Protochlorophyllide: a new photosensitizer for the photodynamic inactivation of Gram-positive and Gram-negative bacteria.
The growing resistance against antibiotics demands the search for alternative treatment strategies. Photodynamic therapy is a promising candidate. The natural intermediate of chlorophyll biosynthesis, protochlorophyllide, was produced, purified and tested as a novel photosensitizer for the inactivation of five model organisms including Staphylococcus aureus, Listeria monocytogenes and Yersinia pseudotuberculosis, all responsible for serious clinical infections. When microorganisms were exposed to white light from a tungsten filament lamp (0.1 mW cm(-2)), Gram-positive S. aureus, L. monocytogenes and Bacillus subtilis were photochemically inactivated at concentrations of 0.5 mg L(-1) protochlorophyllide. Transmission electron microscopy revealed a disordered septum formation during cell division and the partial loss of the cytoplasmic cell contents. Gram-negative Y. pseudotuberculosis and Escherichia coli were found to be insensitive to protochlorophyllide treatment due to the permeability barrier of the outer membrane. However, the two bacteria were rendered susceptible to eradication by protochlorophyllide (10 mg L(-1)) upon addition of polymyxin B nonapeptide at 50 and 20 mg L(-1), respectively. The release of DNA and a detrimental rearrangement of the cytoplasm were observed.


The trxG family histone methyltransferase SET DOMAIN GROUP 26 promotes flowering via a distinctive genetic pathway.
Histone methylation is a major component in numerous processes such as determination of flowering time, which is fine-tuned by multiple genetic pathways that integrate both endogenous and environmental signals. Previous studies identified SET DOMAIN GROUP 26 (SDG26) as a histone methyltransferase involved in the activation of flowering, as loss of function of SDG26 caused a late-flowering phenotype in Arabidopsis thaliana. However, the SDG26 function and the underlying molecular mechanism remain largely unknown. In this study, we undertook a genetic analysis by combining the sdg26 mutant with mutants of other histone methylation enzymes, including the methyltransferase mutants Arabidopsis trithorax1 (atx1), sdg25 and curly leaf (clf), as well as the demethylase double mutant lsd1-like1 lsd1-like2 (ldl1 ldl2). We found that the early-flowering mutants sdg25, atx1 and clf interact antagonistically with the late-flowering mutant sdg26, whereas the late-flowering mutant ldl1 ldl2 interacts synergistically with sdg26. Based on microarray analysis, we observed weak overlaps in the genes that were differentially expressed between sdg26 and the other mutants. Our analyses of the chromatin of flowering genes revealed that the SDG26 protein binds at the key flowering integrator SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1/AGAMOUS-LIKE 20 (SOC1/AGL20), and is required for histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 36 trimethylation (H3K36me3) at this locus. Together, our results indicate that SDG26 promotes flowering time through a distinctive genetic pathway, and that loss of function of SDG26 causes a decrease in H3K4me3 and H3K36me3 at its target gene SOC1, leading to repression of this gene and the late-flowering phenotype.


Evolution of penicillin-binding protein 2 concentration and cell shape during a long-term experiment with Escherichia coli.
Peptidoglycan is the major component of the bacterial cell wall and is involved in osmotic protection and in determining cell shape. Cell shape potentially influences many processes, including nutrient uptake as well as cell survival and growth. Peptidoglycan is a dynamic structure that changes during the growth cycle. Penicillin-binding proteins (PBPs) catalyze the final stages of peptidoglycan synthesis. Although PBPs are biochemically and physiologically well characterized, their broader effects, especially their effects on organismal fitness, are not well understood. In a long-term experiment, 12 populations of Escherichia coli having a common ancestor were allowed to evolve for more than 40,000 generations in a defined environment. We previously identified mutations in the pbpA operon in one-half of these populations; this operon encodes PBP2 and RodA proteins that are involved in cell wall elongation. In this study, we characterized the effects of two of these mutations on competitive fitness and other phenotypes. By constructing and performing competition experiments with strains that are isogenic except for the pbpA alleles, we showed that both mutations that evolved were beneficial in the environment used for the long-term experiment and that these mutations caused parallel phenotypic changes. In particular, they reduced the cellular concentration of PBP2, thereby generating spherical cells with an increased volume. In contrast to their fitness-enhancing effect in the environment where they evolved, both mutations decreased cellular resistance to osmotic stress. Moreover, one mutation reduced fitness during prolonged stationary phase. Therefore, alteration of the PBP2 concentration contributed to physiological trade-offs and ecological specialization during experimental evolution.


Structural and functional analysis of the MutS C-terminal tetramerization domain.
The Escherichia coli DNA mismatch repair (MMR) protein MutS is essential for the correction of DNA replication errors. In vitro, MutS exists in a dimer/tetramer equilibrium that is converted into a monomer/dimer equilibrium upon deletion of the C-terminal 53 amino acids. In vivo and in vitro data have shown that this C-terminal domain (CTD, residues 801-853) is critical for tetramerization and the function of MutS in MMR and anti-recombination. We report the expression, purification and analysis of the E.coli MutS-CTD. Secondary structure prediction and circular dichroism suggest that the CTD is folded, with an alpha-helical content of 30%. Based on sedimentation equilibrium and velocity analyses, MutS-CTD forms a tetramer of asymmetric shape. A single point mutation (D835R) abolishes tetramerization but not dimerization of both MutS-CTD and full-length MutS. Interestingly, the in vivo and in vitro MMR activity of MutS(CF/D835R) is diminished to a similar extent as a truncated MutS variant (MutS800, residues 1-800), which lacks the CTD. Moreover, the dimer-forming MutS(CF/D835R) has comparable DNA binding affinity with the tetramer-forming MutS, but is impaired in mismatch-dependent activation of MutH. Our data support the hypothesis that tetramerization of MutS is important but not essential for MutS function in MMR.


Nationwide Cross-sectional Analysis of Endoscopic Thoracic Sympathectomy to Treat Hyperhidrosis Over 12 years in Brazil: Epidemiology, Costs, and Mortality.
To analyze the number of endoscopic thoracic sympathectomies performed to treat hyperhidrosis in the Universal Public Health System of Brazil, the government reimbursements, and the in-hospital mortality rates. Even though endoscopic thoracic sympathectomy has been widely performed for the definitive treatment of hyperhidrosis, no series reported mortality and there are no population-based studies evaluating its costs or its mortality rate. Data referring to endoscopic thoracic sympathectomy to treat hyperhidrosis between 2008 and 2019 were extracted from the database of the Brazilian Public Health System, which insures more than 160 million inhabitants. Thirteen thousand two hundred one endoscopic thoracic sympathectomies to treat hyperhidrosis were performed from 2008 to 2019, with a rate of 68.44 procedures per 10 million inhabitants per year. There were 6 in-hospital deaths during the whole period, representing a mortality rate of 0.045%. The total expended throughout the years was U$ 6,767,825.14, with an average of U$ 512.68 per patient. We observed a rate of 68.44 thoracoscopic sympathectomies for hyperhidrosis' treatment per 10 million inhabitants per year. The inhospital mortality rate was very low, 0.045%, though not nil. To our knowledge, no published series is larger than ours and we are the first authors to formally report deaths after endoscopic thoracic sympathectomies to treat hyperhidrosis. Moreover, there is no other population-based study addressing costs and mortality rates of every endoscopic thoracic sympathectomy for the treatment of any site of hyperhidrosis in a given period.


Dynamic properties of one-component strongly coupled plasmas: the sum-rule approach.
The dynamic characteristics of strongly coupled one-component plasmas are studied within the moment approach. Our results on the dynamic structure factor and the dynamic local-field correction satisfy the sum rules and other exact relations automatically. A quantitative agreement is obtained with numerous simulation data on the plasma dynamic properties, including the dispersion and decay of collective modes. Our approach allows us to correct and complement the results previously found with other treatments.


Improving the Through-Thickness Thermal Conductivity of Carbon Fiber/Epoxy Laminates by Direct Growth of SiC/Graphene Heterostructures on Carbon Fibers.
Poor thermal conductivity in the through-thickness direction is a critical limitation in the performance of carbon fiber-reinforced polymer (CFRP) composites over a broad range of applications in the aviation industry, where heat dissipation is required (e.g., battery packs, electronic housing, and heat spreaders). In this work, it is demonstrated for the first time that a hierarchical network of vertically oriented graphene nanoflakes (GNFs), with nanoconfined silicon carbide (SiC) nanocrystals, self-assembled on carbon fibers (CFs) can provide significant improvement to the thermal conductivity (TC) of CFRPs in the through-thickness direction. The vertically aligned SiC/GNF heterostructures were grown directly on CFs for the first time by single-step plasma-enhanced chemical vapor deposition (PECVD) employing tetramethylsilane (TMS) and methane (CH4) gases at temperatures of 800 and 950 °C. At the deposition temperature of 950 °C, the controlled introduction of SiC/GNF heterostructures induced a 56% improvement in through-thickness TC over the bare CFRP counterparts while simultaneously preserving the tensile strength. The increase in thermal conductivity is accomplished by SiC nanocrystals, which serve as linkage thermal conducting paths between the vertical graphene layers, further enhancing the smooth transmission of phonons in the vertical direction. The work demonstrates for the first time the unique potential of novel SiC/GNF heterostructures for attaining strong and thermally conductive multifunctional CFRPs.


History of insulin.
The advancement of diabetes treatment has gone from crude extracts of insulin and accidental discovery of sulfa-like drugs in antibiotics to the development of drugs based on improved understanding of the pathophysiology of diabetes mellitus. This article will review the history of the discovery and development of insulin. A companion focusing on non-insulin diabetes agents will follow in the next issue of JCHIMP.


Clinical utility of clonal origin determination in managing recurrent hepatocellular carcinoma.
Recurrence is the driving factor for reduced long-term survival in patients following resected hepatocellular carcinoma (HCC). Extensive research efforts have been conducted to understand the molecular processes precipitating disease recurrence. Modern genomic techniques have identified two distinct mechanisms for recurrent HCC (RHCC): Intrahepatic metastasis (IM-HCC); and multicentric origin (MO-HCC). Medline, EMBASE and Cochrane library were methodically searched for primary research articles in English with the aim of appraising existing literature on the identification of clonal origin of RHCC and its potential clinical utility. Molecular and next-generation sequencing techniques, when applied to clonal origin identification, yield superior accuracy than traditional clinicopathological criteria. Despite various treatment modalities, no optimal therapy has yet been identified for treating clonally differentiated RHCC. Patients with MO-HCC appear to experience improved long-term survival following re-treatment compared to their IM-HCC counterparts (91.7% vs 22.9% 5-year survival, p < 0.001). However, cautious interpretation is advised as heterogeneous classification criteria and small sample sizes restrict the generalizability of such findings. Improved identification of clonal origin in RHCC may facilitate further research on RHCC treatment strategies and enable the development of novel therapeutic targets, potentially leading to individualized treatment approaches in the future.


Efficient implementation of a local tomography reconstruction algorithm.
We propose an efficient implementation of an interior tomography reconstruction method based on a known subregion. This method iteratively refines a reconstruction, aiming at reducing the local tomography artifacts. To cope with the ever increasing data volumes, this method is highly optimized on two aspects: firstly, the problem is reformulated to reduce the number of variables, and secondly, the operators involved in the optimization algorithms are efficiently implemented. Results show that [Formula: see text] slices can be processed in tens of seconds, while being beyond the reach of equivalent exact local tomography method.


Morphometric analysis of cornea in the Slc39a13/Zip13-knockout mice.
Ehlers-Danlos syndrome (EDS) is a group of hereditary diseases caused by mutation of extracellular matrix-related genes. Recently, spondylodysplastic EDS-Zip13 (spEDS-Zip13: OMIM 612350) was recognized as a new EDS type. This current study could reveal various morphometric differences of collagenous population in the proper substance of cornea between the wild type and spEDS-Zip13-knockout (Zip13-KO) mice. Blockade of Smad-signaling pathway might initiate these alterations. Predilected dissimilarity in level of transcriptional activity probably dictated morphology of keratocyte and shape and electron density of its nucleus. In addition, the imbalance of proteoglycans and glycosaminoglycans would also affect the diameter and arrangement of collagen fibrils. These findings would be considered as vulnerable characteristics of corneal stroma of the Zip13-KO mice.


Tetrahydrobiopterin supplementation enhances carotid artery compliance in healthy older men: a pilot study.
We performed a pilot study to test the hypothesis that acute oral ingestion of tetrahydrobiopterin (BH(4)), a key cofactor modulating vascular nitric oxide (NO) synthase activity, improves large elastic artery stiffness with aging in men. Healthy older (63 ± 2 years; n = 8) and young (age 25 ± 1 years; n = 6) men were studied 3 h after ingestion of BH(4) (10 mg·kg(-1) body weight) or placebo on separate days in a randomized, placebo-controlled, double-blind study. Baseline carotid artery compliance was 37% lower (0.17 ± 0.02 vs. 0.22 ± 0.02 mm/mm Hg·10(-1)) and β-stiffness was 42% higher (7.3 ± 1.1 vs. 4.2 ± 0.5 AU) in the older men (both P < 0.05). BH(4) ingestion markedly increased circulating BH(4) concentrations in both groups (17-19-fold, P < 0.05), but increased compliance (+39% to 0.23 ± 0.02 mm/mm Hg·10(-1), P < 0.01) and decreased β-stiffness index (-27% to 5.3 ± 0.7 AU, P < 0.01) only in the older men. BH(4) also reduced carotid systolic blood pressure (SBP) in the older men (P < 0.05). These preliminary results support the possibility that limited BH(4) bioavailability contributes to impaired carotid artery compliance in healthy older men. Further studies are needed to determine if increasing BH(4) bioavailability though oral BH(4) supplementation may have therapeutic efficacy for improving large elastic artery compliance and reducing central SBP with aging.


[Chemical element levels in various human biological media].
Analysis of element composition (sodium, potassium, magnesium, calcium, zinc, copper, iron, total sulfur and its compounds, chloride, and inorganic phosphorus) in 40 normal subjects (22 women and 18 men aged 17-30 years) showed that the composition is specific for each of the analyzed media (blood, plasma, erythrocytes, urine, saliva, exhaled air condensate). Element composition of exhaled air condensate is described for the first time. Analysis of element composition in 102 patients with asthma demonstrated characteristic shifts in the concentrations of some macro- and trace elements, which confirms the clinical significance of analysis and correction of deviations in the element composition of biological media.


Antegrade Jejunojejunal Intussusception: An Unusual Complication Following Feeding Jejunostomy.
Feeding jejunostomy (FJ) is a simple surgical procedure for enteral nutrition. But it can develop complications that may require re-exploration and can be life-threatening. Common complications include mechanical ones such as tube migration or dislocation, infection, gastrointestinal symptoms and fluid and electrolyte imbalances. However, intussusception is a rare complication of FJ. A 54-year-old gentleman underwent a D2 subtotal gastrectomy with Roux-en-Y gastrojejunostomy with FJ. On the sixth postoperative day, he developed severe colicky pain associated with abdominal distension and bilious vomiting. Ultrasonography and computed tomography revealed a 10-cm long jejunojejunal intussusception with the FJ tube at the center of the intussusception with proximal jejunal loops' distension. The patient was taken up for a re-exploratory laparotomy with manual reduction of the intussusception and a new FJ insertion distal to the previous enterotomy site. The patient had an uneventful postoperative recovery.


Annotation-based inference of transporter function.
We present a method for inferring and constructing transport reactions for transporter proteins based primarily on the analysis of the names of individual proteins in the genome annotation of an organism. Transport reactions are declarative descriptions of transporter activities, and thus can be manipulated computationally, unlike free-text protein names. Once transporter activities are encoded as transport reactions, a number of computational analyses are possible including database queries by transporter activity; inclusion of transporters into an automatically generated metabolic-map diagram that can be painted with omics data to aid in their interpretation; detection of anomalies in the metabolic and transport networks, such as substrates that are transported into the cell but are not inputs to any metabolic reaction or pathway; and comparative analyses of the transport capabilities of different organisms. On randomly selected organisms, the method achieves precision and recall rates of 0.93 and 0.90, respectively in identifying transporter proteins by name within the complete genome. The method obtains 67.5% accuracy in predicting complete transport reactions; if allowance is made for predictions that are overly general yet not incorrect, reaction prediction accuracy is 82.5%. The method is implemented as part of PathoLogic, the inference component of the Pathway Tools software. Pathway Tools is freely available to researchers at non-commercial institutions, including source code; a fee applies to commercial institutions. Supplementary data are available at Bioinformatics online.


The Impact of Family Engagement and Child Welfare Services on Maltreatment Re-reports and Substantiated Re-reports.
Despite decades of debate about the most effective ways to intervene with families reported to child protective services (CPS), little evidence exists regarding the types of services or approach that reduce children's risk of additional maltreatment. The current study used data collected during a statewide experimental evaluation of CPS to examine the impact of numerous service variables, family engagement, and family characteristics on the risk of maltreatment re-reports and substantiated re-reports among families initially reported for neglect and risk of harm. The sample included 4,868 families with screened-in reports that were randomly assigned to receive either an investigation or an assessment. The results of the Cox regression analyses found that service duration, intensity, and breadth were unrelated to maltreatment re-report or substantiated re-reports, but caseworker ratings of the service-need match were associated with both. The provision of domestic violence services was related to decreased risk of maltreatment re-reports. Increased levels of family engagement were associated with lowered risk of both maltreatment re-reports and substantiated re-reports. Once the effects of services, engagement, and family characteristics were taken into account, CPS response pathway (investigation or assessment) had no relationship to maltreatment re-reports or substantiated re-reports.


Incidental atypical pheochromocytoma in sporadic type IIb von Hippel-Lindau disease.
To describe the features of an incidentally discovered atypical pheochromocytoma in an asymptomatic patient with normal blood pressure and the de novo appearance of sporadic type IIB von Hippel-Lindau (VHL) disease. We review the clinical manifestations, radiographic findings, and unusual features of a large, atypical pheochromocytoma diagnosed in a patient with the rare type IIB phenotype of VHL disease. A 46-year-old man, who sought medical assistance in the emergency department after a motorcycle accident, had an abdominal roentgenogram that revealed extensive left suprarenal calcification. Computed tomography of the abdomen demonstrated a densely calcified left adrenal mass, bilateral renal cysts, and pancreatic calcifications. The patient was normotensive and asymptomatic and had no history of hypertension. He had undergone resection of a cerebellar hemangioblastoma at age 36 years and a partial left nephrectomy for a renal cyst at age 7 years. Routine biochemical screening demonstrated increased urinary vanillylmandelic acid and normetanephrine levels as well as an elevated plasma norepinephrine level. The adrenal mass was notable for the absence of increased signal intensity on T2-weighted magnetic resonance images. The patient was diagnosed with the type IIB phenotype of VHL disease and underwent resection of a 10.5-cm, 124-g benign pheochromocytoma. Our case emphasizes the importance of recognizing that pheochromocytoma may occur in association with sporadic VHL disease, that not all pheochromocytomas have an increased signal intensity on T2-weighted magnetic resonance images, and that routine biochemical testing for pheochromocytoma is important in all patients with an adrenal "incidentaloma."


Chronic acquired sensory neuron diseases.
Sensory neuron diseases (SND) represent a specific subgroup of peripheral nervous system disorders that are becoming increasingly recognized. We aimed to analyze clinical, neurophysiological, and MRI features in patients with SND. We reviewed clinical and electrophysiological data of 20 individuals fulfilling SND criteria. Patients underwent an additional neurological evaluation and cervical spine MRI. Sensory neuron diseases was associated with dysimmune conditions in six, hepatitis C in one, B12 deficiency in another, and in one patient SND was related to organophosphate intoxication. In the remaining eleven, it was considered as idiopathic. Nineteen patients experienced sensory symptoms. Worse ataxia was related with longer disease duration (P = 0.02). Early CSF assessment was related to higher protein level (P = 0.008). All patients showed widespread impairment in sensory nerve action potential amplitudes. High signal intensity in the posterior columns was observed in most patients when MRI was performed more than 3 years after disease onset. Sensory neuron diseases usually presents with sensory symptoms and ataxia. A high index of suspicion is important because inflammatory changes might be more prominent initially, a period when immunotherapy could be more valuable. Early diagnosis should be based mainly on electrophysiological and clinical grounds, as MRI may be normal initially.


Lungworm (Nematoda: Protostrongylidae) infection in wild and domestic ruminants from Małopolska region of Poland.
The conducted study has focused on domestic, as well as wild ruminant species. The post mortem examination was carried out on 68 animals, including three wild species: roe deer (Capreolus capreolus) (25 indyviduals), red deer (Cervus elaphus) (6), fallow deer (Dama dama) (5) and two domestic: sheep (Ovis aries) (14) and cattle (Bos taurus) (18). Some of the species have also been investigated in the field by the coproscopical analyses. The faecal samples from roe deer (27), fallow deer (20), red deer (36) and moose (Alces alces) (10) were collected from the environment, while from sheep (10) and goat (Capra hircus) (10)--per rectum. Based on the obtained results the following values were calculated: prevalence, mean intensity and intensity range. The post mortem examination did not reveal pulmonary nematodes neither in domestic nor in wild ungulates, however, the larvae of aforementioned parasites were often stated in the stool samples taken from the environment. All wild species, except fallow deer were infected. Consequently, six species of lungworms have been identified. The first stage larvae of Varestrongylus capreoli occurred in 11 samples of roe deer and Varestrongylus alces in one moose. The larvae of Elaphostrongylus cervi were found in 19 red deer and Varestrongylus sagittatus in 3. Furthermore, Elaphostrongylus alces larvae were noted in 6 moose. Within domestic ruminants only one sheep and two goats were infected by Muellerius capillaris.


Direct surface-enhanced Raman scattering analysis of DNA duplexes.
The exploration of the genetic information carried by DNA has become a major scientific challenge. Routine DNA analysis, such as PCR, still suffers from important intrinsic limitations. Surface-enhanced Raman spectroscopy (SERS) has emerged as an outstanding opportunity for the development of DNA analysis, but its application to duplexes (dsDNA) has been largely hampered by reproducibility and/or sensitivity issues. A simple strategy is presented to perform ultrasensitive direct label-free analysis of unmodified dsDNA with the means of SERS by using positively charged silver colloids. Electrostatic adhesion of DNA promotes nanoparticle aggregation into stable clusters yielding intense and reproducible SERS spectra at nanogram level. As potential applications, we report the quantitative recognition of hybridization events as well as the first examples of SERS recognition of single base mismatches and base methylations (5-methylated cytosine and N6-methylated Adenine) in duplexes.


The usefulness of laparoscopic adrenalectomy in the treatment of adrenal neoplasms - a single-centre experience.
Adrenal neoplasms comprise about 10% of all tumours affecting this organ and constitute a significant, at first diagnostic and subsequently therapeutic, problem, especially since a relatively high proportion of neoplastic lesions are asymptomatic. The number of diagnosed metastases to adrenal glands is increasing. Surgical treatment involves both open surgery as well as laparoscopy. There were 245 adrenalectomies performed at our centre due to various indications over the past four years. In 27 (11.5%) cases neoplasms were diagnosed in the final histopahtological examination. In 11 (40.7%) cases primary adrenal cortex tumours were diagnosed, metastases from other solid organ tumours were identified in another 12 (44.4%) patients, and rarer neoplasms were diagnosed in the remaning 4 (14.8%) subjects. Cases of malignant pheochromocytoma were not included in this report. Laparoscopic adrenalectomy was performed in 23 (85.2%) subjects, while the ramaining 4 (12.9%) patients were subject to open adrenalectomy (conversion to open procedure in one case). There were no deaths or significant complications in the perioperative period. Comparing mean duration of open (140 minutes) and laparoscopic (190 minutes) procedures yielded a statistically significant difference (p = 0.02). There was no statistically significant difference found in the duration of operation with regard to laparoscopic adrenalectomies of tumours less than 50 mm and over 55 mm in diameter (p = 0.16). Laparoscopic adrenalectomy is a safe and effective method of treatment of adrenal tumours. Its oncological completeness is comparable (to open surgery) when performed by experienced surgical teams. Laparoscopy is the reason for the smooth postoperative course observed in most patients.


Spatial memory in transgenic mice with impaired glucocorticoid receptor function.
Spatial learning and memory function of transgenic mice with impaired glucocorticoid receptor function was assessed in the Morris water maze and the radial arm maze. Transgenic mice took longer to find a submerged and a visual platform in the water maze task than did mice from the parent strain (B6C/3F1), although performance was improved in the visible platform condition relative to the submerged platform task. In the radial arm maze, transgenic mice made significantly more errors than B6C/3F1 mice. In both tasks, the behavioural strategies adopted by transgenic mice were non-optimal for correct performance. It is suggested that the impaired performance displayed by transgenic mice in both tests is largely attributable to these altered behavioural strategies.


Differential effects of omega-conotoxin GVIA on cholinergic and non-cholinergic secretomotor neurones in the guinea-pig small intestine.
1. Ussing chambers were used to study the effects of the specific N-type Ca2+ channel antagonist, omega-conotoxin GVIA, on neurally evoked secretion across isolated submucosa/mucosa preparations from the small intestine of the guinea-pig. 2. Cholinergic and non-cholinergic neurones were stimulated with 10 microM dimethylphenylpiperazinium (DMPP). Non-cholinergic secretomotor neurones were preferentially stimulated with 100 nM 5-hydroxytryptamine (5-HT), while cholinergic secretomotor neurones were preferentially stimulated with 3 microM 5-HT in the presence of the 5-HT2 receptor antagonist ketanserin (30 nM). 3. omega-Conotoxin GVIA (1 nM-1 microM) depressed the secretion evoked by DMPP in a concentration-dependent manner, but a substantial residual response was observed. Hyoscine (100 nM) significantly depressed secretion evoked by DMPP, but did not prevent further depression of secretion by omega-conotoxin GVIA. 4. The toxin was substantially more effective when the non-cholinergic secretomotor neurones were preferentially activated with 100 nM 5-HT, with a decrease in the response of more than 75% of the control value in the presence of 1 microM omega-conotoxin GVIA. 5. omega-Conotoxin GVIA (1 microM) was relatively ineffective against secretion evoked by preferential activation of cholinergic secretomotor nuerones with 3 microM 5-HT in the presence of 30 nM ketanserin, inhibiting the response by less than 33%. However, this inhibition was significant. Both 100 nM hyoscine and 300 nM tetrodotoxin abolished this effect of omega-conotoxin GVIA. 6. It is concluded that N-type Ca2+ channels play a major role in transmitter release from non-cholinergic secretomotor neurones, but are not important for release from cholinergic secretomotor neurones in the guinea-pig small intestine.


Finite-difference time-domain synthesis of infrasound propagation through an absorbing atmosphere.
Equations applicable to finite-difference time-domain (FDTD) computation of infrasound propagation through an absorbing atmosphere are derived and examined in this paper. It is shown that over altitudes up to 160 km, and at frequencies relevant to global infrasound propagation, i.e., 0.02-5 Hz, the acoustic absorption in dB/m varies approximately as the square of the propagation frequency plus a small constant term. A second-order differential equation is presented for an atmosphere modeled as a compressible Newtonian fluid with low shear viscosity, acted on by a small external damping force. It is shown that the solution to this equation represents pressure fluctuations with the attenuation indicated above. Increased dispersion is predicted at altitudes over 100 km at infrasound frequencies. The governing propagation equation is separated into two partial differential equations that are first order in time for FDTD implementation. A numerical analysis of errors inherent to this FDTD method shows that the attenuation term imposes additional stability constraints on the FDTD algorithm. Comparison of FDTD results for models with and without attenuation shows that the predicted transmission losses for the attenuating media agree with those computed from synthesized waveforms.


Teaching Epidemiology at the Undergraduate Level: Considerations and Approaches.
The rapid growth in undergraduate public health education has offered training in epidemiology to an increasing number of undergraduate students. Epidemiology courses introduce undergraduate students to a population health perspective and provide opportunities for these students to build essential skills and competencies such as ethical reasoning, teamwork, comprehension of scientific methods, critical thinking, quantitative and information literacy, ability to analyze public health information, and effective writing and oral communication. Taking a varied approach and incorporating active learning and assessment strategies can help engage students in the material, improve comprehension of key concepts, and further develop key competencies. In this commentary, we present examples of how epidemiology may be taught in the undergraduate setting. Evaluation of these approaches and others would be a valuable next step.


DFT and TPD study of the role of steps in the adsorption of CO on copper: Cu(4 1 0) versus Cu(1 0 0).
Adsorption of carbon monoxide (CO) was studied on stepped Cu(4 1 0) by temperature programmed desorption (TPD) and density-functional-theory (DFT) calculations. For comparison, the adsorption of CO was characterized also on Cu(1 0 0) by DFT calculations. On Cu(4 1 0) TPD reveals two desorption peaks: a high temperature peak (∼210 K) is attributed to the desorption of CO from step-edge sites and low temperature peak (∼170 K) to desorption from terrace sites. According to DFT calculations, CO prefers to adsorb at step-edges of Cu(4 1 0), although the step-edge versus terrace site preference is rather small at low coverage of 1/16 ML, about 0.05 eV; the respective DFT predicted CO binding energies are -0.89 and -0.84 eV at the step-edge and terrace top sites, whereas the value calculated at top sites of Cu(1 0 0) is -0.86 eV. Although this small step-edge over terrace site preference of 0.05 eV cannot explain the temperature difference of 40 K between the two TPD peaks, when the lateral intermolecular interactions are neglected, it is sufficient that the CO adsorbs almost exclusively at step-edges at low coverage (at 200 K the 0.05 eV corresponds to 3 kT). The emergence of the two TPD peaks on Cu(4 1 0) is therefore attributed to a combination of step-edge preference and lateral repulsion between CO molecules, which increases with increasing coverages and diminishes the net desorption energy of CO. DFT calculations further reveal that the reason for the significant increase of saturation coverage on Cu(4 1 0) compared to Cu(1 0 0) is related to the geometry of the step-edge that allows the CO molecules adsorbed thereon to tilt away from the nearest neighboring CO molecules adsorbed at the terrace and therefore to effectively reduce the lateral repulsion.


Small cell lung cancer.
It can be stated that, depending on the type of lung cancer, the best opportunity for curative treatment is in the early stage of disease, when cancer is limited to the lung and surgical intervention can be indicated. Especially in the case of SCLC, the number of patients presenting with such a limited disease is very low. In SCLC, chemo- and/or radiotherapy can induce initial good responses, which, although not curative in most cases, can elongate life for an average of 10 months. Although changes and refinements in treatment are continuously introduced, further progresses in the outcome have not achieved for the last decennium. Therefore, more fundamental research is needed to indicate new treatment avenues. A number of findings appear promising in this field. Firstly, the development of tissue culture techniques has enabled a better study of the biological properties of both SCLC and non-SCLC. Secondly, the development of monoclonal antibodies has refined the possibilities to type lung cancer. Particularly if monoclonal antibodies could be identified which occurrence turns out to be relevant to prognosis, immunohistopathology could become an important additional tool for the assessment of a pathological diagnosis in lung cancer. In addition, monoclonal antibodies which are specific for lung cancer could be used for an immunotherapeutical approach in the near future. Such a treatment might complement currently available treatment modalities.


Succession of aquatic microbial communities as a result of the water quality variations in continuous water.
The changes of structural and functional parameters of aquatic microbial communities in continuous water on campus of Tsinghua University, China are investigated, by polyurethane foam unit (PFU) method. The measured compositions of the communities include alga, protozoa, and some metazoa (such as rotifers). The measured indicators of water quality include water temperature, pH value, dissolved oxygen (DO), potassium permanganate index (COD(Mn)), total nitrogen (TN), total phosphorus (TP) and chlorophyll-a (Chla). The trophic level, expressed by the trophic level indices (TLIc), is assessed with analytic hierarchy process and principal component analysis (AHP-PCA) method. The changing trends of the structural and functional parameters of aquatic microbial communities, such as Margalef index of diversity (D), Shannon-weaver index of diversity (H), Heterotropy index (HI), number of species when the colonization gets equilibrium (S(eq)), colonizing speed constant (G) and time spent when 90 percent of S(eq) colonized in PFU (T(80%)), are also analyzed. The experimental results showed the succession of aquatic microbial communities along the water flow is consistent with the water quality changes, so the parameters of microbial community can reflect the changes of water quality from the ecological view.


The frequency of marcroamylasemia and the diagnostic value of the amylase to creatinine clearance ratio in patients with elevated serum amylase activity.
190 patients with elevated serum amylase levels were tested for macroamylasemia and the amylase to creatinine clearance ratio. Macroamylasemia was found in 3 patients. In these patients macroamylasemia persisted after the total activity of serum amylase had fallen to nearly normal levels. The Cam/Ccr-ratios were determined 14 times in the 3 macroamylasemic patients. Only one of the 14 values was clearly less than 1%. Cam/Ccr-ratios above 4% were found in 83 patients. In 56 of them the diagnosis of acute pancreatitis could not be confirmed. 19 out of 46 patients with the established diagnosis of acute pancreatitis had Cam/Ccr-ratios below 4%. Cam/Ccr-ratios below 1% were also found in patients without macroamylasemia. It is concluded that high and low Cam/Ccr-ratios are not specific for acute pancreatitis and macroamylasemia, respectively, and--moreover--that a normal Cam/Ccr-ratio excludes neither acute pancreatitis nor macroamylesemia.


Pacemaker Pocket Stabilization Utilizing a Novel Envelope and a Three-Point Anchoring Technique.
A 65-year-old man presented with chronic pain due to frequent movement of a dual chamber pacemaker (PPM) within the device pocket despite being secured to the underlying muscle. Due to chronic pain and possible indolent infection, the PPM was removed and a new device was implanted on the contralateral side via a persistent left superior vena cava. To prevent device movement, it was placed within a CanGaroo® envelope (Aziyo Biologics Inc., Silver Spring, MD, USA), which was secured to the underlying muscle with a silk suture along three of its corners. The envelope, which becomes incorporated into the surrounding tissue forming a vascularized tissue pocket, should further reinforce device stability over time. The patient's left-sided symptoms abated immediately and he remains free of symptoms on the right side over a six-week follow-up period.


Chronic salt loading and adrenergic mechanisms in the Sprague-Dawley rat.
The effect of chronic salt loading on adrenergic mechanisms was evaluated in Sprague-Dawley rats (and NMRI mice) maintained on a high sodium (8%) or normal sodium (0.3%) regime for 4 weeks. The basal blood pressure (carotid artery) was not influenced by the high salt diet but the heart rate and blood pressure increases to mental stress (jet air) were larger in the salt loaded rats. There were indications of an increased sympathetic tone in rats on the high salt diet since in these rats sympathoinhibitory treatment with ganglionic blockade or clonidine induced larger falls in blood pressure and heart rate than in the controls. Central catecholamines (brain stem, striatum, hemispheres) were determined spectrofluorimetrically after cation exchange chromatography. The high salt diet influenced neither the endogenous levels of noradrenaline nor central noradrenaline turnover (disappearance of noradrenaline after synthesis inhibition by alpha-methyltyrosine and accumulation of dihydroxyphenylalanine after decarboxylase inhibition by 3-hydroxybenzylhydrazine). There were no changes in central alpha 2-adrenoceptor responsiveness when assessed as clonidine-induced deceleration of noradrenaline turnover in the brain and in central alpha 1-adrenoceptor responsiveness (clonidine-induced increase of flexor reflex in spinalized rats and clonidine-induced increase of motor activity in reserpinized mice). Peripheral sympathetic function was assessed in pithed rats. The pressor responses to intravenously administered noradrenaline (0.01-10 micrograms/kg) and electrical stimulation of the spinal sympathetic nerves (SNS, 0.25-2 Hz) were similar in the two groups, suggesting that salt did not influence vascular alpha-adrenoceptor responsiveness or transmitter release.(ABSTRACT TRUNCATED AT 250 WORDS)


Laser treatment in subjects with high-risk clinical features of age-related macular degeneration. Posterior pole appearance and retinal function.
To verify that a few laser lesions in the posterior pole can cause drusen to resolve in patients with age-related macular degeneration, and to document central retinal sensitivity as drusen resolve. In a pilot study, 12 patients considered to be at high risk for sight-threatening complications from age-related macular degeneration were treated with 12 argon laser lesions in the posterior pole, with review for 12 to 24 months. Choroidal neovascularization developed in 1 patient 8 months after treatment, with consequent loss of central vision. In 9 of the remaining 11 patients, high-risk characteristics of drusen were reduced. Four patients had retinal pigment epithelial depigmentation, and all maintained 20/40 visual acuity at 12 months. One patient lost 3 lines of vision due to geographic atrophy after 12 months. Scotopic retinal threshold was elevated before treatment in 8 patients, compared with an age-matched comparison group. Of these, 4 patients underwent retesting 3 to 6 months after treatment, and all had improved thresholds, but only 1 patient sustained the improvement at 12 months. At 12 months, 3 of the 8 patients showed an improvement in their mean retinal threshold. Of those in whom the mean retinal threshold worsened, the mean elevation in threshold was not more than 0.6 log units. A few laser lesions in the posterior pole leads to resolution of drusen. There does not appear to be an increased risk for choroidal neovascularization. Retinal threshold measurements show no indication of geographic atrophy at 1 year, but cannot be excluded as a late outcome. Laser treatment may reduce the risk for profound sight-threatening lesions in age-related macular degeneration.


Transient reduction of 5-methylcytosine and 5-hydroxymethylcytosine is associated with active DNA demethylation during regeneration of zebrafish fin.
Although dedifferentiation, transformation of differentiated cells into progenitor cells, is a critical step in the regeneration of amphibians and fish, the molecular mechanisms underlying this process, including epigenetic changes, remain unclear. Dot blot assays and immunohistochemical analyses revealed that, during regeneration of zebrafish fin, the levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are transiently reduced in blastema cells and cells adjacent to the amputation plane at 30 h post-amputation (hpa), and the level of 5mC, but not 5hmC, is almost restored by 72 hpa. We observed that the dedifferentiated cells showed reduced levels of 5mC and 5hmC independent of cell proliferation by 24 hpa. Furthermore, expressions of the proposed demethylation- and DNA repair-related genes were detected during fin regeneration. Taken together, our findings illustrate that the transient reduction of 5mC and 5hmC in dedifferentiated cells is associated with active demethylation during regeneration of zebrafish fin.


Desire for Sterilization Reversal Among U.S. Females: Increasing Inequalities by Educational Level.
For decades, high reliance on female sterilization in the United States has been accompanied by a high level of desire for sterilization reversal, and less-educated women have been more likely than better educated women to use the method and desire a reversal. Little is known about how levels of and educational differentials in such desire have changed in recent decades. Data from 4,147 women who reported being sterile from a tubal sterilization in the 1995, 2002 and 2006-2010 waves of the National Survey of Family Growth were analyzed using chi-square and Wald tests and binary logistic regression analyses. Predicted probabilities were calculated to determine the likelihood of desire for procedure reversal by wave and educational level. The prevalence of desire for sterilization reversal rose by 41%, from 18% in 1995 to 23% in 2002 and 25% in 2006-2010. Overall, women with a bachelor's degree were less likely than those who had not finished high school to desire a reversal (odds ratio, 0.2), and this educational differential was larger in 2006-2010 than in earlier waves. Predicted probabilities indicate that 9% of sterilized women with less than a high school education and 8% of those with a bachelor's degree expressed a desire for procedure reversal in 1995, as did 15% and 3%, respectively, in 2006-2010. Future research should consider how insurance coverage of all methods under the Affordable Care Act may affect use of sterilization and desire for reversal.


Tibial sesamoid planing procedure: an appraisal of 26 feet.
The authors present their findings upon evaluation of 26 feet that had undergone a tibial sesamoid planing procedure. A preoperative method of radiographic evaluation is also presented. The subjective success rate was determined to be 88.8%, whereas the objective success rate was 76.9%, and a successful procedure was performed on feet with a first metatarsal declination angle not exceeding 8 degrees. It was also determined that the apparent postoperative changes in the hallux abductus and intermetatarsal angles were 0.73 degrees and 0.6 degrees, respectively. The authors believe this procedure does not significantly alter the biomechanics of the first metatarsophalangeal joint postoperatively.


IgG-induced experimental immune synovitis: hormonal modulation of in vitro splenic immune responses to homologous antigens.
The effect of oestrogen or anti-oestrogen administration on gross pathology and in vitro cell-mediated immune responses to homologous IgG, native and denatured interstitial collagens and PPD was studied in an IgG-induced rabbit model of immune synovitis. During induction of synovitis, rabbits were administered oestradiol valerate (0.075 mg/kg/day) or tamoxifen, an anti-oestrogen (2.0 mg/kg/day, high dose or 0.5 mg/kg/day, low dose) or placebo injections. Low dose tamoxifen administration was associated with significant improvement P less than 0.05 in immune synovitis with regard to gross pathology, when compared to placebo and the oestradiol treatment group. High dose tamoxifen treatment was not associated with significant improvement in observed synovitis. With regard to cell-mediated immune responses, spleen cells derived from immune synovitis rabbits were observed to increase 3H-thymidine uptake on incubation with native or denatured homologous collagens. Modulation of these immune responses to antigens was observed in anti-oestrogen treated rabbits with immune synovitis. In vitro cell-mediated immune responses to denatured type I, II and III collagens, PPD, as well as native type II and III collagens were not observed in the low dose tamoxifen treatment group. However, in vitro immune responses to these antigens were observed in spleen cell cultures from immune synovitis rabbits treated with either high dose tamoxifen or oestradiol valerate. The data suggest that in vivo anti-oestrogen administration can modulate the in vitro cell-mediated immune response to connective tissue constituents observed in immune synovitis. Concomitant with reduced immune responses is a significant reduction in the observed lesions of the inflammatory response.


Development of a Novel Markov Chain Model for the Prediction of Head and Neck Squamous Cell Carcinoma Dissemination.
Prediction of microscopic tumor spread to regional lymph nodes can assist in radiation planning for cancer treatment. However, it is still challenging to predict tumor spread. In this paper, we present a unique approach to modeling how tumor cells disseminate to form regional metastases. This involves leveraging well established knowledge resources and commonly held notions of how cancer spreads. Using patient data, we utilized our approach to create a model of metastasis for the subset of head and neck squamous cell carcinoma that arises in the mucosa of the lateral tongue. The model was created using a training set extracted from the clinical records of 50 patients with tumors of this type who presented to the University of Washington head and tumor board over a three and half year period. The test sets consist of four case series drawn from the literature.


The RNA aptamer inhibiting human vesicular endothelial growth factor receptor 1 without affecting cytokine binding.
Angiogenesis, a process of new blood vessel formation, is crucial not only for many physiological events but also for a number of diseases. The signaling pathways through members of the vesicular endothelial growth factor (VEGF) family play fundamental roles in angiogenesis. In this study, we identified inhibitory RNA aptamers against human Flt-1, a receptor of VEGF. One of the isolates, aptamer #38, showed a 50% inhibitory concentration (IC50) of 23 nM in the cell-based autophosphorylation assay, and the IC50 value was decreased to 6.3 nM upon removal of 32 dispensable nucleotides from parental #38 with a length of 72 nucleotides. Interestingly, the surface plasmon resonance-based or affinity resin-based binding study revealed that #38 and its shortened derivative, #38Jr, do not interfere with binding of VEGF or heparin, a functional cofactor, to Flt-1. Importantly, aptamer #38 does not affect the decoy activity of soluble Flt-1. These findings suggest that #38 prevents the conformational activation of Flt-1 associated with VEGF. Therefore, aptamer #38 might provide us with a unique tool for blocking the VEGF signaling specific to Flt-1, unlike most other known VEGF signaling blockers such as VEGF inhibitors, anti-Flt-1 antibodies, and decoy soluble receptors.


F1 hybrid-anti-parental H-2b cell-mediated lympholysis: genetic control of target antigens by the H-2D region.
The immunogenetic specificity of (C57BL/6 X DBA/2)F1 anti-parental C57BL/6 cytotoxic T lymphocytes (CTL) induced in primary mixed spleen cell cultures was determined in direct lytic and competitive inhibition assays. A large panel of peritoneal exudate cells (PEC) bearing nonrecombinant and recombinant H-2-Tla haplotypes was the source of target and inhibitor cells. All PEC of H-2b, H-2bc, H-2j, and H-2ja types, irrespective of background genetic constitution, were as susceptible to direct lysis as C57BL/6 PEC, but PEC of H-2a, H-2d, H-2k, H-2q, H-2s, and H-2u types were not. The possible involvement of the Tla region in controlling target antigens was excluded by testing PEC obtained from 4 H-2/Tla or intra-Tla recombinant mouse strains. The genes controlling target antigens were mapped to the D region with the aid of 9 intra-H-2 recombinants; for target PEC to be lysed it was necessary and sufficient that Db antigens be part of the H-2 phenotype. These results were confirmed by competitive inhibition assays. Resident peritoneal cells not exposed to fetal bovine serum were also lysed by F1 anti-parental H-2b CTL, a demonstration that target antigens are expressed on normal cells.


Researching the plant-animal interface: the investigation of ingestive behavior in grazing animals.
Profitable livestock production from forages largely depends on efficiency of converting forages into products. Efficient grazing management systems require an understanding of the roles of system components. However, experimentation should be conducted with regard to the system as a whole rather than on the systems components in isolation. This may necessitate development of computer models. The short-term intake of forage by grazing animals is controlled both by the structure of the forage and by effects of the ingested forage on gut fill as moderated by the hunger-satiety complex. Intake can be defined as the product of bite size, rate of biting and grazing time. Measurement of these variables is facilitated by the use of esophageally fistulated animals and automatic recording devices. Bite size has the greatest influence on intake, with rate of biting and grazing time being compensatory variables. Sward structure influences bite size to varying degrees. In temperate grass swards, leaf surface height appears to be the dominant influence on bite size. But in tropical grass swards, leaf density and leaf:stem ratio have a greater influence on bite size than does leaf surface height. Alternative techniques to conventional grazing trials are described. Diversity of environments and forages in the U.S. requires further research into the development of grazing systems. In the future, small-scale trials and computer simulation techniques likely will be used to a greater extent.


Psychological distress and multimorbidity in primary care.
Psychological distress may decrease adherence to medical treatments and lead to poorer health outcomes of chronic diseases. The aim of this study was to evaluate the relationship between psychological distress and multimorbidity among patients seen in family practice after controlling for potential confounding variables and taking into account the severity of diseases. We evaluated 238 patients to construct quintiles of increasing multimorbidity based on the Cumulative Illness Rating Scale (CIRS), which is a comprehensive multimorbidity index that takes into account disease severity. Patients completed a psychiatric symptom questionnaire as a measurement of their psychological distress. In the first model of logistic regression analyses, we used the counted number of chronic diseases as the independent variable. In subsequent models, we used the quintiles of CIRS. After adjusting for confounding factors, multimorbidity measured by a simple count of chronic diseases was not related to psychological distress (OR, 1.12; 95% CI, 0.97-1.29; P = .188), whereas multimorbidity measured by the CIRS remained significantly associated (OR, 1.67; 95% CI, 1.19-2.37; P = .002). The estimate risk of psychological distress by quintile of CIRS was as follows: Q1/2 = 1.0; Q3 = OR, 1.72; 95% CI, 0.53-5.86; Q4 = OR, 2.99; 95% CI, 1.01-9.74; Q5 = OR, 4.67; 95% CI, 1.61-15.16. Psychological distress increased with multimorbidity when we accounted for disease severity. Clinicians should be aware of the possible presence of psychological distress, which can further complicate the comprehensive management of these complex patients.


The genus and subgenus categories within Culicidae and placement of Ochlerotatus as a subgenus of Aedes.
Many species of Culicidae are of major medical, veterinary, and economic importance. To facilitate discussion among taxonomists, medical entomologists, ecologists, and vector control specialists, it is essential that culicidologists be able to readily recognize individual genera. Adult female mosquitoes, the stage most often encountered in surveys, should be identifiable to genus without dissection with the aid of a good-quality dissecting microscope. Female adult specimens of Ochlerotatus and Aedes as defined by Reinert cannot be identified morphologically without dissection, and no distinct differences in biology, behavior, and ecology distinguish these 2 taxa as currently defined. Use of these names as genera complicates mosquito identification and interferes with information retrieval and communication among taxonomists, medical entomologists, and vector control specialists. Therefore, it is our opinion that Ochlerotatus Lynch Arribalzaga should be placed as a subgenus of Aedes Meigen, Aedes (Ochlerotatus). We believe that the usage of the genus Aedes and the subgenus Ae. (Ochlerotatus) should be restored to the traditional usage during the interval 1906-2000.


Bivalent ligand containing curcumin and cholesterol as fluorescence probe for Aβ plaques in Alzheimer's disease.
A recently developed bivalent ligand BMAOI 14 (7) has been evaluated for its capability to label and detect aggregated β-amyloid (Aβ) peptide as a fluorescent probe. This probe contains curcumin as the Aβ recognition moiety and cholesterol as an anchorage to the neuronal cell membrane/lipid rafts. The results demonstrate that 7 binds to the monomers, oligomers as well as fibrils of Aβ42 with low micromolar to submicromolar binding affinities. This chemical probe also has many of the required optical properties for use in imaging and can rapidly cross the blood-brain barrier (BBB) in vivo. Furthermore, 7 specifically binds to Aβ plaques in both AD human patients and APP transgenic mouse brain tissues. Collectively, these results suggest that 7 is a strong candidate as an Aβ-imaging agent and encourage further optimization of 7 as a new lead to develop the next generation of Aβ-imaging probes.


Liking, salt taste perception and use of table salt when consuming reduced-salt chicken stews in light of South Africa's new salt regulations.
This study investigated the impact of salt reduction on liking, salt taste perception, and use of table salt when consuming chicken stew in light of South Africa's new salt recommendations. In total, 432 South-African consumers (aged 35.2 ± 12.3 years) consumed a full portion of a chicken stew meal once at a central location. Four stock cube powders varying in salt content were used to prepare chicken stews: 1) no reduction - 2013 Na level; regular salt level as currently available on the South African market (24473 mg Na/100 g), 2) salt reduction smaller than 2016 level, i.e. 10%-reduced (22025 mg Na/100 g), 3) 2016 salt level, as per regulatory prescriptions (18000 mg Na/100 g), 4) 2019 salt level, as per regulatory prescriptions (13000 mg Na/100 g). Consumers were randomly allocated to consume one of the four meals. Liking, salt taste perception, and use of table salt and pepper were measured. Chicken stews prepared with reduced-salt stock powders were equally well-liked as chicken stews with the current salt level. Moreover, a gradual reduction of the salt in the chicken stews resulted in a reduced salt intake, up to an average of 19% for the total group compared to the benchmark 2013 Na level stew. However, 19% of consumers compensated by adding salt back to full compensation in some cases. More salt was added with increased reductions of salt in the meals, even to the point of full compensation. Further investigation into the impacts of nutrition communication and education about salt reduction on salt taste perception and use is needed. This research provides new consumer insights on salt use and emphasises the need for consumer-focused behaviour change approaches, in addition to reformulation of products.


SPP1 overexpression is associated with poor outcomes in ALK fusion lung cancer patients without receiving targeted therapy.
The screening of non-small cell lung cancer (NSCLC) tumors for anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements is important because of the dramatically favorable therapy response to ALK inhibitor. However, the exact mechanism of poor survival in ALK fusion lung cancer patients without receiving targeted therapy is unclear. In this study, total of 521 tumor specimens from Chinese patients with lung cancer were screened for ALK fusion by immunohistochemistry (IHC) and confirmed by fluorescence in situ hybridization (FISH). As results, there were no cases of coexisting EGFR and ALK mutations identified. Fourteen cases (2.7%) harbored ALK fusion, including eight solid adenocarcinomas with signet ring cell features, four acinar adenocarcinomas with cribriform pattern containing mucin, one adenosquamous carcinoma and one micropapillary adenocarcinoma with mucin. Six (42.9%) of fourteen patients with ALK-positive lung cancer had stage IV disease, and five ALK-positive patients treated with platinum-based chemotherapy had poor outcome (all patients were dead and the mean survival time was 12 months), compared to 72 months for patients with ALK inhibitor therapy. Furthermore, Five ALK-positive cases were analyzed by whole exome sequencing (WES) and via direct transcript counting using a digital probe-base (NanoString) to explore the driver genes. Deregulation of PI3K/AKT signaling pathway in ALK-positive lung cancer was demonstrated by WES analysis, and significantly increased mRNA of ALK, ROS1, MET, SPP1 and PI3K signaling pathway was identified by NanoString assay. The concordance between NanoString, IHC and FISH methodologies for detecting ALK fusion was 100%. Significant overexpression of SPP1 protein in ALK-positive lung cancer was confirmed by IHC compared to paired adjacent normal tissues and ALK-negative cancers. Thus we concluded that SPP1 overexpression is associated with poor outcomes for patients with ALK fusion lung cancer without receiving targeted therapy and PI3K/AKT/SPP1 pathway may become the promising targets in patients with aggressive lung cancer.


Theoretical Kinetic Isotope Effects in Establishing the Precise Biodegradation Mechanisms of Organic Pollutants.
Compound-specific isotope analysis (CSIA) for natural isotope ratios has been recognized as a promising tool to elucidate biodegradation pathways of organic pollutants by microbial enzymes by relating reported kinetic isotope effects (KIEs) to apparent KIEs (AKIEs) derived from bulk isotope fractionations (εbulk). However, for many environmental reactions, neither are the reference KIE ranges sufficiently narrow nor are the mechanisms elucidated to the point that rate-determining steps have been identified unequivocally. In this work, besides providing reference KIEs and rationalizing AKIEs, good relationships have been explained by DFT computations for diverse biodegradation pathways with known enzymatic models between the theoretical isotope fractionations (εbulk') from intrinsic KIEs on the rate-determining steps and the observed εbulk. (1) To confirm the mechanistic details of previously reported pathway-dependent CSIA, it includes isotope changes in MTBE biodegradation between hydroxylation by CYP450 and SN2 reaction by cobalamin-dependent methyltransferase, the regioselectivity of toluene biodegradation by CYP450, and the rate-determining step in toluene biodegradation by benzylsuccinate synthase. (2) To yield new fundamental insights into some unclear biodegradation pathways, it consists of the oxidative function of toluene dioxygenase in biodegradation of TCE, the epoxidation mode in biodegradation of TCE by toluene 4-monooxygenase, and the weighted average mechanism in biodegradation of cDCE by CYP450.


Performance of forty-one microbial source tracking methods: a twenty-seven lab evaluation study.
The last decade has seen development of numerous new microbial source tracking (MST) methodologies, but many of these have been tested in just a few laboratories with a limited number of fecal samples. This method evaluation study examined the specificity and sensitivity of 41 MST methodologies by analyzing data generated in 27 laboratories. MST methodologies that targeted human, cow, ruminant, dog, gull, pig, horse, and sheep were tested against sewage, septage, human, cow, dog, deer, pig, chicken, pigeon, gull, horse, and goose fecal samples. Each laboratory received 64 blind samples containing a single source (singletons) or two sources (doubletons), as well as diluted singleton samples to assess method sensitivity. Laboratories utilized their own protocols when performing the methods and data were deposited in a central database before samples were unblinded. Between one and seven laboratories tested each method. The most sensitive and specific assays, based on an analysis of presence/absence of each marker in target and non-target fecal samples, were HF183 endpoint and HF183SYBR (human), CF193 and Rum2Bac (ruminant), CowM2 and CowM3 (cow), BacCan (dog), Gull2SYBR and LeeSeaGull (gull), PF163 and pigmtDNA (pig), HoF597 (horse), PhyloChip (pig, horse, chicken, deer), Universal 16S TRFLP (deer), and Bacteroidales 16S TRFLP (pig, horse, chicken, deer); all had sensitivity and specificity higher than 80% in all or the majority of laboratories. When the abundance of MST markers in target and non-target fecal samples was examined, some assays that performed well in the binary analysis were found to not be sensitive enough as median concentrations fell below a minimum abundance criterion (set at 50 copies per colony forming units of enterococci) in target fecal samples. Similarly, some assays that cross-reacted with non-target fecal sources in the binary analysis were found to perform well in a quantitative analysis because the cross-reaction occurred at very low levels. Based on a quantitative analysis, the best performing methods were HF183Taqman and BacH (human), Rum2Bac and BacR (ruminant), LeeSeaGull (gull), and Pig2Bac (pig); no cow or dog-specific assay met the quantitative specificity and sensitivity criteria. Some of the best performing assays in the study were run by just one laboratory so further testing of assay portability is needed. While this study evaluated the marker performance in defined samples, further field testing as well as development of frameworks for fecal source allocation and risk assessment are needed.


Deuterated Ethanol as a Probe for Measuring Equilibrium Isotope Effects for Hydroxyl Exchange.
Equilibrium deuterium isotope effects for exchange of hydroxyl deuterons and protons among tert-butanol, phenol, ethanethiol, diethylamine, and ethanol were measured by using NMR and also calculated theoretically. Deuterated ethanol could be used as a probe for measuring equilibrium isotope effects (EIE) for hydroxyl exchange; tert-butanol, phenol, ethanethiol, diethylamine, and pyrrole were used as five representive examples. A procedure called the "one-atom isotope effect" was used to save time in the calculations.


Solution-Based Processing of Optoelectronically Active Indium Selenide.
Layered indium selenide (InSe) presents unique properties for high-performance electronic and optoelectronic device applications. However, efforts to process InSe using traditional liquid phase exfoliation methods based on surfactant-assisted aqueous dispersions or organic solvents with high boiling points compromise electronic properties due to residual surface contamination and chemical degradation. Here, these limitations are overcome by utilizing a surfactant-free, low boiling point, deoxygenated cosolvent system. The resulting InSe flakes and thin films possess minimal processing residues and are structurally and chemically pristine. When employed in photodetectors, individual InSe nanosheets exhibit a maximum photoresponsivity of ≈5 × 107 A W-1 , which is the highest value of any solution-processed monolithic semiconductor to date. Furthermore, the surfactant-free cosolvent system not only stabilizes InSe dispersions but is also amenable to the assembly of electronically percolating InSe flake arrays without posttreatment, which enables the realization of ultrahigh performance thin-film photodetectors. This surfactant-free, deoxygenated cosolvent approach can be generalized to other layered materials, thereby presenting additional opportunities for solution-processed thin-film electronic and optoelectronic technologies.


Transcutaneous ultrasound of the cervical esophagus in patients with esophageal carcinoma.
Transcutaneous ultrasound of the cervical esophagus was performed in 46 patients with esophageal carcinoma and in 35 controls. The former had 24 upper segmental lesions and 22 lower segmental lesions. The level of the sternoclavicular joint was used to divide the esophagus into the upper segmental (USE) and lower segmental esophagus (LSE). The anterior esophageal wall thickness and luminal dimensions were measured before and immediately after phonation. The mean wall thickness in the controls was 1.8 mm before phonation and 2.1 mm after phonation, with a significant difference (t test, P < 0.05). The mean wall thickness in the USE carcinoma group was 4.3 mm and 4.4 mm before and after phonation respectively. There was a significant difference between the controls and USE carcinoma groups (t test, P < 0.05). The cross sectional area, which was calculated as the product of anterio-posterior and lateral diameters, averaged 28 mm2 before phonation in the controls and increased to 44 mm2 after phonation (t test, P < 0.05). The mean cross sectional area in the USE carcinoma group was significantly smaller before phonation than that in the controls (t test, P < 0.05) and showed little change after phonation. No significant difference was found between LSE carcinoma and control groups. Transcutaneous ultrasound appears to be a promising non-invasive method of investigation for cervical esophageal carcinoma.


Mutant ubiquitin found in neurodegenerative disorders is a ubiquitin fusion degradation substrate that blocks proteasomal degradation.
Loss of neurons in neurodegenerative diseases is usually preceded by the accumulation of protein deposits that contain components of the ubiquitin/proteasome system. Affected neurons in Alzheimer's disease often accumulate UBB(+1), a mutant ubiquitin carrying a 19-amino acid C-terminal extension generated by a transcriptional dinucleotide deletion. Here we show that UBB(+1) is a potent inhibitor of ubiquitin-dependent proteolysis in neuronal cells, and that this inhibitory activity correlates with induction of cell cycle arrest. Surprisingly, UBB(+1) is recognized as a ubiquitin fusion degradation (UFD) proteasome substrate and ubiquitinated at Lys29 and Lys48. Full blockade of proteolysis requires both ubiquitination sites. Moreover, the inhibitory effect was enhanced by the introduction of multiple UFD signals. Our findings suggest that the inhibitory activity of UBB(+1) may be an important determinant of neurotoxicity and contribute to an environment that favors the accumulation of misfolded proteins.


Reproducibility of FCM DNA content from replicate paraffin block samples.
Fifty-five paraffin blocks of morphologically and clinically normal colon specimens were divided in half and the two halves treated as separate aliquots for determination of DNA content using propidium iodide staining and FCM analysis. Forty-five of the 55 samples showed a peak channel difference between the two aliquots from the same block of greater than 1 channel. Seven of the 55 specimens showed peak channel difference greater than or equal to 10 channels. Similar results were seen if the mean channel of the G0G1 peak was used in place of the peak channel, with 5 of the 55 specimens showing mean channel differences of greater than or equal to 10 channels. The seven samples with peak channel difference greater than or equal to 10 channels were reprocessed and five of the seven showed reduced peak channel difference on reanalysis. The mean peak channel difference of the 55 samples was 4.3 +/- 10.5 (mean +/- 2 S.D.) using the first analysis. These data suggest that caution should be used in interpreting ploidy of nuclei extracted from paraffin block material if the interpretation is based on comparing two aliquots from the same block, even if they are processed and analyzed in the same batch.


Systematic review and meta-analysis on the influence of thyroid dysfunction in early pregnancy on pregnancy outcomes under ultrasound guidance.
Thyroid dysfunction during pregnancy has a certain impact on pregnancy outcomes and neonatal growth, but there is no systematic evaluation of the influence of thyroid dysfunction during early pregnancy under ultrasound guidance on pregnancy outcomes. PubMed, Web of Science, Springer, and Science Direct databases were used to screen clinical studies on the effect of thyroid dysfunction during pregnancy on pregnancy outcomes from January 2010 to June 2021. Meta-analysis of data was conducted using RevMan 5.3 software. Differences of indicators were compared between the normal and abnormal thyroid function groups, including the ratio of primiparas, anemia, intrauterine growth restriction, perinatal fetal death, preterm delivery, fetal distress syndrome, cesarean section, preeclampsia, placental abruption, postpartum hemorrhage, and neonatal complications. Heterogeneity of results was assessed by chi-square test and I2 test in RevMan5.3. A total of 788,867 pregnant women were included in 13 studies. Cochrane scores were grade B or above, and Jadad scale scores were higher than 3. Anemia [odds ratio (OR) =0.82, 95% confidence interval (CI): 0.70-0.96, Z=2.48, P=0.01], premature birth (OR =0.56, 95% CI: 0.36-0.86, Z=2.66, P=0.008), fetal distress syndrome (OR =0.76, 95% CI: 0.68-0.85, Z=4.74, P<0.00001), Apgar score <7 (OR =0.52, 95% CI: 0.34-0.80, Z=2.97, P=0.003), preeclampsia (OR =0.65, 95% CI: 0.48-0.87, Z=2.91, P=0.004), placental abruption (OR =0.27, 95% CI: 0.19-0.38, Z=7.31, P<0.00001), and the rate of postpartum hemorrhage (OR =0.62, 95% CI: 0.42-0.92, Z=2.38, P=0.02) were dramatically higher in the abnormal thyroid function group compared with the normal group. Few studies were included on the effect of thyroid dysfunction on abortion, and further validation is needed. Thyroid dysfunction was proven to be associated with a variety of adverse pregnancy outcomes.


Brain keratan sulfate and glial scar formation.
In response to injury to the central nervous system (CNS), reactive astrocytes appear and accumulate in the wounded area, leading to glial scar formation. Glial scar is the physical barrier to axonal regeneration of injured neurons. Chondroitin sulfate proteoglycans are inhibitory to axon outgrowth and are upregulated in reactive astrocytes upon CNS injury. It is known that keratan sulfate proteoglycans (KSPGs) are also augmented after CNS injury and act as inhibitory cues. We give a brief overview of CNS injury and cover our recent data regarding the relationship between glial scar formation and KS. KS expression in the developing brain is detectable with 5D4, a KS-specific monoclonal antibody. These 5D4 immunoreactivities are eliminated in mice deficient in N-acetylglucosamine 6-O-sulfotransferase-1. In adult mice, brain injury apparently upregulates mRNA expression of N-acetylglucosamine 6-O-sulfotransferase-1 as well as 5D4-reactive KS in the wounded area. Intriguingly, the expression of 5D4-reactive KS and reactive astrocyte accumulation in the wounded area are dramatically diminished in the sulfotransferase-deficient mice. Consequently, the deficient mice exhibit a marked reduction in scar formation and enhancement of neuronal regeneration after brain injury. Thus, N-acetylglucosamine 6-O-sulfotransferase-1 plays indispensable roles in brain KS biosynthesis and glial scar formation after brain injury.


Hybrid Physical Gels from Polymers and Self-Assembled Systems: A Novel Path for Making Functional Materials.
In recent years, the synthesis of novel organic molecules that spontaneously self-assemble into a large variety of molecular architecture, particularly the formation of organogels, has yielded new opportunities in the preparation of functional materials. Here, we present an original preparation path of such materials through the fabrication of hybrid gels of these molecules with covalent polymers. Three types of systems are described: (i) intermingled gels where a polymer gel and an organogel pervade one another; (ii) encapsulation of self-assembled filaments in polymer fibrils, which provides a system with unusual magnetic properties; (iii) the reverse situation in which self-assembled nanotubes sheathe polymer fibrils. Two covalent polymers are considered: a neutral polymer, specifically stereoregular polystyrene (isotactic or syndiotactic), and a semi-conducting polymer, P3BT. In the latter case, semi-conducting nanowires are obtained.


Hyperhomocysteinemia as an Early Predictor of Erectile Dysfunction: International Index of Erectile Function (IIEF) and Penile Doppler Ultrasound Correlation With Plasma Levels of Homocysteine.
Erectile dysfunction (ED) is inability to achieve and maintain an erection to permit satisfactory sexual activity. Homocysteine (Hcys) is a sulfur-containing amino acid synthesized from the essential amino acid methionine. Experimental models have elucidated the role of hyperhomocysteinemia (HHcys) as a strong and independent predictor for atherosclerosis progression and impaired cavernosal perfusion. The aim of this study is to investigate the serum levels of Hcys in our cohort of patients with ED, to compare these values with these of control population and to examine Hcys as a predictive marker for those patients who are beginning to complain mild-moderate ED. A total of 431 patients were enrolled in the study. The whole cohort was asked to complete the International Index of Erectile Function (IIEF) questionnaire. The study population was divided in 3 main groups: Group A: 145 patients with no ED serving as a control group; Group B: 145 patients with mild or mild-moderate ED; Group C: 141 patients with moderate or severe ED. Each participant underwent blood analysis. All patients underwent baseline and dynamic penile Doppler ultrasonography. We found in our cohort mean Hcys plasma concentrations significantly higher than the cut-off point in both groups B and C (18.6 ± 4.7 and 28.38 ± 7.8, respectively). Mean IIEF score was 27.9 ± 1.39, 19.5 ± 2.6, and 11.1 ± 2.5 for groups A, B, and C, respectively (P < 0.0001). In the penile Doppler ultrasonography studies, a high significant inverse correlation was detected between the mean values of the 10th minute's peak-systolic velocity (PSV) and Hcys levels for the groups B and C. This establishes a dose-dependent association between Hcys and ED. Furthermore, we showed that Hcys was an earlier predictor of ED than Doppler studies, as the Hcys increase was present in patients with mild ED even before abnormal Doppler values.


Nanostructured protective carbon layer on the jeweller's metallic material--in vitro verification.
In this paper the surface condition of jeweller's metallic material covered by nanostructured carbon layer after the in vitro model test was investigated. The phenomenon of body modification has made that the most popular and the most often applied is jewellery made of metals like stainless steel, titanium and its alloys. However these kinds of metals are not safe and can cause health complications. Biocompatible carbon coatings were used in order to exclude the side effects of metallic jewellery use. Body modification trend is popular among youth to a large degree--they who are always looking for the cheap decorations. Taking this fact into consideration the jewellery made of stainless steel, which is used the most often was exposed to modification by carbon coating. Two methods of plasma activated chemical vapour deposition (PA CVD) were used for the carbon coatings production purpose: radio frequency (RF) and microwave/radio frequency (MW/RF). In order to point the best parameters of these coatings manufacture processes, examinations of physiochemical properties and analysis of surface topography (optical microscopy, scanning electron microscopy with X-ray microanalysis) were made. So modified jewellery was investigated in in vitro model as regards resistance to the biological environment and coatings stability as well. The conducted examinations showed that modifications of decorations made of 316L stainless steel by carbon coatings allow for the creation of biocompatible, non-toxic jewellery. Tests showed that human fibroblasts grow and keep vitality in a presence of jewellery covered by carbon coating, whereas die very fast sticking the non-modified surfaces of decorations. The carbon coating constitutes a barrier which isolates jewellery from the surrounding environment and simultaneously contacts with it in a safe way.


The assembly of Vif ubiquitin E3 ligase for APOBEC3 degradation.
APOBEC3G is a cellular antiviral protein that restricts retroviral infection. In non-permissive cells infected by Vif-deficient HIV-1, the protein mediates the hypermutation of viral DNA through the enzymatic activity of cytidine deaminase. To counteract the antiviral activity of APOBEC3G, an accessory protein of HIV-1, Vif, forms ubiquitin E3 ligase through assembly with CUL5-RBX2, ELOB-ELOC and CBFβ. Subsequently, Vif recruits APOBEC3G to the complex as a substrate adaptor of ubiquitin E3 ligase and induces poly-ubiquitination of APOBEC3G for its proteasomal degradation (Fig. 1). This review briefly summarizes current understanding of protein-protein interaction between Vif and host factors required for APOBEC3 degradation, based on high resolution structures of APOBEC3 proteins and Vif-CUL5NTD-ELOBC-CBFβ complex.


Virus-Like Particles as an Immunogenic Platform for Cancer Vaccines.
Virus-like particles (VLP) spontaneously assemble from viral structural proteins. They are naturally biocompatible and non-infectious. VLP can serve as a platform for many potential vaccine epitopes, display them in a dense repeating array, and elicit antibodies against non-immunogenic substances, including tumor-associated self-antigens. Genetic or chemical conjugation facilitates the multivalent display of a homologous or heterologous epitope. Most VLP range in diameter from 25 to 100 nm and, in most cases, drain freely into the lymphatic vessels and induce antibodies with high titers and affinity without the need for additional adjuvants. VLP administration can be performed using different strategies, regimens, and doses to improve the immunogenicity of the antigen they expose on their surface. This article summarizes the features of VLP and presents them as a relevant platform technology to address not only infectious diseases but also chronic diseases and cancer.


α-Ketoglutarate Accelerates the Initial Differentiation of Primed Human Pluripotent Stem Cells.
Pluripotent stem cells (PSCs) can self-renew or differentiate from naive or more differentiated, primed, pluripotent states established by specific culture conditions. Increased intracellular α-ketoglutarate (αKG) was shown to favor self-renewal in naive mouse embryonic stem cells (mESCs). The effect of αKG or αKG/succinate levels on differentiation from primed human PSCs (hPSCs) or mouse epiblast stem cells (EpiSCs) remains unknown. We examined primed hPSCs and EpiSCs and show that increased αKG or αKG-to-succinate ratios accelerate, and elevated succinate levels delay, primed PSC differentiation. αKG has been shown to inhibit the mitochondrial ATP synthase and to regulate epigenome-modifying dioxygenase enzymes. Mitochondrial uncoupling did not impede αKG-accelerated primed PSC differentiation. Instead, αKG induced, and succinate impaired, global histone and DNA demethylation in primed PSCs. The data support αKG promotion of self-renewal or differentiation depending on the pluripotent state.


Complement receptor lymphocytes. Analysis of immunoglobin on their surface and further evidence of heterogeneity.
Mouse complement receptor lymphocytes (CRL) were detected by a rosetting method. The existence of an immunoglobulin class or subclass on the central rosetting cell wasstudied by immunofluorescence using rabbit antisera specific for mouse IgM, IgG1, IgG2a, IgG2b and IgA. Combining immunofluorescence for each immunoglobulin and for T cells with cytoxic removal of T cells, CRL were demonstrated to include immunoglobulin-bearing cells of all the classes and subclasses tested (IgM being the main one), a 'null' cell subpopulation, and some T cells. A scheme describingthe various nature of CRL is discussed and correlated with possible functions.


The mood variation in mothers of preterm infants in Kangaroo mother care and conventional incubator care.
Preterm babies are more prone to develop disorders and so require immediate intensive care. In the conventional neonatal intensive care, the baby is kept in the incubator, separated from the mother. Some actions have been taken in order to make this mother-child separation less traumatic. One of these actions is the Kangaroo mother care (KMC) characterized by skin-to-skin contact between a mother and her newborn. The objective of this study was to compare the mood variation of mothers enrolled in the KMC program to those in the conventional incubator care. In one general hospital in Sao Paulo, Brazil, 90 mothers were evaluated before and after contact with the baby in the Neonatal Intensive Care Unit. The participants were divided into three groups: 30 mothers of term newborns (TG), 30 mothers of preterm infants included in KMC program (PGK) and 30 preterms with incubator placement (PGI). The Brazilian version of the Visual Analogue Mood Scale (VAMS) was used for the assessment before and after the infant's visit. Results showed that TG mothers reported fewer occurrences of depressive states than PGK and PGI mothers. A significant mood variation was observed for PGK and PGI after the infant's visit. PGK mothers reported feeling calmer, stronger, well-coordinated, energetic, contented, tranquil, quick-witted, relaxed, proficient, happy, friendly and clear-headed. The only variation showed by PGI mothers was an increase in feeling clumsy. This study shows a positive effect of the KMC on the mood variation of preterm mothers and points to the need of a more humane experience during the incubator care.


Are separate black and white MMPI norms needed? An IQ-controlled comparison of accused murderers.
Investigated racial differences in MMPI responding by comparing samples of black and white males charged with murder (N = 160). Mancova was used to control statistically for the effects of intelligence on racial differences. Prior to the use of Mancova blacks had significantly higher scores on F and MA. When the effects of intelligence were controlled F and MA were no longer significantly different for blacks and whites. However, with black and white SS equated on IQ, significant differences emerged on the K and SI scales. These results indicate that construction of separate black and white norms for violent offenders is premature. More research is needed on variables that affect individual differences on the MMPI.


Nonviral cytokine gene therapy on an orthotopic bladder cancer model.
The purpose is to assess cytokine gene transfection in tumor cells and its therapeutic efficacy in an orthotopic mouse bladder cancer model after liposome-mediated gene transfer. A total of 1 x 10(5) MB49 cells was instilled into the bladder of C57BL/6 mice after electrocautery to establish the tumor model. The plasmids were constructed by inserting the coding sequences for murine IFN-alpha1 and granulocyte macrophage colony-stimulating factor into a plasmid vector pBudCE4.1. Transient transfection was performed using a cationic lipid N-[1-(2,3-dioleoyloxyl)propyl]-N,N,N-trimethylammoniummethyl sulfate and methyl-beta-cyclodextrin-solubilized cholesterol. The in vitro expression of cytokines was checked by ELISA. The expression of the transgene in situ was confirmed by immunohistochemistry and 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining. Mice bearing orthotopic tumors were treated with plasmid DNA/liposome complex by intravesical instillation twice a week for 3 weeks. Superficial bladder tumors were established by intravesical instillation of MB49 into cauterized bladders. The expression level of cytokines in transfected cell lines was increased significantly. In situ gene transfer to bladder tumors was accomplished via intravesical instillation of plasmid DNA/N-[1-(2,3-dioleoyloxyl)propyl]-N,N,N-trimethylammoniummethyl sulfate/methyl-beta-cyclodextrin-solubilized cholesterol after a single 2 h in situ transfection. The tumor incidence in the treatment groups was dramatically decreased from 76.9% in the control group to 15.4-30.8% in the treatment groups. We demonstrated in the orthotopic mouse bladder cancer model that successful inhibition of tumor cell growth could be obtained with cytokine gene therapy. The results suggest that our liposome transfection system appears to be a promising method for gene therapy of bladder cancer in vivo.


Single-cell transcriptomes reveal the heterogeneity and microenvironment of vestibular schwannoma.
Vestibular schwannoma (VS) is the most common benign tumor in the cerebellopontine angle and internal auditory canal. Illustrating the heterogeneous cellular components of VS could provide insights into its various growth patterns. Single-cell RNA sequencing was used to profile transcriptomes from 7 VS samples and 2 normal nerves. Multiplex immunofluorescence was employed to verify the dataset results. Bulk RNA sequencing was conducted on 5 normal nerves and 44 VS samples to generate a prediction model for VS growth. A total of 83,611 cells were annotated as 14 distinct cell types. We uncovered the heterogeneity in distinct VS tumors. A subset of Schwann cells with the VEGFA biomarker was significantly associated with fast VS growth through mRNA catabolism and peptide biosynthesis. The macrophages in the normal nerves were largely of the M2 phenotype, while no significant differences in the proportions of M1 and M2 macrophages were found between slow-growing and fast-growing VS. The normal spatial distribution of fibroblasts and vascular cells was destroyed in VS. The communications between Schwann cells and vascular cells were strengthened in VS compared with those in the normal nerve. Three cell clusters were significantly associated with fast VS growth and could refine the growth classification in bulk RNA. Our findings offer novel insights into the VS microenvironment at the single-cell level. It may enhance our understanding of the different clinical phenotypes of VS and help predict growth characteristics. Molecular subtypes should be included in the treatment considerations.


A comparative ultrastructural and behavioral study of the antennal sensory sensilla of the parasitoid Cardiochiles nigriceps (hymenoptera:Braconidae).
Scanning and transmission electron microscopy studies were conducted on the antennal sensory sensilla of the hymenopteran parasitoid, Cardiochiles nigriceps Viereck, of the family Braconidae. Distinct morphological differences were found between the chemoreceptors of the male and female. Curved, non-fluted, thin-walled sensilla were found to be very abundant on the male and restricted in location and number on the female. Trichoid, placoid and fluted basiconic sensilla were numerous on the antennal flagella of both sexes. Smooth basiconic sensilla were restricted in number to one per flagellar segment in both sexes. Behavioral data suggest that bent-tipped, thick-walled sensilla unique to the female are involved in detecting a chemical(s) emitted from the host, Heliothis virescens (Fab.).


Prevalence of high blood pressure and its associated factors among students in Shenyang, China: A cross-sectional study.
There is growing evidence that the prevalence of high blood pressure is increasing, and it may have serious consequences. However, research on the prevalence and influencing factors of high blood pressure among primary and secondary school students is still relatively scarce. This study aims to investigate the prevalence and influencing factors of high blood pressure among primary and secondary school students in Shenyang, in order to provide scientific evidence for the prevention and management of this disease. From April to May 2020, 4892 students aged 7 to 17 years were selected as the survey subjects, and on-site physical measurements and questionnaire surveys were conducted. The prevalence of high blood pressure was described. Restricted cubic spline was used to analyze the dose-response relationship between sleep duration, BMI and the risk of high blood pressure. Logistic regression was used to analyze the risk factors. Multiplicative and additive models were used to analyze the interaction between sleep duration and BMI. The results showed that the overall prevalence of high blood pressure among students aged 7 to 17 years in Shenyang was 9.9%, with a higher prevalence in females than males (12.1% vs 7.9%) and in urban areas than suburban areas (11.8% vs 7.7%). The prevalence was lowest in students with normal weight (8.3%) and highest in those who were obese (12.5%). The prevalence fluctuated to some extent among different age groups, but overall, it increased with age, with the lowest prevalence in primary school students (7.0%), 11.4% in mild school students, and the highest prevalence of 14.3% in high school students. Multivariable analysis showed that the risk of high blood pressure in female students was 1.90 times higher than that in male students (95% CI: 1.54-2.35), and the risk in suburban areas was 0.65 times lower than that in urban areas (95% CI: 0.52-0.81). Students with a BMI ≥ 21 kg/m2 had a 1.58 times higher risk than those with a BMI < 21 kg/m2(95% CI: 1.28-1.96), while those with a sleep time ≥ 8 hours had a 0.80 times lower risk than those with a sleep time < 8 hours (95% CI: 0.65-0.99). Exercise can significantly reduce the risk of high blood pressure, while using electronic devices for more than 0.5 hours significantly increases the risk of high blood pressure. BMI and sleep duration have no interaction effect on the risk of high blood pressure. To reduce the prevalence of high blood pressure, students should reduce the use of electronic devices, ensure adequate exercise, maintain a reasonable weight, and ensure sufficient sleep.


Binding and antilipolytic action of insulin in isolated adipocytes from cortisol-treated rats.
The effects of an in vivo cortisol-treatment to rats (2 X 2 mg/rat/day, for one week) on insulin plasma levels, insulin binding and antilipolytic activity in rat adipose tissue were investigated. Hyperinsulinemia together with an increase in insulin degradation in the serum of cortisol-treated rats were observed. The adipocytes from cortisol-treated animals showed a statistically significant decrease in insulin binding but no change in receptor numbers [cortisol-treated 103,000 +/- 8,000 (n = 8) receptors/cell and controls 138,000 +/- 15,000 (n = 16) receptors/cell], together with unchanged receptor affinity [ED50: cortisol-treated 3 X 10(-9) M and controls 3.2 X 10(-9) M], and a decreased sensitivity to the antilipolytic effect of insulin. The evidence presented for pre-receptor, receptor and post-receptor insulin defects on the action of cortisol in isolated rat adipocytes could represent a coordinated mechanism by which cortisol exerts "insulin resistance" in this tissue.


Intake of dietary phytoestrogen and indices of antioxidant and bone metabolism of pre- and post-menopausal Korean women.
A group of 101 women, aged 40-65 years consisted of 48 premenopausal subjects and 53 postmenopausal ones living in Daegu and Gyeongbuk area in Korea were evaluated with their general characteristics, lifestyle factors, nutrient and phytoestrogen intakes, blood and urinary indices concerning antioxidant status and bone metabolism. Body mass index (BMI), waist hip ratio (WHR) and systolic blood pressure (SBP) of the postmenopausal women were significantly higher (23.8, 0.86, and 126.9 mmHg, respectively) than those of the premenopausal women (22.6, 0.82, and 115.9 mmHg; respectively). Nutrient intakes of the postmenopausal and premenopausal groups were not different except lower fat intake and higher dietary fiber and iron intakes in the postmenopausal group. Daily total phytoestrogen intake was significantly higher in the postmenopausal group (48.54 mg) than the premenopausal (31.41 mg) and was resulted mostly from higher intakes of daidzein and genistein from soy and soy products (45.42 mg vs 28.91 mg). Serum genistein level and excretion of enterolactone, major lignan metabolite, were not very different between the two groups. Serum retinal and alpha- tocopherol levels were higher in the postmenopausal group but TBARS levels were not different between the two groups. Serum osteocalcin (7.18 ng/mL) and urinary deoxypyridinoline (7.15 nmol/mmol creatinine), in the postmenopausal group were significantly higher than those in the premenopausal group (4.80 ng/mL, 5.95 nmol/mmol creatinine). Urinary excretion of enterolactone was positively correlated with serum osetocalcin in premenopausal women and serum genistein negatively correlated with the urinary DPD in postmenopausal women. Dietary phytoestrogen intake was negatively correlated with serum level of TBARS in all subjects. It is concluded that the effect of total phytoestrogen intake is beneficial on body antioxidant status in all middle-aged women regardless of menopause but the effect on bone metabolism appears different by the type of the phytoestrogen and the menopausal state.