Spectroscopic identification of amyl alcohol hydrates through free OH observation.
In this study, we identify the crystal structures of amyl alcohol + CH(4) hydrates and demonstrate that the free OH observation of alcohol hydrates provides evidence of OH incorporation into the host framework occurring in some amyl alcohols. While two amyl alcohols, 3-methyl-2-butanol and 2-methyl-2-butanol, were identified as encaged in the 5(12)6(8) large cage of structure-H hydrate, as expected from their molecular sizes above 7.5 A, two other amyl alcohols, 3-methyl-1-butanol and 2,2-dimethyl-1-propanol, were identified to be abnormally included in the 5(12)6(4) large cage of structure-II hydrate in spite of their too large sizes of 9.04 and 7.76 A, respectively. The Raman spectra of two "normal" amyl alcohol hydrates evolved free OH peaks around 3,600 cm(-1), implying that there is no strong hydrogen bonding interaction between alcohol guest and water host; however, for two "abnormal" amyl alcohol hydrates, the corresponding peaks were not detected, which indicates that the OH is incorporated into the host lattice in order to make the large alcohol guest fit into the relatively small 5(12)6(4) cage of structure-II. The present findings are expected to provide useful information for a better understanding of alcohol guest dynamic behavior that might be significantly affected by structural dimensions and host-guest interactions.


Production of the dammarene sapogenin (protopanaxadiol) in transgenic tobacco plants and cultured cells by heterologous expression of PgDDS and CYP716A47.
Protopanaxadiol (PPD) is an aglycone of dammarene-type ginsenoside and has high medicinal values. In this work, we reported the PPD production in transgenic tobacco co-overexpressing PgDDS and CYP716A47. PPD is an aglycone of ginsenosides produced by Panax species and has a wide range of pharmacological activities. PPD is synthesized via the hydroxylation of dammarenediol-II (DD) by CYP716A47 enzyme. Here, we established a PPD production system via cell suspension culture of transgenic tobacco co-overexpressing the genes for PgDDS and CYP716A47. The concentration of PPD in transgenic tobacco leaves was 2.3-5.7 µg/g dry weight (DW), depending on the transgenic line. Leaf segments were cultured on medium with various types of hormones to induce callus. Auxin treatment, particularly 2,4-D, strongly enhanced the production of DD (783.8 µg g(-1) DW) and PPD (125.9 µg g(-1) DW). Treatment with 2,4-D enhanced the transcription of the HMG-Co reductase (HMGR) and squalene epoxidase genes. PPD production reached 166.9 and 980.9 µg g(-1) DW in a 250-ml shake flask culture and in 5-l airlift bioreactor culture, respectively.


Investigations of the reaction mechanisms of 1,2-indanediones with amino acids.
The reaction mechanisms of amino acids with a new class of fluorogenic reagents were investigated. The structures of colored and fluorescent species formed in these reactions were partially confirmed by experimental evidence. Reaction intermediates, C-N-C 1,3-dipoles derived from imines, were trapped with dipolarophiles in 3 + 2 cycloadditions to form spiropyrrolidines.


In-beam PET at high-energy photon beams: a feasibility study.
For radiation therapy with carbon ion beams, either for the stable isotope (12)C or for the radioactive one (11)C, it has been demonstrated that the beta(+)-activity distribution created or deposited, respectively, within the irradiated volume can be visualized by means of positron emission tomography (PET). The PET images provide valuable information for quality assurance and precision improvement of ion therapy. Dedicated PET scanners have been integrated into treatment sites at the Heavy Ion Medical Accelerator at Chiba (HIMAC), Japan, and the Gesellschaft für Schwerionenforschung (GSI), Germany, to make PET imaging feasible during therapeutic irradiation (in-beam PET). A similar technique may be worthwhile for radiotherapy with high-energy bremsstrahlung. In addition to monitoring the dose delivery process which in-beam PET has been primarily developed for, it may be expected that radiation response of tissue can be detected by means of in-beam PET. We investigate the applicability of PET for treatment control in the case of using bremsstrahlung spectra produced by 15-50 MeV electrons. Target volume activation due to (gamma, n) reactions at energies above 20 MeV yields moderate beta(+)-activity levels, which can be employed for imaging. The radiation from positrons produced by pair production is not presently usable because the detectors are overloaded due to the low duty factor of medical electron linear accelerators. However, the degradation of images caused by positron motion between creation and annihilation seems to be tolerable.


[Overview on omega-3 polyunsaturated fatty acids and heart failure].
Despite aggressive pharmacotherapy, heart failure is still clinical problem. Current therapies improve clinical symptoms and slow progression to heart failure, but overall the prognosis remains poor. Evidence from epidemiological, clinical and experimental studies indicates a beneficial role of the omega-3 polyunsaturated fatty acids (omega-3 PUFA) found in fish oils in the prevention and management of heart failure. Although the mechanisms is still unclear, clinical and animals studies indicate that the benefits of omega-3 PUFA may be attributed to a number of distinct biological effects on lipoprotein metabolism, inflammation response and mitochondrial function. This review summarise the data related to use of omega-3 PUFA supplementation as a potential treatment for heart failure and discussed possible mechanism of action.


Suppressive effect of modified dominant negative RAS mutant on human cancer by gene transfer with non-viral vector.
N116Y, H-RAS mutant, has dominant negative activity in the RAS function and a suppressive effect on the growth of various types of cancer cells. However, a replication error of N116Y is of potential concern for carcinogenesis in clinical application. To decease the concern, we constructed modified N116Y by deleting the carboxyl terminus, which is necessary for the oncogenic function of Ras. One of the C-terminal deletion mutants of N116Y, N116Y-Cdel2 showed a growth-suppressing effect on various human cancer cell lines in vitro: the cervical cancer cell line HeLa, the pancreatic cancer cell line PCI43, the colon cancer cell lines SW480 and LoVo, and the tongue cancer cell line SAS. In addition, the suppressive effect of N116Y-Cdel2 on LoVo cells was also observed in vivo using a nonviral gene transfer vector, HVJ envelope. Our experiments suggest that the modified N116Y is a potential candidate gene for human cancer gene therapy.


Attributions and self-regulatory efficacy for health-related physical activity.
Two studies were conducted to examine associations among past activity behaviour, attributions and self-regulatory efficacy for maintaining physical activity sufficient for health benefits. The studies differed in that success for being sufficiently active for health benefits was externally referenced in the first study, but not in the second. In both studies, results revealed that attributional dimensions improved the prediction of self-regulatory efficacy beyond that of past physical behaviour. Results suggested that while past experience may influence an individual's self-regulatory efficacy to be active enough for health benefits, how people think about their past behaviour also needs to be considered.


Association study between polymorphisms of the PARD3 gene and schizophrenia.
The aim of this study was to investigate whether par-3 partitioning defective 3 homolog (C. elegans) (PARD3) single nucleotide polymorphisms (SNPs) are associated with schizophrenia. A total of 204 Korean schizophrenic patients [117 male, 41.1±9.6 years (mean age ± SD); 87 female, 42.6±11.5] and 351 control subjects (170 male, 43.8±6.6 years; 181 female, 44.2±5.8) were enrolled. We genotyped nine SNPs of the PARD3 gene [rs7075263 (intron), rs10827392 (intron), rs773970 (intron), rs2252655 (intron), rs10763984 (intron), rs3781128 (Ser889Ser), rs1936429 (intron), rs671228 (intron) and rs16935163 (intron)]. Genotypes of PARD3 polymorphisms were evaluated by direct sequencing. We used SNPStats, SPSS 18.0 and Haploview 4.2 software for analysis of genetic data. Multiple logistic regression models were used to calculate the odds ratio (OR), 95% confidence interval (CI), and corresponding p-values (p), controlling for age and gender as covariables. Allele frequencies of the PARD3 SNPs were significantly associated with schizophrenia (rs3781128, p=0.041; rs1936429, p=0.030; rs671228, p=0.028). Certain genotype frequencies of the PARD3 SNPs also showed significant associations with schizophrenia (p<0.05, rs7075263, rs773970, rs2252655, rs10763984, rs3781128, rs1936429, rs16935163). To the best of our knowledge, this is the first report showing that PARD3 is associated with susceptibility to schizophrenia in a Korean population. In conclusion, our findings suggest that PARD3 may contribute to genetic susceptibility to schizophrenia.


Extraction and purification of specific antibody against Pseudomonas aeruginosa by immune affinity chromatography.
Immune affinity chromatography has been used to extract and purify specific immune antibody against P. aeruginosa immunotype 4 from hyperimmune gamma glubulin containing antibody against each of seven major immunotypes of P. aeruginosa. A column with a 4 ml. bed volume was construced which had a "working capacity" of approximately 1,680 agglutination units. With water used as the eluting agent, 100 percent yields of functionally active antibody were obtained when amounts equal to or less than the working capacity were loaded onto the column. The technique appears to be suitable for large scale extraction of specific immune antibody for therapeutic trials or investigative use.


Jitteriness/Anxiety Syndrome Developing Immediately following Initiation of Oral Administration of Sertraline.
Here, we report our experience with patients in whom jitteriness/anxiety syndrome developed immediately following the start of oral sertraline administration. Administration was discontinued in these patients on day 2, and the jitteriness/anxiety syndrome improved the following day. Jitteriness/anxiety syndrome may develop immediately following oral administration of even low doses of sertraline, and improvement can be expected if sertraline is promptly discontinued.


Chronic cerebral blood flow alterations in traumatic brain injury and sports-related concussions.
Traumatic brain injury (TBI) and sports-related concussion (SRC) may result in chronic functional and neuroanatomical changes. We tested the hypothesis that neuroimaging findings (cerebral blood flow (CBF), cortical thickness, and 1H-magnetic resonance (MR) spectroscopy (MRS)) were associated to cognitive function, TBI severity, and sex. Eleven controls, 12 athletes symptomatic following ≥3SRCs and 6 patients with moderate-severe TBI underwent MR scanning for evaluation of cortical thickness, brain metabolites (MRS), and CBF using pseudo-continuous arterial spin labeling (ASL). Cognitive screening was performed using the RBANS cognitive test battery. RBANS-index was impaired in both injury groups and correlated with the injury severity, although not with any neuroimaging parameter. Cortical thickness correlated with injury severity (p = 0.02), while neuronal density, using the MRS marker ((NAA+NAAG)/Cr, did not. On multivariate analysis, injury severity (p = 0.0003) and sex (p = 0.002) were associated with CBF. Patients with TBI had decreased gray (p = 0.02) and white matter (p = 0.02) CBF compared to controls. CBF was significantly lower in total gray, white matter and in 16 of the 20 gray matter brain regions in female but not male athletes when compared to female and male controls, respectively. Injury severity correlated with CBF, cognitive function, and cortical thickness. CBF also correlated with sex and was reduced in female, not male, athletes. Chronic CBF changes may contribute to the persistent injury mechanisms in TBI and rSRC.


Laryngotracheal reconstruction at relapsing polychondritis.
Relapsing polychondritis (RP) is characterized by chronic, recurrent episodes of inflammation with eventual degeneration of cartilaginous tissues including the ears, nose, larynx, trachea, and so on. Tracheobronchomalacia and airway stenosis may be seen in RP. In this report, we describe 3 female patients presenting with progressive dyspnea owing to laryngotracheal involvement of RP who underwent laryngotracheal reconstruction.


Central-To-Peripheral Arterial Stiffness Gradient in Hemodialyzed Patients Depends on the Location of the Upper-limb Vascular Access.
Pulse wave velocity ratio (PWV-ratio), a measure of central-to-peripheral arterial stiffness gradient, is calculated as a quotient between carotid-femoral and carotid-radial PWV (cf-PWV/cr-PWV). This new index has been reported to be significantly associated with increased mortality in hemodialyzed patients. Since several reports showed differences in arterial stiffness regarding the pathway where the vascular access (VA) is, the purpose of this research was: a) to compare arterial stiffness values obtained in the left and right sides of the body in hemodialyzed and non-hemodialyzed patients, and b) to analyze PWV-ratio values obtained on the side of the body where the VA was placed and compare them to its contralateral intact side. Since it is difficult to adequately measure cr-PWV in patients with a VA in the forearm, we measured the carotid- brachial PWV (cb-PWV) and used it to calculate PWV-ratio (cf-PWV/cb-PWV). A Pearson's correlation and Bland & Altman analysis were performed in hemodialyzed (n=135) and non-hemodialyzed (n=77) patients, to quantify the equivalence between arterial stiffness parameters (cf-PWV, cb-PWV, PWV-ratio) obtained on each side of the body with respect to its contralateral side. We conclude that PWV-ratio values measured on the side where the VA is placed were significantly higher than those obtained in its contralateral side, in hemodialyzed patients included in this research. Moreover, cf-PWV, cb-PWV and PWV-ratio values obtained on one side of the body were always highly correlated with its contralateral side. According to this research, any research involving PWV-ratio should always consider the observed territory.


Safety and efficacy of danaparoid (Orgaran) use in children.
Immune-mediated heparin-induced thrombocytopenia (HIT) is an uncommon but serious complication of therapy with heparins. It affects all ages and requires replacement of the causative anticoagulant. However, information on alternative antithrombotic use in children with HIT is limited. This paper reviews 27 published and 7 unpublished case reports of children aged 2 weeks to 17 years treated with danaparoid. Thirty-three suffered from HIT or suspected HIT, and 1 child without HIT had a high bleeding risk. All children had severe underlying problems increasing their thrombotic and/or bleeding risk. HIT diagnosis was confirmed serologically or clinically in 26 cases (78.8%). Danaparoid regimens were similar to those used in adults, but in general, younger children needed higher daily doses of danaparoid to achieve the same target plasma anti-Xa levels than teenagers or adults. Of those with a known outcome 28/33 children (84.8%) survived, 7 having suffered from a serious adverse event. Five deaths occurred including 1 thrombotic and 2 major bleeds. Three of the in total 4 major bleeding events occurred in children undergoing surgery with cardiopulmonary bypass. We conclude that despite the reported adverse events danaparoid can be used as an alternative antithrombotic for children who are intolerant of the heparins, except in cases requiring cardiopulmonary bypass surgery.


Expansion and hepatocytic differentiation of liver progenitor cells in vivo using a vascularized tissue engineering chamber in mice.
Current cell-based treatment alternatives to organ transplantation for liver failure remain unsatisfactory. Hepatocytes have a strong tendency to dedifferentiate and apoptose when isolated and maintained in culture. In contrast, liver progenitor cells (LPCs) are robust, easy to culture and have been shown to replace damaged hepatocytes in liver disease. In this study we investigate whether isolated LPCs can survive and differentiate toward mature hepatocytes in vivo when implanted into a heterotopic mouse tissue engineering chamber model. Healthy Balb/c mice and those put on a choline-deficient ethionin-supplemented diet to induce chronic liver disease were implanted with a tissue engineering chamber based on the epigastric flow through pedicle model, containing either 1 × 10(6) LPCs suspended in Matrigel, or LPC-spheroids produced by preculture for 1 week in Matrigel. Four weeks after implantation the chamber contents were harvested. In all four groups, progenitor cells persisted in large numbers to 4 weeks and demonstrated evidence of considerable proliferation judged by Ki67-positive cells. Periodic acid Schiff staining demonstrated differentiation of some cells into mature hepatocytes. Constructs grown from LPC-spheroids demonstrated considerably greater LPC survival than those from LPCs that were grown as monolayers and implanted as dissociated cells. The combined use of LPC spheroids and the vascularized chamber model could be the basis for a viable alternative to current treatments for chronic liver failure.


Gastric emptying of solids is markedly delayed when meals are fried.
We studied the effect of heat-treated fats on gastric emptying. Eight healthy asymptomatic volunteers (five males; age 28-41 years) ate on different days and in random order two meals identical in contents (pasta, tomato, beef, olive oil, carrots, orange, water; 870 kcal males, 700 kcal females; 47% of calories from carbohydrate, 36% from fat, 17% from protein), but cooked differently (fats fried or not). Ultrasound measurement of antral diameters was used to calculate basal antral section, its maximal dilation after the meal, the time necessary for total emptying, and the percent retention at hourly intervals. No difference was found in basal and maximal antral diameters after the two meals. On the contrary, total gastric emptying was significantly delayed after the fried meal [317.1 (24.12) vs 226.7 (18.4) min, mean (1 SEM); P < 0.002]. A significantly greater percentage of maximal antral distension was still present between 120 and 240 min after the fried meal. The glycemic response and hunger feeling were the same after the two meals, whereas there was a longer persistence of satiety and epigastric fullness after the fried meal. In conclusion, gastric emptying can be influenced not only by the meal content, but also by the way it is cooked.


Once-daily tigecycline for outpatient parenteral antibiotic therapy: a single-centre observational study.
Tigecycline has potential utility in the treatment of complex polymicrobial infections or those caused by MDR organisms in the ambulatory care setting owing to its breadth of antimicrobial coverage. Whilst licensed for twice-daily IV administration, its long half-life permits once-daily administration, which may facilitate successful outpatient parenteral antibiotic therapy (OPAT). A retrospective case series of patients receiving once-daily tigecycline under OPAT was analysed at a single-centre NHS acute hospital (January 2016-June 2018). Patient demographics, including comorbidities, antimicrobial indication, concurrent antimicrobial therapies, treatment duration and adverse events related to treatment were recorded using medical records. Treatment outcomes were defined using the BSAC National Outcomes Registry System (NORS). A total of 25 treatment episodes (24 individual patients) were analysed. The most common indications were bone and joint infections (n = 8) and intra-abdominal infections (n = 7). MDR organisms were common, including ESBL-producing Enterobacterales (n = 13) and glycopeptide-resistant enterococci (n = 4). Median treatment duration was 18 days. Nineteen of 25 (76%) cases had complete cure of treatment, 3 patients experienced treatment-related adverse reactions necessitating cessation of therapy and 3 experienced failure due to disease progression. Eight patients experienced non-limiting adverse effects, such as nausea, vomiting and rash, and one patient had a transient rise in amylase 3 times the upper normal limit (with no evidence of pancreatitis). Once-daily tigecycline can be successfully used for management of complex infections in the OPAT setting, with predominantly mild adverse effects, which can be managed with antiemetics or slow administration.


Reduced phosphorylation of the TGF-Beta signal transducer Smad2 in emphysematous human lung.
Chronic obstructive pulmonary disease (COPD) is characterized by inflammatory immune response, emphysematous destruction of alveolar structures and obstruction in the small conducting airways. Transforming growth factor (TGF)-beta is involved in the maintenance of normal lung tissue homeostasis as a regulator of extracellular proteolysis, tissue repair and inflammatory functions. This study was undertaken to characterize TGF-beta signaling in pathologically distinct areas of COPD lungs. Using Smad2 phosporylation (P-Smad2) as an indicator of TGF-beta signaling activity we analyzed COPD patient tissues and controls by immunohistochemistry. Emphysematous lung showed significantly reduced P-Smad2 immunoreactivity both in the alveolar and bronchiolar epithelium, which is evidence of reduced TGF-beta signaling activity. On the contrary, in the thickened peribronchial areas there was an increase in the amount of P-Smad2 positive cells. Isolated COPD lung fibroblasts also displayed increased TGF-beta signaling and target gene expression suggesting that the fibroblasts are characteristic to the small airway disease phenotype. Our results indicate that TGF-beta signaling activity is differentially regulated in distinct areas of COPD lung and likely contributes to both emphysematous development and small airway obstruction.


Nickel bioaccumulation in bivalves from the New Caledonia lagoon: seawater and food exposure.
The New Caledonian lagoon is submitted to intense heavy metal input from land-based Ni mining. Therefore, the use of sentinel species is strongly recommended in order to develop and implement coastal zone management programmes of the metal contamination. The tropical oysters Isognomon isognomon and Malleus regula and the clam Gafrarium tumidum were previously proposed as such possible sentinel organisms and were thus investigated in this context. The three species were exposed to Ni via seawater or food using radiotracer techniques. Results indicate that uptake and retention efficiencies of Ni are independent of the dissolved Ni concentrations in the surrounding seawater. Hence, for the three species, body concentrations of Ni taken up from the dissolved phase are directly proportional to the ambient dissolved concentrations. Biokinetic patterns indicated that the major part of Ni was rapidly lost from bivalves during the first days of depuration, whereas 7 to 47% of 63Ni were retained in tissues with a biological half-life not significantly different from infinity. Finally, feeding experiments showed that Ni ingested with food (phytoplankton) was assimilated more efficiently in clams (assimilation efficiency, AE = 61%) than in oysters (AE = 17%), and was strongly retained (T(b1/2) > or = 35 d) in the tissues of both bivalves. It is concluded that the investigated species examined are efficient bioaccumulators of Ni from both the surrounding seawater and the food, and that they would be useful bioindicators for monitoring the status of Ni contamination in tropical coastal waters.


New national osteoporosis guidance-implications for geriatricians.
Fragility fractures are painful, debilitating, often life-changing and accounted for an estimated 2.4% of pre-pandemic health care spending in the UK. Those who are older, frail and multimorbid have the highest fracture risk and therefore the most to gain from anti-osteoporosis treatments to reduce this risk. Currently, an unacceptable treatment gap exists between those eligible for and those who receive treatment. This commentary discusses the major changes to the new, National Institute for Health and Care Excellence accredited, UK National Osteoporosis Guideline Group (NOGG) guidance (published March 2022) most relevant to the management of older people's bone health. Changes include intervention thresholds; using fracture probabilities from FRAX; for patients too frail to undergo DXA; greater emphasis on vertebral fracture detection and the use of intravenous zoledronate as a first-line anti-osteoporosis therapy; the new concept of 'very high fracture risk' which should prompt consideration of use of parenteral anti-osteoporosis therapy; new guidance regarding anabolic treatment options; concerns regarding denosumab cessation; and the urgent need to get patients with a fragility fracture onto treatment to reduce re-fracture risk with follow-up to check tolerance and ensure adherence.


Pipeline embolization device for giant internal carotid artery aneurysms: 9-month follow-up results of two cases.
The pipeline™ embolization device (PED) is a braided, tubular, bimetallic endoluminal implant used for occlusion of intracranial aneurysms through flow disruption along the aneurysm neck. The authors report on two cases of giant internal carotid artery aneurysm treated with the PED. In the first case, an aneurysm measuring 26.4 mm was observed at the C3-C4 portion of the left internal carotid artery in a 64-year-old woman who underwent magnetic resonance imaging (MRI) for dizziness and diplopia. In the second case, MRI showed an aneurysm measuring 25 mm at the C4-C5 portion of the right internal carotid artery in a 39-year-old woman with right ptosis and diplopia. Each giant aneurysm was treated with deployment of a PED (3.75 mm diameter/20 mm length and 4.5 mm diameter/25 mm length, respectively). Nine months later, both cases showed complete radiological occlusion of the giant intracranial aneurysm and sac shrinkage. We suggest that use of the PED can be a therapeutic option for giant intracranial aneurysms.


Nature and origin of the RNA associated with simian virus 40 large tumor antigen.
Simian virus 40 (SV40) large tumor (T) antigen isolated from mammalian cells undergoing lytic or transforming infection is associated with small RNA fragments ("T-antigen RNA") that are protected from nuclease digestion. The rather high complexity of the ribonuclease T1 fingerprints of T-antigen RNA suggested that it is mainly derived from cellular heterogeneous nuclear RNAs. In the present study, 5'-32P-labeled T-antigen RNA was hybridized to monkey, mouse, and human Alu and SV40 DNA, and the nucleotide sequence of 37 T1 oligonucleotides was determined. The results suggest that the bulk of T-antigen RNA is derived from noncoding, double-stranded, ordered regions of cellular heterogeneous nuclear RNAs that exhibit sequence homologies with interspersed repetitive elements of the cellular genome. The possible biological implications of these results are discussed.


Potential of Colocasia leaves in human nutrition: Review on nutritional and phytochemical properties.
Colocasia esculenta leaves possess vital nutritive and nonnutritive components in significant amounts, but are underutilized, and lesser explored. The chemical composition varies significantly depending upon climatic conditions and other agronomical factors of the location of cultivation and variety. Micronutrients, viz. iron (3.4-11.7 mg 100 g-1 ), copper (0.29-0.8 mg 100 g-1 ), magnesium (170-752 mg 100 g-1 ), potassium (0.4-2.4 g 100 g-1 ), and zinc (0.6-4.2 mg 100 g-1 ) are present in high amounts. The ratio of sodium to potassium (1:40) in the leaves add specifically to the antihypertensive properties. Preclinical and clinical studies provide evidence of its antidiabetic, antihemorrhagic, neuropharmacological properties, and as a remedy for stomach and liver ailments. Assessment of phytochemical compounds like chlorogenic acid, anthraquinones, cinnamic acid derivatives, and other phenolics validates these biological properties. The major limiting factor of this plant is oxalate that can be suppressed through food processing strategies. Colocasia leaves are promising green leafy vegetables with nutritional and clinical potential. PRACTICAL APPLICATIONS: Colocasia leaves have demonstrated the ability of antidiabetic, antihypertensive, immunoprotective, neuroprotective, and anticarcinogenic activities. The detailed assessment of phytochemical compounds present in various extracts of the leaves shows the presence of active chemical compounds like anthraquinones, apigenin, catechins, cinnamic acid derivatives, vitexin, and isovitexin which are possibly responsible for the exhibited biological properties. Colocasia leaves are rich sources of micronutrients; however, the presence of oxalates can prohibit proper utilization of these nutrients. Various food processing strategies like soaking, cooking, and so on can significantly reduce the antinutritional content and make these nutrients available for utilization. Documentation of traditional uses and food products from Colocasia leaves show that these leaves have immense potential in the functional food product as well as drug development.


Association between Medicaid Expansion under the Affordable Care Act and Preemptive Listings for Kidney Transplantation.
Before 2014, low-income individuals in the United States with non-dialysis-dependent CKD had fewer options to attain health insurance, limiting their opportunities to be preemptively wait-listed for kidney transplantation. We examined whether expanding Medicaid under the Affordable Care Act was associated with differences in the number of individuals who were pre-emptively wait-listed with Medicaid coverage. Using the United Network of Organ Sharing database, we performed a retrospective observational study of adults (age≥18 years) listed for kidney transplantation before dialysis dependence between January 1, 2011-December 31, 2013 (pre-Medicaid expansion) and January 1, 2014-December 31, 2016 (post-Medicaid expansion). In multinomial logistic regression models, we compared trends in insurance types used for pre-emptive wait-listing in states that did and did not expand Medicaid with a difference-in-differences approach. States that fully implemented Medicaid expansion on January 1, 2014 ("expansion states," n=24 and the District of Columbia) had a 59% relative increase in Medicaid-covered pre-emptive listings from the pre-expansion to postexpansion period (from 1094 to 1737 listings), compared with an 8.8% relative increase (from 330 to 359 listings) among 19 Medicaid nonexpansion states (P<0.001). From the pre- to postexpansion period, the adjusted proportion of listings with Medicaid coverage decreased by 0.3 percentage points among nonexpansion states (from 4.0% to 3.7%, P=0.09), and increased by 3.0 percentage points among expansion states (from 7.0% to 10.0%, P<0.001). Medicaid expansion was associated with absolute increases in Medicaid coverage by 1.4 percentage points among white listings, 4.0 percentage points among black listings, 5.9 percentage points among Hispanic listings, and 5.3 percentage points among other listings (P<0.001 for all comparisons). Medicaid expansion was associated with an increase in the proportion of new pre-emptive listings for kidney transplantation with Medicaid coverage, with larger increases in Medicaid coverage among racial and ethnic minority listings than among white listings.


Incidence and prevalence of non-melanoma skin cancer in Australia: A systematic review.
Non-melanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common cancer occurring in people with fair skin. Australia has been reported to have the highest incidence of NMSC in the world. Using a systematic search of the literature in EMBASE and Medline, we identified 21 studies that investigated the incidence or prevalence of NMSC in Australia. Studies published between 1948 and 2011 were identified and included in the analysis. There were six studies that were conducted on national level, two at state level and 13 at the regional level. Overall, the incidence of NMSC had steadily increased over calendar-years in Australia. The incidence of NMSC per 100,000 person-years was estimated to be 555 in 1985; 977 in 1990; 1109 in 1995; 1170 in 2002 and 2448 in 2011. The incidence was higher for men than women and higher for BCC than SCC. Incidence varied across the states of Australia, with the highest in Queensland. The prevalence of NMSC was estimated to be 2% in Australia in 2002. The incidence and prevalence of NMSC still need to be accurately established at both national and state levels to determine the costs and burden of the disease on the public health system in Australia.


PEG2-Induced Pyroptosis Regulates the Expression of HMGB1 and Promotes hEM15A Migration in Endometriosis.
Endometriosis (EMS) is a common gynecological disease. Prostaglandin E2 (PGE2), which induces chronic pelvic inflammation and cell pyroptosis, a form of programmed cell death based on inflammasome activation, are involved in EMS, but the extent of their involvement and roles remain unclear. The present study aimed to evaluate PGE2-induced pyroptosis in EMS and the influence of PGE2 in EMS progression. Using western blotting, it was found that the expressions of PGE2 and pyroptosis-related proteins (NLRP3, cleaved caspase-1, interleukin (IL)-1β and IL-18) were higher in EMS tissues than in normal endometrial tissues. The levels of PGE2, IL-1β, and IL-18 in the serum of patients with EMS and cell culture fluids were also detected. Using the transwell assay, we verified that PGE2 promoted hEM15A migration via the NLRP3/caspase-1 pyroptotic pathway, and PGE2-induced pyroptosis upregulated the expressions of high mobility group box 1 (HMGB1), E-cadherin, and vimentin. Immunohistochemistry analysis confirmed that PGE2-induced pyroptosis contributed to EMS invasion. These results suggest that PGE2-induced pyroptosis affects the progression of EMS by changing the migration ability of pyroptotic cells and upregulating the expression of HMGB1, E-cadherin, and vimentin. Our findings provide crucial evidence for new treatment pathways and use of anti-inflammatory drugs in EMS.


Myeloma of the head of the pancreas. A case report.
A 45-year-old man was diagnosed with multiple myeloma, IgA-kappa, in 1975. Thirteen years later he presented with obstructive jaundice. Computed tomography (CT) showed a 6-cm mass in the head of the pancreas. Needle aspiration showed myeloma. The jaundice resolved after treatment with radiotherapy. Extraosseous involvement by myeloma is frequently found at autopsy but obstructive jaundice from myeloma of the head of the pancreas is quite rare. This atypical complication of myeloma may be related to the patient's long survival.


Immunodeficiency and prognosis in patients with non-Hodgkin's lymphomas.
Monocyte depleted blood lymphocyte subpopulations, their functions and relation to prognosis were studied in 68 untreated adult patients with non-Hodgkin's lymphomas classified according to the Kiel nomenclature. The median observation time was 48 months (range 41-60). The mean total blood lymphocyte and T (SRBC-rosetting) cell counts were significantly decreased as compared with age-matched controls (n = 57). Twenty-five per cent of the patients had a monoclonal blood B lymphocyte population. The spontaneous lymphocyte DNA synthesis, measured as incorporation of 14C-thymidine, was increased and the response to mitogen and antigen stimulation was decreased. Blood lymphocyte counts and functions before treatment were not related to the rates of remission or survival.


Lessons from genetically altered mesenchymal stem cells (MSCs): candidates for improved MSC-directed myocardial repair.
The regenerative and reparative potential of mesenchymal stem cells (MSCs) make them attractive candidates for numerous cell-directed therapies. The variant degree of tissue repair by transplanted MSCs has been assessed in several published reports. There are many gaps in the knowledge of MSC biology and the underlying reasons for their disparate effectiveness in tissue repair. This review examines successful preclinical models of MSC-directed repair, particularly of myocardial repair, in an attempt to shed light into the events dictating MSC therapeutic efficacy. The reparative advantage of genetically altered MSCs will be described. This overview will elucidate possible molecular mechanisms that can influence MSC engraftment, differentiation, self-renewal, and ultimately increase wound repair.


Stress applied during primary immunization affects the secondary humoral immune response in the rat: involvement of opioid peptides.
The effect of unpredictable, inescapable and uncontrollable electric tail shocks (ES) on the humoral immune response to bovine serum albumin (BSA) was investigated in the rat. Contributions of the procedures that accompany shock delivery, such as witnessing the ES procedure (stress witnessing, SW) and exposure to the apparatus for shock delivery (apparatus control, AC) to the changes in specific immunity induced by ES were also tested. All procedures were applied during primary and/or secondary immunization. It was demonstrated that exposure to ES during primary immunization with BSA significantly suppressed specific anti-BSA antibody production after secondary and tertiary immunization with the same antigen. Exposure to the SW procedure during primary immunization with BSA enhanced the specific antibody level after secondary immunization, while exposure to the apparatus alone did not influence the development of either the primary or secondary humoral immune response to BSA. Both ES-induced suppression and SW-induced potentiation of the humoral immune response were partially inhibited by prior treatment with the opioid receptor antagonist naloxone. Additionally, treatments with the opioid peptides methionine- and leucine-enkephalin decreased anti-BSA antibody level, mimicking to some extent the effects of ES. It is suggested that ES and endogenous opioid peptides had long-term effects on humoral immunity through mechanisms involving immunologic memory.


Assay Integrity of a PCR Influenza Point-of-Care Test Remains Following Artificial System Contamination.
Healthcare providers who have access to tests at the point of care (POC) are increasingly requesting the same performance from the POC test as they expect from the laboratory. With the introduction of the cobas® Liat instrument, highly sensitive molecular diagnostic testing can be performed closer to the patient in CLIA-waived, POC settings. As more sensitive tests become available, there is concern regarding contamination of instrumentation owing to improper handling, mistakes made when processing, or environmental contamination. Recent concerns were raised when a nurse performed environmental surveillance for flu A/B by inserting a dry swab into the cobas Liat instrument and then ran it as a sample on the instrument, generating a positive result. This finding stimulated questions about the possibility of system contamination contributing to false-positive results, ultimately leading to the possibility of providing incorrect treatment to patients. To assess the likelihood of system contamination contributing to the generation of false-positive results, in this study we contaminated a cobas Liat System with flu A/B-positive control material. The system contamination was then assessed by swabbing exposed surfaces. Following confirmed system contamination, negative control samples were processed to determine whether system contamination had an impact on the expected negative results. Instrument contamination was confirmed, and no detectable flu A/B signal was observed for any of the negative control tubes run immediately following confirmation of system contamination. Environmental contamination of the Liat instrument does not have an impact on the integrity of the result.


[Unstable angina: a diagnosis of the past].
The diagnosis acute coronary syndrome includes myocardial infarction together with unstable angina. The definition of the latter diagnosis continues to evolve. Due to widespread clinical application of sensitive markers of myocardial necrosis, including high sensitive cardiac troponin (hs-cTn) assays, the diagnosis for many newly presenting patients will now be myocardial infarction rather than unstable angina. However, patients presenting with chest pain and very low (< 0.05 ng/L) or undetectable levels of hs-cTn have been found to be at extremely low risk of development of myocardial infarction and/or death. Consequently, such patients cannot be classified as having unstable angina. A detailed clinical assessment and reasoning will be necessary to establish the true cause of their--often non-cardiac--symptoms.


Metallodendrimers and dendrimer nanocomposites.
Dendrimers are polymeric compounds with highly branched structures and functionally tunable peripheral groups. Because of their low polydispersity, high degree of molecular uniformity, and precisely controlled structure, dendrimers are excellent models for demonstrating a variety of biological activities. With the attachment of metals ions and/or metals, metallodendrimers or dendrimer nanocomposites, respectively, provide diverse characters for a variety of applications. Functionalization with additional moieties, such as targeted peptides or chromophores, yields metallodendrimers that can find powerful applications and exceed the capabilities of nondendritic molecules or small molecule analogs. This review introduces the background of metallodendrimers and dendrimer nanocomposites. Biomedical applications of metallodendrimers and dendrimer nanocomposites will be discussed, including biomimetic catalysts, imaging contrast agents (especially for MRI imaging), or biomedical sensors and therapeutic agents.


[Quality of neuronal signal registered in the monkey motor cortex with chronically implanted multiple microwires].
Disconnection of central and peripheral parts of motor system leads to severe forms of disability. However, current research of brain-computer interfaces will solve the problem of rehabilitation of patients with motor disorders in future. Chronic recordings of single-unit activity in specialized areas of cerebral cortex could provide appropriate control signal for effectors with multiple degrees of freedom. In present article we evaluated the quality of chronic single-unit recordings in the primary motor cortex of awake behaving monkeys obtained with bundles of multiple microwires. Action potentials of proper quality were recorded from single units during three months. In some cases up to 7 single units could be extracted on a channel. Recording quality stabilized after 40 days since electrodes were implanted. Ultimately, functionality of multiple electrodes bundle makes it highly usable and reliable instrument for obtaining of control neurophysiologic signal from populations of neurons for brain-computer interfaces.


SWI/SNF-dependent long-range remodeling of yeast HIS3 chromatin.
Current models for the role of the SWISNF chromatin remodeling complex in gene regulation are focused on promoters, where the most obvious changes in chromatin structure occur. Here we present evidence that the SWISNF complex is involved in the remodeling of the chromatin structure of an entire gene in vivo. We compared the native chromatin structures of a small yeast plasmid containing the HIS3 gene purified from uninduced and induced cells. Relative to uninduced chromatin, induced chromatin displayed a large reduction in negative supercoiling, a large reduction in sedimentation rate, and increased accessibility to restriction enzymes with sites located both near and far from the HIS3 promoter. These observations indicate that the entire plasmid was remodeled as a result of induction. Loss of supercoiling required the presence of the SWISNF remodeling complex and the activator Gcn4p in vivo. The TATA boxes were not required, suggesting that remodeling was not the result of transcription. The induction-dependent loss of negative supercoiling was not apparent in cells, indicating that the supercoils were lost preferentially from induced chromatin during purification. Thus, induced HIS3 chromatin has a highly labile structure that is revealed as a result of purification. It is concluded that induction of HIS3 creates a domain of labile chromatin structure that extends far beyond the promoter to include the entire gene. We propose that the SWISNF complex is recruited to the HIS3 promoter by Gcn4p and then directs remodeling of a chromatin domain, with important implications for transcription.


Interactional role of microRNAs and bHLH-PAS proteins in cancer (Review).
MicroRNAs (miRNAs) are recognized as an emerging class of master regulators that regulate human gene expression at the post-transcriptional level and are involved in many normal and pathological cellular processes. Mammalian basic HLH (helix-loop-helix)-PER-ARNT-SIM (bHLH-PAS) proteins are heterodimeric transcriptional regulators that sense and respond to environmental signals (such as chemical pollutants) or to physiological signals (for instance hypoxia). In the normal state, bHLH-PAS proteins are responsible for multiple critical aspects of physiology to ensure the cell accurate homeostasis, but dysregulation of these proteins has been shown to contribute to carcinogenic events such as tumor initiation, promotion, and progression. Increasing epidemiological and experimental studies have shown that bHLH-PAS proteins regulate a panel of miRNAs, whereas some miRNAs also target bHLH-PAS proteins. The interaction between miRNAs and certain bHLH-PAS proteins [hypoxia-inducible factor (HIF) and aryl hydrocarbon receptor (AHR)] is relevant to many vital events associated with tumorigenesis. This review will summarize recent findings on the interesting and complicated underlying mechanisms that miRNAs interact with HIFs or AHR in tumors, hopefully to benefit the discovery of novel drug-interfering targets for cancer therapy.


Dendritic cell subsets in primary and secondary T cell responses at body surfaces.
We examine the role of dendritic cells subsets in immunity to peripheral infections, with emphasis on the differences in the regulation of primary and secondary T cell responses to viruses. Our major focus is on new developments in the understanding of immunity to infections of the skin and lung, which are crucial entry points for a variety of infectious pathogens. Initially we describe a diverse network of dendritic cell subsets, but then we argue for a more generalized model of reduced complexity.


Scavenger function of sinusoidal liver cells. Acetylated low-density lipoprotein is endocytosed via a route distinct from formaldehyde-treated serum albumin.
Chemically modified proteins such as acetylated low-density lipoprotein (acetyl-LDL) and formaldehyde-treated serum albumin (f-Alb) infused intravenously are known to undergo receptor-mediated endocytosis by sinusoidal liver cells, major intravascular scavenger cells in vivo. The aim of the present study was to elucidate whether the endocytic uptake of acetyl-LDL and f-Alb is mediated by the same receptor or not. Experiments on the binding of 125I-acetyl-LDL to isolated rat liver sinusoidal cells revealed the presence of a specific, high-affinity, saturable, membrane-associated receptor with an apparent Kd = 7 micrograms of the ligand at 0 degrees C. Unlabeled acetyl-LDL effectively inhibited 125I-f-Alb binding to the cells. By contrast, the binding of 125I-acetyl-LDL to the cells was affected neither by unlabeled f-Alb nor by the antibody raised against the f-Alb receptor. These results indicate that the scavenger receptors for these two ligands are distinct from each other but similarly sensitive to polyanionic compounds.


Torque teno sus virus 1 and 2 viral loads in postweaning multisystemic wasting syndrome (PMWS) and porcine dermatitis and nephropathy syndrome (PDNS) affected pigs.
Torque teno viruses (TTV) are small, non-enveloped viruses with a circular single-stranded DNA genome, which are considered non-pathogenic. However, TTVs have been eventually linked to human diseases. TTVs infecting pigs, Torque teno sus virus 1 (TTSuV1) and 2 (TTSuV2), have been recently associated to porcine circovirus diseases (PCVD). To get more insights into such potential disease association, the aim of this study was to quantify TTSuV1 and TTSuV2 viral loads in serum of pigs affected by two PCVDs, postweaning multisystemic wasting syndrome (PMWS) and porcine dermatitis and nephropathy syndrome (PDNS). Such study was carried out by means of a newly developed real-time quantitative PCR (qPCR) method. Both TTSuVs were highly prevalent among studied pigs. TTSuV2 viral loads were significantly higher in PMWS affected animals, further supporting the previously suggested association between TTSuV2 and PMWS. On the contrary, TTSuV1 prevalence and loads were not related with the studied PCVDs.


Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage.
Topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and meiosis and is a highly attractive target for chemotherapeutic agents. We have identified previously topoisomerase II and heat shock protein 90 (Hsp90) as part of a complex. In this paper we demonstrate that drug combinations targeting these two enzymes cause a synergistic increase in apoptosis. The objective of our study was to identify the mode of cell killing and the mechanism behind the increase in topoisomerase II mediated DNA damage. Importantly we demonstrate that Hsp90 inhibition results in an increased topoiosmerase II activity but not degradation of topoisomerase II and it is this, in the presence of a topoisomerase II poison that causes the increase in cell death. Our results suggest a novel mechanism of action where the inhibition of Hsp90 disrupts the Hsp90-topoisomerase II interaction leading to an increase in and activation of unbound topoisomerase II, which, in the presence of a topoisomerase II poison leads to the formation of an increased number of cleavable complexes ultimately resulting in rise in DNA damage and a subsequent increase cell death.


Neural basis of decision-making and assessment: issues on testability and philosophical relevance.
Decision-making is an intricate subject in neuroscience. It is often argued that laboratorial research is not capable of dealing with the necessary complexity to study the issue. Whereas philosophers in general neglect the physiological features that constitute the main aspects of thought and behaviour, I advocate that cutting-edge neuroscientific experiments can offer us a framework to explain human behaviour in its relationship with will, self-control, inhibition, emotion and reasoning. It is my contention that self-control mechanisms can modulate more basic stimuli. Assuming the aforementioned standpoints, I show the physiological mechanisms underlying social assessment and decision-making. I also establish a difference between veridical and adaptive decision-making, useful to create experimental designs that can better mimic the complexity of our day-by-day decisions in more ecologically relevant laboratorial research. Moreover, I analyse some experiments in order to develop an epistemological reflection about the necessary neural mechanisms to social assessment and decision-making.


DmGTSF1 is necessary for Piwi-piRISC-mediated transcriptional transposon silencing in the Drosophila ovary.
The Piwi-piRNA (PIWI-interacting RNA) complex (Piwi-piRISC) in Drosophila ovarian somatic cells represses transposons transcriptionally to maintain genome integrity; however, the underlying mechanisms remain obscure. Here, we reveal that DmGTSF1, a Drosophila homolog of gametocyte-specific factor 1 (GTSF1) (which is required for transposon silencing in mouse testes), is necessary for Piwi-piRISC to repress target transposons and neighboring genes. DmGTSF1 depletion affected neither piRNA biogenesis nor nuclear import of Piwi-piRISC. DmGTSF1 mutations caused derepression of transposons and loss of ovary follicle layers, resulting in female infertility. We suggest that DmGTSF1, a nuclear Piwi interactor, is an integral factor in Piwi-piRISC-mediated transcriptional silencing.


Spiral multislice computed tomography coronary angiography: a current status report.
Multislice computed tomography coronary angiography (MSCT-CA) has emerged as a powerful noninvasive diagnostic modality to visualize the coronary arteries and to detect significant coronary stenoses. The latest generation 64-slice computed tomography (CT) scanners is a robust technique which allows high-resolution, isotropic, nearly motion-free coronary imaging. Coronary stenoses are detected with high sensitivity and a normal scan accurately rules out the presence of a coronary stenosis. With the introduction of further novel concepts in CT-technology one may expect that MSCT-CA will become a clinically used diagnostic tool.


The role of fat in flavor perception: effect of partition and viscosity in model emulsions.
Decreasing the fat content of a food, while maintaining the same aroma content, changes both aroma release (due to partition effects) and the viscosity of the food. To understand the relative contribution of these two factors on flavor perception, a series of flavored emulsions were prepared to control aroma release and viscosity using different aroma, oil, and hydroxypropyl methyl cellulose (HPMC) contents. Samples were formulated to deliver the same aroma-release in vitro and in vivo, and their viscosity was measured using the Kokini oral shear stress parameter. Despite the in vivo aroma release being constant, there were perceptual differences between the samples, and the flavor intensity decreased as in-mouth viscosity increased. For these iso release samples, the Kokini oral shear stress parameter correlated well with the decrease in perception, suggesting that there may be a viscosity stimulus or that the viscosity affects release of tastant and hinders aroma-taste interactions.


[Overview and follow up study of cleft patients.].
On the average 8.2 children with different types of facial clefts are born in Iceland every year, which means approximately 1.87 per 1000 births. Until just before the middle of this century most of those children were treated by general surgeons or not at all, and a few were sent abroad. Around 1950 an orthopedic surgeon with some training in plastic surgery joined the staff at Landspitalinn (University Hospital in Reykjavik). Soon practically all children with clefts were referred to him and as the only obstetrical and gynaecological and only pediatric unit in the country were stationed there, Landspitalinn became a center for cleft treatment and has remained so. The senior author (AB) took over the treatment of clefts between 1955 and 1960 and treated about 90% of the children until 1993. The aim of the paper is to give an overview over treatment of clefts in Iceland over this period. Landspitalinn was founded in 1930. All hospital records for patients with clefts were looked into, classified and devided into three groups after the ICD system. A simple record was made for each patient with general informations and special records for those born between 1955-1984, 312 in all, for special scrutiny. In those records all known informations are to be found; kinship, mothers use of drugs in pregnancy, operations, time of operations and surgeon's name were recorded. The operations were devided into main groups and sub groups, auxiliary treatment was recorded as were all complications and diseases related to the clefts. It was also recorded if the cleft was a part of a syndrome or associated with other major congenital deformities. The informations so gained will be a basis for further studies related to evaluation of the treatment and further genetic studies.


The lichen flora of Supraśl as the health resort.
This study presents the actual lichen flora of Supraśl. 68 species have been collected in the investigated area. Among these, 53 are epiphytic species, 12 are epilithic species and 17--epiksylithic species. On the basis of lichens scale, Supraśl was classified to 6th bioindicative zone, where air pollution of SO2 was 30-40 mg/m3.


Beta D305A mutant of tryptophan synthase shows strongly perturbed allosteric regulation and substrate specificity.
Substrate channeling in the tryptophan synthase bienzyme is regulated by allosteric interactions. Allosteric signals are transmitted via a scaffolding of structural elements that includes a monovalent cation-binding site and salt-bridging interactions between the side chains of betaAsp 305, betaArg 141, betaLys 167, and alphaAsp 56 that appear to modulate the interconversion between open and closed conformations. betaAsp 305 also interacts with the hydroxyl group of the substrate L-Ser in some structures. One possible functional role for betaAsp 305 is to ensure the allosteric transmission that triggers the switching of alphabeta-dimeric units between open and closed conformations of low and high activity. This work shows that substitution of betaAsp 305 with Ala (betaD305A) decreases the affinity of the beta-site for the substrate L-Ser, destabilizes the enzyme-bound alpha-aminoacrylate, E(A-A), and quinonoid species, E(Q), and changes the nucleophile specificity of the beta-reaction. The altered specificity provides a biosynthetic route for new L-amino acids derived from substrate analogues. betaD305A also shows an increased rate of formation of pyruvate upon reaction with L-Ser relative to the wild-type enzyme. The formation of pyruvate is strongly inhibited by the binding of benzimidazole to E(A-A). Upon reaction with L-Ser and in the presence of the alpha-site substrate analogue, alpha-glycerol phosphate, the Na(+) form of betaD305A undergoes inactivation via reaction of nascent alpha-aminoacrylate with bound PLP. This work establishes important roles for betaAsp 305 both in the conformational change between open and closed states that takes place at the beta-site during the formation of the E(A-A) and in substrate binding and recognition.


Gene duplication and adaptive evolution of digestive proteases in Drosophila arizonae female reproductive tracts.
It frequently has been postulated that intersexual coevolution between the male ejaculate and the female reproductive tract is a driving force in the rapid evolution of reproductive proteins. The dearth of research on female tracts, however, presents a major obstacle to empirical tests of this hypothesis. Here, we employ a comparative EST approach to identify 241 candidate female reproductive proteins in Drosophila arizonae, a repleta group species in which physiological ejaculate-female coevolution has been documented. Thirty-one of these proteins exhibit elevated amino acid substitution rates, making them candidates for molecular coevolution with the male ejaculate. Strikingly, we also discovered 12 unique digestive proteases whose expression is specific to the D. arizonae lower female reproductive tract. These enzymes belong to classes most commonly found in the gastrointestinal tracts of a diverse array of organisms. We show that these proteases are associated with recent, lineage-specific gene duplications in the Drosophila repleta species group, and exhibit strong signatures of positive selection. Observation of adaptive evolution in several female reproductive tract proteins indicates they are active players in the evolution of reproductive tract interactions. Additionally, pervasive gene duplication, adaptive evolution, and rapid acquisition of a novel digestive function by the female reproductive tract points to a novel coevolutionary mechanism of ejaculate-female interaction.


Recombinant DNA and surgery.
We have the ability to isolate DNA from tissue, determine its base-pair sequence, and ask if a gene of interest is present. DNA strands can be isolated from one type of cell or organism, cleaved, and inserted (recombined) with DNA from another cell or organism. Recombinant DNA techniques have already improved health care by providing clinically useful quantities of pure human protein hormones such as erythropoietin, insulin, and growth hormone. Furthermore these techniques may increase our understanding of cellular growth control mechanisms to a level that was previously unattainable. They will also increase our knowledge of the development of major diseases and provide a means of specific nontoxic therapies for these diseases. Surgeons will need to understand basic DNA research terminology to keep up with the revolution in medical therapies that these techniques will cause. Our purpose is to begin the process of linking surgery to DNA.


Laparoscopic sleeve gastrectomy: long-term weight loss outcomes.
Laparoscopic sleeve gastrectomy (LSG) has become an increasingly popular stand-alone weight loss surgery, but there is a paucity of long-term efficacy data. To determine long-term outcomes for patients undergoing LSG. Tertiary care university hospital in the United States. This study presents a case series of the first 16 patients undergoing LSG at our institution. Inclusion criteria were accepted indications for bariatric surgery, and exclusion criteria were any prior bariatric surgery, gastrectomy, substance abuse, uncontrolled psychiatric illness, end-stage organ disease, or advanced-stage cancer. Patients were followed for 7 years. Outcomes included percent excess weight loss (%EWL), percent weight loss (%WL), resolution of co-morbidities, and major and minor complications. Patients enrolled in this study had a mean body mass index (BMI) of 43.5 kg/m(2) and a mean age of 49, and 14 of 16 patients were women. Fourteen of 16 patients had 7-year follow-ups with a mean %WL of 29.6%±8.95 and a mean %EWL of 59.6%±89.9%. At 7 years, 11 of 14 patients achieved>50% EWL. One-year follow-up data revealed a mean EWL of 72%±20%, which was significantly greater than the %EWL at 7 years (P = .005). Complications included 1 partial obstruction at the gastric incisura angularis and 1 subacute leak; both were managed endoscopically. There were no reoperations and no deaths. Five of 14 patients experienced new-onset gastroesophageal reflux disease. At 7 years postoperative, the LSG remained a durable and successful operation.


National crisis, supranational opportunity: the Irish construction of abortion as a European service.
In the late 1980s, the anti-abortion movement successfully sought injunctions against pregnancy counselling centres and students' unions in Ireland, preventing them from distributing information on how to obtain an abortion abroad. One of the defensive arguments that the students' unions employed was to claim that the distribution of abortion information was protected as an aspect of the free movement of services under European Community law. This paper addresses the implications of categorising abortion as a supranational economic service for feminist legal strategy. The advantages of categorising abortion as a service to which women have access as consumers are that it legitimates abortion and it provides a new strategy for making abortion claims. The disadvantages are that a woman's legal interest in abortion is based on her capacity to buy the service, fetal life is rendered devoid of value, and the service supplier has as much say about the abortion transaction as the woman consumer. If feminist legal strategy is to successfully use the legal construction of abortion as an economic service, it must work to minimise such negative implications.


Conservation in the Amazon rainforest and Google searches: A DCCA approach.
In this paper we analyze the descriptive statistics of the Google search volume for the terms related to the National Reserve of Copper and Associates (RENCA), a Brazilian mineral reserve in the Amazon of 4.6 million hectares, before and after the government signed the decree releasing it for exploration. First, we analyze the volume of searches for expressions related to RENCA in Google Trends using descriptive statistics; second, we assess the cross-correlation coefficient ρDCCA, which measures the cross-correlation between two nonstationary time series across different time scales. After the government announced the release of the RENCA reserve, there was an increase in the average volume of Google searches for related terms, showing people's concern about the announcement. By using the cross-correlation coefficient ρDCCA, we identify strong cross-correlations between the different expressions related to RENCA in Google Trends. Our work shows the utility of Google Trends as an indicator of the perception of environmental policies. Additionally, we show that ρDCCA can be used as a tool to measure the cross-correlation between synonyms extracted from Google Trends for various time scales.


Weight cycling induces innate immune memory in adipose tissue macrophages.
Weight loss improves obesity-associated diabetes risk. However, most individuals regain weight, which worsens the risk of developing diabetes and cardiovascular disease. We previously reported that male mice retain obesity-associated immunological changes even after weight loss, suggesting that immune cells may remember the state of obesity. Therefore, we hypothesized that cycles of weight gain and loss, otherwise known as weight cycling, can induce innate memory in adipose macrophages. Bone marrow derived macrophages were primed with palmitic acid or adipose tissue conditioned media in a culture model of innate immune memory. Mice also put on low fat or high fat diets over 14-27 weeks to induce weight gain, weight loss, and weight cycling. Priming cells with palmitic acid or adipose tissue conditioned media from obese mice increased maximal glycolysis and oxidative phosphorylation and increased LPS-induced TNFα and IL-6 production. Palmitic acid effects were dependent on TLR4 and impaired by methyltransferase inhibition and AMPK activation. While weight loss improved glucose tolerance in mice, adipose macrophages were primed for greater activation to subsequent stimulation by LPS ex vivo as measured by cytokine production. In the model of weight cycling, adipose macrophages had elevated metabolism and secreted higher levels of basal TNFα, suggesting that weight loss can also prime macrophages for heighted activation to weight regain. Together, these data suggest that weight loss following obesity can prime adipose macrophages for enhanced inflammation upon weight regain. This innate immune memory response may contribute to worsened glucose tolerance following weight cycling.


Guidelines for reporting of biocatalytic reactions.
Enzymes and whole cells are being increasingly applied in research and industry, but the adoption of biocatalysis relies strongly on useful scientific literature. Unfortunately, too many published papers lack essential information needed to reproduce and understand the results. Here, members of the scientific committee of the European Federation of Biotechnology Section on Applied Biocatalysis (ESAB) provide practical guidelines for reporting experiments. The document embraces the recommendations of the STRENDA initiative (Standards for Reporting Enzymology Data) in the context of pure enzymology and provides further guidelines and explanations on topics of crucial relevance for biocatalysis. In particular, guidelines are given on issues such as the selectivity, specificity, productivity and stability of biocatalysts, as well as on methodological problems related to reactions in multiphase systems. We believe that adoption and use of these guidelines could greatly increase the value and impact of published work in biocatalysis, and hence promote the further growth of applications.


Osteology and skeletal development of Apalone spinifera (Reptilia: Testudines: Trionychidae).
Despite considerable attention that other groups of reptiles have received, few descriptions of the development and sequences of chondrification and ossification of the entire skeleton of turtles exist. Herein, the adult skeleton of the spiny softshell turtle, Apalone spinifera (Testudines: Trionychidae), is described; this description forms a basis of comparison for the embryonic skeleton and its ontogenesis. Descriptions are made on the basis of cleared and double-stained embryos and dry skeletal postembryonic specimens. The embryonic chondrocranium of A. spinifera is described and compared to those of Emys orbicularis and Caretta caretta, the sequence of chondrification of fore- and hindlimbs are compared with published descriptions of Chelydra serpentina and Chrysemys picta, and the sequence of ossification of elements is compared with those of C. serpentina, Lacerta vivipara, and Alligator mississippiensis. In A. spinifera, the first elements that ossify (Stage 17) are associated with the dermatocranium and mandible, followed by elements of the dermal skull table, lower jaw, and dermal elements of the plastron. In A. spinifera, the sequence of chondrification of limb elements is similar to that of C. serpentina; however, the sequence of ossification varies greatly among Apalone, Chelydra, Lacerta, and Alligator.


Apathy and Anhedonia: Clinical and Neurophysiological Assessment of a Romanian Cohort.
Patients with Parkinson's disease (PD) often have, besides the characteristic motor manifestations, a wide variety of non-motor symptoms. These include apathy and anhedonia, common issues in PD, which can be quantified with the help of evaluation scales recommended by the literature. There are sensory non-motor manifestations of PD, some of which are easy to detect through electrophysiological studies. Our aim was to investigate the possible association of apathy and anhedonia with the severity of the motor status in a sample of PD patients in Romania. We also examined the prevalence of latency changes in the P100 wave of visual evoked potentials (VEPs) and how they correlated with motor status, apathy, and anhedonia in PD patients. Thirty-four patients with PD participated in this study. All were assessed for motor status using the Unified Parkinson's Disease Rating Scale (UPDRS) and were rated on the Hoehn and Yahr scales. The presence and severity of apathy and anhedonia were assessed using the Apathy Evaluation Scale (AES), the Dimensional Apathy Scale (DAS), the Lille Apathy Rating Scale (LARS), and the Snaith-Hamilton Pleasure Scale (SHAPS). The latency of the P100 wave of the VEP was measured in all the patients. Apathy and anhedonia were common among the patients with PD (35% and 58.8%, respectively). The presence of apathy/anhedonia was correlated with the severity of motor symptoms, as assessed using the UPDRS scale (p < 0.001), and with the stage of the disease according to the Hoehn and Yahr scale (p < 0.001). A prolonged latency of the P100 wave of the VEP was observed among apathetic (p < 0.001)/anhedonic (p < 0.01) patients and those with increased disease severity (p < 0.001). Apathy and anhedonia are common in PD and may correlate with the severity of motor symptoms. There may be visual impairment in these patients, evidenced by a prolonged P100 latency, which correlates with the severity of disease. Scales for assessing apathy and anhedonia, as well as measuring VEP latency, could be useful in assessing the severity of disease.


Study of the stability of EPR signals after irradiation of fingernail samples.
Previous studies have suggested that the electron paramagnetic resonance in fingernails can be used for radiation dosimetry purposes. Use of fingernails as an emergency dosimeter has benefits of easy, noninvasive sampling and fast dose measurements (∼10 min) potentially in field conditions and almost immediately after an exposure event. This study represents the next step in the development of EPR fingernail dosimetry; e.g., evaluation of the stability of the radiation-induced signal (RIS) at different storage and irradiation conditions. RIS fading during storage in both stressed (untreated) and unstressed (soaked in water) samples (n = 20) was studied at two temperature conditions: freezing (temp ≈ -20°C) and room temperature (20-24°C). Fingernail samples with the same clipping size and number and irradiated to 15 and 20 Gy were measured for over 200 d. Those irradiated to 100 and 200 Gy were measured for 114 d. The other group of samples irradiated to 1, 3, 8, and 20 Gy was followed for 25 mo of storage time. This study demonstrated that all samples that were kept at low freezing temperatures showed a stable RIS with no significant fading. All samples that were kept at room temperatures showed an initial fading of the signal with a slow rise of the EPR signal after irradiation with time to a saturation level. Obtained results allow making recommendations on the appropriate storage conditions of fingernails for EPR dosimetry use.


Tissue Factor/Factor FVII Complex Inhibitors in Cardiovascular Disease. Are Things Going Well?
Blood coagulation is a complex biological mechanism aimed to avoid bleeding in which a highly regulated and coordinated interplay of specific proteins and cellular components respond quickly to a vascular injury. However, when this mechanisms occurs in the coronary circulation, it has not a "protective" effect, but rather, it plays a pivotal role in determining acute coronary syndromes. Coagulation recognizes Tissue Factor (TF), the main physiological initiator of the extrinsic coagulation pathway, as its starter.Since TF:VIIa complex is the critical point of the blood coagulation cascade, it is a pharmacological attractive issue for the development of agents with anti thrombotic properties that can exert their activity by inhibiting complex formation and/or its catalytic activity. In fact, it is intuitive that an antithrombotic agent able to inhibit this initial step of the coagulation pathway has several theoretical, extremely important, advantages if compared with drugs active downstream the coagulation pathway, such as FXa or thrombin. The present report gives a brief overview of TF pathophysiology, highlighting the most recent advances in the field of inhibitors of the complex TF/VIIa potentially useful in cardiovascular disease.


Chiral modular n-butyllithium aggregates: nbuli complexes with anisyl fencholates.
Chiral, enantiopure aggregates are formed spontaneously by mixing solutions of n-butyllithium with anisyl fenchols. X-ray crystal analyses reveal the structures of these aggregates with different ortho substituents in the anisyl moieties (X), X = H (1-H), SiMe3 (2-H), tBu (3-H) SiMe2(tBu) (4-H) and Me (5-H). While the complex of 1-BuLi shows a 3:1 composition, 2-BuLi, 3-BuLi and 4-BuLi yield 2:2 stoichiometries. The aggregate 5-BuLi crystallizes with a 2:4 composition and hence is a derivative of hexameric n-butyllithium, in which two trans-situated nBuLi molecules are substituted by lithium fencholate moieties. The variety in the synthesized chiral nBuLi aggregates demonstrates the high propensity of anisyl fencholates to chirally modify nBuLi. Variations in the modular ligand structures by alterations of the ortho-substituents (X) enable tunings of compositions and also of enantioselectivities in nBuLi additions to benzaldehyde.


Effect of nanoparticle polydispersity on the self-assembly of polymer tethered nanospheres.
Recent simulations predict that aggregating nanospheres functionalized with polymer "tethers" can self-assemble to form a cylinder, perforated lamellae, lamellae, and even the double gyroid phase, which are phases also seen in block copolymer and surfactant systems. Nanoparticle size polydispersity is likely to be a characteristic of these systems. If too high, polydispersity may destabilize a phase. Using multiple thermodynamic paths to explore the phase diagram as a function of temperature and polydispersity, we explore the effect of nanosphere size polydispersity on the phase diagram. We show that in the portions of the phase diagram characterized by an icosahedral local nanoparticle packing motif, a low amount of polydispersity lowers the energy and a large amount of polydispersity raises the energy of the system by disrupting the icosahedral packing. In general, regions of the phase diagram characterized by liquid-like icosahedral packing have high terminal polydispersities from 15% to more than 30%. In the regions of the phase diagram characterized by crystalline local packing, polydispersity raises the energy of the system and induces a phase transition from crystalline to liquid-like ordering within the nanosphere rich regions of the microphase. We find the bilayer crystalline lamellae phase has a terminal polydispersity of 6%, but may still be partially crystalline up to 12%.


Interstitial nephritis secondary to bevacizumab treatment in metastatic leiomyosarcoma.
To report a case of interstitial nephritis associated with the administration of bevacizumab. A 26-year-old man diagnosed with metastatic rectal leiomyosarcoma was treated with intravenous bevacizumab 5 mg/kg and received a total of 3 doses at 2 week intervals. His creatinine had increased from 1.0 mg/dL at baseline to 1.6 mg/dL after 2 doses of bevacizumab and to 4.7 mg/dL after the third dose, prompting admission. Acute renal failure was diagnosed, and hemodialysis was initiated. A renal biopsy revealed interstitial nephritis. Renal failure resolved with cessation of the drug, and the patient did not require further hemodialysis. Bevacizumab is a recombinant humanized monoclonal immunoglobulin G antibody to vascular endothelial growth factor. Bevacizumab has shown efficacy in treatment of patients with renal cell carcinoma and colorectal cancer and has been approved by the Food and Drug Administration as a first-line treatment for metastatic colorectal cancer. Our patient had no other confounding factors that might have caused renal failure. The presence of primary glomerular disease was excluded by biopsy. According to the Naranjo probability scale, bevacizumab was the probable cause of acute renal failure in this patient. Bevacizumab can cause acute renal failure by inducing interstitial nephritis. Renal function should be monitored during bevacizumab therapy.


Mixed electronic and oxide ionic conduction and migration mechanisms in digermanate La2-xCaxGe2O7-x/2.
Mixed electronic and oxide ionic conduction was enabled in digermanate-type La2-xCaxGe2O7-x/2 containing Ge3O10 chains and isolated GeO4 units by substitution of La3+ with Ca2+. The structure and solid solution limit of Ca doped La2Ge2O7 were studied by systematic experiments, including rotation electron diffraction (RED), X-ray diffraction (XRD) and neutron powder diffraction (NPD) experiments, etc. The preferred occupation of Ca2+ and oxygen vacancies was investigated by Rietveld analysis of the NPD data. The obtained conducting material La1.925Ca0.075Ge2O6.963 exhibits superior thermal stability and an order of magnitude improvement in conductivity compared to the parent La2Ge2O7 (∼9 × 10-5 S cm-1 at 1000 °C). BVEL calculations reveal that the oxygen vacancies were stabilized and transported within the framework of La2Ge2O7 by sharing oxygen and oxygen exchange between the adjacent Ge3O10 chains and GeO4 units, exhibiting a three-dimensional oxide ion transport nature.


The cardiometabolic syndrome and sarcopenic obesity in older persons.
The aging of the world's population is a major contributor to the growing prevalence of the cardiometabolic syndrome (CMS) because older persons are more affected by the constellation of cardiovascular risk factors that constitute the syndrome. The prevalence of CMS has been related to the increasing prevalence of obesity, which is growing progressively even among older age groups. Indeed, obesity and aging are 2 overlapping mounting public health problems. It is currently accepted that CMS predicts cardiovascular mortality and/or the development of type 2 diabetes mellitus, and this is also true in studies including older persons. CMS is further complicated by modifications in body composition and fat redistribution during aging; older adults are at higher risk for developing central obesity and sarcopenia or sarcopenic obesity, a condition characterized by an important reduction in lean body mass associated with obesity, linked to an increased production of inflammatory adipokines that may alter insulin sensitivity and muscle mass and strength. A better understanding of the pathophysiologic mechanisms of sarcopenic obesity may help to elucidate the complex relationship between CMS and mortality/morbidity in older adults.


Protein degradation and the regulation of protein balance in muscle.
The rate of of protein degradation in muscle changes in many states but the nature of these changes is often paradoxical. Thus there can be increases during growth (anabolic increases) as well as during wasting (catabolic increases). Decreases can occur during growth (anabolic decreases) as well as during wasting (catabolic decreases). These changes are observed in man (as judged by changes in 3-methylhistidine excretion) and in experimental animals. The nature of the changes is not understood but it is possible that muscle growth induces increased degradation as part of the accompanying myofibre remodelling. The rate of protein degradation can also be influenced by thyroid status, since in thyroid deficiency degradation is reduced and can be stimulated by triiodothyronine. This response is independent of changes in muscle growth. Finally, acute exercise suppresses protein degradation in vivo in man as well as suppressing protein synthesis (in vivo in rats). When protein degradation rates change, acid proteinase activities also change in muscle. The anabolic increase in degradation appears to involve increases in mainly cathepsin D whereas catabolic increases in degradation are associated with an increase mainly in pepstatin-insensitive acid autolytic activity.


Evaluation of efficacy expectations for novel and non-chemical helminth control strategies in ruminants.
The interest in novel methods of controlling helminth infections in ruminants is driven primarily by the development of parasite resistance to currently available anthelmintics. While the purpose of anthelmintics is to achieve high efficacy, i.e. >90% reduction of adult and/or larval parasites in the target host animal, the purpose of novel parasite control methods is rather to assist in maintaining parasite infections below the economic threshold. The ability to maintain parasite levels below the economic threshold is related not only to the efficacy of the control method, but also to the epidemiology of the parasites, climatic conditions, the livestock management program, and integration in a sustainable parasite control program. Because of this fundamental difference, novel parasite control methods need to be evaluated using efficacy criteria different from that adopted for anthelmintics. Although the efficacy of novel parasite control methods may be demonstrated in classic dose-confirmation studies, the impact on livestock production parameters can only be evaluated when tested on-farm. In this paper, the rationale for evaluating novel methods differently from anthelmintics is reviewed, potential performance expectations are presented, and four novel parasite control methods (vaccines, nematophagous fungi, condensed tannins, and immunonutrition) are assessed based on the potential performance criteria.


Crystal structure of the GlnZ-DraG complex reveals a different form of PII-target interaction.
Nitrogen metabolism in bacteria and archaea is regulated by a ubiquitous class of proteins belonging to the P(II)family. P(II) proteins act as sensors of cellular nitrogen, carbon, and energy levels, and they control the activities of a wide range of target proteins by protein-protein interaction. The sensing mechanism relies on conformational changes induced by the binding of small molecules to P(II) and also by P(II) posttranslational modifications. In the diazotrophic bacterium Azospirillum brasilense, high levels of extracellular ammonium inactivate the nitrogenase regulatory enzyme DraG by relocalizing it from the cytoplasm to the cell membrane. Membrane localization of DraG occurs through the formation of a ternary complex in which the P(II) protein GlnZ interacts simultaneously with DraG and the ammonia channel AmtB. Here we describe the crystal structure of the GlnZ-DraG complex at 2.1 Å resolution, and confirm the physiological relevance of the structural data by site-directed mutagenesis. In contrast to other known P(II) complexes, the majority of contacts with the target protein do not involve the T-loop region of P(II). Hence this structure identifies a different mode of P(II) interaction with a target protein and demonstrates the potential for P(II) proteins to interact simultaneously with two different targets. A structural model of the AmtB-GlnZ-DraG ternary complex is presented. The results explain how the intracellular levels of ATP, ADP, and 2-oxoglutarate regulate the interaction between these three proteins and how DraG discriminates GlnZ from its close paralogue GlnB.


Community-Based Knowledge Translation Strategies for Maternal, Neonatal, and Perinatal Outcomes: A Systematic Review of Quantitative and Qualitative Data.
Objective: To identify and assess the effect of community-based Knowledge Translation Strategies (KTS) on maternal, neonatal, and perinatal outcomes. Methods: We conducted systematic searches in Medline, Embase, CENTRAL, CINAHL, PsycInfo, LILACS, Wholis, Web of Science, ERIC, Jstor, and Epistemonikos. We assessed the certainty of the evidence of the studies using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: We identified seven quantitative and seven qualitative studies. Quantitative findings suggest that there is a possible effect on reducing maternal mortality (RR 0.65; 95% CI, 0.48-0.87; moderate evidence certainty); neonatal mortality (RR 0.79; 95% CI 0.70-0.90; moderate evidence certainty); and perinatal mortality (RR 0.84; 95% CI 0.77-0.91; moderate evidence certainty) in women exposed to KTS compared to those who received conventional interventions or no intervention at all. Analysis of qualitative studies identified elements that allowed to generate benefit effects in improving maternal, neonatal, and perinatal outcomes. Conclusion: The KTS in maternal, neonatal, and perinatal outcomes might encourage the autonomy of communities despite that the certainty of evidence was moderate.


The pathogenic role of Maillard reaction in the aging eye.
The proteins of the human eye are highly susceptible to the formation of advanced glycation end products (AGEs) from the reaction of sugars and carbonyl compounds. AGEs progressively accumulate in the aging lens and retina and accumulate at a higher rate in diseases that adversely affect vision such as, cataract, diabetic retinopathy and age-related macular degeneration. In the lens AGEs induce irreversible changes in structural proteins, which lead to lens protein aggregation and formation of high-molecular-weight aggregates that scatter light and impede vision. In the retina AGEs modify intra- and extracellular proteins that lead to an increase in oxidative stress and formation of pro-inflammatory cytokines, which promote vascular dysfunction. This review outlines recent advances in AGE research focusing on the mechanisms of their formation and their role in cataract and pathologies of the retina. The therapeutic action and pharmacological strategies of anti-AGE agents that can inhibit or prevent AGE formation in the eye are also discussed.


Process scale separation of an anti-CD22 immunotoxin charge variant.
We describe the analytical characterization and process scale separation of a deamidated variant of an immunotoxin. The different charge variants of the immunotoxin were separated using analytical ion-exchange HPLC. These charge variants were analyzed by peptide mapping and LC-MS/MS to identify the site of modification, which was determined to reside in the toxin portion of the molecule. Using a cell-based bioassay it was also determined that deamidation led to reduced biological activity, requiring it be controlled during manufacturing. This was accomplished using process scale anion-exchange chromatography. The process was capable of reducing the deamidated form to a level low enough for the resulting product to maintain acceptable biological activity. Keys to the successful control of this impurity at process scale were a good understanding of structure-function relationship and the availability of an analytical HPLC assay to provide a surrogate for the cell-based bioassay.


Anoxic Brain Injury Presenting as Pseudosubarachnoid Hemorrhage in the Medical Intensive Care Unit.
Anoxic encephalopathy is frequently encountered in the medical intensive care unit (ICU). Cerebral edema as a result of anoxic brain injury can result in increased attenuation in the basal cisterns and subarachnoid spaces on computerized tomography (CT) scans of the head. These findings can mimic those seen in acute subarachnoid hemorrhage (SAH) and are referred to as pseudosubarachnoid hemorrhage (pseudo-SAH). Pseudo-SAH is a diagnosis critical care physicians should be aware of as they treat and evaluate their patients with presumed SAH, which is a medical emergency. This lack of awareness could have important clinical implications on outcomes and impact management decisions if patients with anoxic brain injury are inappropriately treated for SAH. We describe three patients who presented to the hospital with anoxic brain injury. Subsequent CT head suggested SAH, which was subsequently proven to be pseudo-SAH.


Orbital Glial Heterotopia: A Report of 2 Cases and Review of the Literature.
To review the clinical radiographic and histopathologic findings associated with orbital glial heterotopia. A literature search in PubMed and Scopus was performed to include all articles published in English between 1980 and January 1, 2019. A case series including 29 case reports of 29 patients, as well as the authors' 2 cases, were considered in the literature review. The majority of the cases had onset of symptoms (86%) and age at presentation (71%) before 5 years of age. The most common presenting symptoms and signs were swelling (45%), strabismus (32%), and proptosis (26%). The most common lesion locations described were inferolateral (19%) or primarily posterior orbital or apical (19%). The most common findings associated with orbital glial heterotopia were microphthalmia (10%) and anophthalmia (6%); however, the majority did not have systemic abnormalities (71%). The most common imaging modality was CT scan (71%). Diagnosis was made with histologic analysis in all cases, and confirmed after subtotal resection (35%), total resection (39%), or incisional biopsy (26%). The majority of the cases report no growth on repeat imaging, with only 3 reports of recurrence. Glial heterotopia in the orbit is a rare clinical entity most commonly presenting in children. We present 2 cases of orbital glial heterotopia in adults, with a literature on these lesions in both the pediatric and adult populations. Surgeons and pathologists should be aware of this atypical presentation in adulthood. Biopsy is required for diagnosis but is not without risk. Prognosis is generally favorable.Orbital glial heterotopia, commonly considered a rare congenital lesion generally presenting in children, may first become symptomatic in adulthood. Biopsy is required for diagnosis, with symptoms and prognosis dependent on location and growth of the lesion.


Pituitary microadenoma treated with antipsychotic drug aripiprazole.
Male patient 24 years old with a pituitary microadenoma and mental and behavioural disorders due to multiple drug use and use of other psychoactive substances (cocaine, cannabis and alcohol) were treated with haloperidol (dopamine receptor blocker) 10 mg daily. In the last control, the patient presented mammary hypertrophy; laboratory testing and brain magnetic resonance imaging (MRI) was performed, reporting the presence of a pituitary microadenoma syndrome with hormonal alteration (Prolactin levels 28.4 ng/ml). Haloperidol, carbamazepine and levomepromazine were then discontinued. He was started on aripiprazole 15 mg po daily for 4 days; the dosage was then increased to 30 mg po daily, with Valproic Acid 500 mg po tid. After 3 weeks on aripiprazole, the mammary hypertrophy that had increased in the patient had resolved. After 10 weeks follow up of prolactin revealed a normal level, at 4.33 ng/ml. Insomnia, aggressiveness, irritability, visual, tactile and auditory hallucinations remained absent after treatment with aripiprazole which is not a first line drug in multiple drug use patient with psychosis. We also consider the correlation of drug use in patient with psychosis, haloperidol treatment, pituitary microadenoma syndrome, hyperprolactinemia, and dopamine D2- receptor partial agonist aripiprazole treatment. This article also summarizes some relevant patents.


Retrograde response by reactive oxygen/nitrogen species in plants involving different cellular organelles.
During oxidative and nitrosative stress conditions cellular organelles convey information to the nucleus to express specific sets of genes to withstand the stress condition and to reorganize their growth and developmental pattern. This organelle to nucleus communication is termed retrograde signaling. In the plant system chloroplast and peroxisomes are mainly involved with little involvement of mitochondria and other organelles in oxidative stress-mediated retrograde signaling. In this review, we will discuss retrograde signaling in plant systems with factors that regulate this signaling cascade.


[Relationship between central visual acuity and retinal volume of macular fovea accessed by spectral domain optical coherence tomography in Stargardt disease].
To assess the relationship between central visual acuity and retinal volume of macular fovea in patients with Stargardt disease by spectral-domain optical coherence tomography (SD OCT). It was a retrospective case series study. Twenty eyes of 10 patients with Stargardt disease were investigated by three-dimensional spectral-domain optical coherence tomography. SD OCT images were obtained and retrospectively analyzed. The retinal volumes of macular fovea were measured by SD OCT, whose diameters were set as 3 mm and 1 mm separately (volume 3 and volume 1). The retinal thickness of macular fovea (macular thickness) and the width of IS/OS conjunction loss of macular fovea (IS/OS loss) were also measured by SD OCT. We correlated the logMAR BCVA with IS/OS loss, macular thickness, volume 3 and volume 1 by linear regression analysis. LogMAR BCVA was from 0.3 to 1.22. IS/OS loss was from 847 µm to 5306 µm. Macular thickness was from 20 µm to 126 µm. Volume 3 and volume 1 was from 1.06 to 1.76 mm(3) and 0.06 to 0.13 mm(3). LogMAR BCVA correlated with the IS/OS loss (r = 0.695, P < 0.05), macular thickness (r = -0.601, P < 0.05), and volume 3(r = -0.725, P < 0.05). LogMAR BCVA did not correlate with volume 1(r = -0.364, P > 0.05). SD OCT could demonstrate the retinal structure of Stargardt disease clearly. The retinal volume of macular fovea accessed by SD OCT correlated with the visual acuity of Stargardt disease.


Coxsackievirus infections and NOD mice: relevant models of protection from, and induction of, type 1 diabetes.
Human enteroviruses (HEVs) like the group B coxsackieviruses (CVBs) are prime candidates for infectious, environmental causes of human type 1 diabetes (T1D). Non-obese diabetic (NOD) female mice are well protected from T1D onset if inoculated with CVB when young. Older, prediabetic NOD mice can rapidly develop T1D following inoculation with CVB, mimicking clinical reports of disease-associated T1D onset. The ability to induce rapid T1D in NOD mice is linked to the rate of replication of the CVB strain in beta cell cultures and pancreatic tissue, indicating that any CVB strain is potentially diabetogenic under the correct conditions. Rapid T1D onset is preceded by CVB replication in islet cells including beta cells. Although CVB strains do not productively infect healthy islets of young mice, CVBs can replicate in healthy islets in the presence of murine IL-4. These models expand much of what is known or suspected regarding the etiologic role of HEVs in human T1D.


Comparison between hand and electronic timing of 40-yd dash performance in college football players.
The purpose of this study was to determine the difference between hand and electronic timing of 40-yd dashes in college football players. National Collegiate Athletic Association Division II players (n = 59) were measured during a 40-yd sprint by electronic timing and simultaneously by 7 experienced hand timers using digital stopwatches. Electronic times were initiated by lifting the hand from a switch mat and stopped by the torso passing through an infrared beam. Hand timers initiated timing on first movement of the player from a 3-point stance. To establish performance and timing reliabilities, 32 players completed a second trial. Interrater reliability for hand timing was intraclass correlation coefficient (ICC) = 0.987 (p < 0.001). Five of the 7 timers did not differ significantly (p > 0.05) in their timing. The maximum difference among the hand timers on any given trial was 0.19 +/- 0.14 seconds, with a 95% confidence interval (CI) of -0.08 to 0.41 seconds. Hand timing (4.85 +/- 0.28 seconds) was significantly faster (p < 0.001) than electronic timing (5.16 +/- 0.28 seconds), producing an average difference of 0.31 +/- 0.07 seconds (6.0 +/- 1.3%) and a 95% CI on the average difference of -0.44 to -0.18 seconds. The correlation between electronic timing and hand timing was ICC = 0.985 (p < 0.001). Practically speaking, electronic timing produces the best measurement of 40-yd dash speed, and using the hand timing produces consistently but significantly faster times.