Alpha 2-adrenergic agonists induce basic fibroblast growth factor expression in photoreceptors in vivo and ameliorate light damage.
We observed an induction of basic fibroblast growth factor (bFGF) mRNA in the rat retina after systemic administration of the alpha 2-adrenergic agonists xylazine and clonidine. A single injection of xylazine or clonidine transiently increased bFGF mRNA. Preinjection of yohimbine, an alpha 2-adrenergic antagonist, completely inhibited this increase. Higher dosage of yohimbine inhibited the baseline expression of bFGF. Of particular interest is the finding that the induced bFGF expression occurred almost exclusively in the inner segment region of photoreceptors. No increase in bFGF mRNA was found in the brain after either xylazine or clonidine injection. Xylazine or clonidine given systemically before and during constant light exposure also reduces photoreceptor degeneration in albino rats. These results indicate that regulation of bFGF expression in photoreceptors is unique in the CNS and suggest that endogenous bFGF promotes photoreceptor survival.


Neonatal seizures in Nigerian infants.
Nigerian newborns presenting with convulsion in University of Calabar Teaching Hospital, Calabar during the period January 1989 to December 1990 were prospectively studied to determine the aetiology and pattern of their seizures. There were 60 patients representing 4% of admissions into the Newborn Unit during the period. Birth asphyxia, infections and hypoglycaemia were the important identifiable aetiological factors which operated either singly (48% of cases) or in concert (in another 48%) of the infants. Detectable infections included meningitis and septicaemia caused predominantly by coliforms and Staphylococcus aureus. Hypocalcaemia and electrolyte imbalance did not feature. There was an unusually high prevalence (63% of cases) of the generalised type of seizures probably due to the high frequency of mixed aetiology. The mortality rate of 50% encountered appears to be related to the underlying aetiology and prematurity. Detectable caused of neonatal seizures in our environment appear to be potentially preventable by improved obstetric and neonatal care. There is dire need also to provide modern facilities for investigating newborn seizures in order to improve upon the diagnostic yield.


Case report: Mitral valve replacement for Libman-Sacks endocarditis and cerebral embolism of primary antiphospholipid syndrome.
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by recurrent arteriovenous thrombosis and/or morbid pregnancy. Valve involvement is the most common cardiac manifestation of APS, with lesions characterized by valve thickening and vegetations known as Libman-Sacks endocarditis (LSE). This report discussed a rare case of a 26-year-old young woman diagnosed with primary APS with multiple cerebral infarctions and right middle cerebral artery occlusion that occured 3 years ago. During the investigation, transthoracic echocardiography (TTE) revealed vegetations on both leaflets of the mitral valve with mild to moderate mitral regurgitation. One year following corticosteroid and anticoagulant treatment, mitral valve fibrosis and moderate to severe regurgitation were noted, after which mitral mechanical valve replacement was finally performed. Accordingly, this report suggests that LSE occurrence should be alerted during the examination of APS patients especially in those with cerebrovascular disease. Furthermore, establishing an early diagnosis and conducting close follow-ups are necessary for its timely intervention and treatment.


Microcomputer-based multiplexer for performing depth profiling with an Auger electron spectrometer.
A microcomputer-based instrument for the automated profiling of samples with an Auger electron spectrometer and Ion Gun is described. The instrument records the changing heights of spectral peaks as it controls spectrometer scanning over predefined windows. Interactive front panel controls are used to set up a run and control profiling operations. The generated data is stored on a magnetic disk for later analysis and plotting. Implementation of the device using an LSI-11 microcomputer and interfacing hardware is detailed, along with the characteristics of the fortran iv driving software. An exploration of future capabilities and applications of the multiplexer is also given.


HF dimer in small helium clusters: interchange-tunneling dynamics in a quantum environment.
We present diffusion quantum Monte Carlo calculations of the interchange tunneling splitting of (4)He(n)(HF)(2) clusters, n = 1-10. The tunneling splitting decreases rapidly for n = 1-4 clusters, and much more slowly for n>4. The decrease calculated for (4)He(n)(HF)(2) represents 74% of the reduction in the tunneling splitting measured recently for HF dimer in nanodroplets of more than 2000 He atoms. The first four He atoms quench the interchange tunneling very efficiently by virtue of occupying the equatorial ring which encircles the C(2h) transition state of the tunneling pathway.


Apoptosis-inducing factor (AIF) nuclear translocation mediated caspase-independent mechanism involves in X-ray-induced MCF-7 cell death.
Breast cancer is the most common cancer among women and radiotherapy is a conventional therapy following surgery. Previous studies have demonstrated that except the caspase-dependent pathway, caspase-independent pathway is also involved in the cell death responding to irradiation, despite the unclear mechanism. The purpose of the present study was to observe the role of apoptosis-inducing factor (AIF), the first identified caspase-independent molecule, in X-ray-induced breast cancer cell (MCF-7) cell death. In this study, WST-1 assay, DAPI nuclear staining and clonogenic survival assay were used to test the cell response to different treatments; Western blot was used to detect the protein expression; RT-PCR and plasmid transfection were used to observe the role of AIF. X-ray-induced AIF transferred from the mitochondrion to the nucleus. Inhibition of AIF expression reduced X-ray-induced MCF-7 cell death. Further, AIF nuclear translocation is in a caspase-independent manner in this process, but not caspase-dependent manner. The present study revealed that AIF nuclear translocation proceeded in X-ray-induced MCF-7 cell death in a caspase-independent manner.


Noncanonical genomic imprinting in the monoamine system determines naturalistic foraging and brain-adrenal axis functions.
Noncanonical genomic imprinting can cause biased expression of one parental allele in a tissue; however, the functional relevance of such biases is unclear. To investigate ethological roles for noncanonical imprinting in dopa decarboxylase (Ddc) and tyrosine hydroxylase (Th), we use machine learning to decompose naturalistic foraging in maternal and paternal allele mutant heterozygous mice. We uncover distinct roles for the maternal versus paternal alleles on foraging, where maternal alleles affect sons while daughters are under paternal allelic control. Each parental allele controls specific action sequences reflecting decisions in naive or familiar contexts. The maternal Ddc allele is preferentially expressed in subsets of hypothalamic GABAergic neurons, while the paternal allele predominates in subsets of adrenal cells. Each Ddc allele affects distinct molecular and endocrine components of the brain-adrenal axis. Thus, monoaminergic noncanonical imprinting has ethological roles in foraging and endocrine functions and operates by affecting discrete subsets of cells.


Generation of clean iron nanocrystals on an ultra-thin SiO(x) film on Si(001).
Upon exposure to Fe(CO)(5), the formation of pure cubic Fe nanocrystals with dimensions up to ~75 nm is reported on ultra-thin SiO(x) films (thickness ≈ 0.5 nm) on Si(001), which have been prepared in situ under UHV conditions. The active centers for initial decomposition of Fe(CO)(5) resulting in the growth of the Fe clusters are proposed to be SiO sites. After nucleation at these sites, further crystal growth is observed due to autocatalytic dissociation of Fe(CO)(5) at room temperature. The density of the Fe clusters can be increased by irradiating the surface with a focused electron beam (15 keV) prior to gas exposure. The formation of the active SiO sites upon electron irradiation is attributed to oxygen desorption via the Knotek-Feibelman mechanism.


Percutaneous Balloon Mitral Valvuloplasty During Antenatal Care and Apgar Score: The ANC-Valve Study.
The present study aimed to evaluate maternal and fetal outcomes in patients who underwent percutaneous balloon mitral valvuloplasty (PBMV) during antenatal care. Analysis of 117 pregnant women who underwent PBMV for rheumatic mitral stenosis. Demographic, clinical, echocardiographic, hemodynamic, and Doppler examinations were performed. The pregnant women were stratified according to New York Heart Association classification. Apgar scores were recorded at 1, 5, and 10 minutes to assess the neonatal outcomes. In our study cohort, 74.36% underwent PBMV during their second trimester, at gestational age of 22.49 ± 5.82. Term birth, mode of delivery, birth weight, and Apgar score at 5 minutes were significantly associated with pregnancy and neonatal outcomes. Mitral valve area, mitral valve gradient, and pulmonary artery systolic pressure were significantly improved (P<.001) after PBMV. Pulmonary edema, medical termination of pregnancy, hypothyroidism, hepatitis B infection, pneumonia, and postprocedural delivery, as well as postprocedure severe mitral regurgitation requiring surgery in 2 patients, were the few complications observed. Mean fluoroscopy time was 4 minutes, 50 seconds, with 100% success rate. No maternal mortality was observed. PBMV is a safe and effective intervention for mitral stenosis in pregnant women, with favorable maternal and short-term neonatal outcomes. PBMV offers excellent results in terms of symptomatic relief, hemodynamic improvement, and 100% success rate. Hence, it could be regarded as a preferred choice of intervention in managing symptomatic moderate to severe rheumatic mitral stenosis in pregnant women.


Theory of Mind as a potential trait marker of schizophrenia: a family study.
Although there is some evidence that Theory of Mind (ToM) deficits may be trait markers of schizophrenia it is not clear yet if ToM deficits are primary deficits, that is, to be independent of deficits in general intellectual abilities and executive function. The aim was to examine if ToM deficits may be trait markers of the illness and the effect of cognitive inhibition, general intellectual abilities and depression on ToM abilities of patients with schizophrenia and their unaffected parents. We assessed ToM abilities (first-order and second-order ToM stories, The Revised Eyes Test), cognitive inhibition (Stroop Task), general intellectual ability (Standard Progressive Matrices Test Plus) in patients with schizophrenia (N=21) and their unaffected fathers (N=21) and mothers (N=21) in comparison with healthy control families (healthy control males, N=21, healthy control fathers, N=21, healthy control mothers, N=21) Patients showed deficits in first-order ToM tasks but some of these deficits were mediated by general intellectual abilities. Impairments in cognitive inhibition mediated only patients' performance in The Revised Eyes Test. Patients showed deficits in second-order ToM stories independently of deficits in general intellectual abilities and cognitive inhibition. Unaffected parents did not show deficits in first-order ToM tasks, whereas they showed deficits in second-order ToM stories. However, the deficits that unaffected parents showed in second-order ToM stories were mediated by their deficits in general intellectual abilities, and there was an effect of remitted depression on the unaffected mothers' performance. The results suggest that intact neurocognitive and general intellectual abilities are necessary in order patients and their unaffected parents to pass successfully ToM tasks. Patients and their unaffected parents show ToM deficits but these deficits are not similar. Patients show ToM deficits but these deficits seem to be a component of the pathophysiology of the illness (e.g., deficits in executive function, general intellectual abilities).


Reduced expression of PDCD5 is associated with high-grade astrocytic gliomas.
Programmed cell death 5 (PDCD5) is a novel apoptosis-promoting protein. Recently, a decreased expression of PDCD5 has been found in several types of human tumors. However, the expression level of PDCD5 in human gliomas has not been investigated. In the present study, we examined the expression of PDCD5 in 88 human glioma samples at both mRNA and protein levels by RT-PCR, Western blotting and immunohistochemistry. We found that 53.3% (16/30) of the glioma samples had a reduced expression of PDCD5 mRNA and 70.5% (62/88) had a reduced expression of the PDCD5 protein as compared to normal brain tissue. Furthermore, we studied the correlation of the expression level of PDCD5 with the clinicopathological grade and survival of patients with astrocytomas. Although longitudinal studies of a cohort of patients with astrocytoma revealed that PDCD5 expression was not able to predict clinical outcome (p>0.05), a decreased expression of PDCD5 correlated significantly with high-grade astrocytomas (p<0.001). In conclusion, our data suggest that reduced PDCD5 expression may contribute to the pathogenesis of human gliomas.


Effect of dietary full-fat flax seed with and without antioxidant on the fatty acid composition of major lipid classes of chicken meats.
Male broiler chicks (Hubbard x Hubbard) were raised to 6 wk on one of five test diets: corn-soybean meal control diet and 15% full-fat flax seed (FFS) with and without the antioxidants mixed tocopherol (T), canthaxanthin (C), or both (FFS, FFS + T, FFS + C, FFS + T + C). The effects of the antioxidants on broiler performance, carcass yield, and fatty acid composition of the white and dark meat lipid were investigated. Particular attention was paid to the n-3 fatty acid composition of triglyceride, phosphatidyl ethanolamine, and phosphatidyl choline fractions. The antioxidants influenced neither broiler performance nor yield. The birds did not utilize the experimental diets as efficiently as the corn-soybean meal diet. The fatty acid compositions of white and dark meat lipids of broilers were influenced by dietary fatty acids, but to different extents among the lipid fractions. Fatty acids with 20 or more carbon atoms were moderately distributed in the phosphatidyl choline fraction as compared with the triglyceride and phosphatidyl ethanolamine fractions. The presence or absence of antioxidants influenced the fatty acid composition and distribution in the phosphatidyl ethanolamine fraction of white meat. The white meat from birds fed FFS + T, FSS + C, and FFS + T + C diets had elevated levels of C18:3n3, C20:5n3, C22:5n3, and C22:6n3 and reduced levels of total saturates and n-6:n-3 as opposed to the FFS and corn-soybean meal groups. From a nutritional standpoint, the lower n-6:n-3 ratio, observed from birds fed the FFS diet seemed to be more desirable.


Policy issues related to prospective payment for pediatric hospitalization.
Children's hospitals have been excluded from the Medicare prospective payment system (PPS) because of concerns over the applicability of the DRG case-mix system and PPS payment weights to pediatric hospitalization. Nevertheless, DRG-based payment systems are being adopted by State Medicaid agencies and private third-party payers, and the Health Care Financing Administration has been mandated to report to Congress on the feasibility of including children's hospitals in the Federal PPS. This article summarizes policy research on this issue and discusses options in the design of prospective payment systems for pediatric hospitalization.


Implications of increased intercellular variability of lipofuscin content with age in dentate gyrus granule cells in the mouse.
The purpose of this study was to further characterize lipofuscin (LF) accumulation with aging in brain cells, with a specific focus on the amount of intercellular variability of lipofuscin content within an apparently a homogenous population of dentate gyrus granule cells in the hippocampus of mice, as a function of age and caloric restriction (CR). Three age groups of CR and control mice including groups at maximum lifespan were studied. This study demonstrated that the intercellular variability of lipofuscin content was significantly greater in older mice and was significantly less in mice calorically restricted. Increased variability of metabolic function among cells with age, as measured by increased intercellular variability of lipofuscin content, may represent a definitive mechanism underlying the overall decreased efficiency of tissue and organ functioning that occurs with age. That this is so, is supported by the fact that CR, which has been shown to maintain the "youthful" state of many physiological functions, has been shown in this study to maintain the "youthful" state of low intercellular variability of lipofuscin content within a population of cells. LF accumulation may be a marker for the intrusion of entropy into cell metabolism.


Perceptions of the first family physicians to adopt advanced access in the province of Quebec, Canada.
In Quebec, several primary care physicians have made the transition to the advanced access model to address the crisis of limited access to primary care. The objectives are to describe the implementation of the advanced access model, as perceived by the first family physicians; to analyze the factors influencing the implementation of its principles; and to document the physicians' perceptions of its effects on their practice, colleagues and patients. Qualitative methods were used to explore, through semi-structured interviews, the experiences of 21 family physicians who had made the transition to advanced access. Of the 21 physicians, 16 succeeded in adopting all five advanced access principles to varying degrees. Core implementation issues revolved around the dynamics of collaboration between physicians, nurses and other colleagues. Secretaries' functions, in particular, had to be expanded. Facilitating factors were mainly related to the physicians' leadership and the professional resources available in the organizations. Impediments related to resource availability and team functioning were also encountered. This is the first exploratory study to examine the factors influencing the adoption of the advanced access model conducted with early-adopter family physicians. The lessons drawn will inform discussions on scaling up to other settings experiencing the same problems. Copyright © 2016 John Wiley & Sons, Ltd.


Epigenetic effects on the mouse mandible: common features and discrepancies in remodeling due to muscular dystrophy and response to food consistency.
In wild populations phenotypic differentiation of skeletal structures is influenced by many factors including epigenetic interactions and plastic response to environmental influences, possibly blurring the expression of genetic differences. In contrast, laboratory animals provide the opportunity to separate environmental from genetic effects. The mouse mandible is particularly prone to such plastic variations because bone remodeling occurs late in postnatal ontogeny, in interaction with muscular loading. In order to understand the impact of this process on mandible morphology, we investigated how change in the masticatory function affects the mandible shape, and its pattern of variation. Breeding laboratory mice on food of different consistencies mimicked a natural variation in feeding ecology, whereas mice affected by the murine analogue of the Duchenne muscular dystrophy provided a case of pathological modification of the mastication process. Food consistency as well as dystrophy caused significant shape changes in the mouse mandible. Further differences were observed between laboratory strains and between sexes within strains, muscular dystrophy causing the largest morphological change. The directions of the morphological changes due to food consistency and muscular dystrophy were discrepant, despite the fact that both are related to bone remodeling. In contrast, directions of greatest variance were comparable among most groups, and the direction of the change due to sexual dimorphism was parallel to the direction of main variance. Bone remodeling is confirmed as an important factor driving mandible shape differences, evidenced by differences due to both the consistency of the food ingested and muscular dystrophy. However, the resulting shape change will depend on how the masticatory function is affected. Muscular dystrophy caused shape changes distributed all over the mandible, all muscles being affected although possibly to a different degree. In contrast, the chewing function was mostly affected when the mice were fed on hard vs. soft food, whereas grinding likely occurred normally; accordingly, shape change was more localized. The direction of greatest variance, however, was remarkably comparable among groups, although we found a residual variance discarding age, sex, and food differences. This suggests that whatever the context in which bone remodeling occurs, some parts of the mandible such as the angular process are more prone to remodeling during late postnatal growth.


Discrimination and emission of temporal intervals by pigeons.
Because the frequency distribution of IRTs showed little or no control by a DRL schedule, the schedule was modified so that the pigeon's behavior after each IRT would indicate whether or not it had discriminated the duration of the IRT. After every two pecks on a red key, the key changed to blue for 30 sec. Then it automatically became red again. Pecks on the blue key were reinforced with food on a VI schedule only when the preceding IRT on the red key had been longer than 18 sec. The birds did not selectively emit longer IRTs on the red key: the value of IRTs/op did not increase with IRT duration. However, they did discriminate the duration of the IRT emitted on the red key: the rate of pecking on the blue key was an increasing function of the duration of the preceding IRT on the red key.


Abscission: support for a role of ethylene modification of auxin transport.
Three types of whole plant experiments are presented to substantiate the concept that an important function of ethylene in abscission is to reduce the transport of auxin from the leaf to the abscission zone. (a) The inhibitory effect of ethylene on auxin transport, like ethylene-stimulated abscission, persists only as long as the gas is continuously present. Cotton (Gossypium hirsutum L. cv. Stoneville 213) and bean (Phaseolus vulgaris L. cv. Resistant Black Valentine) plants placed in 14 mul/l of ethylene for 24 or 48 hours showed an increase in leaf abscission and a reduced capacity to transport auxin; but when returned to air, auxin transport gradually increased and abscission ceased. (b) Ethylene-induced abscission and auxin transport inhibition show similar sensitivities to temperature. A 24-hour exposure of cotton plants to 14 mul/l of ethylene at 8 C resulted in no abscission and no significant inhibition of auxin transport. Increasing the temperature during ethylene treatment resulted in a progressively greater reduction in auxin transport with abscission occurring at [unk]27 C where auxin transport was inhibited over 70%. (c) Auxin pretreatment reduced both ethylene-induced abscission and auxin transport inhibition. No abscission occurred, and auxin transport was inhibited only 18% in cotton plants which were pretreated with 250 mg/l of naphthalene acetic acid and then placed in 14 mul/l of ethylene for 24 hours. In contrast, over 30% abscission occurred, and auxin transport was inhibited 58% in the corresponding control plants.Collectively, the results presented here and elsewhere indicate that ethylene regulates the sensitivity of the cells in the abscission zone to the more direct actions of the gas (e.g., enzyme induction, secretion) by reducing auxin transport.


The crosstalk between autophagic and endo-/exosomal pathways in antigen processing for MHC presentation in anticancer T cell immune responses.
T cells recognize antigen fragments from proteolytic products that are presented to them in the form of peptides on major histocompatibility complex (MHC) molecules, which is crucial for the T cell to identify infected or transformed cells. Autophagy, a process that delivers cytoplasmic constituents for lysosomal degradation, has been observed to provide a substantial source of intra- and extracellular antigens for MHC presentation to T cells, which will impact the tumor-specific immune response. Meanwhile, extracellular components are transported to cytoplasm for the degradation/secretion process by the endo-/exosomal pathway and are thus involved in multiple physiological and pathological processes, including immune responses. Autophagy and endo-/exosomal pathways are intertwined in a highly intricate manner and both are closely involved in antigen processing for MHC presentation; thus, we propose that they may coordinate in antigen processing and presentation in anticancer T cell immune responses. In this article, we discuss the molecular and functional crosstalk between autophagy and endo-/exosomal pathways and their contributions to antigen processing for MHC presentation in anticancer T cell immune responses.


Concise review: heart regeneration and the role of cardiac stem cells.
Acute myocardial infarction leads to irreversible loss of cardiac myocytes, thereby diminishing the pump function of the heart. As a result, the strenuous workload imposed on the remaining cardiac myocytes often gives rise to subsequent cell loss until the vicious circle ends in chronic heart failure (CHF). Thus, we are in need of a therapy that could ameliorate or even reverse the disease progression of CHF. Endogenous regeneration of the mammalian heart has been shown in the neonatal heart, and the discovery that it may still persist in adulthood sparked hope for novel cardioregenerative therapies. As the basis for cardiomyocyte renewal, multipotent cardiac stem/progenitor cells (CSCs) that reside in the heart have been shown to differentiate into cardiac myocytes, smooth muscle cells, and vascular endothelial cells. These CSCs do have the potential to actively regenerate the heart but clearly fail to do so after abundant and segmental loss of cells, such as what occurs with myocardial infarction. Therefore, it is vital to continue research for the most optimal therapy based on the use or in situ stimulation of these CSCs. In this review, we discuss the current status of the cardioregenerative field. In particular, we summarize the current knowledge of CSCs as the regenerative substrate in the adult heart and their use in preclinical and clinical studies to repair the injured myocardium.


DeepFRET, a software for rapid and automated single-molecule FRET data classification using deep learning.
Single-molecule Förster Resonance energy transfer (smFRET) is an adaptable method for studying the structure and dynamics of biomolecules. The development of high throughput methodologies and the growth of commercial instrumentation have outpaced the development of rapid, standardized, and automated methodologies to objectively analyze the wealth of produced data. Here we present DeepFRET, an automated, open-source standalone solution based on deep learning, where the only crucial human intervention in transiting from raw microscope images to histograms of biomolecule behavior, is a user-adjustable quality threshold. Integrating standard features of smFRET analysis, DeepFRET consequently outputs the common kinetic information metrics. Its classification accuracy on ground truth data reached >95% outperforming human operators and commonly used threshold, only requiring ~1% of the time. Its precise and rapid operation on real data demonstrates DeepFRET's capacity to objectively quantify biomolecular dynamics and the potential to contribute to benchmarking smFRET for dynamic structural biology.


Differential Expression Profile of microRNAs and Tight Junction in the Lung Tissues of Rat With Mitomycin-C-Induced Pulmonary Veno-Occlusive Disease.
Pulmonary veno-occlusive disease (PVOD) is characterized by increased pulmonary vascular resistance. Currently, there is a lack of effective treatment. It is of great significance to explore molecular targets for treatment. This study investigated the differential expression profile of miRNAs and tight junction in the lung tissues of rats with mitomycin-C (MMC)-induced PVOD. A total of 14 rats were divided into the control group and he PVOD group. We measured mean pulmonary arterial pressure (mPAP) and right ventricular hypertrophy index (RVHI). Pathological changes including those in lung tissues, pulmonary venules, and capillary were detected by H&E and orcein staining. Western blot was used to detect GCN2, ZO-1, occludin, and claudin-5 expression. We analyzed the miRNAs profile in the rat lung tissues by high-throughput sequencing. The top differentially expressed miRNAs were validated by using real-time polymerase chain reaction (RT-PCR). There were severe pulmonary artery hypertrophy/hyperplasia, thickening, and occlusion in the small pulmonary veins, pulmonary edema, and dilated capillaries in MMC-induced rats with PVOD. In addition, mPAP and RVHI were significantly increased (P < 0.05). The expression of GCN2 was significantly decreased (P < 0.05). A total of 106 differentially expressed miRNAs were identified. According to the fold changes, the top ten upregulated miRNAs were miRNA-543-3p, miRNA-802-5p, miRNA-493-3p, miRNA-539-3p, miRNA-495, miRNA-380-5p, miRNA-214-5p, miRNA-539-5p, miRNA-190a-3p, and miRNA-431. The top 10 downregulated miRNAs were miRNA-201-3p, miRNA-141-3p, miRNA-1912-3p, miRNA-500-5p, miRNA-3585-5p, miRNA-448-3p, miRNA-509-5p, miRNA-3585-3p, miRNA-449c-5p, and miRNA-509-3p. RT-PCR confirmed that miRNA-214-5p was upregulated, while miRNA-141-3p was downregulated (P < 0.05). Functional analysis showed various signaling pathways and metabolic processes, such as fatty acid biosynthesis, tight junction, and the mTOR signaling pathway. In addition, the expression of the tight junction-related protein of ZO-1, occludin, and claudin-5 was significantly decreased in rats with PVOD (P < 0.05). miRNAs may be involved in the pathogenesis of PVOD. Furthermore, ZO-1, occludin, and claudin-5 verification confirmed that the tight junction may be involved in the development of the disease.


Highly conserved cross-reactive CD4+ T-cell HA-epitopes of seasonal and the 2009 pandemic influenza viruses.
The relatively mild nature of the 2009 influenza pandemic (nH1N1) highlights the overriding importance of pre-existing immune memory. The absence of cross-reactive antibodies to nH1N1 in most individuals suggests that such attenuation may be attributed to pre-existing cellular immune responses to epitopes shared between nH1N1 virus and previously circulating strains of inter-pandemic influenza A viruses. We sought to identify potential CD4+ T cell epitopes and predict the level of cross-reactivity of responding T cells. By performing large-scale major histocompatibility complex II analyses on Hemagglutinin (HA) proteins, we investigated the degree of T-cell cross-reactivity between seasonal influenza A (sH1N1, H3N2) from 1968 to 2009 and nH1N1 strains. Each epitope was examined against all the protein sequences that correspond to sH1N1, H3N2, and nH1N1. T-cell cross-reactivity was estimated to be 52%, and maximum conservancy was found between sH1N1 and nH1N1 with a significant correlation (P < 0.05). Given the importance of cellular responses in kinetics of influenza infection in humans, our findings underscore the role of T-cell assays for understanding the inter-pandemic variability in severity and for planning treatment methods for emerging influenza viruses.


Nitrated and parent PAHs in the surface water of Lake Taihu, China: Occurrence, distribution, source, and human health risk assessment.
Nitrated polycyclic aromatic hydrocarbons (NPAHs) have toxic potentials that are higher than those of their corresponding parent polycyclic aromatic hydrocarbons (PAHs) and thus have received increasing attention in recent years. In this study, the occurrence, distribution, source, and human health risk assessment of 15 NPAHs and 16 PAHs were investigated in the surface water from 20 sampling sites of Lake Taihu during the dry, normal, and flood seasons of 2018. The ΣPAH concentrations ranged from 255 to 7298 ng/L and the ΣNPAH concentrations ranged from not-detected (ND) to 212 ng/L. Among the target analytes, 2-nitrofluorene (2-nFlu) was the predominant NPAH, with a detection frequency ranging from 85% to 90% and a maximum concentration of 56.2 ng/L. The three-ringed and four-ringed NPAHs and PAHs comprised the majority of the detected compounds. In terms of seasonal variation, the highest levels of the ΣNPAHs and ΣPAHs were in the dry season and flood season, respectively. Diagnostic ratio analysis indicated that the prime source of NPAHs was direct combustion, whereas in the case of PAHs the contribution was predominantly from a mixed pattern including pollution from unburned petroleum and petroleum combustion. The human health risk of NPAHs and PAHs was evaluated using a lifetime carcinogenic risk assessment model. The carcinogenic risk level of the targets ranged from 2.09 × 10-7 to 5.75 × 10-5 and some surface water samples posed a potential health risk.


Aortic valve interstitial cells: an evaluation of cell viability and cell phenotype over time.
In investigating the mechanisms of aortic valve disease processes and to accurately construct tissue-engineered heart valve prostheses, a complete understanding of the native interstitial cell population is required. Previously, autopsy samples have been deemed unsuitable for immunocytochemical studies due to the ischemic time before harvesting. In this study, the viability and phenotypic profile of cells explanted from normal porcine heart valves up to 120 h post mortem was examined. The aortic valve leaflets of porcine hearts were excised at 0, 6, 24, 48, 72, 96 and 120 h post mortem; one half of the tissue was used to explant cells, and the other half was fixed in 3.7% formalin for sectioning. Samples taken at each time point were cultured and cell viability was determined using a trypan blue exclusion assay. Immunocytochemical and immunohistochemical analyses, using specific markers for fibroblasts, myofibroblasts and smooth muscle cells, were used to compare cell phenotypes both in vitro and in situ. Absolute numbers of cells obtained from each leaflet decreased significantly over time; however, cell viability in culture was unaffected up to 96 h. At each time point, explanted cell populations expressed similar phenotypes when compared with histological samples prepared from the same valves. Porcine aortic valve interstitial cells may be explanted up to and including 96 h post mortem, with no statistically significant change in cell viability in vitro, and with a population that phenotypically resembles aortic valve interstitial cells in situ. These data suggest that human aortic valve interstitial cells may be successfully harvested at autopsy for in vitro studies.


Ethanol Does Not Promote MeIQx-initiated Rat Colon Carcinogenesis Based on Evidence from Analysis of a Colon Cancer Surrogate Marker.
Epidemiological studies suggest that alcohol consumption increases the risk of developing colorectal cancer. However, the data are confounded by numerous cosegregating variables. To cast further light on the relationships between alcohol intake and colon cancer development, 21-day-old male F344/DuCrj rats were fed 200 ppm 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in their diet for 8 weeks and doses of 0, 0.1, 0.3, 1, 3, 10 and 20% of ethanol in their drinking water ad libitum for 16 weeks thereafter. The rats were sacrificed after 24 weeks of experiment, and aberrant crypt foci (ACF), surrogate lesions for colon cancer, were examined under a light microscope at low magnification. Ethanol was found not to affect the ACF formation at any dose compared with the initiated-controls. Furthermore, ethanol did not alter colon epithelial cell proliferation. These data, obtained by analysis of a colon cancer surrogate marker lesion, indicate that ethanol lacks promotion activity for MeIQx-initiated rat colon carcinogenesis.


High genetic variability of the Streptococcus thermophilus cse central part, a repeat rich region required for full cell segregation activity.
The cse gene of Streptococcus thermophilus encodes an extracytoplasmic protein involved in cell segregation. The Cse protein consists of two putative domains: a cell wall attachment LysM domain and a catalytic CHAP domain. These two domains are spaced by an interdomain linker, known as Var-Cse, previously reported to be highly divergent between two S. thermophilus strains. The aim of this study was to assess the extent of this intraspecific variability and the functional involvement of the var-cse region in cell segregation. Analysis of the var-cse sequence of 19 different strains allowed detection of 11 different alleles, varying from 390 bp to 543 bp, all containing interspersed and tandem nucleotides repeats. Overall, 11 different repeat units were identified and some series of these small repeats, named supermotifs, form large repeats. Results suggested that var-cse evolved by deletion of all or part of the repeats and by duplication of repeats or supermotifs. Moreover, sequence analysis of the whole cse locus revealed that the cse ORF is mosaic suggesting that var-cse polymorphism resulted from horizontal transfer. The partial deletion of the var-cse region of the S. thermophilus strain CNRZ368 led to the lengthening of the number of cells per streptococcal chain, indicating that this region is required for full cell segregation in S. thermophilus strain CNRZ368.


Michelson interferometer vibrometer using self-correcting synthetic-heterodyne demodulation.
Synthetic-heterodyne demodulation is a useful technique for dynamic displacement and velocity detection in interferometric sensors, as it can provide an output signal that is immune to interferometric drift. With the advent of cost-effective, high-speed real-time signal-processing systems and software, processing of the complex signals encountered in interferometry has become more feasible. In synthetic heterodyne, to obtain the actual dynamic displacement or vibration of the object under test requires knowledge of the interferometer visibility and also the argument of two Bessel functions. In this paper, a method is described for determining the former and setting the Bessel function argument to a set value, which ensures maximum sensitivity. Conventional synthetic-heterodyne demodulation requires the use of two in-phase local oscillators; however, the relative phase of these oscillators relative to the interferometric signal is unknown. It is shown that, by using two additional quadrature local oscillators, a demodulated signal can be obtained that is independent of this phase difference. The experimental interferometer is a Michelson configuration using a visible single-mode laser, whose current is sinusoidally modulated at a frequency of 20 kHz. The detected interferometer output is acquired using a 250 kHz analog-to-digital converter and processed in real time. The system is used to measure the displacement sensitivity frequency response and linearity of a piezoelectric mirror shifter over a range of 500 Hz to 10 kHz. The experimental results show good agreement with two data-obtained independent techniques: the signal coincidence and denominated n-commuted Pernick method.


Fracture Management in Pyknodysostosis - A Rare Case Report.
Pyknodysostosis is congenital osteosclerotic skeletal dysplasia of a rare entity. It is an autosomal recessive disease which presents with short stature and generalized osteosclerosis of skeleton as result of decreased bone turnover. Here, the authors report a case of pyknodysostosis who presented to our emergency room with a pathological fracture in the shaft of the femur for which operative intervention was carried out. A 30-year-old female presented to our emergency room with a history of trivial injury to right thigh region and was diagnosed as fracture in her right femur shaft region. After a detailed clinical, radiological, and blood investigations, the patient was taken up for operative modality of intervention in the form of plate osteosynthesis. As the medullary canal was narrow and bone was osteosclerotic, the option of closed intramedullary interlocking nailing was ruled out. Hence, we proceeded with open reduction and internal fixation with plate osteosynthesis using a board dynamic compression plate. Post-operative period was uneventful. Patient underwent non-weight bearing mobilization for 2 months. At 10-week post-operative follow-up, the patient presented with pain over surgical site and radiological examination showed no signs of union. The patient underwent additional plating augmented with bone grafting using grafts harvested from iliac crest and synthetic bone graft. The patient developed deep-seated infection immediate post-operative period for which she was treated with wound debridement, and appropriate intravenous antibiotics were given 2 weeks and orally for 4 weeks. At 6-month follow-up, the patient is able to carry her day-to-day activity with complete recovery and radiological signs of union. The patient had classical clinical features suggestive of pyknodysostosis. Patient has 2 siblings of same family (one brother and sister) with similar clinical and radiological features. Recognition of these clinical and radiological signs is important to make the diagnosis of pyknodysostosis and prevent possible complications. Additional care must be taken in treating these patients.


Health literacy, cervical cancer risk factors, and distress in low-income African-American women seeking colposcopy.
To describe the relationship between health literacy, distress, and cervical cancer risk factors in women at high risk for developing cervical cancer. Cross-sectional, prospective cohort design. Two university-based gynecological oncology colposcopy clinics and 3 Planned Parenthood community dinics. One hundred-thirty English-speaking African-American women > or = 18 years referred for colposcopy following abnormal Pap testing. Avoidance and Intrusion subscales of the Impact of Events Scale (IES), Rapid Estimate of Adult Literacy in Medicine (REALM), and demographics. Forty-five percent of women had a low level of health literacy (< 9th grade). Low health literacy was related to fewer risk factors (P < .01) and higher levels of distress on the Impact of Events avoidance subscale (P < .05) after controlling for covariates. Forty-three percent of women with low literacy had excessive levels of distress as compared to 25% in women with high literacy (P < .05). A low level of health literacy is associated with increased levels of distress among women at high risk for developing cervical cancer. To the extent that distress serves as a barrier to treatment, culturally informed, effective interventions are needed.


[Fusion imaging of 3D MR cisternography/angiography for differential diagnosis of internal carotid-posterior communicating artery aneurysms and infundibular dilations].
By using a fusion imaging of three-dimensional (3D) magnetic resonance cisternography (MRC) and coregistered magnetic resonance angiography (MRA), protrusions at the bifurcation of the internal carotid-posterior communication artery, detected by MRA, were investigated to differentiate between the infundibular dilations and aneurysms. The MRA, obtained by the 3D time-of-flight sequence, showed the flow-related arterial structures by means of an inflow effect mainly induced by the peak systolic flow velocity. The MRC, obtained by 3D fast spin-echo sequence, depicted the contours of the vascular structures within the cisternal space in contrast to the surrounding cerebrospinal fluid. Fusion images of 3D MRC/MRA showed the anatomy of protrusions from the different viewpoints with flow-related intraluminal images (MRA) in conjunction with outer-wall configuration images of the vascular structures (MRC). This imaging technique may be useful to differentiate the infundibular dilations from the internal carotid-posterior communicating artery aneurysms.


[Placenta percreta with a contribution of 1 clinical case].
Placenta accreta and its variants increta and percreta is one of the biggest challenges in clinical obstetric practice. The frequency of this life-threatening abnormality in the placenta tends to increase, this trend is directly linked to increasing rates of Caesarean section. The author describes clinical case of unrecognized before birth Placenta percreta, risk factors for this condition and modern methods for timely diagnosis and behavior.


Photocatalytic Metal-Organic Frameworks for Selective 2,2,2-Trifluoroethylation of Styrenes.
Synthesis of CF3-containing compounds is of great interest because of their broad use in the pharmaceutical and agrochemical industries. Herein, selective 2,2,2-trifluoroethylation of styrenes was catalyzed by Zr(IV)-based MOFs bearing visible-light photocatalysts in the form of Ir(III) polypyridyl complexes. When compared to the homogeneous Ir(III) catalyst, the MOF-based catalyst suppressed the dimerization of benzyl radicals, thus enhancing the selectivity of the desired hydroxytrifluoroethyl compounds.


Pre-mitotic genome re-organisation bookends the B cell differentiation process.
During cellular differentiation chromosome conformation is intricately remodelled to support the lineage-specific transcriptional programs required for initiating and maintaining lineage identity. When these changes occur in relation to cell cycle, division and time in response to cellular activation and differentiation signals has yet to be explored, although it has been proposed to occur during DNA synthesis or after mitosis. Here, we elucidate the chromosome conformational changes in B lymphocytes as they differentiate and expand from a naive, quiescent state into antibody secreting plasma cells. We find gene-regulatory chromosome reorganization in late G1 phase before the first division, and that this configuration is remarkably stable as the cells massively and rapidly clonally expand. A second wave of conformational change occurs as cells terminally differentiate into plasma cells, coincident with increased time in G1 phase. These results provide further explanation for how lymphocyte fate is imprinted prior to the first division. They also suggest that chromosome reconfiguration occurs prior to DNA replication and mitosis, and is linked to a gene expression program that controls the differentiation process required for the generation of immunity.


Redox pioneer: professor Barry Halliwell.
Professor Barry Halliwell is recognized as a Redox Pioneer because he has published eight articles on redox biology that have been each cited more than 1000 times, and 158 articles that have been each cited more than 100 times. His contributions go back as far as 1976, when he was involved in elucidation of the Foyer-Halliwell-Asada cycle, an efficient mechanism for preventing oxidative damage to chloroplasts. His subsequent work established the important role of iron and zinc in free radical reactions and their relevance to human pathologies. Professor Halliwell is also a leader in developing novel methodology for detecting free radical intermediates in vivo, and his contributions to our knowledge of reactive nitrogen species are highly significant. His sustained excellence won him the top-cited scientist award in the United Kingdom in biomedical sciences in 1999, and in 2003 he was recognized as a highly cited scientist by Institute of Scientific Information (ISI) for work on plant antioxidants, and the same year ranked 28 out of 5494 biochemists/biologists for scientific impact. Two pieces of his scholarly work have been listed as Citation Classics by ISI, and in 2007 his laboratory was ranked number 1 worldwide based on highest citation score in research on free radicals.


Exploiting active nuclear import for efficient delivery of Auger electron emitters into the cell nucleus.
The most attractive features of Auger electrons (AEs) in cancer therapy are their extremely short range and sufficiently high linear energy transfer (LET) for a majority of them. The cytotoxic effects of AE emitters can be realized only in close vicinity to sensitive cellular targets and they are negligible if the emitters are located outside the cell. The nucleus is considered the compartment most sensitive to high LET particles. Therefore, the use of AE emitters could be most useful in specific recognition of a cancer cell and delivery of AE emitters into its nucleus. This review describes the studies aimed at developing effective anticancer agents for the delivery of AE emitters to the nuclei of target cancer cells. The use of peptide-based conjugates, nanoparticles, recombinant proteins, and other constructs for AE emitter targeted intranuclear delivery as well as their advantages and limitations are discussed. Transport from the cytoplasm to the nucleus along with binding to the cancer cell is one of the key stages in the delivery of AE emitters; therefore, several constructs for exploitation of this transport have been developed. The transport is carried out through a nuclear pore complex (NPC) with the use of specific amino acid nuclear localization sequences (NLS) and carrier proteins named importins, which are located in the cytosol. Therefore, the effectiveness of NLS-containing delivery constructs designed to provide energy-dependent transport of AE emitter into the nuclei of cancer cells also depends on their efficient entry into the cytosol of the target cell.


Developmental regulation of CUP gene expression through DNA methylation in Mucor spp.
Inserts which carried the CUP gene from Saccharomyces cerevisiae or Mucor racemosus were used as hybridization probes to measure the methylation state and expression of the CUP gene from Mucor rouxii at different stages of growth. It was observed that the fungus contains a CUP multigene family. All the CUP genes were present in a hypermethylated DNA region in nongrowing and isodiametrically growing spores and were not transcribed at these stages. After germ tube emergence, CUP genes became demethylated and transcriptionally active. Development, demethylation, and transcription of CUP genes were blocked by the ornithine decarboxylase inhibitor 1,4-diaminobutanone. These results suggest that genes that are activated during development became demethylated in this fungus.


Natural Silkworm Cocoon Composites with High Strength and Stiffness Constructed in Confined Cocooning Space.
In this study, using round paper tubes (PTs) and rectangular cardboard boxes (CBs) as external constraints to control the size of the cocooning space, we fabricated a series of modified silkworm cocoons (PT cocoons and CB cocoons). Their microstructures, morphologies, compositions, and mechanical properties were characterized and compared with normal silkworm cocoons. These two kinds of modified silkworm cocoons exhibit dense and homogeneous layer structures. Tensile test results indicate that above a size limit of cocooning space, their tensile strengths, Young's moduli, and strain energy densities increase with the decrease in cocooning space. Especially in comparison with the normal cocoons, the tensile strength and Young's modulus of the PT-14 cocoon increase by 44% and 100%, respectively. Meanwhile, PT cocoons and CB cocoons, except PT-12, also possess better peeling resistance than normal cocoons. Owing to the dense structure and low porosity, the modified cocoons form robust fiber networks that result in high strength and toughness. This study provides a green and efficient method to fabricate mechanically enhanced silkworm cocoons with special shapes and dense layer structures. The method can be easily subjected to further modification processes and has potential applications in the production of high-performance green cocoon composites and biomimetic materials.


Outcomes of video-assisted thoracoscopic decortication.
Video-assisted thoracoscopic surgical decortication (VATSD) is widely used for treatment of early empyema and hemothorax, but conversion to open thoracotomy for decortication (OD) is more frequent in the setting of complex, chronic empyema. This study compared indications for and outcomes associated with VATSD and OD. The outcomes of 420 consecutive patients undergoing VATSD or OD for benign conditions from 1996 to 2006 were reviewed and compared with respect to baseline characteristics, preoperative management, and operative and postoperative course. Patients were analyzed on an intention-to-treat basis. The cohort consisted of 326 VATSD and 94 OD patients. The conversion rate from VATSD to OD was 11.4%. The operative time and median in-hospital length of stay were shorter for the VATSD group: 97 vs 155 minutes (p < 0.001), and 15 vs 21 days (p = 0.03), respectively. The median postoperative length of stay was 7 days for the VATSD group vs 10 days for the OD group (p < 0.001). Significantly fewer postoperative complications occurred in the VATSD group in the following categories: atelectasis, prolonged air leak, reintubation, ventilator dependence, need for tracheostomy, blood transfusion, sepsis, and 30-day mortality. Thoracoscopic decortication for empyema, complex pleural effusion, and hemothorax yields results that are at least equivalent to open decortication. Patients undergoing VATSD have fewer postoperative complications. The conversion and reoperation rates are low, suggesting that a thoracoscopic approach is an effective and reasonable first option for most patients with complex pleural effusions and empyema.


Thresholding in PET images of static and moving targets.
Continued therapeutic gain in the treatment of non-small-cell lung cancer (NSCLC) will depend upon our ability to escalate the dose to the primary tumour while minimizing normal tissue toxicity. Both these objectives are facilitated by the accurate definition of a target volume that is as small as possible. To this end, both tumour immobilizations via deep inspiratory breath-hold, along with positron emission tomography (PET), have emerged as two promising approaches. Though PET is an excellent means of defining the general location of a tumour focus, its ability to define exactly the geometric extent of such a focus strongly depends upon selection of an appropriate image threshold. However, in clinical practice, the image threshold is typically not chosen according to consistent, well-established criteria. This study explores the relationship between image threshold and the resultant PET-defined volume using a series of F-18 radiotracer-filled hollow spheres of known internal volumes, both static and under oscillatory motion. The effects of both image threshold and tumour motion on the resultant PET image are examined. Imaging data are further collected from a series of simulated gated PET acquisitions in order to test the feasibility of a patient-controlled gating mechanism during deep inspiratory breath-hold. This study illustrates quantitatively considerable variability in resultant PET-defined tumour volumes depending upon numerous factors, including image threshold, size of the lesion, the presence of tumour motion and the scanning protocol. In this regard, when using PET in treatment planning for NSCLC, the radiation oncologist must select the image threshold very carefully to avoid either under-dosing the tumour or overdosing normal tissues.


Examining influences on the availability of and access to opioids for pain management and palliative care.
This commentary relates to the recently published essay in PLOS Medicine, entitled "Untreated Pain, Narcotics Regulation, and Global Health Ideologies." That essay describes regulatory and other systemic barriers preventing the accessibility of opioid analgesics and contributing to patients not receiving adequate pain relief. Four main points highlighted in the essay are discussed in this commentary: (1) the role of international treaties in medication availability; (2) the role of the International Narcotics Control Board in medication availability; (3) the role of regulatory policy in treating pain; and (4) the role of opioid analgesics in treating pain. Recent authoritative statements and activities suggest a strengthened infrastructure within which governments currently can work to improve the availability of controlled medicines to enhance patient pain and palliative care services.


''NODUS''-a sensitive new instrument for analyzing the composition of surfaces.
A novel type of ion-scattering spectrometer for analyzing the composition of surfaces is described. By means of a specially designed cylindrical mirror analyzer the sensitivity of the instrument is increased by two or three orders of magnitude as compared with that of equipment used hitherto. The increased sensitivity allows analyses to be performed using extremely low ion doses. Under these conditions, destruction of the surface is negligible. The use of a differential pumping system guarantees UHV conditions at the target, thus minimizing contamination.


Low expression of DDX5 is associated with poor prognosis in patients with pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies. Hence, there is a need for new markers and treatment strategies. P68/DEAD box protein 5 (DDX5) is an ATP-dependent RNA helicase of the DEAD box protein family. It is a prognostic marker for several cancers. In this study, we aimed to evaluate the expression and clinical relevance of DDX5 in PDAC. DDX5 expression in tissue microarray blocks containing 230 PDAC samples was examined using immunohistochemical analysis. DDX5 expression was considered high when more than 50% of the cells were stained and low when less than 50% of the cells were stained. We investigated the association between DDX5 expression and clinicopathological parameters, including patient survival. The nuclei of normal pancreatic ducts, normal acinar cells and PDAC cells were stained positive for DDX5 although the intensity and distribution of DDX5 expression varied. Islet cells showed strong and diffuse staining of DDX5. DDX5 expression was low and high in 148 (64.3%) and 82 cases (35.7%), respectively. Low DDX5 expression was significantly associated with an advanced pT factor (pT2-pT3: tumour size,>20 mm), lymphatic involvement, advanced tumour-node-metastasis (TNM) stage (stages IIB, III, and IV), and venous involvement. In addition, the multivariate analysis revealed that DDX5 expression is an independent prognostic factor for PDAC. These results suggest that DDX5 plays an important role in tumour invasiveness and PDAC prognosis.


Interference of two diverging beams reflected from a plane parallel plate: stationary fringes with characteristic stable period.
We investigated interference fringes due to superposition of diverging light waves reflected from the two sides of a plane parallel plate. A non-localized fringe pattern of high contrast was obtained as a function of incident angle when we used a coherent diverging beam. We found that the fringe density increased to a certain angle and then decreased thereafter, against the common belief that the fringe density increases monotonically with the angle of incidence. Because the fringe density is maximum at this angle and does not change rapidly in the vicinity, we could employ Fourier analysis to estimate interferometric parameters, such as thickness, refractive index, and wavelength, that determine the characteristic stationary fringe density.


[Correlation of netrin-1 expression with invasion of extra villous trophoblasts].
To investigate mechanism of netrin-1 regulating invasion of extra villous trophoblasts. RT-PCR was used to detect six receptors expression including UNC5A, UNC5B, UNC5C, UNC5D, DCC and neogenin in extra villous trophoblast cell line TEV-1. The TEV-1 cells were cultured and devided into seven groups according to the concentration of netrin-1 adding into the medium, which include 10 microg/L, 50 microg/L, 100 microg/L, 500 microg/L, 1000 microg/L, 5000 microg/L and the control (the concentration of netrin-1 was 0 microg/L)groups. The proliferation and invasion of TEV-1 induced by netrin-1 were determined by CCK-8 assay and transwell invasion assay respectively. (1) Only neogenin and UNC5B were found to be expressed on TEV-1 by RT-PCR method. (2) In CCK-8 proliferation assay, after 72 hours culture, the proliferation of TEV-1 were 1.55 +/- 0.29 in 10 microg/L, 1.72 +/- 0.31 in 50 microg/L, 2.15 +/- 0.35 in 100 microg/L, 1.42 +/- 0.25 in 500 microg/L, 1.50 +/- 0.27 in 1000 microg/L, and 1.38 +/- 0.23 in 5000 microg/L group, which were all higher than 1.00 +/- 0.16 in control group significantly (P < 0.05). (3) In matrigel invasion assay, after 6 hours culture, the number of the trans-membrane cells in various netrin-1 group, including 41 +/- 4 in 10 microg/L, 47 +/- 5 in 50 microg/L, 55 +/- 6 in 100 microg/L, 44 +/- 5 in 500 microg/L, 43 +/- 5 in 1000 microg/L and 42 +/- 5 in 5000 microg/L group, were all higher than 30 +/- 4 in control group with statistical significance (P < 0.05). (4) The fold changes of neogenin were 1.50 +/- 0.16 in 10 microg/L, 1.83 +/- 0.19 in 50 microg/L, 2.24 +/- 0.25 in 100 microg/L, 2.12 +/- 0.24 in 500 microg/L, 2.12 +/- 0.23 in 1000 microg/L and 2.13 +/- 0.23 in 5000 microg/L group, which were all higher than 1.00 +/- 0.11 in control group significantly (P < 0.05). There were significant difference between group 10 microg/L and 50 microg/L, group 50 microg/L and 100 microg/L (P < 0.05). There were no significant difference between group 100 microg/L and 500 microg/L, group 1000 microg/L and 5000 microg/L (P > 0.05). (5) The fold changes of UNC5B 1.09 +/- 0.11 in 10 microg/L, 1.47 +/- 0.14 in 50 microg/L, 1.61 +/- 0.16 in 100 microg/L, 1.85 +/- 0.19 in 500 microg/L, 2.21 +/- 0.21 in 1000 microg/L and 2.42 +/- 0.23 in 5000 microg/L group, were all higher significantly when compared with 1.00 +/- 0.07 in control group (P < 0.05). There were significant difference between all groups (P < 0.05). Netrin-1 can promote the potential of proliferation and invasion of extravillous trophoblasts in vitro through its receptors including neogenin and UNC5B.


Cooling improves the writing performance of patients with writer's cramp.
Cooling of hand and forearm muscles by immersion in 15 degrees C cold water for 5 minutes improved the writing performance of patients with writer's cramp. Since abnormal processing of muscle spindle afferent discharges contributes to the pathology of writer's cramp, this effect might result from a reduction in muscle spindle activity by lowering muscle temperature. Cooling is a simple, cheap, and safe procedure, providing temporary relief for patients with writer's cramp.


Pregnancy induced hypertension and antithrombin-III.
This study was undertaken to determine the coagulation profile of women with pregnancy induced hypertension and to evaluate the changes in the level of AT-III in pre-eclampsia and eclampsia and its correlation with severity of disease in order to evaluate if it can be used as a marker for severity of PIH. 119 women with PIH in the third trimester of pregnancy constituted the study group. Age and parity matched 25 normal pregnant and 25 non-pregnant women were taken as control group. No significant difference between the coagulation profile of non-pregnant and normal pregnant women was seen. There is evidence of consumption coagulopathy in PIH patients and AT-III activity shows a gradual and almost linear reduction in various groups ranging from normal pregnant women to eclampsia. Reduction in AT-III activity has positive correlation with PIH and it can be a useful marker for severity of PIH.


Metabolite profile of sibutramine in human urine: a liquid chromatography-electrospray ionization mass spectrometric study.
We present a detailed experimental approach to detection and subsequent structural characterization of unknown metabolites of sibutramine, using liquid chromatography-mass spectrometric techniques. The full-, precursor ion, and constant neutral loss scan modes of a triple quadrupole mass spectrometer were used for screening sibutramine metabolites in human urine. The structural assessment of unknown metabolites was based on MSn ion trap mass spectrometric analysis and comparison of MSn spectra between the standards and compounds detected. Two phase-I (M1 and M2) and eight phase-II (M3-M6) metabolites of sibutramine were found in human urine. Metabolites M1 and M2, which were found as minor metabolites, originated from N-demethylation of sibutramine. Carbamoyl glucuronides formed from metabolites M1, M2, and their hydroxylated analogs were the main metabolites of sibutramine and were characterized by tandem mass spectrometric analysis and by the chemical modification of their structure. We demonstrate the usefulness of the chemical derivatization approach for estimation of the site of glucuronidation and propose the formation of hydroxylated regioisomers of metabolites M4 and M6.


Necropsy findings in rhesus monkeys experimentally infected with cultured simian immunodeficiency virus (SIV)/delta.
Lesions induced in rhesus monkeys by different isolates of simian immunodeficiency virus (SIV)/Delta were studied at necropsy. Four groups of monkeys were inoculated with SIV/Delta isolated from other experimentally infected rhesus monkeys, while one group was inoculated with SIV/Delta from an asymptomatic mangabey monkey. Three rhesus isolates and the mangabey isolate were virulent, killing 75-100% of infected monkeys. One rhesus isolate, which had been extensively passaged in vitro, was attenuated but was restored to virulence by single animal passage. Clinically, infected monkeys had lymphadenopathy, splenomegaly, diarrhea, and a rash. Most monkeys died of enteric disease. The following lesions were seen: weight loss, thymic atrophy, lymphoid atrophy, bone marrow hyperplasia, encephalitis, colitis, amyloidosis, hepatitis, glomerulosclerosis, and the presence of syncytial cells. One Rh Epstein-Barr virus (EBV)-related lymphoma occurred. Opportunistic agents were identified: cytomegalovirus, adenovirus, Cryptosporidia, and Pneumocystis. Shigella and Campylobacter often caused colitis.


Enhancing azithromycin antibacterial activity by encapsulation in liposomes/liposomal-N-acetylcysteine formulations against resistant clinical strains of Escherichia coli.
E. coli is an Enterobacteriaceae that could develop resistance to various antibiotics and become a multi-drug resistant (MDR) bacterium. Options for treating MDR E. coli are limited and the pipeline is somewhat dry when it comes to antibiotics for MDR bacteria, so we aimed to explore more options to help in treating MDR E. coli. The purpose of this study is to examine the synergistic effect of a liposomal formulations of co-encapsulated azithromycin and N-acetylcysteine against E. coli. Liposomal azithromycin (LA) and liposomal azithromycin/N-acetylcysteine (LAN) were compared to free azithromycin. A broth dilution was used to measure the MIC and MBC of both formulations. The biofilm reduction activity, thermal stability measurements, stability studies, and cell toxicity analysis were performed. LA and LAN effectively reduced the MIC of E. coli SA10 strain, to 3 μg/ml and 2.5 μg/ml respectively. LAN at 1 × MIC recorded a 93.22% effectiveness in reducing an E. coli SA10 biofilm. The LA and LAN formulations were also structurally stable to 212 ± 2 °C and 198 ± 3 °C, respectively. In biological conditions, the formulations were largely stable in PBS conditions; however, they illustrated limited stability in sputum and plasma. We conclude that the formulation presented could be a promising therapy for E. coli resistance circumstances, providing the stability conditions have been enhanced.


Hear How I Feel.
In an effort to heighten the awareness of the high school population, a support group program for young people whose parents were diagnosed with cancer received funding to produce an educational video titled Hear How I Feel. This article reports on the evaluation of the video by 146 high school teachers, guidance counselors, and students; elementary school teachers; university undergraduate social work students; and health care and social service providers. A qualitative analysis of the evaluations indicated that high school teachers and guidance counselors were reluctant to use the video in the high school setting because they could not respond expertly to emotions that might be elicited. The findings suggest that youths desire a forum in which difficult issues can be addressed, teachers and guidance counselors need training that would enhance their skill in responding to students' emotional responses, and cancer patients and their families have psychosocial needs that must be met.


Novel insight into triple-negative breast cancers, the emerging role of angiogenesis, and antiangiogenic therapy.
Triple-negative breast cancer (TNBC) is a heterogeneous group of tumours characterised by lack of expression of oestrogen-, progesterone- and human epidermal growth factor receptors. TNBC, which represents approximately 15% of all mammary tumours, has a poor prognosis because of an aggressive behaviour and the lack of specific treatment. Accordingly, TNBC has become a major focus of research into breast cancer and is now classified into several molecular subtypes, each with a different prognosis. Pathological angiogenesis occurs at a late stage in the proliferation of TNBC and is associated with invasion and metastasis; there is an association with metabolic syndrome. Semaphorins are a versatile family of proteins with multiple roles in angiogenesis, tumour growth and metastasis and may represent a clinically useful focus for therapeutic targeting in this type of breast cancer. Another important field of investigation into the control of pathological angiogenesis is related to the expression of noncoding RNA (ncRNA) - these molecules can be considered as a therapeutic target or as a biomarker. Several molecular agents for intervening in the activity of different signalling pathways are being explored in TNBC, but none has so far proved effective in clinical trials and the disease continues to pose a defining challenge for clinical management as well as innovative cancer research.


Bupropion and its photoreactive analog (±)-SADU-3-72 interact with luminal and non-luminal sites at human α4β2 nicotinic acetylcholine receptors.
The interaction of (±)-bupropion [(±)-BP] with the human (h) α4β2 nicotinic acetylcholine receptor (AChR) was compared to that for its photoreactive analog (±)-2-(N-tert-butylamino)-3'-iodo-4'-azidopropiophenone [(±)-SADU-3-72]. Ca2+ influx results indicated that (±)-SADU-3-72 and (±)-BP inhibit hα4β2 AChRs with practically the same potency. However, (±)-SADU-3-72 binds to the [3H]imipramine sites at resting and desensitized hα4β2 AChRs with 3-fold higher affinity compared to that for (±)-BP, which is supported by molecular docking results. The docking results also indicate that each isomer of BP and SADU-3-72, in the protonated state, interacts with luminal and non-luminal sites. In the channel lumen, both ligands bind to two overlapping subsites, one that overlaps the imipramine site, and another much closer to the cytoplasmic side. The results suggest, for the first time, three differentiated non-luminal domains, including the transmembrane (TMD), extracellular (ECD), and ECD-TMD junction. In the ECD-TMD junction, BP and SADU-3-72 bind to overlapping sites. Interestingly, only SADU-3-72 binds to intrasubunit and intersubunit sites in the TMD, and to additional sites in the ECD. Our results are consistent with a model where BP and SADU-3-72 bind to overlapping sites in the luminal and ECD-TMD junctional domains of the hα4β2, whereas only SADU-3-72 binds to additional non-luminal sites. The BP junctional site opens the door for additional inhibitory mechanisms. The pharmacological properties of (±)-SADU-3-72 showed in this work support further photolabeling studies to mapping the BP binding sites in the hα4β2 AChR.


Changes in symptoms of anxiety and depression following diagnostic angiography: a prospective cohort study.
Coronary angiography is the gold standard diagnostic test for coronary artery disease (CAD), and the diagnostic results can have an immediate effect on symptoms. The aim of this study was to explore the long-term impact of diagnostic angiography on symptoms of anxiety and depression in a group of patients without previous CAD. The prospective cohort study included 459 consecutive patients undergoing invasive angiography and was approved by the regional board of ethics. Data were collected at baseline and after 6 and 12 months using self-reports. Symptoms of anxiety and depression were measured with the Hospital Anxiety and Depression Scale (HADS). The sample population had a mean age of 62 years and included 197 (43%) women. Fifty-three percent had hypertension, and 17% had diabetes. The diagnostic results indicated that 41% of patients had normal vessels; 21% had wall changes; and 38% had obstructive stenosis. No significant difference was found between the diagnostic groups at baseline regarding the levels of anxiety or depression. After 6 months, participants with obstructive stenosis had significantly lower levels of anxiety than those without obstructive stenosis. Improvements were observed in all groups over time in both HADS subscale scores; the largest improvement occurred in patients with obstructive stenosis. This study demonstrates that patients with normal coronary arteries or minimal coronary disease/non-obstructive coronary disease do not seem to obtain the same benefit from the receipt of information about their coronary status in terms of anxiety and depression as patients with significant obstructive stenosis.


Comparison of fine needle aspirates of breast cancers to imprint smears by means of digital cell image analysis.
Morphonuclear assessments were performed using the SAMBA 2005 cell image processor on cell nuclei in fine needle aspirates and corresponding imprint smears from 17 not-otherwise-specified (NOS) breast carcinomas to study the influence of cell sampling on the morphonuclear measurements. Fourteen parameters related to densitometric (nuclear DNA content), morphometric (nuclear area) and textural (chromatin organization and distribution) characteristics were computed for each nucleus. The results demonstrated that such morphonuclear features evolved significantly and positively with respect to conventional histopathologic grading. The method of cell sampling significantly influenced the results, but without altering the general conclusions regarding evolution of the morphonuclear features.


Implementing a geriatric resource nurse model.
The aging of the American population and its effects on healthcare centers require strategies and programs to ensure best practices for older patients. The authors describe an educational program, modification of a Geriatric Resource Nurse Model, and the use of a Geriatric Nurse Practitioner in implementing and integrating the clinical, psychosocial, and financial aspects that influence care needed by elderly patients and their families.


Amyloid β-peptide oligomers stimulate RyR-mediated Ca2+ release inducing mitochondrial fragmentation in hippocampal neurons and prevent RyR-mediated dendritic spine remodeling produced by BDNF.
Soluble amyloid β-peptide oligomers (AβOs), increasingly recognized as causative agents of Alzheimer's disease (AD), disrupt neuronal Ca(2+) homeostasis and synaptic function. Here, we report that AβOs at sublethal concentrations generate prolonged Ca(2+) signals in primary hippocampal neurons; incubation in Ca(2+)-free solutions, inhibition of ryanodine receptors (RyRs) or N-methyl-d-aspartate receptors (NMDARs), or preincubation with N-acetyl-l-cysteine abolished these signals. AβOs decreased (6 h) RyR2 and RyR3 mRNA and RyR2 protein, and promoted mitochondrial fragmentation after 24 h. NMDAR inhibition abolished the RyR2 decrease, whereas RyR inhibition prevented significantly the RyR2 protein decrease and mitochondrial fragmentation induced by AβOs. Incubation with AβOs (6 h) eliminated the RyR2 increase induced by brain-derived nerve factor (BDNF) and the dendritic spine remodeling induced within minutes by BDNF or the RyR agonist caffeine. Addition of BDNF to neurons incubated with AβOs for 24 h, which had RyR2 similar to and slightly higher RyR3 protein content than those of controls, induced dendritic spine growth but at slower rates than in controls. These combined effects of sublethal AβOs concentrations (which include redox-sensitive stimulation of RyR-mediated Ca(2+) release, decreased RyR2 protein expression, mitochondrial fragmentation, and prevention of RyR-mediated spine remodeling) may contribute to impairing the synaptic plasticity in AD.


Blood flow Restriction training After patellar INStability (BRAINS Trial).
Patellar instability is a common and understudied condition that disproportionally affects athletes and military personnel. The rate of post-traumatic osteoarthritis that develops following a patellar dislocation can be up to 50% of individuals 5-15 years after injury. Conservative treatment is the standard of care for patellar instability however, there are no evidence-informed rehabilitation guidelines in the scientific literature. The purpose of this study is to assess the effectiveness of blood-flow restriction training (BFRT) for patellar instability. Our hypotheses are that this strategy will improve patient-reported outcomes and accelerate restoration of symmetric strength and knee biomechanics necessary to safely return to activity. This is a parallel-group, superiority, randomized, double-blinded, placebo-controlled clinical trial at the University of Kentucky, sports medicine clinic that aims to recruit 78 patients with acute patellar dislocations randomly allocated into two groups: (1) sham BFRT and (2) BFRT. Both groups will receive the current standard of care physical therapy 3 times per week for up to 9 weeks. Physical therapy sessions will consist of typical standard of care treatment followed by BFRT or sham BFRT. Primary outcomes include the Norwich Patellar Instability Scale, quadriceps strength, and imaging and biochemical biomarkers of cartilage degradation. The current standard of care for non-operative treatment of patellar instability is highly variable does not adequately address the mechanisms necessary to restore lower extremity function and protect the long-term health of articular cartilage following injury. This proposed novel intervention strategy uses an easily implementable therapy to evaluate if BFRT significantly improves patient-reported outcomes, function, and joint health over the first year of recovery. Blood Flow Restriction Training, Aspiration, and Intraarticular Normal Saline (BRAINS) NCT04554212 . Registered on 18 September 2020.


Maternal factors contributing to asphyxia neonatorum.
The objective was to identify maternal risk factors for birth asphyxia, and took the form of a retrospective study over 3 years of 15,964 deliveries. The antenatal and intrapartum course of 68 mothers who delivered babies with birth asphyxia was studied. Babies < 34 weeks/< or = 2000 g at birth were excluded. A 5-min Apgar score < 6 was regarded as abnormal. The incidence of asphyxia neonatorum was 4.6/1000. Most mothers (76 per cent), resided locally, booked (91 per cent), and had satisfactory antenatal clinic attendance (average seven visits). The distribution showed a disproportionately large number of grand multiparas (10 per cent). Labour was characterized by prolonged first (49 per cent) and second (36 per cent) stages with a high incidence of meconium in the amniotic fluid (47 per cent). Most deliveries (53 per cent) were by caesarian section of which 44 per cent were performed for fetal distress. Meconium aspiration was common (34 per cent). High risk signs in labour can be recognized. The judicious use of the partogram, fetal scalp blood pH, and amino-infusion are encouraged.


Depletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation induced with tissue factor: evidence supporting a physiologic role for EPI as a natural anticoagulant.
Although in vitro experiments have established that extrinsic pathway inhibitor (EPI) is the only known plasma inhibitor of factor VIIa-tissue factor (TF) catalytic activity of potential physiologic significance, evidence of its function in vivo has been lacking. TF-induced intravascular coagulation may occur in patients despite normal plasma levels of EPI and, in our earlier studies, normal plasma EPI levels did not protect rabbits from intravascular coagulation induced by an infusion of purified TF (1 microgram/kg). Studies have now been carried out in which plasma EPI levels were reduced in rabbits to below 20% of the initial level by injection of anti-rabbit EPI IgG. Infusion into such animals of purified rabbit TF apoprotein (0.25 microgram/kg) reconstituted into phospholipid vesicles induced substantial disseminated intravascular coagulation. Infusion of control saline or phospholipid vesicles not containing TF was without significant effect as was infusion of TF (0.25 microgram/kg) into animals injected with nonimmune goat IgG. These data establish that EPI can dampen TF-induced intravascular coagulation in rabbits. They support the hypothesis that EPI plays a significant role in regulating coagulation resulting from the exposure of blood to trace concentrations of TF during the illnesses and minor injuries of normal existence.


Tipping the balance between replicative and simple transposition.
The bacterial insertion sequence IS903 has the unusual ability to transpose both replicatively and non-replicatively. The majority of products are simple insertions, while co-integrates, the product of replicative transposition, occur at a low frequency (<0.1% of simple insertions). In order to define the critical steps that determine the outcome of IS903 transposition, we have isolated mutants that specifically increase the rate of replicative transposition. Here we show that the nucleotide immediately flanking the transposon influences both overall transposition frequency and co-integrate formation. In particular, when the 3'-flanking nucleotide is A, co-integrates are increased 500-fold compared with a 3' C. In addition, we have isolated five transposase mutants that increase replicative transposition. These residues are close to the catalytic residues and are thus likely to be part of the active site. These are the first transposase mutations described that affect the product of transposition. Our results are consistent with the hypothesis that a delay in cleavage of the 5'-flanking DNA will increase the effective half-life of the 3'-nicked transposon intermediate and consequently enhance co-integrate formation.


Structural requirements for selective binding of ISC1 to anionic phospholipids.
Yeast ISC1 (Yer019w) encodes inositolphosphosphingolipid-phospholipase C and is activated by phosphatidylserine (PS) and cardiolipin (CL) (Sawai, H., Okamoto, Y., Lubert, C., Mao, C., Bielawska, A., Domae, M., and Hannun, Y. A. (2000) J. Biol. Chem. 275, 39793-39798). In this study, the structural requirements for anionic phospholipid-selective binding of ISC1 were determined using site-directed and deletion mutants. FLAG-tagged Isc1p was activated by PS, CL, and phosphatidylglycerol (PG) in a dose-dependent manner. Using lipid-protein overlay assays, Isc1p interacted specifically and directly with PS/CL/PG. Lipid-protein binding studies of a series of deletion mutants demonstrated that the second transmembrane domain (TMII) and the C terminus were required for PS binding. Moreover, the TMII and the C terminus domain were sufficient to impart PS binding to a heterologous protein, green fluorescence protein. In addition, mutations of positively charged amino acid residues at the C terminus of ISC1 reduced the activating effects of PS, suggesting involvement of these amino acids in interaction with PS/CL/PG and in the activation of the enzyme. Finally, when separate fragments containing the N terminus-TMI and TMII-C terminus were expressed heterologously, enzyme activity was reconstituted, demonstrating that the interaction of the N terminus and the C terminus is required for activity of Isc1p. These results raise the hypothesis that in the presence of PS/CL/PG, the catalytic domain in the N terminus of Isc1p is "pulled" to the membrane to interact with substrate. These studies provide unique insights into the properties of ISC1 and define a novel mechanism for activation of enzymes by lipids cofactors.


Multiple sex partners and perceived risk of HIV infection in Zambia: attitudinal determinants and gender differences.
While there is much attention on perceived risk of HIV and subsequent cautionary behavior, evidence of the reciprocity of the relationship between recent risky sexual behavior and perceived risks of HIV infection remains scarce. This paper tests the hypothesis that having multiple sex partners within the last 12 months influences individual's perceived risk of HIV among Zambian men and women. It also examines attitudinal factors associated with having multiple sex partners and perceived HIV risk. Data come from the 2005 Household and Community Surveys of the Health Communication Partnership project. The sample includes 2610 men and women, and 445 community leaders in 36 districts. Tests of exogeneity confirm that having multiple sex partners is exogenous to perceived risk of HIV infection. Structural equation modeling is employed to test the hypothesis. Findings show that having multiple partners is the strongest predictor of perceived risk of HIV. Men were also more likely than women to have multiple sex partners, but less likely to consider themselves at risk of HIV, compared to women. Men were also more likely to be influenced by their peers and community members. Women were more likely than men to report some risk of HIV if they were aware of their partner's serostatus and had more interpersonal communication on HIV. Married women were less likely to consider themselves at risk than unmarried women. The findings indicate that it is essential for men to recognize the connections between unsafe sex behaviors and risks of HIV infection and that distinct intervention approaches to Zambian men and women are needed. While couple communication needs to be enhanced for both, community-based interventions that approach men are particularly important.


Antifungal agents, Part 11. Biphenyl analogues of naftifine: synthesis and antifungal activities.
A series of naftifine analogues having the biphenyl instead of the naphthyl moiety have been synthesized in a search devoted to study bioanalogues of clinically efficacious antifungal agents. The new derivatives were tested against Candida albicans by the direct contact method. They were also assayed against Gram-positive and Gram-negative bacteria and against some isolates of plant pathogenic fungi. Derivatives 8a, 8c, and 9a were found to be active against Candida albicans, derivative 5a was active against E. coli, a very resistant species to antimycotic agents, and derivatives 8a and 8b inhibited the plant pathogenic Rhizoctonia solani.


Targeting 5-HT2A receptors and Kv7 channels in PFC to attenuate chronic neuropathic pain in rats using a spared nerve injury model.
Chronic pain remains a disabling disease with limited therapeutic options. Pyramidal neurons in the prefrontal cortex (PFC) express excitatory Gq-coupled 5-HT2A receptors (5-HT2AR) and their effector system, the inhibitory Kv7 ion channel. While recent publications show these cells innervate brainstem regions important for regulating pain, the cellular mechanisms underlying the transition to chronic pain are not well understood. The present study examined whether local blockade of 5-HT2AR or enhanced Kv7 ion channel activity in the PFC would attenuate mechanical allodynia associated with spared nerve injury (SNI) in rats. Following SNI, we show that inhibition of PFC 5-HT2ARs with M100907 or opening of PFC Kv7 channels with retigabine reduced mechanical allodynia. Parallel proteomic and RNAScope experiments evaluated 5-HT2AR/Kv7 channel protein and mRNA. Our results support the role of 5-HT2ARs and Kv7 channels in the PFC in the maintenance of chronic pain.


School reopening during COVID-19 pandemic: Considering students with disabilities.
Over 80% of the children in the world have had their education impacted by COVID-19. For children with disabilities who receive special education services, access to in-person education and other resources at school is particularly important. The American Academy of Pediatrics advocates for students to attend school in person, without specifics for how children with disabilities can safely return to school. To appropriately plan and accommodate children with disabilities we must prioritize safety, allow for adherence to the Individuals with Disabilities Education Act, and preserve essential school staff. The less cumbersome default of confining students with disabilities to home is not acceptable. We provide an outline describing why Individual Education Plans and 504 plans are important, how they are related to the COVID-19 pandemic, and recommendations for measures to help with safe return to school for children with disabilities.


PCR amplification of triosephosphate isomerase gene of Giardia lamblia in formalin-fixed feces.
Giardia lamblia (syn G. intestinalis, G. duodenalis) is the intestinal protozoan producing non-bacterial diarrhea most prevalent in the world. PCR genotype classification of Giardia in feces depends on the quality and quantity of purified DNA and the removal of a great number of inhibitors. The aim of this study was to adapt a PCR protocol to the amplification of the triosephosphate isomerase (tpi) gene of Giardia lamblia in formalin-fixed feces. The tpi gene of G. lamblia was amplified in 28 of the 34 analyzed samples (82.35%) and the B genotype was obtained in all cases. Two major modifications were implemented to improve the performance of PCR from formolated fecal matter. One of these improvements was the use of polyvinylpyrrolidone (PVP) and the other was the addition of bovine serum albumin (BSA). The PCR protocol used in this study showed an amplification percentage exceeding the values reported by other authors with high sensibility and specificity.


[Shear stress and platelet-derived microparticles].
One of the responses of activated platelets to certain stimuli is the shedding of microparticles. Many studies have attempted to characterize the role of microparticles under various clinical situations or experimental conditions. Pathological levels of fluid shear stress may occur in diseased small arteries and arterioles partially obstructed by atherosclerosis or vasospasm and such shear stress may induce the activation and aggregation of circulating platelets. We investigated whether high shear stress could cause both platelet aggregation and shedding of microparticles from the platelet plasma membrane. A cone-plate viscometer was used to apply shear stress and microparticle formation was measured by flow cytometry. It was found that microparticle formation increased as the duration of shear stress increased. Both microparticles and remnant platelets showed procoagulant activity on their surfaces. Investigation of the mechanisms involved in shear-dependent microparticle generation showed that binding of von Willebrand factor to platelet glycoprotein Ib, influx of extracellular calcium, and activation of platelet calpain were required to generate microparticles under high shear stress conditions. Activation of protein kinase C promoted shear-dependent microparticle formation. These findings suggest that local generation of microparticles in atherosclerotic arteries, the site at which pathological levels of shear stress could occur, contributes to arterial thrombosis by providing and expanding a catalytic surface for the coagulation cascade.


Biological and clinical implications of heat shock protein 27,000 (Hsp27): a review.
Heat shock and other environmental and pathophysiologic stresses stimulate synthesis of heat shock proteins (Hsps). These proteins enable the cell to survive and recover from stressful conditions by as yet uncompletely understood mechanisms. Hsp27 is an important small Hsp (molecular weight, 27,000) found in human cells--both cancer cells and normal cells. This protein, besides its putative role in thermotolerance, is of special clinical interest because of recent data suggesting it may also play a role in drug resistance. In adults, Hsp27 is found particularly in several cell types such as breast, uterus, cervix, placenta, skin, and platelets. Although low-molecular-weight (small) Hsps have been found to be involved in embryogenesis of Xenopus and Drosophila, they have not been detected in human fetal organs. Regulation of expression of the Hsp gene (also known as HSPB1) has been considered a paradigm of gene regulation and is actively being studied in both prokaryotes and eukaryotes. In prokaryotes, the major Hsp genes are transcriptionally regulated by positively and negatively acting transcription factors. In eukaryotes, the genes encoding Hsps contain a regulatory DNA motif (inverted repeats of the pentameric sequence nGAAn) known as the heat shock element. Hsp27 may function as a molecular chaperone and in signal transduction pathways of different cell regulators, and Hsp27 and other Hsps may be active in development of resistance to stressful conditions and agents including cytotoxic drugs. Study findings indicate that some but not all estrogen-positive breast cancers express Hsp27, and overexpression of Hsp27 has been associated with both good and poor prognosis. In endometrial carcinomas, the presence of Hsp27 is correlated with the degree of tumor differentiation as well as with the presence of estrogen and progesterone receptors. Studies suggest, however, that detection of Hsp27 should not be considered to be a method for identifying hormone-responsive tumors or detecting estrogen receptors. Hsp27 seems to be a biochemical marker of estrogenic endometrial response. In patients with cervical cancer, Hsp27 is predominantly expressed in well-differentiated and moderately differentiated squamous cell carcinomas. In addition, expression of Hsp27 seems to be a negative prognostic factor for gastric cancer. Different isoforms of Hsp27 have been found in lymphoid tissue of patients with acute lymphoblastic leukemia, and the protein has also been associated with viral infections. These aspects are summarized and discussed in the present review.


[Early measurement of intracranial pressure in polytrauma with associated craniocerebral trauma. I: Principles].
In West Germany, head injury is the major cause both of death following trauma and of irreversible cerebral damage. The successful management of these cases largely depends on the prevention and treatment of secondary rises in intracranial pressure. The only certain way of detecting such increases is with the invasive technique of intracranial pressure monitoring. The pressure module should be implanted as soon as possible, ideally, before extensive definitive surgical treatment is carried out. Ease of usage has led us to prefer epidural pressure monitoring systems. Being relatively easy to learn and apply, this form of monitoring should be used in all hospitals involved in the treatment of severe head injury.


Identifying Patients at Higher Risk of Depression Among Patients with Vitiligo at Outpatient Setting.
Chronic skin diseases including vitiligo could have profound psychological burden. The factors influencing the expression of depression in patients with vitiligo received little attention both nationally and internationally. The aim of the current study was to estimate the burden and severity of depression and to characterize their associated sociodemographic and clinical characteristics among patients with vitiligo. A cross-sectional survey study was conducted among patients with vitiligo of both genders attending dermatology outpatient clinics at a tertiary care hospital during 2019. Modified Beck Depression Inventory Scale was used for screening for depression. A total 308 patients with vitiligo have been included in the current analysis. The average age was 27±14.5 years. Approximately 59.7% of the patients were males and the majority (63.6%) were single. A total 168 (54.5%) patients had some depressive symptoms. The majority of these patients had mild depression (52.4%), followed by moderate (33.3%) and severe (14.3%) depression. Moderate and/or severe depression were significantly higher among children and adolescents (p=0.036), single patients (p=0.006), those with lower than high school education (p<0.001), those with shorter duration of the disease (p<0.001), and those using phototherapy (p=0.003). Depression burden and severity were not significantly associated with gender and lesion distribution. Sociodemographic and clinical characteristics can easily characterize the risk of depression among patients with vitiligo. The current findings may help dermatologist to pick patients at higher risk of depression early after diagnosis of vitiligo. Dermatologists should have low threshold for referring such patients to psychiatry clinics.