Cervical Facet Joint Pain and Cervicogenic Headache Treated With Radiofrequency Ablation: A Systematic Review.
Chronic neck pain is often multifactorial and is a leading cause of pain and disability. Cervical facet joint pain is a common cause of neck pain and, in addition to more conservative modalities, can be treated with radiofrequency ablation (RFA) of the respective medial branch nerves. Cervicogenic headaches are a frequent complaint in pain clinics in the United States and can be targeted via a similar procedural approach. We evaluated randomized controlled trials of cervical facet joint pain and cervicogenic headaches with the goal of establishing a current level of evidence for treating these etiologies of pain with RFA. Systematic review. Database search, from inception through July 2021, was performed identifying randomized controlled trials for cervical medial branch RFA. Two reviewers independently evaluated the studies to identify those meeting criteria. Primary outcome measures included pain relief and duration of pain relief. Secondary outcome measures included function, sleep, mood, return to work, additional treatments, and complications. Four randomized controlled studies met inclusion criteria and were selected for this review, each demonstrated low risk of bias. Of these studies, 3 were unique with the fourth being a subgroup analysis. Primary outcome measures of pain relief and duration of relief were variable with successful relief ranging from 30% to 50% and median duration of pain relief also demonstrating a wide variety. Function and psychological distress were also variably reported and found variable relief to treatment with no difference between groups in 2 of the studies. Primary limitations of the review are the paucity of randomized controlled trials and the variability in measured outcome measures. Based on this systematic review, efficacy of cervical facet RFA in treatment of chronic neck pain has Level II evidence.


Expanded endothelial progenitor cells mitigate lung injury in septic mice.
Endothelial progenitor cells (EPCs) improve survival and reduce organ failure in cecal ligation and puncture-induced sepsis; however, expanded EPCs may represent an even better approach for vascular repair. To date, no study has compared the effects of non-expanded EPCs (EPC-NEXP) with those of expanded EPCs (EPC-EXP) and mesenchymal stromal cells of human (MSC-HUMAN) and mouse (MSC-MICE) origin in experimental sepsis. One day after cecal ligation and puncture sepsis induction, BALB/c mice were randomized to receive saline, EPC-EXP, EPC-NEXP, MSC-HUMAN or MSC-MICE (1 × 10(5)) intravenously. EPC-EXP, EPC-NEXP, MSC-HUMAN, and MSC-MICE displayed differences in phenotypic characterization. On days 1 and 3, cecal ligation and puncture mice showed decreased survival rate, and increased elastance, diffuse alveolar damage, and levels of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-α, vascular endothelial growth factor, and platelet-derived growth factor in lung tissue. EPC-EXP and MSC-HUMAN had reduced elastance, diffuse alveolar damage, and platelet-derived growth factor compared to no-cell treatment. Tumor necrosis factor-α levels decreased in the EPC-EXP, MSC-HUMAN, and MSC-MICE groups. IL-1β levels decreased in the EPC-EXP group, while IL-10 decreased in the MSC-MICE. IL-6 levels decreased both in the EPC-EXP and MSC-MICE groups. Vascular endothelial growth factor levels were reduced regardless of therapy. In conclusion, EPC-EXP and MSC-HUMAN yielded better lung function and reduced histologic damage in septic mice.


Type D Personality as a Risk Factor in Coronary Heart Disease: a Review of Current Evidence.
This review article synthesizes recent research findings on the psychological context of Type D personality and the mechanisms through which Type D affects disease progression and prognosis among patients with coronary heart disease (CHD). One in four patients with CHD has a Distressed (Type D) personality, which is characterized by two stable traits: social inhibition and negative affectivity. Type D personality predicts increased mortality and morbidity burden, and poorer health-related quality of life. Type D is part of a family of psychosocial risk factors that affect CHD prognosis. The pattern of co-occurrence of these psychosocial factors and intra-individual differences in psychosocial profiles may affect risk prediction accuracy. Multiple biological and behavioral processes have been associated with Type D personality. Identifying pathways explaining the observed associations between Type D personality and CHD is important to improve etiological and pathophysiological knowledge and to design personalized interventions, and targeting specific risk-associated pathways.


Upregulation of SLUG expression in canine mammary gland tumors and its prognostic significance.
SLUG (also known as snai2), which is a transcription factor in epithelial-mesenchymal transition (EMT), plays an important role in tumorigenesis. Several human studies have revealed that SLUG expression downregulates E-cadherin activity to induce metastasis and invasion of tumor cells, and its association with tumor mechanisms is under constant evaluation. In clinical veterinary medicine, one study revealed upregulated SLUG expression in canine oral squamous cell carcinoma. However, the association between canine mammary gland tumors (MGT), the most common neoplasm in intact female dogs, and SLUG has not been investigated yet. Therefore, this study aimed to evaluate the differences in SLUG expression among canine normal mammary gland tissue and MGTs using immunohistochemistry. In addition, its prognostic significance was evaluated by analyzing the correlation with the Ki-67 proliferation index and various clinicopathological features. SLUG expression increased substantially from normal mammary gland tissues to MGTs, especially showing the strongest expression in malignant MGT than in benign MGT. Negative SLUG expression was observed in mostly normal mammary gland tissues, whereas all tissues in malignant MGT showed positive SLUG expression. Furthermore, positive SLUG expression was associated with higher Ki-67 index, larger tumor size (> 3 cm), and metastasis. Kaplan-Meier survival curve analysis revealed that positive SLUG expression was significantly associated with poor overall and disease-free survival. These results indicate that SLUG is upregulated in canine MGTs and positive SLUG expression is positively correlated with poor prognosis. Thus, SLUG protein can be a novel biomarker and therapeutic target for canine patients with MGT.


A feasibility study on AI-controlled closed-loop electrical stimulation implants.
Miniaturized electrical stimulation (ES) implants show great promise in practice, but their real-time control by means of biophysical mechanistic algorithms is not feasible due to computational complexity. Here, we study the feasibility of more computationally efficient machine learning methods to control ES implants. For this, we estimate the normalized twitch force of the stimulated extensor digitorum longus muscle on n = 11 Wistar rats with intra- and cross-subject calibration. After 2000 training stimulations, we reach a mean absolute error of 0.03 in an intra-subject setting and 0.2 in a cross-subject setting with a random forest regressor. To the best of our knowledge, this work is the first experiment showing the feasibility of AI to simulate complex ES mechanistic models. However, the results of cross-subject training motivate more research on error reduction methods for this setting.


Bone marrow cells as precursors of the tumor stroma.
Cancer is a systemic disease. Local and distant factors conspire to promote or inhibit tumorigenesis. The bone marrow is one important source of tumor promoting cells. These include the important mature and immature hematopoietic cells as well as circulating mesenchymal progenitors. Recruited bone marrow cells influence carcinogenesis at the primary site, within the lymphoreticular system and even presage metastasis through their recruitment to distant organs. In this review we focus on the origins and contribution of cancer-associated fibroblasts in tumorigenesis. Mesenchymal cells present an important opportunity for targeted cancer prevention and therapy.


Agentic and communal personality traits: relations to disordered eating behavior, body shape concern, and depressive symptoms.
This study was designed to examine links between agentic and communal personality traits and disordered eating behavior and related problems (i.e., body shape concern and depressive symptoms) in a sample of 298 undergraduates. As predicted, unmitigated agency was positively associated with uncontrolled eating, and unmitigated communion was positively related to emotional eating and fasting for at least 24 h in order to control weight. When controlling for depressive symptomatology, unmitigated communion was no longer associated with emotional eating. Whereas unmitigated agentic and communal characteristics were positively associated with problematic eating patterns, agency was negatively associated with fasting and body shape concern. Findings suggest that further examination of the potential influence of gender-linked personality traits on disordered eating behavior is warranted.


Failure to detect fetal obstructive uropathy by second trimester ultrasound.
The prenatal diagnosis, management and outcome of an hereditary obstructive uropathy is presented. Serial ultrasonic assessment of the fetal urinary tract was carried out from the early second trimester onward. Slight bilateral hydronephrosis as a first sign of obstructive uropathy was only established as late as 30 weeks of gestation. On the basis of weekly ultrasound scans, a conservative approach was adopted. In view of fetal maturity, labour was induced at 36 weeks resulting in the vaginal delivery of a male infant with moderate bilateral hydronephrosis. Neonatally, anuria developed due to bilateral obstruction of the ureters as a result of increasing bladder wall hypertrophy due to urethral valves. A bilateral uretero-cutaneostomy was carried out. The infant so far develops normally, and renal function is normal for age. Women at risk for fetal obstructive uropathy should have ultrasonic monitoring throughout pregnancy.


Effects and associations of nutrition in patients with venous leg ulcers: A systematic review.
To identify the associations and effects of nutritional characteristics and interventions on ulcer outcomes in adult patients with venous leg ulcers. Venous leg ulcers are the most prevalent type of lower limb ulcer; however, little evidence exists regarding the relationship between nutritional status and ulcer healing. A systematic search of English language articles was conducted using the Cochrane Collaboration Handbook for Systematic Reviews of Interventions. A search of databases Ovid MEDLINE, EMBASE, Cochrane, CINAHL and Scopus was performed for studies published between January 2004 - May 2017. Quality of the included studies was assessed using the Cochrane Collaboration's Risk of Bias Assessment tool and the relevant Joanna Briggs Institute quality appraisal checklists. Twenty studies met the inclusion criteria. All participants had Clinical Aetiology Anatomy Pathophysiology classification C5 (healed) or C6 (active) ulcers. Studies were conducted in a range of clinical settings with relatively small sample sizes. The majority of patients were overweight or obese. Increased body mass index was associated with delayed wound healing. Vitamin D, folic acid and flavonoids were associated with some beneficial effects on ulcer healing. Dietary intakes of omega-3 fatty acids, vitamin C and zinc were low for some patients. Current evidence suggests that venous leg ulcer patients are more likely to be overweight or obese. However, evidence for weight management improving wound healing is lacking. Micronutrients, including vitamin D and folic acid, may improve wound healing in at-risk patients.


Time course study on the effects of iodinated contrast medium on intrarenal water transport function using diffusion-weighted MRI.
To assess the effects of intravenous-injected iodinated contrast medium (CM) on intrarenal water diffusion using noninvasive diffusion-weighted MRI (DW-MRI). Ten New Zealand White rabbits were randomized to receive a 6 mL/kg body weight intravenous injection of clinically used iopamidol-370 (n = 7) or an equivalent amount of 0.9% physiological saline (n = 3). A sequential DW-MRI was performed to estimate the intrarenal apparent diffusion coefficient (ADC) at 24 h before and 1 h, 24 h, 48 h, and 72 h after administration. Iopamidol produced a progressive ADC reduction in inner stripes of the renal outer medulla (IS) by 13.92% (P = 0.05) at 1 h, 17.52% (P = 0.02) at 24 h, 20.23% (P = 0.01) at 48 h and 16.31% (P = 0.04) at 72 h after injection. Cortical ADC was decreased by 14.14% (P = 0.01) at 48 h and 14.12% (P = 0.01) at 72 h after injection. Iopamidol produced slight decrease of ADCs in outer stripes of the outer medulla (OS) and inner medulla (IM) of kidney but without statistical difference. In control group, no significant ADC changes was observed in each anatomic compartment due to saline injection (P > 0.05). As demonstrated by DW-MRI, intravenous iopamidol injection resulted in a successive reduction of intrarenal water diffusion, particularly in IS of kidney. This MR technique may be used as a noninvasive tool to perform a time course study of the pathogenesis associated with contrast-induced nephropathy (CIN).


Acoustic Communication in Fishes and Potential Effects of Noise.
Many soniferous fishes such as cods and groupers are commercially important. Sounds are produced during courtship and spawning, and there is the potential for aquatic noise to interfere with critical behaviors and affect populations. There are few data on the response of wild populations of sound-producing fishes to acoustic noise. New motion and sound exposure fish tags could be used to assess the behavioral responses of large numbers of fish to noise exposure. Many factors, such as fishing mortality and environmental variability in prey supply, could also affect populations and potentially interact with the behavioral responses to noise.


TLR2 and AP-1/NF-kappaB are involved in the regulation of MMP-9 elicited by heat killed Listeria monocytogenes in human monocytic THP-1 cells.
MMP-9 is crucial for a normal immune response, but excessive release of this enzyme leads to severe tissue damage. Listeria monocytogenes (LM) is an opportunistic food-borne pathogen causing listerosis, meningitis and sepsis. Heat killed Listeria monocytogenes (HKLM) activates immune system and leads production of cytokines and chemokines. However, nothing is known about the involvement of HKLM in MMP-9 regulation. Therefore we investigated the role of HKLM in the regulation of MMP-9 gene expression in THP-1 cells. Commercially available heat killed Listeria monocytogenes was used in this study. HKLM-induced MMP-9 expression was assessed with quantitative real-time qPCR and ELISA. Action of HKLM in different signaling pathways were studied by using THP-1-XBlue™ cells (THP-1-cells with NF-κB/AP-1 reporter construct), THP-1-XBlue™-defMyD cells (MyD88(-/-) THP-1 cells), anti-TLR2 mAb and pharmacological inhibitors. Phospho and total proteins were determined by Western blotting. Increased MMP-9 production (mRNA: 395-Fold; Protein: 8141 pg/ml; P < 0.05) was observed in HKLM stimulated THP-1 cells as compared to the un-stimulated THP-1 cells. This production of MMP-9 was completely abrogated by anti-TLR2 blocking mAb (P = 0.0024). Furthermore, THP-1-XBlue™-defMyD cells were unable to produce MMP-9 in response to HKLM. HKLM- induced activation of NF-kappaB/AP-1 was also observed in THP-1-XBlue™ Cells. In addition, inhibitors of JNK (SP600125), MEK/ERK (U0126; PD98056), p38 MAPK (SB203580) and NF-kappaB (BAY 11-7085, Triptolide and Resveratrol) significantly suppressed (P < 0.05) HKLM-stimulated MMP-9 expression. Our results indicate that HKLM activates TLR2 and NF-κB/AP-1 signaling pathways, leading to up-regulation of MMP-9 production in THP-1 cells. Thus, MMP-9 could be an appropriate therapeutic target to stop severe tissue damage caused by infection or chronic inflammation.


A case of autochthonous Plasmodium vivax malaria, Corsica, August 2006.
A case of Plasmodium vivax malaria was diagnosed in Corsica in summer 2006. This is the first case of autochthonous transmission of malaria to be reported in Corsica since 1972. Corsica is a well-known malaria endemic region characterised, for several years now by an anophelism situation without malaria disease, due to the presence of An. labranchiae and An. saccharovi able to transmit P. vivax. The occurring sequence of malaria signs in an imported case on 9 July and in an autochthonous case on 5 August, both in Porto, implies a transmission by local Anopheles. This suspicion is reinforced by the results of entomological investigations. However, from June to September 2006, no other P. vivax malaria case and no other autochthonous case were detected in Corsica. Therefore, it seems that no permanent malaria transmission occurs in this island. Mosquito eradication actions and anti-vectorial measures have been reinforced as well as individual prevention measures against imported diseases while travelling in tropical countries. Obviously, detection of one exceptional autochthonous transmission of one malaria case in Corsica does not justify proposing malaria protection to tourists.


Synthesis, characterization and DNA-binding studies of 2-carboxybenzaldehydeisonicotinoylhydrazone and its La(III), Sm(III) and Eu(III) complexes.
2-Carboxybenzaldehydeisonicotinoylhydrazone (HL), and its three lanthanide complexes, LnL(3).4H2O [Ln=La(1), Sm(2), Eu(3)], have been synthesized and characterized on the basis of elemental analyses, molar conductivities, IR spectra and thermal analyses. In addition, the DNA-binding properties of the ligand and its complexes have been investigated by absorption, fluorescence and viscosity measurements. The experimental results indicated that the complexes (2) and (3) can bind to DNA, but the ligand and the complex (1) cannot; the binding affinity of the complex (3) is higher than that of the complex (2) and the intrinsic binding constant Kb of the complex (3) is 7.86x10(4) M-1.


Treating lung cancer.
Practice profiles are reflective pieces written by nurses in practice and based on continuing professional development articles. This week Ruth Garner discusses the role of the lung cancer nurse.


Time-of-day effect on the torque and neuromuscular properties of dominant and non-dominant quadriceps femoris.
The study was conducted first, to determine the possibility of a dichotomy between circadian rhythm of maximal torque production of the knee extensors of the dominant and non-dominant legs, and second, to determine whether the possible dichotomy could be linked to a change in the downward drive of the central nervous system and/or to phenomena prevailing at the muscular level. The dominant leg was defined as the one with which subjects spontaneously kick a football. Tests were performed at 06:00, 10:00, 14:00, 18:00, and 22:00 h. To distinguish the neural and muscular mechanisms that influence muscle strength, the electromyographic and mechanical muscle responses associated with electrically evoked and/or voluntary contractions of the human quadriceps and semi-tendinosus muscles for each leg were recorded and compared. The main finding was an absence of interaction between time-of-day and dominance effects on the torque associated with maximal voluntary contraction (MVC) of both quadriceps. A significant time-of-day effect on MVC torque of the knee extensors was observed for the dominant and non-dominant legs when the data were collapsed, with highest values occurring at 18:00 h (p < 0.01). From cosinor analysis, a circadian rhythm was documented (p < 0.001) with the peak (acrophase) estimated at 18:18 +/- 00:12 h and amplitude (one-half the peak-to-trough variation) of 3.3 +/- 1.1%. Independent of the leg tested, peripheral mechanisms demonstrated a significant time-of-day effect (p < 0.05) on the peak-torque of the single and doublet stimulations, with maximal levels attained at 18:00 h. The central activation of the quadriceps muscle of each leg remained unchanged during the day. The present results confirmed previous observations that muscle torque changes in a predictable manner during the 24 h period, and that the changes are linked to modifications prevailing at the muscular, rather than the neural, level. The similar rhythmicity observed in this study between the dominant and non-dominant legs provides evidence that it is not essential to test both legs when simple motor tasks are investigated as a function of the time of day.


Rho GTPase signalling in cell migration.
Cells migrate in multiple different ways depending on their environment, which includes the extracellular matrix composition, interactions with other cells, and chemical stimuli. For all types of cell migration, Rho GTPases play a central role, although the relative contribution of each Rho GTPase depends on the environment and cell type. Here, I review recent advances in our understanding of how Rho GTPases contribute to different types of migration, comparing lamellipodium-driven versus bleb-driven migration modes. I also describe how cells migrate across the endothelium. In addition to Rho, Rac and Cdc42, which are well known to regulate migration, I discuss the roles of other less-well characterized members of the Rho family.


Hyperalgesia following agonistic encounters in DBA/2 intruder mice is not associated with recuperative behaviours.
Recent findings concerning the time-course of opioid-mediated social conflict analgesia have revealed the existence of two distinct nociceptive phases. Analgesia lasting between 30-45 minutes postattack is evident in the early phase whilst hyperalgesia is observed in the late phase at around 70-75 min postattack. This pattern of nociception has similarities with that envisaged in the Perceptual-Defensive-Recuperative (PDR) model of fear and pain and is predictive of defense/fear reactions being seen whilst animals are analgesic with recuperative behaviours becoming evident in the hyperalgesic phase. Detailed ethological analysis was conducted on DBA/2 mice exposed to opioid-activating attack parameters in a resident-intruder paradigm and tested in the presence of a nonaggressive conspecific. During the analgesic phase, at 10 min postagonistic encounter, a profile was observed consisting largely of increased measures of static, self-directed, possibly recuperative, behaviours (immobile crouch and autogrooming). In contrast, during the hyperalgesic phase, at 70 minutes postencounter, there was evidence of increased environmental exploration, attending to and avoiding nonaggressive conspecifics but no increases in autogrooming or any other behaviours that could be viewed as being recuperative. It is concluded that under present test conditions, using DBA/2 mice exposed to opioid activating attack parameters, predictions based on the PDR model of fear and pain are not supported.


Statins (HMG-coenzyme A reductase inhibitors)-biomimetic membrane binding mechanism investigated by molecular chromatography.
Many studies have demonstrated that the statin beneficial effects on cardiovascular diseases like coronary are linked to their hypocholesterolemic properties. These lipid-lowering drugs are the first-line pharmacologic therapy for hypercholesterolemia. In this paper, the interaction of a series of statin molecules STCOOH (pravastatin (prava), mevastatin (meva), simvastatin (simva) and fluvastatin (fluva)) with a phosphatidylcholine monolayer immobilized on to porous silica particles has been studied using a biochromatographic approach (molecular chromatography). The immobilized artificial membrane (IAM) provided a biophysical model system to study the binding of the statin molecules to a lipid membrane. For all the test statin molecules, linear retention plots were observed at all temperatures. An analysis of the thermodynamics (i.e., enthalpy (DeltaH(0)), entropy (DeltaS(0)*)) of the interaction of the statin molecules with the immobilized monolayer was also carried out. The DeltaH(0) and DeltaS(0)* values were negative due to van der Waals interactions and hydrogen bonding between the statin molecules with the polar head groups of the phospholipid monolayer (polar retention effect). The statin elution order was: Prava<<<Meva<Atorva<<Simva<Fluva. This result associated with IC50 data of each statin molecule confirmed that pravastatin, which exhibited the lowest association with the lipid monolayer, was taken up by a membrane transporter. In addition, the logarithm of the statin retention factor with the lipid membrane extrapolated to a total aqueous bulk solvent at pH 7.0 (log k'(w-IAM)) was measured and compared to the octanol-water partition coefficient (logP). The observed significant correlation showed an affinity enhanced with the increase in the molecule lipophilicity and confirmed that the hydrophobic forces played an important role in the statin molecule-biomembrane association mechanism. As well, the affinity of STCOOH to IAM is high and changes slightly with the bulk solvent pH, because the number of protons linked to binding is low. This confirmed the importance to take into account the electrostatic interaction in this association mechanism. At pHs lower than approximately 7.0, the binding process is accompanied by protons release and at higher pHs protons are taken up. A change in the phospholipid monolayer phosphate group pK(a) has been proposed to contribute to the positive number of protons exchanged at pHs higher than approximately 7.0. This demonstrated that this phosphate residue could function as a general base/proton shuttle by facilitating the deprotonation of STCOOH, i.e., this hyper-reactive residue in the IAM surface could play a catalytic function.


Acquired pendular nystagmus.
Acquired pendular nystagmus is comprised of quasi-sinusoidal oscillations of the eyes significantly affecting gaze holding and clarity of vision. The most common causes of acquired pendular nystagmus include demyelinating disorders such as multiple sclerosis and the syndrome of ocular palatal tremor. However, several other deficits, such as pharmacological intoxication, metabolic and genetic disorders, and granulomatous disorders can lead to syndromes mimicking acquired pendular nystagmus. Study of the kinematic features of acquired pendular nystagmus has suggested a putative pathophysiology of an otherwise mysterious neurological disorder. Here we review clinical features of neurological deficits that co-occur with acquired pendular nystagmus. Subsequent discussion of the pathophysiology of individual forms of pendular nystagmus speculates on mechanisms of the underlying disease while providing insights into pharmacotherapy of nystagmus.


The BCL-2 family protein BCL-RAMBO interacts and cooperates with GRP75 to promote its apoptosis signaling pathway.
The BCL-2 family protein BCL-RAMBO, also known as BCL2-like 13, anchors at the outer mitochondrial membrane and regulates apoptosis, mitochondrial fragmentation, and mitophagy. However, the mechanisms underlying the proapoptotic role of BCL-RAMBO remain unclear. In the present study, we demonstrated that BCL-RAMBO interacted with glucose-regulated protein 75 (GRP75), also known as heat shock protein family A member 9, and mortalin using co-immunoprecipitation and glutathione S-transferase-based pull-down assays. BCL-RAMBO interacted with GRP75 via its No BCL-2 homology domain. The interaction between BCL-RAMBO and GRP75 was confirmed by genetic interactions in Drosophila because a rough eye phenotype caused by the ectopic expression of BCL-RAMBO was partially suppressed by mutations in Hsc70-5, a mammalian GRP75 ortholog. In human embryonic kidney 293T cells, the co-expression of BCL-RAMBO and GRP75 facilitated an elevation in executioner caspase activity and poly (ADP-ribose) polymerase 1 (PARP-1) cleavage. In contrast, the knockdown of GRP75 suppressed elevated executioner caspase activity and PARP-1 cleavage in BCL-RAMBO-transfected cells. The mitochondrial release of cytochrome c induced by BCL-RAMBO was also attenuated by the knockdown of GRP75. These results indicate that GRP75 interacts with BCL-RAMBO and plays a crucial role in the BCL-RAMBO-dependent apoptosis signaling pathway.


The uncommon longitudinal relaxation dispersion of human brain white matter.
Human brain white matter exhibits an uncommonly strong dispersion of 1/T1 at high fields. An additional relaxation pathway via the myelin lipids, which are not directly visible to medical NMR due to their fast T2 decay, is proposed. Relaxation dispersion data are successfully analyzed on the basis of this model.


Making the right match. These eight lessons can help boards explore the strategic partnership decision.
Working through eight lessons can help boards clarify the strategic partnership decision.


The accuracy and precision of saccades to small and large targets.
Subjects made saccades to point and spatially-extended targets located at a randomly-selected eccentricity (3.8-4.2 deg) under conditions designed to promote best possible accuracy based only on the visual information present in a single trial. Saccadic errors to point targets were small. The average difference between mean saccade size and target eccentricity was about 1% of eccentricity. Precision was excellent (SD = 5-6% of eccentricity), rivaling the precision of relative perceptual localization. This level of performance was maintained for targets up to 3 deg in diameter. Corrective saccades were infrequent and limited almost exclusively to the point targets. We conclude that the saccadic system has access to a precise representation of a central reference position within spatially-extended targets and that, when explicitly required to do so, the saccadic system is capable of demonstrating remarkably accurate and precise performance.


Correction to: Two Randomized Controlled Trials of Bacillus Calmette-Guérin Vaccination to reduce absenteeism among health care workers and hospital admission by elderly persons during the COVID-19 pandemic: A structured summary of the study protocols for two randomised controlled trials.
An amendment to this paper has been published and can be accessed via the original article.


Ultrasound-guided transversus abdominis plane block in children: a randomised comparison with wound infiltration.
The transversus abdominis plane (TAP) block is a new regional anaesthesia technique applicable to infants and children. The present study was designed to evaluate the analgesic efficacy of ultrasound-guided TAP block with high volume local anaesthetic (0.5 ml kg) during the first 24 h after surgery in children undergoing inguinal hernia repair. Randomised comparative study. Gaziantep University Hospital between December 2010 and May 2011. Fifty-seven children between 2 and 8 years of age undergoing unilateral inguinal hernia repair were randomised to TAP block (group T, n = 29) or to wound infiltration (group C, n = 28). A TAP block using ultrasound guidance with 0.25% levobupivacaine 0.5 ml kg(-1) or wound infiltration with 0.2 ml kg(-1) 0.25% levobupivacaine, was performed on the same side as the hernia under general anaesthesia. Time to first analgesic, cumulative number of doses of analgesic, pain scores and adverse effects were assessed over the course of 24 h. The time to first analgesic (mean ± SD) was significantly longer in group T than in group C (17 ± 6.8 vs. 4.7 ± 1.6 h, respectively; P < 0.001). Thirteen (45%) patients in group T did not require any analgesic within the first 24 h. The cumulative number of doses of analgesic was significantly lower in group T than in group C (1.3 ± 1.2 vs. 3.6 ± 0.7, respectively, P < 0.001). Pain scores were significantly different between the groups at all time points except at 1, 20 and 24 h (P < 0.001). Ultrasound-guided TAP block with high volume (0.5 ml kg) 0.25% levobupivacaine provides prolonged postoperative analgesia and reduced analgesic use without any clinical side-effects after unilateral hernia repair in children. ACTRN12611000585921 (7/06/2011) from Australian New Zealand Clinical Trials Registry.


[Treatment of rectal atresia with rectal and urinary fistulas in newborn infants].
It is the authors' opinion that one-moment proctoplasty with careful disjunction of fistulas is the best method of treatment of newborn infants with recto-anal atresia and urinary tract fistulas. The results of the treatment in 43 cases are described.


Pulmonary tuberculosis presenting as diffuse cystic lung disease: An atypical manifestation.
Pulmonary tuberculosis has varied patterns of clinical presentation. Here, we report a case of tuberculosis in a 44 year immunocompetent female patient who presented to us with multiple cysts in the lung parenchyma. The diagnosis was confirmed by the analysis of bronchoalveolar lavage fluid. She had secondary spontaneous pneumothorax and progressive respiratory failure despite anti-tubercular therapy. Acute or sub acute onset of multiple lung cysts is usually associated with pulmonary infection. Tuberculosis presenting as cystic lung disease is less common and atypical. High index of suspicion and early initiation of therapy is pivotal in management of such cases.


Gamma-aminobutric acid and glutamate decarboxylas (l-glutamate 1-carboxy-lyase e.c. 18.104.22.168) in the nervous system of the cockroach, periplaneta americana.i.regional distribution and properties of the enzyme.
Both the central and peripheral nervous system of the cockroach Periplaneta americana contain gamma-aminobutyric acid (GABA) and glutamate decarboxylase (GAD). In the central ganglia of the cockroach, an average of more that 60 mumoles of GABA are formed from glutamate (Glu) per gram wet weight of tissue per hour. This activity level of the GAD apoenzyme is considerably higher than that found in the central nervous system of crustaceans, amphibians, avians and mammals but is similar to that reported for nervous system tissues from other insect species. A comparison of properties of the crude cockroach enzyme with GAD from crustacean and mammalian origin revealed both similarities and differences: whereas crude cockroach GAD has cofactor requirements and an affinity for Glu substrate (Km 2.8 X 10-2) which are similar to GAD from lobster and mouse, it is uniquely inhibited by both Cl-and by GABA. The GAD from cockroach nervous tissues has two apparent pH optima of which the lower one is preferentially inhibited by a compound which is found in the nerve sheath and the fat body tissue adjacent to ganglia and axons.


Front pattern of invasion in squamous cell carcinoma of the penis: new prognostic factor for predicting risk of lymph node metastases.
Treatment of penile carcinoma is based on excision of the primary tumor and regional lymphadenectomies. Lymph node metastasis is the most important prognostic factor, yet it cannot be reliably evaluated by imaging studies or clinical examinations; thus, new prognostic factors such as the pattern of invasion must be investigated. The data of 112 patients with penile carcinoma who underwent amputation and lymphadenectomy were analyzed. The clinicopathologic variables were studied, in addition to the front pattern of invasion according to the standards established by the modified criteria of Anneroth and Bryne first used as a part of a prognostic score in squamous cell carcinoma of the oral cavity. The pattern of invasion expresses the tumor-host tissue relationship, demonstrating the infiltrative tumor characteristics. This pattern was defined as infiltrating (invasion in blocks of small solid strands of cell tumors that broadly infiltrated the organ's stroma) and pushing infiltration (tumor cells have invaded large cell blocks with well-defined tumor-host interfaces). The variables that were significantly associated with the presence of lymph node metastases on univariate analysis were clinical N stage (P = 0.011), lymphatic permeation (P <0.001), venous embolization (P = 0.025), and the pattern of invasion (P <0.001). In the multivariate model, the lymphatic permeation, clinical N stage, and invasion type were independent risk factors for lymph node metastases. The follow-up varied from 0.1 to 452.8 months (mean 76.9, median 27.3). Lymphatic permeation, clinical N stage, and standard infiltrating invasion were independent prognostic variables for the risk of lymph node metastasis.


Incidence and relationship between behavioural and psychological symptoms in Alzheimer's disease.
To evaluate the frequency and type of psychological and behavioural symptoms in Alzheimer's disease (AD) patients in Poland, in various stages of the disease. One hundred and sixty-nine patients with a diagnosis of probable AD in Global Deterioration (GDS) stages 3, 4, 5, 6 and 7 of dementia were examined in a search for behavioural and psychological symptoms. Behavioural and psychotic symptoms were most often found in GDS stages 5 and 6 of AD, except for depressive disorder, which was observed most frequently in GDS stage 4 and whose frequently decreased towards the terminal stages of dementia. From an analysis of the relationship between behavioural symptoms in the Polish AD patients, the following syndromes may be discriminated: psychotic syndrome (delusions and hallucinations), delusions with aggressive behaviour and hallucinations and anxiety. With more severe dementia, the syndromes, which could be the result of delirium, became more common. Diagnosis of delirium should be considered in moderately severe and severe dementia whenever a sudden change in patients' behaviour occurs.


Morphological characteristics of perforated synapses in the latter stages of synaptogenesis in rat neocortex: stereological and three-dimensional approaches.
Over recent years attention has been focused on perforated synapses (PSs), on account of their possible involvement in synaptic plasticity in the nervous system. The mechanism invoked has involved the conversion of conventional (non-perforated) synapses into perforated ones, with the latter subsequently splitting to form new daughter synapses. Data challenging this mechanism have emerged from studies using unbiased stereological and three-dimensional reconstruction procedures in early synaptogenesis and also in early- to mid-adulthood. The present study is an attempt to complement these earlier studies by concentrating on the latter part of synaptogenesis and early adulthood in rats (7-60 days postnatal). Using the disector method, the frequency of perforated synapses increases with age from 12% at seven days to 33% at 60 days. Reconstruction of the perforated synapses has led to the description of three sub-types, while quantitation of the reconstructions has highlighted major differences between perforated and non-perforated synapses over this developmental period. For instance, the postsynaptic density of perforated synapses increases in size with age, but remains static in the non-perforated variety; in addition, it is 2-3 times larger in perforated synapses. The proportion of the synaptic contact zone occupied by the postsynaptic density increases in perforated synapses with increasing age, but is static in non-perforated synapses. No evidence has been found to support a perforated synapse splitting model, since perforated synapses are present from early in synaptogenesis, the frequency of non-perforated synapses reaches a peak prior to, but not following, that of perforated synapses, and the size of the postsynaptic density of non-perforated synapses remains constant throughout the period of the study.


Polyelectrolyte coating of cryo-EM grids improves lateral distribution and prevents aggregation of macromolecules.
Cryo-electron microscopy (cryo-EM) is one of the primary methods used to determine the structures of macromolecules and their complexes. With the increased availability of cryo-electron microscopes, the preparation of high-quality samples has become a bottleneck in the cryo-EM structure-determination pipeline. Macromolecules can be damaged during the purification or preparation of vitrified samples for cryo-EM, making them prone to binding to the grid support, to aggregation or to the adoption of preferential orientations at the air-water interface. Here, it is shown that coating cryo-EM grids with a negatively charged polyelectrolyte, such as single-stranded DNA, before applying the sample reduces the aggregation of macromolecules and improves their distribution. The single-stranded DNA-coated grids enabled the determination of high-resolution structures from samples that aggregated on conventional grids. The polyelectrolyte coating reduces the diffusion of macromolecules and thus may limit the negative effects of the contact of macromolecules with the grid support and blotting paper, as well as of the shear forces on macromolecules during grid blotting. Coating grids with polyelectrolytes can readily be employed in any laboratory dealing with cryo-EM sample preparation, since it is fast, simple, inexpensive and does not require specialized equipment.


14-fold increased prevalence of rare glucokinase gene variant carriers in unselected Danish patients with newly diagnosed type 2 diabetes.
Rare variants in the glucokinase gene (GCK) cause Maturity-Onset Diabetes of the Young (MODY2/GCK-MODY). We investigated the prevalence of GCK variants, phenotypic characteristics, micro- and macrovascular disease at baseline and follow-up, and treatment among individuals with and without pathogenic GCK variants. This is a cross-sectional study in a population-based cohort of 5,433 individuals without diabetes (Inter99 cohort) and in 2,855 patients with a new clinical diagnosis of type 2 diabetes (DD2 cohort) with sequencing of GCK. Phenotypic characteristics, presence of micro- and macrovascular disease and treatment information were available for patients in the DD2 cohort at baseline and after an average follow-up of 7.4 years. Twenty-two carriers of potentially deleterious GCK variants were found among patients with type 2 diabetes compared to three among 5,433 nondiabetic individuals [OR = 14.1 (95 % CI 4.2; 47.0), p = 8.9*10-6]. Patients with type 2 diabetes carrying GCK variants had significantly lower waist circumference, hip circumference and BMI, compared to non-carriers. Three GCK variant carriers with diabetes had microvascular complications during follow-up. Approximately 0.8% of Danish patients with newly diagnosed type 2 diabetes carry non-synonymous variants in GCK and resemble patients with GCK-MODY. Glucose-lowering treatment cessation should be considered in this subset of diabetes patients.


Tubular basement membrane change occurs pari passu with the development of cyst formation.
Our previous studies have shown that 2-amino-4,5-diphenyl thiazole hydrochloride (DPT) administered orally to rats induces a urine concentrating defect (within 1 to 2 days) and progressive, but reversible, cystic change of all collecting tubules (prominent between 4 and 8 weeks). Cystic change was characterized by tubular cell and basement membrane changes consisting of alterations in cellular biosynthetic/secretory organelles, followed by thickening of the basement membrane with marked reduction (approximately 50%) of the de novo synthesis of sulfated proteoglycans, suggesting that altered synthesis of tubular basement membrane plays a role in the development of cystic disease. In this study, following the administration of [14C]-DPT in vivo, a major urinary metabolite (greater than 70%) was isolated by HPLC and characterized by gas chromatographic-mass spectral and NMR analyses as 2-amino-4-hydroxyphenyl-5 phenyl thiazole, designated phenol II. Phenol II was synthesized and administered orally to rats for four days to compare its biological effects with DPT. Phenol II induced a significantly greater impairment of concentrating ability and tubular cystic transformation than DPT. At day 5, in phenol II treated animals, basement membranes lining cysts were thickened several-fold and exhibited extensive loss and disorder of ruthenium red binding sites, indicative of loss of sulfated proteoglycans (heparin sulfate proteoglycan). The basement membrane changes occurred in tandem with the development of cystic transformation and strongly suggests that the basement membrane has a key role in the pathogenesis of PKD. The findings support the hypothesis that PKD may be due to a defect in the synthesis/degradation of one or more basement membrane components (sulfated proteoglycans) resulting in faulty tubular morphogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)


Solidarity and HIV Testing Willingness During the COVID-19 Epidemic: A Study Among Men Who Have Sex With Men in China.
Background: Solidarity, such as community connectedness and social cohesion, may be useful in improving HIV testing uptake among men who have sex with men (MSM). This study aimed to evaluate the impact of solidarity on HIV testing before the coronavirus disease 2019 (COVID-19) and HIV testing willingness during COVID-19 among MSM in China. Materials and Methods: An online survey was conducted to collect sociodemographic, sexual behavioral, and solidarity items' information from the participants. We first used factor analysis to reveal the principal component of the solidarity items and then used logistic regression to study the impact of solidarity on HIV testing, by adjusting the possible confounding factors, such as age and education. Results: Social cohesion and community connectedness were revealed by the factor analysis. MSM with high community connectedness were more willing to undergo HIV testing before the epidemic adjusted by age [odds ratio (OR): 1.07, 95% CI: 1.01-1.13]. The community connectedness was also related to the willingness of HIV testing during the epidemic, with adjustments of 1.09 (95% CI: 1.03-1.15). People who did not test for HIV before the COVID-19 epidemic were more willing to have the HIV test during the epidemic, which was correlated with the community connectedness, and the OR value was 1.14 (95%: 1.03-1.25). Conclusion: A high level of community connectedness helped to increase the HIV testing rate before COVID-19 and the willingness of HIV testing during the epidemic among MSM. Strategies can strengthen the role of the community in the management and service of MSM.


Chlamydia trachomatis genes whose products are related to energy metabolism are expressed differentially in active vs. persistent infection.
The Chlamydia trachomatis genome encodes glycolysis and pentose phosphate pathway enzymes, two ATP/ADP exchange proteins, and other energy transduction-related components. We asked if and when chlamydial genes specifying products related to energy transduction are expressed during active vs. persistent infection in in vitro models and in synovia from Chlamydia-associated arthritis patients. Hep-2 cells infected with K serovar were harvested from 0-48 h post-infection (active infection). Human monocytes identically infected were harvested at 1, 2, 3, 5 days post-infection (persistent). RNA from each preparation and from synovial samples PCR-positive/-negative for Chlamydia DNA was subjected to RT-PCR targeting (a) chlamydial primary rRNA transcripts and adt1 mRNA, (b) chlamydial mRNA encoding enzymes of the glycolysis (pyk, gap, pgk) and pentose phosphate (gnd, tal) pathways, the TCA cycle (mdhC, fumC), electron transport system (cydA, cydB), and sigma factors (rpoD, rpsD, rpoN). Primary rRNA transcripts and adt1 mRNA were present in each infected preparation and patient sample; controls were negative for chlamydial RNA. In infected Hep-2 cells, all energy transduction-related genes were expressed by approximately 11 h post-infection. In monocytes, pyk, gap, pgk, gnd, tal, cydA mRNA were present in 1-2-day-infected cells but absent at 3 days and after; cydB, mdhC, fumC were expressed through 5 days post-infection. RT-PCR targeting mRNA from sigma factor genes indicated that lack of these gene products cannot explain selective transcriptional down-regulation during persistence. Analyses of RNA from synovial tissues mirrored those from the monocyte system. These data suggest that in the first phase of active chlamydial infection, ADP/ATP exchange provides energy required for metabolism; in active growth, glycolysis supplements host ATP. In persistence host, rather than bacterially produced, ATP is the primary energy source. Metabolic rate in persistent C. trachomatis is lower than in actively growing cells, as judged from assays for relative chlamydial primary rRNA transcript levels in persistent vs. actively growing cells.


Headache Induced by Fibrous Dysplasia of the Sphenoid Sinus: A Case Report.
Although is a rare disease entity and it is not enough to know about the causal relationship between fibrous dysplasia (FD) of the sphenoid sinus and headache, we should keep in mind the headache is the most common symptom among wide spectrum of potential symptoms in craniofacial FD.


Aldol Reactions of Biorenewable Triacetic Acid Lactone Precursor Evaluated Using Desorption Electrospray Ionization Mass Spectrometry High-Throughput Experimentation and Validated by Continuous Flow Synthesis.
Desorption electrospray ionization-mass spectrometry (DESI-MS) was used as a high-throughput experimentation (HTE) tool to rapidly identify derivatives of the biobased platform molecule triacetic acid lactone (TAL). TAL is a platform molecule capable of conversion to a wide range of useful commodity chemicals, agrochemicals, and advanced pharmaceutical intermediates. In the present study, a diverse family of aldol reaction mixtures were prepared in high-density microtiter plates with a liquid handling robot, then printed with a pin tool onto a PTFE surface for analysis by DESI-MS. Our DESI-MS results indicate that aldol products of TAL were obtained for each substrate tested, in good agreement with previously reported TAL reactivity. These HTE experiments also revealed solvent-dependent reactivity trends that facilitated reaction scale up. Our findings suggest that DESI-MS analysis can rapidly inform the selection of optimal reaction conditions from a wide variety of conditions for scale up using continuous synthesis conditions.


Monocyte and macrophage immunometabolism in atherosclerosis.
Atherosclerosis is characterized by chronic low grade inflammation of arteries that results in the development of lipid dense plaques. Chronic inflammation induced by Western-type diet is associated with the risk of developing atherosclerosis, and new insights shed light on the importance of metabolic and functional reprogramming in monocytes and macrophages for progression of atherosclerosis. This review aims to provide an overview of our current understanding into how the metabolic reprogramming of glucose, cholesterol, fatty acid, and amino acid metabolism in macrophages contributes to inflammation during atherosclerosis. Recent insights suggest that transcriptional and epigenetic adaptation within innate immune cells (termed trained immunity) play an important role in the pathogenesis of atherosclerosis. We propose that metabolic changes induced by pro-atherogenic lipoproteins partly mediate these changes in trained macrophages. Finally, we discuss the possibility of manipulating cellular metabolism of immune cells for targeted therapeutic intervention against atherosclerosis.


The Selective Estrogen Receptor Modulator, Raloxifene, Is Protective Against Renal Ischemia-reperfusion Injury.
There is increasing evidence that estrogen is responsible for improved outcomes in female kidney transplant recipients. Although the exact mechanism is not yet known, estrogen appears to exert its protective effects by ameliorating ischemia-reperfusion injury (IRI). In this study, we have examined whether the beneficial effects of exogenous estrogen in renal IRI are replicated by therapy with any one of several selective estrogen receptor modulators. C57BL/6 adult mice underwent standardized warm renal ischemia for 28 min after being injected with the selective estrogen receptor modulators, raloxifene, lasofoxifene, tamoxifen, bazedoxifene, or control vehicle (dimethyl sulfoxide), at 16 and 1 h before IRI. Plasma concentrations of blood urea nitrogen and creatinine were assessed 24, 48, 72, and 96 h post-IRI. Tissue was collected 30 d postischemia for fibrosis analysis using Sirius Red staining. Raloxifene treatment in female mice resulted in significantly lower blood urea nitrogen and creatinine after IRI and significantly lower fibrosis 30 d following IRI. Raloxifene is protective against both acute kidney injury and fibrosis resulting from renal IRI in a mouse model.


Angular dependence of the upper critical induction of cleans- anddx2-y2-wave superconductors with self-consistent ellipsoidal effective mass and Zeeman anisotropies.
We employ the Schrödinger-Dirac method generalized to an ellipsoidal effective mass anisotropy in order to treat the spin and orbital effective mass anisotropies self consistently, which is important when Pauli-limiting effects on the upper critical field characteristic of singlet superconductivity are present. By employing the Klemm-Clem transformations to map the equations of motion into isotropic form, we then calculate the upper critical magnetic inductionBc2(θ,ϕ,T)at arbitrary directions and temperaturesTfor isotropics-wave and for anisotropicdx2-y2-wave superconducting order parameters. As for anisotropics-wave superconductors,Bc2is largest in the direction of the lowest effective mass, and is proportional to the universal orientation factorα(θ,ϕ). However, fordx2-y2-wave pairing and vanishing planar effective mass anisotropy,Bc2(π/2,ϕ,T)exhibits a four-fold azimuthal pattern withC4symmetry the maxima of which are along the crystal axes just below the transition temperatureTc, but these maxima are rotated byπ/4about thezaxis asTis lowered to 0. However fordx2-y2-wave pairing with weak planar effective mass anisotropy,Bc2(π/2,ϕ,T)exhibits a two-fold pattern withC2symmetry for allT ⩽ Tc, which also rotates byπ/4about thezaxis asTis lowered to 0. These low planar effective mass anisotropy cases provide a new method to distinguishs-wave anddx2-y2-wave pairing symmetries in clean unconventional superconductors.


Monitoring superficial peroneal nerve somatosensory evoked potential during L4-5 lumbar root decompression.
Posttibial nerve somatosensory evoked potential (PTN-SSEP) often fails to detect individual nerve root dysfunction, whereas dermatomal somatosensory evoked potential (DSSEP) can be difficult to obtain in anesthetized patients. The main aim of this study is to investigate whether the superficial peroneal nerve SSEP (SPN-SSEP), a cutaneous nerve SSEP derived from L4-5 roots, can be relied on as an intraoperative neurophysiological assessment for L4-5 roots. Retrospective review of consecutive case series. Thirty-five consecutive patients who underwent lumbar root microdecompression were reviewed. The control group consisted of 11 patients who underwent anterior cervical discectomy and fusion (ACDF). Intraoperative SSEP measures defined outcome measures. Data from 35 patients undergoing SPN-SSEP, PTN-SSEP, and sural nerve SSEP (SN-SSEP) monitoring during lumbar surgeries were analyzed and compared with the control group of patients underwent ACDF surgery. Cortical SPN-SSEP could be readily recorded in more than 90% patients from both groups. The waveforms of SPN-SSEP were about 30% smaller than PTN-SSEP, but very similar to SN-SSEP. Importantly, SPN-SSEP was capable of detecting intraoperative L4-5 root dysfunction without the corresponding PTN-SSEP or SN-SSEP alterations. Overall, SPN-SSEP displayed twofold greater sensitivity over PTN-SSEP or SN-SSEP. SPN-SSEP was a more sensitive measure for intraoperative L4-5 nerve root dysfunction in comparison with PTN-SSEP and SN-SSEP.


[On the management of aged patients in intensive and emergency care services].
The management of the elderly patients by the emergency medical service and in the intensive care unit refers to the human and professional experience of the medical team. The treatment of this kind of patients lays down a rule of conduct with the point of view of the economical and moral aspect.


Glycocholic acid aggravates liver fibrosis by promoting the up-regulation of connective tissue growth factor in hepatocytes.
The precise role of bile acid in the progression of liver fibrosis has yet to be elucidated. In this study, common bile duct ligation was used as an in vivo mouse model for the evaluation of bile acids that promote liver connective tissue growth factor expression. Primary rat and mice hepatocytes, as well as primary rat hepatic stellate and HepaRG cells were evaluated as in vitro models for promoting the expression of connective tissue growth factor by bile acids. Compared with taurochenodeoxycholic acid, glycochenodeoxycholic acid, and taurocholic acid, glycocholic acid (GCA) most strongly promoted the secretion of connective tissue growth factor in mouse primary hepatocytes, rat primary hepatocytes and HepaRGs. GCA did not directly promote the activation of hepatic stellate cells. The administration of GCA in mice with ligated bile ducts promotes the progression of liver fibrosis, which may promote the yes-associated protein of hepatocytes into the nucleus, resulting in the hepatocytes secreting more connective tissue growth factor for hepatic stellate cell activation. In conclusion, our data showed that GCA can induce the expression of connective tissue growth factor in hepatocytes by promoting the nuclear translocation of yes-associated protein, thereby activating hepatic stellate cells. Our findings help to elucidate the contribution of GCA to the progression of hepatic fibrosis in cholestatic disease and aid the clinical monitoring of cholestatic liver fibrosis development.


On the taxonomy of Negeta semialba Hampson, 1918 with descriptions of two new Leucobaeta Lszl, Ronkay amp; Witt, 2010 species (Lepidoptera, Nolidae, Nolinae).
The taxonomic position of the West African Negeta semialba Hampson, 1918 is revised and the species is transferred from the genus Negeta Walker, 1862 of Westermanniinae to Leucobaeta Lszl, Ronkay Witt, 2010 of Nolinae: Leucobaeta semialba (Hampson, 1918) comb. n., based on morphological analysis. The hitherto unknown male adult and genitalia of both sexes are described and illustrated. Leucobaeta semialba is compared to the superficially similar Afrotropical Negeta mesoleuca (Holland, 1894) and N. ruficeps (Hampson, 1902); two sibling species from East Africa and Madagascar are described as new to science: L. smithi and L. malagassa spp. n. Pairwise genetic distances of COI-5P sequences between the taxa are provided.


Gene expression analysis of Canine Demodicosis; A milieu promoting immune tolerance.
Canine demodicosis is a common skin disease seen in companion animal practice that results from an overpopulation of the commensal Demodex mite species. Common predisposing factors to the development of canine demodicosis include immunosuppressive diseases, such as neoplasia and hypothyroidism, and administration of immunosuppressive therapies, such as corticosteroids. Despite this, the pathogenesis of development of canine demodicosis remains unclear. Previous studies have implicated a role for increased expression of toll like receptor 2 (TLR2), increased production of interleukin (IL)-10) and T cell exhaustion. Here, we investigate gene expression of formalin fixed paraffin embedded skin samples from twelve cases of canine demodicosis in comparison to twelve healthy controls, using a 770 gene panel (NanoString Canine IO Panel). Results show an increase in the T cell population, specifically Th1 and Treg cells in dogs with demodicosis. In addition, while there is an upregulation of immunosuppressive cytokines such as IL-10 and IL-13, there is also an upregulation of immune check point molecules including PD-1/PD-L1 and CTLA-4. These findings suggest that Demodex spp. mites are modulating the host immune system to their advantage through upregulation of several immune tolerance promoting pathways.


Numerical examination of performance of some exchange-correlation functionals for molecules containing heavy elements.
The performance of 17 exchange-correlation functionals for molecules containing heavy elements are numerically examined through four-component relativistic density DFT calculations. The examined functionals show the similar accuracy as they do for the molecules containing light elements only except for bond lengths. LDA and OP86 produce good results for bond lengths and frequencies but bad bond energies. Different functionals do not show much different performance for bond energies except LDA. BP86 and GP86 produce results with average accuracy while LYP does not perform well. Although encouraging results are obtained with functional B97GGA-1, other heavily parameterized and meta-GGA functionals do not produce impressive results.


Cell death pathology: perspective for human diseases.
Apoptosis, a genetically regulated form of cell death with distinct biochemical and morphological features, plays a relevant physiological and pathological role in the organism, being pivotal in the maintenance of tissue development and homeostasis in the adult as well as in the regulation of immune responses. Deregulation of this process causes several human disorders including cancer, autoimmune and neurodegenerative diseases. Thus, modulation of the apoptotic process and of cell death in general, is a potential therapeutic approach for the treatment of several human pathologies.


Computational neuropsychiatry - schizophrenia as a cognitive brain network disorder.
Computational modeling of functional brain networks in fMRI data has advanced the understanding of higher cognitive function. It is hypothesized that functional networks mediating higher cognitive processes are disrupted in people with schizophrenia. In this article, we review studies that applied measures of functional and effective connectivity to fMRI data during cognitive tasks, in particular working memory fMRI studies. We provide a conceptual summary of the main findings in fMRI data and their relationship with neurotransmitter systems, which are known to be altered in individuals with schizophrenia. We consider possible developments in computational neuropsychiatry, which are likely to further our understanding of how key functional networks are altered in schizophrenia.


Glutamate and GABA immunocytochemical electron microscopy in the hippocampal dentate gyrus of normal and genetic absence epilepsy rats.
It is generally accepted that absence epilepsy results from the impairment of GABAergic and glutamatergic neurotransmission. In particular, besides excessive GABA mediation within the thalamo-cortico-thalamic circuit in absence epilepsy, neuronal networks of the hippocampus have recently received attention. In the present study, we examined the density of glutamate and GABA neurotransmitter immunolabeling in the dentate gyrus of the hippocampus of genetic absence epilepsy rats from Strasbourg (GAERS) compared to the control group. GABA and glutamate were found to exist in synaptic vesicles of the mossy fiber terminals of the control and GAERS groups. The density of glutamate immunolabeling within the mossy fiber terminals in the hilar region of GAERS hippocampus was found to be significantly decreased compared to the control group. There was no difference in the density of immunolabeling within GABA nerve terminals between GAERS and control group. The findings of this study suggest that mechanisms underlying absence seizures in GAERS may also manifest themselves in other brain regions such as the hippocampus. The presence of GABA within synaptic vesicles of mossy fiber terminals, as revealed by high resolution ultrastructural immunocytochemistry, has provided additional evidence to the possible modulatory role of GABA on synaptic transmission between the mossy fiber and the target cell.


Molecular modeling reveals the possible importance of a carbonyl oxygen binding pocket for the catalytic mechanism of p-hydroxybenzoate hydroxylase.
p-Hydroxybenzoate hydroxylase catalyzes the hydroxylation of an aromatic substrate and uses flavin as a cofactor. The reaction probably occurs via a flavin 4a-hydroperoxide intermediate. In this study the crystal structure of 4a,5-epoxyethano-3-methyl-4a,5-dihydrolumiflavin, an analogue of the flavin 4a-hydroperoxide intermediate, was fitted to the active site in the crystal structure of the p-hydroxybenzoate hydroxylase-3,4-dihydroxybenzoate complex. This model of an important catalytic intermediate fitted very well in the active site of p-hydroxybenzoate hydroxylase. The most striking result was that whereas with the normal flavin, the 0-4 of the flavin ring makes only poor hydrogen bonds with the protein, with the flavin 4a-hydroperoxide analogue, the same 0-4 makes strong hydrogen bonds with the NH groups of Gly-46 and Val-47. These two NH groups form a carbonyl oxygen binding pocket which has a geometry almost identical to the oxyanion hole found in several proteases. The possible consequences of this model for the reaction mechanism of p-hydroxybenzoate hydroxylase are discussed.


Clinical applications of Scheimpflug imaging in cataract surgery.
Since the Scheimpflug principle was first described over a century ago, there has been a great interest among ophthalmologists for the use of Scheimpflug camera in anterior segment imaging. Scheimpflug imaging has since advanced significantly and modern day instruments provide comprehensive imaging and topographic data of the anterior segment. In this article the clinical applications and limitations of Scheimpflug imaging in modern cataract surgery patients are discussed. This article reviews recent work on assessment of lens transparency for cataract grading and integrity, using preoperative lens density measurements to help predict phacoemulsification parameters, its utility in challenging situations like capsular bag distension syndrome and traumatic cataract and assessment of density of the posterior capsule for objectively quantifying posterior-capsule opacification.


Feasibility of measuring acoustic streaming for improved diagnosis of rhinosinusitis.
No noninvasive methods exist currently with the capability of distinguishing between various stages of a sinus infection. We studied a method based on induced acoustic streaming in the accumulated fluid within the maxillary sinuses. The hypothesis was that acoustic streaming will not be induced at clinically acceptable intensity levels in infectious mucous fluid because of its high viscosity, whereas detected acoustic streaming is a strong indication that the sinus content is a noninfectious serous fluid. As a model, an anthropomorphic sinus phantom with bovine cortical bone to mimic the bone surrounding the maxillary sinus was constructed. Milk (1.5% fat content) was used as model fluid. From fluid and bone attenuation measurements, an ultrasound frequency of about 5 MHz was estimated to produce the highest acoustic streaming in the sinus phantom. Simulations of the acoustic streaming in a sealed cavity also showed that the width of the ultrasound beam should be about half the size of the cavity to optimize the streaming velocity. With a 4.9-MHz continuous-wave transducer operating at a spatial peak temporal average intensity (I(spta)) of 640 mW/cm(2), an acoustic streaming velocity of 0.19 cm/s was generated and detected in the sinus phantom.


Changes of serum growth factors (IGF-I,-II and IGFBP-2,-3) prior to and after stem cell transplantation in children with acute leukemia.
Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) may play an important role in tumor proliferation. This study aimed to investigate the IGF system in children with acute leukemia prior to and after hematological stem cell transplantation (HSCT). In 51 patients (AML n=27; ALL n=24; mean age 11.2+/-4.8 years), serum parameters (IGF-I,-II, IGFBP-2,-3) were investigated up to 18 months after HSCT by RIA. Patients with AML showed a significant increase of IGFBP-2 up to 100 days after HSCT (mean +/-s.d. prior to HSCT: 3.2+/-3.6 SDS vs 100 days after HSCT: 5.3 degrees +/-3.4 SDS, P=0.005). Furthermore, IGF-I and IGFBP-3 were significantly decreased (IGF-I: -0.3+/-1.5 vs -0.7 +/-1.2 SDS, P=0.001; IGFBP-3: -0.3+/-1.1 vs -1.0+/-1.1 SDS, P=0.02). Children with AML showed significantly higher IGFBP-2 (P=0.04) and significantly lower IGF-I (P=0.03) and IGFBP-3 (P=0.05) levels than children with ALL at day 100 after HSCT. We conclude that children with acute leukemia show important changes in the IGF system after HSCT. In particular, IGFBP-2 was significantly elevated at day 100 after HSCT. Increased IGFBP-2 and decreased IGF-I and IGFBP-3 may be associated with the increased proliferation rate of transplanted bone marrow.


Bcl2 mitigates Ca2+ entry and mitochondrial Ca2+ overload through downregulation of L-type Ca2+ channels in PC12 cells.
Altered calcium homeostasis and increased cytosolic calcium concentrations ([Ca2+]c) are linked to neuronal apoptosis in epilepsy and in cerebral ischemia, respectively. Apoptotic programmed cell death is regulated by the antiapoptotic Bcl2 family of proteins. Here, we investigated the role of Bcl2 on calcium (Ca2+) homeostasis in PC12 cells, focusing on L-type voltage-dependent calcium channels (VDCC). Cytosolic Ca2+ transients ([Ca2+]c) and changes of mitochondrial Ca2+ concentrations ([Ca2+]m) were monitored using cytosolic and mitochondrially targeted aequorins of control PC12 cells and PC12 cells stably overexpressing Bcl2. We found that: (i) the [Ca2+]c and [Ca2+]m elevations elicited by K+ pulses were markedly depressed in Bcl2 cells, with respect to control cells; (ii) such depression of [Ca2+]m was not seen either in digitonin-permeabilized cells or in intact cells treated with ionomycin; (iii) the [Ca2+]c transient depression seen in Bcl2 cells was reversed by shRNA transfection, as well as by the Bcl2 inhibitor HA14-1; (iv) the L-type Ca2+ channel agonist Bay K 8644 enhanced K(+)-evoked [Ca2+]m peak fourfold in Bcl2, and twofold in control cells; (v) in current-clamped cells the depolarization evoked by K+ generated a more hyperpolarized voltage step in Bcl2, as compared to control cells. Taken together, our experiments suggest that the reduction of the [Ca2+]c and [Ca2+]m transients elicited by K+, in PC12 cells overexpressing Bcl2, is related to the reduction of Ca2+ entry through L-type Ca2+ channels. This may be due to the fact that Bcl2 mitigates cell depolarization, thus diminishing the recruitment of L-type Ca2+ channels, the subsequent Ca2+ entry, and mitochondrial Ca2+ overload.


Structure and histogenesis of the principal sensory nucleus of the trigeminal nerve: effects of prenatal exposure to ethanol.
Clinical and experimental evidence shows that prenatal exposure to ethanol causes craniofacial malformations, microcephaly, and abnormal development of the central nervous system. This study describes the effects of ethanol on the development of the principal sensory nucleus of the trigeminal nerve (PSN). The offspring of two groups of rats were examined. Pregnant females in one group were fed a liquid diet containing 6.7% (v/v) ethanol (Et) and rats in the other group were fed an isocaloric liquid control diet (Ct). Each pregnant rat was administered [3H]thymidine on one day during the period from gestational day (G) 10 to G22. After pups grew to 30 days of age, they were killed and their brains were processed by an autoradiographic procedure. Qualitatively, the PSN of Ct- and Et-treated rats appeared similar; they were composed chiefly of small neurons and a few scattered large neurons. On the other hand, quantitative analyses revealed significant differences between both groups. Although the volume of the PSN of Et-treated rats was not significantly different (-3.2%) than that for Ct-treated rats, the PSN of Et-treated rats had significantly (P less than 0.01) fewer (30.0%) neurons than did the PSN of Ct-treated rats. The number of the small neurons, but not of the large neurons, was affected most by the ethanol exposure. Prenatal exposure to ethanol also altered the generation of PSN neurons. Most neurons in the PSN of Ct-treated rats were born between G12 and G15, the small neurons being generated before the large neurons. In Et-treated rats, too, small neurons were born before the large neurons; however, the time frame of neuronogenesis was delayed as it occurred between G13 and G16. Thus, prenatal exposure to ethanol produces profound developmental abnormalities that lead to permanent alterations in the structure of the mature central nervous system.


Reduced choroidal blood flow can induce visual field defect in open angle glaucoma patients without intraocular pressure elevation following encircling scleral buckling.
To determine the cause of the progressive glaucomatous visual field defects in three patients after an encircling scleral buckle for a rhegmatogenous retinal detachment (RRD). Scanning laser Doppler flowmetry and visual field tests were performed on three cases with unilateral progressive visual field defect after an encircling scleral buckling for a RRD. Similar measurements were made after the buckle was removed. After implanting the scleral buckle, the intraocular pressure was normal and chamber angle was open. The blood flow in the neuroretinal rim of the optic disk was lower than that in the healthy fellow eye. After removing the buckle, the blood flow improved to normal levels and a further worsening of the visual field was not detected. These results suggest that an encircling scleral buckle may impair choroidal circulation and lead to visual field defects similar to eyes with normal tension glaucoma.


Biomaterial-embedded extracellular vesicles improve recovery of the dysfunctional myocardium.
Extracellular vesicles (EV) are increasingly recognized as a therapeutic option in heart failure. They are usually administered by direct intramyocardial injections with the caveat of a rapid wash-out from the myocardium which might weaken their therapeutic efficacy. To improve their delivery in the failing myocardium, we designed a system consisting of loading EV into a clinical-grade hyaluronic acid (HA) biomaterial. EV were isolated from umbilical cord-derived mesenchymal stromal cells. The suitability of HA as a delivery platform was then assessed in vitro. Rheology studies demonstrated the viscoelastic and shear thinning behaviors of the selected HA allowing its easy injection. Moreover, the release of HA-embedded EV was sustained over more than 10 days, and EV bioactivity was not altered by the biomaterial. In a rat model of myocardial ischemia reperfusion, we showed that HA-embedded EV preserved cardiac function (echocardiography), improved angiogenesis and decreased both apoptosis and fibrosis (histology and transcriptomics) when compared to intramyocardial administration of EV alone. These data thus strengthen the concept that inclusion of EV into a clinically useable biomaterial might optimize their beneficial effects on post-ischemic cardiac repair.


Cellular expression of alpha 4 subunit mRNA of the nicotinic acetylcholine receptor in the developing rat telencephalon.
By contrast to adult brain, little is known on the development of nicotinic acetylcholine receptor (nAChR) expression. Using a digoxigenin-labeled riboprobe for in situ hybridization, alpha 4 nAChR subunit mRNA expression was studied in embryonic and postnatal rat neocortex and hippocampus where it was transiently increased in neuronal subpopulations and preceded cholinergic fiber ingrowth. alpha 4 expression was increased in neocortical layer VIb between E20 and P2 and, about birth, in dentate gyrus granule cells subsequently decreasing to adult levels. nAChR mRNA expression is increased at the developing neuromuscular endplate preceding cholinergic innervation which triggers changes in non-alpha nAChR isoform expression. It has to be elucidated whether similar changes may occur in the telencephalon.


Development and validation of a hybrid simulator for ultrasound-guided laparoscopic common bile duct exploration.
Ultrasound-guided laparoscopic common bile duct exploration (LCBDE) is the surgical management of choledocholithiasis. The procedure presents significant benefits to patients but still fails to be generalised because of the complex set of skills it requires. A simulator for ultrasound-guided LCBDE would allow trainee surgeons as well as experienced surgeons who perform this surgery seldomly to practice and gain confidence. This article presents the development and validation of an easily reproducible hybrid simulator for ultrasound-guided LCBDE which integrates real and virtual components of the task. We first developed a physical model made of silicone. The fabrication technique is replicable and allows quick and easy production of multiple models. We then applied virtual components onto the model to create training for laparoscopic ultrasound examination. Combined with a commercially available lap-trainer and surgical equipment, the model can be used for training the fundamental steps of the surgery through the trans-cystic or trans-choledochal approaches. The simulator was evaluated through face, content, and construct validation. Two novices, eight middle grades, and three experts were recruited to test the simulator. The results of the face validation showed that the surgeons found the model realistic visually and felt realistic when performing the different steps of the surgery. The content validation indicated the usefulness of having a training system to practice the choledochotomy, the choledochoscopy and stone retrieval, and the suturing. The construct validation highlighted the ability of the simulator to differentiate between surgeons with various levels of expertise. The hybrid simulator presented is a low-cost yet realistic model which allows the surgeons to practice the technical skills required for trans-cystic and trans-choledochal ultrasound-guided LCBDE.


Toxic effects of acrylamide on survival, development and haemocytes of Musca domestica.
The influence of acrylamide, a potentially toxic substance present in some types of food, on survival, postembryonic development and haemocytes, insect's blood cells, of the housefly was examined. Larvae were reared on media contaminated with acrylamide at concentrations of 82 microg/g, 164 microg/g or 246 microg/g. The length of larval and pupal stages as well as the survival of larvae and pupae was examined. To study the effects of acrylamide on haemocytes, the analysis of their index and morphology was performed in the third instar larva. The obtained data showed that the survival of larvae exposed to 82 microg/g and 164 microg/g concentrations of acrylamide decreased by 50% and 85%, respectively, whereas 246 microg/g concentration was lethal. In both groups of flies, larval and pupal stages were significantly lengthened by about 1.5 day in comparison with control. Moreover, acrylamide increased the number of prohaemocytes and intermediate cells while the number of plasmatocytes and granulocytes decreased. The size of plasmatocytes decreased in acrylamide-treated larvae when compared with these cells of control flies. The reduced survival of animals is probably due to affecting haemocytes involved in immune responses in insects. Moreover, the housefly's blood cells showed to be sensitive to toxin, which suggests their usefulness to test toxicity of substances present in food products.


Starmerella lactis-condensi, a yeast that has adapted to the conditions in the oenological environment.
The yeast Starmerella (Candida) lactis-condensi is considered a food contaminant microorganism. The aim of our research was to determine why St. lactis-condensi could become the dominant species of Essences, the top sweet wine speciality of Tokaj wine region in Hungary. We investigated the physiological properties of these yeasts based on parameters that may influence their ability to selectively proliferate and persist during maturation in wines with very high sugar content. These include glucose and fructose, alcohol, and sulphur tolerance. Our studies have shown that St. lactis-condensi is a fructophilic yeast that is able to adapt quickly to very high sugar concentrations (up to 500 g/L) in the Essences. The high glucose concentration inhibits its growth, as well as that of the St. bacillaris (Candida zemplinina) strains tested. The type and amount of sugars in the Essences, together with the sulphur and alcohol content, influence the composition of the dominant yeast biota. Analysis of (GTG)5 microsatellite in the nuclear genome and mtDNA-RFLP studies demonstrate that a diverse population of St. lactis-condensi occurs in the Tokaj wine region, in the Essences. This yeast species is characterised by both physiological and genetic biodiversity. GC-MS analysis of Essences colonised exclusively with these yeasts showed no deterioration in quality.


B-cell epitopes in HIV-1 Tat and Rev proteins colocalize with T-cell epitopes and with functional domains.
We describe the characterization of the B-cell epitopes of HIV-1 regulatory proteins Tat and Rev. The prevalence of antibodies to these proteins among human immunodeficiency virus (HIV)-1-infected individuals was examined by enzyme-linked immunosorbent assay (ELISA) and by Western blotting. The Tat and Rev antibody-positive sera were selected for epitope mapping performed with partially overlapping synthetic peptides bound to polyethylene pins. Eighteen and twelve percent of HIV-infected individuals had antibodies against Tat or Rev, respectively. In Tat, four epitopic regions were identified, situated within amino acids 6-10 (PRLEP), 21-37 (ACTNCYCKKCCFHCQVC), 39-58 (ITKALGISYGRKKRRQRRRA) and 74-82 (TSQSRGDPT). The most frequently recognized epitopic regions were located in the middle of the protein. In Rev, the two most frequently recognized epitopic regions were near the amino terminus of the protein within amino acids 12-20 (LIRTVRLIK) and 38-49 (RRNRRRRWRERQ). A third epitope was mapped around amino acids 55-62 (ISERILGT) and a fourth around amino acids 78-83 (LERLTU). To analyze the specificity of Tat and Rev epitopes, soluble synthetic peptides representing the identified epitopes were used in an ELISA assay, and the recognition of most epitopes was shown to be specific for HIV-1-infected individuals. In addition, many of the Tat and Rev epitopes were shown to overlap with regions having functional activity or with regions previously identified as T-cell epitopes.


Histologic examination of decellularized porcine intestinal submucosa extracellular matrix (CorMatrix) in pediatric congenital heart surgery.
CorMatrix is a decellularized porcine small intestinal submucosa extracellular matrix that has gained attention as a promising alternative to current materials used in cardiac repair. While animal models demonstrate integration of CorMatrix material with host tissue, the histologic characteristics of CorMatrix used in humans are less well-characterized. In this retrospective study, we report our experience with CorMatrix material used in pediatric congenital heart surgery and describe the histology of CorMatrix material and of surrounding native tissue in explanted specimens. Records were reviewed of all pediatric patients implanted with CorMatrix from a single institution (2011-2014). Histologic examinations were performed on CorMatrix and other tissues removed. Explanted samples of CorMatrix and adherent tissues were evaluated for inflammation (acute and chronic), fibrosis, necrosis, degenerative changes, eosinophil response, foreign-body giant cell reaction, neovascularization, and calcification of tissues on a semiquantitative basis (0, none; 1, mild; 2, moderate; 3, marked). Presence of degeneration within CorMatrix and necrosis of surrounding tissue were noted. CorMatrix was utilized in 532 pediatric heart reconstruction procedures since 2011. Twelve explanted CorMatrix specimens from 11 pediatric patients including 4 valves (2 mitral and 2 aortic) and 8 outflow/septal/conduit patches were identified and evaluated. Six cases (5 patients) demonstrated clinical evidence of graft failure prior to surgery (n=6, 1%). Chronic inflammation was seen in adjacent native tissue in 11/12 cases and consisted predominantly of a mixed population of lymphocytes, macrophages, and plasma cells. Acute inflammation was seen in three cases (3/12). Fibrosis of the surrounding native tissue was seen in all CorMatrix specimens. Eosinophils were present in 6/12 cases. Calcification in surrounding tissue was present in 3/12 cases. Giant cell reaction in adjacent native tissue was seen in 8/12 cases. Neovascularization was seen in surrounding native tissue in 5/12 cases. Degeneration of CorMatrix material was seen in 9/12 cases. Necrosis of surrounding tissue was also identified in 5/12 cases. CorMatrix was not resorbed and no cases demonstrated any remodeling of CorMatrix material by integration of native mesenchymal cells or myocytes. CorMatrix may be associated with a marked inflammatory response, including a foreign-body giant cell reaction and fibrosis of the surrounding native tissue. Degenerative changes of CorMatrix material are also seen in a majority of explanted specimens. No histologic differences were seen between patients with clinical evidence of graft failure versus patients requiring graft removal due to other factors. Additionally, no cases showed evidence of tissue integration or recellularization of patch material. Our overall clinical experience with CorMatrix demonstrates a favorable outcome for pediatric patients undergoing cardiac reconstructive surgery. However, there is no histologic evidence that CorMatrix acts as a scaffold for reconstitution of the native cardiovascular structures.


A method for the collection and determination of phenol and bisphenol A in air.
An analytical method has been developed for the determination of phenol and bisphenol A in air. Air samples are concentrated on commercial silica by the well established tube-pump method. The trapped components are desorbed and analyzed by HPLC using UV detection at 275 nm. The method has been validated for a concentration range of 0.5-50 mg m-3 (based on a 10-l air sample) for both compounds. Linearity of response, adsorption/desorption efficiency, influence of humidity on sample collection and influence of temperature and time on storage of collected samples were studied. The reported technique provides a selective and sensitive method for environmental monitoring in industrial atmospheres as well as for personnel exposure measurement.


Use of a modified zirconia support in the separation of immunoproteins.
Zirconia beads (25-38 microm in diameter) were modified with N,N,N',N'-ethylenediaminetetramethylenephosphonic acid to generate a zirconia based pseudoaffinity support, further referred to as r_PEZ. The influence of pH, salt concentration and temperature on the binding of human immunoglobulin G (hIgG) to r_PEZ was studied. Temperature had no significant impact on the maximum binding capacity (Qmax), and the equilibrium-binding constant (Kd), whereas pH and the salt concentration had a noticeable impact on both Qmax and Kd. The Qmax value of 55 mg hIgG/ml of bead was obtained at a pH of 5.5 and found to decrease with an increase of pH. The modified zirconia support allowed the separation of immunoglobulins (IgG, IgA and IgM) from untreated human serum. Elution was possible under mild conditions with a step salt gradient. Overall protein recoveries in the range of 109-125% were obtained with human serum. Human IgG, human IgA, and human IgM yields of 29.50+/-6.3, 3.22+/-0.7, and 6.84+/-0.7%, respectively, were obtained at a linear velocity of 4.32 cm/min. Purity of products, obtained from a single chromatographic step was estimated to be greater than 89.0+/-2.6%. The utility of r_PEZ in the selective removal of immunoglobulins, as in immunoadsorption was discussed.


Multiple imputation methods for missing multilevel ordinal outcomes.
Multiple imputation (MI) is an established technique for handling missing data in observational studies. Joint modelling (JM) and fully conditional specification (FCS) are commonly used methods for imputing multilevel data. However, MI methods for multilevel ordinal outcome variables have not been well studied, especially when cluster size is informative on the outcome. The purpose of this study is to describe and compare different MI strategies for dealing with multilevel ordinal outcomes when informative cluster size (ICS) exists. We conducted comprehensive Monte Carlo simulation studies to compare the performance of five strategies: complete case analysis (CCA), FCS, FCS+CS (including cluster size (CS) in the imputation model), JM, and JM+CS under various scenarios. We evaluated their performance using a proportional odds logistic regression model estimated with cluster weighted generalized estimating equations (CWGEE). The simulation results showed that including CS in the imputation model can significantly improve estimation accuracy when ICS exists. FCS provided more accurate and robust estimation than JM, followed by CCA for multilevel ordinal outcomes. We further applied these strategies to a real dental study to assess the association between metabolic syndrome and clinical attachment loss scores. The results based on FCS + CS indicated that the power of the analysis would increase after carrying out the appropriate MI strategy. MI is an effective tool to increase the accuracy and power of the downstream statistical analysis for missing ordinal outcomes. FCS slightly outperforms JM when imputing multilevel ordinal outcomes. When there is plausible ICS, we recommend including CS in the imputation phase.


A systematic approach to the use of the multiplanar display in evaluation of abnormal vascular connections to the fetal heart using 4-dimensional ultrasonography.
The multiplanar display is a modality that allows the simultaneous visualization of 3 orthogonal planes from volume data sets obtained with 3- and 4-dimensional ultrasonography. Simultaneous display of standard views used in fetal echocardiography and their orthogonal planes may provide novel ultrasonographic views for examination of the fetal heart and its vascular connections. This study was designed to determine the clinical utility of the multiplanar display in the examination of abnormal vascular connections to the fetal heart. We reviewed 4-dimensional volume data sets, acquired with the spatiotemporal image correlation technique, from patients with abnormal vascular connections to the fetal heart. Multiplanar views of the fetal heart were used to simultaneously display standard planes used in fetal echocardiography and their corresponding orthogonal planes. This study included 4 volume data sets from fetuses with confirmed abnormal vascular connections to the heart, including: (1) an interrupted inferior vena cava with azygos or hemiazygos vein continuation; (2) a persistent left superior vena cava draining into a dilated coronary sinus; and (3) a dilated superior vena cava associated with a thoracic lymphangioma. Simultaneous visualization of orthogonal planes displaying abnormal vascular connections to the fetal heart facilitated identification of the abnormal vessels and their spatial relationships with other vascular structures. Multiplanar imaging can be used to assess abnormal vascular connections to the fetal heart and may provide novel ultrasonographic planes for fetal echocardiography using 3- and 4-dimensional ultrasonography.


Synthesis, crystal structure, Hirshfeld surface and void analysis of bis-(μ2-4-amino-benzoato-κ2 O:O')bis-[bis-(4-amino-benzoato-κ2 O,O')di-aquathulium(III)] dihydrate.
The asymmetric unit of the title compound, [Tm2(C7H6NO2)6(H2O)4]·2H2O, contains three 4-amino-benzoate (4ABA) ligands, two coordinated water mol-ecules, a thulium metal ion, and a water mol-ecule of crystallization. The overall structure of the complex (4ABA-Tm) is in the form of a dimer. In the dinuclear thulium complex, symmetry-relevant TmO8 coordination polyhedra are formed by the O atoms of two chelating 4-amino-benzoate ligands, the O atoms of two non-chelating 4-amino-benzoate ligands, and two water mol-ecules. The Tm-O bond lengths range from 2.216 (3) to 2.471 (3) Å with the Tm⋯Tm separation in the dinuclear complex being 4.7863 (5) Å. The crystal structure features O-H⋯N, N-H⋯O, and O-H⋯O hydrogen-bonding inter-actions. Further stabilization of the crystal packing is due to C-H⋯π and off-set π-π stacking inter-actions. Hirshfeld surface analysis indicates that H⋯H contacts are the most significant contributors to the crystal packing (45.9%). In addition, a void analysis was performed to check the strength of the crystal packing.


The Gecko visual pigment: the dark exchange reaction and the effects of anions.
A dark reaction is known to occur in retinal extracts of the gecko (Gekko gekko), in which the natural 11-cis-chromophore of the 521-pigment is apparently replaced by adding 9-cis-retinal to form the 9-cis-photopigment. With chloride-deficient extracts the reaction involves some 70% of the 521-pigment. Anions like nitrate, azide, thiocyanate and cyanate that shift the spectrum toward the blue do not affect this 70% exchange. Anions like fluoride, iodide and sulfate likewise do not alter this magnitude of reaction. In contrast, chloride and bromide that induce a bathochromic spectral shift lead to a decrease in this dark replacement of the 11-cis chromophore. This protection is similar to the action of these two anions in antagonizing the pigment loss by NH2OH and by temperature, both occurring in the dark. Apparently, chloride and bromide alter the opsin conformation so as to stabilize and/or protect the Schiff's base linkage but nitrate, azide, thiocyanate and cyanate act at a different opsin site or by a different mechanism.


Application of the small-angle X-ray scattering technique for the study of equilibrium enzyme-substrate interactions of phenylalanyl-tRNA synthetase from E. coli with tRNAPhe.
The small-angle X-ray scattering technique (SAXS) is proposed for the investigation of equilibrium macromolecular interactions of the enzyme-substrate type in solution. Experimental procedures and methods of analysing the data obtained from SAXS have been elaborated. The algorithm for the data analysis allows one to determine the stoichiometric, equilibrium and structural parameters of the enzyme-substrate complexes obtained. The thermodynamic characteristics for the formation of complexes of tRNAPhe with phenylalanyl-tRNA synthetase have been determined and demonstrate negative cooperativity for binding of the two tRNAPhe molecules. The structural parameters (Rg, Rc, semi-axes) have been determined for free phenylalanyl-tRNA synthetase and tRNAPhe from E. coli MRE-600 and of enzyme complexes possessing one and two tRNAPhe molecules, indicating structural rearrangements of the enzyme in the interaction with tRNAPhe.


Plant serine/arginine-rich proteins: versatile players in RNA processing.
Serine/arginine-rich (SR) proteins participate in RNA processing by interacting with precursor mRNAs or other splicing factors to maintain plant growth and stress responses. Alternative splicing is an important mechanism involved in mRNA processing and regulation of gene expression at the posttranscriptional level, which is the main reason for the diversity of genes and proteins. The process of alternative splicing requires the participation of many specific splicing factors. The SR protein family is a splicing factor in eukaryotes. The vast majority of SR proteins' existence is an essential survival factor. Through its RS domain and other unique domains, SR proteins can interact with specific sequences of precursor mRNA or other splicing factors and cooperate to complete the correct selection of splicing sites or promote the formation of spliceosomes. They play essential roles in the composition and alternative splicing of precursor mRNAs, providing pivotal functions to maintain growth and stress responses in animals and plants. Although SR proteins have been identified in plants for three decades, their evolutionary trajectory, molecular function, and regulatory network remain largely unknown compared to their animal counterparts. This article reviews the current understanding of this gene family in eukaryotes and proposes potential key research priorities for future functional studies.


5,5-trans lactone-containing inhibitors of serine proteases: identification of a novel, acylating thrombin inhibitor.
Synthesis of a variety of 5,5-trans fused lactones, related to compounds found in extracts of Lantana camara, has provided a series of novel acylating inhibitors of human thrombin, trypsin, chymotrypsin and human leucocyte elastase. The most effective thrombin inhibitor is 7 with an IC50 of 130 nM and a Kobs/[1] of 4,000 M-1 s-1.


Navigating Uncertainty in Respiratory Assessment: The Interaction of Culture and Technology During Phase I Postanesthetic Recovery.
To explore postanesthesia care unit (PACU) nurses' interactions with technology during the critical Phase I recovery period. Interpretive description was used to understand nurses' experiences. Nine PACU nurses were recruited from three mid-sized hospitals within the same health authority in a Western Canadian province. Nurse participants were interviewed using a semistructured interview guide. Nurses' interactions with technology were significantly influenced by PACU culture, as they constantly navigated a level of uncertainly about their patient's respiratory status. Three themes from the study are described. Theme 1 described nurses' confidence and trust in a visual sensory respiratory assessment process and the influence of anesthesia providers. Theme 2 described PACU nurses' guarded trust or rationalized mistrust in technology. Theme 3 highlighted the contextual influences, which sustained nurses' approach to respiratory assessment. PACU nurses practiced their intuitive sensory assessments with a projected strong sense of expert practice and minimal dependence on technology. PACU nurses expressed frustrations with current PACU bedside technology, particularly the respiratory module and described some experiences with delayed identification of hypoventilation and hypoxia. Rationalized behaviors with technology and alarm suppression were commonplace. Workplace culture sustained PACU nurses' respiratory assessment practices.