagus, maximal dose, or volume of the organ treated beyond a threshold dose. However, when using oblique beams, a portion of the esophageal circumference may be outside the treated field, resulting in partial esophageal irradiation. Therefore, our aim was to determine whether the irradiated esophageal surface area and/or esophageal volume are predictive of acute esophagitis in relation to other clinical and treatment-related factors. Complete dose-volume information was gathered for 166 patients receiving definitive RT for Stage I-IIIB non-small-cell carcinoma of the lung at our institution. Seventy-eight patients received chemotherapy (37 before RT and 41 concurrently). All patients were treated to doses of 60-74 Gy (median, 70 Gy) delivered in single daily fractions of 1.8-2.1 Gy. The doses were prescribed to the isocenter without using heterogeneity corrections; however, the doses were corrected to account for lung heterogeneity in this report. Esophageal contrast was used to contour the esophagus from the cricoid to the gastroesophageal junction in each case. Esophagitis was scored according to the Radiation Therapy Oncology Group criteria with Grade 2 or worse considered clinically significant. To determine the importance of the irradiated surface area, the volumetric treatment plan for each patient was prepared for analysis by relating a surface area to each point of the esophagus contour. Spearman's rank correlation was used to correlate the esophagitis score with A(d), where A represents the surface area (in centimeters squared) receiving the dose, d, or greater (in Gray), or V(d), where V represents the volume (in centimeters cubed) receiving d (in Gray). The surface areas studied were A(5)-A(80) or V(5)-V(80) in 5-Gy increments. The clinical parameters studied in univariate analysis included patient age, stage, performance status, use of pretreatment chemotherapy, and use of concurrent chemotherapy. Step-wise regression analysis was then used to determine the statistically significant factors predicting acute esophagitis. Forty-five patients (27%) developed Grade 2 or worse esophagitis, 37 developed Grade 2, 7 Grade 3, and 1 Grade 4. No deaths resulted from this complication. The most statistically significant single parameters for predicting acute esophagitis were A(55), V(60), and the use of concurrent chemotherapy. Age, stage, performance status, and pre-RT chemotherapy had no statistically significant influence on the incidence of acute esophagitis. On logistic regression analysis, A(55) (p < or =0.0005), V(60) (p < or =0.001), and the use of concurrent chemotherapy (p = 0.001) emerged as statistically significant correlates of acute esophagitis. The esophageal surface area receiving > or =55 Gy, the esophageal volume receiving > or =60 Gy, and the use of concurrent chemotherapy were the most statistically significant predictive factors for early esophagitis. Adequate dosimetric coverage of the planning target volume remains the goal of RT planning. High values of A(55) and/or V(60) are indicative of the development of acute esophagitis and may indicate a need to explore alternative RT planning options.


Statistical tools for the temporal analysis and classification of lung lesions.
Lung cancer remains one of the most common cancers globally. Temporal evaluation is an important tool for analyzing the malignant behavior of lesions during treatment, or of indeterminate lesions that may be benign. This work proposes a methodology for the analysis, quantification, and visualization of small (local) and large (global) changes in lung lesions. In addition, we extract textural features for the classification of lesions as benign or malignant. We employ the statistical concept of uncertainty to associate each voxel of a lesion to a probability that changes occur in the lesion over time. We employ the Jensen divergence and hypothesis test locally to verify voxel-to-voxel changes, and globally to capture changes in lesion volumes. For the local hypothesis test, we determine that the change in density varies by between 3.84 and 40.01% of the lesion volume in a public database of malignant lesions under treatment, and by between 5.76 and 35.43% in a private database of benign lung nodules. From the texture analysis of regions in which the density changes occur, we are able to discriminate lung lesions with an accuracy of 98.41%, which shows that these changes can indicate the true nature of the lesion. In addition to the visual aspects of the density changes occurring in the lesions over time, we quantify these changes and analyze the entire set using volumetry. In the case of malignant lesions, large b-divergence values are associated with major changes in lesion volume. In addition, this occurs when the change in volume is small but is associated with significant changes in density, as indicated by the histogram divergence. For benign lesions, the methodology shows that even in cases where the change in volume is small, a change of density occurs. This proves that even in lesions that appear stable, a change in density occurs.


Production of Cardiomyocytes by microRNA-Mediated Reprogramming in Optimized Reprogramming Media.
There are currently no effective treatments to regenerate the heart after cardiac injury. Following cardiac injury, heart muscle cells, also known as cardiomyocytes, die in large numbers. The adult mammalian heart does not have the ability to replace these dead cardiomyocytes. In their place, fibroblasts invade the injury zone and generate a scar. The scar impairs cardiac function. An important approach to cardiac regeneration is direct cardiac reprogramming, whereby cardiac fibroblasts within the scar are directly converted into functional cardiomyocytes. Several laboratories have achieved direct cardiac reprogramming via overexpression of the cardiac transcription factors. In contrast, we utilize a combination of four miRNAs (miR-1, miR-133, miR-208, miR-499) that we call miR Combo. One common issue regarding direct cardiac reprogramming strategies is low efficiency. Recently, we have demonstrated that the efficiency of direct cardiac reprogramming is enhanced in the chemically defined reprogramming media.


Evaluation of real-time QRS detection algorithms in variable contexts.
A method is presented to evaluate the detection performance of real-time QRS detection algorithms to propose a strategy for the adaptive selection of ORS detectors, in variable signal contexts. Signal contexts are defined as different combinations of QRS morphologies and clinical noise. Four QRS detectors are compared in these contexts by means of a multivariate analysis. This evaluation strategy is general and can be easily extended to a larger number of detectors. A set of morphology contexts, corresponding to eight QRS morphologies (normal, PVC, premature atrial beat, paced beat, LBBB, fusion, RBBB, junctional premature beat), was extracted from 17 standard ECG records. For each morphology context, the set of extracted beats, ranging from 30 to 23000, was resampled to generate 50 realisations of 20 concatenated beats. These realisations were then used as input to the QRS detectors, without noise, and with three different types of additive clinical noise (electrode motion artifact, muscle artifact, baseline wander) at three signal-to-noise ratios (5 dB, -5 dB, -15 dB). Performance was assessed by the number of errors, which reflected both false alarms and missed beats. The results show that the evaluated detectors are indeed complementary. For example, the Pan-Tompkins detector is the best in most contexts but the Okada detector generates fewer errors in the presence of electrode motion artifact. These results will be particularly useful to the development of a real-time system that will be able to choose the best ORS detector according to the current context.


Primary Care Physician Use and Frequency of Visits Among Physicians in Ontario, Canada.
Maintaining a healthy physician workforce includes the routine use of primary care physician (PCP) services; however, physicians may face barriers to attaining formal care. To analyze access to and frequency of visits to PCPs among physicians compared with nonphysicians. This population-based, retrospective cohort study used registration data from the College of Physicians and Surgeons of Ontario, Canada, from January 1, 1990, to March 31, 2018. Data for all newly practicing physicians as of March 31, 2018, were linked to Ontario health administrative databases. Data were analyzed from August 25, 2020, to August 6, 2021. The main outcomes were enrollment in a PCP practice and visits with a PCP. Generalized estimating equations compared primary care visits between physicians and nonphysicians, matched 1:5 based on age, sex, neighborhood income quintile, and health region. Among 19 581 physicians (mean [SD] age, 43.99 [8.94] years; 53.27% male) matched to 97 905 nonphysicians, physicians were less likely to be enrolled with a PCP than were nonphysicians (81.8% vs 86.4%; absolute difference, 4.6%; adjusted odds ratio [OR], 0.75; 95% CI, 0.72-0.79) and had fewer primary care visits during the preceding 2 years (median [IQR], 2 [0-4] vs 4 [1-7]; adjusted relative rate ratio [RRR], 0.59; 95% CI, 0.58-0.60). Physicians aged 40 years or older and male physicians were less likely to be rostered (ages 40-44 years: OR, 0.70 [95% CI, 0.64-0.77]; male: OR, 0.60 [95% CI, 0.57-0.63]) and more likely to have a lower frequency of PCP visits (ages 40-44 years: RRR, 0.53 [95% CI, 0.51-0.56]; male: RRR, 0.50 [95% CI, 0.50-0.51]) compared with nonphysicians. In this retrospective cohort study, enrollment with a PCP practice and frequency of visits were lower among physicians compared with a matched general population of nonphysicians. Individual, system, and medical cultural factors associated with these results need to be better understood so that physicians can take better care of themselves and their patients.


A questionnaire study on the impact on oral health-related quality of life by conventional rehabilitation of edentulous patient.
This study aimed to determine whether complete dentures improve the oral health-related quality of life (OHRQoL) of edentulous patients, and to assess any associations related to age, gender, and OHRQoL. Hundred edentulous patients who required conventional complete denture treatment were selected for this study. The following inclusion criteria were established: edentulous in both jaws with no previous history of denture treatment and no significant medical history. The patients were selected who satisfied the criteria associated with the class I prosthodoctic diagnostic index. OHRQoL of the patients were assessed twice, once pre treatment (at the first visit) and once post treatment (8 weeks post insertion of dentures) using an instrument called OHIP-EDENT-N. Significant differences in the OHIP-EDENT-N scores between pre treatment and post treatment were calculated using the Wilcoxon Signed-Rank test. Gender differences were assessed using the Mann-Whitney test. After provision of new complete dentures, all domains of the OHIP-EDENT-N showed significant improvements except physical pain and social disability. The results of this study indicated that conventional complete denture improved the OHRQoL of edentulous patients.


COVID-19 vaccination, incidence, and mortality rates among individuals with mental disorders in South Korea: A nationwide retrospective study.
We examined COVID-19 vaccination, incidence, and mortality rates among patients with mental health disorders in South Korea from 1 January 2020 to 31 December 2021. The study found that individuals with mental disorders had higher COVID-19 incidence and mortality than those without. Patients with mood disorders had higher vaccination rates and COVID-19 incidence and mortality than those without mental disorders. In contrast, patients with schizophrenia had lower vaccination rates, slightly lower COVID-19 incidence, and higher COVID-19 mortality. Patients with mental health disorders have been vulnerable to COVID-19, and more attention should be paid to their vaccination and health needs.


Which items on the distress thermometer problem list are the most distressing?
The importance of distress identification and management in oncology has been established. We examined the relationship between distress and unmet bio-psychosocial needs, applying advanced statistical techniques, to identify which needs have the closest relationship to distress. Oncology outpatients (n = 1066) undergoing QUICATOUCH screening in an Australian cancer centre completed the distress thermometer (DT) and problem list (PL). Principal component analysis (PCA), logistic regression and classification and regression tree (CART) analyses tested the relationship between DT score (at a cut-off point of 4) and PL items. Sixteen items were reported by <5 % of participants. PCA analysis identified four major components. Logistic regression analysis indicated three of these component scores, and four individual items (20 items in total) demonstrated a significant independent relationship with distress. The best CART model contained only two PL items: 'worry' and 'depression'. The DT and PL function as intended, quantifying negative emotional experience (distress) and identifying bio-psychosocial sources of distress. We offer two suggestions to minimise PL response time whilst targeting PL items most related to distress, thereby increasing clinical utility. To identify patients who might require specialised psychological services, we suggest the DT followed by a short, case-finding instrument for patients over threshold on the DT. To identify other important sources of distress, we suggest using a modified PL of 14 key items, with the 15th item 'any other problem' as a simple safety net question. Shorter times for patient completion and clinician response to endorsed PL items will maximise acceptance and clinical utility.


In vitro and in vivo effects of combination of Trastuzumab (Herceptin) and Tamoxifen in breast cancer.
Extensive interactions between estrogen receptor alpha (ERalpha) and HER2 signaling pathways have been described. Using BT-474 human breast cancer cells, we have previously shown that the combination of tamoxifen (TAM) and Herceptin results in strong synergistic growth inhibition, enhancement of G(0)-G(1) cell cycle accumulation, inhibition of HER2 activity and a cytostatic effect without cell death. To further examine the underlying mechanism of synergy, we investigated the effect of this drug combination on ERalpha function and growth factor downstream signaling. TAM caused a small increase in ERalpha levels while Herceptin had no effect, and both drugs caused an increase in the level of Ser118-phosphorylated ERalpha. However, both TAM and Herceptin individually inhibited ERalpha transcriptional activity, although the combination did not have a greater effect than either single agent. Herceptin inhibited MAPK and Akt activity, while TAM had no effect on these either as a single agent or when added to Herceptin. Using a BALB/c athymic BT-474 in vivo xenograft model, the drug combination (Herceptin 0.3 mg/kg i.p. twice weekly, TAM 1.0 mg/mouse i.p. three times per week) showed a greater inhibition of tumor growth compared to either single agent. Tumor extracts and fixed sections were examined at the end of the treatment period for treatment-specific alterations: we noted a paradoxical proliferation-inducing effect of TAM that was reversed by the addition of Herceptin. Our results indicate that combined targeting of both peptide growth factor receptors and ERalpha represents a promising breast cancer treatment strategy.


Expression of Cathepsin S in BCG converts it into a pro-apoptotic and highly immunogenic strain.
BCG vaccine, introduced almost 100years ago, is the only option to prevent TB disease. It effectively protects newborns from meningeal TB but fails to prevent adult pulmonary TB. TB kills 1.3million people annually in areas where BCG vaccination is widely practiced. Thus, more effective TB vaccines are urgently needed. Others and we have shown that BCG mimics features of virulent M. tuberculosis, in particular attenuation of essential macrophage functions such as phagosome maturation and antigen presentation. One of these studies revealed that defect in antigen presentation is largely due to down-regulation of the cysteine protease Cathepsin S (CatS), which prevents MHC II molecule maturation and proper antigen peptide loading. Recent studies also suggested a potential role for cysteine proteases in the regulation of apoptosis, a key cellular process used by the macrophage to (i) contain and process ingested bacteria and (ii) facilitate cross-talk antigen presentation between the macrophage and dendritic cells. To reverse the phenotype of vaccine-mediated macrophage attenuation, we engineered a novel BCG strain that expresses and secretes active CatS (rBCG-CatS) to examine its pro-apoptotic properties in vitro, and subsequently, immunogenicity in mice. Transcriptomic profiling of macrophages infected with rBCG-CatS, but not BCG, revealed upregulation of key pro-apoptotic genes and downregulation of anti-apoptotic genes, which were further confirmed by RT-qPCR analyses of expression of selected genes. Macrophages infected with rBCG-CatS undergo apoptosis as indicated by increased levels of annexin V staining and intracellular caspase-3 cleavage. Consistent with these findings, mice vaccinated with rBCG-CatS showed increased antigen-specific CD4+ T-cell responses, as well as enhanced cytokine production and proliferation in CD4+ upon ex vivo re-stimulation. Collectively, this study shows that a pro-apoptotic BCG strain alleviates adverse traits of the wild-type strain, resulting in a highly immunogenic TB vaccine.


[Using the lesser saphenous vein as graft for coronary revascularization].
To investigate the possibility of using the lesser saphenous vein as the alternative bypass graft in coronary artery bypasss graft (CABG). Seven pieces of lesser saphenous veins of 6 patients were harvested as the single or sequential grafts of CABG procedure with No-touch technique. The diameter and length of lesser saphaneous vein met the requirement of graft for entire revascularization. All grafts achieved good flow without significant complications. The lesser saphenous vein graft is an excellent choice for CABG patient who lacks routine grafts as an alternative material.


Subtypes of Parkinson's Disease: What Do They Tell Us About Disease Progression?
Parkinson's disease is a widely heterogeneous disorder with a broad list of motor and nonmotor manifestations. Identifying subtypes of Parkinson's disease is one of the top clinical and research priorities. This review aims to summarize the most valid conventional and recent subtyping solutions that have been introduced so far and to update our current knowledge with recent discoveries on the association between subtypes and disease progression. We also discuss the challenges of subtyping in the context of Parkinson's disease, stability of the subtypes over time, and potential clinical implications. Sophisticated evidence show that there are distinct subtypes of Parkinson's disease with diverging trends of progression. A more holistic view of subtyping to merge traditional motor features with key nonmotor manifestations is a promising approach to identify subgroups with different prognosis. Subtyping could improve further by adding continuing to add data from imaging, CSF, and genetic biomarkers.


Calcium and vitamin D fortified milk reduces bone turnover and improves bone density in postmenopausal women over 1 year.
In Malaysia, hip fracture incidence is higher in Chinese women than other ethnic groups. This study compared the effects of a high-calcium vitamin D fortified milk with added FOS-inulin versus regular milk over 1 year on aspects of bone health in Chinese postmenopausal women in Malaysia. One-hundred and twenty-one women (mean age 59 (± 4) years) were randomized into two groups: control (n = 60; regular milk, 428 mg calcium per day) or intervention (n = 61; fortified milk at 1200 mg calcium, 96 mg magnesium, 2.4 mg zinc, 15 μg vitamin D and 4 g FOS-inulin per day). At baseline, weeks 12, 24, 36 and 52, parathyroid hormone (PTH), C-Telopeptide of Type I Collagen (CTx-1), Procollagen I Intact N-Terminal propeptide (PINP) and vitamin D levels were assessed. Bone density (BMD) was measured at baseline and week 52 using a GE Lunar iDXA. Body mass index, lumbar spine and femoral neck BMD did not differ between groups at baseline. Over 52 weeks, mean plasma 25 (OH) D3 levels increased to 74.8 nmol/L (intervention group) or remained at 63.1 nmol/L (control group) (p < 0.001 between groups). PTH levels increased in the control group (p = 0.001). The intervention resulted in a significant suppression of CTx-1 and PINP at p = 0.018 and p = 0.004. Femoral neck BMD remained stable in the intervention group but decreased significantly in the controls, with a borderline treatment effect (p = 0.07). Compared with regular milk, the fortified milk suppressed bone turnover markers and tended to increase femoral neck BMD.


Levels of polyadenylation factor CstF-64 control IgM heavy chain mRNA accumulation and other events associated with B cell differentiation.
Cleavage stimulation factor (CstF) is one of the multiple factors required for mRNA polyadenylation. The concentration of one CstF subunit (CstF-64) increases during activation of B cells, and this is sufficient to switch IgM heavy chain mRNA expression from membrane-bound form to secreted form. To extend this observation, we disrupted the endogenous CstF-64 gene in the B cell line DT40 and replaced it with a regulatable transgene. Strikingly, a 10-fold decrease in CstF-64 concentration did not markedly affect cell growth but specifically and dramatically reduced accumulation of IgM heavy chain mRNA. Further reduction caused reversible cell cycle arrest in G0/G1 phase, while depletion resulted in apoptotic cell death. Our results indicate that CstF-64 plays unexpected roles in regulating gene expression and cell growth in B cells.


Vascular endothelial growth factor-165 overexpression stimulates angiogenesis and induces cyst formation and macrophage infiltration in human ovarian cancer xenografts.
Vascular endothelial growth factor (VEGF) is suggested to be an important regulator of angiogenesis in ovarian cancer. We have evaluated the effects of VEGF overexpression on the histology and growth rate of human ovarian cancer xenografts. OVCAR-3 human ovarian cancer cells were stably transfected with an expression vector encoding the 165-amino acid isoform of VEGF. As subcutaneous xenografts, moderately and highly VEGF(165)-overexpressing OVCAR-3 cells formed tumors with large cysts. Immunohistochemistry demonstrated an increase in the number of CD31-positive microvessels, some of which were larger in diameter than those in the parental tumors, as well as extensive vascular rimming around the cysts. Weakly VEGF(165)-overexpressing tumors also contained an increased number of CD31-positive microvessels and occasional vascular rimming, but cysts were not present. Immunohistochemistry further revealed the presence of monocytes and macrophages in both parental and VEGF(165)-overexpressing xenografts. Interestingly, the number of monocytes/macrophages was greatly increased in moderately and highly VEGF(165)-overexpressing xenografts and large areas populated with monocytes/macrophages were detected within the tumor stroma. Although the higher number of CD31-positive cells would suggest a better vascularization pattern in VEGF(165)-overexpressing xenografts, tumor growth rates were not increased when compared with that of parental xenografts. These data provide functional evidence for a role of VEGF(165) in cyst formation and monocyte/macrophage infiltration.


[Tension type headaches : Quo vadis?]
Episodic tension type headache is considered to be the most prevalent primary headache. If tension type headache occurs on more than 15 days per month for at least 3 consecutive months, it is classified as chronic tension type headache. In recent years, it has become obvious that it is difficult to distinguish between episodic tension type headache and a moderate migraine attack and also between chronic tension type headache and chronic migraine. In the paper, we discuss how the differential diagnosis can be more specific and which therapy is supported by the literature. In addition, we discuss differences and similarities of tension type headache and migraine and a possible similar pathophysiology of both (convergence hypothesis).


Prognostic value of estrogen receptors in primary breast cancer.
The estrogen receptor status in 335 primary breast carcinomas was correlated with disease-free interval, survival and site of recurrent disease. Estrogen receptor positive carcinomas had a longer disease-free interval, a longer survival (mastectomy-death) and a longer time interval between recurrence and death. These parameters were also influenced by the lymph node status at mastectomy. Estrogen receptor positive cancers had a significantly better chance of survival independent of lymph node status. Estrogen receptors also delayed recurrence in node-positive carcinomas, but this advantage gradually disappeared with increasing interval after mastectomy. Estrogen receptor positive or estrogen receptor negative primary carcinomas did not show any predilection for spread to any particular site.


Pregnancy-induced periodontal inflammation: Influence of salivary cytokines and antimicrobial proteins.
The aim of this study was to evaluate the association between pregnancy-induced periodontal inflammation and levels of some salivary cytokines and antimicrobial proteins (AMPs). The study was a cohort longitudinal study that included pregnant women attending a secondary health facility. Consented participants had oral examination and saliva sampling during pregnancy and post-partum (three months after pregnancy). Saliva samples were used for the analysis of cytokines (TNF-α, IFN-gamma and IL-1β) and AMPs (Lactoferin, Lysozyme, and β defensin-1) using ELISA. Data are presented as median with interquartile range and compared using related sample Wilcoxon signed rank test. Correlations between levels of the salivary factors and indices of periodontal inflammation were determined using Spearman's correlation test. Salivary flow rate, pH, levels of salivary IL-1β and IFN-gamma were significantly lower; while gingival index, periodontal index and level of salivary TNF-α were significantly higher during pregnancy compared with postpartum period. However, salivary lactoferin, lysozyme and β defensin-1 did not show significant difference comparing during pregnancy and postpartum period. Level of salivary IFN-gamma showed negative correlation with gingival index while level of salivary TNF-α showed positive correlation with gingival and periodontal indices. Lower levels of salivary IL-1β and IFN-gamma along with higher TNF-α concentration during pregnancy suggest their contributions to the pathophysiology of pregnancy-induced periodontal inflammation.


Protective action of series of new mono-pyridinium salts and their effect on "aging" of acetylcholine esterase inhibited by fluostigmine.
The protection of acetylcholine esterase (AChE) and the influence on "aging" of AChE--inhibitor complex of several new methylpyridinium derivatives was studied in human blood cells and in mice poisoned with diisopropyl phosphorofluoridate (fluostigmine, DFP). A correlation between the chemical structure of the compounds and their biological activity has been found. The most potent was compound PAN-W-24, having 4-N(CH3)3 substitutent, which markedly prolonged the half-life of "aging" of the AChE-fluostigmine complex.


DEC1 represses cardiomyocyte hypertrophy by recruiting PRP19 as an E3 ligase to promote ubiquitination-proteasome-mediated degradation of GATA4.
Although the pro-hypertrophic role of GATA binding protein 4 (GATA4) during cardiac hypertrophy has been well established, the negative regulatory mechanism to counteract its hyperactivation remains elusive. We hypothesized that the hyperactivation of GATA4 could be a result of loss of interaction between GATA4 with specific suppressors. Using high throughput mass spectrometry technology, we carried out a proteomic screen for endogenous suppressor of GATA4, which disassociated with GATA4 during the hypertrophic response in a cultured cardiac myoblast cell line (H9C2 cells). We identified differentiated embryo chondrocyte 1 (DEC1) negatively regulated the function of GATA4 through physical interaction and negatively regulated cardiac hypertrophy both in vivo and in vitro. Particularly, DEC1 promoted the ubiquitination and proteasome-mediated degradation of GATA4, but did not function as an E3 ligase. Again, using mass spectrometry technology, we systematically identified pre-mRNA processing factor 19 (PRP19) as a newfound E3 ligase, which promoted the K6-linked ubiquitination of GATA4 at its lysine 256. Functional experiments performed in cultured neonatal rat ventricular myocytes and H9C2 cells demonstrated that both DEC1 and PRP19 negatively regulated agonist-induced cardiomyocyte hypertrophic responses. Furthermore, rescue experiments performed in these cells revealed that DEC1 and PRP19 suppressed cardiomyocyte hypertrophy by inhibiting the function of GATA4. Our study thus defined the novel DEC1-PRP19-GATA4 axis to be a previously unknown mechanism in regulating cardiomyocyte hypertrophy. Although GATA4 is indispensable for normal cardiac function, harnessing DEC1- or PRP19-mediated negative regulation to counteract the hyperactivation of GATA4 might serve as a novel therapeutic strategy for pathological cardiac hypertrophy.


Differentiation Between Internal Carotid Artery Hypoplasia and Acquired Narrowing by Neurovascular Ultrasound: Case Series and Literature Review.
Uniformly narrowed internal carotid artery (ICA) without proximal steno-occlusion or parietal anomalies is often subject to misdiagnosis due to lack of awareness. We combined our experiences of 4 cases with 29 previously published cases to form a retrospective series including 18 cases of ICA hypoplasia and 15 cases of ICA acquired narrowing. The ultrasonic manifestations of ICA acquired narrowing and ICA hypoplasia are extremely similar, but narrowed ICA without intracranial occlusion or bottle-neck-sign highly indicates ICA hypoplasia, whereas moyamoya vessels favor ICA acquired narrowing, thus promoting the understanding of and discriminability between the two on neurovascular ultrasound.


Verrucous lupus erythematosus: ultrastructural studies on a distinct variant of chronic discoid lupus erythematosus.
Ten patients with classic discoid lupus erythematosus of the face associated with verrucous, papulonodular lesions on the arms and hands were studied by electron microscopy. The ultrastructural findings on the verrucous lesions included apoptotic keratinocytes, intraepidermal lymphocytes, and gapping, detachment, and reduplication of the basal lamina. Also, tubuloreticular inclusion bodies were present in the endothelial cells. These observations, together with the clinical, histopathologic, and immunofluorescence findings, suggest that the verrucous lesions represent a rare, but distinct, variant of chronic discoid lupus erythematosus.