Lymphopoiesis in protein deficiency. Stathmokinetic and tritiated thymidine uptake studies of the mesenteric lymph node of the guinea pig.
In view of the depressed immunity in protein malnutrition, an assessment of the lymphoproliferative activity of the constantly stimulated mesenteric lymph node of the guinea pig was undertaken. A significant reduction of this activity was observed in protein deficiency. a) The germinal centers were reduced in number and size; new formation in the medulla was rarely seen. Lymphoid cells showed lowering of mitotic index and mitotic rate and prolongation of mitotic duration and turnover time. Nuclear labeling with (3)H-thymidine was focal and localized to the peripheral zone. b) Mitotic activity and nuclear labeling were less pronounced in the outer cortex and medulla and least in the paracortical area. Specific uptake of (3)H-thymidine paralleled the low labeling index. c) No appreciable reduction in the number of plasma cells in the medulla was observed. Serum gamma-globulin levels were not significantly altered, but albumin levels were consistently reduced. This was suggestive of preferential preservation of plasma cell activity in the malnourished host. d) There were significant lymphopenia and neutropenia with relative increase of neutrophils in the peripheral blood. This might indicate more severe involvement of lymphopoiesis than myelopoiesis in protein malnutrition.


Amide-I relaxation-induced hydrogen bond distortion: An intermediate in electron capture dissociation mass spectrometry of alpha-helical peptides?
Electron capture dissociation (ECD) of peptides and proteins in the gas phase is a powerful tool in tandem mass spectrometry whose current description is not sufficient to explain many experimental observations. Here, we attempt to bridge the current understanding of the vibrational dynamics in alpha-helices with the recent experimental results on ECD of alpha-helical peptides through consideration of amide-I relaxation-induced hydrogen bond distortion. Based on a single spine of H-bonded peptide units, we assume that charge neutralization upon electron capture by a charged alpha-helix excites a nearby amide-I mode, which relaxes over a few picoseconds due to Fermi resonances with intramolecular normal modes. The amide-I population plays the role of an external force, which drives the displacements of each peptide unit. It induces a large immobile contraction of the H bonds surrounding the excited site whose lifetime is about the amide-I lifetime. In addition, it creates two lattice deformations describing H bond stretchings, which propagate from the excited region toward both termini of the alpha-helix, get reflected at the termini and yield H bond contractions which move back to the excited region. Consequently, we show that H bonds experience rather large contractions whose amplitude depends on general features such as the position of the amide-I mode, the peptide length and the H bond force constants. When an H bond contraction is sufficiently large, it may promote a hydrogen atom transfer between two neighboring peptide units leading to the formation of a radical at charge site remote carbonyl carbon which is known to be a precursor to the rupture of the corresponding N[Single Bond]C(alpha) bond. The introduced here way of excitation energy generation and transfer may significantly advance ECD understanding and complement existing ECD mechanisms.


The expression and functional analysis of the sialyl-T antigen in prostate cancer.
Aberrant glycosylation is a featured characteristic of cancer and plays a role in cancer pathology; thus an understanding of the compositions and functions of glycans is critical for discovering diagnostic biomarkers and therapeutic targets for cancer. In this study, we used MALDI-TOF-MS analysis to determine the O-glycan profiles of prostate cancer cells metastasized to bone (PC-3), brain (DU145), lymph node (LNCaP), and vertebra (VCaP) in comparison to immortalized RWPE-1 cells derived from normal prostatic tissue. Prostate cancer (CaP) cells exhibited an elevation of simple/short O-glycans, with a reduction of complex O-glycans, increased O-glycan sialylation and decreased fucosylation. Core 1 sialylation was increased dramatically in all CaP cells, and especially in PC-3 cells. The expression of Neu5Acα2-3Galβ1-3GalNAc- (sialyl-3T antigen) which is the product of α2,3-sialyltransferase-I (ST3Gal-I) was substantially increased. We therefore focused on exploring the possible function of ST3Gal-I in PC-3 cells. ST3Gal-I silencing studies showed that ST3Gal-I was associated with PC-3 cell proliferation, migration and apoptosis. Further in vivo studies demonstrated that down regulation of ST3Gal-I reduced the tumor size in xenograft mouse model, indicating that sialyl-3T can serve as a biomarker for metastatic prostate cancer prognosis, and that ST3Gal-I could be a target for therapeutic intervention in cancer treatment.


Low-intensity exercise exerts beneficial effects on plasma lipids via PPARgamma.
An important mechanism by which physical activity reduces the risk of cardiovascular disease is through regulating plasma lipids. We investigated whether low-intensity exercise modulates lipid metabolism and the transcription factors peroxisome proliferator-activated receptor gamma (PPARgamma) and liver X receptor alpha (LXRalpha) responsible for controlling reverse cholesterol transport (RCT). Thirty-four sedentary adults, mean age 45.6 +/- 11.1 yr, participated in an 8-wk low-intensity exercise program consisting of walking 10,000 steps, three times a week. Subjects were randomly allocated to either an exercise group or a sedentary control group, and serum lipid or lipoprotein concentrations were determined. Compared with controls, there was a significant decrease in total cholesterol (preexercise, 5.73 +/- 1.39 mmol x L; postexercise, 5.32 +/- 1.28 mmol x L) and a significant increase in HDL (preexercise, 1.46 +/- 0.47 mmol x L; postexercise, 1.56 +/- 0.50 mmol x L) after the exercise program. There was a significant increase in serum oxidized LDL (oxLDL) concentrations in the exercise group before and after exercise (0 wk, 554 +/- 107 ng x mL; 4 wk, 698 +/- 134 ng x mL; 8 wk, 588 +/- 145 ng x mL). A significant increase in leukocyte mRNA expression for PPARgamma (4 wk, 1.8 +/- 0.9-fold; 8 wk, 4.3 +/- 1.9-fold) was observed, which was reinforced by increased PPARgamma DNA-binding activity postexercise (preexercise, 0.22 +/- 0.09 OD units; postexercise, 1.13 +/- 0.29 OD units). A significant increase in gene expression was observed for the oxLDL scavenger receptor CD36 (4 wk, 3.8 +/- 0.6-fold; 8 wk, 2.7 +/- 0.5-fold) and LXRalpha (8 wk, 3.5 +/- 0.8-fold). Two LXRalpha-regulated genes involved in RCT, namely, ATP-binding cassette transporters A1 and GI (ABCA1 and ABCG1, respectively), were significantly up-regulated postexercise (8 wk: ABCA1, 3.46 +/- 0.56-fold; ABCG1, 3.06 +/- 0.47-fold). We propose that the net effect of these changes may be to increase oxLDL uptake, to stimulate RCT, and thus to promote clearance of proatherogenic lipids from the vasculature, ultimately contributing to the cardiovascular benefits of low-intensity aerobic exercise.


Amplitude noise suppression in cavity-driven oscillations of a mechanical resonator.
We analyze the amplitude and phase noise of limit-cycle oscillations in a mechanical resonator coupled parametrically to an optical cavity driven above its resonant frequency. At a given temperature the limit-cycle oscillations have lower amplitude noise than states of the same average amplitude excited by a pure harmonic drive; for sufficiently low thermal noise a sub-Poissonian resonator state can be produced. We also calculate the linewidth narrowing that occurs in the limit-cycle states and show that while the minimum is set by direct phase diffusion, diffusion due to the optical spring effect can dominate if the cavity is not driven exactly at a sideband resonance.


Hepatoprotective effect of the ethanol extract of Vitis thunbergii on carbon tetrachloride-induced acute hepatotoxicity in rats through anti-oxidative activities.
Vitis thunbergii var. taiwaniana are traditionally used for the treatment of diarrhea, fracture and injury, jaundice, and hepatitis in Taiwan. The hepatoprotective activity of its plant extracts seems to be been associated with its antioxidant activity. This paper aims to investigate the in vitro and in vivo antioxidant effects of the ethanol extract of Vitis thunbergii (EVT). In HPLC analysis, the fingerprint chromatogram of EVT was established. Antioxidant ability of EVT was investigated by employing several established in vitro methods. In vivo antioxidant activity was tested against CCl(4)-induced toxicity in mice. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected in the blood to indicate hepatic injury. Product of lipid peroxidation (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) contents were evaluated for oxidative stress in hepatic injury. Moreover, histopathological observation was assayed for the degree of hepatic injury. EVT exhibited strong antioxidant ability in vitro. After oral administration of EVT significantly decreased ALT and AST, and ameliorated the oxidative stress in hepatic tissue and increased the activity of CAT, SOD, GPx, and GSH. Serum tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and nitric oxide (NO) were decreased in the group treated with CCl(4) plus EVT. Western blotting revealed that EVT blocked protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in CCl(4)-treated rats, significantly. Histopathological examination of livers showed that EVT reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl(4)-treated rats. This study suggests that EVT possesses antioxidant effects in vitro and hepatoprotective effect on acute liver injuries induced by CCl(4)in vivo, and the results suggested that the effect of EVT against CCl(4)-induced liver damage is related to its antioxidant properties.


Gender differences in silencing following childhood sexual abuse.
The clinical literature commonly asserts that males are less likely than females to disclose child sexual abuse at the time it occurs and take longer to discuss their experiences. These hypotheses were tested in this study. This study included 145 men and 151 women. Participants were asked about disclosure at the time of the abuse and the length of time it took for them to discuss the experience. Comparison across these two studies found that boys were significantly less likely than girls to disclose the abuse at the time it occurred and also took significantly longer to discuss their childhood experiences later in life.


Endothelial Nitric Oxide Synthase and Angiotensin Converting Enzyme Gene Polymorphisms in Migraine Patients.
In this study, we investigated the association of migraine with the Variable Number of Tandem Repeats (VNTR), repeated as 27 base pair, gene polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) and the insertion/deletion of angiotensin converting enzyme (ACE) gene polymorphisms. One hundred and five migraine and ninety seven healthy female control subjects were enrolled in the study. The patients were subdivided as migraine with aura and without aura, and the frequency and severity of migraine headaches were recorded. The eNOS VNTR (eNOS 4 a/b) and ACE insertion/deletion gene polymorphisms (ACE I/D) were assessed by polymerase chain reactions. The allele and genotype frequencies of eNOS 4 a/b gene polymorphism showed no difference between the migraine and control groups. The genotypic distribution of the ACE I/D gene polymorphism in the migraine group significantly differed from that in the control group. The DD and ID genotype increased the risk of migraine as much as 2.571 (95% CI-1.138-5.811) and 4.453 (95% CI-2.006-9.883) compared to the II genotype. The same increased risk sustained for both genotypes in the migraine with aura subgroup, but only the ID genotype remained as the risk factor in the migraine without aura subgroup (OR-3.750, 95% CI-1.493-9.420). No association of gene polymorphisms with migraine frequency and severity was observed. Our findings support the relationship between migraine and the ACE I/D gene polymorphism. However, no association was found between migraine and the eNOS 4 a/b gene polymorphism.


Starch Structure of Raw Materials with Different Amylose Contents and the Brewing Quality Characteristics of Korean Rice Beer.
This study aimed to explore suitable processing materials for rice beer (RB) production by analyzing the starch structure of the raw materials utilized for brewing beer and the quality characteristics of RB. We used malt, employing the Heugho cultivar as the main ingredient, and produced beer containing 30% rice. The regular amylose-containing cultivars Samgwang (SA) and Hangaru (HA) and the high-amylose-containing cultivar Dodamssal (DO) were used as adjuncts. Distribution of the short molecular chains of the starch amylopectin was the highest for SA and malt at 29.3% and 27.1%, respectively. Glucose content was the highest in the wort prepared with 100% malt and 30% SA + 70% malt. The alcohol content in SA RB and HA RB was higher than that in beer prepared with 100% malt. DO RB had the least bitterness and volatile components, such as acetaldehyde and ethyl acetate. The three rice cultivars tested in this study are suitable as starch adjuncts for RB production. The characteristics of RBs varied depending on the molecular structure of the ingredients, irrespective of their amylose contents. SA could be considered a craft beer with quality characteristics and rich flavor components, similar to 100% malt beer, compared to other RBs.


Particle-hole symmetric Luttinger liquids in a quantum Hall circuit.
We report current transmission data through a split-gate constriction fabricated onto a two-dimensional electron system in the integer quantum Hall (QH) regime. Split-gate biasing drives interedge backscattering and is shown to lead to suppressed or enhanced transmission, in marked contrast to the expected linear Fermi-liquid behavior. This evolution is described in terms of particle-hole symmetry and allows us to conclude that an unexpected class of gate-controlled particle-hole-symmetric chiral Luttinger liquids (CLLs) can exist at the edges of our QH circuit. These results highlight the role of particle-hole symmetry on the properties of CLL edge states.


Scalable generation of universal platelets from human induced pluripotent stem cells.
Human induced pluripotent stem cells (iPSCs) provide a potentially replenishable source for the production of transfusable platelets. Here, we describe a method to generate megakaryocytes (MKs) and functional platelets from iPSCs in a scalable manner under serum/feeder-free conditions. The method also permits the cryopreservation of MK progenitors, enabling a rapid "surge" capacity when large numbers of platelets are needed. Ultrastructural/morphological analyses show no major differences between iPSC platelets and human blood platelets. iPSC platelets form aggregates, lamellipodia, and filopodia after activation and circulate in macrophage-depleted animals and incorporate into developing mouse thrombi in a manner identical to human platelets. By knocking out the β2-microglobulin gene, we have generated platelets that are negative for the major histocompatibility antigens. The scalable generation of HLA-ABC-negative platelets from a renewable cell source represents an important step toward generating universal platelets for transfusion as well as a potential strategy for the management of platelet refractoriness.


[Immunological mechanisms involved in obesity and their role in metabolic syndrome].
In the past 50 years, the occurrence of human obesity has risen dramatically across the globe. The WHO reported that at least 1.9 billion (1.9 × 10(9)) adults are overweight and 600 million are obese, and the numbers are expected to rise dramatically in the future without intervention. The recent increase in human obesity is caused by increased energy intake and reduced energy expenditure that results in a massive increase in adipose tissue, which is generally harmful to our health. Indeed, the increase in human obesity is strongly associated with an increase in many diseases such as type 2 diabetes (T2D), biliary disease, cardiovascular disease, hepatic steatosis, airway disease, neurodegeneration and certain cancers. The metabolic and immune systems are closely linked and functionally dependent. As a result, excessive nutrient consumption associated with obesity can be recognized as a harmful, stress-inducing biological event by innate pattern recognition receptors (PRRs). This activates inflammatory and stress responses in various metabolic tissues, leading to the chronic low-grade inflammation called metabolic inflammation or "metainflammation". Adipose tissue is mainly composed of adipocytes, although other cell types contribute to its growth and function, including pre-adipocytes, macrophages, lymphocytes, fibroblasts and vascular cells. Obesity can result in profound changes in the cell composition of fat tissue and can lead to the modulation of individual cell phenotypes. Many factors are involved in development of metainflammation, including hypoxia of adipocytes, oxidative stress, endoplasmic reticulum stress, activation of inflammasomes, adipocyte death, activation of TLR and abnormal gut flora.


Improving data transparency in clinical trials using blockchain smart contracts.
The scientific credibility of findings from clinical trials can be undermined by a range of problems including missing data, endpoint switching, data dredging, and selective publication. Together, these issues have contributed to systematically distorted perceptions regarding the benefits and risks of treatments. While these issues have been well documented and widely discussed within the profession, legislative intervention has seen limited success. Recently, a method was described for using a blockchain to prove the existence of documents describing pre-specified endpoints in clinical trials. Here, we extend the idea by using smart contracts - code, and data, that resides at a specific address in a blockchain, and whose execution is cryptographically validated by the network - to demonstrate how trust in clinical trials can be enforced and data manipulation eliminated. We show that blockchain smart contracts provide a novel technological solution to the data manipulation problem, by acting as trusted administrators and providing an immutable record of trial history.


[Effects of organic aerosols on the respiratory system in occupational exposure].
The effects of organic dusts on the respiratory system of workers employed in food processing, in textile workers, as well as in agricultural and livestock farmers are reported. Deposition and elimination of particles from the lung as well as the possible mechanisms of the organic dust effects on respiratory system are described. Separately are presented results of our investigations on the prevalence of respiratory symptoms and diseases as well as lung function tests as indicators of the condition of the respiratory system. Data on the experimental studies with aqueous extracts of organic dusts on smooth muscle of isolated guinea pig trachea suggest that the bronchoconstrictive effects in humans can be reproduced in nonsensitized guinea pigs. The preventive measures in the development of respiratory impairments in subjects occupationally exposed to organic dusts are described.


Ultrasonic tissue characterization and Doppler tissue imaging in the analysis of left ventricular function in essential arterial hypertension: a preliminary study.
It is not known if diastolic abnormalities are independent of systolic dysfunction in arterial hypertension. We studied three groups of 10 male subjects of comparable mean age (31.6 +/- 3.5 years), weight, and height: Athletes (A) (cyclists), essential hypertensive patients (H), and controls (C). Ultrasonic myocardial integrated backscatter signals (IBS) of the septum and the posterior wall were analyzed, while the systo-diastolic variation of the backscatter was considered as a cyclic variation index (CVI(ibs)). Myocardial velocities across the left ventricular major axis were sampled at septum and lateral wall levels by pulsed-wave Doppler tissue imaging (DTI). CVI(ibs) at the septum and the posterior wall were significantly lower in the hypertensive group in comparison with athletes and controls, who were comparable. Early diastolic myocardial velocity (E(m)) of the lateral wall and of the septum were significantly lower in hypertensives, while the late diastolic myocardial velocity (A(m)) was significantly higher in hypertensives in comparison with athletes. The E(m)/A(m) at the septum level was significantly lower in hypertensives in comparison with athletes and controls. Significant correlations were found between CVI and DTI parameters: CVI(ibs) and E(m)/A(m) septum (r = 0.50, P < 0.002). Furthermore, significant correlations were found between mean arterial pressure (MAP) and E(m)/A(m) septum (r = - 0.65, P < 0.001). Ultrasonic tissue characterization with the intrinsic contractility study and the evaluation of the regional diastolic function should, therefore, represent a new integrated diagnostic modality for the evaluation of left ventricular hypertrophied intramyocardial function. This study demonstrated that diastolic abnormalities of left ventricular function, in arterial hypertension, are related and progress with systolic intrinsic dysfunction.


Comparison of quality of speech after Veau-Wardill-Kilner pushback operation and the Cronin modification in the primary treatment of cleft palate.
The quality of speech was compared in 124 young adults with isolated cleft palate. Forty-seven subjects were excluded because of the presence of factors that might have biased the evaluation of the success rate of the two operations studied, leaving 77 subjects who had undergone primary palatoplasty for analysis. One stage closure of the soft and hard palate was done for 43 patients by the mucoperiosteal palatal V to Y pushback technique (Veau-Wardill-Kilner, group V), and 34 underwent the Cronin modification (group C). Their speech was tape recorded, analysed by three qualified listeners, and hypernasality assessed by four published hypernasality indexes. More subjects in group C achieved normal resonance than in group V, who had higher hypernasality index scores than group C. The groups managed pressure consonants similarly. Only a few patients had weak plosives, audible nasal air emission, or compensatory articulation. Similar numbers of secondary operations were done for both groups. However, group V would have actually required secondary surgery more frequently than group C.


A new danger in the air: how pulmonary innate immunity copes with man-made airborne xenobiotics.
The pulmonary innate immune system has evolved over millions of years to provide swift detection of inhaled microbial agents and trigger well-balanced protective responses. Much more recent on the evolutionary scale is human activity, which has resulted in the release of a new class of potentially harmful, non-microbial compounds into the air. These xenobiotics include combustion by-products such as reactive oxygen species and polycyclic aromatic hydrocarbons. This review will summarize evidence showing how airborne xenobiotics can engage pulmonary innate immunity components at many levels. We will focus on potential effects of xenobiotics on airway dendritic cells, as these constitute key innate immune sensors in the lung, with the unique ability to initiate adaptive immunity. We propose that the aberrant processing of inhaled xenobiotics by an innate immune system that is now evolutionarily maladapted underlies the increase in chronic inflammatory lung diseases in modern times.


Albendazole in the conservative management of multiple hydatid disease.
Hydatid disease is quite common in Greece and is routinely treated by surgery. Nevertheless, multiple cysts constitute a difficult problem for treatment. Patients with multiple cysts have already undergone several operations, and their general condition may be poor. We investigated the effect of albendazole [a drug not FDA approved in the US], in the conservative management of multiple hydatid disease in 44 patients with a high antiechinococcal antibody titer who had already undergone two or three operations for the disease (21 men, mean age 51.05; 24 women, mean age 53.42). Albendazole was administered daily in a 10 mg/kg dose for 5 months to 33 patients and for 2 months to 11 patients. Cysts disappeared in 5 patients and decreased in size in 12 patients. Side effects included allergic shock (1 patient), reversible increase in SGOT and SGPT (3 patients), reversible fever and fall in leukocyte number (1 patient). We conclude that surgery remains the treatment of choice for this condition and that albendazole may have a place in the elimination of recurrence of the disease.


EGF-like factors induce expansion of the cumulus cell-oocyte complexes by activating calpain-mediated cell movement.
Cumulus cell-oocyte complex (COC) expansion is obligatory for LH-induced ovulation and is initiated by LH induction of the epidermal growth factor (EGF)-like factors that mediate the synthesis of the hyaluronan-rich matrix and hyaluronan-stabilizing factors. COC expansion also involves the movement of cumulus cells within the matrix by mechanisms that have not been characterized. We document herein that two proteases, calpain 2 and to a lesser extent calpain 1, are expressed in cumulus cells and that the proteolytic activity of these enzymes is rapidly and significantly increased in COC isolated from human chorionic gonadotropin-induced ovulatory follicles in vivo. Stimulation of calpain activity was associated with proteolytic degradation of paxillin and talin (two components of focal adhesion complexes), cell detachment, and the formation of cell surface bleb-like protrusions. Injection of a calpain inhibitor in vivo reduced 1) human chorionic gonadotropin-stimulated calpain enzyme activity, 2) cell detachment, 3) membrane protrusion formation, and 4) COC expansion by mechanisms that did not alter Has2 expression. During EGF-like factor induction of COC expansion in culture, calpain activity was increased by ERK1/2 and intracellular Ca(2+) signaling pathways. Inhibition of calpain activity in cultured COC blocked cumulus cell detachment, protrusion formation, and the vigorous movement of cumulus cells. As a consequence, COC expansion was impaired. Collectively, these results show that two highly coordinated processes control COC expansion. One process involves the synthesis of the hyaluronan matrix, and the other mediates cumulus cell detachment and movement. The latter are controlled by calpain activation downstream of the EGF receptor activation of the Ca(2+) pathway and ERK1/2 pathways.


Purity issues require a cool head.
According to water purification equipment suppliers, estates and facilities teams are now increasingly involved in specifying, purchasing, configuring, and maintaining the sophisticated equipment required to clean and disinfect endoscopes, and, more especially, the water purification equipment needed to ensure an effective "clean". However, changing guidelines on the levels of water purity required for thorough "reprocessing", varying standards of incoming mains water, and differing opinions on which sanitisation methods best combat bacteria, make it vital that they fully understand the issues before specifying potentially costly purification equipment which may otherwise not perform quite as expected.


Increased risk of prostate cancer following sexually transmitted infection in an Asian population.
The relationship between sexually transmitted infections (STIs) and prostate cancer (PC) remains inconclusive. Moreover, all such studies to date have been conducted in Western populations. This study aimed to investigate the risk of PC following STI using a population-based matched-cohort design in Taiwan. The study cohort comprised 1055 patients with STIs, and 10 550 randomly selected subjects were used as a comparison cohort. Cox proportional hazards regression analysis revealed that the hazard ratio for PC during the 5-year follow-up period for patients with a STI was 1.95 (95% confidence interval 1.18-3.23), that of comparison subjects after adjusting for urbanization level, geographical region, monthly income, hypertension, diabetes, hyperlipidaemia, obesity, chronic prostatitis, history of vasectomy, tobacco use disorder, and alcohol abuse. We concluded that the risk of PC was higher for men who were diagnosed with a STI in an Asian population.


Spaceflight and protein metabolism, with special reference to humans.
Human space missions have shown that human spaceflight is associated with a loss of body protein. Specific changes include a loss of lean body mass, decreased muscle mass in the calves, decreased muscle strength, and changes in plasma proteins and amino acids. The major muscle loss is believed to be associated with the antigravity (postural) muscle. The most significant loss of protein appears to occur during the first month of flight. The etiology is believed to be multifactorial with contributions from disuse atrophy, undernutrition, and a stress type of response. This article reviews the results of American and Russian space missions to investigate this problem in humans, monkeys, and rats. The relationship of the flight results with ground-based models including bedrest for humans and hindlimb unweighting for rats is also discussed. The results suggest that humans adapt to spaceflight much better than either monkeys or rats.


Including arm exercise during a cold water immersion recovery better assists restoration of sprint cycling performance.
Sprint (high-intensity) exercise performance is reduced when immediately preceded by cold water immersion (CWI). We aimed to investigate whether this performance effect could be attenuated by combining an active recovery (arm exercise) with hip-level CWI, and whether this attenuation may be related to an effect on core temperature (Tcore ). Participants (n = 8) completed three Wingate tests before (Ex1) and after (Ex2) four different 30-min recovery interventions: CWI at 15 °C (CW15), arm exercise during CWI at 15 °C (CW15+AE), arm exercise during thermoneutral immersion at 34 °C (TW34+AE) and non-immersed arm exercise (AE). After AE and TW34+AE, performance during Ex2 was not different from Ex1; while after CW15+AE and CW15, performance was reduced by 4.9% and 7.6%, respectively. Arm exercise maintained Tcore during recovery in CW15+AE, while it declined to a larger extent upon commencement of Ex2 (-0.9 °C) when compared with CW15 (-0.6 °C). This suggests similar leg muscle cooling during recovery in CW15 and CW15+AE. Without any other significant effects (e.g., on blood lactate), these data suggest that the improvement in sprint performance following an active CWI recovery, over CWI alone, may be related to maintained Tcore and its effect on neurophysiological mechanisms that drive muscle activation, but not by reduced muscle cooling.


Comparative study on serum-induced arthritis in the temporomandibular and limb joint of mice.
The subject of the present study was a systematic comparative analysis of the rheumatoid arthritis (RA)-induced pathomechanisms in the temporomandibular joint with those of the limb joints using the serum-induced arthritis K/BxN model. In 18 BALB/c mice the induction of RA was performed according to the Kouskoff method. Another healthy cohort served as controls (n = 12). Joint swelling of the paws was measured using a micrometer. Functional data were obtained analyzing locomotion. Three-dimensional examination of the temporomandibular joint was performed with micro-computed tomography imaging, followed by histological evaluation of the extremity joints and the temporomandibular joint. Additionally, immunohistochemical investigations were carried out to evaluate inflammatory and immunological changes. Measurement of joint swelling showed a significant increase in the diameter of the paws, as well as a decrease in locomotor activity compared to control animals and the time before arthritis induction. Histological and immunohistochemical investigations showed clear signs of inflammation in the extremity joints. In contrast, no histological or immunohistochemical indications of an inflammatory process were detectable in the temporomandibular joint. In addition, the three-dimensional analysis by micro-computed tomography of the temporomandibular joints did not show any obvious morphological changes. For the first time, using the K/BxN model we could demonstrate that, due to its anatomical and mechanical conditions, the temporomandibular joint seems to be less susceptible to the initiation of RA compared to limb joints. Therefore, additional investigations are needed on other arthritis models as well, in order to further improve our understanding of the pathogenesis and defense mechanisms of the disease.


A hyaluronic acid-based hydrogel enabling CD44-mediated chondrocyte binding and gapmer oligonucleotide release for modulation of gene expression in osteoarthritis.
Hyaluronic acid (HA) is an attractive biomaterial for osteoarthritis (OA) treatment due to inherent functional and compatibility properties as an endogenous knee joint component. In this work, we describe a HA-based hydrogel with the dual functionality of increased CD44-dependent chondrocyte binding and controlled release of gapmer antisense oligonucleotides for unassisted cellular entry and subsequent gene silencing activity. A Schiff base-mediated gelation method was used to produce a panel of hydrogels varying in the aldehyde-modified HA (900kDa) to chitosan ratios (3:7, 5:5 and 7:3) for identifying designs displaying optimal engagement of OA patient-derived CD44-expressing chondrocytes. Correlation was found between cell binding and CD44 expression, with maximal binding exhibited at a HA/chitosan ratio of 7:3, that was 181% higher than CD44-negative MCF-7 cell control cells. Transfection agent-free uptake into OA chondrocytes of fluorescent 13-mer DNA oligonucleotides with a flanked locked nucleic acid (LNA) gapmer design, in contrast to naked siRNA, was demonstrated by confocal and flow cytometric analysis. A sustained and complete release over 5days was found with the 7:3 hydrogel, in contrast, the 5:5 and 3:7 hydrogel released 60% and 43% of loaded gapmers, respectively over the same period. A COX-2-specific gapmer designed with maximal chondrocyte gene silencing (~70% silencing efficiency at 500nM compared with a mismatch gapmer sequence) resulted in effective COX-2 silencing over 14days in hydrogels seeded with OA chondrocytes, with significant difference exhibited between day 3 and 10. This work introduces a novel HA-based CD44-mediated cellular binding and gapmer controlled release platform to modulate cellular gene expression.


In-hospital medical complications and long-term mortality after ischemic stroke.
Inhospital medical complications account for a considerable portion of deaths during the early stage of stroke. However, relatively few studies have examined their long-term effects on mortality in stroke patients. We prospectively and consecutively collected data on 579 patients with acute ischemic stroke from November 1998 to February 2001. Mortality was confirmed using national death certificate data from 1999 to 2003. During admission, one or more medical complications requiring intervention developed in 160 of these 579 patients (27.6%). For these 160 subjects, the 30-day, 90-day, 1-year, 2-year, 3-year, and 4-year mortalities were 16.3, 29.4, 46.9, 55.6, 61.3, and 70.7%, whereas the mortality figures for those without such complications (n=419) were 1.4, 3.8, 8.8, 15.0, 19.1, and 22.4 (P<0.001 with log-rank test). To eliminate the short-term effects of these complications and thus reveal their long-term effects, we investigated differences in mortality versus the presence of inhospital complications at more than 30 days, 90 days, 1 year, 2 years, and 3 years after stroke, respectively. Cox's proportional hazard regression analysis was applied at these times after stroke and showed that all hazard ratios of medical complications in terms of mortality were statistically larger than one, regardless of adjusting for effects of potential predictors on mortality. Our study shows that stroke patient mortality is influenced by inhospital medical complications significantly up to the chronic stage. This finding suggests that the appropriate prevention and management of inhospital complications could improve short-term and long-term prognoses after stroke.


Metabolic syndrome increases operative mortality in patients with impaired left ventricular systolic function who undergo coronary artery bypass grafting: a retrospective observational study.
Metabolic syndrome (MetS) is a prevalent risk factor for coronary artery disease progression. Past studies have shown that MetS and its components tends to increase mortality after coronary artery bypass grafting (CABG), but data on the impact of MetS on postoperative outcome in patients with a left ventricular (LV) ejection fraction (EF) < 50% are still lacking. Out of 2300 patients who underwent CABG between 2008 and 2018 in our center, 190 patients were identified as having impaired LV systolic function (EF < 50%). The patients were divided into two groups: those with MetS (n = 87, 45.8%) and those without MetS (n = 103, 54.2%). The influence of MetS on postoperative mortality and major complications was investigated. Postoperative mortality occurred in 12.6% of patients with MetS and in 3.9% of patients without MetS (p < 0.05). Multivariate analysis showed that patients with MetS had a significantly greater risk of mortality compared with patients without MetS (relative risk 7.23, p < 0.05). After adjustment for other risk factors, the risk of mortality was increased 6.47-fold [95% confidence interval (CI):1.25-33.6; p < 0.05] in patients with MetS and diabetes and 5.4-fold (95% CI: 1.12-29.7; p < 0.05) in patients with MetS and without diabetes, whereas it was not significantly increased in patients with diabetes and without MetS. MetS is an important predictor of increased mortality in patients with LVEF<50% who undergo CABG. The components of MetS have synergistic effect in postoperative mortality. Multifactorial intervention in MetS is required to improve surgical efficacy in these patients.


Metal oxide gas sensor drift compensation using a dynamic classifier ensemble based on fitting.
Sensor drift is currently the most challenging problem in gas sensing. We propose a novel ensemble method with dynamic weights based on fitting (DWF) to solve the gas discrimination problem, regardless of the gas concentration, with high accuracy over extended periods of time. The DWF method uses a dynamic weighted combination of support vector machine (SVM) classifiers trained by the datasets that are collected at different time periods. In the testing of future datasets, the classifier weights are predicted by fitting functions, which are obtained by the proper fitting of the optimal weights during training. We compare the performance of the DWF method with that of competing methods in an experiment based on a public dataset that was compiled over a period of three years. The experimental results demonstrate that the DWF method outperforms the other methods considered. Furthermore, the DWF method can be further optimized by applying a fitting function that more closely matches the variation of the optimal weight over time.


Rethinking counselling in prenatal screening: An ethical analysis of informed consent in the context of non-invasive prenatal testing (NIPT).
Informed consent is a key condition for prenatal screening programmes to reach their aim of promoting reproductive autonomy. Reaching this aim is currently being challenged with the introduction of non-invasive prenatal testing (NIPT) in first-trimester prenatal screening programmes: amongst others its procedural ease-it only requires a blood draw and reaches high levels of reliability-might hinder women's understanding that they should make a personal, informed decision about screening. We offer arguments for a renewed recognition and use of informed consent compared to informed choice, and for a focus on value-consistent choices and personalized informational preferences. We argue for a three-step counselling model in which three decision moments are distinguished and differently addressed: (1) professionals explore women's values concerning whether and why they wish to know whether their baby has a genetic disorder; (2) women receive layered medical-technical information and are asked to make a decision about screening; (3) during post-test counselling, women are supported in decision-making about the continuation or termination of their pregnancy. This model might also be applicable in other fields of genetic (pre-test) counselling, where techniques for expanding genome analysis and burdensome test-outcomes challenge counselling of patients.


Efinaconazole Topical Solution, 10%: Factors Contributing to Onychomycosis Success.
To provide an adequate therapeutic effect against onychomycosis, it has been suggested that topical drugs should have two properties: drug permeability through the nail plate and into the nail bed, and retention of their antifungal activity in the disease-affected areas. Only recently has the importance of other delivery routes (such as subungual) been discussed. Efinaconazole has been shown to have a more potent antifungal activity in vitro than the most commonly used onychomycosis treatments. The low keratin affinity of efinaconazole contributes to its effective delivery through the nail plate and retention of its antifungal activity. Its unique low surface tension formulation provides good wetting properties affording drug delivery both through and under the nail. High antifungal drug concentrations have been demonstrated in the nail of onychomycosis patients, and effectiveness of efinaconazole topical solution, 10% confirmed in two large well-controlled multicenter Phase 3 clinical studies in patients with mild-to-moderate disease.


[SENSITIVITY STUDY OF ANTIMICROBIAL PNEUMOCOCCI IN CENTRAL KAZAKHSTAN].
To determine the epidemiological pattern of antibiotic resistance strains of S. Pneumoniae studied the sensitivity of nasopharyngeal isolates of pneumococci isolated from healthy children attending sports clubs Karaganda region. The frequency of allocation of pneumococci was 35.57%. In accordance with the values of the minimum inhibitory concentration resistant pneumococci was: penicillin - 5.41%, erythromycin - 8.1%, clindamycin - 4.05%, amoxicillin-6.76%, tetracycline 28.38%. Resistance to beta-lactam antibiotics in the studied children is not a significant problem. Worthy of attention is the high proportion of resistance to tetracycline, which has recently been used for medical purposes much less than macrolides and betalaktamy. This finding suggests the presence of other resistance mechanisms of formation.


Effects of the alpha 1a-adrenoceptor antagonist RS-17053 on phenylpropanolamine-induced anorexia in rats.
Activation of alpha 1-Adrenergic receptors via systemic administration of drugs such as phenylpropanolamine (PPA) and cirazoline results in the suppression of feeding in rats. Whether PPA acts via activation of the three currently identified alpha 1-Adrenoceptor subtypes is unknown. The intent of the present study was thus to examine the effects of systemic administration of the novel alpha 1a-Adrenoceptor antagonist RS-17053 on PPA-induced anorexia. Adult male rats (n = 6 to 8 per group) were pretreated (IP) with either 0, 0.1, 0.5, 2.5, or 10.0 mg/kg RS-17053 or with 2.0 mg/kg of the prototypical alpha 1-Adrenoceptor antagonist prazosin. Five minutes later, each rat was treated (IP) with either 0, 5, 10 or 15 mg/kg PPA. Food and water intakes were recorded for a 30 min period starting 10 min after the the treatment injection. Rats pretreated with vehicle and then treated with PPA exhibited a dose-dependent suppression of feeding with a maximal effect evident at the 15 mg/kg dose of PPA. Pretreatment with 2.0 mg/kg prazosin reversed the anorexic activity of PPA. Pretreatment with RS-17053 (0.1-2.5 mg/kg) did not alter either baseline feeding or the anorexic action of PPA. These results suggest that PPA does not act via the alpha 1a-Adrenergic receptor subtype to suppress food intake.


Structural and biochemical analysis of the Hordeum vulgare L. HvGR-RBP1 protein, a glycine-rich RNA-binding protein involved in the regulation of barley plant development and stress response.
The timing of whole-plant senescence influences important agricultural traits such as yield and grain protein content. Post-transcriptional regulation by plant RNA-binding proteins is essential for proper control of gene expression, development, and stress responses. Here, we report the three-dimensional solution NMR structure and nucleic acid-binding properties of the barley glycine-rich RNA-binding protein HvGR-RBP1, whose transcript has been identified as being >45-fold up-regulated in early-as compared to late-senescing near-isogenic barley germplasm. NMR analysis reveals that HvGR-RBP1 is a multidomain protein comprising a well-folded N-terminal RNA Recognition Motif (RRM) and a structurally disordered C-terminal glycine-rich domain. Chemical shift differences observed in 2D (1)H-(15)N correlation (HSQC) NMR spectra of full-length HvGR-RBP1 and N-HvGR-RBP1 (RRM domain only) suggest that the two domains can interact both in-trans and intramolecularly, similar to what is observed in the tobacco NtGR-RBP1 protein. Further, we show that the RRM domain of HvGR-RBP1 binds single-stranded DNA nucleotide fragments containing the consensus nucleotide sequence 5'-TTCTGX-3' with low micromolar affinity in vitro. We also demonstrate that the C-terminal glycine-rich (HvGR) domain of Hv-GR-RBP1 can interact nonspecifically with ssRNA in vitro. Structural similarities with other plant glycine-rich RNA-binding proteins suggest that HvGR-RBP1 may be multifunctional. Based on gene expression analysis following cold stress in barley and E. coli growth studies following cold shock treatment, we conclude that HvGR-RBP1 functions in a manner similar to cold-shock proteins and harbors RNA chaperone activity. HvGR-RBP1 is therefore not only involved in the regulation of barley development including senescence, but also functions in plant responses to environmental stress.


A novel prognostic index based on the analysis of glycolysis-related genes in idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a lung disease that is both chronic and progressive and is characterized by glycolysis. However, glycolysis's function and its clinical significance in IPF are still not well understood. We accessed the Gene Expression Omnibus database to retrieve mRNA expression information for lung tissue and other samples. We identified genes associated with glycolysis that had differential expression levels between IPF and controls. In this work, we conducted a comprehensive bioinformatic analysis to systematically examine the glycolysis-associated genes with differential expression and subsequently investigated the possible prognostic significance of these genes. Additionally, the expression profiles of the associated prognostic genes were further investigated via quantitative real-time polymerase chain reaction in our cohort. In this investigation, we found that the expression of 16 genes involved in glycolysis was differentially expressed. Among them, 12 were upregulated and 4 were downregulated. We found that 3 glycolysis-related genes (stanniocalcin 2, transketolase like 1, artemin) might serve as hub genes for anticipating patient prognosis. The data from these genes were used to generate the prognostic models. The findings confirmed that high-risk IPF patients recorded a shorter overall survival relative to low-risk patients. This prognostic model yielded 1-, 2-, and 3-year survival rates of 0.666, 0.651, and 0.717, correspondingly, based on the area under the curve of the survival-dependent receiver operating characteristic. The GSE27957 and GSE70866 cohorts validated these findings, indicating the model has a good predictive performance. All 3 glycolysis-associated genes were validated to be expressed in our cohort. Finally, we used mRNA levels from 3 genes to produce a nomogram to quantitatively predict the prognosis of IPF individuals. As possible indicators for the prognosis of IPF, the glycolysis-related genes stanniocalcin 2, transketolase like 1, and artemin were shown to be promising candidate markers.


Does knowledge on diabetes management influence glycemic control? A nationwide study in patients with type 1 diabetes in Brazil.
The purpose of this study is to establish demographic and clinical data associated with the knowledge on diabetes management and its influence on glycemic control in patients with type 1 diabetes. This was a retrospective, observational, multicenter study conducted with 1,760 patients between August 2011 and August 2014 in 10 cities of Brazil. Overall, 1,190 (67.6%) patients knew what glycated hemoglobin (HbA1c) means. These patients were older, had longer disease duration, longer follow-up in each center, reported lower frequency of self-reported hypoglycemia, and were more frequently Caucasians and at glycemic goal. Multivariate analysis showed that knowledge on what HbA1c means was related to more years of school attendance, self-reported ethnicity (Caucasians), severe hypoglycemia, economic status, follow-up time in each center, and participation on diabetes educational programs. Good glycemic control was related to older age, more years of school attendance, higher frequency of daily self-monitoring of blood glucose, higher adherence to diet, and knowledge on what HbA1c means. Patients with a knowledge on what HbA1c means had a better chance of reaching an adequate glycemic control that was not found in the majority of our patients. Diabetes care teams should rethink the approaches to patients and change them to more proactive schedules, reinforcing education, patients' skills, and empowerment to have positive attitudes toward reaching and maintaining a better glycemic control. Finally, the glucocentric approach to diabetes management should be changed to actions that include patients' psychosocial aspects aiming to reduce the stress of living with diabetes, improving glycemic control, and avoiding adverse outcomes.


Effect of hypertension on bacteria composition of prostate biopsy in patients with benign prostatic hyperplasia and prostate cancer in PSA grey-zone.
Diagnostic prostate cancer (PC) is difficult to diagnose by prostate biopsy, even in patients with markedly elevated PSA levels. Therefore, we aimed to identify a new, better technique to detect PC in a more consistent manner. A variety of steps were employed to validate this proposed method, including DNA extraction, polymerase chain reaction (PCR) amplification, denaturing gradient gel electrophoresis (DGGE) and DGGE band sequencing. Four transperineal prostate biopsy specimens were obtained from male patients. The patients were under the age of 65 and PSA levels were 4-10 ng/ml. We also investigated the bacteria composition of transperineal prostate biopsy in patients with benign prostatic hyperplasia (BPH) and PC by PCR-DGGE profiling. Sequences from selected bands 2 and 4 both matched with Sphingomonas, which is present in lower amounts in PC without hypertension as compared to PC with hypertension, while there were no particular differences in the BPH group. Specific bacteria from the prostate biopsy tissues provide further confidence in PC diagnosis based on a PCR approach as a diagnostic tool, while hypertension was found to be a disturbing factor that can affect the diagnosis of BPH and PC in grey-zone.


Prevalence of hospital-acquired enterococci infections in two primary-care hospitals in osogbo, southwestern Nigeria.
Enterococci are opportunistic bacteria that become pathogenic when they colonize niches where they are not normally found. Of recent, they have become major cause of nosocomial infections, especially of the bloodstream, urinary tract and surgical sites. The aim of this study is to determine the point-prevalence rate of human enterococci infections among hospitalized patients in Osogbo, Nigeria. The study was conducted between January and June 2009 in two primary-care hospitals in Osogbo and involved a total of 118 patients who developed clinical evidence of infection at least 48 hours after hospital admission. Appropriate clinical samples were collected from the patients after an informed consent and cultured for isolation/biochemical identification of Enterococcus species at the Bacteriology Laboratory of Ladoke Akintola University of Technology, Osogbo using standard microbiological methods. There were 525 hospital admissions within the time frame of the study of which 118 (22.5%) developed hospital acquired infection (HAI); 58 (49.2%) of which cultured positive for bacterial pathogens. Enterococci were isolated from infective focus in 7 patients, giving a prevalence rate of hospital-acquired enterococci infection of 5.9%. Two species of Enterococcus were identified; Enterococcus faecalis from urinary tract infection (UTI) and surgical site infection (SSI) of 6 (85.7%) patients and Enterococcus faecium from UTI in 1 (14.3%) patient. Other bacteria recovered from other infective foci were Klebsiella spp 31.0%, Pseudomonas spp 20.7%, Staphylococcus aureus 17.2%, Escherichia coli 12.1%, Staphylococcus epidermidis 3.4%, Streptococcus pneumoniae 1.7% and Serratia spp 1.7%. All the enterococci isolates were multiply antibiotic resistant, and 42.9% were vancomycin-resistant enterococci (VRE) with the VRE strains showing resistance to wider range of antibiotics than the vancomycin-sensitive strains. Other Gram-positive and Gram negative bacterial isolates also demonstrated multiple resistance to all commonly available antibiotics in this community except E. coli and Pseudomonas spp which were relatively sensitive to ciprofloxacin and ceftazidime. This limited study demonstrated a high prevalence rate of multiple antibiotic resistant enterococci infections among hospitalized patients in this environment. There is need for systematic surveillance of hospitals for enterococci infections; prudent use and rational prescription of antibiotics and stringent measures to reduce the prevalence rate by health education on infection control measures such as isolation, cleaning, disinfection and sterilization.


Poisonings with pesticides in the Federal District of Brazil.
Pesticides are the second major cause of poisoning in Brazil, but information about the chemicals involved and the clinical management of patients is scarce. This study is a retrospective review of 709 pesticide cases reported to a toxicological information center from 2004 to 2007. Over 90% of the cases occurred after accidental or self-poisoning; more than 60% of the accidents involved children up to 4 years old, mainly with domestic pyrethroid insecticides. One hundred ninety-four cases involved chumbinho, an illegal rodenticide known to contain acetylcholinesterase inhibitor insecticides, mainly aldicarb. In about half the cases, the individuals were admitted to hospitals. Those poisoned with acetylcholinesterase inhibitors stayed longer and most of them displayed pronounced clinical signs of poisoning (Poisoning Severity Score grades 2-4); 14 of the 18 deaths reported occurred with these products. Atropine was given to about 30% of the individuals, including to some with no cholinergic symptoms or exposed to non-acetylcholinesterase inhibitors. All 81 poisonings with coumarin were asymptomatic, but in half of the cases the individuals received vitamin K. The lack of laboratory support to confirm the chemical involved in the poisonings certainly contributed to the unnecessary antidote administration. In spite of continuing government efforts, poisoning with chumbinho is still a major problem in the country.


Bilateral tonic-clonic epileptic seizures in non-benign familial neonatal convulsions.
We report an electroclinical pattern considered characteristic of benign familial neonatal convulsions (BFNC) in two neonates without BFNC. Both neonates were products of uncomplicated pregnancies, labor, and deliveries. The cause of the seizures was not established. There was no family history of seizures or epilepsy. Seizures started on the second and third days after birth. Ten seizures were captured by continuous video-EEG telemetry. The electroclinical events began with generalized tonic posturing coinciding with the appearance of diffuse attenuation of the EEG activity. After several seconds, bilateral clonic movements accompanied by bilateral repetitive sharp waves or spikes occurred in the EEG. One patient had normal development; the other became autistic. We conclude that the electroclinical pattern occurring in BFNC can occur in other types of neonatal seizures.


[Analysis of Mycobacterium tuberculosis Complex Strains Isolated from the Samples of Patients Living in Northern Syria].
Tuberculosis causes serious mortality and morbidity worldwide each year. A lot of effort and money is spent for the diagnosis and treatment of tuberculosis all over the world. The importance that countries give to health policies and public health is inversely proportional to the incidence of tuberculosis and multidrug resistant tuberculosis. The aim of our study was to evaluate the resistance profiles of Mycobacterium tuberculosis complex strains which were isolated from sputum samples, collected by World Health Organisation from patients living in the northern region of Syria, where health services were disrupted due to the civil war. According to the protocol signed between the World Health Organization and our hospital; sputum samples taken from tuberculosis patients living in Afrin, Azez and Idlib regions or suspected of being resistant to anti-tuberculosis drugs were studied in our hospital. The cultivation process was performed in our laboratory using Löwenstein Jensen media and MGIT-960 system. The susceptibility tests for primary anti-tuberculosis drugs were performed using MGIT-960 system for M.tuberculosis complex isolates. The isolates identified as MDR/RD-TB (multi-drug-resistant-rifampicin-resistant tuberculosis) were sent to National Tuberculosis Reference Laboratory of Public Health Institution of Türkiye for susceptibility testing to first and second line drugs. Mutation and wild-type determination were studied by "Line Probe Assay (LPA)" method to investigate the susceptibility of the isolates to isoniazid, rifampicin, fluoroquinolone and aminoglycoside/cyclic peptide. The results obtained from the patients were collected and evaluated retrospectively from the records. Growth was observed in 18 samples out of 171 sputum samples from 67 patients; 13 isolates were detected as MDR-TB while one isolate was detected as mono RR-TB. The rate of mono RR-TB was 1.5% and the rate of MDR-TB was 19.4%. MUT3 causing rifampicin resistance was detected in 17.9% of the patients, katG/MUT1 causing isoniazid resistance in 17.9% and WT loss causing aminoglycoside/cyclic peptide resistance were detected in 19.4% of the patients. Neither fluoroquinolone resistance nor a mutation leading to fluoroquinolone resistance was detected in the study. When the sputum samples taken from the patients living in Northern Syria were examined, the frequency of MDR-TB was found to be quite high. MDR-TB, which is an important public health problem, was found at high rates due to the internal turmoil in the region and poor accessibility to health services. Since the gene mutations causing drug resistance with the LPA method differ with the conducted studies, it is important to evaluate the dominant gene mutations for determining the TB treatment strategies in the region.


Leaf cellulose density as the key determinant of inter- and intra-specific variation in leaf fracture toughness in a species-rich tropical forest.
Leaves as the main photosynthetic organ of plants must be well protected against various hazards to achieve their optimal lifespans. Yet, within-species variation and the material basis of leaf strength have been explored for very few species. Here, we present a large dataset of leaf fracture toughness from a species-rich humid tropical forest on Barro Colorado Island, Panama, reporting both among- and within-species variation in relation to light environment (sun-lit canopy versus shaded understorey) and ontogeny (seedlings versus adults). In this dataset encompassing 281 free-standing woody species and 428 species-light combinations, lamina fracture toughness varied ca 10 times. A central objective of our study was to identify generalizable patterns in the structural and material basis for interspecific variation in leaf lamina fracture toughness. The leaf lamina is a heterogeneous structure in which strong materials in cell walls, such as cellulose and lignin, contribute disproportionately to fracture toughness. We found significant increases in leaf fracture toughness from shade to sun and from seedling leaves to adult leaves. Both within and across species, leaf fracture toughness increased with total bulk density (dry biomass per unit volume) and cellulose mass concentration, but decreased with mass concentrations of lignin and hemicelluose. These bivariate relationships shift between light environments, but leaf cellulose density (cellulose mass per unit leaf volume) exhibits a common relationship with lamina fracture toughness between light environments and through ontogeny. Hence, leaf cellulose density is probably a universal predictor of leaf fracture toughness.


Associations between social jetlag trajectories and body mass index among young adults.
This study employed longitudinal data collected repeatedly from individuals over the course of several years to examine the trajectories of social jetlag from ages 11 to 22 years and their associations with subsequent BMI. Potential sex differences were also investigated. Data were obtained from 2 longitudinal studies conducted in Taiwan (N = 4287). Social jetlag was defined as ≥2 h of absolute difference in sleep midpoint between weekdays and weekends. BMI was calculated using weight (kg)/height(m)2 and categorized as underweight (<18 kg/m2), normal weight (18 kg/m2 ≤ BMI < 24 kg/m2), overweight (24 kg/m2 ≤ BMI < 27 kg/m2), and obese (≥27 kg/m2). Group-based trajectory modeling and multinomial logistic regression were applied to investigate study objectives. Four distinct trajectories of social jetlag throughout the adolescent years were identified, with corresponding proportions as follows: low-stable (42%), moderate-decreasing (19%), low-increasing (22%), and chronic (17%) trajectories. Among males, the risk of being underweight (aOR, 1.96; 95% CI, 1.35-2.84) or obese (aOR, 1.40; 95% CI, 1.02-1.92) was higher in individuals with a low-increasing trajectory than in those with a low-stable trajectory. Among females, those with a low-increasing (aOR, 1.61; 95% CI, 1.02-2.54) or chronic (aOR, 2.04; 95% CI, 1.27-3.25) trajectory were at a higher risk of being obese relative to those with a low-stable trajectory. Addressing the development of increasing or chronic social jetlag during adolescence can help prevent abnormal BMI in young adulthood. Practitioners should consider sex differences in treatment or consultation.


Phenotypic and genotypic characterization of clinically relevant bacteria isolated from dental waste and waste workers' hands, mucosas and coats.
Infectious wastes are potential sources of pathogenic micro-organisms, which may represent a risk to the professionals who manage them. In this study, we aimed to characterize the infectious bacteria present in dental waste and waste workers. The dental waste produced over 24 h was collected and waste workers were sampled by swabbing. Isolate resistance profiles were characterized by Vitek® and PCR and biofilm formation by Congo Red agar, string test and microtitre assay. To assess similarity between the waste and the workers' samples, a random amplified polymorphic DNA test was used. Twenty-eight bacteria were identified as clinically relevant. The most frequent gene was blaTEM present in five Gram-negative micro-organisms, and one blaSHV in Klebsiella pneumoniae. All Pseudomonas aeruginosa were positive to extracellular polymeric substances formation, except one isolated from a worker. Klebsiella pneumoniae had negative results for the string test. Pseudomonas aeruginosa showed better adherence at 25°C after 48 h of incubation and K. pneumonia had the best biofilm formation at the same temperature, after 24 h. The similarity between P. aeruginosa recovered from dental waste and from workers was low, however, it is important to note that a pathogen was found on a worker's hands and that improvements in biosafety are required. Infectious dental waste can contain clinically relevant bacteria with important resistance and biofilm profiles. These micro-organisms could be transmitted to waste workers, other professionals and patients if the principles of biosafety measures are neglected. To our knowledge, no study has ever evaluated the microbial characterization and the potential contamination risk of dental infectious waste and waste handlers. The presence of clinically relevant bacteria in the hands and nasal mucosa of waste workers highlights the need for studies in this field to clarify the risk of these pathogens in dental healthcare services, and to stress the need for an efficient waste management.


Differential item functioning of the SF-12 in a population-based regional joint replacement registry.
Joint replacement, an increasingly common procedure amongst older adults, can substantially improve health-related quality of life (HRQoL). However, differential item functioning (DIF) may affect the accurate interpretation of differences in HRQoL amongst patients with different demographic and health status characteristics but the same underlying (i.e., latent) level of the investigated construct. This study tested for DIF in pre-operative SF-12 physical health (PH) and mental health (MH) sub-scale items amongst patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). Data were from a population-based joint replacement registry from the Canadian province of Manitoba. TKA and THA patients who had surgery between 2009 and 2015 and completed a pre-operative assessment were included. DIF was tested using the multiple indicators multiple causes (MIMIC) method with sex, age group, body weight status, and presence of multiple comorbid conditions (i.e., multimorbidity) as covariates. Analyses were stratified by joint type. The study cohort included 8820 patients; 42.1% underwent THA, 57.3% were female, 32.7% were 70+ years, and 52.8% were obese. For each sub-scale, four of the six items exhibited DIF in both THA and TKA groups. Differences in the covariate effect estimates for DIF and No-DIF models on the MH latent variable were largest for age and body weight status for the THA group, and for sex and multimorbidity for the TKA group. All of the differences were small for PH. Multimorbidity had the strongest association with PH and age and sex had the strongest association with MH in the DIF models. Demographic and health status characteristics influenced SF-12 PH and MH item responses in joint replacement populations, although the size of the effects were not large for PH. We recommend testing and adjusting for DIF effects to ensure comparability of HRQoL measures in joint replacement populations.


Laboratory medicine: challenges and opportunities.
Technologic innovations have substantially improved the productivity of clinical laboratories, but the services provided by clinical laboratories are increasingly becoming commoditized. We reflect on how current developments may affect the future of laboratory medicine and how to deal with these changes. We argue that to be prepared for the future, clinical laboratories should enhance efficiency and reduce costs by forming alliances and networks; consolidating, integrating, or outsourcing; and more importantly, create additional value by providing knowledge services related to in vitro diagnostics.


Metabolic Syndrome Prevalence and Reduction in Inmates Prescribed Antipsychotic Medications.
The principal aim of this study was to establish whether a metabolic monitoring program implemented for second-generation antipsychotic medications (SGAs) was associated with any reduction in the prevalence of metabolic syndrome in adult inmates treated with antipsychotic medications in the New Jersey Department of Corrections. The average prevalence of metabolic syndrome in those prescribed SGAs decreased from 17.9% during the years before metabolic monitoring to 14.3% during the years of monitoring. The number of patients prescribed antipsychotic medication decreased a net 35% over 9 years of the study. We conclude that metabolic monitoring was one of the several administrative interventions over the study period that reduced the unnecessary exposure of inmates to the risks of antipsychotic medications.


Molecular basis for type 1 antithrombin deficiency: identification of two novel point mutations and evidence for a de novo splice site mutation.
Inherited type 1 antithrombin (AT) deficiency is characterized by a reduction in both immunologically and functionally detectable protein. The disorder is associated with a high risk of thromboembolic disease. We have investigated the molecular basis of type 1 AT deficiency in three unrelated families. We have used the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis, followed by direct sequencing of the seven exons and the intron-exon junctions of the AT gene. Two novel point mutations were identified. A T to C single-base substitution was found in codon 421 in exon 6 (nucleotide position 13380), leading to an AT 421 isoleucine to threonine substitution. In another kindred, one of three Cs at nucleotide (nt) positions 5448 to 5450 in exon 3A (codon 151 or 152) was deleted, resulting in a frameshift mutation and predicting premature termination of protein translation at codon 251. In a third family, a previously reported G to A substitution, at nt position 9788 in intron 4, 14 bp in front of exon 5, was found. We have demonstrated the creation of a de novo exon 5 splice site by ectopic transcript analysis of lymphocyte mRNA. In all cases, the affected individuals were heterozygous for the mutation and no variant AT protein was detected.


Satellite-Based Wireless Sensor Development and Deployment Studies for Surface Wave Testing.
Although cable-based seismic sensing systems have provided reliable data in the past several decades, they become a bottleneck for large-area monitoring and critical environmental (volcanic eruptions) sensing because of their cost, difficulty in deploying and expanding, and lack of accurate three-dimensional geographic information. In this paper, a new wireless sensing system is designed consisting of a portable satellite device, a self-sustaining power source, a low-cost computational core, and a high-precision sensor. The emphasis of this paper is to implement in low-cost hardware without requirements of highly specialized and expensive data acquisition instruments. Meanwhile, a computational-core-embedded algorithm based on compressive sensing (CS) is also developed to compress data size for transmission and encrypt the measured data preventing information loss. Seismic data captured by the accelerometer sensor are coded into compressive data packages and then transferred via satellite communication to a cloud-based server for storage. Acceleration and GPS information is decrypted by the ℓ1-norm minimization optimization algorithm for further processing. In this research, the feasibility of the proposed sensing system for the acquisition of seismic testing is investigated in an outdoor field surface wave testing. Results indicate the proposed low-cost wireless sensing system has the capability of collecting ground motions, transferring data, and sharing GPS information via satellite communication for large area monitoring. In addition, it has a great potential of recovering measurements even with significant data package loss.


Pregnenolone functions in centriole cohesion during mitosis.
Cell division is controlled by a multitude of protein enzymes, but little is known about roles of metabolites in this mechanism. Here, we show that pregnenolone (P5), a steroid that is produced from cholesterol by the steroidogenic enzyme Cyp11a1, has an essential role in centriole cohesion during mitosis. During prometa-metaphase, P5 is accumulated around the spindle poles. Depletion of P5 induces multipolar spindles that result from premature centriole disengagement, which are rescued by ectopic introduction of P5, but not its downstream metabolites, into the cells. Premature centriole disengagement, induced by loss of P5, is not a result of precocious activation of separase, a key factor for the centriole disengagement in anaphase. Rather, P5 directly binds to the N-terminal coiled-coil domain of short-form of shugoshin 1 (sSgo1), a protector for centriole cohesion and recruits it to spindle poles in mitosis. Our results thus reveal a steroid-mediated centriole protection mechanism.


[Experience in posterolateral mini-incision total hip arthroplasty].
To explore the surgical techniques in posterolateral mini-incision total hip arthroplasty and clinical efficacy. A total of 94 patients (98 hips) had posterolateral mini-incision total hip arthroplasty, from December 2006 to December 2008, and were randomly divided into a posterolateral miniincision total hip arthroplasty group (Group A) and a conventional group of posterolateral incision for total hip arthroplasty (Group B). Forty-nine patients (50 hips) in Group A had posterolateral small incision total hip arthroplasty [26 males, 23 females, between 37.0 and 95.0 years (average 68.9 years), body mass index (BMI) between 20.3 and 29.7 (average BMI 25.4)]. Forty-five patients (48 hips) in Group B had the conventional posterolateral incision [27 males, 18 females, between 45.0 and 92.0 years (average 69.7 years), BMI between 18.7 and 34.1 (average BMI 26.9)]. The incision length, blood loss, drainage, operation time, and postoperative Harris scores were compared between the 2 groups. The incision length was 6.0~10.5 (average length 7.4) cm, average blood loss was 387.6 (140.0~1000.0) mL, average drainage was 143.1 (63.0~375.0) mL, average blood transfusion was 77.6 (0~400.0) mL, average operation time was 84.6 (63.0~130.0) min, and vitalock abduction angle imaging after the operation was 41.6° (averagely 38.0°~57.0°) in Group A. The incision length was 15.0~23.0 (average length 20.0) cm, average blood loss was 513.1 (210.0~1350.0) mL, average drainage was 152.3 (70.0~520.0) mL, average blood transfusion was 142.2 (0~800.0) mL, average operation time was 84.0 (71.0~115.0) min, and postoperative radiographic acetabular cup abduction angle was 42.3° (37.0°~54.0°) in Group B. The follow-up showed that the prosthesis of the 2 groups was in a good position, Harris score was significantly improved with no complications after total hip arthroplasty in the 2 groups. With the correct selection of indications and adept operation skills and other circumstances, posterolateral mini-incision total hip arthroplasty may do little damage to the soft tissue with a small scar on the skin. The imaging evaluation after the operation and the Harris score show no difference between the 2 groups. Patients are satisfied with their joint function and postoperative recovery.


The role of the factor V Leiden mutation in osteonecrosis of the hip.
We examined the hypothesis that the factor V Leiden (FVL) and G20101A prothrombin gene mutations are commonly associated with hip osteonecrosis. We prospectively evaluated 244 consecutively referred adults with osteonecrosis (ON), 161 idiopathic and 83 secondary. Cases (n = 244) did not differ from 104 normal controls by race. Of the 244 patients, 23 (9.4%) were FVL heterozygotes versus 2 of 104 controls (1.9%), P = .013, risk ratio (RR) = 4.90, 95% confidence interval (CI) 1.18 to 20.4. Of the 161 patients with idiopathic ON, 15 (9.3%) were FVL heterozygotes versus 2 of 104 normal controls (1.9%), P = .017, RR = 4.84, 95% CI 1.13 to 20.8. Of the 83 patients with secondary ON, 8 (9.6%) FVL heterozygotes versus 2 of 104 normal controls (1.9%), P = .024, RR = 5.01, 95% CI 1.09 to 23.0. Prothrombin gene heterozygosity in normal controls (2.9%) did not differ from ON cases (3.4%), P = 1.0. The thrombophilic FVL mutation is commonly associated with and may be pathoetiologic for hip osteonecrosis.


A case of laparoscopically detected cholangiocarcinoma of a few millimeters in size, with portal fibrosis.
A 54-year-old male with no subjective complaints was admitted to our hospital with fatty liver and low echoic lesion of 3 X 4 cm, thereafter revealed to be a hemangioma. A white lesion of few millimeters in size was detected in the left lobe of the liver at laparoscopic examination, and histologically diagnosed in an aimed biopsy as cholangiocarcinoma. Another 5 lesions (three white spots, a white longitudinal protrusion and a white lesion with a lacy pattern) suggestive of malignancy were also selectively biopsied, but all proved histologically negative. Microwave coagulation was applied to all biopsied sites as anti-cancer therapy.


[Oocyte donation: ethical aspects related to the donor].
This paper analyses the reasons that brings couples to apprehend very differently the oocyte and sperm donation and highlights the difficulty of donor recruitment in those programs. The various types of donors (occasional, relational, IVF patient and professional) are described with their motivations, resistances, advantages and disadvantages. The contradictory consequences between free or paid donation, the particular risks of eggs donation (in comparison to sperm donation) for the donor as for the recipient are also highlighted. The problem of anonymity is also analysed in ethical terms but also in terms of technical efficacy: it is shown that anonymity, by authorizing sharing oocytes between recipients increases treatment efficacy by avoiding wasting this rare and precious resource of oocytes offered as a donation.


Scaling of the space-time correlation function of particle currents in a suspension of hard-sphere-like particles: exposing when the motion of particles is Brownian.
The current correlation function is determined from dynamic light scattering measurements of a suspension of particles with hard spherelike interactions. For suspensions in thermodynamic equilibrium we find scaling of the space and time variables of the current correlation function. This finding supports the notion that the movement of suspended particles can be described in terms of uncorrelated Brownian encounters. However, in the metastable fluid, at volume fractions above freezing, this scaling fails.


Patient compliance with MAO inhibitor therapy.
Exaggerated fears of monoamine oxidase inhibitors (MAOIs) and of their interactions with foods often restrict their use. A review of the literature reveals seven food items most likely to produce a hypertensive crisis in combination with MAOI administration: aged cheeses, smoked or pickled fish, beef or chicken liver, dry fermented sausage, pods of broad beans, brewer's yeast products, and certain alcoholic beverages. Improved understanding of the dietary restrictions, benefits, and mechanism of action of the MAOIs can enhance cooperation with the prescribed treatment program.


Caries in preschool children in Amman, Jordan and the relationship to socio-demographic factors.
To determine the prevalence and severity of caries in children attending kindergartens in Amman and the relationship between caries experience and socio-demographic factors including age, social class based on the father's occupation, the level of mother's education and the fee level of the kindergarten attended. Cross sectional survey including a dental examination of the child and a questionnaire completed by the parents. Kindergarten schools in Amman. 1,140 children including 569 4-year-olds and 571 5-year-olds. Prevalence of caries in 4 year olds was 62% and in 5 year olds it was 73%. The dmft values were 3.1 and 4.1 in 4 and 5 year olds respectively. Lower caries prevalence was recorded for children of families where the father had a non-manual occupation, those whose mothers had higher levels of educational attainment and for children attending kindergartens with higher tuition fees. Caries prevalence and severity in children attending kindergarten schools in Amman are similar to those seen in studies of children of the same age in Saudi Arabia and higher than those in children in westernised countries such as the UK. As in other countries, caries experience in young children in Amman is clearly related to social factors. Findings illustrate the need for effective oral health promotion accessible to all social groups in this middle eastern capital. Fee scale of the schools appears to be an effective measure to use in designing appropriate strategies.


[Research progress of application of middle and lower cervical anterior transpedicular screw fixation].
To review the present situation of experimental study and clinical application of middle and lower cervical anterior transpedicular screw (CATPS) fixation. The literature on the CATPS fixation was reviewed and summarized. There is a safe area to implement the CATPS fixation and anterior decompression, and fusion can be done at the same time. It can provide a new idea for surgical treatment of complex cervical disease. Although it has so many advantages, its complex operating methods and optimal design of plate should be attended. Long-term effectiveness and specific indications still should be researched. Middle and lower cervical anterior transpedicular screw is an effective and safe fixation for cervical diseases. But the time for clinical use is short, the long-term effectiveness, surgical technique, and internal fixation devices are still need further study.


Intraorbital arteriovenous malformation: issues in surgical management.
Intraorbital arteriovenous malformations are infrequent but, when present, typically require complex surgical management. Computed tomography and magnetic resonance imaging help characterize lesion structure, location, and relationship to intraorbital anatomy. Frequently complex, intervention should be prompted by significant proptosis, increased intraocular pressure, pain, bleeding, ulceration, or high-output cardiac complications. For more controlled surgical debridement, angiographic embolization may help occlude the nidus and feeding vessels temporarily. Utmost caution must be taken to avoid injury to the optic nerve and ophthalmic artery. We present a rare case of complex, intraorbital arteriovenous malformation, as well as discuss aspects of management and relevant literature.


Symptoms of Prolonged Social Withdrawal, Problematic Internet Use, and Psychotic-Like Experiences in Emerging Adulthood: A Moderation Model.
Prolonged social withdrawal (PSW) or hikikomori and problematic internet use (PIU) have attracted the attention of mental health experts worldwide. The scientific literature suggests a complex relationship between these conditions and psychotic-like experiences (PLEs) or disorders. In the present cross-sectional study, we tested the role of PIU symptoms as a moderator of the relationship between symptoms of PSW and PLEs in a sample of 238 Italian emerging adults. Data was collected using the 25-item Hikikomori Questionnaire, the Internet Disorder Scale, the Brief Prodromal Questionnaire, and the Brief Symptom Inventory. In addition, lifetime psychological disorders and drug and alcohol use during the last month were explored. No participant reported a lifetime episode of schizophrenia or other psychotic disorder. Symptoms of PSW and PIU were significantly associated with PLEs total distress and PLEs total number of symptoms endorsed, after adjustment for age and symptoms of depression and anxiety. Further, PIU symptoms moderated the relationship between symptoms of PSW and PLEs total distress (b= 2.745, s.e.= 1.089, p= 0.012). However, PIU symptoms did not moderate the relationship between PSW and PLEs total symptoms (b= 0.615, s.e.= 0.349, p= 0.078). This study is limited because the participants were most likely university students and because of the cross-sectional design. Findings from this study partially support the role of high symptoms of PIU as a risk factor in the relationship between symptoms of PSW and PLEs. Future longitudinal research is needed to confirm our findings examining the temporal relationship between PSW, PIU, and PLEs using both dimensional and categorical approaches.


Identification of a highly immunogenic HLA-A*01-binding T cell epitope of WT1.
The transcription factor Wilms tumor protein 1 (WT1) belongs to a new generation of tumor antigens, as it is essential for tumor cell proliferation and is highly expressed in various hematologic and solid malignancies. The aim of this study was to apply a modified reverse immunology strategy to identify immunogenic epitopes of WT1 which could be useful for immunotherapy. Potential HLA-A*01 epitopes predicted by a MHC binding algorithm were screened for recognition by peripheral blood mononuclear cells (PBMC) from patients with spontaneous T cell responses using intracellular cytokine cytometry. Epitope processing was shown by proteasomal cleavage. Epitope-specific T cells were generated from CD4+CD25+ regulatory T cell-depleted PBMC. One of five predicted HLA-A*01-binding candidate epitopes showed high immunogenicity as 5 of 14 patients with hematologic malignancies had WT1.317-327-reactive T cells ranging from 0.4% to 1.5% of CD3+CD8+ T cells. Proteasomal degradation assays indicated the cleavage of WT1.317-327. The depletion of regulatory T cells from PBMCs enabled the rapid expansion of WT1.317-327-specific CTL, whereas no CTL could be generated from unfractionated PBMC. WT1.317-327-specific CTL efficiently lysed an autologous WT1-expressing tumor cell line but not HLA-A*01-negative WT1-expressing tumor cells. Immunogenicity of the epitope across histologies was verified by the demonstration of spontaneous ex vivo WT1.317-327-specific T cell responses in two of six patients with HLA-A*01-positive melanoma or lung cancer. In this study, a modified reverse immunology strategy was employed to identify a first immunogenic HLA-A*01-restricted T cell epitope of the tumor antigen WT1, which is of considerable interest for use in vaccination trials.


The biochemistry of bacteriolysis: paradoxes, facts and myths.
Degradation of cell wall components of certain microbial species following phagocytosis by neutrophils and macrophages might involve the activation, by leucocyte cationic proteins, of the bacterial autolytic wall enzymes, leading to bacteriolysis. Lysozyme (a distinct cationic agent), which is the main muramidase present in leucocytes and in body fluids, might function not only as an enzyme but also as a potent activator of autolysis. Sulphated polyelectrolytes, proteolytic enzymes and oxygen radicals, which are released in inflammatory sites, might inactivate the autolytic wall enzymes, leading to the accumulation of peptidoglycan-polysaccharide complexes within macrophages. Activated macrophages are instrumental in initiating chronic inflammatory reactions. Undegraded microbial cell wall components also function as immunomodulators and as enhancers of non-specific resistance to infections and to malignancy.


Exchange coupling in transition-metal complexes via density-functional theory: comparison and reliability of different basis set approaches.
Theoretical methods based on density-functional theory with Gaussian, plane waves, and numerical basis sets were employed to evaluate the exchange coupling constants in transition-metal complexes. In the case of the numerical basis set, the effect of different computational parameters was tested. We analyzed whether and how the use of pseudopotentials affects the calculation of the exchange coupling constants. For the three different basis sets, a comparison of the exchange coupling constants and spin distributions shows that both the plane-wave and the numerical basis set approaches are accurate and reliable alternatives to the more established Gaussian basis functions.


Isolating large nested deletions in bacterial and P1 artificial chromosomes by in vivo P1 packaging of products of Cre-catalysed recombination between the endogenous and a transposed loxP site.
A general approach for isolating large nested deletions in P1 artificial chromosomes (PACs) and bacterial artificial chromosomes (BACs) by retrofitting with a loxP site-containing Tn10 mini-transposon is described. Cre-mediated recombination between the loxP site existing in these clones and one introduced by transposition leads to deletions and inversions of the DNA between these sites. Large deletions are selectively recovered by transducing the retrofitted PAC or BAC clones with P1 phage. The requirement that both loxP sites in the cointegrate be packaged into a P1 head ensures that only large deletions are rescued. PCR analyses identified these deletions as products of legitimate recombination between loxP sites mediated by Cre protein. BACs produce deletions much more efficiently than PACs although the former cannot be induced to greater than unit copy in cells. Mammalian cell-responsive antibiotic resistance markers are introduced as part of the transposon into genomic clone deletions for subsequent functional analysis. Most importantly, the loxP site retrofitting and P1 transduction can be performed in the same bacterial host containing these clones directly isolated from PAC or BAC libraries. These procedures should facilitate physical and functional mapping of genes and regulatory elements in these large plasmids.


Aqueous two-phase assisted by ultrasound for the extraction of anthocyanins from Lycium ruthenicum Murr.
In this study, an efficient ultrasound-assisted aqueous two-phase extraction method was used for the extraction of anthocyanins from Lycium ruthenicum Murr. An ethanol/ammonium sulfate system was chosen for the aqueous two-phase system due to its fine partitioning and recycling behaviors. Single-factor experiments were conducted to determine the optimized composition of the system, and the response surface methodology was used for the further optimization of the ultrasound-assisted aqueous two-phase extraction. The optimal conditions were as follows: a salt concentration of 20%, an ethanol concentration of 25%, an extraction time of 33.7 min, an extraction temperature of 25°C, a liquid/solid ratio of 50:1 w/w, pH value of 3.98, and an ultrasound power of 600 W. Under the above conditions, the yields of anthocyanins reached 4.71 mg/g dry sample. For the further purification, D-101 resin was used, and the purity of anthocyanins reached 25.3%. In conclusion, ultrasound-assisted aqueous two-phase extraction was an efficient, ecofriendly, and economical method, and it may be a promising technique for extracting bioactive components from plants.


Transverse Pericardial Sinus Hematoma From Type A Aortic Dissection: A Diagnostic Challenge.
Ascending (type A) aortic dissection can rarely result in contained transverse pericardial sinus hematoma that compresses adjacent structures making diagnosis more challenging. We present a rare case of a 77-year-old man who presented with sudden-onset chest pain and was admitted for a presumed acute coronary syndrome. Coronary angiography did not show significant stenosis and ruled out acute coronary syndrome. Transthoracic echocardiogram showed extracardiac structure compressing on the left atrium; hence, we performed transesophageal echocardiogram which confirmed aortic dissection and revealed a hematoma in the transverse pericardial sinus. Intraoperatively, a large hematoma in the transverse pericardial sinus was extracted and revealed a posterior perforation of the ascending aorta that extended into the left atrium.


Metformin preferentially provides neuroprotection following cardiac ischemia/reperfusion in non-diabetic rats.
Following acute myocardial infarction, re-establishment of coronary perfusion aggravates further injuries in the heart and remote organs including the brain as a consequence of ischemia/reperfusion (I/R) injury. Since pretreatment with metformin attenuated both cardiac and cerebral I/R injury via AMP-activated protein kinase (AMPK) pathways, we hypothesized that metformin given after ischemia mitigates both cardiac and brain pathologies following cardiac I/R. Male Wistar rats were subjected to either cardiac I/R (30 min-ischemia/120 min-reperfusion; n = 30) or sham operation (n = 5). Metformin 200 mg/kg was given intravenously to the cardiac I/R group (n = 10/group), either during ischemia (D-MET) or at the onset of reperfusion (R-MET). Left ventricular ejection fraction (LVEF) and arrhythmia scores were determined. The heart and brain tissues were collected to determine the extent of injury, mitochondrial function, and apoptosis. Additionally, microglial morphology, Alzheimer's proteins, and dendritic spine density were determined in the brain. Cardiac I/R led to not only reduced LVEF, cardiac mitochondrial dysfunction, and arrhythmias, but also brain mitochondrial dysfunction, apoptosis, Alzheimer's protein aggregation, microglial activation, and dendritic spine loss. A single dose of metformin did not alter p-AMPK/AMPK in both organs. In the heart, impaired LVEF, arrhythmias, infarct size expansion, mitochondrial dysfunction, and apoptosis were not alleviated. On the contrary, metformin attenuated brain mitochondrial dysfunction, apoptosis, and Alzheimer's protein levels. Microglial morphology and dendritic spine density were additionally preserved in D-MET group. In conclusion, metformin given during ischemia preferentially provides neuroprotection against brain mitochondrial dysfunction, apoptosis, microglial activation, and dendritic spine loss in an AMPK-independent manner following cardiac I/R injury.


Differentiation between recurrent gliomas and radiation necrosis using arterial spin labeling perfusion imaging.
Arterial spin labeling (ASL) magnetic resonance (MR) perfusion imaging has been proposed as an effective method to measure brain tumor perfusion. The aim of the present study was to evaluate the utility of this technique in the differentiation of recurrent gliomas from radiation necrosis. Twenty-one patients with surgically treated primary gliomas, including 16 cases of recurrent glioma and 5 of radiation necrosis were examined using 3.0T MR imaging (MRI). ASL and dynamic susceptibility contrast-weighted (DSC) perfusion MRI scans were performed. Maps of normalized cerebral blood flow (CBF) in ASL imaging and cerebral blood volume (CBV) in DSC imaging were computed and analyzed in the regions of interest. In cases of glioma recurrence, the normalized ASL-CBF ratio (4.45±2.72) was higher than that in cases of radiation injury (1.22±0.61) (P<0.01). The normalized DSC-relative CBV ratio was also significantly higher in glioma recurrence (3.38±2.08) than it was in radiation injury (1.09±0.55) (P<0.05). A close linear correlation was found between the ASL and DSC MRI techniques (linear regression coefficient, R=0.85; P=0.005) in the differentiation of recurrent glioma from radiation injury. The results indicate that ASL perfusion is an accurate method of distinguishing between glioma recurrence and radiation necrosis.


Revision of Lutnes Cameron (Hymenoptera: Eupelmidae).
Argaleostatus Gibson, 1995 is synonymized under Lutnes Cameron, 1884 (Hymenoptera: Chalcidoidea: Eupelmidae: Eupelminae) n. syn. and its type species, Eupelmus testaceus Cameron, 1884, is transferred to Lutnes as L. testaceus (Cameron) n. comb. The species of Lutnes are revised and six species are recognized, including the type species, Lutnes ornaticornis Cameron, 1884, plus L. testaceus, L. biguttatus (Girault, 1913), and three new species, L. aurantimacula Gibson n. sp. (Ecuador), L. infucatus Gibson n. sp. (Ecuador), and L. afrotropicus Gibson n. sp. (Cameroon). The first five species are based on females from the Neotropical region, whereas the last species is based on a female from Cameroon. This Afrotropical record is the first for the genus outside of the Neotropical region. Males are unrecognized for the genus. Monophyly and relationships of the genus are discussed and the species are keyed and illustrated through macrophotography.


Plasma thermal effect on the relativistic current-filamentation and two-stream instabilities in a hot-beam warm-plasma system.
Based on fully kinetic model using drift-Maxwellian distributions and taking into account the transverse electrostatic field (TEF), it is shown that the current-filamentation instability (CFI) grows unexpectedly with the plasma temperature. The growth is attributed to the decreasing of the TEF as the plasma becomes hot. In the low-temperature plasma regime where the TEF is strong, it is identified that the TEF can dominate over the thermal pressure in suppressing the CFI. Since the TEF originates from the temperature difference between the beam and the plasma, the plasma temperature plays a significant role for the development of the CFI and the quasistatic magnetic fields in a hot-beam warm-plasma system. Particle-in-cell simulations verify the above results.