Differential development of tolerance to the functional and behavioral effects of repeated baclofen treatment in rats.
Baclofen, a gamma-aminobutyric acid (GABA)B receptor agonist, has been used clinically to treat muscle spasticity, rigidity and pain. More recently, interest in the use of baclofen as an addiction medicine has grown, with promising preclinical cocaine and amphetamine data and demonstrated clinical benefit from alcohol and nicotine studies. Few preclinical investigations, however, have utilized chronic dosing of baclofen, which is important given that tolerance can occur to many of its effects. Thus the question of whether chronic treatment of baclofen maintains the efficacy of acute doses is imperative. The neural substrates that underlie the effects of baclofen, particularly those after chronic treatment, are also not known. In the present study, therefore, rats were treated with either a) vehicle, b) acute baclofen (5 mg/kg) or c) chronic baclofen (5 mg/kg, t.i.d. for 5 days). The effects of acute and chronic baclofen administration, compared to vehicle, were assessed using locomotor activity and changes in brain glucose metabolism (a measure of functional brain activity). Acute baclofen significantly reduced locomotor activity (horizontal and total distance traveled), while chronic baclofen failed to affect locomotor activity. Acute baclofen resulted in significantly lower rates of local cerebral glucose utilization throughout many areas of the brain, including the prefrontal cortex, caudate putamen, septum and hippocampus. The majority of these functional effects, with the exception of the caudate putamen and septum, were absent in animals chronically treated with baclofen. Despite the tolerance to the locomotor and functional effects of baclofen following repeated treatment, these persistent effects on functional activity in the caudate putamen and septum may provide insights into the way in which baclofen alters the reinforcing effects of abused substances such as cocaine, alcohol, and methamphetamine both in humans and animal models.


Presynaptic muscarinic receptors inhibiting endogenous noradrenaline release in the portal vein of the freely moving rat.
1. In the portal vein of the freely moving unanaesthetized rat, the existence of presynaptically located inhibitory muscarinic receptors was investigated by use of the muscarinic agonist methacholine (MCh) 2. Infusion of MCh (0.3 micrograms min-1) did not significantly inhibit the endogenous noradrenaline (NA) overflow in portal plasma. However, after inducing high intra-synaptic concentrations of NA by blocking the presynaptic alpha 2-adrenoceptors with yohimbine (1 mg kg-1), MCh (0.3 microgram min-1) was able to reduce the yohimbine-induced enhanced NA overflow by 38%. 3. The MCh-induced inhibition was almost completely abolished after blockade of the presynaptic muscarinic receptors with atropine (0.6 mg kg-1). 4. During electrical stimulation of the portal vein nervous plexus the evoked NA overflow was strongly inhibited (95%) during MCh-infusion (0.3 microgram min-1). Again atropine (0.6 mg kg-1) was able to reverse this inhibition. 5. These results show the existence of presynaptic muscarinic receptors inhibiting endogenous NA overflow from the portal vein nervous plexus under conditions of enhanced sympathetic activity in the freely moving rat.


Leaking mycotic aneurysm of renal artery in a child.
A case of staphylococcal endocarditis, complicated by a leaking mycotic aneurysm of the right artery in a boy is presented. An emergency nephrectomy was lifesaving. The clinical course and pathology are discussed and the literature is reviewed.


A molecular ruler regulates cytoskeletal remodelling by the Rho kinases.
The Rho-associated coiled-coil kinases (ROCK) are essential regulators of the actin cytoskeleton; however, the structure of a full-length ROCK is unknown and the mechanisms by which its kinase activity is controlled are not well understood. Here we determine the low-resolution structure of human ROCK2 using electron microscopy, revealing it to be a constitutive dimer, 120 nm in length, with a long coiled-coil tether linking the kinase and membrane-binding domains. We find, in contrast to previous reports, that ROCK2 activity does not appear to be directly regulated by binding to membranes, RhoA, or by phosphorylation. Instead, we show that changing the length of the tether modulates ROCK2 function in cells, suggesting that it acts as a molecular ruler. We present a model in which ROCK activity is restricted to a discrete region of the actin cytoskeleton, governed by the length of its coiled-coil. This represents a new type of spatial control, and hence a new paradigm for kinase regulation.


Successful localization of abnormal parathyroid tissue with ultrasound-guided methylene blue dye injection before surgery for metastatic or recurrent thyroid cancers and parathyroid adenomas.
A surgery to be performed on a previously operated neck includes difficulties such as increased risk of complications and prolonged operation time. The aim of the present study is to analyze the benefit of pre-anesthetic ultrasound-guided injection of methylene blue into parathyroid adenomas and abnormal lymph nodes to simplify their safe and satisfactory extraction. We analyzed the case series records of 14 patients who were operated for reoperative neck surgery due to recurrent thyroid cancer (8 patients) and parathyroid adenoma (6 patients) and in the technique; 0.2 ml of a 1:5 dilution of 1 % methylene blue solution was injected directly onto the target during real-time ultrasound guidance before the operating room. In adenomas, ultrasound-guided methylene blue injection was successfully applied in all cases, an average of 33.1 min before entering the operating room (range = 28-38 min). There were no complications related to dye injection. For patients with recurrent thyroid tumors, preoperative ultrasound-guided methylene blue injection was successfully applied in all patients, on average 27.5 min before entering the operating room (range = 20-35 min). No complications occurred due to dye injection. The blue stained lesion was easily identified during surgery. We analyzed the feasibility of the injection process, the certainty of defining pathological lymph nodes, and the complications of the procedure. Preoperative administration of methylene blue preserved its intraoperative efficacy and maintained the easy the detection of reoperative or primary pathologies. The present study suggest that methylene blue dye injection is a safe, sufficient, and quietly effective method for identifying recurrent tumors and parathyroid adenomas in scarred reoperative neck surgeries. Our cases had comparatively short operative times and lower complication rates.


A DOTAM-based paraCEST agent favoring TSAP geometry for enhanced amide proton chemical shift dispersion and temperature sensitivity.
The Tm(3+) chelate of DOTAM [1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane] possessing sterically demanding t-butyl amide substitution favors TSAP geometry. This chelate displayed a paraCEST signal associated with the highly shifted amide proton signal at approximately -100 ppm that was beyond the frequency of macromolecule magnetization transfer. This signal also displayed high temperature dependence (0.57 ppm °C(-1)) in the range of 35-42 °C and at neutral pH.


A pedigree with bilateral preaxial polydactyly from India.
Preaxial polydactyly in 15 males and 5 females of 6 generations display a bilateral duplication of the big toe in a pedigree from Andhra Pradesh, India, with reduced penetrance and variable expressivity.


[Chronic tic disorders in children and adolescents and their treatment with adaptol].
We examined 162 patients, aged from 10 to 15 years, with tic hyperkineses. Transient and chronic tic disorders were observed in 82 and 80 patients, respectively. The relationship of clinical features, frequency, psychological and encephalographic characteristics of the patients with age-at-onset was studied. The effect of adaptol on the course of chronic tic disorders was evaluated. In addition to our results reported previously for transient tic disorders, we demonstrated the efficacy of adaptol administered in dose 1000 mg per day during 60 days in patients with chronic tic disorders.


Arsenic Concentrations in Household Drinking Water: A Cross-Sectional Survey of Pregnant Women in Tacna, Peru, 2019.
The World Health Organization (WHO) estimates that around ~150 million people in 70 different countries have been consuming water with arsenic levels higher than the recommended limit of 10 μg/L. Here we describe the concentrations of inorganic arsenic in drinking water in homes of pregnant women living in the province of Tacna, near the southern border of Peru. 161 pregnant women were enrolled in their second trimester of pregnancy. A total of 100mL drinking water was collected in each household from the source of most common use. Inorganic arsenic was categorized into 3 levels with a commercial kit. Thirty percent of women had drinking water ≤10 μg/L (the WHO recommended level), 35% had 25 μg/L, and 35% had greater than 50 μg/L. Low arsenic levels were found in the southernmost homes, supplied by groundwater, while high levels were found in the northern and metropolitan homes supplied by river water.


The ingestion and assimilation of algae by Nais elinguis (Oligochaeta: Naididae).
Nais elinguis was offered equal densities of three algal species under controlled conditions. Colonies of Scenedesmus quadricauda were ingested at significantly lower rates than cell of Nitzschia kutzingiana and Chlorella vulgaris. Labelled cells of N. kutzingiana were more rapidly and more efficiently assimilated than those of the other algae. Cells of S. quadricauda were viable in the faeces.This work confirmed conclusions from other studies with respect to the role of algae in the nutrition of Nais elinguis and other freshwater benthic herbivores.


[Biodegradation of Cellulose-Containing Substrates by Micromycetes Followed by Bioconversion into Biogas].
The ability of micromycetes Trichoderma viride and Aspergillus terreus to decompose the cellulose-containing substrates was studied. Office paper and cardboard, as well as a paper mixture, were found to be the most hydrolyzable. The cellulolytic activity of T. viride was 2-3 times higher than that of A. terreus; the highest values of 0.80 and 0.73 U/mLwere obtained from office paper and the paper mixture, respectively. The micromycete cultivation conditions (composition of culture medium, sucrose cosubstrate addition, seeding method) and the conditions of the fungus biomass treatment for its subsequent bioconversion into biogas by anaerobic microbial communities were optimized. It was shown that pretreatment improves the efficiency of biogas production from lignocellulosic materials under seeding with microbial community of bovine animal manure. After pretreatment of the Jerusalem artichoke phytomass (stems and leaves) and its subsequent bioconversion into biogas by methanogenic community, the biogas yield was increased by 1.5 times.


Quantification of ventilation characteristics of a helmet.
Despite the augmented safety offered by wearing a cyclist crash helmet, many cyclists still refuse to wear one because of the thermal discomfort that comes along with wearing it. In this paper, a method is described that quantifies the ventilation characteristics of a helmet using tracer gas experiments. A Data-Based Mechanistic model was applied to provide a physically meaningful description of the dominant internal dynamics of mass transfer in the imperfectly mixed fluid under the helmet. By using a physical mass balance, the local ventilation efficiency could be described by using a single input-single output system. Using this approach, ventilation efficiency ranging from 0.06 volume refreshments per second (s(-1)) at the side of the helmet to 0.22s(-1) at the rear ventilation opening were found on the investigated helmet. The zones at the side were poorly ventilated. The influence of the angle of inclination on ventilation efficiency was dependent on the position between head and helmet. General comfort of the helmet can be improved by increasing the ventilation efficiency of fresh air at the problem zones.


Inhibition of human platelet aggregation and membrane lipid peroxidation by food spice, saffron.
The inhibitory activity of saffron extract was studied on human platelets. Platelet aggregation and lipid peroxidation were evaluated with platelet rich plasma (PRP) and platelet membranes respectively obtained from blood of healthy human volunteers. Human platelets were subjected to stimulation with a variety of agonists like ADP (61 microM), epinephrine (76 microM), collagen (11 microg/ml), calcium ionophore A 23187 (6 microM) and ristocetin (1.25 microg/ml) in the presence and absence of saffron extract with IC50 being 0.66, 0.35, 0.86 and 0.59 mg respectively and no inhibition with ristocetin. The inhibitory effect was dose dependent with concentrations varying between 0.16 to 0.80 mg and time dependent at IC50. A significant decrease was observed in malondialdehyde (MDA) formed, one of the end products of arachidonic acid metabolism and of serotonin released from dense granules of platelets at respective IC50. Lipid peroxidation in platelet membranes induced by iron-ascorbic acid system was inhibited by saffron extract significantly with IC50 of 0.33 mg. Hence, it may be said that aqueous extract of saffron may have component(s), which protect platelets from aggregation and lipid peroxidation.


Comparison of Methods for Analyzing Human Adipose Tissue Macrophage Content.
The relationship between inflammation, obesity, and adverse metabolic conditions is associated with adipose tissue macrophages (ATM). This study compared the measurements of human ATM using flow cytometry, immunohistochemistry (IHC), and real-time polymerase chain reaction (RT-PCR) of ATM markers. A new software program (AMCounter) was evaluated to help measure ATM using IHC, and this was compared to flow cytometry and RT-PCR. IHC had good intraindividual reproducibility for total (CD68), proinflammatory (CD14), and anti-inflammatory (CD206) ATM. The AMCounter improved interreader agreement and was more time efficient. Flow cytometry had acceptable intraindividual reproducibility for the percentage of CD68+ cells that were CD14+ or CD206+ , but not for ATMs per gram of tissue. ATMs per gram of tissue was much greater using IHC than flow cytometry. The flow cytometry and IHC measures of ATM from the same biopsies were not correlated. There were statistically significant correlations between RT-PCR CD68 and IHC CD68, CD14, and CD206 ATMs per 100 adipocytes. Also of interest were statistically significant correlations between RT-PCR CD68 and IHC CD68, CD14, and adipose flow cytometry measures of CD68+ , CD68+ /CD14+ , and CD68+ /CD206+ ATMs per gram of tissue. The AMCounter software helps provide reproducible and efficient measures of IHC ATMs. Flow cytometry, IHC, and RT-PCR measures of adipose inflammation provide somewhat different information.


Evaluation of cardiac output from a tidally ventilated homogeneous lung model.
We used the direct Fick measurements to validate a method for estimating cardiac output by iteratively fitting VCO(2) at the mouth to lung model values. This model was run using a series of 50, 30 and 10 breaths to test sensitivity to number of breaths used for fitting. The lung was treated as a catenary two-compartment lung model consisting of a dead space compartment connected with a single alveolar space compartment, perfused with constant pulmonary blood flow. The implemented mathematical modeling described variations in O(2) and CO(2) compartmental fractions and alveolar volume. This model also included pulmonary capillary gas exchange. Experimental data were collected from measurements performed on six healthy subjects at rest and during 20, 40, 60 and 85-90% of peak V(O)(2). The correlation between the two methods was highest and the average agreement between the methods was best using 50 breaths R = 095; P < 0.0001; Q(model) = 1.1Q(Fick) - 2.3). The mean difference and lower to upper limits of agreement between measured and estimated data were 0.7 l/min (-2.7 to 4.1 l/min) for cardiac output; -0.9 ml/100 ml (-1.3 to -0.5 ml/100 ml) for arterial O(2) content; -0.8 ml/100 ml (-3.8 to 2.2 ml/100 ml) for mixed venous O(2) content and -0.1 ml/100 ml (-2.9 to 2.7 ml/100 ml) for arteriovenous difference O(2) content. The cardiac output estimated by the lung model was in good agreement with the direct Fick measurements in young healthy subjects.


Integration of trauma and rehabilitation services is the answer to more cost-effective care.
The pathway from acute trauma care to inpatient rehabilitation has not been previously studied in New South Wales (NSW), Australia. This study aimed to examine the outcomes of patients transferred from a trauma service to its 'in-house' rehabilitation service (Group A) compared with outcomes of patients transferred from a designated trauma centre to an external rehabilitation service (Group B). This is carried out to identify any inefficiencies, delays and opportunities for improvement. This is a retrospective cohort study using linked registry data. This study included all patients admitted after a motor vehicle collision to trauma services in NSW over the period of 2009-2012, who required inpatient rehabilitation. Those requiring specialized brain or spinal injury rehabilitation or those who went to private rehabilitation units were excluded. There were 249 patients in this cohort with majority (59%) in Group A and the remainder in Group B. There was no significant difference between the age of the patients, injury severity or acute length of stay (LOS) between the two groups. Admission and discharge functional independence measure scores were also similar between the two groups. There was a significant difference in the LOS in rehabilitation (30 days for Group A compared with 40 days in Group B, P = 0.02). Transferring patients to an external rehabilitation service from a designated trauma service is less efficient than providing the same care by the 'in-house' rehabilitation service. There may be opportunities to improve the efficiency of trauma management and reduce costs.


Vertebral fracture assessment in asymptomatic men and its impact on management.
Recognition of vertebral fractures (VFs) change the patient's diagnostic classification, estimation of fracture risk, and threshold for pharmacological intervention. Vertebral fracture assessment (VFA) enables the detection of VFs in the same session as bone mineral density (BMD) testing. To study prevalence and risk factors of VFs using VFA in asymptomatic men and measure its impact on patients' management. We enrolled 791 men aged between 45 and 89 (mean age, weight and BMI of 62.4±8.6) (45 to 89) years, 74.9±12.7 (40 to 163) and 26.3±4.0 (16.6 to 43.8) kg/m(2), respectively. Lateral VFA images and scans of the lumbar spine and proximal femur were obtained using a GE Healthcare Lunar Prodigy densitometer. VFs were defined using a combination of Genant semiquantitative (SQ) approach and morphometry. VFs were identified in 318 (40.3%): 206 (26.0%) had grade 1 and 112 (14.2%) had grade 2 or 3. As would be expected, the prevalence of VFA-detected fractures globally increased significantly with age and as BMI and BMD declined. A fracture was identified on VFA in 85 (32.4%) of men with normal BMD (6.9% had grade 2/3 VFs) and in 144 (35.8%) with osteopenia (11.7% had grade 2/3 VFs). Stepwise regression analysis showed that presence of VFs was independently related to the osteoporotic status (OR=4.761, 95%CI [2.956-7.668]; p<0.0001) and current smoking (OR=1.717, 95%CI [1.268-2.323]; p=0.002). Our results support the recommendation to enlarge the indications of VFA to all the men referred for DXA measurement.


Any physiological role for prostacyclin in regulation of fetal vessel tone?
This study investigates the contribution of endogenous prostacyclin and nitric oxide (NO) for maintenance of umbilical artery tone in vitro. Treatment with indomethacin as well as removal of the endothelium was followed by contractions of umbilical arteries and a reduced formation of prostacyclin. In contrast, vessel tone was not affected by inhibition of NO synthesis, using nitro-L-arginine. Thus, prostacyclin rather than nitric oxide appears to be the endogenous endothelium-derived factor in the umbilical circulation that is involved in regulation of vessel tone.


Near-Infrared Lanthanide-Based Emission from Fused Bis[Ln(III)/Zn(II) 14-metallacrown-5] Coordination Compounds.
A set of (Ln[14-MCZn(II)N(quinHA)-5])2Ln2Zn2(quinHA)2(ph)2(Hph)4(OH)8(H2O)4 metallacrowns (Ln-1, Ln = Tb, Gd, or Yb; H2quinHA = quinaldic hydroxamic acid, H2ph = phthalic acid) have been synthesized via solution-state self-assembly. The metallacrowns possess an uncommon topology within the metallacrown family where two rarely seen 14-metallacrown-5 moieties are fused by a Yb2Zn2(quinHA)2 bridge. Moreover, Yb-1 analyzed in the solid state exhibits a characteristic near-infrared luminescence signal arising from Yb3+ 2F5/2→2F7/2 transition despite the proximity of high energy O-H oscillators.


Fine-needle antegrade pyelography of transplanted kidneys.
Ureteral obstruction or perforation must be considered as a cause of poorly functioning renal transplants. Sonography and radionuclide scanning will demonstrate outflow obstruction and/or pararenal fluid collection, but do not usually provide sufficient information on the site of the lesion. In these cases we have successfully used fine-needle puncture of the renal pelvis under sonographic guidance, and antegrade pyelography. This technique shows excellent anatomical details of the renal pelvis and ureter.


A sensitive and rapid determination of zinc ion (Zn2+) using electrochemical sensor based on f-MWCNTs/CS/PB/AuE in drinking water.
An electrochemical method for detecting the presence of zinc (Zn2+) ions in drinking water was developed using functionalized multi-walled carbon nanotubes (f-MWCNTs) and chitosan (CS). Numerous cylinder-shaped graphene molecules make up f-MWCNTs, which have a high mechanical and electrical conductivity. CS benefits from nanomaterials include biocompatibility, biodegradability, and low toxicity, which are excellent in capacity absorption of metal ions. Dangerous levels of metal ions such as zinc are currently present in drinking water as a result of human and natural activity. Zinc toxicity is associated with a variety of disorders, including Alzheimer's, Parkinson's, diabetes, and cancer. This study incorporated f-MWCNTs and CS with Prussian blue (PB) immobilised on a gold electrode (AuE). Several parameters, including as buffers, pH, scan rate, redox indicator, accumulation time, and volume, were optimised using the cyclic voltammetry (CV) method. According to the CV method, the optimal parameters were phosphate buffered saline (0.1 M, pH 2), 5 mM Prussian blue, 200 mVs-1 scan rate, and 5 s accumulation time. Under ideal circumstances, the differential pulse voltammetry (DPV) method was used to determine the Zn2+ ions concentration range of 0.2-7.0 ppm. The limit of detection (LOD) was 2.60 × 10-7 mol L-1 with a correlation coefficient of R2 = 0.9777. The recovery rate of the developed sensor (f-MWCNTs/CS/PB/AuE) ranged from 95.78 to 98.96%. The developed sensor showed a variety of advantages for detecting Zn2+ in drinking water, including a quick setup process, quick detection, high sensitivity, and mobility. This study developed the essential sensor for monitoring Zn2+ levels in drinking water in the future.


Motor and Cerebellar Architectural Abnormalities during the Early Progression of Ataxia in a Mouse Model of SCA1 and How Early Prevention Leads to a Better Outcome Later in Life.
Exposing developing cerebellar Purkinje neurons (PNs) to mutant Ataxin1 (ATXN1) in 82Q spinocerebellar ataxia type 1 (SCA1) mice disrupts motor behavior and cerebellar climbing fiber (CF) architecture from as early as 4 weeks of age. In contrast, if mutant ATXN1 expression is silenced until after cerebellar development is complete, then its impact on motor behavior and cerebellar architecture is greatly reduced. Under these conditions even 6 month old SCA1 mice exhibit largely intact motor behavior and molecular layer (ML) and CF architecture but show a modest reduction in PN soma area as a first sign of cerebellar disruption. Our results contrast the sensitivity of the developing cerebellum and remarkable resilience of the adult cerebellum to mutant ATXN1 and imply that SCA1 in this mouse model is both a developmental and neurodegenerative disorder.


Downregulation of Apaf-1 and caspase-3 by RNA interference in human glioma cells: consequences for erucylphosphocholine-induced apoptosis.
Erucylphosphocholine (ErPC) exerts strong anticancer activity in vivo and in vitroand induces apoptosis even in chemoresistant glioma cell lines. We investigated the contribution of Apaf-1 and caspase-3 to the apoptotic response to ErPC using RNA interference (RNAi) in human glioblastoma cells. We could demonstrate that human glioma cell lines are susceptible to RNAi. Apaf-1 and caspase-3 are amenable to specific small interfering RNA (siRNA)-induced degradation resulting in a reduction of protein levels to 8-33% (Apaf-1) and to 30-50% (caspase-3). Transfection of siRNA directed to Apaf-1 and caspase-3 specifically reduced caspase-3 processing induced by ErPC treatment and yielded a reduction in cells that undergo ErPC-induced apoptosis to 17-33% (Apaf-1) and to 38-50% (caspase-3). The caspase-3 siRNA experiments were corroborated in caspase-3-deficient and -reconstituted MCF-7 breast cancer cells. Survival assays and morphological observations revealed that caspase-3 reconstitution significantly sensitized MCF-7 cells to ErPC. Exploring the caspase cascade responsible for ErPC-induced apoptosis MCF-7 cells provided evidence that caspase-3 is required for the activation of caspases-2, -6 and -8 and also participates in a feedback amplification loop. Our results provide evidence that Apaf-1 and caspase-3 are major determinants of ErPC-induced apoptosis and the possible use of ErPC in a clinical setting is discussed.


Bioaccessibility, sources and health risk assessment of trace metals in urban park dust in Nanjing, Southeast China.
Arsenic, Cd, Co, Cr, Cu, Mn, Ni, Pb, V, and Zn total concentrations and bioaccessibilities in 15 urban park dust samples were determined. The oral bioaccessibility measured by the Simple Bioaccessibility Extraction Test (SBET) decreased in the order of Pb>Cd>Zn>Mn>Cu>Co>V>Ni>As>Cr. The Tomlinson pollution load index (PLI) and geoaccumulation index (I(geo)) were calculated to evaluate the pollution extent to which the samples were contaminated. Sources were identified using principal component analysis and Pb isotope compositions. Most elements except Co and V were considered to mainly originate from anthropogenic sources. Non-carcinogenic and carcinogenic risks to humans through urban park dust exposure were assessed using the oral bioaccessibilities of the elements. Ingestion was the main pathway for non-carcinogenic risk. The hazard quotients were below the safe level (=1) for all elements, however, Pb (0.154) and As (0.184) posed potential higher risks to children than adults. The carcinogenic effects occurring were below the acceptable level (10(-4)) for As and <10(-6) for Cd, Co, Cr, and Ni.


Wheat growth, applied water use efficiency and flag leaf metabolome under continuous and pulsed deficit irrigation.
The intensity and frequency of precipitation events are predicted to change over the coming decades. For many areas, longer periods without rainfall are expected. We investigated the importance of irrigation frequency under water deficit conditions for growth, physiology and chemistry of wheat (Triticum aestivum). Drought-stressed plants received 40% of the water provided for control plants and were either watered every other day (continuous drought, cd) or every eight days (pulsed drought, pd). Maximum quantum yield of photosystem II (Fv/Fm), aboveground biomass, applied water use efficiency (WUEapl) and the flag leaf metabolome were assessed twice during development. Fv/Fm was not affected by irrigation. Drought-exposed plants produced less biomass, but had higher WUEapl than control plants. More metabolic features responded to the pd compared to the cd treatment and more features were increased than decreased in pool size in flag leaves. Salicylic acid glucoside was generally decreased under drought. In pd plants, two benzoxazinoid glucosides were enhanced at the first time point and concentrations of several flavonoid glycosides were modulated. This study extends our knowledge about drought effects on wheat; it highlights that the frequency of watering determines how plant growth, physiology and metabolism are affected by drought.


[The evolving career profile of radiation therapists].
Over the last few years, the radiation therapist profession has undergone major developments. In radiotherapy, the teams, and their organization as well as the techniques have changed, however always with the goal of improving treatment quality for patients. Throughout interviews, this article offers to show three missions that have been assigned to French radiation therapists, such as the initial consultation, the role of the radiation therapist with the linear accelerator with onboard MRI, and paramedical research. The contribution of new technologies, the modification of the types of participants on the patient journey, as well as the thought process about the use of evidence-based practice and radiation therapist research have initiated changes for the job description, the beginning of more advanced practices, and a perspective of evolution within this profession.


Small-animal blood exchange is an emerging approach for systemic aging research.
We describe a small-animal blood exchange approach developed for aging research as an alternative to heterochronic parabiosis or plasma injections. In parabiosis, animals are surgically coupled, which has several disadvantages, including difficulty controlling experimental procedure, the effects of shared organs, environmental enrichment from jointly exploring the housing enclosure, involuntary exercise and an imprecise onset of blood sharing. Likewise, in plasma injections, the added volumes need to be small, and there is little flexibility in changing the relative contributions of ectopic to endogenous blood components. These factors complicate the conclusions and interpretations, including the identification of key mechanisms and molecular or cellular determinants. Our approach, where blood is exchanged between animals without them being surgically coupled, is less invasive than parabiosis. The percentage of exchanged blood or other exchanged fluids is known and precise. The age of plasma and cells can be mixed and matched at all desired relative contributions to the endogenous systemic milieu, and the onset of the effects can be accurately delineated. In this protocol, we describe the preparatory and animal surgery steps required for small-animal blood exchange in mice and compare this process with parabiosis and plasma injections. We also provide the design, hardware and software for the blood exchange device and compare automated and manual exchange methods. Lastly, we report mathematical modeling of the dilution of blood factors. The fluid exchange takes ~30 min when performed by a well-trained biomedical scientist; the entire process takes ~2 h.


Fibrous bands associated with higher Masaoka stage and poor recurrence-free survival in patients with thymoma.
Fibrous bands (FBs) are one of the histological features in tumors which can be confirmed by hematoxylin and eosin (H&E)-stained slides. FBs have been reported to correlate with malignancy in various tumors. This study aimed to investigate whether the presence of FBs is associated with malignancy in thymoma. A total of 123 consecutive patients with thymoma who underwent microscopically complete resections from January 2000 to December 2018 were enrolled into this study. H&E-stained slides of all thymoma patients were re-examined. Study patients were classified into two groups: with FBs (n = 36) and without FBs (n = 87). Clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) were compared between the two groups. Furthermore, multivariate analyses were performed to identify whether the presence of FBs was associated with higher Masaoka stage and poor prognosis in patients with thymoma. The Masaoka stage was found to be higher and recurrence more likely in thymoma patients with FBs than in those without. RFS was significantly poorer in thymoma patients with FBs than in those without, although no significant difference was observed in OS between them. The presence of FBs was significantly associated with higher Masaoka stage in the multivariate analysis using logistic regression. Additionally, the presence of FBs was an independent prognostic factor for poor RFS in multivariate analysis using Cox's proportional hazards model. The presence of FBs in patients with thymoma was associated with higher Masaoka stage, higher recurrence rate, and poorer RFS. SIGNIFICANT FINDINGS OF THE STUDY: Fibrous bands (FBs) are bands of fibrosis dividing tumors into different-sized irregular islands. The presence of FBs is associated with higher Masaoka stage and poor recurrence-free survival in patients with thymoma. The presence of fibrous bands might be associated with the malignant behavior of thymoma. Confirming the presence or absence of FBs may result in personalized medication for patients with thymoma.


B-Cell depletion therapy in IgG4-related disease: State of the art and future perspectives.
IgG4-related disease (IgG4-RD) is an increasingly recognized immune-mediated fibroinflammatory disorder that promptly responds to glucocorticoids but commonly relapses during steroid tapering or after discontinuation. In the last few years, B-cell depletion therapy with rituximab (RTX) proved to be effective in the induction of remission and maintenance treatment of IgG4-RD, providing a new powerful tool in the management of this emerging condition. In this review, we outline the pathogenetic rationale for using B-cell depleting agents in IgG4-RD, we summarize available clinical experience with RTX in this disease, and we describe future possible therapies targeting B-lymphocytes that are now in the pipeline.


Modulation of base selectivity for a base-discriminating fluorescent nucleobase by addition of mercury ion.
We altered the fluorescence emission selectivity of a base-discriminating fluorescent base, (Py)U, from A-selective to T-selective by the addition of mercury ion. The strong fluorescence from a duplex containing the (Py)U/T base pair was specific to the mercury ion among divalent metal ions, providing a unique method for sensing mercury ions in aqueous solutions.


Results of surgical treatment in patients with arachnoid cysts.
A retrospective study of 35 patients operated upon for arachnoid cysts during the last 10 years was carried out. In 19 patients treated by craniotomy, membrane resection and drainage into the basal cisterns, clinical improvement could be noted in 13 cases. Correspondingly on the CT-controls the cysts were found to have disappeared in two cases and were reduced in size in seven patients. In 11 patients, however, who were initially treated by a shunting procedure, seven patients became free of symptoms. Postoperative CT-controls showed in three cases a significant reduction of the size of the cyst, which remained unchanged in two other cases. In five patients with the combination of a nonspace-occupying arachnoid cyst and subdural effusions, drainage of the latter only was sufficient to relieve the clinical symptoms. The prominent findings were the high complication rate of the primary or secondary shunting procedures (48%), as well as the close correlation between the clinical outcome and the postoperative CT-controls.


Effects of microplastics and nanoplastics in shrimp: Mechanisms of plastic particle and contaminant distribution and subsequent effects after uptake.
To date, previous studies have reported the adverse effects of microplastics (MPs) and nanoplastics (NPs) on both freshwater and marine organisms. However, the information on MPs' and NPs' effects on shrimp species is scarce. In addition, the factors influencing the distribution of these particles in aquatic systems have been explained, yet the mechanisms behind MPs and NPs distribution and consumption, specifically to crustaceans and shrimp, have not been elucidated in detail. The effects of MPs and NPs as well as plastic-carried contaminants and pathogens on shrimp are critical to shrimp production and subsequent human consumption. Recent findings are required to review and discuss to open up new avenues for emerging Shrimp and crustacean research for sustainability. This review summarizes the distribution and fate of MPs and NPs along with contaminants and pathogens and identifies potential risks to shrimp health. The transport of MPs and NPs is influenced by their plastic properties, hydrodynamics, and water properties. Additionally, the fate of these particles on a plastic surface (plastisphere) is regulated by contaminant properties. Pathogens thriving on plastic surfaces and contaminants adsorbed can reach aquatic organisms directly with plastic particles or indirectly after release to an aquatic environment. MPs and NPs can be absorbed by shrimp through their gills and mouth and accumulate in their internal organs. Innate immunity influenced the degree of survival rate, tissue damage, alteration of gut microbiota, and increased oxidative stress caused by MPs and NPs accumulation. The studies on the effects of MPs and NPs are still not sufficient to understand how these particles are absorbed from various parts of the shrimp body and the fate of these plastics inside the body.


A review of gestational diabetes mellitus management, risk factors, maternal and neonatal outcomes in two major maternity hospitals in the United Arab Emirates: A report from Dubai.
This study was conducted in order to explore and analyze the status of gestational diabetes (GDM) amongst pregnant women in Dubai, United Arab Emirates (UAE); a country with high prevalence of diabetes. We aimed to describe GDM-associated risk factors and clinical outcomes of pregnant women and their neonates. Our objective was to contribute to the broader literature on reproductive health disparities and to inform efforts to improve GDM care at our region. Chart review of case records were used to collect data on both maternal and neonatal parameters and outcomes during the specified study period from two main maternity hospitals in Dubai. UAE national women with GDM were more prone to be obese or overweight compared to non-UAE women (p < 0.0001, and p < 0.0001 respectively). In addition, UAE national women with GDM had higher history of GDM in previous pregnancies (p < 0.0001) and more family history of diabetes (p < 0.0001).The neonate admission into NICU was significantly associated with cesarean section (p < 0.0001), twins (p < 0.0001), preeclampsia (p = 0.02), receiving MgSO4 (p = 0.02), birth weight less than 2500 g (p < 0.0001), low Apgar scores (p < 0.0001), baby with congenital anomaly (p < 0.0001), and neonatal hypoglycemia (p < 0.0001). Our results demonstrate that pregnant women with GDM who are UAE nationals and have higher parity need to be under special attention during their pregnancy in order to improve both maternal and neonatal outcomes.


[Maternal morbidity and mortality in Brazil and the urgency of a national surveillance system for maternal near miss].
The World Health Organization (WHO) recommends the analysis of severe maternal morbidity/maternal near miss cases as complementary to the analysis of maternal deaths since the incidence is higher and the predictive factors of the two outcomes are similar. Considering that the reasons for maternal mortality in Brazil have remained constant despite the commitment made during the General Assembly of the United Nations in 2015, this article aims to propose a nationwide maternal near miss surveillance system. We propose the inclusion of maternal near miss events in the National List of Compulsory Notification of Diseases, Injuries, and Public Health Events, via the compatibility of the diagnostic criteria of maternal near miss, informed by the WHO, with the codes of the International Classification of Diseases for the identification of cases. Considering that health surveillance is based on several sources of information, notification could be made by health service professionals as soon as a confirmed or suspected case is identified. With the study of the factors associated with the outcomes, we expect a qualified evaluation of the services focused on obstetric care and consequent implementation of more efficient policies to prevent not only maternal death but also events that can both cause irreversible sequelae to women's health and increase the risk of fetal and neonatal death.


Transfer technique of an anomalous coronary artery from the anterior pulmonary artery.
We describe a simple rerouting technique for an anteriorly situated anomalous left coronary artery from the pulmonary artery (ALCAPA), extending the left main coronary trunk with autologous aortic and pulmonary tissue. This technique is reproducible. It provides a tension-free aortocoronary anastomosis and a full potential for future growth.


Bivariate spline solution of time dependent nonlinear PDE for a population density over irregular domains.
We study a time dependent partial differential equation (PDE) which arises from classic models in ecology involving logistic growth with Allee effect by introducing a discrete weak solution. Existence, uniqueness and stability of the discrete weak solutions are discussed. We use bivariate splines to approximate the discrete weak solution of the nonlinear PDE. A computational algorithm is designed to solve this PDE. A convergence analysis of the algorithm is presented. We present some simulations of population development over some irregular domains. Finally, we discuss applications in epidemiology and other ecological problems.


The Characteristics, Uses, and Biases of Studies Related to Malignancies Using Google Trends: Systematic Review.
The internet is a primary source of health information for patients, supplementing physician care. Google Trends (GT), a popular tool, allows the exploration of public interest in health-related phenomena. Despite the growing volume of GT studies, none have focused explicitly on oncology, creating a need for a systematic review to bridge this gap. We aimed to systematically characterize studies related to oncology using GT to describe its utilities and biases. We included all studies that used GT to analyze Google searches related to malignancies. We excluded studies written in languages other than English. The search was performed using the PubMed engine on August 1, 2022. We used the following search input: "Google trends" AND ("oncology" OR "cancer" or "malignancy" OR "tumor" OR "lymphoma" OR "multiple myeloma" OR "leukemia"). We analyzed sources of bias that included using search terms instead of topics, lack of confrontation of GT statistics with real-world data, and absence of sensitivity analysis. We performed descriptive statistics. A total of 85 articles were included. The first study using GT for oncology research was published in 2013, and since then, the number of publications has increased annually. The studies were categorized as follows: 22% (19/85) were related to prophylaxis, 20% (17/85) pertained to awareness events, 11% (9/85) were celebrity-related, 13% (11/85) were related to COVID-19, and 47% (40/85) fell into other categories. The most frequently analyzed cancers were breast (n=28), prostate (n=26), lung (n=18), and colorectal cancers (n=18). We discovered that of the 85 studies, 17 (20%) acknowledged using GT topics instead of search terms, 79 (93%) disclosed all search input details necessary for replicating their results, and 34 (40%) compared GT statistics with real-world data. The most prevalent methods for analyzing the GT data were correlation analysis (55/85, 65%) and peak analysis (43/85, 51%). The authors of only 11% (9/85) of the studies performed a sensitivity analysis. The number of studies related to oncology using GT data has increased annually. The studies included in this systematic review demonstrate a variety of concerning topics, search strategies, and statistical methodologies. The most frequently analyzed cancers were breast, prostate, lung, colorectal, skin, and cervical cancers, potentially reflecting their prevalence in the population or public interest. Although most researchers provided reproducible search inputs, only one-fifth used GT topics instead of search terms, and many studies lacked a sensitivity analysis. Scientists using GT for medical research should ensure the quality of studies by providing a transparent search strategy to reproduce results, preferring to use topics over search terms, and performing robust statistical calculations coupled with sensitivity analysis.


Whole blood transcriptional profiling reveals highly deregulated atherosclerosis genes in Philadelphia-chromosome negative myeloproliferative neoplasms.
The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are associated with a huge comorbidity burden, including an increased risk of cardiovascular diseases. Recently, chronic inflammation has been suggested to be the driving force for clonal evolution and disease progression in MPN but also potentially having an impact upon the development of accelerated (premature) atherosclerosis. Since chronic inflammation, atherosclerosis, and atherothrombosis are prevalent in MPNs and we have previously shown oxidative stress genes to be markedly upregulated in MPNs, we hypothesized that genes linked to development of atherosclerosis might be highly deregulated as well. Using whole blood gene expression profiling in patients with essential thrombocythemia (ET; n = 19), polycythemia vera (PV; n = 41), or primary myelofibrosis (PMF; n = 9), we herein for the first time report aberrant expression of several atherosclerosis genes. Of 84 atherosclerosis genes, 45, 56, and 46 genes were deregulated in patients with ET, PV, or PMF, respectively. Furthermore, BCL2L1, MMP1, PDGFA, PTGS1, and THBS4 were progressively significantly upregulated and BCL2 progressively significantly downregulated from ET over PV to PMF (all FDR <0.05). We have for the first time shown massive deregulation of atherosclerosis genes in MPNs, likely reflecting the inflammatory state in MPNs in association with in vivo activation of leukocytes, platelets, and endothelial cells being deeply involved in the atherosclerotic process.


A "building block" approach to the new influenza A virus entry inhibitors with reduced cellular toxicities.
Influenza A virus (IAV) is a severe worldwide threat to public health and economic development that results in the emergence of drug-resistant or highly virulent strains. Therefore, it is imperative to develop potent anti-IAV drugs with different modes of action to currently available drugs. Herein, we show a new class of antiviral peptides generated by conjugating two known short antiviral peptides: part-1 (named Jp with the sequence of ARLPR) and part-2 (named Hp with the sequence of KKWK). The new peptides were thus created by hybridization of these two domains at C- and N- termini, respectively. The anti-IAV screening results identified that C20-Jp-Hp was the most potent peptide with IC50 value of 0.53 μM against A/Puerto Rico/8/34 (H1N1) strain. Interestingly, these new peptides display lower toxicities toward mammalian cells and higher therapeutic indices than their prototypes. In addition, the mechanism of action of C20-Jp-Hp was extensively investigated.


Comparison of peritoneal dialysis catheter insertion techniques: Peritoneoscopic, radiological and laparoscopic : A single-centre study.
Our centre introduced peritoneoscopic insertion of peritoneal dialysis (PD) catheter by nephrologists as a new method in August 2009 for its potential benefits. The aim of this study was to compare perioperative complications and catheter survival of three techniques: peritoneoscopic, surgical and radiological techniques within a single dialysis centre. This study used retrospective analysis of all PD catheter inserted from 1 August 2009 to 31 July 2013 within Counties Manukau DHB, Auckland, New Zealand. During the study period, 293 PD catheters were inserted, 84 (29%) peritoneoscopic (P), 140 (48%) surgical (S) and 69 (23%) radiological (R). Total duration of follow-up was 5848 catheter-months, with median follow-up of 17 months. There was no difference in perioperative exit-site infections and overall early infections. There was however increased overall perioperative complications in P compared with R (HR 2.08; P < 0.05), predominantly from catheter removal within 60 days. Although there was no difference observed in first catheter 1-year and overall survival between insertion techniques, there was poorer complication-free survival comparing P to S (HR 1.82, P = 0.001) but not to R. Analyses of the latter cohort of P confirmed improvement in catheter survival compared with an earlier cohort and to other insertion techniques. Peritoneoscopic PD catheter insertion is demonstrated to be a suitable alternative technique. As with any new procedure, 'learning curve' effects and development of operator expertise need to be taken into consideration.


Effects of digitalis on the normal and the failing heart.
Although it has been known for more than a century that digitalis glycosides exert a powerful beneficial effect on patients with heart failure, atrial fibrillation and a rapid ventricular rate, it was believed for many years that the drug exerts this clinical effect primarily by slowing the heart rate. It was also thought that the extra-cardiac vascular actions of digitalis might be responsible for its therapeutic effect. It has now been established that cardiac glycosides cause arteriolar and venous constriction in a variety of mammalian species including human beings, and that this vasoconstriction involves the coronary vascular bed as well, but it is believed that these actions are not responsible for any beneficial clinical effect. A variety of investigations on cardiac muscle in vitro, anesthetized and conscious dogs and anesthetized and conscious human subjects have shown that cardiac glycosides improve the contractility of failing mammalian myocardium. It has become clear that digitalis also stimulates the contractility of the nonfailing heart. The degree of augmentation of contractility induced by cardiac glycosides is related inversely to the baseline contractile state. Myocardial oxygen consumption, which is increased in the normal heart by the positive inotropic action of glycosides, is actually reduced or remains constant in the failing heart. Cardiac glycosides increase the contractility of the globally ischemic heart, but their actions in chronic ischemic heart disease with regional impairment of function are complex. Deterioration of segmental performance occurs in ischemic and necrotic segments, while improvement of contractility occurs in adjacent normal segments.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of the Effectiveness of Ring-Stripping Retrograde Endarterectomy and Carotid Artery Crossover Bypass in the Treatment of Patients with Symptomatic Riles Type 1A Common Carotid Artery Occlusion.
The surgical procedure most appropriate for treating symptomatic Riles type 1A common carotid artery occlusion (CCAO) is unclear. This study compares the effects of ring-stripping retrograde endarterectomy (RSRE) and carotid artery crossover bypass (CACB) on cerebral perfusion improvement in patients with symptomatic Riles type 1A CCAO. We conducted a retrospective analysis of symptomatic Riles type 1A CCAO patients treated at our centre. Postoperative improvements in the ipsilateral internal carotid artery (ICA) flow rate, ipsilateral cerebral blood perfusion (CBP) and the stroke recurrence rate were compared between patients who underwent RSRE and those who underwent CACB. A total of 20 CCAO patients were surgically treated at our centre from 2011 to 2018. Nine of these patients underwent RSRE, and eleven underwent CACB. No significant differences were identified between the groups in the ipsilateral blood flow rate of the ICA immediately after surgery and the ipsilateral-to-contralateral mean transit time ratios 1 day after surgery. However, the flow rate in the ICA was significantly higher in the RSRE group than in the CACB group 1 year after surgery (135.44 ± 19.22 ml/min vs. 116.36 ± 17.70 ml/min, p = 0.033). For CBP, the ipsilateral-to-contralateral mean transit time ratios were significantly lower in RSRE patients than in CACB patients 1 year after surgery (1.005 ± 0.052 vs. 1.064 ± 0.066, p = 0.044). In addition, the postoperative modified Rankin scale (mRS) score at the latest follow-up point (p = 0.884) and the stroke recurrence rate during the follow-up (88.9% vs. 90.9%, p > 0.999) were not significantly different between the two groups. Although the postoperative mRS score and the stroke recurrence rate were not significantly different between RSRE and CACB patients, compared to CACB, RSRE was better for improving the ipsilateral ICA flow rate and cerebral perfusion in symptomatic Riles type 1A CCAO patients.


Overlapping morphological and functional properties between M4 and M5 intrinsically photosensitive retinal ganglion cells.
Multiple retinal ganglion cell (RGC) types in the mouse retina mediate pattern vision by responding to specific features of the visual scene. The M4 and M5 melanopsin-expressing, intrinsically photosensitive retinal ganglion cell (ipRGC) subtypes are two RGC types that are thought to play major roles in pattern vision. The M4 ipRGCs overlap in population with ON-alpha RGCs, while M5 ipRGCs were recently reported to exhibit opponent responses to different wavelengths of light (color opponency). Despite their seemingly distinct roles in visual processing, previous reports have suggested that these two populations may exhibit overlap in their morphological and functional properties, which calls into question whether these are in fact distinct RGC types. Here, we show that M4 and M5 ipRGCs are distinct morphological classes of ipRGCs, but they cannot be exclusively differentiated based on color opponency and dendritic morphology as previously reported. Instead, we find that M4 and M5 ipRGCs can only be distinguished based on soma size and the number of dendritic branch points in combination with SMI-32 immunoreactivity. These results have important implications for clearly defining RGC types and their roles in visual behavior.


Effects of waste glass and waste marble on mechanical and durability performance of concrete.
Industrial waste has been rapidly increased day by day because of the fast-growing population which results environmental pollutions. It has been recommended that the disposal of industrial waste would be greatly reduced if it could be incorporated in concrete production. In cement concrete technology, there are many possibilities to use waste materials either as cement replacement or aggregate in concrete production. Two major industrials waste are glass and marble waste. The basic objective of this investigation is to examine the characteristics of concrete waste glass (WG) as binding material in proportions 10%, 20% and 30% by weight of cement. Furthermore, to obtain high strength concrete, waste marble in proportion of 40%, 50% and 60% by weight cement as fine aggregate were used as a filler material to fill the voids between concrete ingredients. Fresh properties were evaluated through slump cone test while mechanical performance was evaluated through compressive strength and split tensile strength which were performed after 7 days, 28 days and 56 days curing. Results show that, workability of concrete decreased with incorporation of waste glass and marble waste. Furthermore, mechanical performance improved considerably up 20% and 50% substitution of waste glass and waste marble respectively. Statistical approach of Response Surface Methodology (RSM) was used optimize both waste materials in concrete. Results indicate better agreement between statistical and experimental results.


Determining subcellular localization of novel drug targets by transient transfection in COS cells.
Genomics-based approaches are increasingly being used to identify disease-associated genes that represent potential new drug targets. As a first step in the validation of genes of unknown function, we describe a method for rapidly determining the subcellular localization of the gene product. If an immunotherapeutic approach is being considered, it is of particular interest to identify targets that are either on the cell-surface or secreted. Transient expression in COS cells combined with immunofluorescent staining provides a semi-high throughput method for determining the subcellular localization of multiple targets in parallel. COS cells are ideal for this purpose since: (i) they transfect easily; (ii) the high levels of expression that can be achieved transiently allow detection after 24 h; and (iii) the relatively large size and spread morphology of these cells allows the subcellular organelles to be easily visualized. To evaluate the system, we show prototype staining patterns for known cytoplasmic,secreted, Golgi-associated, endoplasmic reticulum-associated, and plasma membrane proteins, as well as data for novel targets. The localization of novel secretory and cell-surface proteins as determined by immunofluorescent staining, was confirmed by independent methods.


Vegetation complexity and the dynamics of modelled grazing systems.
The dynamics of a one-herbivore-many-plants system can often be summarised by a one-herbivore-one-plant model. The many plants are modelled as if they were a single plant species whose intrinsic rate of increase equals the harmonic mean of the specific intrinsic rates. The relationship between the parameters of the simple and complex system is given, and exceptions, nuances and stability properties are explored.


Rapid screening for 31 mutations and polymorphisms in the cystic fibrosis transmembrane conductance regulator gene by Lminex xMAP suspension array.
A suspension array hybridization assay is described for the detection of 31 mutations and polymorphisms in the cystic fibrosis transmembrane conductance regulator (CFTR) gene using Luminex xMAP technology. The Luminex xMAP system allows simultaneous detection of up to 100 different targets in a single multiplexed reaction. Included in the method are the procedures for design of oligonucleotide capture probes and PCR amplification primers, coupling oligonucleotide capture probes to carboxylated microspheres, hybridization of coupled microspheres to oligonucleotide targets, production of targets from DNA samples by multiplexed PCR amplification, and detection of PCR-amplified targets by direct hybridization to probe-coupled microspheres. Mutation screening with the system is rapid, requires relatively few sample manipulations, and provides adequate resolution to reliably genotype the 25 CFTR mutations and 6 CFTR polymorphisms contained in the ACMG/ACOG/NIH-recommended core mutation panel for general population CF carrier screening.


Comparative vascular responses in elasmobranchs to different structures of neuropeptide Y and peptide YY.
The vascular responses to neuropeptide Y (NPY) and peptide YY (PYY) were tested in several species of elasmobranchs to assess whether changes in sequence in these neuropeptides from elasmobranchs to mammals are associated with different physiological responses. NPY-like immunoreactivity was detected in the gut and in nerve fibres surrounding some, but not all, blood vessels of six species. Intravenous injection of dogfish, frog and human NPY in anaesthetised fish caused similar vasopressor effects in the three species tested, except human NPY which lowered blood pressure in one of the three. Dogfish NPY and PYY were equipotent pressor agents in two species, but PYY was significantly more potent than NPY in one species. NPY and PYY both contracted isolated gut arteries from three species, but had no effect on isolated efferent arteries tested. In conclusion, differential vascular responses in elasmobranchs are not associated with changes in NPY sequence across vertebrates, but may be with changes in PYY in some species.


Early undernutrition is associated with attenuated inflammatory response and alteration in pharmacological efficacy of indomethacin in rats.
The intent of this study is to examine whether intrauterine malnutrition provokes alterations in the progression of the acute and subchronic inflammatory response, and its influence on the pharmacological effect of indomethacin. Rat offspring of dams which were fed from the first day of their gestation to term receiving a balanced diet (Labina) or a basic regional diet (BRD) from northeastern Brazil. According to their dams, the offspring were divided in two groups: Control-N (nourished) and BRD-g (undernourished during gestation). At 2 months of age, the animals were divided into groups (n=06): (1) Animals that were subjected to carrageenan or (2) zymosan-induce paw edema (acute inflammation models) and (3) Animals that were subjected to cotton pellet-induced granuloma (subchronic inflammation model). All animals received (saline 0.9%; p.o.). Another set of adult offspring was submitted to the same procedure as above, but instead of saline they received (via gavage) a single oral dose of indomethacin (10mg/kg) for the animals subjected to acute inflammation models or 2mg/kg for seven consecutive days for the animals subjected to subchronic inflammation model. The animals were further divided in two groups: Control-NI (Control-N treated with indomethacin), and BRDI-g (BRD-g treated with indomethacin). The volume of hind paw swelling (mL) was measured at time zero (before), 30, 60, 120, 180 and 240 min after carrageenan or zymosan injection. In the subchronic model of inflammation, the pellets were removed and dried to a constant weight. Hind paw swelling, weight of granuloma, blood albumin and C-reactive protein (CRP) levels, leukocyte count and cytokine levels were evaluated as indicators of inflammation. Undernutrition during pregnancy caused fetal growth retardation which was shown in terms of low birth weight (5.38±0.28), when compared to the Control-N (7.26±0.64) group. The volume of paw edema, the serum levels of CRP and albumin and cytokine levels were lower than those in the BRD-g group when compared to those in the Control-N groups, in both models of acute inflammation studied. However, no difference was found in the total leukocyte count. When compared to the respective groups treated with saline (Control-N and BRD-g), the antiinflammatory effect of indomethacin in the animals of BRDI-g groups was lower than in the Control-NI groups, in the model of acute inflammation. In the model of subchronic inflammation, the pharmacological effect of indomethacin was effective only in nourished animals. Malnutrition in the early stages of development attenuated the severity of the acute inflammatory response, but there was no statistically significant change in subchronic inflammation induced by granulomatous lesion. Our findings provide impetus for larger trials to assess the influence of undernutrition on the pharmacokinetics/pharmacodynamics of indomethacin.


Hyperglycemia suppresses the sympatho-adrenal response to hypoxia, but not to handling stress.
We hypothesized that the ability of prior hyperglycemia to suppress the sympatho-adrenal response would depend on the type of stress. To test this hypothesis, hyperglycemia was induced in chronically catheterized rats, before submitting them to either hypoxia (7.5% O2) or handling stress. Central venous blood samples were drawn for the determination of plasma glucose, epinephrine (EPI), norepinephrine (NOR) and insulin concentrations. Hypoxia caused significant increases in plasma EPI and NOR concentrations (deltaEPI = + 2.95+/-0.68 nmol/l, deltaNOR = + 12.45+/-1.29 nmol/l). Hyperglycemia, antecedent to hypoxia, dose dependently reduced the sympatho-adrenal response. In contrast, the sympatho-adrenal response to handling stress was not affected by even marked antecedent hyperglycemia (deltaEPI = + 2.48+/-0.46 nmol/l, deltaNOR = + 3.12+/-0.69 nmol/l at glucose = 20.7+/-0.6 mmol/l; vs. deltaEPI = + 2.48 + 0.58 nmol/l, deltaNOR= +2.97+/-0.11 nmol/l at glucose = 6.77+/-0.17 mg/dl). Thus, antecedent hyperglycemia suppresses the hypoxia-induced activation of both the sympathetic nerves and the adrenal medulla, but not the activation induced by handling. We conclude that the ability of hyperglycemia to suppress sympathetic activation depends on the stress producing the activation. We therefore speculate that hypoxic stress has a metabolic component to its central activation that handling stress does not.


Distance delivery of mindfulness-based cognitive therapy for depression: project UPLIFT.
This study evaluated the efficacy of a newly developed, home-based depression intervention for people with epilepsy. Based on mindfulness-based cognitive therapy (MBCT), the eight-session, weekly intervention was designed for group delivery via the Internet or telephone. Forty participants were randomly assigned to intervention or waitlist. Depressive symptoms and other outcomes were measured at baseline, after intervening in the intervention group (~8 weeks), and after intervening in the waitlist group (~16 weeks). Depressive symptoms decreased significantly more in the intervention group than the waitlist group; Internet and telephone did not differ. This effect persisted over the 8 weeks when those waitlisted received the intervention. Knowledge/skills increased significantly more in the intervention than the waitlist group. All other changes, though not significant, were in the expected direction. Findings indicate that distance delivery of group MBCT can be effective in reducing symptoms of depression in people with epilepsy. Directions for future research are proposed.


Antimicrobial activity of daptomycin and selected comparators tested against bloodstream Staphylococcus aureus isolates from hemodialysis patients.
Patients on long-term hemodialysis are at a significantly higher risk for catheter-related bloodstream infections (BSI) than the general population. These infections are generally caused by gram-positive organisms, especially Staphylococcus aureus. In the present study, we evaluated the antimicrobial susceptibility patterns of S. aureus causing BSI in dialysis patients compared to those causing BSI in other patient populations. The potencies of daptomycin and various comparator agents were evaluated by reference broth microdilution methods for S. aureus bloodstream isolates from dialysis patients (606 strains) in 43 hospitals in North America and Europe. Susceptibility patterns for the dialysis isolate set were compared to those S. aureus causing BSI in other patient populations in the same hospitals and time period. Daptomycin was highly potent against S. aureus causing bacteremia in dialysis patients (MIC(50)/MIC(90), 0.25/0.5 microg/ml). Vancomycin (MIC(50)/MIC(90), 1/1 microg/ml) and linezolid (MIC(50)/MIC(90), 2/2 microg/ml) showed similar potency, and overall susceptibility rates for the three antibiotics were 99.8-100.0% susceptible. Linezolid and vancomycin were four- to eight-fold less potent than daptomycin. The overall susceptibility patterns of S. aureus strains from dialysis patients were very similar to those of non-dialysis patients.


Activation of insulin-sensitive phosphodiesterase by lectins and insulin-dextran complex in rat fat cells.
Membrane-bound low-Km cAMP phosphodiesterase was activated by concanavalin A, wheat germ agglutinin, and insulin-dextran complex under conditions of incubation with intact rat fat cells. Concanavalin A rapidly stimulated the enzyme activities and maximum was reached at 10 to 15 minutes. As little as 10 micrograms/mL concanavalin A activated the enzyme and a maximal response was obtained at 100 to 300 micrograms/mL, but concanavalin A and wheat germ agglutinin were less potent than insulin. Specific saccharide inhibitors completely abolished activation of the enzyme by lectins, but had no effect on the activation of insulin. Digestion of fat cells with 1 mg/mL trypsin for 15 minutes completely inhibited activation of the enzyme by insulin. However, concanavalin A was less sensitive to trypsinization. The insulin-dextran complex, which did not penetrate the plasma membrane, activated the enzyme and was one tenth as effective as the native insulin. These results suggest that the insulin-like actions of these lectins are provoked through coupling with the carbohydrate moiety on the cell membrane close to insulin receptors.


Prolonged hypoperfusion in the cerebral cortex following cardiac arrest and resuscitation in dogs.
Increasing cerebral vascular resistance and brain perfusion failure occur within 90 minutes following cardiac arrest and resuscitation. This study followed cortical perfusion for 18 hours after a 15-minute cardiac arrest. Six dogs were anesthetized with ketamine and gallamine and then mechanically ventilated. They were instrumented for arterial pressure, central venous pressure, and regional cerebral cortical blood flow (rCCBF) determined by thermodilution. A left thoracotomy and pericardiotomy were done. Two dogs served as non-arrest controls. Cardiac arrest was produced in four dogs with an intravenous bolus of KCl at 1 mEq/kg. After 15 minutes of cardiac arrest, the animals were resuscitated with internal massage, NaHCO3, epinephrine, and internal defibrillation. Cortical blood flow was followed for 18 hours. Arterial core temperature was never less than 35 C. Pre-arrest cortical blood flows were 0.86 cc/min/g (+/- 0.11). The two control animals had stable rCCBF (0.74 +/- 0.17) for all determinations during the 18-hour follow-up period. Determinations of rCCBF from 6 to 18 hours in post-arrest animals were 7% to 14% of pre-arrest values. We conclude that the post-resuscitation perfusion failure in the cortex is prolonged. Any potential for neuronal recovery, unless perfusion is protected, would not be realized given this phenomenon.


Development of the Japanese version of the Pediatric Quality of Life Inventory™ Transplant Module.
Health-related quality of life (HRQOL) is an important outcome in pediatric solid organ transplantation. Considering the emerging problems after transplantation, an evaluation of transplant-specific aspects of HRQOL is essential, but no validated HRQOL measure is available in Japan. The aim of this study was therefore to develop the Japanese version of the Pediatric Quality of Life Inventory™ (PedsQL) Transplant Module Child Self-Report and to investigate its feasibility, reliability, and validity. Based on the PedsQL linguistic validation process, the Japanese version of the PedsQL Transplant Module was developed through translation and cognitive interviews (patient testing). The scale's reliability and validity were investigated, using statistical analyses of field tests of the target population. Eighty-seven pairs of pediatric liver-transplant recipients and their parents participated in the field test. The pediatric patients completed the measure in 3-7 min, and the rate of missing items was low (0.27%). Excellent internal consistency and test-retest reliability were confirmed. Known-groups validity, concurrent validity, and convergent and discriminant validity also were confirmed. Excellent feasibility, reliability, and validity of this Japanese self-report version of the PedsQL Transplant Module Child Self-Report were verified. As a measure of transplant-specific aspects of HRQOL in Japanese pediatric patients who have undergone organ transplants, the Japanese version of the PedsQL Transplant Module is appropriate for use in clinical and research settings.


Isolation, identification and characterization of a novel Ralstonia sp. FD-1, capable of degrading 4-fluoroaniline.
A gram-negative strain, designated as FD-1, isolated from aerobic activated sludge was capable of metabolizing 4-fluoroaniline (4-FA) as its sole carbon and nitrogen source and energy supply. According to the Biolog GNIII detection method 17 of 71 carbon substrates were easily utilized, while 12 of 23 substrates did not inhibit strain FD-1. The 16S rDNA sequence from strain FD-1 was 99 % similar to Ralstonia sp., suggesting that it belonged to the genus Ralstonia. The optimal conditions for growth and 4-FA degradation were pH 7 and 30 °C. The tolerance to 4-FA were 1,250 mg/L, while the tolerance to salinity was 15 g/L. Catechol 2,3-dioxygenase activity was detected and degradation intermediates were analyzed by liquid chromatography mass spectrometry leading to a proposed degradation pathway and suggesting that extradiol cleavage was involved in 4-FA degradation. This is the first report on the degradation of 4-FA by a bacterium from the Ralstonia genus.


Intracystic Papillary Neoplasm of Gallbladder Mimicking Metastatic Malignancy on PET/CT.
Intracystic papillary neoplasm of the gallbladder is a rare preinvasive neoplastic lesion with similar characteristics as intraductal papillary mucinous neoplasm and other papillary neoplasms of pancreaticobiliary system. We report a case of 48-year-old woman with a history of recurrent right flank chondrosarcoma and gallbladder lesion on MRI and PET/CT interpreted as indeterminate for metastatic disease. Subsequent cholecystectomy showed intracystic papillary neoplasm. With gallbladder lesions being rare on PET/CT, this case illustrates the importance of considering both primary and secondary tumors in the differential diagnosis.


[Ketogenic diet as a trigger for diabetic euglycaemic ketoacidosis in a patient under treatment with iSGLT2].
Euglycaemic diabetic ketoacidosis is a possible adverse effect of selective sodium-glucose cotransporter inhibitors 2 (isGLT2) in patients with diabetes. However, the main scientific societies have recently recommended low or very low carbohydrate diets for the treatment of diabetes, relating the latter with the onset of ketosis. The combination of treatment with these drugs and following this type of diet can be dangerous. We present the case of a 64-year-old patient, suffering from LADA type diabetes, under usual treatment with intensive insulin therapy in 4 doses, who a few days after starting empagliflocin and a very low carbohydrate diet presented severe euglycaemic ketoacidotic decompensation.


Magnetic resonance urography in patients with neurogenic bladder dysfunction and spinal dysraphism.
To investigate the reliability of magnetic resonance urography (MRU) using heavily T2-weighted very fast spin-echo sequences in imaging the upper urinary tract in patients with spinal dysraphism and neuropathic bladder dysfunction. Patients with neuropathic bladder dysfunction secondary to spinal dysraphism may have gross spinal deformity, which makes assessing the urinary tract extremely difficult by ultrasonography or intravenous urography. The study included 50 patients (median age 33 years, range 19-52) with a median (range) Cobb's angle of 60 (0-240) degrees. No contrast medium was given but all patients received 20 mg of intramuscular frusemide 20-30 min before MRU. Thirty-five patients had previous ultrasonography, during which only 42 kidneys and no ureters were visible. Of the 94 renal tracts, MRU visualized all kidneys and 86 (89%) ureters. There was good agreement amongst observers on assessing the kidneys and pelvicalyceal systems (kappa > or = 0.61) but only moderate agreement on evaluating the ureters (kappa < or = 0.61). There was disagreement on normality vs renal parenchymal scarring in 14 (15%) kidneys, about no dilatation vs dilatation of the pelvicalyceal system in 14 (15%) systems and about no dilatation vs dilatation of the ureter in 20 (22%) ureters. The overall quality of the MRU images was rated highly, with a mean (range) score of 4.6 (3-5). MRU provides a reliable noninvasive technique for imaging the upper tract in patients who were previously difficult to investigate.


The role of Roux-en-Y hepaticojejunostomy for the management of biliary complications after living donor liver transplantation.
Post living donor liver transplantation (LDLT) biliary complications can be troublesome over the post-operative course of patients, especially those with recurrent cholangitis or choledocholithiasis. Thus, in this study, we aimed to evaluate the risks and benefits of Roux-en-Y hepaticojejunostomy (RYHJ) performed after LDLT as a last option to deal with post-LDLT biliary complications. Retrospectively, of the 594 adult LDLTs performed in a single medical center in Changhua, Taiwan from July 2005 to September 2021, 22 patients underwent post-LDLT RYHJ. Indications for RYHJ included choledocholithiasis formation with bile duct stricture, previous intervention failure, and other factors. Restenosis was defined if further intervention was needed to treat biliary complications after RYHJ was performed. Thereafter, patients were categorized into success group (n = 15) and restenosis group (n = 4). The overall success rate of RYHJ in the management of post-LDLT biliary complications was 78.9% (15/19). Mean follow-up time was 33.4 months. As per our findings, four patients experienced recurrence after RYHJ (21.2%), and mean recurrence time was 12.5 months. Three cases were recorded as hospital mortality (13.6%). Outcome and risk analysis presented no significant differences between the two groups. A higher risk of recurrence tended to be related to patients with ABO incompatible (ABOi). RYHJ served well as either a rescue but definite procedure for recurrent biliary complications or a safe and effective solution to biliary complications after LDLT. A higher risk of recurrence tended to be related to patients with ABOi; however, further research would be needed.


Prostaglandin E1 raises the cAMP content of peripheral nerve tissue.
Prostaglandins of the E type have been found to increase the cAMP content in peripheral nerve tissue of several species. In rabbit vagus nerve, for example, the effect is rapid (1--5 min), it can be elicited by 10(-6) M PGE1 and it is maximal at 10(-5) M. In this preparation the increase of the cAMP content caused by PGE1 is about 4-fold, whereas it is about 2-fold in the vagus of calf. PGE1 also causes an increase in cAMP level in the superior cervical ganglion of calf, rat and rabbit. In these tissues, however, the presence of a phosphodiesterase inhibitor is required for cAMP accumulation.


Diagnosis of triple negative breast cancer based on radiomics signatures extracted from preoperative contrast-enhanced chest computed tomography.
To explore the diagnostic value of radiomics features of preoperative computed tomography (CT) for triple negative breast cancer (TNBC) for better treatment of patients with breast cancer. A total of 890 patients with breast cancer admitted to our hospital from June 2016 to January 2018 were analyzed. They were diagnosed by surgery and pathology to have mass and invasive breast cancer and had contrast-enhanced chest CT examination before operation. 300 patients were randomly selected for the study, including 100 TNBC and 200 non-TNBC (NTNBC) patients. Among them 180 were used in discovery group and 120 were used in validation group. The molecular subtypes of breast cancer in the patients were determined immunohistochemistrially. Radiomics features were extracted from three dimensional CT-images. The LASSO logistic method was used to select image features and calculate radiomics scores. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of radiomics scores for TNBC. Five image features were found to be related to TNBC subtype (P < 0.001). These image features based-radiomic signatures had good predictive values for TNBC with the areas under ROC curve (AUC) of 0.881 (95% CI: 0.781-0.921) in the discovery group and 0.851 (95% CI: 0.761-0.961) in the validation group, respectively. The sensitivities and specificities were 0.767, and 0.873 in the discovery group and 0.785 and 0.915 in the validation group. Radiomic signature based on preoperative CT is capable of distinguishing patients with TNBC and NTNBC. It adds additional value for conventional chest contrast-enhanced CT and helps plan the strategy for clinical treatment of the patients.


Eosinophils and tissue remodeling: Relevance to airway disease.
The ability of human tissue to reorganize and restore its existing structure underlies tissue homeostasis in the healthy airways, but in disease can persist without normal resolution, leading to an altered airway structure. Eosinophils play a cardinal role in airway remodeling both in health and disease, driving epithelial homeostasis and extracellular matrix turnover. Physiological consequences associated with eosinophil-driven remodeling include impaired lung function and reduced bronchodilator reversibility in asthma, and obstructed airflow in chronic rhinosinusitis with nasal polyps. Given the contribution of airway remodeling to the development and persistence of symptoms in airways disease, targeting remodeling is an important therapeutic consideration. Indeed, there is early evidence that eosinophil attenuation may reduce remodeling and disease progression in asthma. This review provides an overview of tissue remodeling in both health and airway disease with a particular focus on eosinophilic asthma and chronic rhinosinusitis with nasal polyps, as well as the role of eosinophils in these processes and the implications for therapeutic interventions. Areas for future research are also noted, to help improve our understanding of the homeostatic and pathological roles of eosinophils in tissue remodeling, which should aid the development of targeted and effective treatments for eosinophilic diseases of the airways.


Distribution of radioactivity after administration of 3H-5-hydroxytryptamine by three different routes to the mussel Mytilus edulis.
Intracardiac injection gives proportionately higher and earlier peak concentration in tissues that specifically accumulates it, i.m. injection gives slower but longer lasting accumulations, and topical application to a ganglia essentially localizes the drug in that structure.


Altered elementary calcium release events and enhanced calcium release by thymol in rat skeletal muscle.
The effects of thymol on steps of excitation-contraction coupling were studied on fast-twitch muscles of rodents. Thymol was found to increase the depolarization-induced release of calcium from the sarcoplasmic reticulum, which could not be attributed to a decreased calcium-dependent inactivation of calcium release channels/ryanodine receptors or altered intramembrane charge movement, but rather to a more efficient coupling of depolarization to channel opening. Thymol increased ryanodine binding to heavy sarcoplasmic reticulum vesicles, with a half-activating concentration of 144 micro M and a Hill coefficient of 1.89, and the open probability of the isolated and reconstituted ryanodine receptors, from 0.09 +/- 0.03 to 0.22 +/- 0.04 at 30 micro M. At higher concentrations the drug induced long-lasting open events on a full conducting state. Elementary calcium release events imaged using laser scanning confocal microscopy in the line-scan mode were reduced in size, 0.92 +/- 0.01 vs. 0.70 +/- 0.01, but increased in duration, 56 +/- 1 vs. 79 +/- 1 ms, by 30 micro M thymol, with an increase in the relative proportion of lone embers. Higher concentrations favored long events, resembling embers in control, with duration often exceeding 500 ms. These findings provide direct experimental evidence that the opening of a single release channel will generate an ember, rather than a spark, in mammalian skeletal muscle.


In vivo effect of cyclic nucleotides on velocity and chemotaxis of neutrophil granulocytes.
Neutrophil granulocytes velocity and chemotaxis were obeserved by a direct method. Only chemotaxis could be inhibited by dibutyryl Cyclic AMP, this phenomenon could be reversed by cyclic GMP.


Intracardiac and Vascular Hemodynamics with Cardiovascular Magnetic Resonance in Heart Failure.
In heart failure (HF), the impaired heart loses its ability to competently eject blood during systole or fill with blood during diastole, manifesting in multifaceted abnormal intracardiac or intravascular flow dynamics. Conventional imaging techniques are limited in their ability to evaluate multidirectional multidimensional flow alterations in HF. Four-dimensional (4-D) flow magnetic resonance imaging (MRI) has emerged as a promising technique to comprehensively visualize and quantify changes in 3-dimensional blood flow dynamics in complex cardiovascular diseases. This article reviews emerging applications of 4-D flow MRI hemodynamic markers in HF and etiologies at risk of progressing to HF.


Comparative biochemical and transcriptomic analysis reveals the phosphate-starving tolerance of two ramie varieties.
Ramie (Boehmeria nivea L.) is a highly valued fiber crop. Its yield is often limited by lack of available phosphate (Pi) in the soil, but the underlying molecular mechanisms of ramie's response to Pi deficiency remain largely unknown. To investigate how ramie adapts to low Pi stress, we selected a low Pi-tolerant variety (H-5) and a low Pi-sensitive variety (XYL), and conducted a biochemical and transcriptomic analysis on roots and leaves of both varieties. After subjecting the plants to Pi-deficient and Pi-sufficient conditions for 15 days, we found that H-5 exhibited higher dry weight, longer root systems, and higher levels of Pi, galactolipids, and organic acids when subjected to Pi deprivation, compared to XYL. Transcriptomic analysis further revealed that Pi-responsive genes involved in lipid metabolism, Pi transport, organic acid synthesis, and acid phosphatase activities were more induced in the tolerant variety H-5. Furthermore, weighted gene co-expression network analysis (WGCNA) identified five hub genes, including phosphate transporter, SPX domain-containing protein and sulfoquinovosyl transferase, which played key roles in low Pi tolerance in ramie. The present study will broaden our comprehension of the differences and molecular mechanisms of different ramie cultivars in response to Pi starvation, and lay a foundation for future agronomic improvements in ramie and other fiber crops.


Management of Ground-Glass Nodules: When and How to Operate?
With the increased popularity of low-dose computed tomography (LDCT), many patients present with pulmonary ground-glass nodules (GGNs), and the appropriate diagnostic and management strategy of those lesions make physicians be on the horn of the clinical dilemma. As there is not enough data available to set universally acceptable guidelines, the management of GGNs may be different. If GGN is an incidental finding through LDCT, the lesion should be followed according to the current guidelines. We recommend a multidisciplinary team discussion to be initiated if a new solid component develops or the solid portion size grows on follow-up CT as the risk of malignancy is high. Attempts to preoperatively biopsy solid components in part-solid GGNs are often not feasible and not helpful in clinical settings. Currently, if malignancy is suspected, a surgical biopsy with the guidance of various localization methods is recommended. If malignancy is confirmed, sub-lobar resection may provide an excellent oncologic outcome.


[Radioprotective and toxicological properties on some 4-oxyhexa- and 1,2,3,6-tetrahydroprimidine-2-thione derivatives].
Test on mice demonstrated the radio-protective activity of 12 derivatives of 4-oxyhexahydropyrimidinethione-2 and 1,2,3,6-tetrahydropyrimidinethione-2 well-marked with intraperitoneal administration 10--20 minutes prior to irradiation (1000 r, exposure dose rate--10 r/min). As a whole the tetrahydroderivates are more toxic.


The multifaceted role of CARD9 in inflammatory bowel disease.
Inflammatory bowel disease (IBD) involves a dysregulated immune response to the gut microbiota. Emerging evidence has demonstrated that dysfunctions in caspase recruitment domain-containing protein 9 (CARD9) may contribute to the pathogenesis of IBD. Interestingly, an allelic series of Card9 variants have both a common predisposing and rare protective function in IBD patients. In this review, we provide mechanistic insights into the role of the CARD9 adaptor molecule in intestinal inflammation and determine a potential CARD9-targeting therapeutic approach against IBD.


A small-conductance Cl- channel in the mouse thick ascending limb that is activated by ATP and protein kinase A.
1. Chloride channels were identified in the basolateral membrane of isolated cortical thick ascending limbs (CTALs) of the mouse nephron by the patch-clamp technique. A channel with a conductance of 45 pS, previously shown to be Cl- selective, was detected in 21% of cell-attached patches when CTAL fragments were pre-incubated with 10 mumol l-4 forskolin for at least 15 min. The same channel was found in only 8.5% of cell-attached patches formed on unstimulated tubules. 2. Another channel with a smaller conductance (7-9 pS) was found in 42.8% of cell-attached patches and 57% of inside-out patches in unstimulated CTAL tubules, but in 82-87% of patches from forskolin-treated tubules. 3. The small channels was Cl- selective (Cl(-)-to-Na+ permeability ratio, PCl/PNa = 9.8) with the permeability sequence: NO3- > Br- > Cl- > F- > gluconate. Channel activity decreased (Br-) or disappeared (NO3-) at negative voltages. At 140 mmol l-1, I- completely inhibited channel activity at all voltages, but a PI/PCl ratio of 1.6 was estimated using a low I- concentration (10 mmol l-1). 4. Internal adenosine triphosphate (ATP) increased normalized current (nPo) in 48% of inside-out patches containing Cl- channels from unstimulated tubules and in 63% of patches from forskolin-treated CTAL tubules. The non-hydrolysable ATP analogue, adenosine 5'-adenylyl imidodiphosphate (AMP-PNP) did not increase channel activity. 5. Adding the catalytic subunit of protein kinase A to the bath in the presence of ATP increased the activity of the small channel in 58% of inside-out patches from unstimulated tubules, but it had no effect on the 45 pS channel. 6. The Cl- channel blockers 5-nitro-2-(3-phenylpropylamine)-benzoic acid (NPPB), 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) or glibenclamide, all at 0.1 mmol l-1, and diphenylamine-2-carboxylic acid (DPC), at 1 mmol l-1, inhibited the small channel activity by 80-100% in inside-out patches. 7. These results indicate that two Cl- channels with contrasting properties mediate the basolateral step of NaCl absorption in the thick ascending limb of the loop of Henle.


Echocardiographic evaluation of patients with severe heart failure and impairment of intraventricular conduction following cardiac resynchronisation therapy.
Echocardiographic examination is essential for clinical assessment of patients after cardiac resynchronisation therapy (CRT). To assess the benefit of CRT in patients with end-stage heart failure at long-term follow-up. 28 patients with end-stage heart failure, NYHA class >or= III (>or= II in patients with indications for implantable cardioverter defibrillator and echocardiographic signs of ventricular mechanical systolic dyssynchrony), left ventricular ejection fraction (LVEF) <35%, QRS duration >120 ms and left bundle branch block morphology received a biventricular device. Standard colour Doppler echocardiography examination was performed at baseline, and then every 6 months, up to 2 years. Parameters of systolic and diastolic LV function, mitral insufficiency and right ventricular (RV) pressure were evaluated. Following CRT, a statistically significant improvement of LV dimensions (p<0.05), and LVEF (p<0.001) was recorded. CRT also resulted in a mitral regurgitation decrement (p<0.01). Interventricular mechanical delay was shortened (p=0.0005). After 2 years, non-significant worsening of LV dimensions was observed. At long-term follow-up CRT did not result in LV volume, left atrium, RV dimension or RV pressure reduction. CRT is associated with reverse remodelling of the LV at mid-term follow-up.


Utility of stool CBNAAT in the diagnosis of pediatric pulmonary tuberculosis in India.
India houses 27% of the tuberculosis cases worldwide. Pediatric tuberculosis accounts for 11% cases worldwide. Microbiological confirmation of diagnosis is difficult in children. We aimed to study the proportion of Stool CBNAAT (Cartridge Based Nucleic Acid Amplification Test) and GA CBNAAT positive cases among the presumptive cases of tuberculosis in children and assess diagnostic utility of the Stool CBNAAT in comparison to GA CBNAAT and culture. Ours was a cross sectional study. 75 children, aged 6 months to 12 years who were presumptive cases of pulmonary tuberculosis and who were unable to expectorate, were enrolled. Gastric aspirate and stool samples were obtained and CBNAAT and culture was done. Results of stool CBNAAT were compared with GA CBNAAT and culture. Of the 75 children enrolled, 28 were started on antitubercular therapy, 12 of whom were microbiologically confirmed and 16 were started on clinical grounds. Overall, 10 (13.3%) and 11 (14.6%) were positive by Stool CBNAAT and GA CBNAAT respectively. GA CBNAAT and Stool CBNAAT were found to have near perfect agreement (Cohen's kappa 0.834). Stool CBNAAT had sensitivity and specificity of 73% and 97% as compared to culture. Stool CBNAAT may be used for bacteriological confirmation of pediatric pulmonary tuberculosis. It was found to have a high degree of concordance with the conventionally used GA CBNAAT. This test would be helpful in endemic countries where there is a dearth of trained staff, especially in the periphery, to obtain gastric aspirate. Discomfort associated with sampling would be avoided.


Seasonal variations in the stable oxygen isotope ratio of wood cellulose reveal annual rings of trees in a Central Amazon terra firme forest.
In Amazonian non-flooded forests with a moderate dry season, many trees do not form anatomically definite annual rings. Alternative indicators of annual rings, such as the oxygen (δ(18)Owc) and carbon stable isotope ratios of wood cellulose (δ(13)Cwc), have been proposed; however, their applicability in Amazonian forests remains unclear. We examined seasonal variations in the δ(18)Owc and δ(13)Cwc of three common species (Eschweilera coriacea, Iryanthera coriacea, and Protium hebetatum) in Manaus, Brazil (Central Amazon). E. coriacea was also sampled in two other regions to determine the synchronicity of the isotopic signals among different regions. The annual cyclicity of δ(18)Owc variation was cross-checked by (14)C dating. The δ(18)Owc showed distinct seasonal variations that matched the amplitude observed in the δ(18)O of precipitation, whereas seasonal δ(13)Cwc variations were less distinct in most cases. The δ(18)Owc variation patterns were similar within and between some individual trees in Manaus. However, the δ(18)Owc patterns of E. coriacea differed by region. The ages of some samples estimated from the δ(18)Owc cycles were offset from the ages estimated by (14)C dating. In the case of E. coriacea, this phenomenon suggested that missing or wedging rings may occur frequently even in well-grown individuals. Successful cross-dating may be facilitated by establishing δ(18)Owc master chronologies at both seasonal and inter-annual scales for tree species with distinct annual rings in each region.


Panther Fusion® Respiratory Virus Assays for the detection of influenza and other respiratory viruses.
Nucleic acid amplification tests (NAATs), such as PCR, are preferred for respiratory virus testing, due to superior diagnostic accuracy and faster turnaround time. Panther Fusion® Respiratory Assays (Fusion), which includes FluA/B/RSV (FFABR), Paraflu and AdV/hMPV/RV, offers a modular approach to syndromic testing on a fully automated platform while improving gene targets and expanding the test menu. We evaluated Fusion using 275 consecutive nasopharyngeal specimens previously used in an analysis of five PCRs, as well as 225 archived specimens. Of the combined 500 specimens, 134 were positive for influenza A (FluA), 54 for FluB, 65 for RSV, 64 for parainfluenza (PIV), 24 for adenovirus (AdV), 21 for humanmetapneumovirus (hMPV), and 40 for rhinovirus (RV) with Fusion. Of the positive samples Fusion correlated with historical results for all but one, despite multiple freeze-thaws cycles of this collection. Fusion was positive for an additional 33 samples, including 11 FluAs, 7 RSVs, 3 PIV3s, 3 AdV, 6 hMPV and 3 RVs. These samples were retested with corresponding Prodesse (Pro) assays using quadruple sample volume. This resolver test confirmed Fusion results for an additional 4 FluAs, 4 RSVs, 1 PIV3 and 3 AdVs. The sensitivity and specificity ranges of Fusion were 99-100% and 98-100%. Limit of detection (LOD) analyses were performed on a variety of Flu isolates. The LODs ranged from 2.69 to 2.99 log copies/ml and demonstrated superior LOD as compared to previously published data for some assays or to concurrent analyses with two new commercial tests.