Influence of cholestatic jaundice on the weight variance in an experimental model.
To evaluate the influence of cholestatic jaundice in weight variation. We used 64 adult rats divided into six groups: F1 (n = 6): normal females; F2 (n = 6): laparotomy females; F3 (n = 20): jaundiced females; M1 (n = 6): normal males; M2 (n = 6): laparotomy males; M3 (n = 20): jaundiced males. Jaundice was obtained by ligation and section of the biliopancreatic duct. The animal weights were recorded weekly for seven weeks. On the 14th day of the experiment, bilirubin and gonadal hormones were assessed. After the seventh week a histological study of the liver was performed. The animals in groups F3 and M3 showed elevated bilirubin and decreased body mass when compared to the other groups. The weight differences were significant from the fourth week on amongst females and from the fifth in males. In Jaundiced animals there was increased estradiol and decreased progesterone and testosterone. Perivenular septa and periportal fibrosis, cholangitis and bile duct hyperplasia occurred in the liver of jaundiced rats. No animal showed cirrhosis. There was decrease in murine body weight in the presence of cholestatic jaundice in both genders.


Hydrophilic spacer-arm containing magnetic nanoparticles for immobilization of proteinase K: Employment for speciation of proteins for mass spectrometry-based analysis.
Proteinase K (ProK) is used for the degradation of proteins in cell lysates to isolate nucleic acids, and for the speciation of proteins for mass spectrometry analysis. In this work, a novel and sensitive immobilization process was developed for examination of protein mixtures by combining MALDI-ToF-MS and nLC-TIMS-ToF-MS/MS systems. To achieve these goals, magnetic nanoparticles (MPs) were prepared via thermal coprecipitation reaction under alkaline condition. The MPs were grafted with a silica layer (i.e., 3-(2,3-epoxypropoxy) propyltrimethoxysilane; EPTES) containing reactive epoxy groups. Then, the silica-grafted magnetic particles were coated with a long chain hydrophilic poly(ethylene glycol) diamine polymer (PEGDAP). The prepared materials were characterized by the Brunauer-Emmett-Teller (BET) method, X-ray diffraction (XRD), scanning electron microscopy (SEM) and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy. The VSM data show that the MPs@EPTES@PEGDAP has paramagnetic performance with a saturation magnetization of approximately 32.3 emu g-1. Proteinase K (EC 188.8.131.52) was covalently immobilized on the MPs@EPTES by reaction of its epoxy groups with amine groups of the enzyme. On the other hand, the ProK was immobilized on the MPs@EPTES@PEGDAP after activation with glutaraldehyde and the immobilization reaction was realized by the coupling reaction between aldehyde groups of the support and amine groups of the enzyme. The amounts of immobilized ProK on the MPs@EPTES and MPs@EPTES@PEGDAP were found to be 27.4 and 19.6 mg g-1and the retained activities were determined to be 29 and 87%, respectively. For the first time, some important features such as thermal and storage stabilities, reusability and potential use in protein speciation for mass spectrometry-based techniques were also evaluated. For examples, after six weeks of storage at 4 °C, the immobilized ProK on the MPs@EPTES@PEGDAP-ProK still maintained 59% of its initial activity. However, at the end of the six-week storage period, its free counterpart had lost all of its initial activity. The immobilized ProK was also utilized for degradation and identification of model proteins (i.e., α-2-HS glycoprotein, β-casein, bovine serum albumin and immunoglobulin). After enzymatic treatment, the digested peptides were analyzed and mapped by using nLC-TIMS-ToF-MS/MS systems.


[Surgical treatment of tuberculosis of non-pulmonary localization].
Experiments in 86 rabbits and observation of 360 patients have shown the antibacterial therapy to be of limited use for the treatment of non-pulmonary tuberculosis. It was found that the antibacterial therapy failed to result in healing the caseous-destructive foci and to cure turebculosis of kidneys, bones, joints, female genitals and lymph nodes. It is considered to be a reason for surgical procedures according to principles of the focal surgery on non-pulmonary tuberculosis elaborated by P. G. Kornev and his school.


Versatile carboxymethyl chitin and chitosan nanomaterials: a review.
Biocompatibility, biodegradability, and low cost of chitin and chitosan have drawn immense attention in many fields including medicine, bioinspired material science, pharmaceuticals, and agriculture. Their handling and processing are difficult owing to its insolubility in neutral aqueous solution or organic solvents. One of the methods used to improve the solubility characteristics of chitin and chitosan is chemical modification. Introducing a carboxymethyl group is the most advantageous method of increasing the solubility of chitosan at neutral and alkaline pH. Carboxymethyl chitin (CMC) and carboxymethyl chitosan (CMCS) are water soluble derivatives formed by introducing CH₂COOH function into the polymer which endows it with better biological properties. The functional group makes CMC/CMCS nanoparticles (NPs) efficient vehicles for the delivery of DNA, proteins, and drugs. This review provides an overview of the characteristics of CMC/CMCS NPs as well as fulfills the task of describing and discussing its important roles primarily in cancer nanomedicine detailing the targeted drug delivery aspect. The application of these NPs in imaging, agriculture, and textiles has also been highlighted. The review also elaborates the advantages of using the CMC and CMCS NPs for drug and gene delivery.


Efficient Electron Hopping Transport through Azurin-Based Junctions.
We conducted a theoretical study of electron transport through junctions of the blue-copper azurin from Pseudomonas aeruginosa. We found that single-site hopping can lead to either higher or lower current values compared to fully coherent transport. This depends on the structural details of the junctions as well as the alignment of the protein orbitals. Moreover, we show how the asymmetry of the IV curves can be affected by the position of the tip in the junction and that, under specific conditions, such a hopping mechanism is consistent with a fairly low temperature dependence of the current. Finally, we show that increasing the number of hopping sites leads to higher hopping currents. Our findings, from fully quantum calculations, provide deep insight to help guide the interpretation of experimental IV curves on highly complex systems.


Frontal dysfunction in patients with restless legs syndrome performing a visual oddball task: an event-related potential source imaging study.
Restless legs syndrome (RLS) is a sensorimotor neurological disorder that is accompanied by the compelling urge to move one's legs, and unpleasant, disturbing sensations in the legs. Several neuropsychological studies have shown that RLS is associated with deficits in cognitive functions, such as attention, working memory, and frontal executive function, presumably due to abnormal frontal activities. However, the mechanism underlying the cognitive deficits in RLS patients is mostly unknown. To investigate the cortical origin of cognitive dysfunction in RLS, we analyzed the P2 and P3 event-related potential (ERP) components evoked by a visual oddball task using distributed cortical source localization via low-resolution brain electromagnetic tomography (LORETA) algorithm. A total of 17 female drug-naive RLS patients and 13 healthy volunteers were enrolled. Multichannel ERPs were recorded while performing a visual oddball task. We identified that the P2 and P3 ERP components were significantly reduced in RLS patients. These patients showed a reduction of the cortical current source densities in temporal periods corresponding to P2 and P3, compared to normal controls. Significant differences between RLS patients and normal controls were mainly found in the frontal region; that is, in the medial prefrontal cortex at the P2 epoch and the anterior cingulate cortex at the P3 epoch. Our neurophysiological results imply that the abnormal activities in the frontal region results in a cognitive deficit in RLS patients, which should be compared with neuropsychological evaluations in a further study.


[Globalization, the Camisea Project and the Matsigenkas health].
Globalization has been the consequence of an important opening of the economies, achieved through the reduction in the obstacles to commerce, elimination of the capital controls and exchange restrictions. The impact of the Camisea Project in the Peruvian economy has aroused great interest and controversy with respect to the future social and economic national impact, and especially, in the Matsigenka population, located in the 88 and 56 lots, where gas extraction is being done. The area of Camisea gas exploitation offers the challenge of a complex sanitary problem, not only because of the impacts and risks produced by the hidrocarbon exploitation, but also due to a legacy of economical and sanitary precariousness that has accumulated from other times. At the same time, this area offers the opportunity to rethink the public health system according to the indigenous reality. It is necessary to take action in the social determinants of inequity and poverty in order to reach the positive effects the globalization can have in health, ensuring the interests of developing countries and vulnerable populations.


Dependence and caregiver burden in Alzheimer's disease and mild cognitive impairment.
The dependence scale has been designed to be sensitive to the overall care needs of the patient and is considered distinct from standard measures of functional ability in this regard. Little is known regarding the relationship between patient dependence and caregiver burden. We recruited 100 patients with Alzheimer's disease or mild cognitive impairment and their caregivers through a memory clinic. Patient function, dependence, hours of care, cognition, neuropsychiatric symptoms, and caregiver burden were assessed. Dependence was significantly correlated with caregiver burden. Functional decline and dependence were most predictive of caregiver burden in patients with mild impairment while behavioral symptoms were most predictive in patients with moderate to severe disease. The dependence scale demonstrated good utility as a predictor of caregiver burden. Interventions to reduce caregiver burden should address patient dependence, functional decline, and behavioral symptoms while successful management of the latter becomes more critical with disease progression.


Modeling Breast Cancer in Human Breast Tissue using a Microphysiological System.
Breast cancer (BC) remains a leading cause of death for women. Despite more than $700 million invested in BC research annually, 97% of candidate BC drugs fail clinical trials. Therefore, new models are needed to improve our understanding of the disease. The NIH Microphysiological Systems (MPS) program was developed to improve the clinical translation of basic science discoveries and promising new therapeutic strategies. Here we present a method for generating MPS for breast cancers (BC-MPS). This model adapts a previously described approach of culturing primary human white adipose tissue (WAT) by sandwiching WAT between adipose-derived stem cell sheets (ASC)s. Novel aspects of our BC-MPS include seeding BC cells into non-diseased human breast tissue (HBT) containing native extracellular matrix, mature adipocytes, resident fibroblasts, and immune cells; and sandwiching the BC-HBT admixture between HBT-derived ASC sheets. The resulting BC-MPS is stable in culture ex vivo for at least 14 days. This model system contains multiple elements of the microenvironment that influence BC including adipocytes, stromal cells, immune cells, and the extracellular matrix. Thus BC-MPS can be used to study the interactions between BC and its microenvironment. We demonstrate the advantages of our BC-MPS by studying two BC behaviors known to influence cancer progression and metastasis: 1) BC motility and 2) BC-HBT metabolic crosstalk. While BC motility has previously been demonstrated using intravital imaging, BC-MPS allows for high-resolution time-lapse imaging using fluorescence microscopy over several days. Furthermore, while metabolic crosstalk was previously demonstrated using BC cells and murine pre-adipocytes differentiated into immature adipocytes, our BC-MPS model is the first system to demonstrate this crosstalk between primary human mammary adipocytes and BC cells in vitro.


Nitric oxide fumigation for postharvest pest control on lettuce.
The lettuce aphid, Nasonovia ribisnigri, and western flower thrips, Frankliniella occidentalis, are quarantine pests of lettuce in Asian markets and, therefore, require treatments on lettuce exported from USA to Japan and Taiwan, respectively. Nitric oxide (NO) is a newly discovered fumigant for postharvest pest control and has been demonstrated as safe to fresh fruit and vegetables. In this study, small-scale NO fumigations were conducted to determine effective treatments and large-scale confirmatory tests were conducted to determine the efficacy against N. ribisnigri and F. occidentalis on commercially packed lettuce. The safety of NO fumigation to postharvest quality of lettuce was also evaluated. In small-scale experiments, complete control of N. ribisnigri was achieved in 3, 8, and 16 h fumigations with 2.0%, 1.0%, and 0.5% NO, respectively, at 2 °C on both iceberg and romaine lettuce. In a large-scale experiment, complete control of both N. ribisnigri and F. occidentalis was achieved in a 16 h fumigation with 0.5% NO at 2 °C. The fumigation treatment had no effect on either external or internal postharvest quality of lettuce at 14 days after treatment. Nitric oxide fumigation was demonstrated to be effective against both N. ribisnigri and F. occidentalis and safe to lettuce quality in large-scale fumigations of commercially packed lettuce. The study suggests that NO fumigation has the potential to be an alternative treatment to methyl bromide for postharvest pest control on harvested lettuce. © 2018 Society of Chemical Industry.


A novel HDAC1/2 inhibitor suppresses colorectal cancer through apoptosis induction and cell cycle regulation.
Colorectal cancer (CRC) is one of the leading causes of death around the world, and synthetic chemicals targeting specific proteins or various molecular pathways for tumor suppression, such as histone deacetylases (HADC) inhibitors, are under intensively studied. The target of HDAC involves in regulating critical cellular mechanisms and underpins the progression of anticancer therapy. However, little is known about the antitumor mechanisms of class I specific HDAC inhibitors in CRC. We structurally designed and synthesized benzamide-based compounds, examined their anticancer activity in several solid tumors, and identified compound 9 with high potential. Results from the in vitro enzyme and cell-based studies demonstrated that compound 9 as a selective HDAC1/2 inhibitor that possessed short-term and long-term suppression capacities against colorectal cancer cells. Investigation of molecular regulatory mechanisms of 9 in colorectal cancer cells by biological functional assays evidenced that treatment of compound 9 could activate apoptosis, induce cell cycle arrest, facilitate DNA damage process, and suppress cancer migration. A non-cancerous cell line and the in vivo zebrafish model were applied for safety evaluation. In summary, our results demonstrate that compound 9 is a promising lead drug worth further investigation for development of future cancer therapeutic agents.


Purinergic and nitrergic junction potential in the human colon.
The aim of the present work is to investigate a putative junction transmission [nitric oxide (NO) and ATP] in the human colon and to characterize the electrophysiological and mechanical responses that might explain different functions from both neurotransmitters. Muscle bath and microelectrode techniques were performed on human colonic circular muscle strips. The NO donor sodium nitroprusside (10 microM), but not the P2Y receptor agonist adenosine 5'-O-2-thiodiphosphate (10 microM), was able to cause a sustained relaxation. NG-nitro-L-arginine (L-NNA) (1 mM), a NO synthase inhibitor, but not 2'-deoxy-N6-methyl adenosine 3',5'-diphosphate tetraammonium salt (MRS 2179) (10 microM), a P2Y antagonist, increased spontaneous motility. Electrical field stimulation (EFS) at 1 Hz caused fast inhibitory junction potentials (fIJPs) and a relaxation sensitive to MRS 2179 (10 microM). EFS at higher frequencies (5 Hz) showed biphasic IJP with fast hyperpolarization sensitive to MRS 2179 followed by sustained hyperpolarization sensitive to L-NNA; both drugs were needed to fully block the EFS relaxation at 2 and 5 Hz. Two consecutive single pulses induced MRS 2179-sensitive fIJPs that showed a rundown. The rundown mechanism was not dependent on the degree of hyperpolarization and was present after incubation with L-NNA (1 mM), hexamethonium (100 microM), MRS 2179 (1 microM), and NF023 (10 microM). We concluded that single pulses elicit ATP release from enteric motor neurons that cause a fIJP and a transient relaxation that is difficult to maintain over time; also, NO is released at higher frequencies causing a sustained hyperpolarization and relaxation. These differences might be responsible for complementary mechanisms of relaxation being phasic (ATP) and tonic (NO).


Financial advantages of operating a skilled nursing unit.
Hospitals may accrue specific financial advantages from the operations of a skilled nursing unit (SNU), such as the ability to allocate some fixed costs to a hospital-based unit that receives cost-based reimbursement from Medicare. The level of reimbursement SNUs receive from Medicare, however, can be optimized by obtaining an exemption or an exception to routine cost limits.


ALK1 Gene Rearranged Pulmonary Sarcomatoid Carcinoma Masquerading as Tuberculosis in a Young Male.
Pulmonary sarcomatoid carcinoma is rare, with limited treatment options and poor prognosis. In contrast to other non small cell lung carcinomas, not much is known about its molecular biology. In an endemic country like India, lung cancer is often masked by tuberculosis and presents in advanced stages. We report here an unusual case of pulmonary sarcomatoid carcinoma, in a young non-smoker male, who had co-existent tuberculosis masking and delaying the diagnosis of malignancy. On molecular study, the tumor showed ALK gene rearrangement, both by immunohistochemistry and fluorescence in-situ hybridization, which has been reported only twice previously. Presence of ALK gene rearrangements in sarcomatoid carcinoma has significant therapeutic implications and potential for altering the prognosis of this fatal disease. Hence we recommend performing ALK gene rearrangement analysis in all cases of sarcomatoid lung carcinomas. The report discusses the diagnostic approach and provides insight into the molecular pathogenesis of this exceedingly rare malignancy.


Tart cherry supplementation improves working memory, hippocampal inflammation, and autophagy in aged rats.
High consumption of fruits and vegetables has been associated with reduced risk of debilitating diseases and improved cognition in aged populations. These beneficial effects have been attributed to the phytochemicals found in fruits and vegetables, which have previously been shown to be anti-inflammatory and modulate autophagy. Tart cherries contain a variety of potentially beneficial phytochemicals; however, little research has been done to investigate the effects of tart cherry on the aging brain. Therefore, the purpose of this study was to determine if tart cherry supplementation can improve cognitive and motor function of aged rats via modulation of inflammation and autophagy in the brain. Thirty 19-month-old male Fischer 344 rats were weight-matched and assigned to receive either a control diet or a diet supplemented with 2 % Montmorency tart cherry. After 6 weeks on the diet, rats were given a battery of behavioral tests to assess for strength, stamina, balance, and coordination, as well as learning and working memory. Although no significant effects were observed on tests of motor performance, tart cherry improved working memory of aged rats. Following behavioral testing, the hippocampus was collected for western/densitometric analysis of inflammatory (GFAP, NOX-2, and COX-2) and autophagy (phosphorylated mTOR, Beclin 1, and p62/SQSTM) markers. Tart cherry supplementation significantly reduced inflammatory markers and improved autophagy function. Daily consumption of tart cherry reduced age-associated inflammation and promoted protein/cellular homeostasis in the hippocampus, along with improvements in working memory. Therefore, addition of tart cherry to the diet may promote healthy aging and/or delay the onset of neurodegenerative diseases.


Inhibition of Ni release from NiTi and NiTiCu orthodontic archwires by nitrogen diffusion treatment.
The effects of nickel (Ni) allergy from NiTi alloys were reduced due to the titanium nitrided coating obtained by nitrogen gas diffusion at different temperatures. The samples were immersed in artificial saliva at 37 degrees C for different periods demonstrating that the titanium nitride coating prevents biodegradation. In addition, the lack of low friction coefficient for the NiTi super-elastic archwires makes the optimal use of these materials in orthodontic applications difficult. In this study, the reduction in this friction coefficient was achieved by nitrogen diffusion heat treatments. (Journal of Applied Biomaterials & Biomechanics 2004; 2: 151-5).


Changes in dog gracilis muscle adenosine during exercise and acetate infusion.
We have previously reported that tissue acetate content increases in the canine gracilis muscle during exercise at natural flow. We here report the effects of exercise and infusion of acetate on adenosine content. Muscles were vascularly isolated, perfused naturally, and stimulated to contract isometrically at 0.5, 1.0, or 2.0 Hz for 10 min (n = 6 each). Exercising and contralateral control gracilis muscles were freeze clamped in situ in Wollenberger tongs at the temperature of liquid N2. Force development was maintained during contraction. Resistance decreased as a function of contraction frequency, and adenosine content increased. Tissue adenosine content correlated inversely with resistance (r = -0.57, P less than 0.001), suggesting a role for adenosine in exercise hyperemia. During intra-arterial infusion of sodium acetate into resting muscle, tissue acetate and adenosine contents increased (417-2,193 and 0.88-3.07 nmol/g, respectively), and vascular resistance decreased (17.5-6.01 mmHg X ml-1/min/100 g). Acetate and adenosine contents correlated negatively with resistance (r = -0.83, P less than 0.001, and r = -0.60, P less than 0.05, respectively) and positively with one another (r = 0.58, P less than 0.05). Relative to an infusion of sodium chloride, oxygen consumption, venous PO2, and venous ionized calcium were unaffected. The vasodilatory effect of acetate may be due, in part, to its ability to increase tissue adenosine.


Mapping the tree of life: progress and prospects.
The intent of this article is to provide a critical assessment of our current understanding of life's phylogenetic diversity. Phylogenetic comparison of gene sequences is a natural way to identify microorganisms and can also be used to infer the course of evolution. Three decades of molecular phylogenetic studies with various molecular markers have provided the outlines of a universal tree of life (ToL), the three-domain pattern of archaea, bacteria, and eucarya. The sequence-based perspective on microbial identification additionally opened the way to the identification of environmental microbes without the requirement for culture, particularly through analysis of rRNA gene sequences. Environmental rRNA sequences, which now far outnumber those from cultivars, expand our knowledge of the extent of microbial diversity and contribute increasingly heavily to the emerging ToL. Although the three-domain structure of the ToL is established, the deep phylogenetic structure of each of the domains remains murky and sometimes controversial. Obstacles to accurate inference of deep phylogenetic relationships are both systematic, in molecular phylogenetic calculations, and practical, due to a paucity of sequence representation for many groups of organisms.


Deception dissociates from false belief reasoning in deaf children: implications for the implicit versus explicit theory of mind distinction.
Deception is a controversial aspect of theory of mind, and researchers disagree about whether it entails an understanding of the false beliefs of one's opponent. The present study asks whether children with delayed language and delayed explicit false belief reasoning can succeed on explicit deception tasks. Participants were 45 orally taught deaf children with varying language delays aged 4.5-8 years and 45 hearing children aged 3.5-6 years. Participants received a battery of language, executive function, deception, and both verbal and low-verbal false belief tasks. The result reveal a dissociation of deception and false belief tasks: the deaf children are on par with their hearing peers on deception games, but show significant delays in false belief tasks even when the language demands are made minimal. Furthermore, different skills are predictors of success for the two types of task in the deaf children: language, and in particular complement syntax, is the best predictor of false belief reasoning; but executive function skills, especially inhibitory control, are the best predictors of deception. It is argued that deception at this level can be handled by behaviour rules without reference to mental states.


Indentation Depth-Dependent Hardness of Metal-Organic Framework Crystals: The Effect of Local Amorphization Induced by Indentation.
The hardness of metal-organic frameworks (MOFs) is an important mechanical property metric measuring their resistance to the permanent plastic deformation. The hardness of most MOFs measured from nanoindentation experiments usually exhibits the similar unique indentation depth dependence feature, the mechanism of which still remains unclear. In order to explain the effect of the indentation depth on the hardness of MOFs, we conducted nanoindentation simulations on HKUST-1 by using reactive molecular dynamics simulations. Our simulations reveal that the HKUST-1 material near the indenter can transform from the parent crystalline phase to a new amorphous phase due to the high pressure generated, while its counterpart far from the indenter remains in the crystalline phase. By considering the crystalline-amorphous interface in the energy analysis of MOFs, we derived an analytical expression of the hardness at different indentation depths. It is found that the interface effect can greatly increase the hardness of MOFs, as observed in nanoindentation simulations. Moreover, the proposed analytical expression can well explain the indentation depth-dependent hardness of many MOF crystals measured in nanoindentation experiments. Overall, this work can provide a better understanding of the indentation depth dependence of the hardness of MOFs.


The effect of substituents on the surface modification of anatase nanoparticles with catecholate-type ligands: a combined DFT and experimental study.
The surface modification of nanocrystalline TiO2 particles (45 Å) with catecholate-type ligands having different electron donating/electron withdrawing substituent groups, specifically 3-methylcatechol, 4-methylcatechol, 3-methoxycatechol, 3,4-dihydroxybenzaldehyde and 4-nitrocatechol, was found to alter the optical properties of nanoparticles in a similar way to catechol. The formation of the inner-sphere charge-transfer (CT) complexes results in a red shift of the semiconductor absorption compared to unmodified nanocrystallites and a reduction of the effective band gap, being slightly less pronounced in the case of electron withdrawing substituents. The investigated ligands have the optimal geometry for binding to surface Ti atoms, resulting in ring coordination complexes of the catecholate type (binuclear bidentate binding-bridging) thus restoring six-coordinated octahedral geometry of surface Ti atoms. From the absorption measurements (Benesi-Hildebrand plot), the stability constants in methanol/water = 90/10 solutions at pH 2 in the order of 10(3) M(-1) have been determined. The binding structures were investigated by using FTIR spectroscopy. Thermal stability of CT-complexes was investigated by using TG/DSC/MS analysis. Quantum chemical calculations on model systems using density functional theory (DFT) were performed to obtain the vibrational frequencies of charge transfer complexes, and the calculated values were compared with the experimental data.


Lymphangioleiomyomatosis: what do we know and what are we looking for?
Lymphangioleiomyomatosis (LAM) is a rare disease characterised by proliferation of abnormal smooth muscle-like cells (LAM cells) leading to progressive cystic destruction of the lung, lymphatic abnormalities and abdominal tumours. It affects predominantly females and can occur sporadically or in patients with tuberous sclerosis complex. This review describes the recent progress in our understanding of the molecular pathogenesis of the disease and LAM cell biology. It also summarises current therapeutic approaches and the most promising areas of research for future therapeutic strategies.


Oryza sativa polyamine oxidase 1 back-converts tetraamines, spermine and thermospermine, to spermidine.
Oryza sativa polyamine oxidase 1 back-converts spermine (or thermospermine) to spermidine. Considering the previous work, major path of polyamine catabolism in rice plant is suggestive to be back-conversion but not terminal catabolism. Rice (Oryza sativa) contains seven genes encoding polyamine oxidases (PAOs), termed OsPAO1 to OsPAO7, based on their chromosomal number and gene ID number. We previously showed that three of these members, OsPAO3, OsPAO4 and OsPAO5, are abundantly expressed, that their products localize to peroxisomes and that they catalyze the polyamine back-conversion reaction. Here, we have focused on OsPAO1. The OsPAO1 gene product shares a high level of identity with those of Arabidopsis PAO5 and Brassica juncea PAO. Expression of OsPAO1 appears to be quite low under physiological conditions, but is markedly induced in rice roots by spermine (Spm) or T-Spm treatment. Consistent with the above finding, the recombinant OsPAO1 prefers T-Spm as a substrate at pH 6.0 and Spm at pH 8.5 and, in both cases, back-converts these tetraamines to spermidine, but not to putrescine. OsPAO1 localizes to the cytoplasm of onion epidermal cells. Differing in subcellular localization, four out of seven rice PAOs, OsPAO1, OsPAO3, OsPAO4 and OsPAO5, catalyze back-conversion reactions of PAs. Based on the results, we discuss the catabolic path(s) of PAs in rice plant.


Universal scaling of optimal current distribution in transportation networks.
Transportation networks are inevitably selected with reference to their global cost which depends on the strengths and the distribution of the embedded currents. We prove that optimal current distributions for a uniformly injected d -dimensional network exhibit robust scale-invariance properties, independently of the particular cost function considered, as long as it is convex. We find that, in the limit of large currents, the distribution decays as a power law with an exponent equal to (2d-1)/(d-1). The current distribution can be exactly calculated in d=2 for all values of the current. Numerical simulations further suggest that the scaling properties remain unchanged for both random injections and by randomizing the convex cost functions.


Investigation of nanotopography on SOCE mediated cell migration via live-cell : Imaging on opaque implant surface.
The exploration of cell response to nanotopography has attracted considerable attentions for years. This article focuses on the influence of nanotopography on the intracellular Ca2+ dynamics, the most ubiquitous but ignored second messenger. The classic titanium nanotubes (NT) were fabricated by anodization to formulate nanoporous surfaces. Firstly, the store operative calcium entry (SOCE) in endoplasmic reticulum (ER) and functional Ca2+ release-activated Ca2+ (CRAC) channels were significantly enhanced on NT surfaces that revealed by live-cell Ca2+ imaging and fluorescence resonance energy transfer (FRET) identification of orai1-stim1 connection. To investigate the potential implication of Ca2+ elevation, the dynamic cell migration trajectory was monitored by a self-made holder, which could not only be suitable for the opaque implant surface but also guarantee the focus fields identical during samples shifting. The cell migration on NT surface was more vigorous and rapid, which was correlated with higher focal adhesion proteins expression, Ca2+-dependent calpain activity and stim1 level. In conclusion, this study has confirmed the novel ER Ca2+ hemostasis pathway on nanosurfaces and its crucial role in cell migration regulation, which may help for more biofavorable implant surface design.


Increased biliary transferrin excretion following parenteral aluminium administration to rats.
Aluminium accumulates in the livers of patients receiving either parenteral nutrition or haemodialysis. When given parenterally to rats, aluminium causes cholestasis. However, the mechanism of hepatic aluminium uptake and the fate of aluminum in the liver are poorly understood. We examined the effect of parenteral aluminium administration on biliary excretion of transferrin, the major circulating aluminum-binding protein. Male Wistar rats were given parenterally aluminum 5 mg/kg/day for 1-14 days. Bile was collected for 3 hr at the end of the study period. Biliary total protein concentration and IgA/total protein were unaffected by up to 14 days of parenteral aluminium administration. However, biliary transferrin excretion increased with duration of aluminum administration up to five-fold by day 14. Biliary transferrin concentration and transferrin/total protein was higher in aluminum treated rats than controls after 7 and 14 days of study. Hepatic aluminum concentration reached a maximum after 4 days of parenteral aluminum administration, at which time serum bile acid and alanine amino transferase values were not different from controls. Since biliary transferrin is normally derived from the serum, it is likely that aluminum promotes hepatocellular uptake of transferrin and that aluminum enters the hepatocyte bound to transferrin. We postulate that transferrin may direct aluminum to intracellular sites where its toxic effects would be minimized.


Toxic wavelength of blue light changes as insects grow.
Short-wavelength visible light (blue light: 400-500 nm) has lethal effects on various insects, such as fruit flies, mosquitoes, and flour beetles. However, the most toxic wavelengths of blue light might differ across developmental stages. Here, we investigate how the toxicity of blue light changes with the developmental stages of an insect by irradiating Drosophila melanogaster with different wavelengths of blue light. Specifically, the lethal effect on eggs increased at shorter light wavelengths (i.e., toward 405 nm). In contrast, wavelengths from 405 to 466 nm had similar lethal effects on larvae. A wavelength of 466 nm had the strongest lethal effect on pupae; however, mortality declined as pupae grew. A wavelength of 417 nm was the most harmful to adults at low photon flux density, while 466 nm was the most harmful to adults at high photon flux density. These findings suggest that, as the morphology of D. melanogaster changes with growth, the most harmful wavelength also changes. In addition, our results indicated that reactive oxygen species influence the lethal effect of blue light. Our findings show that blue light irradiation could be used as an effective pest control method by adjusting the wavelength to target specific developmental stages.


Large-scale implementation of sequential protein and peptide immunoaffinity enrichment LC/nanoLC-MS/MS for human β-nerve growth factor.
A previously described immunoaffinity (IA)-LC-MS/MS assay for human β-nerve growth factor (β-NGF) was implemented to support large-scale sample testing for multiple clinical trials. Methodology & results: The procedure was modified to increase throughput by simultaneous preparation of two 96-well plates and LC duty-cycle reduction. Robustness of the LC method and nano-ESI was ensured during large-scale assay execution by closely monitoring and, if needed, replacing system components prior to failure. Following validation, the assay was used to analyze approximately 19,000 samples from multiple clinical studies over several years. Routine implementation of the β-NGF IA-LC-MS/MS assay supported drug development programs. This optimized assay format now serves as a template for other clinical protein biomarker assays.


Relationship between spine osteoarthritis, bone mineral density and bone turn over markers in post menopausal women.
Several studies have observed an inverse relationship between osteoporosis and spinal osteoarthritis, the latter being considered as possibly delaying the development of osteoporosis. The aim of this study was to determine the association between individual radiographic features of spine degeneration, bone mineral density (BMD) and bone-turn over markers. It was a cross sectional study of 277 post menopausal women. BMD of all patients was assessed at the spine and hip using dual-energy X-ray absorptiometry. Lateral spinal radiographs were evaluated for features of disc degeneration. Each vertebral level from L1/2 to L4/5 was assessed for the presence and severity of osteophytes and disc space narrowing (DSN). For Bone turn-over markers, we assessed serum osteocalcin and C-terminal cross-linking telopeptide of type I collagen (CTX). Linear regressions and partial correlation were used respectively to determine the association between each of disc degeneration features, BMD, and both CTX and osteocalcin. Mean age of patients was 58.7 +/- 7.7 years. Eighty four patients (31.2%) were osteoporotic and 88.44% had spine osteoarthritis. At all measured sites, there was an increase in BMD with increasing severity of disc narrowing while there was no association between severity of osteophytes and BMD. After adjustment for age and BMI, there was a significant negative correlation between CTX and DSN. However, no significant correlation was found between CTX and osteophytes and between osteocalcin and both osteophytes or DSN. In post menopausal women the severity of disc narrowing, but not osteophytes, is associated with a generalized increase in BMD and a decreased rate of bone resorption. These results are consistent with the hypothesis that osteoarthritis, through DSN, has a protective effect against bone loss, mediated by a lower rate of bone resorption. However, spine BMD is not a relevant surrogate marker for the assessment of osteoporosis in the spine in patients with osteoarthritis and debate as to the relationship between OA and OP is still open because of the contradictory data in the literature.


Evaluation of Abbreviated Impactor Measurements (AIM) and Efficient Data Analysis (EDA) for Dry Powder Inhalers (DPIs) Against the Full-Resolution Next Generation Impactor (NGI).
The full-resolution next generation impactor (NGI) and three abbreviated impactor systems were used to obtain the apparent aerodynamic particle size distribution (APSD) and other quality measures for marketed dry powder inhalers (DPIs) using the compendial method and efficient data analysis (EDA). APSD for the active pharmaceutical ingredient (API) in Spiriva® Handihaler®, Foradil® Aerolizer®, and Relenza® Diskhaler® was obtained using a full-resolution NGI at 39, 60, and 90 L/min, respectively. Two reduced NGI (rNGI) configurations, the filter-only configuration (rNGI-f) and the modified-cup configuration (rNGI-mc), and the fast-screening impactor (FSI) with appropriate inserts to provide a 5-μm cut size were evaluated. The fine particle dose (FPD) obtained using the FSI for Spiriva was statistically similar to that obtained using the full NGI. However, the FPD for both Foradil and Relenza obtained using the FSI was significantly different from that obtained using the full NGI. Despite this, no significant differences were observed for the fine particle fraction (FPF) obtained using the FSI relative to that obtained from the full NGI for any of the DPIs. The use of abbreviated impactor systems appears promising with good agreement observed with the full-resolution NGI, except for small differences observed for the rNGI-mc configuration. These small differences may be product- and/or flow rate-specific, and further evaluation will be required to resolve these differences.


Assessment of quality of care for hospitalized non-COVID-19 older adult patients with pneumonia before and after the COVID-19 pandemic.
There is limited research into the clinical implications of the coronavirus disease 2019 (COVID-19) pandemic for non-COVID-19 pneumonia in older adults, as well as their quality of care or outcomes. This study aims to assess the process and outcome quality of care for hospitalized older adult patients with pneumonia before and after the pandemic. A retrospective cohort of older adult patients (age ≥ 65) hospitalized for non-COVID pneumonia were recruited from five Korean hospitals (January 20, 2019, to January 19, 2021). The quality of care before and after the COVID-19 pandemic was evaluated. A total of 7356 hospitalization episodes of older adult pneumonia were identified, and 978 cases (552 pre-pandemic and 426 during the pandemic) were analyzed. The pneumonia severity score was higher during the pandemic, and the waiting time from the emergency room to admission was also longer. Furthermore, the pneumonia mortality rate during the pandemic was higher than that in the pre-pandemic period (in-hospital mortality: 10.1% vs. 18.1%; 90-day mortality: 11.6% vs. 22.3%). A significantly higher mortality risk was observed during the pandemic than in the period prior (adjusted odds ratio: 1.74, 95% confidence interval: 1.14-2.63). While the quality of care for hospitalized pneumonia has been maintained during the pandemic, there has been an increase in mortality rates. Further investigations are needed to understand the underlying causes of this increase.


Legumin- and vicilin-like proteins from spores of the fern Matteuccia struthiopteris.
Legumin- and vicilin-like proteins have been isolated from spores of the fern Matteuccia struthiopteris. Their relationship with seed legumin and vicilin was demonstrated by cross-reactivities of antibodies directed against respective storage globulins from Vicia faba as evidenced by Western blotting. The Matteuccia legumin-like protein was characterised as a 300-340 kDa holoprotein preferentially consisting of a 32 kDa alpha-chain and a 24 kDa beta-chain. Patterns of limited proteolysis of the spore legumin-like protein and seed legumins were similar as well. In contrast to seed legumins, the Matteuccia legumin-like protein is devoid of disulfide bridges between alpha- and beta-chains. A 52 kDa polypeptide of the Matteuccia vicilin-like protein, first detected by SDS gel electrophoresis, is probably encoded by a vicilin-like gene specifically expressed in Matteuccia struthiopteris spores (Shutov et al. 1998). The vicilin-like holoprotein was found to form a complex of 600 kDa apparent molecular mass, presumably composed of four vicilin-like trimers.


Anterior and posterior neck muscle activation during a variety of biting tasks.
Bruxism may be involved in the aetiology of myofascial neck pain. The objective of this study was to test the hypothesis that anterior and posterior neck muscles co-contract during jaw clenching. Ten test subjects developed different feedback-controlled submaximum bite forces in a variety of bite-force directions by means of bite-force transducers. The electromyographic activity of the sternocleidomastoid and supra/infrahyoidal muscles, and of the semispinalis capitis, semispinalis cervicis, and multifidi muscles was recorded by use of surface electrodes and intramuscular wire electrodes, respectively. For normalization of electromyography data, maximum voluntary contraction tasks of the neck muscles were conducted in eight different loading directions. The results confirmed co-contraction of the neck muscles in the range of 2-14% of the maximum voluntary contraction at a bite force ranging from 50 to 300 N. Significant activity differences were observed as a result of the different force levels and force directions exerted by the jaw muscles. Long-lasting tonic activation of specific neck muscles triggered by the jaw-clenching tasks was also detected. These findings support the assumption of a relationship between jaw clenching and the activity of the neck muscles investigated. The low level of co-contraction activity, however, requires further study to elucidate possible pathophysiological interactions at the level of single motor units.


[Parasitic Acari of wild boar (Sus scrofa L.) from Pomerania lake district].
In years 1994-1998, 553 Wild Boars (Sus scrofa L.) were examined in the area of north-western part of Poland. Four species of parasitic acarids were found: Demodex phylloides, Sarcoptes scabiei, Dermacentor reticulatus and Ixodes ricinus. The highest infestation was observed in the case of D. phylloides (30%), the next from the top was presented by Ixodes ricinus (17%). S. scabiei and D. reticulatus occured seldom.


4D Flow Assessment of Vorticity in Right Ventricular Diastolic Dysfunction.
Diastolic dysfunction, a leading cause of heart failure in the US, is a complex pathology which manifests morphological and hemodynamic changes in the heart and circulatory system. Recent advances in time-resolved phase-contrast cardiac magnetic resonance imaging (4D Flow) have allowed for characterization of blood flow in the right ventricle (RV) and right atrium (RA), including calculation of vorticity and qualitative visual assessment of coherent flow patterns. We hypothesize that right ventricular diastolic dysfunction (RVDD) is associated with changes in vorticity and right heart blood flow. This paper presents background on RVDD, and 4D Flow tools and techniques used for quantitative and qualitative analysis of cardiac flows in the normal and disease states. In this study, 20 patients with RVDD and 14 controls underwent cardiac 4D Flow and echocardiography. A method for determining the time-step for peak early diastole using 4D Flow data is described. Spatially integrated early diastolic vorticity was extracted from the RV, RA, and combined RV/RA regions of each subject using a range of vorticity thresholding and scaling methods. Statistically significant differences in vorticity were found in the RA and combined RA/RV in RVDD subjects compared to controls when vorticity vectors were both thresholded and scaled by cardiac index.


The effect of long acting somatostatin analogue SMS 201.995 therapy on tumour kinetic measurements and serum tumour marker concentrations in primary rectal cancer.
Twelve patients with rectal carcinoma were treated for 2 weeks with the somatostatin analogue SMS 201.995. Effects of this therapy were assessed using serum marker concentration, Ki67 and gastrin-immunoreactivity of the primary tumour. In four out of 12 patients, a significant decrease in Ki67 immunoreactivity was seen during SMS 201.995 treatment while in the remaining eight patients there was no significant change in Ki67 expression. Four patients had elevated pretreatment serum carcinoembryonic antigen (CEA) levels. In two of these four patients, serum CEA levels fell modestly during SMS 201.995 therapy. This is the first clinical evidence that a somatostatin analogue can inhibit the growth of some colorectal cancers.


Long period fiber gratings for the mitigation of parasitic laser effects in mid-infrared fiber amplifiers.
A concept to mitigate parasitic lasing in mid-IR fiber amplifiers using a single long period fiber grating is shown. Using tightly confined ultrashort laser pulses at 800 nm, a grating was directly inscribed into the core of an erbium doped fluoride glass fiber showing a strong attenuation down to -27 dB at desired wavelength. The concept reveals great potential to improve the average output power and attainable spectral range of low repetition rate in-amplifier supercontinuum generation.


Effects of phenylephrine on systemic and cerebral circulations in humans: a systematic review with mechanistic explanations.
We conducted a systematic review of the literature reporting phenylephrine-induced changes in blood pressure, cardiac output, cerebral blood flow and cerebral tissue oxygen saturation as measured by near-infrared spectroscopy in humans. We used the proportion change of the group mean values reported by the original studies in our analysis. Phenylephrine elevates blood pressure whilst concurrently inducing a reduction in cardiac output. Furthermore, despite increasing cerebral blood flow, it decreases cerebral tissue oxygen saturation. The extent of phenylephrine's influence on cardiac output (r = -0.54 and p = 0.09 in awake humans; r = -0.55 and p = 0.007 in anaesthetised humans), cerebral blood flow (r = 0.65 and p = 0.002 in awake humans; r = 0.80 and p = 0.003 in anaesthetised humans) and cerebral tissue oxygen saturation (r = -0.72 and p = 0.03 in awake humans; r = -0.24 and p = 0.48 in anaesthetised humans) appears closely linked to the magnitude of phenylephrine-induced blood pressure changes. When comparing the effects of phenylephrine in awake and anaesthetised humans, we found no evidence of a significant difference in cardiac output, cerebral blood flow or cerebral tissue oxygen saturation. There was also no evidence of a significant difference in effect on systemic and cerebral circulations whether phenylephrine was given by bolus or infusion. We explore the underlying mechanisms driving the phenylephrine-induced cardiac output reduction, cerebral blood flow increase and cerebral tissue oxygen saturation decrease. Individualised treatment approaches, close monitoring and consideration of potential risks and benefits remain vital to the safe and effective use of phenylephrine in acute care.


Resting heart rate and incident venous thromboembolism: the Multi-Ethnic Study of Atherosclerosis.
Venous thromboembolism (VTE) is associated with significant morbidity and mortality. Resting heart rate (RHR), which may be modifiable through lifestyle changes, has been shown to be associated with cardiovascular disease risk and with inflammatory markers that have been predictive of VTE incidence. We examined whether RHR is also associated with VTE incidence independent of these risk factors. We studied 6479 Multi-Ethnic Study of Atherosclerosis participants free from clinical VTE at baseline who had baseline RHR ascertained by 12-lead ECG. VTE events were recorded from hospital records and death certificates using International Classification of Diseases (ICD)-9 and ICD-10 codes. We categorised RHR as <60, 60-69, 70-79 and ≥80 bpm. We used Cox hazard models to determine the association of incident VTE by RHR. Participants had mean (SD) age of 62 (10) years and RHR of 63 (10) bpm. RHR was cross-sectionally correlated with multiple inflammatory and coagulation factors. There were 236 VTE cases after a median follow-up of 14 years. Compared with those with RHR<60 bpm, the HR (95% CI) for incident VTE for RHR≥80 bpm was 2.08 (1.31 to 3.30), after adjusting for demographics, physical activity, smoking, diabetes and use of atrioventricular (AV)-nodal blockers, aspirin and anticoagulants, and remained significant after further adjustment for inflammatory markers (2.05 (1.29 to 3.26)). Results were similar after excluding those taking AV-nodal blocker medications. There was no effect modification of these associations by sex or age. Elevated RHR was positively associated with VTE incidence after a median of 14 years; this association was independent of several traditional VTE and inflammatory markers.


A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration.
New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone) nanofibrous implant (from 700 μm to 1 cm thick) was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII), 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days' implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7 therapeutic implant by adding human mesenchymal stem cells (hMSCs). The activity of this BMP-7-functionalized implant was again further enhanced by the addition of hMSCs to the implant (living materials), in vivo, as demonstrated by the analysis of new bone formation and calcification after 30 days' implantation in mice with calvaria defects. Therefore, implants functionalized with BMP-7 nanocontainers associated with hMSCs can act as an accelerator of in vivo bone mineralization and regeneration.


Perineal injuries in children.
Over a 12-year period, 463 children under 13 years of age were treated for perineal injuries. The most common cause of injury was a fall astride, but motor vehicle trauma and rape were responsible for most of the severe and multiple injuries. Physical or sexual abuse was evident in 178 (38 per cent) of children, and four sustained injuries from forceful enema. Minor abrasions or first degree tears (88 per cent) and second degree tears (6 per cent) were sutured primarily or allowed to granulate with sepsis rates of 1.2 per cent and 14 per cent respectively. Twenty-nine (6 per cent) children sustained third degree lacerations; one died from secondary pelvic haemorrhage. In the 28 survivors, the outcome of primary (18) or delayed (ten) surgical repair was related to whether or not early defunctioning colostomy had been performed.


Chemotherapy-induced genotoxic damage to bone marrow cells: long-term implications.
Mesenchymal stem/stromal cells (MSCs) within the bone marrow (BM) are vitally important in forming the micro-environment supporting haematopoiesis after myeloablative chemotherapy. MSCs are known to be damaged phenotypically and functionally by chemotherapy; however, to the best our knowledge, the persistence of genotoxic effects of chemotherapy on the BM micro-environment has not been studied. We therefore aimed to evaluate genotoxic effects of chemotherapy on the BM both in vitro and in vivo, using the comet and micronucleus assays, focussing on the persistence of DNA lesions that may contribute to complications in the patient. The MSC cell line (HS-5) and primary cord blood mononuclear cells (CBMNCs: a source of undamaged DNA) were exposed to the chemotherapeutic agent cyclophosphamide (CY) within a physiologically relevant in vitro model. CY treatment resulted in significant increases in CBMNC DNA damage at all time points tested (3-48 h exposure). Similarly, HS-5 cells exposed to CY exhibited significant increases in DNA damage as measured by the comet assay, with increased numbers of abnormal cells visible in the micronucleus assay. In addition, even 48 h after removal of 48-h CY treatment, DNA damage remains significantly increased in treated cells relative to controls. In patients treated with chemotherapy for haematological malignancy, highly significant increases in damaged DNA were seen in BM cells isolated from one individual 1 year after completion of therapy for acute leukaemia compared with pretreatment (P < 0.001). Similarly, two individuals treated 7 and 17 years previously with chemotherapy exhibited significant increases of damaged DNA in MSC compared with untreated age- and sex-matched controls (P < 0.05). Unlike haematopoietic cells, MSCs are not replaced following a stem cell transplant. Therefore, long-term damage to MSC may impact on engraftment of either allogeneic or autologous transplants. In addition, persistence of DNA lesions may lead to genetic instability, correlating with the significant number of chemotherapy-treated individuals who have therapy-related malignancies.


Differential localization of four subspecies of protein kinase C in the rat striatum and substantia nigra.
The distribution of protein kinase C (PKC) subspecies and their colocalization with neurotransmitters were examined in the rat striatum and substantia nigra (SN), using immunocytochemistry. The alpha- and beta I-PKC immunoreactivies were seen predominantly in the perikarya of the neurons in the striatum and SN. In contrast, the beta II- and gamma-PKC immunoreactivities were abundant in both the perikarya and the neuropils in the striatum and only in the neuropils in the SN. From electron microscopic studies, the alpha- and beta I-PKC immunoreactivities were seen adjacent to the plasma membrane, while the beta II-PKC immunoreactivity was observed in the cytoplasm around the Golgi complex. The gamma-PKC immunoreaction was dense throughout the cytoplasm. The double-staining and lesion studies revealed that the alpha-PKC-immunopositive neurons in the striatum were intrinsic cholinergic neurons, and that most of the alpha-PKC-immunoreactive neurons in the SN were dopaminergic neurons. The beta I-PKC-immunoreactive neurons were intrinsic GABAergic neurons in the striatum. Moreover, most of the beta II- and gamma-PKC-immunoreactive neurons were medium-sized neurons projecting to the SN, and over 90% of GABAergic neurons in the caudate-putamen contained beta II-PKC. The beta II-PKC-immunoreactive neurons showed no gamma-PKC immunoreactivity, and the gamma-PKC-immunoreactive neurons were not beta II-PKC immunoreactive. These findings suggest that alpha-PKC is related to the function of the nigral dopaminergic and the striatal cholinergic neurons, and that the beta I-PKC is involved in the function of the striatal intrinsic GABAergic neurons. The beta II- and gamma-PKC may also modulate a specific neuronal function in the striatonigral system.


Correction of lower limb deformities in children with renal osteodystrophy by the Ilizarov method.
Children with renal osteodystrophy (ROD) may develop severe angular deformities of the limbs. Various methods, both medical and surgical, have been described for correction of these deformities, but a literature search showed only 1 child previously treated by the Ilizarov method. The purpose of this study was to characterize the deformities found in our group of patients and to describe our experience in treating these patients with the Ilizarov method. Correction of angular deformity by the Ilizarov method was performed on 8 limb segments in 5 patients with ROD. Mean age was 14.9 years. Two patients were on hemodialysis, and 3 had functioning kidney grafts. Surgery was deferred until stabilization of metabolic parameters. There was 1 varus and 7 valgus deformities. Preoperative coronal deformity averaged 29 degrees (18-38 degrees). The Ilizarov apparatus was used in all cases. Correction time averaged 23 days (20-28 days). The time from completion of correction to frame removal averaged 71 days (48-113 days). There were no changes in metabolic parameters or frequency of hemodialysis throughout the treatment. Restoration of a normal mechanical axis was achieved in 4 of the 5 patients. One case failed due to intraarticular instability. There were no major complications. Minor complications included pin tract infections, which responded to antibiotic treatment, and premature consolidation in 1 case. Follow-up averaged 6.5 years (1-10 years). The alignment obtained at surgery was maintained in all 4 patients, and they are functional and symptom-free. The patient for whom the surgery failed remains wheelchair-bound. The Ilizarov method was found to be safe and effective for correction of malalignment due to ROD. Optimization of metabolic parameters is essential before surgery and throughout correction. The procedure is contraindicated in patients with significant intraarticular knee pathology.


[Kallikrein-kinin system in acute empyema of pleura and pyopneumothorax].
In 56 patients with acute empyema of the pleura the level of aggregate kininogen and prekallikrein, free kallikrein and kininase activities in blood plasma and supernatant of pleural exudate were studied. It was established that epsilon-aminocapronic acid, contrykal and gordox suppress free kallikrein activity in the blood plasma and supernatant of pleural exudate. Intravenous and local application of proteolysis inhibitors resulted in improvement of the outcomes of the disease.


Plasma-mediated alterations of erythrocyte deformability by perfluorochemical blood substitutes.
The effect of perfluorochemical blood substitutes (eg, Oxypherol or Fluosol-DA) on red cell deformability was investigated because these emulsions are in direct contact with red cells when they are used as temporary circulatory aids. Erythrocyte deformability was assessed by a constant volumetric flow rate filtration method. The results of in vitro incubation experiments indicate that perfluorotributylamine causes the deformability of human red cells to decrease significantly in the presence of plasma. However, there is no obvious loss in the deformability when washed cells are used. Neither mean cell volume nor white cells appear to be responsible for the observed effects of perfluorotributylamine. Perfluorodecalin and perfluorotripropylamine, two perfluorochemical compounds that are widely applied clinically, do not induce significant changes in red cell deformability with or without plasma. These results indicate the need for in vitro testing in the development of perfluorochemicals as blood substitutes.


Performance and dynamic characteristics of microbial communities in an internal circulation reactor for treating brewery wastewater.
A laboratory-scale internal circulation (IC) anaerobic reactor fed with brewery wastewater was operated at 35 degrees C + 1 degrees C. The influent was pumped into the bottom of the IC reactor by a pulse pump, whereas the effluent was drawn from the upper outlet and allowed to flow into the effluent tank. The biogas volume was recorded using a gas container connected to a biogas metre. The results indicated that the maximum organic loading rate (OLR) of the IC reactor was 19.5 kg chemical oxygen demand (COD)/m3/day; at which point, the dominant archaeal populations found in the sludge using the polymerase chain reaction with denaturing gradient gel electrophoresis were Methanosaeta species. The COD removal efficiencies of the reactor exceeded 85%, with a maximum specific methane production rate of 210 mL CH4/g volatile suspended solids (VSS)/day and a coenzyme F420 content of 0.16 micromol/g VSS, respectively. The main archaeal species in the sludge samples at different OLRs varied greatly, as compared with the organisms in the inoculated sludge. The dominant archaeal species in the treated sludge at low OLRs were Methanosarcina species, whereas those at high OLRs were Methanosaeta species.


The pain, depression, disability pathway in those with low back pain: a moderation analysis of health locus of control.
Low back pain (LBP) is common, impacts on the individual and society, and is a major health concern. Psychological consequences of LBP, such as depression, are significant barriers to recovery, but mechanisms for the development of depression are less well understood. One potential mechanism is the individual's health locus of control (HLoC), that is, perception of the level of control an individual has over their health. The objective of this study is to investigate the moderation effect of HLoC on the pain-depression-disability pathway in those with LBP. The design is a nested cross-sectional analysis of two existing cohorts of patients (n=637) who had previously consulted their primary care physician about LBP. Measures were taken of HLoC, pain intensity and interference, depression, disability, and bothersomeness. Structural Equation Modeling analysis was applied to two path models that examined the pain to depression to disability pathway moderated by the HLoC constructs of Internality and Externality, respectively. Critical ratio (CR) difference tests were applied to the coefficients using pairwise comparisons. The results show that both models had an acceptable model fit and pathways were significant. CR tests indicated a significant moderation effect, with stronger pathway coefficients for depression for those who report low Internality (β 0.48), compared to those with high Internality (β 0.28). No moderation effects were found within the Externality model. HLoC Internality significantly moderates the pain-depression pathway in those with LBP, meaning that those who have a low perception of control report greater levels of depression. HLoC may signify depression among people with LBP, and could potentially be a target for intervention.


Randomized controlled trial of intravenous acetaminophen for postcesarean delivery pain control.
Cesarean delivery is a common surgery in the United States, with 1.3 million performed during 2009.1 Obstetricians must balance the growing concern with opioid abuse, dependence, and side effects with optimal postoperative pain control. Intravenous acetaminophen may represent an additional method to decrease the reliance on opioid medications and improve postoperative pain following cesarean delivery. The objective of the study was to determine whether the administration of intravenous acetaminophen following routine scheduled cesarean delivery would decrease the need for narcotic medications to control postoperative pain. This was an institutional review board-approved, double-blind, placebo-controlled, randomized trial, registered on clinicaltrials.gov (number 02046382). Women scheduled to undergo cesarean delivery with regional anesthesia at term were recruited. All perioperative and postpartum care was standardized via study order sets. Study patients were given all medications in a standardized manner receiving either acetaminophen 1000 mg intravenously or 100 mL saline (placebo) every 8 hours for 48 hours for a total of 6 doses. The pharmacy prepared intravenous acetaminophen and saline in identical administration bags labeled study drug to ensure blinding. The initial dose of study drug was given within 60 minutes of skin incision. Quantity of breakthrough and scheduled analgesic medications and self-reported pain levels on the Faces Pain Scale (0-10) before and after study drug administration were collected. Patient demographics were extracted from the chart. Power calculation determined that 45 patients per arm were required to detect a 30% reduction in postcesarean narcotic requirement with 80% power and a significance level of P = .05. A total of 133 patients were consented for the study. Twenty-nine were excluded and 104 patients completed the study: 57 received intravenous acetaminophen and 47 received placebo. There were no differences in baseline demographic characteristics including patient age, body mass index, gravidity, parity, race, comorbidities, or number of prior cesarean deliveries. There were no differences between groups in estimated blood loss or length of stay. The total amount of oral narcotic medications consumed by patients receiving intravenous acetaminophen was significantly reduced when compared with the placebo group (47 mg vs 65 mg of oxycodone; P = .034). The total amount of ibuprofen used between groups was not different. There was no difference in pain scores between groups before and after study dose administration. There was no significant difference in narcotic side effects (nausea/emesis, respiratory depression, constipation) in either study arm. Intravenous acetaminophen in the postoperative period following cesarean delivery resulted in a significant decrease in oral narcotic consumption for pain control.


Detecting short spatial scale local adaptation and epistatic selection in climate-related candidate genes in European beech (Fagus sylvatica) populations.
Detecting signatures of selection in tree populations threatened by climate change is currently a major research priority. Here, we investigated the signature of local adaptation over a short spatial scale using 96 European beech (Fagus sylvatica L.) individuals originating from two pairs of populations on the northern and southern slopes of Mont Ventoux (south-eastern France). We performed both single and multilocus analysis of selection based on 53 climate-related candidate genes containing 546 SNPs. FST outlier methods at the SNP level revealed a weak signal of selection, with three marginally significant outliers in the northern populations. At the gene level, considering haplotypes as alleles, two additional marginally significant outliers were detected, one on each slope. To account for the uncertainty of haplotype inference, we averaged the Bayes factors over many possible phase reconstructions. Epistatic selection offers a realistic multilocus model of selection in natural populations. Here, we used a test suggested by Ohta based on the decomposition of the variance of linkage disequilibrium. Overall populations, 0.23% of the SNP pairs (haplotypes) showed evidence of epistatic selection, with nearly 80% of them being within genes. One of the between gene epistatic selection signals arose between an FST outlier and a nonsynonymous mutation in a drought response gene. Additionally, we identified haplotypes containing selectively advantageous allele combinations which were unique to high or low elevations and northern or southern populations. Several haplotypes contained nonsynonymous mutations situated in genes with known functional importance for adaptation to climatic factors.


Mouse and zebrafish Hoxa3 orthologues have nonequivalent in vivo protein function.
Hox genes play evolutionarily conserved roles in specifying axial position during embryogenesis. A prevailing paradigm is that changes in Hox gene expression drive evolution of metazoan body plans. Conservation of Hox function across species, and among paralogous Hox genes within a species, supports a model of functional equivalence. In this report, we demonstrate that zebrafish hoxa3a (zfhoxa3a) expressed from the mouse Hoxa3 locus can substitute for mouse Hoxa3 in some tissues, but has distinct or null phenotypes in others. We further show, by using an allele encoding a chimeric protein, that this difference maps primarily to the zfhoxa3a C-terminal domain. Our data imply that the mouse and zebrafish proteins have diverged considerably since their last common ancestor, and that the major difference between them resides in the C-terminal domain. Our data further show that Hox protein function can evolve independently in different cell types or for specific functions. The inability of zfhoxa3a to perform all of the normal roles of mouse Hoxa3 illustrates that Hox orthologues are not always functionally interchangeable.


Improving performances of Fresnel CPV systems: Fresnel-RXI Köhler concentrator.
The optical design presented here has been done in order to achieve superior optical performance in comparison with the state-of-the-art Fresnel CPV systems. The design consists of a Photovoltaic Concentrator (CPV) comprising a Fresnel lens (F) as a Primary Optical Element (POE) and a dielectric solid RXI as a Secondary Optical Element (SOE), both with free-form surfaces (i.e. neither rotational nor linearly symmetric). It is the first time the RXI-type geometry has been applied to a CPV secondary. This concentrator has ultra-high CAP value ready to accommodate more efficient cells eventually to be developed and used commercially in future.


Rapid Detection of Nocardia by Next-Generation Sequencing.
In this original study, we retrospectively reviewed the cases of nocardiosis diagnosed through culture and next-generation sequencing (NGS) methods between 2014 and 2018 in Huashan Hospital and found out that the latter way can not only improve the detection rate of Nocardia spp. but also greatly reduce the turnaround time. In addition, by comparing nocardiosis and non-nocardiosis patients both of whose samples had Nocardia spp. detected by NGS, we found that Nocardia's specific reads ranking among top two might be a satisfactory cutoff value for clinical diagnosis of the disease. Our study introduced the promising value of the NGS method in the rapid diagnosis of nocardiosis.


[Effects of calcium supplementation using AAACa or milk on nocturnal bone resorption in young women].
In order to study the effect of calcium supplementation on bone resorption, a randomized controlled crossover study was carried out on eight healthy 18-19 year old female volunteers using either AAACa heated oyster shell with vacuum-heated seaweed or milk. Regimen A consisted of an oral dose of 200 mg calcium in the form of AAACa. B 200 ml milk after breakfast and supper and at bedtime, and C control with no calcium supplement. Early morning fasting blood and urine sampling was carried out after 7 days of calcium supplementation. Serum calcium was higher in groups A and B than in C, and serum intact parathyroid hormone (PTH) was significantly lower in group A than in groups B and C, according to a paired t-test. Urinary excretion of crosslinked collagen degradation product, pyridinoline and deoxypyridinoline showed a similar decrease in groups A and B but not in C. The more effective suppression of PTH by AAACa than by milk may be due to its higher bioavailability and the absence of phosphate stimulating PTH secretion.


Panel of polymorphic heterologous microsatellite loci to genotype critically endangered Bengal tiger: a pilot study.
In India, six landscapes and source populations that are important for long-term conservation of Bengal tigers (Panthera tigris tigris) have been identified. Except for a few studies, nothing is known regarding the genetic structure and extent of gene flow among most of the tiger populations across India as the majority of them are small, fragmented and isolated. Thus, individual-based relationships are required to understand the species ecology and biology for planning effective conservation and genetics-based individual identification has been widely used. But this needs screening and describing characteristics of microsatellite loci from DNA from good-quality sources so that the required number of loci can be selected and the genotyping error rate minimized. In the studies so far conducted on the Bengal tiger, a very small number of loci (n = 35) have been tested with high-quality source of DNA, and information on locus-specific characteristics is lacking. The use of such characteristics has been strongly recommended in the literature to minimize the error rate and by the International Society for Forensic Genetics (ISFG) for forensic purposes. Therefore, we describe for the first time locus-specific genetic and genotyping profile characteristics, crucial for population genetic studies, using high-quality source of DNA of the Bengal tiger. We screened 39 heterologous microsatellite loci (Sumatran tiger, domestic cat, Asiatic lion and snow leopard) in captive individuals (n = 8), of which 21 loci are being reported for the first time in the Bengal tiger, providing an additional choice for selection. The mean relatedness coefficient (R = -0.143) indicates that the selected tigers were unrelated. Thirty-four loci were polymorphic, with the number of alleles ranging from 2 to 7 per locus, and the remaining five loci were monomorphic. Based on the PIC values (> 0.500), and other characteristics, we suggest that 16 loci (3 to 7 alleles) be used for genetic and forensic study purposes. The probabilities of matching genotypes of unrelated individuals (3.692 × 10(-19)) and siblings (4.003 × 10(-6)) are within the values needed for undertaking studies in population genetics, relatedness, sociobiology and forensics.


Recent insights into the cell biology of thyroid angiofollicular units.
In thyrocytes, cell polarity is of crucial importance for proper thyroid function. Many intrinsic mechanisms of self-regulation control how the key players involved in thyroid hormone (TH) biosynthesis interact in apical microvilli, so that hazardous biochemical processes may occur without detriment to the cell. In some pathological conditions, this enzymatic complex is disrupted, with some components abnormally activated into the cytoplasm, which can lead to further morphological and functional breakdown. When iodine intake is altered, autoregulatory mechanisms outside the thyrocytes are activated. They involve adjacent capillaries that, together with thyrocytes, form the angiofollicular units (AFUs) that can be considered as the functional and morphological units of the thyroid. In response to iodine shortage, a rapid expansion of the microvasculature occurs, which, in addition to nutrients and oxygen, optimizes iodide supply. These changes are triggered by angiogenic signals released from thyrocytes via a reactive oxygen species/hypoxia-inducible factor/vascular endothelial growth factor pathway. When intra- and extrathyrocyte autoregulation fails, other forms of adaptation arise, such as euthyroid goiters. From onset, goiters are morphologically and functionally heterogeneous due to the polyclonal nature of the cells, with nodules distributed around areas of quiescent AFUs containing globules of compact thyroglobulin (Tg) and surrounded by a hypotrophic microvasculature. Upon TSH stimulation, quiescent AFUs are activated with Tg globules undergoing fragmentation into soluble Tg, proteins involved in TH biosynthesis being expressed and the local microvascular network extending. Over time and depending on physiological needs, AFUs may undergo repetitive phases of high, moderate, or low cell and tissue activity, which may ultimately culminate in multinodular goiters.


Light-induced nuclear translocation of endogenous pea phytochrome A visualized by immunocytochemical procedures.
Although the physiological functions of phytochrome A (PhyA) are now known, the distribution of endogenous PhyA has not been examined. We have visualized endogenous PhyA apoprotein (PHYA) by immunolabeling cryosections of pea tissue, using PHYA-deficient mutants as negative controls. By this method, we examined the distribution of PHYA in different tissues and changes in its intracellular distribution in response to light. In apical hook cells of etiolated seedlings, PHYA immunolabeling was distributed diffusely in the cytosol. Exposure to continuous far-red (cFR) light caused a redistribution of the immunolabeling to the nucleus, first detectable after 1.5 hr and greatest at 4.5 hr. During this time, the amounts of spectrally active phytochrome and PHYA did not decline substantially. Exposure to continuous red (cR) light or to a brief pulse of red light also resulted in redistribution of immunolabeling to the nucleus, but this occurred much more rapidly and with a different pattern of intranuclear distribution than it did in response to cFR light. Exposures to cR light resulted in loss of immunolabeling, which was associated with PHYA degradation. These results indicate that the light-induced intracellular location of PHYA is wavelength dependent and imply that this is important for PhyA activity.


Risk factors for general medicine readmissions and association with mortality.
To investigate general medicine readmissions for risk factors and association with mortality. A case control study was performed comparing the characteristics of 30-day general medicine patients readmitted between 1 January to 30 June 2012 to a general medicine service at Capital and Coast District Health Board (Wellington region, New Zealand) with an equal number of randomly selected patients not readmitted to the service during the same time period. 197 patients discharged from general medicine were readmitted during the 6-month study period. There were no differences in the sex, ethnicity, residential care at admission, history of dementia, length of admission or weekend discharge of readmitted patients compared to non-readmitted patients. The mean age, number of medications and comorbidities score were higher in the readmission group. Readmission (even after controlling for age, polypharmacy, and comorbidities) was a strong predictor of 1-year all-cause mortality, with an odds ratio of 2.2. Twenty-one percent of readmission patients had more than one general medicine readmission, up to 30 days between each, with even higher mortality rate compared to one readmission (49% vs. 28%). Readmission to general medicine is strongly associated with older age, polypharmacy, and multiple comorbidities. Readmission is an independent strong risk factor for 1-year mortality, with this risk increasing after multiple readmissions. Readmissions can be a marker of deteriorating patient's condition, and a discussion in relation to prognosis, ceiling of treatment, resuscitation status documentation and advance directive may be warranted.


Metabolite characterization in drug discovery utilizing robotic liquid-handling, quadruple time-of-flight mass spectrometry and in-silico prediction.
An assay method for identification of metabolites from in vitro microsomal incubations was developed for use in the early stage of drug discovery. We have developed a practical approach which involves integrated sample generation, sample preparation, bioanalysis, and data handling to maximize sample throughput and speed up the process for identification of metabolites. The assay system consisted of a robotic liquid handler (Genesis workstation) to generate and process samples, PALLAS MetabolExpert software to predict possible metabolites, exact mass measurement via a tandem quadrupole time-of-flight mass spectrometer (QTOF-MS) coupled with liquid chromatography to analyze samples, MetaboLynx software to find potential metabolites and Advanced Chemistry Development/MS (ACD/MS) software to provide guidance to the most likely hypothetical metabolite chemical structures. For purposes of evaluating this new method, dextromethorphan, alprenolol, and propranolol were incubated separately for up to 60 minutes with rat and human hepatic microsomes. The incubation and sample preparation were carried out in 96-well plates using the Genesis workstation. The bioanalysis was performed by LC-MS/MS using QTOF with MetaboLynx software to find metabolites. Metabolic products formed in vitro by rat and human microsomes were separated using an analytical column C18 with gradient elution at flow rate of 250 micro l/min. The internal mass calibration was performed by continuous postcolumn infusion of Haloperidol. The mass spectra from incubations containing NADPH were compared to those without NADPH (control) using the MetaboLynx software to find potential metabolites. Finally, the MS/MS spectra were processed by the ACD/MS software to predict the chemical structure. MetaboLynx software successfully identified metabolites for each of the drugs studied by automatically discerning expected metabolites. Exact differences in masses between each metabolite and parent drug were measured from five replicate sample injections. All measured values are accurate to less than 0.001Da or 3.8 ppm with the standard deviation within 0.0015 Da, which allowed good prediction/confirmation of empirical formulae. Hypothetical chemical structures were achieved by the ACD/MS software and provided a useful tool to assist in prediction of the metabolic pathways of the drugs. The metabolites identified were in good agreement with previously published results for all three compounds. This new method will greatly enhance throughput, which in turn will facilitate our ability to rapidly provide this guidance to the synthetic chemist.


Short Communication: Low Expression of Activation and Inhibitory Molecules on NK Cells and CD4(+) T Cells Is Associated with Viral Control.
Chronic HIV-1 infection induces severe immune alterations, including hyperactivation, exhaustion, and apoptosis. In fact, viral control has been associated with low frequencies of these processes. Here, we evaluated the expression of activation and inhibitory molecules on natural killer (NK) and CD4(+) T cells and plasma levels of proinflammatory cytokines in individuals exhibiting viral control: a cohort of HIV-1-exposed-seronegative individuals (HESN) and a cohort of HIV controllers. There was lower expression of CD69, LAG-3, PD-1, and TIM-3 in both cohorts when compared to a low-risk population or HIV progressors. In addition, HIV controllers exhibited lower plasma levels of proinflamatory molecules TNF-α and IP-10. These findings suggest that individuals exhibiting viral control have lower basal expression of markers associated with cellular activation and particularly immune exhaustion.


Spreading and migration of human glioma and rat C6 cells on central nervous system myelin in vitro is correlated with tumor malignancy and involves a metalloproteolytic activity.
Malignant gliomas infiltrate the brain preferentially along myelinated fiber tracts. Central nervous system (CNS) myelin, however, contains inhibitory proteins that block axon regeneration, neurite outgrowth, and cell spreading of astrocytes and fibroblasts. We tested 5 human brain tumor cell lines, 1 rat brain tumor cell line, and 29 short-term cultured specimens from human brain tumors for their ability to spread and migrate on a CNS myelin substrate. Low-grade and pilocytic astrocytoma, ependymoma, medulloblastoma, and meningioma cell lines as well as primary cultures were strongly sensitive to the inhibitory proteins present in the CNS myelin. In contrast, glioblastomas, anaplastic astrocytomas, and oligodendrogliomas were able to spread and migrate on CNS myelin-coated culture dishes, demonstrating that within the gliomas, the ability to overcome the inhibitory effects of the CNS myelin is correlated with the grade of malignancy of the original tumor. Cell spreading of glioblastomas and anaplastic astrocytomas specifically on a CNS myelin substrate was strongly inhibited by the metalloprotease blocker O-phenanthroline and the peptide derivative carbobenzoxy-Phe-Ala-Phe-Tyr-amide, whereas blockers for serine, aspartyl, and cysteine proteases had no effect. Enzymatic peptide degradation assays revealed the presence of a phosphoramidon-sensitive and thiorphan-insensitive metalloproteolytic activity in the plasma membranes of high-grade glioma cells. These results suggest a crucial involvement of a membrane-bound metalloendoprotease in the process of invasive migration of malignant gliomas along CNS white matter fiber tracts.


Modulation of reflex and voluntary EMG activity in wrist flexors by stimulation of digital nerves in hemiplegic humans.
Changes in EMG activity in the wrist flexor muscles were studied in response to electrical stimulation of digital nerves and to sudden extension perturbations at the wrist produced by a torque motor in human subjects with unilateral cerebral hemisphere lesions. With the subjects maintaining a steady voluntary contraction against a constant load, digital nerve stimulation produced a series of excitatory and inhibitory changes in tonic EMG activity from the wrist flexors in both the normal and paretic arm. The most consistent response was a period of EMG inhibition beginning approximately 38 msec after the stimulus and lasting approximately 35 msec. With relatively weak electrical stimuli, there was less EMG inhibition in the paretic arm than in the normal arm; with stronger stimuli, the inhibitory response was similar in the two arms. The electrical stimuli and mechanical perturbations were then delivered together, with the interval between them adjusted so that the expected period of inhibition following electrical stimulation coincided with either the early (M1) or the long latency (M2) components of the stretch reflex. In the normal arm electrical stimulation produced more inhibition of the M2 component than of the M1 component. In the paretic arm, inhibition during the M2 component was less marked and similar in degree to that which occurred during M1. These results are compatible with the view that M1 and M2 are normally mediated by separate neural pathways. The long latency EMG activity evoked by muscle stretch in the paretic arm of hemiplegic patients may be generated by pathways or mechanisms different from those in the intact arm.


Role of Organic Anion-Transporting Polypeptides (OATPs) in Cancer Therapy.
The superfamily of organic anion-transporting polypeptides (OATPs, gene symbol SLCO) includes important transporters handling a variety of endogenous and xenobiotic substrates. Currently, 11 human OATPs are known and their substrates include endogenous hormones and their conjugates, anticancer drugs, and imaging agents. The contribution of OATPs to the in vivo disposition of these substrates has been extensively investigated. An accumulating body of evidence also indicates that the expression of some OATPs may be up- or downregulated in several types of cancers, suggesting potential pathogenic roles during the development and progression of cancer. Given that the role of OATPs in handling cancer therapeutics has been already covered by several excellent reviews, this review will focus on the recent progresses on the topic, in particular the role of OATPs in the disposition of anticancer drugs, the impact of OATP genetic variations on the function of OATPs, and the OATPs differentially expressed in cancer and their potential roles in cancer development, progression, and treatment.


Rickettsial actin-based motility: behavior and involvement of cytoskeletal regulators.
Actin-based motility (ABM) is employed by spotted fever group (SFG) rickettsiae, such as Rickettsia rickettsii, to promote cell-to-cell spread. Time-lapse video microscopy revealed that ABM is not strictly confined to SFG rickettsiae as typhus group R. typhi moved at approximately the same rate as R. rickettsii (approximately 4 micro m/min), but in a highly erratic fashion. A number of common behaviors were observed between ABM of R. typhi and R. rickettsii, such as entrance into plasma membrane protrusions, formation of new actin tails only on the old surface of newly formed daughter cells, and quick (within 15 sec) reassembly of the actin tail to the opposite pole upon contact with cellular structures that impede forward movement. This last behavior suggests that the rickettsial protein(s) required for ABM is uniformly localized to both poles of the bacterium and possibly throughout the rickettsial surface. Functional roles in rickettsial ABM for neuronal Wiskott-Aldrich syndrome protein (N-WASP) and the actin-related protein (Arp)2/3 complex, critical regulators of ABM of other pathogens, have not been established. Domains of N-WASP that have characterized inhibitory effects on N-WASP or Arp2/3 complex function were expressed in HeLa cells infected with R. rickettsii. Shigella flexneri-infected cells were used as a control. When ectopically expressed, the VCA domain of N-WASP (VCA) acts as a dominant/negative with respect to Arp2/3 complex function and N-WASP missing VCA (DeltaVCA) acts as a dominant/negative form of N-WASP. Expression of VCA or DeltaVCA severely inhibited S. flexneri ABM (no Shigella motility observed in the majority of expressing cells) while only moderately inhibiting ABM of R. rickettsii (approximately 35% decrease in the rate of ABM). In addition, ectopically expressed full-length GFP-N-WASP was recruited by S. flexneri but not R. rickettsii, and Arp3 was detected by indirect immunofluorescence in S. flexneri actin tails but not within R. rickettsii actin tails. Collectively, these data suggest that rickettsial ABM is independent of N-WASP and Arp2/3 complex function.


[Survey of surgical and radiological semiology modules and their adaptation to the Arabic cultural environment].
Many professors of medicine oppose the Arabization of the teaching of medical science in the Maghreb countries, under pretext of the inability of Arabic to convey scientific concepts objectively compared with French. We made a qualitative survey of surgical and radiological semiology used in the Faculty of Medecine, Ibn El Jazzar. Terms, expressions and synonyms were identified and classified according to their cultural load into two categories: "culturally adapted terms" and "culturally strange terms" in relation to the national culture. It was evident that the majority of the recorded expression were based on Western culture. Thus the hypothesis of the neutrality of the French language in the medical teaching is invalid. Furthermore the use of French poses difficulties for students in understanding the scientific matter taught, and indirectly promotes Western culture within the medical academic establishments of the Arabic world. The use of the mother tongue in teaching medicine is today an educational necessity.


Safe Mechanical Preparation with Reciprocation Movement without Glide Path Creation: Result from a Pool of 673 Root Canals.
The aim of the present study was to prospectively assess the frequency of teeth in which the Reciproc instruments were able to reach the full working length (WL). This case series study enrolled 277 consecutive teeth requiring primary endodontic treatment performed with the Reciproc system (VDW) without a previous glide path by 3 experienced endodontists. Instruments R25, R40 or R50 were selected, respectively, for narrow, medium and large canals, according to the preoperative radiographs, as per manufacturer recommendation. Canals were instrumented and classified as reaching the full WL (RFWL) and not reaching the full WL (NRFWL), according to the ability of the Reciproc instrument to reach without a glide path the full electronically determined WL. Finally, canals were filled using a single matched cone technique. Pearson's squared-chi test compared the frequency distributions of canals classified as RFWL and NRFWL. From a total pool of 673 root canals, Reciproc instruments reached the FWL in 96.28% of cases and 3 fractures occurred. For narrow canals the percentage of RFWL was 95.37% with 3 fractures. For medium and large canals, the R40 or R50 instruments reached the FWL in 98.51% and 97.62% of the cases respectively, with no fracture. Enlarging of root canals using the Reciproc instruments up to the FWL without a glide path is successful in a great percentage of cases. This case series suggests the possibility of using a single instrument to enlarge the root canal space of teeth by a simpler approach without an a prioriglide path procedure.


Antipsychotics, Metabolic Adverse Effects, and Cognitive Function in Schizophrenia.
Cognitive impairment is a core symptom domain of schizophrenia. The effect of antipsychotics, the cornerstone of treatment in schizophrenia, on this domain is not fully clear. There is some evidence suggesting that antipsychotics may partially improve cognitive function, and that this improvement may vary depending on the specific cognitive domain. However, this research is confounded by various factors, such as age, duration/stage of illness, medication adherence, and extrapyramidal side effects that complicate the relationship between antipsychotics and cognitive improvement. Furthermore, antipsychotics-particularly the second generation, or "atypical" antipsychotics-can induce serious metabolic side effects, such as obesity, dyslipidemia and type 2 diabetes, illnesses which themselves have been linked to impairments in cognition. Thus, the inter-relationships between cognition and metabolic side effects are complex, and this review aims to examine them in the context of schizophrenia and antipsychotic treatment. The review also speculates on potential mechanisms underlying cognitive functioning and metabolic risk in schizophrenia. We conclude that the available literature examining the inter-section of antipsychotics, cognition, and metabolic effects in schizophrenia is sparse, but suggests a relationship between metabolic comorbidity and worse cognitive function in patients with schizophrenia. Further research is required to determine if there is a causal connection between the well-recognized metabolic adverse effects of antipsychotics and cognitive deficits over the course of the illness of schizophrenia, as well as, to determine underlying mechanisms. In addition, findings from this review highlight the importance of monitoring metabolic disturbances in parallel with cognition, as well as, the importance of interventions to minimize metabolic abnormalities for both physical and cognitive health.