Localization of high-affinity GABA uptake and GABA content in the rat duodenum during development.
The localization of high-affinity uptake sites for 3H gamma-aminobutyric acid (3H-GABA) was investigated in the rat duodenum during ontogenesis and also at the adult stage (from 15.5 days of fetal life up to 105 days post natum) by means of low- and high-resolution autoradiography. At all stages studied, specific endocrine cell types of the epithelium were labelled and an intense uptake was detected in the nervous tissue, especially in glial cells but also in scarce neurones. When the incubation medium was supplemented with beta-alanine (1 mM), a blocker of the glial uptake for GABA, the labelling persisted only in endocrine cells and in few neurones. The intensity and the frequency of the labelling decreased at later periods compared to the earlier developmental stages. The GABA content of the duodenum as measured by a new ion-exchange column chromatography-HPLC-coupled method was higher in the early postnatal period compared to later stages. These observations suggest that GABA, in addition to being a neurotransmitter, may play an important role during development of the duodenum.


A study of NO trafficking from dinitrosyl-iron complexes to the recombinant E. coli transcriptional factor SoxR.
SoxR is a transcriptional factor in Escherichia coli that induces the expression of SoxS to initiate the production of enzymes in response to oxidative stress. In addition to superoxide, SoxR is also sensitive to cellular NO to produce a protein-bound dinitrosyl-iron complex (DNIC) with a characteristic electron paramagnetic resonance (EPR) signal at g(av)=2.03. Toward developing a strategy for NO sensing based on this property of SoxR, we have overexpressed and purified the recombinant His-tagged SoxR protein. Upon treatment of the purified protein under anaerobic conditions with (1) NO solution, (2) S-nitrosothiol (RSNO), and (3) chemically synthesized low molecular weight DNICs (LMW-DNICs), we have observed enhancement of the EPR signal at g(av)=2.03 from the protein-bound DNICs over time, reflecting the redistribution of NO from the NO solution, RSNO and LMW-DNICs to the SoxR. We have exploited this NO exchange to investigate the kinetics and mechanisms of release and delivery of NO from various LMW-DNICs to an isopropyl-beta-D-thiogalactopyranoside-dependent SoxR expressed in E. coli cells. These experiments revealed that the NO from RSNO and LMW-DNICs could cross the biological membrane and enter the cytoplasm of the cell to form the SoxR protein-bound DNIC complex. For comparison, we have also studied the direct NO transfer from the LMW-DNICs to the SoxR protein in buffer. The NO transfer was found to be rapid. From the kinetic data derived, we showed that LMW-DNICs with bidentate thiolate ligands displayed greater stability in aqueous solution but exhibited more facile NO delivery to cytoplasmic SoxR in whole cells.


[Cardiac resynchronization: past, present and future].
Growing interest in dyssynchrony and cardiac resynchronisation therapy (CRT) has opened the way for new hemodynamic indications of cardiac stimulation. French investigators have played a key role in the formulation of new concepts based on clinical observation, as well as the development of resynchronisation devices in collaboration with industry, and their clinical evaluation. This review summarizes recent knowledge and perspectives pertaining to atrial, atrioventricular (AV) and ventricular dyssynchrony and resynchronisation. Some of these concepts have been validated by robust clinical evidence, on which scientific recommendations have been based. Others have been less successful but probably merit further attention.


Microextraction by packed sorbent of some β-blocker drugs with chitosan@mof-199 bio-composite in human saliva, plasma, and urine samples.
The current study introduces microextraction by packed sorbent (MEPS) to extract three beta-blocker drugs (propranolol, atenolol, and betaxolol) from biological samples. The separation and detection of the drugs were performed by high performance liquid chromatography followed by UV detection. A green approach was applied for synthesizing chitosan@MOF-199 bio-composite, which was packed into the initial part of a metal spinal (22 gage). The effective parameters on the adsorption and desorption efficiencies, including sample solution pH, eluent flow rate, cycle numbers, type and volume of eluent solvent were evaluated and optimized. Under optimal conditions linear ranges (LRs = 5-600 µg L-1), limits of detection (LODs = 1.5-4.5 µg L-1), and relative standard deviations (RSDs% = 4.7 -5.3% with three replicates and concentration of 100 µg L-1) were obtained. Relative recoveries (RR%) for plasma (77-99%), saliva (81-108%), and urine (80-112%) samples were obtained. In this study, the drug release profile of propranolol in urine was evaluated. The results showed that the highest amount of propranolol is released 4 h after taking the drug. Based on the obtained results, this is an effective, fast, sensitive, reproducible, green, and user-friendly method for beta-blocker drug extraction in biological samples.


Corpus luteum number and the maternal renin-angiotensin-aldosterone system as determinants of utero-placental (vascular) development: the Rotterdam Periconceptional Cohort.
Pregnancies with > 1 corpus luteum (CL) display a hyperdynamic circulation and an increased risk of small-for-gestational age deliveries. Among the factors released by the CL is prorenin, the inactive precursor of renin. Since the renin-angiotensin-aldosterone system (RAAS) is involved in early hemodynamic pregnancy adaptation, we linked both CL number and first-trimester concentrations of prorenin (as an indicator of RAAS activity) and the aldosterone/renin ratio (as an indicator of angiotensin-independent aldosterone effectiveness) to non-invasive markers of utero-placental (vascular) development, measured longitudinally from the first trimester onwards. A total of 201 women, who conceived naturally or after in-vitro fertilization treatment (with 0 (n = 8), 1 (n = 143), or > 1 (n = 51) CL), were selected from the Rotterdam Periconceptional Cohort. Maternal RAAS components were determined at 11 weeks gestation. Placental volume and utero-placental vascular volume were measured from transvaginal 3D ultrasound scans at 7, 9 and 11 weeks gestation, pulsatility and resistance indices of the uterine arteries were assessed by pulsed wave Doppler ultrasounds at 7, 9, 11, 13, 22 and 32 weeks gestation. At birth placental weight was obtained using standardized procedures. Pregnancies without a CL show lower uterine artery indices throughout gestation than 1 CL and > 1 CL pregnancies, while parameters of placental development are comparable among the CL groups. After adjustment for patient- and treatment-related factors, first-trimester prorenin concentrations are positively associated with uterine artery pulsatility and resistance indices (β 0.06, 95% CI 0.01;0.12, p = 0.04 and β 0.10, 95% CI 0.01;0.20, p = 0.04, respectively), while high prorenin concentrations are negatively associated with first-trimester utero-placental vascular volume (β -0.23, 95% CI -0.44;-0.02, p = 0.04) and placental weight (β -93.8, 95%CI -160.3;-27.4, p = 0.006). In contrast, the aldosterone/renin ratio is positively associated with first-trimester placental volume (β 0.12, 95% CI 0.01;0.24, p = 0.04). The absence of a CL, resulting in low prorenin concentrations, associates with low uterine artery pulsatility and resistance, while high prorenin concentrations associate with a low utero-placental vascular volume and weight. These data support a scenario in which excess prorenin, by upregulating angiotensin II, increases uterine resistance, thereby preventing normal placental (vascular) development, and increasing the risk of small-for-gestational age deliveries. Simultaneously, high aldosterone concentrations, by ensuring volume expansion, exert the opposite.


P50 gating at acute and post-acute phases of first-episode schizophrenia.
Deficit in P50 sensory gating has repeatedly been shown in schizophrenia. In order to determine the contribution of trait and/or state features to P50 gating deficit in schizophrenia we evaluated the P50 gating in patients with first-episode schizophrenia (FES) at acute and post-acute phases. Subject groups comprised 16 patients with FES and 24 healthy controls. Patients were tested at the acute phase of the illness and retested at the post-acute phase when their positive symptoms improved. During the testing at the acute phase five patients were neuroleptic-naive and the others were taking atypical antipsychotics which were started recently in order to control the acute excitation. Patients were receiving risperidone, olanzapine or quetiapine treatment at the post-acute phase. P50 gating was impaired in patients at the acute phase compared to controls. However, at the post-acute phase P50 gating was increased compared to the acute phase, reaching to the gating values of controls. P50 gating improvement might be emerged from atypical antipsychotic medication, although this can only be definitively determined by randomized studies including different antipsychotics.


Synthesis of carboxyl-modified rod-like SBA-15 by rapid co-condensation.
Carboxyl-modified SBA-15 rod-like mesoporous materials have been synthesized by a facile rapid co-condensation of tetraethylorthosilicate (TEOS) and 2-cyanoethyltriethoxysilane (CTES), followed by hydrolysis of cyanide groups in sulfuric acid. The concentration of carboxylic groups was varied by changing the silica source ratio of CTES/TEOS from 0.05 to 0.3. X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that the uniform ordered mesoporous structure and rod-like morphology of SBA-15 have been preserved even at the high concentration of carboxylic groups employed. Characterization by Fourier transformed infrared spectroscopy (FTIR), solid-state NMR investigation indicated that carboxylic groups have been successfully grafted onto the surface of SBA-15 through siloxane bonds [(O(3))SiCH(2)CH(2)COOH. The negative charges of the modified SBA-15 materials were enhanced by the presence of the carboxylic groups on the surface. The capacity of lysozyme adsorption of the modified SBA-15 materials were found to be significantly improved as compared with pure silica SBA-15. The maximum amount of lysozyme adsorption on carboxyl-modified was increased with the pH of solution increased from 5.5 to 9.0.


Morphological and molecular characteristics of fungal species associated with crown rot of strawberry in South Korea.
Crown and root rot is the most important and destructive strawberry diseases in Korea as it causes substantial economic loss. In August 2020, a severe outbreak of crown and root rot on strawberries (Fragaria × ananassa Duch.) was observed in the greenhouse at Sangju, South Korea. Infected plantlets displayed browning rot within the crown and root, stunted growth, and poor rooting. Thirty fungal isolates were obtained from the affected plantlet. Isolates were identified based on morphological characteristics and pathogenicity test as well as sequence data obtained from internal transcribed spacer, large subunit ribosomal ribonucleic acid, translation elongation factor, and RNA polymerase II-second largest subunit. Results showed that the crown and root rot of strawberry in Korea was caused by three distinct fungal species: Fusarium oxysporum f. sp. fragariae, F. solani, and Plectosphaerella cucumerina. To the best of our knowledge, F. solani, and P. cucumerina are reported for the first time as the causal agents of the crown and root rot of strawberry in South Korea. Pathogenicity tests confirmed that these isolates are pathogenic to strawberry. Understanding the composition and biology of the pathogen population will be helpful to provide effective control strategies for the disease.


In vitro assessment of the effects of cadmium and zinc on mammalian nerve fibres.
Zinc and cadmium are environmental contaminants that have a wide range of effects on the nervous system, but zinc is also considered to be an important metal in the human body. In this study the effect of CdCl(2) and ZnCl(2), at concentrations of 50,150, 250 and 500 microM, on the nerve fibres of the sciatic nerve of the rat isolated in a three-chamber recording bath were studied. At the same concentrations, CdCl(2) and ZnCl(2) were found to have almost the same inhibitory effect on the compound action potential (CAP) of the nerve fibres. Their concentration-effect curves almost overlap and there was no significant difference in their EC(50) which for CdCl(2) is 250.1+/-18 microM (n=5) and for ZnCl(2) is 282.2+/-25 microM (n=5) correspondingly (P>0.05). The no-observed-effect concentration (NOEC) was estimated to be 50-100 microM for both metals. The identical inhibitory effect of both metals on the sciatic nerve fibres indicates a common mode of action which is related to their potential to generate reactive oxygen species (ROS).


[Reconstruction of maxillary sinus superior wall fractures with calcium phosphate cement/recombinant human bonemorphogenetic protein 7 compound implanted material in rabbit].
To evaluate the osteogenetic character and repairing maxillary sinus superior wall fractures capability of calcium phosphate cement (CPC) before and after combined with recombinant human bone morphogenetie protein-7(rhBMP-7). A 10 mmX5 mm bone defect in the maxillary sinus superior wall was induced by surgery in all 24 New Zealand white rabbits. These 24 rabbits were randomly divided into two groups. The defects were repaired with CPC group (n = 12) and CPC/rhBMP-7 group (n = 12). The osteogenesis of bone defect was monitored by gro'ss observation, histological examination, observation under scanning electron microscope and measurement of ALP activity at 6 and 12 weeks after the implantation. In group CPC,new bone was found to form slowly and little by little. In group CPC/rhBMP-7, however, new bone was observed to form early and massively. The ALP activity in group CPC showed significant statistical difference with that of group CPC/rhBMP-7 (P < 0.05). The CPC/rhBMP-7 composite has osteoconductibility and osteoinductibility, comparing the use of CPC/rhBMP-7 with CPC for the repair of orbital fracture, the former show obvious advantage repairing ability in maxillary sinus superior wall defect.


A paradigm for determination of direct drug-induced modulatory alterations in Purkinje cell activity during treadmill locomotion.
This paper describes a paradigm employing chronic single unit recording techniques and videotape analysis of treadmill locomotion in order to determine drug-induced modulation of sensorimotor neuronal activity. Animals implanted with a chronic headstage microdrive unit and an indwelling jugular cannula are trained to walk on a treadmill (10 s on, 10 s off). Characteristically, cerebellar Purkinje cells recorded 1-1.5 mm from midline, exhibit increased rates of discharge in phase with movement of specific limbs during a particular stage of the step-swing cycle, as assessed by video analysis of locomotor patterns. Drug-induced alterations in this movement-correlated discharge relative to changes in the spontaneous firing rate can then be determined to assess drug-induced neuromodulatory effects beyond general non-specific excitatory or inhibitory actions.


Evaluation of a Touchless Angiography Suite Computer Controller for Neuroendovascular Procedures.
The GestSure system is an Food and Drugs Administration (FDA)-registered depth-sensing infrared device initially developed for touchless image navigation during open surgery. The goal of this study was to explore the feasibility of this technology with medical students, residents, fellows and staff neurointerventionalists, using cases of intracranial aneurysm coiling. This was a prospective cohort study of operative performance using standard keyboard and mouse against a gestural interface. A total of four medical students, six residents, six fellows and five staff neurointerventionalists were involved in the training and subsequent testing. Training involved description and demonstration of a set of gestures optimized for 3D software functions. Cases were selected from the set of patients who underwent endovascular aneurysm coiling at the Toronto Western Hospital. For the overall group 15/21 (71.4%) individuals learned the left anterior oblique 30 degrees (LAO30) task within 20 cases, 17/21 (80.9%) learned the aneurysm neck task within 20 cases, 16/21 (76.2%) learned the parent vessel task and 14/21 (66%) learned the neck and parent vessel (anatomical) tasks. Staff were more consistent (i.e. smallest standard deviation) amongst the groups compared to medical students and residents; however, it was noted that a significant learning effect was observed in participants across every level of medical and angiographic expertise. Touchless angiography suite control with a gestural interface is feasible for the manipulation of angiographic images for neuroendovascular procedures. Learning to use the system was rapid across any level of medical training but greatest for staff neurointerventionalists.


Predictor role of heart rate variability in subarachnoid hemorrhage: A systematic review.
Background- Subarachnoid hemorrhage (SAH) is one of the most devastating diseases with a high rate of morbidity and mortality. The heart rate variability (HRV) is a non-invasive method of monitoring various components of the autonomic nervous system activity that can be utilized to delineate autonomic dysfunctions associated with various physiological and pathological conditions. The reliability of HRV as a predictor of clinical outcome in aneurysmal subarachnoid hemorrhage (aSAH) is not yet well investigated in literature. Methods- A systematic review and in depth analysis of 10 articles on early HRV changes in SAH patients was performed. Results- This systematic review demonstrates a correlation between early changes in HRV indices (time and frequency domain) and the development of neuro-cardiogenic complications and poor neurologic outcome in patients with SAH. Conclusions- A correlation between absolute values or changes of the LF/HF ratio and neurologic and cardiovascular complications was found in multiple studies. Because of significant limitations of included studies, a large prospective study with proper handling of confounders is needed to generate high-quality recommendations regarding HRV as a predictor of post SAH complications and poor neurologic outcome.


Construction, expression, and characterization of AG11-843 and AG11-1581.
This data article contains descriptive and experimental data on the construction, expression, and simple characterization of AG11-843 and AG11-1581. AG1 is an important member of the DUF1220 protein family. It׳s hard to get the recombinant protein because of its DNA sequence. The DNA sequence were optimized by proper design, cloned by overlap PCR and constructed into expression vector. AG11-843 and AG11-1581.were over expressed in Escherichia coli, purified and analyzed by dynamic light scattering and gel filtration analysis. An effective technique is provided to construct and express proteins with complicated sequences.


Monohalogenated acetamide-induced cellular stress and genotoxicity are related to electrophilic softness and thiol/thiolate reactivity.
Haloacetamides (HAMs) are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residues through an SN2 reaction mechanism. Toxicity of the monohalogenated HAMs (iodoacetamide, IAM; bromoacetamide, BAM; or chloroacetamide, CAM) varied depending on the halogen substituent. The aim of this research was to investigate how the halogen atom affects the reactivity and toxicological properties of HAMs, measured as induction of oxidative/electrophilic stress response and genotoxicity. Additionally, we wanted to determine how well in silico estimates of electrophilic softness matched thiol/thiolate reactivity and in vitro toxicological endpoints. Each of the HAMs significantly induced nuclear Rad51 accumulation and ARE signaling activity compared to a negative control. The rank order of effect was IAM>BAM>CAM for Rad51, and BAM≈IAM>CAM for ARE. In general, electrophilic softness and in chemico thiol/thiolate reactivity provided a qualitative indicator of toxicity, as the softer electrophiles IAM and BAM were more thiol/thiolate reactive and were more toxic than CAM.


Characterization of the perivascular reticulin network in a case of primary brain lymphoma. Immunohistochemical demonstration of collagen types I, III, IV, and V; laminin; and fibronectin.
The character of the silver positive reticulin network was analyzed with immunofluorescence and immunoperoxidase methods in an intra vitam diagnosed case of primary brain lymphoma. The network was shown to contain connective tissue proteins rich in hexose-sugars, such as type III collagen (classical "reticulin"), basal lamina constituents type IV collagen and laminin, pericellular type V collagen, as well as fibronectin (protein involved in cell adhesion). On the other hand, very little of the fibrous type I collagen was discernible. Similarly as the silver positive network, the immunohistochemically demonstrable reticulum seemed to hold the cells in the perivascular location, and once it was broken diffuse spread into the tissue occurred. Since malignant cells of B-lymphocyte origin are not known to synthesize so-called reticulin, it is suggested that the network in primary brain lymphomas is produced by cells in the brain parenchyma (possibly pericytes or astrocytes) as a protective attempt to restrict the spread of foreign cells into the brain.


Beta IGH3, a TGF-beta inducible gene, is overexpressed in lung cancer.
Transforming growth factor-beta (TGF-beta) is capable of affecting the proliferation of many cell types. beta IGH3, TGF-beta inducible gene, was originally isolated from lung adenocarcinoma cell line (A549). We have hypothesized that beta IGH3 mRNA levels could be predictors of the development and invasion of lung cancer. The study included 71 lung cancer cases. The beta IGH3 mRNA levels were quantified by real time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler. The beta IGH3 mRNA levels were elevated in tumor tissues from lung cancer (1.058 +/- 1.212) compared with non-malignant lung tissues (0.304 +/- 0.159) (p = 0.0001). No significant difference in beta IGH3 mRNA levels was found among gender, age, pathological subtype and lymph node metastasis. The beta IGH3 mRNA levels were elevated in tumor tissues from T4 lung cancer (1.425 +/- 1.470) compared with those from T1 lung cancer (0.702 +/- 0.655) (p = 0.05) and T2 lung cancer (0.736 +/- 0.734) (p = 0.044). Using the LightCycler RT-PCR assay, the determination of beta IGH3 mRNA level might provide a potential marker for the aggressiveness of lung cancer. However, further studies and a longer follow-up are needed to confirm the impact of beta IGH3 on the biological behavior of the tumor.


Positive and negative feedback regulation of choline acetyltransferase mRNA levels in Drosophila: a study using temperature-sensitive mutants and embryo cell cultures.
Steady state levels of the mRNA coding for the neurotransmitter biosynthetic enzyme, acetylCoA-choline-O-acetyltransferase (ChAT, EC 22.214.171.124), were measured in wild type Drosophila and two temperature-sensitive mutants (Chats1 and Chats2) using the RNase protection method. At a permissive temperature the relative amounts of ChAT mRNA were: wild type: Chats1:Chats2 = 1:2.09 (+/- 0.39):3.37 (+/- 0.57) (mean +/- S.E.M.) indicating that mutant flies may compensate, for making a thermolabile form of enzyme, by producing and/or maintaining higher levels of ChAT mRNA. At a restrictive temperature the ChAT mRNA levels decreased in both mutants and increased in wild type flies. The regulatory mechanism(s) responsible for increasing ChAT mRNA in wild type flies appears to have failed in the mutants at high temperature. Steady state mRNA levels were also measured in embryonic cell cultures prepared from wild type embryos. Cultures grown in the presence of two pharmacologic agents (carbamylcholine and d-tubocurarine) which should interfere with cholinergic neurotransmission, showed less mRNA resulting from a decrease in levels of ChAT gene transcription. Our results imply that neurotransmission and the rate of neurotransmitter biosynthetic enzyme gene transcription are coupled for the cholinergic system in Drosophila.


Mosaïcplasty.
Management of the patient with symptomatic full-thickness chondral or osteochondral defects of the knee presents a challenging problem for the orthopedic surgeon. The natural history of untreated lesions demonstrates progressive degenerative changes and deterioration in functional outcome scores. Medical management, osteotomies, lavage, and debridement procedures temporize symptoms and slow progression. Cartilage restoration procedures such as microfracture and cell-based therapies have shown promise, but there are concerns of the long-term durability of these procedures in the active population. Mosaicplasty allows for restoration of articular defects with hyaline cartilage, and has shown excellent durability. Articular defect should measure between 1 to 4 cm(2) in diameter and extend 10 mm into subchondral bone. Mosaicplasty can be challenging when attempted arthroscopically, and the threshold to convert to an open procedure should be low when adequate visualization is not achieved. Use of variable graft size maximizes defect fill with hyaline cartilage. Avoidance of graft prominence >1 mm and attention to the contour of the joint optimizes the recreation of articular surface. This is achieved by placing central grafts in a large defect slightly prouder to obtain a convex shape to the articular surface. With attention to the nuances of the surgical technique, mosaicplasty offers an excellent option for cartilage restoration in the young active patient.


Identification of hub pathways and drug candidates in gastric cancer through systems biology.
Gastric cancer is the fourth cause of cancer death globally, and gastric adenocarcinoma is its most common type. Efforts for the treatment of gastric cancer have increased its median survival rate by only seven months. Due to the relatively low response of gastric cancer to surgery and adjuvant therapy, as well as the complex role of risk factors in its incidences, such as protein-pomp inhibitors (PPIs) and viral and bacterial infections, we aimed to study the pathological pathways involved in gastric cancer development and investigate possible medications by systems biology and bioinformatics tools. In this study, the protein-protein interaction network was analyzed based on microarray data, and possible effective compounds were discovered. Non-coding RNA versus coding RNA interaction network and gene-disease network were also reconstructed to better understand the underlying mechanisms. It was found that compounds such as amiloride, imatinib, omeprazole, troglitazone, pantoprazole, and fostamatinib might be effective in gastric cancer treatment. In a gene-disease network, it was indicated that diseases such as liver carcinoma, breast carcinoma, liver fibrosis, prostate cancer, ovarian carcinoma, and lung cancer were correlated with gastric adenocarcinoma through specific genes, including hgf, mt2a, mmp2, fbn1, col1a1, and col1a2. It was shown that signaling pathways such as cell cycle, cell division, and extracellular matrix organization were overexpressed, while digestion and ion transport pathways were underexpressed. Based on a multilevel systems biology analysis, hub genes in gastric adenocarcinoma showed participation in the pathways such as focal adhesion, platelet activation, gastric acid secretion, HPV infection, and cell cycle. PPIs are hypothesized to have a therapeutic effect on patients with gastric cancer. Fostamatinib seems a potential therapeutic drug in gastric cancer due to its inhibitory effect on two survival genes. However, these findings should be confirmed through experimental investigations.


Expanding the base for teaching of percutaneous coronary interventions: the explicit approach.
Accelerate and improve the training and learning process of operators performing percutaneous coronary interventions (PCI). Operator cognitive, in particular decision-making skills and technical skills are a major factor for the success of coronary interventions. Currently, cognitive skills are commonly developed by three methods: (1) Cognitive learning of rules for which statistical evidence is available. This is very incomprehensive and isolates cognitive learning from skill acquisition. (2) Informal tutoring received from experienced operators, and (3) personal experience by trial-and-error are both very slow. We propose in this concept article a conceptual framework to elicit, capture, and transfer expert PCI skills to complement the current approach. This includes the development of an in-depth understanding of the nature of PCI skills, terminology, and nomenclature needed to streamline communication, propensity of reproducible performance assessment, and in particular an explication of intervention planning and intra-intervention decision-making. We illustrate the impact of improved decision-making by simulation results based on a stochastic model of intervention risk. We identify several key concepts that form the basis of this conceptual framework, in particular different risk types and the notions of strategy, interventional module, and tactic. The increasing complexity of cases have brought PCI to the point where the decision-making skills of master operators need to be made explicit to make them systematically learnable such that the skills of beginner and intermediate operators can be improved much faster than is currently possible.


Vaginal changes after ovariectomy in ewes: A large animal model for genitourinary syndrome of menopause.
To evaluate the effect of iatrogenic menopause on the physiology of the vagina of the ewe and to evaluate if vaginal changes in ewes can be translated to women with genitourinary syndrome of menopause (GSM). Preclinical research with Dohne Merino ewes. Iatrogenic menopause was induced by bilateral ovariectomy (OVX). Animals were randomized for surgery, blinded for allocation and outcome assessment. Differences between groups were determined by linear regression analyses at 5 months after OVX. Outcome measures were vaginal epithelial thickness, pH, vaginal maturation value, vaginal maturation index, epithelial glycogen accumulation, content of elastin fibers, collagen, and vascularity. OVX ewes (n = 20) showed epithelial thinning of the vaginal wall from 146 μm to 47 μm (mean, P < 0.001). Furthermore, epithelial glycogen accumulation and vascularity of the vaginal wall significantly decreased (43% and 23%, respectively) as compared with the control group (no intervention; n = 5). No significant differences were found for other outcome measures. This study established the ewe as a suitable large animal model for GSM. Furthermore, the similar relevant outcomes in humans and ewes hold great value for future translational research for the evaluation and optimization of different treatment modalities for GSM.


Brain pericytes in culture display diverse morphological and functional phenotypes.
Pericytes play several important functions in the neurovascular unit including contractile control of capillaries, maintenance of the BBB, regulation of angiogenesis, and neuroinflammation. There exists a continuum of pericyte subtypes along the vascular tree which exhibit both morphological and transcriptomic differences. While different functions have been associated with the pericyte subtypes in vivo, numerous recent publications have used a primary human brain vascular pericytes (HBVP) cell line where this pericyte heterogeneity has not been considered. Here, we used primary HBVP cultures, high-definition imaging, cell motility tracking, and immunocytochemistry to characterise morphology, protein expression, and contractile behaviour to determine whether heterogeneity of pericytes also exists in cultures. We identified five distinct morphological subtypes that were defined using both qualitative criteria and quantitative shape analysis. The proportion of each subtype present within the culture changed as passage number increased, but pericytes did not change morphological subtype over short time periods. The rate and extent of cellular and membrane motility differed across the subtypes. Immunocytochemistry revealed differential expression of alpha-smooth muscle actin (αSMA) across subtypes. αSMA is essential for cell contractility, and consequently, only subtypes with high αSMA expression contracted in response to physiological vasoconstrictors endothelin-1 (ET1) and noradrenaline (NA). We conclude that there are distinct morphological subtypes in HBVP culture, which display different behaviours. This has significance for the use of HBVP when modelling pericyte physiology in vitro where relevance to in vivo pericyte subtypes along the vascular tree must be considered.


MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase.
B lymphocytes perform somatic hypermutation and class-switch recombination (CSR) of the immunoglobulin locus to generate an antibody repertoire diverse in both affinity and function. These somatic diversification processes are catalyzed by activation-induced cytidine deaminase (AID), a potent DNA mutator whose expression and function are highly regulated. Here we show that AID was regulated posttranscriptionally by a lymphocyte-specific microRNA, miR-155. We found that miR-155 was upregulated in murine B lymphocytes undergoing CSR and that it targeted a conserved site in the 3'-untranslated region of the mRNA encoding AID. Disruption of this target site in vivo resulted in quantitative and temporal deregulation of AID expression, along with functional consequences for CSR and affinity maturation. Thus, miR-155, which has recently been shown to play important roles in regulating the germinal-center reaction, does so in part by directly downmodulating AID expression.


Optimization of amorphadiene production in engineered yeast by response surface methodology.
Isoprenoids are among the most diverse bioactive compounds synthesized by biological systems. The superiority of these compounds has expanded their utility from pharmaceutical to fragrances, including biofuel industries. In the present study, an engineered yeast strain Saccharomyces cerevisiae (YCF-AD1) was optimized for production of Amorpha-4, 11-diene, a precursor of anti-malarial drug using response surface methodology. The effect of four critical parameters such as KH2PO4, methionine, pH and temperature were evaluated both qualitatively and quantitatively and further optimized for enhanced amorphadiene production by using a central composite design and model validation. The "goodness of fit" of the regression equation and model fit (R2) of 0.9896 demonstrate this study to be an effective model. Further, this model will be used to validate theoretically and experimentally at the higher level of amorphadiene production with the combination of the optimized values of KH2PO4 (4.0), methionine (1.49), pH (5.4) and temperature (33 °C).


[Strangulation of the toes by hair (author's transl)].
The purpose of this report is to call attention to human hair as a potential source of injury to young children's toes. The toe tourniquest syndrom is an entity described by Quinn but the autors suspected intentional wrapping.


Myocardial protection by PJ34, a novel potent poly (ADP-ribose) synthetase inhibitor.
The activation of poly (ADP-ribose) synthetase plays an important role in the pathogenesis leading to myocardial ischemia-reperfusion injury. The aim of this study was to determine if a novel potent inhibitor of poly (ADP-ribose) synthetase, PJ34, provides myocardial protection. Pigs were subjected to 60 minutes of regional ischemia followed by 180 minutes of reperfusion. Ten mg/kg of PJ34 (PJ34; n = 6) was administrated intravenously (treated group) from 15 to 5 minutes before reperfusion followed by 3 mg/kg/hour of PJ34 from 5 minutes before reperfusion to the end of 180 minutes reperfusion. Control pigs (n = 7) received vehicle only. Arterial and left ventricular pressure and coronary flow were monitored. The PJ34 showed significant reduction on infarct size (37.5%+/-4.5% and 50.5%+/-4.8% of the area at risk) for PJ34 and control pigs groups, respectively, (p < 0.05). Significant reduction in postsystolic shortening, as well as improvement on segment shortening, and positive first derivative of pressure over time (+dP/dt) maximum were also observed in PJ34 versus control pigs (p < 0.05). Our results suggest that PJ34 provides cardioprotection by decreasing myocardial infarct size and enhancing postischemic regional and global functional recovery.


Characterization of human T suppressor-inducer, -precursor and -effector lymphocytes in the antigen-specific plaque-forming cell response.
Suppression of an antigen-specific plaque-forming cell response of human blood lymphocytes can be effected by T mu+ cells that have been primed previously by antigen in vitro for 6 days. While lacking the capacity to suppress the plaque-forming response directly, these primed T mu+ suppressor-inducer cells stimulate a subpopulation of unprimed T mu gamma- cells to differentiate to T gamma + suppressor-effector cells. The T mu+, T gamma+ and T mu gamma- subsets have been shown to be heterogeneous populations of cells. Therefore, the functionally defined T suppressor-inducer, -precursor and -effector cells were characterized by OKT monoclonal antibodies and by the capacity to form rosettes with autologous erythrocytes (ar+). Evidence will be presented that in vitro a T4+mu+ar- cell induces a T8+mu gamma-ar+ precursor cell to differentiate to a T8+gamma+ar- suppressor-effector cell. A similar T suppressor-effector cell can also be isolated directly from peripheral blood of normal donors.


Pulsed dye laser treatment, a review of indications and outcome based on published trials.
Pulsed dye laser (PDL) treatment is based on the principle of selective photothermolysis and is widely considered to be the treatment of choice for a variety of cutaneous vascular lesions. To review the indications and outcome of PDL treatment and summarise new developments. A literature-based study has been conducted entailing the review of publications over the period January 1993-December 2003 using the databases Medline and Cochrane CENTRAL. The PDL was found to be effective in port wine stain, facial telangiectasia, leg telangiectasia <0.5 mm, scars, hypertrophic scars and ulcerated haemangioma. Essential characteristics of lesions suitable for PDL treatment are discussed and guidelines are presented for future research.


Simple technique to manage redundant skin after laparoscopic ventral hernia repair.
The redundant skin left behind after laparoscopic ventral hernia repair overlies a dead space that is a potential site for seroma formation. This predisposes patients to surgical-site infection and compromises the cosmetic outcome of the procedure, which is a key feature of the minimally invasive approach. We present a simple technique to deal with this problem. This technique was used in six patients who underwent laparoscopic ventral hernia repair. Two patients were men and four were women. At the end of the procedure, glue (fibrin sealant) was injected in the dead space underneath the redundant skin and pressure was applied for some time; this attached the excessive skin to the underlying tissue. This obliterated the potential dead space, reducing the chances of seroma formation, and improved the cosmetic outcome of the procedure. Patients were reviewed 8 weeks after the procedure, and their body contours had returned to normal, with no skin redundancy. Minimally invasive surgery offers the advantage of a shorter hospital stay, faster recovery and improved cosmetic outcome, achieving better patient satisfaction as a result. This simple technique at the end of laparoscopic ventral hernia repair, in which the redundant skin is attached to the underlying tissue, improves the immediate postoperative cosmetic outcome and also obliterates any potential dead space for seroma formation.


Doppler myocardial imaging to evaluate the effectiveness of pacing sites in patients receiving biventricular pacing.
The goal of this study was to compare the efficacy of biventricular pacing (BIV) at the most delayed wall of the left ventricle (LV) and at other LV walls. Biventricular pacing could provide additional benefit when it is applied at the most delayed site. In 31 patients with advanced nonischemic heart failure, the activation delay was defined, in blind before BIV, by regional noninvasive Tissue Doppler Imaging as the time interval between the end of the A-wave (C point) and the beginning of the E-wave (O point) from the basal level of each wall. The left pacing site was considered concordant with the most delayed site when the lead was inserted at the wall with the greatest regional interval between C and O points (CO(R)). After BIV, patients were divided into group A (13/31) (i.e., paced at the most delayed site) and group B (18/31) (i.e., paced at any other site). After BIV, in all patients LV end-diastolic (LVEDV) and end-systolic (LVESV) volumes decreased (p = 0.025 and 0.001), LV ejection fraction (LVEF) increased (p = 0.002), QRS narrowed (p = 0.000), New York Heart Association class decreased (p = 0.006), 6-min walked distance (WD) increased (p = 0.046), the interval between closure and opening of mitral valve (CO) and isovolumic contraction time (ICT) decreased (p = 0.001 and 0.000), diastolic time (EA) and Q-P(2) interval increased (p = 0.003 and 0.000), while Q-A(2) interval and mean performance index (MPI) did not change. Group A showed greater improvement over group B in LVESV (p = 0.04), LVEF (p = 0.04), bicycle stress testing work (p = 0.03) and time (p = 0.08) capacity, CO (p = 0.04) and ICT (p = 0.02). After BIV, LV performance improved significantly in all patients; however, the greatest improvement was found in patients paced at the most delayed site.


Constitutive activation of AKT pathway inhibits TNF-induced apoptosis in mitochondrial DNA-deficient human myelogenous leukemia ML-1a.
TNF plus protein synthesis inhibitor cycloheximide-induced apoptosis in human myelogenous leukemia ML-1a but not in C19, respiration minus mitochondrial DNA-deficient C19 cells, derived from ML-1a. To investigate how mitochondrial DNA depletion inhibits apoptosis, we investigated AKT. Both AKT and its phosphorylated form were observed only in C19, indicating that depletion of mtDNA increased protein and the active form of AKT. Treatment of C19 with LY294002, which inhibits PI-3 kinase and inhibits AKT, significantly increased apoptosis induction by TNF plus cycloheximide and eliminated phosphorylation of AKT. These results indicate that AKT activation was induced by the depletion of mtDNA and inhibited TNF-induced apoptosis.


iTRAQ and RNA-Seq analyses revealed the effects of grafting on fruit development and ripening of oriental melon (Cucumis melo L. var. makuwa).
Rootstocks are among the primary factors that influence fruit yield and quality as well as melon development. To understand the differences in the molecular mechanisms and gene expression networks of fruit development between grafted and nongrafted plants in oriental melon, we performed a comprehensive analysis of the transcriptome and proteome dynamic gene/protein expression profiles during fruit development in oriental melon (Cucumis melo L. var. makuwa). Using pairwise comparisons between grafted and nongrafted samples by transcriptome analysis, we identified a large number of candidate genes involved in hormonal signaling pathways, transcription factors, resistance-related biosynthetic pathways and photosynthesis-related metabolic pathways. Many transcription factor-encoded genes were significantly more strongly expressed in the grafted samples, for example, AP2/ERF, C2H2, MYB, bHLH, and AUX/IAA, which are well-known participants in the regulation of developmental processes and hormonal signaling metabolism. Some differentially expressed genes (DEGs) were enriched in flavonoid biosynthesis and phenylpropanoid biosynthesis and determined plant resistance. In addition, some differentially expressed proteins (DEPs) were enriched in photosynthesis-related pathways, which could improve fruit quality and yield. Moreover, through weighted gene coexpression network analyses, we identified modules of coexpressed genes and hub genes specifically related to grafting for different fruit developmental stages. The results suggested that graft-related modules and hub genes were primarily associated with photosynthate metabolism and hormonal signaling pathways. The results obtained in this study provide a valuable resource for dissecting the role of candidate genes governing graft-related metabolism in oriental melon fruit, suggesting an interesting correlation with the effects of rootstock on fruit development.


Neural network for autonomous segmentation and volumetric assessment of clot and edema in acute and subacute intracerebral hemorrhages.
Minimally-invasive surgical techniques for intracerebral hemorrhage (ICH) evacuation use imaging to guide the suction, lysing and/or drainage from the hemorrhage site via various designs. A previous international surgical study has shown that reduction of hematoma volume below 15 ml is indicative of improved long term patient outcomes. The study noted a need for tools to periodically visualize remaining clot during intervention to increase the likelihood of evacuating sufficient clot volumes without endangering rebleeds. Robust segmentation of MRI could guide surgeons and radiologists regarding remaining regions and approaches for prudent evacuation. We thus propose a Convolutional Neural Network (CNN) to identify and autonomously segment clot and peripheral edema in MR images of the brain and generate an estimate of the remaining clot volume. We used a retrospective, locally-acquired dataset of ICH patient scans taken on 3 T MRI scanners. Three sets of ground truth manual segmentations were independently generated by two imaging scientists and one radiology fellow. Evaluation of clot age was determined based on relative contrast of hemorrhage components and reviewed by a neurosurgeon. Model accuracy was determined by pixel-wise Dice coefficient (DC) calculations between each ground truth manual segmentation and the machine-derived autonomous segmentations. The model produced autonomous segmentations of clot core with an average DC of 0.75 ± 0.21 relative to manual segmentations of the same scans. For edema, it produced segmentations with an average DC of 0.68 ± 0.16 relative to manual. From these pixel-wise segmentations, clot volume can be calculated. Model-produced segmentations underestimated clot volumes by an average of 17% relative to ground-truth. The machine learning models were able to identify and segment volumes of ICH components swiftly and accurately.


Effect of varying accelerometry criteria on physical activity: the look ahead study.
The importance of physical activity in weight management is widely documented. Although accelerometers offer an objective measure of activity that provide a valuable tool for intervention research, considerations for processing these data need further development. This study tests the effects of using different criteria for accelerometry data reduction. Data were obtained from 2,240 overweight and obese individuals with type 2 diabetes mellitus (T2DM) from the Look AHEAD study, with 2,177 baseline accelerometer files used for analysis. Number, duration, and intensity of moderate (≥ 3 metabolic equivalents (METS)) and vigorous (≥ 6 METS) activity bouts were compared using various data reduction criteria. Daily wear time was identified as 1,440 min/day minus non-wear time. Comparisons of physical activity patterns for non-wear time (using either 20, 30, or 60 min of continuous zeros), minimal daily wear time (8, 10, and 12 h), number of days with available data (4, 5, and 6 days), weekdays vs. weekends, and 1- or 2-min time interruptions in an activity bout were performed. In this mostly obese population with T2DM (BMI = 36.4 kg/m(2) ; mean age = 59.0 years), there were minimal differences in physical activity patterns using the different methods of data reduction. Altering criteria led to differences in the number of available data (sample size) meeting specific criteria. Although our results are likely directly applicable only to obese individuals with T2DM, an understudied population with regards to physical activity, the systematic analysis for data reduction employed can be more generalizable and provide guidance in this area in the absence of standard procedures.


Deoxynivalenol Inhibits Porcine Intestinal Trefoil Factors Expression in Weanling Piglets and IPEC-J2 Cells.
Trefoil factors (TFFs) are regulatory peptides playing critical roles in mucosal repair and protection against a variety of insults within the gastrointestinal tract. This work aimed to explore the effects of deoxynivalenol (DON) on intestinal TFFs expression using in vivo and in vitro models. In an animal trial, twenty-four 28-d-old barrows (Duroc × Landrace × Large White; initial body weight = 7.6 ± 0.7 kg) were randomly divided into three treatments for 28 days, including a control diet (0.61 mg DON/kg feed), and two levels of DON-contaminated diets containing 1.28 and 2.89 mg DON/kg feed, respectively. Piglets exposed to DON had lower mRNA expression of TFF1, TFF2, TFF3, as well as Claudin-4 in the intestine (P < 0.05). Dietary DON exposure decreased the protein levels of TFF2 and TFF3 in the jejunum as demonstrated by western blot and immunohistochemistry. In intestinal porcine epithelial cells (IPEC-J2), DON depressed the mRNA expression of TFF2, TFF3, and Claudin-4. Overexpression of sterile alpha motif (SAM) pointed domain E26 transformation-specific (ETS) factor (SPDEF) was found to attenuate DON-induced suppression of TFFs in IPEC-J2 cells. Altogether, our work shows, for the first time, that dietary DON exposure depresses the expression of intestinal TFFs in piglets. Given the fundamental role of TFFs in intestinal mucosal homeostasis, our observations indicate that the DON content in animal feed should be strictly controlled based on the existing regulation for DON.


[Evaluation of the appropriateness of pharmacotherapy in patients with high comorbidity].
[corrected] To analyze the appropriateness of pharmacotherapy and, if necessary, carry out interventions for its improvement in a cohort of patients with multiple chronic conditions. Descriptive, prospective study of 21 months duration. Hospital Universitario Virgen del Rocío. Patients with multiple chronic conditions included in a project for integrated healthcare. The primary endpoint was the number of inappropriate treatments. To evaluate the appropriateness of pharmacotherapy, the specialist in hospital pharmacy followed a standardized procedure consisting of the Medication Appropriateness Index (MAI) questionnaire, modified as an implicit method, and the list of criteria of the Screening Tool of Older Person's Potentially Inappropriate Prescription/Screening Tool to Alert doctors to the Right (STOPP-START) as an explicit method. A total of 244 patients were included, with a mean age of 76 ± 8 (± SD) years. Half (50%) of the patients were men. The mean number of diagnoses per patient was 8 ± 3 (± SD) and 12 ± 4 drugs (± SD). A total of 840 inappropriate treatments were detected, most of them being due to the presence of interactions. The STOPP criteria most not complied with, were duplicate drug class, and prolonged use of benzodiazepines with long half-life or long-acting metabolites, and START for ACE inhibitors in chronic heart failure and statins and antiplatelets in diabetes mellitus, if one or more coexisting risk factors. We detected a large number of inappropriate treatments. This highlights the importance of evaluating the appropriateness of drug treatment in patients with multiple conditions. It is advisable to use a combined pharmacist intervention strategy that includes both an implicit method and an explicit method.


The Prevalence of Allergic Rhinitis and Associated Risk Factors Among University Students in Anatolia.
Allergic rhinitis is a common disease in Turkey. However, there are not enough studies on its prevalence. Survey-based studies conducted by experienced and qualified researchers to large populations provide information about the prevalence of allergic rhinitis and risk factors associated with it. The aim of this study was to determine the prevalence of allergic rhinitis and related factors in university students in Anatolia. An extended and modified form of "The European Community Respiratory Health Survey" was conducted to university students in Turkey. The data were obtained through a face-to-face interview method. R version 4.0.2 was used for statistical analysis. Data were presented as frequency and percentage. Chi-squared test of independence was used to analyze the relationship between allergic rhinitis diagnosis and other variables. Statistically significant variables were further analyzed with multivariate logistic regression test. Data was collected from a total of 2020 participants, but 1714 participants were eligible for multivariate analysis. The mean age of the participants was 20.71 ± 3.12 years; 42.88 (n= 735) were male, and 57.12% (n= 979) were female. While the rate of those who thought that they had nasal allergies was 23.862% (n = 409), the rate of those diagnosed by a doctor was 15.986% (n = 274). The most common allergic symptom in the participants was sneezing, and the most common triggering factor was house dust. We found a high prevalence of 15.986% doctor diagnosed allergic rhinitis among university students in Anatolia. Genetic, environmental and economic factors were associated with high prevalence of allergic rhinitis.


Continuous-time random-walk theory of interfering diffusion and chemical reaction with an application to electrochemical impedance spectra of oxidized Zr-1%Nb.
A microscopic theory is developed for the interplay of diffusion and chemical reaction and the results are compared with electrode impedance measurements on an oxide electrode. The theory is based on the ideas of continuous-time random walk and accounts for the interference of diffusion and recombination of the charge carriers in the oxide. The treatment results in a dispersive diffusivity with two time constants, one of them corresponding to the random walk, the other to the reaction. Combining this diffusivity with the Warburg electrode admittance expression, which refers to cases where the rate-limiting step is diffusion in a semi-infinite medium bounded by a plane, an admittance function is obtained. The phase angle is found to be higher than 45 degrees distinguishing it from the Gerischer impedance which was developed for a related problem. The oxides were produced by hydrothermal oxidation of Zr-l%Nb alloy, a metal used as cladding material for nuclear fuel elements. The electrode impedance spectra of Zr/Zr-oxide electrodes in aqueous SO(3) (2-) solutions were taken at various anodic voltages between 1 Hz and 100 kHz and temperatures between 278 and 333 K. The theoretical admittance functions could be successfully compared with the observed spectra. Both the functional forms and the fitted parameter values support our theory which is also in keeping with Macdonald's point-defect model.


Function of BrSOC1b gene in flowering regulation of Chinese cabbage and its protein interaction.
BrSOC1b may promote early flowering of Chinese cabbage by acting on BrAGL9 a, BrAGL9 b, BrAGL2 and BrAGL8 proteins. SOC1 is a flowering signal integrator that acts as a key regulator in controlling plant flowering time. This study focuses on the cloning of the open reading frame of SOC1b (BrSOC1b, Gene ID: Bra000393) gene, and analyzes its structure and phylogenetic relationships. Additionally, various techniques such as vector construction, transgenic technology, virus-induced gene silencing technology, and protein interaction technology were employed to investigate the function of the BrSOC1b gene and its interactions with other proteins. The results indicate that BrSOC1b consists of 642 bp and encodes 213 amino acids. It contains conserved domains such as the MADS domain, K (keratin-like) domain, and SOC1 box. The phylogenetic analysis reveals that BrSOC1b shares the closest homology with BjSOC1 from Brassica juncea. Tissue localization analysis demonstrates that BrSOC1b exhibits the highest expression in the stem during the seedling stage and the highest expression in flowers during the early stage of pod formation. Sub-cellular localization analysis reveals that BrSOC1b is localized in the nucleus and plasma membrane. Furthermore, through genetic transformation of the BrSOC1b gene, it was observed that Arabidopsis thaliana plants expressing BrSOC1b flowered earlier and bolted earlier than wild-type plants. Conversely, Chinese cabbage plants with silenced BrSOC1b exhibited delayed bolting and flowering compared to the control plants. These findings indicate that BrSOC1b promotes early flowering in Chinese cabbage. Yeast two-hybrid and quantitative real-time PCR (qRT-PCR) analyses suggest that BrSOC1b may participate in the regulation of flowering by interacting with BrAGL9a, BrAGL9b, BrAGL2, and BrAGL8 proteins. Overall, this research holds significant implications for the analysis of key genes involved in regulating bolting and flowering in Chinese cabbage, as well as for enhancing germplasm innovation in Chinese cabbage breeding.


Shifts in patterns of microhabitat occupation by six closely related species of mosses along a complex altitudinal gradient.
Changes in patterns of microhabitat occupation were examined for six closely related moss species (family Polytrichaceae) found growing together along a complex altitudinal gradient on the northeast face of Mount Washington, New Hampshire. Little evidence could be found to support the hypothesis that the relative distributions of these six moss species were determined by competitive interactions occurring among them. Instead, the data support the hypothesis that changing patterns in the relative distributions of these six moss species result from differences in microhabitat availability among sites. The moss species appear to behave in an opportunistic manner, occupying a wide array of microhabitats as these microhabitats become available to them.


[Compatibility of occupation with nursing relatives in small and medium-sized businesses : Results of an explorative study in a "rural urban" center in eastern Lower Saxony].
In view of the increasing duties of employees as caregivers for relatives, questions arise concerning the compatibility of work and caregiving in the context of small and medium-sized enterprises. The aim of this exploratory study was to give first insights into this issue whereby the related perceptions and needs of this group were investigated. The research included semi-structured interviews with company executives and two workshops with employees according to the photovoice method. The results showed that the enterprises preferred informal in contrast to formal arrangements. Also, they did not have any knowledge concerning the care-related needs of their employees. The chief executive officers showed a highly superficial awareness of this problem. On the employees side the organizational efforts to maintain the care arrangement at home were articulated as a main issue, which could be supported by flexible working time regulations; however, in the current practice this was granted by the employers at the expense of their employees.


Effect of Shen-Fu Injection () on Hemodynamics in Early Volume Resuscitation Treated Septic Shock Patients.
To investigate the hemodynamic effect of Shen-Fu Injection (, SFI) in early volume resuscitation treated septic shock patients by monitoring pulse indicator continuous cardiac output (PICCO). All septic shock patients admitted in the Intensive Care Unit of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 1st, 2014 to December 31th, 2015, were reviewed, and totally 65 were enrolled in this study. They were assigned to SFI group (33 cases) and control group (32 cases). All 65 patients underwent conventional treatment mainly including volume resuscitation, antibiotics and vasoactive drugs therapy. The patients of the SFI group received additional 100 mL of SFI intravenously every 12 h. In all 65 patients, the PICCO arterial catheter and vein catheter were implanted within 1 h after the diagnosis of septic shock. In the course of early volume resuscitation, hemodynamic data of patients were recorded by PICCO monitor at 0, 12, and 24 h after the catheter implantation. The hemodynamic indices of the two groups showed no significant differences at the beginning of 0 h (P>0.05). At 12 and 24 h, the hemodynamic indices of SFI group were significantly improved in comparison with the control group (P<0.05), including cardiac index (CI), global end diastolic volume index (GEDI), mean arterial pressure (MAP) and heart rate (HR). In addition, there was no significant change of extra-vascular lung water index between the two groups (P>0.05). SFI significantly improved hemodynamic indices such as CI, GEDI, MAP and HR in early volume resuscitation treated septic shock patients.


C-H...O hydrogen bonding in 4-phenyl-benzaldehyde: a comprehensive crystallographic, spectroscopic and computational study.
The crystal structure of 4-phenyl-benzaldehyde reveals the presence of a dimer linked by the C=O and C9-H groups of adjacent molecules. In the liquid phase, the presence of C-H...O bonded forms is revealed by both vibrational and NMR spectroscopy. A DeltaH value of -8.2 +/- 0.5 kJ mol(-1) for the dimerisation equilibrium is established from the temperature-dependent intensities of the bands assigned to the carbonyl-stretching modes. The NMR data suggest the preferential engagement of the C(2,6)-H and C(10/12)/C(11)-H groups as hydrogen bond donors, instead of the C(9)-H group. While ab initio calculations for the isolated dimers are unable to corroborate these NMR results, the radial distribution functions obtained from molecular dynamics simulations show a preference for C(2,6)-H and C(10/12)/C(11)-H...O contacts relative to the C(9)-H...O ones.


Functional and clinical findings in 3 female siblings with crystalline retinopathy.
To present functional and clinical findings in three female siblings with crystalline retinopathy. Functional and clinical examinations, including full-field and multi-focal electroretinograms (ERG), visual field, dark adaptation and fundus fluorescein angiography (FFA) were performed in three female siblings of a nonconsanguineous Chinese family, who exhibited characteristic retinal crystalline flecks of Bietti crystalline retinopathy. Ophthalmological examination revealed similar findings in the first and second daughter of the family. Best-corrected visual acuity was hand movement and finger counting respectively and funduscopic examination showed RPE clumping and relatively fewer yellow-white deposits in the posterior pole and mid-peripheral retina. FFA revealed massive RPE and choriocapillaris destruction. Ganzfeld ERG was undetectable or reduced markedly and multifocal ERG showed all responses were markedly depressed. Ophthalmological examination showed relative preservation of retinal function in the third daughter of the family (the proband). Best-corrected visual acuity was 0.5 in the right eye and 0.4 in the left eye. Funduscopic examination showed numerous crystal deposits scattered throughout the posterior pole. Dark adaptation revealed rod thresholds elevated dramatically and visual field examination demonstrated paracentral scotomas in both eyes. Full-field ERG was decreased slightly and multifocal ERG showed the central responses were markedly depressed. The present study describes typical crystalline retinopathy affecting three female siblings in a family.


[Gastric diverticulum. Report of a clinical case and review of the literature].
The author reports a case of pericardial diverticulum with gastro-oesophageal reflux treated surgically. The diagnosis and the type of treatment that must be adopted are defined. He reviews the literature and compares the described data with the observed case.


Severe left ventricular systolic dysfunction is independently associated with high on-clopidogrel platelet reactivity.
The purpose of the present study was to investigate the association between left ventricular systolic function and the response to clopidogrel. The efficacy of clopidogrel was measured by the vasodilator-stimulated phosphoprotein phosphorylation 20 ± 4 h after 600 mg of clopidogrel. High on-clopidogrel platelet reactivity (HCPR) was defined as a platelet reactivity index (PRI) ≥50%. The 30-day combined incidence of death, non-fatal acute coronary syndrome, re-percutaneous coronary intervention (PCI), stent thrombosis, and stroke was also investigated. The study group consisted of 519 patients undergoing PCI. The values (mean and 95% confidence interval) of the PRI were as follows: 40.4% (37.8-43.0) in patients with left ventricular ejection fraction (LVEF) >50%, 42.4% (39.3-45.6) in patients with LVEF 35-50%, and 46.7% (40.6-52.9) in patients with LVEF <35% (p = 0.013). The proportions of patients with HCPR were 35.9% in patients with LVEF ≥35 and 51.9% in patients with LVEF <35% (p = 0.022). After adjustment for variables that significantly influenced clopidogrel efficacy, LVEF <35% was found to be independently associated with HCPR (p = 0.039). The 30-day combined clinical endpoint occurred in 18% of patients with LVEF <35% and in 7.3% of patients with LVEF ≥35% (p = 0.026). The 30-day incidence of all-cause mortality was 14% in patients with LVEF <35 and 1.0% in patients with LVEF ≥35% (p < 0.001). An LVEF <35% was found to be independently associated with HCPR.


Influence of Maternity Leave on Exclusive Breastfeeding: Analysis from Two Surveys Conducted in the Federal District of Brazil.
Since the 1980s, Brazil has implemented several initiatives to support breastfeeding. Maternity leave, paid in full for 16 weeks, has been available since 1988. However, few studies in Brazil have analyzed the impacts of maternity leave on breastfeeding using population-based indicators. The aim was to analyze the association between maternity leave and exclusive breastfeeding interruption in children younger than 4 months residing in the Federal District of Brazil, in 2008 and 2014. Data from two surveys were used: the 2008 Second National Survey on Prevalence of Breastfeeding and the 2014 Monitoring of Infant Feeding Practices. The sample included 1,742 mothers with children younger than 4 months residing in the Federal District and using the Public Unified Health System. The main independent variable was the mother being on maternity leave and the outcome was interruption of exclusive breastfeeding. Multiple analyses were performed to test the association between maternity leave and the risk of interrupting exclusive breastfeeding, adjusting for socioeconomic, demographic, and biomedical characteristics. In 2008 and 2014, the prevalence of exclusive breastfeeding was 60% and 71.4% and prevalence of maternity leave was 27% and 41%, respectively. The lack of maternity leave was strongly associated with interruption of exclusive breastfeeding in 2008 (prevalence ratio [PR] = 1.78, 95% confidence interval [CI] [1.12, 2.82]) and in 2014 (PR = 3.95, 95% CI [1.88, 8.31]) after adjusting for confounding variables. Not being on maternity leave was strongly associated with the interruption of exclusive breastfeeding among employed women residing in the Federal District.


Weight change after smoking cessation and incident metabolic syndrome in middle-aged Korean men: an observational study.
We aimed to examine the effect of weight change attributable to cessation of cigarette smoking on newly diagnosed metabolic syndrome (MetS). We prospectively followed 5,809 men aged between 40 to 69 years without MetS at baseline in the Health Examinees-Gem (HEXA-G) study up to 4 years. The participants were grouped into continual smokers, quitters with weight gain, quitters without weight change, quitters with weight loss, and never smokers. We constructed multivariable logistic regression models adjusted for sociodemographic factors, health status, and health conditions to estimate the odds of newly diagnosed MetS. During the follow-up, there were 609 cases of newly diagnosed MetS in 5,809 men of the HEXA-G study. After adjustment for potential confounders, the odd ratios (OR) and 95% confidence intervals (95% CI) for MetS were 1.90 (95% CI: 1.43-2.52) in quitters with weight gain, 0.77 (95% CI: 0.60-1.00) in quitters without weight change, and 0.40 (95% CI: 0.28-0.57) in quitters with weight loss compared with continual smokers. Never smokers also had lower odds of MetS (OR = 0.54; 95% CI: 0.42-0.71) compared to continual smokers. Weight management program following smoking cessation may be necessary in clinical practice to reduce worsening of cardiometabolic risk factors related to post-cessation weight gain.


Association of Elevated Body Mass Index with Functional Outcome and Mortality following Acute Ischemic Stroke: The Obesity Paradox Revisited.
Previous literature has identified a survival advantage in acute ischemic stroke (AIS) patients with elevated body mass indices (BMIs), a phenomenon termed the "obesity paradox." The aim of this study was to evaluate the independent association between obesity and clinical outcomes following AIS. Weighted discharge data from the National Inpatient Sample were queried to identify AIS patients from 2015 to 2018. Multivariable logistic regression and Cox proportional hazards modeling were performed to evaluate associations between obesity (BMI ≥ 30) and clinical endpoints following adjustment for acute stroke severity and comorbidity burden. Among 1,687,805 AIS patients, 216,775 (12.8%) were obese. Compared to nonobese individuals, these patients were younger (64 vs. 72 mean years), had lower baseline NIHSS scores (6.9 vs. 7.9 mean score), and a higher comorbidity burden. Multivariable analysis demonstrated independent associations between obesity and lower likelihood of mortality (adjusted odds ratio [aOR] 0.76, 95% confidence interval [CI]: 0.71, 0.82, p < 0.001; hazard ratio 0.84, 95% CI: 0.73, 0.97, p = 0.015), intracranial hemorrhage (aOR 0.87, 95% CI: 0.82, 0.93, p < 0.001), and routine discharge to home (aOR 0.97, 95% CI: 0.95, 0.99; p = 0.015). Mortality rates between obese and nonobese patients were significantly lower across stroke severity thresholds, but this difference was attenuated among high severity (NIHSS > 20) strokes (21.6% vs. 23.2%, p = 0.358). Further stratification of the cohort into BMI categories demonstrated a "U-shaped" association with mortality (underweight aOR 1.58, 95% CI: 1.39, 1.79; p < 0.001, overweight aOR 0.64, 95% CI: 0.42, 0.99; p = 0.046, obese aOR 0.77, 95% CI: 0.71, 0.83; p < 0.001, severely obese aOR 1.18, 95% CI: 0.74, 1.87; p = 0.485). Sub-cohort assessment of thrombectomy-treated patients demonstrated an independent association of obesity (BMI 30-40) with lower mortality (aOR 0.79, 95% CI: 0.65, 0.96; p = 0.015), but not with routine discharge. This cross-sectional analysis demonstrates a lower likelihood of discharge to home as well as in-hospital mortality in obese patients following AIS, suggestive of a protective effect of obesity against mortality but not against all poststroke neurological deficits in the short term which would necessitate placement in acute rehabilitation and long-term care facilities.


Large-scale production and antiviral efficacy of multi-target double-stranded RNA for the prevention of white spot syndrome virus (WSSV) in shrimp.
RNA interference (RNAi) is a specific and effective approach for inhibiting viral replication by introducing double-stranded (ds)RNA targeting the viral gene. In this study, we employed a combinatorial approach to interfere multiple gene functions of white spot syndrome virus (WSSV), the most lethal shrimp virus, using a single-batch of dsRNA, so-called "multi-WSSV dsRNA." A co-cultivation of RNase-deficient E. coli was developed to produce dsRNA targeting a major structural protein (VP28) and a hub protein (WSSV051) with high number of interacting protein partners. For a co-cultivation of transformed E. coli, use of Terrific broth (TB) medium was shown to improve the growth of the E. coli and multi-WSSV dsRNA yields as compared to the use of Luria Bertani (LB) broth. Co-culture expression was conducted under glycerol feeding fed-batch fermentation. Estimated yield of multi-WSSV dsRNA (μg/mL culture) from the fed-batch process was 30 times higher than that obtained under a lab-scale culture with LB broth. Oral delivery of the resulting multi-WSSV dsRNA reduced % cumulative mortality and delayed average time to death compared to the non-treated group after WSSV challenge. The present study suggests a co-cultivation technique for production of antiviral dsRNA with multiple viral targets. The optimal multi-WSSV dsRNA production was achieved by the use of glycerol feeding fed-batch cultivation with controlled pH and dissolved oxygen. The cultivation technique developed herein should be feasible for industrial-scale RNAi applications in shrimp aquaculture. Interference of multiple viral protein functions by a single-batch dsRNA should also be an ideal approach for RNAi-mediated fighting against viruses, especially the large and complicated WSSV.


Different mechanisms are used by insulin to repress three genes that contain a homologous thymine-rich insulin response element.
Insulin rapidly and completely inhibits expression of the hepatic insulin-like growth factor binding protein-1 (IGFBP-1), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) genes. This inhibition is mediated through a phosphatidyl inositol 3-kinase-dependent regulation of a DNA element, termed the thymine-rich insulin response element, found within the promoters of each of these genes. This has led to the conclusion that these three promoters are regulated by insulin using the same molecular mechanism. However, we recently found that the regulation of the IGFBP1 but not the PEPCK or G6Pase genes by insulin was sensitive to rapamycin, an inhibitor of mTOR. Here, we present further evidence that different regulatory pathways mediate the insulin regulation of these promoters. Importantly, we identify a protein phosphatase activity in the pathway connecting mTOR to the IGFBP-1 promoter. These data have major implications for the development of molecular therapeutics for the treatment of insulin-resistant states such as diabetes and hypertension.


Regulation of cyclic AMP levels by phorbol esters in bovine adrenal medullary cells.
Cyclic AMP responses to phorbol esters were studied in cultured bovine adrenal medullary cells. Phorbol esters that activate protein kinase C (PKC: phorbol 12,13-dibutyrate, phorbol 12,13-didecanoate) increased cellular cyclic AMP levels by up to 100% over 5 min, and this was maintained for up to 3 h. The effect was mimicked by 1,2-dioctanoyl-sn-glycerol but not by inactive phorbol esters. The effect of active phorbol esters was concentration dependent over the range 50-500 nM, and was abolished by the PKC inhibitor, Ro 31-8220 (10 microM). The response was enhanced by 3-isobutyl-1-methylxanthine (1 mM) and by forskolin (0.3 microM), was enhanced following pertussis toxin pretreatment (100 ng/ml, 7.5 h) and was unaffected by removing extracellular Ca2+. The phorbol ester cyclic AMP response was additive with that to K+ depolarisation, and synergised with those to prostaglandin E1 and dimaprit. The results indicate PKC activation increases cyclic AMP formation in bovine adrenal medullary cells, probably by a direct action on adenylate cyclase or Gs.


Growing the molecular architecture of imidazole-like ligands in HO-1 complexes.
Up-regulation of HO-1 had been frequently reported in different cases and types of human malignancies. Since poor clinical outcomes are reported in these cases, this enzyme's inhibition is considered a valuable and proven anticancer approach. To identify novel HO-1 inhibitors suitable for drug development, we report a structure-guided fragment-based approach to identify new lead compounds. Different parts of the selected molecules were analyzed, and the different series of novel compounds were virtually evaluated. The growing experiments of the classical HO-1 inhibitors structure led us to different hit-compounds. A synthetic pathway for six selected molecules was designed, and the compounds were synthesized. The biological activity revealed that molecules 10 and 12 inhibit the HO-1 activity with an IC50 of 1.01 and 0.90 μM, respectively. This study suggested that our growing approach was successful, and these results are ongoing for further development.


Characterization of a genetically segregating determinant of chicken fetal antigen by a new hapten inhibition of microcytotoxicity (HIM) assay.
The immunodominant structure of a chicken fetal antigen (CFA) determinant was investigated using a new hapten inhibition of microcytotoxicity (HIM) assay. This HIM assay employing avian erythrocytes was shown to be a highly sensitive, economical technique and was verified in a separate experiment using bovine serum albumin (BSA) coupled to Japanese quail peripheral red blood cells (QPRBCs). Inhibition of microcytotoxicity was measured following preincubation of 1 microliter of specific antiserum with 1 microliter of antigen solution. A concentration of 21.1 nM BSA was found to produce effective (50%) inhibition of microcytotoxicity of BSA-coated QPRBCs. The percentage cytotoxicity was determined by estimating the proportion of intact RBCs to free nuclei using an inverted microscope. Staining of the reaction mixtures was not required for scoring. Application of this technique for the characterization of immunodominant structures was demonstrated by the analysis of a CFA determinant known to exhibit both developmental expression and genetic segregation. R-anti-CFA-10 was effectively inhibited only by D-galactose (35.5 mM) and the galactose-containing sugars lactose (28.2 mM), raffinose (29.9 mM), and stachyose (39.8 mM). Implications of the carbohydrate nature of CFA are discussed.


Analysis on EZH2: mechanism identification of related CeRNA and its immunoassay in hepatocellular carcinoma.
To screen the possible potential signaling pathways related to enhancer of zeste homolog 2 (EZH2) based on ceRNA mechanism, and to analyze the correlation between E2H2 and depths of various immune cell infiltration depths. The relationship between different immune checkpoints were also analyzed. First, the expression of EZH2 in pan-cancer (18 malignancies) was analyzed with the TCGA database. Hepatocellular carcinoma (HCC) tissues of 374 cases and normal tissues of 50 cases were analyzed in terms of the differential expression, overall survival (OS) and progression-free-survival (PFS). Then, we conducted GO and KEGG enrichment analysis on target gene. We also analyzed mRNA-miRNA and MicroRNA (miRNA)- long non-coding RNA (lncRNA) correlation with starbase databse, so as to determine the potential ceRNA mechanism associated with EZH2. Finally, immunoassay and drug-sensitivity analysis of EZH2 was performed. Seven potential EZH2-related ceRNA pathways were screened out, namely lncRNA: Small Nucleolar RNA Host Gene 1 (SNHG1), SNHG 3, and SNHG 6-miR-101-3p-EZH2; and lncRNA: Long Intergenic Non-Protein Coding RNA 1978 (LINC01978), SNHG12, Ring Finger Protein 216 Pseudogene 1 (RNF216P1), and Coiled-coil Domain Containing 18 Antisense RNA 1 (CCDC18-AS1)-let-7c-5p-EZH2. Finally, 4 potential EZH2-related ceRNA pathways were identified through qPCR.According to immune correlation analysis, EZH2 may be positively correlated with T cells follicular helper, T cells Cluster of differentiation (CD)4 memory activated, Macrophages M0, and B cells memory (P < 0.05, cof > 0.2); while be negatively correlated with T cells CD4 + memory resting (P < 0.05, cof < -0.2). And EZH2 is positively correlated with Programmed Cell Death 1 (PDCD1) (R = 0.22), CD274 (R = 0.3) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4) (R = 0.23). According to drug sensitivity analysis, patients in the high expression group were more susceptible to the effects of various drugs including Sorafenib, 5-Fluorouracil, Doxorubicin, Etoposide, Paclitaxel, and Vinorelbine than those with low expression. This study revealed seven potential pathways of Enhancer of Zeste Homolog 2 (EZH2)-related ceRNA mechanisms: lncRNA (SNHG3, 6) -Mir-101-3P-ezh2; lncRNA (SNHG12, RNF216P1)-let-7c-5p-EZH2. We also analyzed the immunity and drug sensitivity of EZH2. Our study proves that EZH2 still has great research prospects in HCC.


Movement of horseradish peroxidase after its entry into intact and damaged peripheral nerve axons.
After application of a solution of horseradish peroxidase (HRP) around intact sciatic nerve axons in the rat, numerous HRP-labeled neurons were found in the ipsilateral L5 dorsal root ganglion and spinal cord ventral horn. These findings indicate that HRP enters intact peripheral nerve axons, and is transported retrogradely from its site of entry to their cell bodies of origin.


[Therapy of refractory chronic polyarthritis with tumor necrosis factor alpha receptor fusion proteins (TNFR55-IgG1)--results of double-blind placebo-controlled studies over 3 months].
AIM OF STUDIES: To determine the optimal dose regimen for i.v. TNFR55-IgG1 in refractory rheumatoid arthritis. 218 patients with refractory rheumatoid arthritis were enrolled for two double-blind placebo-controlled multicenter trials (Europe and USA). They were treated with monthly i.v. placebo, 0.01, 0.05, 0.1 or 0.5 mg/kg TNFR55-IgG1 after a 4 week wash-out of DMARDs. An additional German trial compared biweekly i.v. 20 mg TNFR55-IgG1 and monthly 50 mg following a loading does of 100 mg in 60 patients. TNFR55-IgG1 induced a substantial improvement already apparent one day after the first infusion. A maximal, dose dependent effect was reached after two weeks. Later, efficacy declined in parallel to an increase in anti-TNFR55-IgG1 antibodies resulting in an increased drug clearance. The drug was well tolerated with predominantly mild or moderate adverse events. Intravenous TNFR55-IgG1 was well tolerated and effective in refractory rheumatoid arthritis but the treatment schedules tested could not stabilise the initial improvement.


A comparison of clinical pregnancy rates and multiple gestation rates with 2 vs 3 embryos transferred with pairs matched for embryo quality.
To determine the impact of embryo quality on multiple birth rates. A retrospective review of in vitro fertilization-embryo transfer (IVF-ET) cycles over ten years was performed. The data was stratified by number of embryos transferred (two vs three) and by percentage of embryos with < 6 vs > or = 6 blastomeres. Pregnancy rates (PRs) increase with the greater number of embryos with a higher blastomere count. However transferring more embryos with less blastomeres does not lower the risk of multiple births. Couples should consult the table, e.g. presented here, so they can make their best choice of how many embryos to transfer considering the importance of a higher pregnancy rate vs the risk of the complication of multiple births.


Surface activation of carbon film supports for biological electron microscopy.
The effect of glow-discharging on naked carbon-filmed grids has been evaluated. The effect of different locations of the grids within a DC discharge, operated in the normal glow, was analyzed by applying various biological specimens to the grids. Two locations were found to give consistent results: (a) in Crookes dark space, particulate specimens, negatively stained, spread evenly--suggesting a new negative surface charge of the support; (b) below the anode, nucleic acids, selectively (positively) stained, appeared as well spread filaments, indicating a net positive surface charge.


Cellular issues relating to the resistance of HIV to antiretroviral agents.
It has been proposed that the declining efficiency of antiretroviral agents in human immunodeficiency virus (HIV) infection may also depend on cellular factors at their site of action. Two in particular have been proposed: (i) the defective intracellular metabolism of NRTI in target cells and the altered uptake; and (ii) efflux of nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PI) by cellular transporter molecules. Several studies have shown that: changes in the activities of various purine and pyrimidine biosynthetic enzymes may occur in lymphocytes of HIV-infected patients; HIV-infected patients on prolonged treatment with nucleoside analogues, e.g. zidovudine, show significantly decreased activity of thymidine kinase (TK) compared with untreated HIV-infected people; and NRTI and PI are substrates for the multidrug membrane transporters. With regard to the latter issue, it is known that the ATP-binding cassette transporter proteins such as the P-glycoprotein (MDR), and the newly discovered family of multidrug resistance-associated proteins (MRP1-6), promote the active extracellular efflux of a wide variety of therapeutics drugs and overexpression of some of them lowers intracellular concentration of PI. In the very near future such mechanisms, also called 'cellular drug resistance', might be taken into account, together with other immunological, virological and behavioural factors, to explain the 'drug failure' and/or the variability of response in HIV patients undergoing antiretroviral treatment.


Geochemical evidence for the internal migration of gas condensate in a major unconventional tight petroleum system.
Unconventional petroleum systems go through multiple episodes of internal hydrocarbon migration in response to evolving temperature and pressure conditions during burial and uplift. Migrated fluid signatures can be recognized using stable carbon isotope and PVT compositional data from produced samples representative of in-situ petroleum fluids. Such samples, however, are seldom collected due to operational complexity and high cost. Here, we use carbon isotope and PVT data from co-produced hydrocarbon gas and liquid to provide evidence for widespread migration of gas-condensate in the Montney unconventional petroleum system of western Canada. Extended C1-C33 isotopic profiles exhibit convex upward signatures with C4-C5 maxima at low molecular weight, and increasing or nearly uniform signatures at high molecular weight. Additionally, recombination PVT compositional data show C6-C15 condensate concentrations are higher than expected for unmodified oils. The combined convex upward and increasing or uniform isotopic signatures are interpreted as mixing profiles formed by the introduction of high-maturity gas-condensate (C1-C15) to shallower zones with in-situ hydrocarbon fluids of lower thermal maturity. The recognition of widespread gas-condensate migration adds to the complex history of internal hydrocarbon migration within the Montney tight-petroleum system including previously identified migration episodes of early oil and late-stage methane-rich gas.


Murine model to study the invasion and survival of Mycobacterium tuberculosis in the central nervous system.
Tuberculosis of the central nervous system (CNS) is a serious, often fatal disease primarily affecting young children. It develops after hematogenous dissemination and subsequent invasion of the CNS by Mycobacterium tuberculosis. The microbial determinants involved in CNS disease are poorly characterized. Hematogenously disseminated M. tuberculosis infection was simulated in BALB/c mice by intravenous challenge. Bacteria were recovered using standard culture techniques. Host immune response to M. tuberculosis infection was assessed by histopathological and cytokine profile analysis. By means of a pooled infection with genotypically defined M. tuberculosis mutants, bacterial genes required for invasion or survival were determined in the CNS and lung tissue. M. tuberculosis were detected in whole mouse brains as early as 1 day after intravenous infection and at all time points assessed thereafter. No significant immune response was elicited in the infected brain tissue, compared with extensive inflammation in the infected lung tissue at the same time point. We identified mutants for 5 M. tuberculosis genes (Rv0311, Rv0805, Rv0931c, Rv0986, and MT3280) with CNS-specific phenotypes, absent in lung tissue. We have identified CNS-specific M. tuberculosis genes involved in the pathogenesis of tuberculosis. Further characterization of these genes will help in understanding the microbial pathogenesis of CNS tuberculosis.


Association between maternal parenting styles and behavioral problems in children with ASD: Moderating effect of maternal autistic traits.
Children with autism spectrum disorder (ASD) are at high risk of experiencing externalizing and internalizing problems. This study aimed to reveal how maternal parenting styles and autistic traits influence behavioral problems in children with ASD. This study recruited 70 2-5 years children with ASD and 98 typically developing (TD) children. The Parental Behavior Inventory (PBI) and Autism Spectrum Quotient (AQ) were used to collect the maternal parenting styles and autistic traits, respectively. The children's behavioral problems were reported by the mothers using the Strengths and Difficulties Questionnaire (SDQ). Hierarchical moderated regression analyses were used to determine whether maternal autistic traits moderated the association between parenting style and behavioral problems in the children. Compared to TD children, children with ASD exhibited more severe externalizing and internalizing problems (t = 4.85, p < 0.01). The ASD group scored lower in the maternal supportive/engaged parenting style than the TD group (t = 3.20, p < 0.01). In the TD group, the maternal AQ attention switching domain was positively correlated with internalizing problems in the children (β = 0.30, p = 0.03). In the ASD group, hostile/coercive parenting style was significantly correlated with externalizing problems in the children (β = 0.30, p = 0.02), whereas maternal AQ attention switching domain was negatively correlated with externalizing problems (β = -0.35, p = 0.02). Moreover, the maternal AQ attention switching domain moderated the association between hostile/coercive parenting style and children's externalizing problems (β = 0.33, p = 0.04). Among ASD children, a hostile/coercive parenting style can increase the risks of children's externalizing problems, especially in the context of high levels of maternal attention-switching problems. Hence, the current study has important implications for the clinical practice of early family-level interventions for children with ASD.


Associations of eczema phenotypes with emotional and behavioural problems from birth until school age. The Generation R Study.
Eczema phenotypes and emotional and behavioural problems are highly prevalent in childhood, but their mutual relationship is not fully clear. To examine the associations of eczema phenotypes with school-age emotional and behavioural problems, and the bidirectional associations of eczema and emotional and behavioural problems from birth until 10 years. This study among 5265 individuals was embedded in a prospective population-based cohort study. Never, early transient, mid-transient, late transient and persistent eczema phenotypes were identified based on parent-reported, physician-diagnosed eczema from age 6 months until 10 years. Emotional (internalizing) and behavioural (externalizing) problems were measured repeatedly using the Child Behavior Checklist from age 1·5 to 10 years. Cross-lagged models were applied for bidirectional analyses. All eczema phenotypes were associated with more internalizing problems and attention problems at age 10 years, compared with never having eczema: range of Z-score differences 0·14 [95% confidence interval (CI) 0·01-0·27] to 0·39 (95% CI 0·18-0·60). Children with early transient eczema had more aggressive behaviour symptoms at age 10 years (Z = 0·16, 95% CI 0·05-0·27). Bidirectional analysis showed that eczema at 0-2 years was associated with more internalizing and externalizing problems at ages 3-6 and 10 years, while, inversely, only internalizing problems at 0-2 years were associated with an increased risk of eczema at age 10 years. Eczema phenotypes are very modestly associated with more somatic symptoms and attention problems at school age. Early transient eczema is associated with more aggressive behaviour symptoms. Directional effects seem to occur from early-life eczema to later-life internalizing and externalizing problems, rather than the reverse.


Remarkable G2/M phase arrest and apoptotic effect performed by 2-(6-aryl-3-hexen-1,5-diynyl) benzonitrile antitumor agents.
2-(6-aryl-3-hexen-1,5-diynyl)benzonitriles 3a-j showed growth inhibition effects on a full panel of 60 human cancer cell lines in low micro-concentrations, in which compounds 3c,d displayed a significant G2/M arrest in the cell growth cycle compared with other derivatives and an apoptotic progress induction were also shown by 3a-d.


Intracranial epidural haematomas in elderly patients: observations in 14 patients.
Up to now, extra-dural haematomas (EDH) in elderly patients have been known for their poor prognosis and few studies have focused on the particularity of EDH in the elderly. Most clinical studies relating to EDH have generally focused on its occurrence in children and the middle-aged, grouping people of over 50 and 60 years together as the elderly. The purpose of this paper is to present a series of EDH cases in the elderly. 500 EDH patients (of all ages) were admitted to our Department from January 1990 to December 2003 and this is a retrospective study of 14 of those patients who were aged 70 years and over. The study consists of 8 women and 6 men with an average age of 74 years. A high incidence of disease predisposes elderly to falls, which are the most frequent cause of head trauma. The elderly are less likely to manifest signs or symptoms of increased intracranial pressure due to cerebral atrophy, and almost all haematomas occurred in the parietal area. Post-operative results were satisfactory and only one death was recorded. This study shows that the elderly, presenting EDH after a fall, have a better prognosis than is often feared.


Pituitary adrenocorticotrophic (ACTH) cells during reproductive cycle in a Vespertilionid bat, Scotophilus heathi.
Present study described the pituitary adrenocorticotropic (ACTH)-cells during different phases of reproductive cycle of Indian Vespertilionid bat, S. heathi. ACTH-cells were identified by histochemical, immunocytochemical and electron microscopic techniques. These cells shows round to polygonal in shape and be easily distinguished by histochemical staining. The body weight attains peak during recrudescence phase due to accumulation of fat. The mean areal fraction occupied by ACTH-cells were higher in recrudescence and winter dormancy as compared with other reproductive phases. The size and granulation pattern of these cells showed variation in relation with the seasonal fat cycle. The possible significance of ACTH-cells during periods of recrudescence and winter dormancy, which is also coincided with period of delayed ovulation in this species, were discussed.


Bilateral optic neuritis in acute human immunodeficiency virus infection.
To report a case of acute viral disease accompanied by bilateral optic neuritis with substantial paraclinical evidence that human immunodeficiency virus was the causative agent. Clinical and paraclinical examination. Magnetic resonance imaging. Virus and antibody titers as well as reverse lymphocytosis were consistent with acute infection by the human immunodeficiency virus-1. Human immunodeficiency virus infection should be considered in the differential diagnosis of acute optic neuritis.


A new sea-level record for the Neogene/Quaternary boundary reveals transition to a more stable East Antarctic Ice Sheet.
Sea-level rise resulting from the instability of polar continental ice sheets represents a major socioeconomic hazard arising from anthropogenic warming, but the response of the largest component of Earth's cryosphere, the East Antarctic Ice Sheet (EAIS), to global warming is poorly understood. Here we present a detailed record of North Atlantic deep-ocean temperature, global sea-level, and ice-volume change for ∼2.75 to 2.4 Ma ago, when atmospheric partial pressure of carbon dioxide (pCO2) ranged from present-day (>400 parts per million volume, ppmv) to preindustrial (<280 ppmv) values. Our data reveal clear glacial-interglacial cycles in global ice volume and sea level largely driven by the growth and decay of ice sheets in the Northern Hemisphere. Yet, sea-level values during Marine Isotope Stage (MIS) 101 (∼2.55 Ma) also signal substantial melting of the EAIS, and peak sea levels during MIS G7 (∼2.75 Ma) and, perhaps, MIS G1 (∼2.63 Ma) are also suggestive of EAIS instability. During the succeeding glacial-interglacial cycles (MIS 100 to 95), sea levels were distinctly lower than before, strongly suggesting a link between greater stability of the EAIS and increased land-ice volumes in the Northern Hemisphere. We propose that lower sea levels driven by ice-sheet growth in the Northern Hemisphere decreased EAIS susceptibility to ocean melting. Our findings have implications for future EAIS vulnerability to a rapidly warming world.