Ventricular and Periventricular Anomalies in the Aging and Cognitively Impaired Brain.
Ventriculomegaly (expansion of the brain's fluid-filled ventricles), a condition commonly found in the aging brain, results in areas of gliosis where the ependymal cells are replaced with dense astrocytic patches. Loss of ependymal cells would compromise trans-ependymal bulk flow mechanisms required for clearance of proteins and metabolites from the brain parenchyma. However, little is known about the interplay between age-related ventricle expansion, the decline in ependymal integrity, altered periventricular fluid homeostasis, abnormal protein accumulation and cognitive impairment. In collaboration with the Baltimore Longitudinal Study of Aging (BLSA) and Alzheimer's Disease Neuroimaging Initiative (ADNI), we analyzed longitudinal structural magnetic resonance imaging (MRI) and subject-matched fluid-attenuated inversion recovery (FLAIR) MRI and periventricular biospecimens to map spatiotemporally the progression of ventricle expansion and associated periventricular edema and loss of transependymal exchange functions in healthy aging individuals and those with varying degrees of cognitive impairment. We found that the trajectory of ventricle expansion and periventricular edema progression correlated with degree of cognitive impairment in both speed and severity, and confirmed that areas of expansion showed ventricle surface gliosis accompanied by edema and periventricular accumulation of protein aggregates, suggesting impaired clearance mechanisms in these regions. These findings reveal pathophysiological outcomes associated with normal brain aging and cognitive impairment, and indicate that a multifactorial analysis is best suited to predict and monitor cognitive decline.


A new technique allowing prolonged temporary cerebral artery occlusion.
Clipping of complex cerebral aneurysms often requires temporary vessel occlusion. The risk of stroke, however, increases exponentially with occlusion time. The authors hypothesized that prolonged temporary occlusion might be tolerated if the occluded vessels were perfused with cold physiological saline solution (CPSS). A low-flow perfusion rate would permit surgical manipulation of an aneurysm distal to the occlusion. To test this hypothesis, the authors temporarily occluded the middle cerebral artery (MCA) with an endovascular catheter in 6 rats. Three animals, the treatment group, were perfused with 5-ml CPSS/hour through the occluding endovascular catheter into the MCA, and the other 3 served as an ischemic control group. In both groups, the catheter was removed after 90 minutes of occlusion. The brain temperature was monitored with a stereotactically placed probe in the caudate-putamen in 2 separate experimental groups (11 animals). Magnetic resonance imaging perfusion scanning during vessel occlusion confirmed similar reduction of cerebral blood flow during MCA occlusion in both the simple-occlusion and perfusion-occlusion groups. Magnetic resonance imaging diffusion scans performed 24 hours after temporary occlusion revealed infarcts in the ischemic control group of 138.3 +/- 28.0 mm(3) versus 9.9 +/- 9.9 mm(3) in the cold saline group (p < 0.005). A focal cooling effect during perfusion with CPSS was demonstrated (p < 0.05). Prolonged temporary cerebral vessel occlusion can be tolerated using superselective CPSS perfusion through an occluding endovascular catheter into the ischemic territory. This technique could possibly be applied in neurosurgery practice to the management of complex intracranial aneurysms.


Improving Learning Outcomes: The iPad and Preschool Children with Disabilities.
The digital age has reached early childhood, and the use of touch screens by young children is common place. Research on the use of touch screen tablets with young children is becoming more prevalent; however, less information is available on the use of touch screen tablets to support young children with disabilities. Touch screen tablets may offer possibilities to preschool children with disabilities to participate in learning in a digital way. The iPad provides easy interaction on the touch screen and access to a multitude of engaging early learning applications. This paper summarizes a pilot study with 8 young children with disabilities included in a preschool classroom, who were given iPads to use in class and at home for a period of 21 weeks. Systematic observations, classroom assessments, and teacher and parent interviews documented the improvements in learning outcomes for each child in many areas including, but not limited to: shape and color recognition, letter recognition, and tracing letters throughout six research cycles.


Interactions of aflatoxin with histones and DNA.
The interactions of aflatoxin B(1) with certain histone fractions and DNA were investigated by means of viscosity measurements and equilibrium dialysis. Two main histone fractions (F2b and F1), both lysine-rich, were examined after treatment with the toxin. Fraction 2b and 1 differ in amino acid composition and behave differently, in regard to gross conformation, in the presence of electrolytes. Aflatoxin increased the viscosity of fraction 2b but affected the viscosity of fraction 1 only slightly. Equilibrium dialysis experiments showed that aflatoxin was bound to both histone fractions. Aflatoxin also increased the viscosity of DNA and equilibrium dialysis showed that 1 molecule of the toxin was bound to approximately every 5 nucleotides of the nucleic acid. Binding constants for the aflatoxin complexes were calculated as 1000 for F2b, 700 for F1, and 5500 for DNA. The biological implications of these data, in regard to the effect aflatoxin has on the information-transcription process, are discussed.


[The chemical composition of Aureobasidium (Pullularia) pullulans cells].
Amino acid composition of total protein, free intracellular amino acids, reducing substances, nucleic acids, lipids, vitamins of the B group, and mineral composition were studied in the cells of Aureobasidium (Pullularia) pullulans, strain 8. Protein contained all 11 essential amino acids. The content of these substances was the following: nucleic acids, 1.5%; protein, 30.83+/-0.2%; reducing substances, 35.3+/-0.1%; lipids, 14.03+/-0.36%; ash, 794+/-4 mg%. Among six studied vitamins (B1, B3, B6, PP, B7, B8), the content of inositol was highest (398.2 mcg/g), B3 was not found, and only traces of other vitamins were detected.


Coupled slow and fast surface dynamics in an electrocatalytic oscillator: model and simulations.
The co-existence of disparate time scales is pervasive in many systems. In particular for surface reactions, it has been shown that the long-term evolution of the core oscillator is decisively influenced by slow surface changes, such as progressing deactivation. Here we present an in-depth numerical investigation of the coupled slow and fast surface dynamics in an electrocatalytic oscillator. The model consists of four nonlinear coupled ordinary differential equations, investigated over a wide parameter range. Besides the conventional bifurcation analysis, the system was studied by means of high-resolution period and Lyapunov diagrams. It was observed that the bifurcation diagram changes considerably as the irreversible surface poisoning evolves, and the oscillatory region shrinks. The qualitative dynamics changes accordingly and the chaotic oscillations are dramatically suppressed. Nevertheless, periodic cascades are preserved in a confined region of the resistance vs. voltage diagram. Numerical results are compared to experiments published earlier and the latter reinterpreted. Finally, the comprehensive description of the time-evolution in the period and Lyapunov diagrams suggests further experimental studies correlating the evolution of the system's dynamics with changes of the catalyst structure.


An International Perspective on Feigned Mental Disabilities: Conceptual Issues and Continuing Controversies.
In forensic contexts, an increased prevalence of feigned symptom presentations should be expected, although it will probably vary by the context and specific forensic issue. Forensic experts should examine this possibility proactively while maintaining a balanced perspective that actively considers clinical data for both feigning and genuine responding. Psychological measures and standardized methods developed for feigning and other response styles can facilitate these often complex determinations. The current article provides an international perspective on the issue of feigned mental disabilities. In particular, important conceptual issues are discussed, such as the categorical versus dimensional approaches to feigning, and the advisability of well-defined rather than single-point cut scores for accuracy in clinical decision-making. Salient problems of differential diagnosis include a spectrum from malingering and factitious disorders to somatoform and conversion disorders. In rendering these important diagnostic distinctions, the questions of motivations and intentions remain key. However, the establishment of motivation cannot be facilely assumed from the context. Instead, forensic psychologists and psychiatrists bear the professional burden of carefully evaluating motivation and recognizing the clinical reality that sometimes the motivation in especially challenging cases may not be fully determined. Copyright © 2017 John Wiley & Sons, Ltd.


Trends in the prevalence and severity of periodontal diseases in the US: a public health problem?
This article reviews trends in the prevalence and severity of periodontal diseases in US adults and examines the implications of these trends regarding the recognition of periodontal disease as a public health problem. Data from the National Center for Health Statistics (NCHS) examination surveys, 1960-62 and 1971-74, and the National Institute of Dental Research (NIDR) 1985-86 Survey of Employed and Senior Adults are examined. Issues of comparability and generalizability are discussed. Changes in the prevalence and severity of gingivitis and periodontitis are presented for the time periods 1960-62 to 1971-74 and 1971-74 to 1985-86. We concluded (1) it is difficult to document the changes occurring in the prevalence of gingivitis; however, given the available evidence, the prevalence and severity of gingivitis have probably declined; (2) it appears that periodontitis continues to affect approximately the same proportions of the overall US adult population; but with those affected, the extent and severity of the disease have declined; and (3) older adults continue to exhibit more disease and greater levels of severe disease than the younger age groups. Renewed efforts to clarify the epidemiologic confusion concerning trends in the prevalence and severity of periodontal disease should remain high on the agenda for public health dentistry.


[Do kinins have significance for the antihypertensive effect of angiotensin-converting enzyme inhibitors?].
Inhibition of angiotensin I converting enzyme (ACE, kininase II) results in a reduced release of angiotensin II and in an accumulation of kinins. By pretreatment with inhibitors of the kallikrein-kinin systems, the blood pressure lowering effect of the ACE-inhibitors will be diminished. These results suggest that potentiation of kinins will participate in the blood pressure reduction by ACE-inhibitors. However, other studies contradict this hypothesis, showing that the inhibition of kallikrein-kinin systems per se will often result in a reduction of stimulated renin activity. Even the measurement of kinins in the blood cannot clarify the role of kinins in ACE-inhibition. Some new investigations discuss only a local and tissue-specific enhancement of kinins after ACE-inhibition, but up to now strong evidence for participation of kinins by local mechanisms in the action of ACE-inhibitors is still missing.


A systematic review of MRI, scintigraphy, FDG-PET and PET/CT for diagnosis of multiple myeloma related bone disease--which is best?
The purpose of the current study was to conduct a systematic review of the published literature to evaluate the diagnostic accuracy of FDG-PET, PTE/CT, MRI and scintigraphy for multiple myeloma related bone disease. Through a search of PubMed, EMBASE, and the Cochrane Library, two reviewers independently assessed the methodological quality of each study. We estimated pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), and two sample Z-tests were conducted to evaluate for differences in sensitivity, specificity, area under the curve (AUC), and the Q* index between any two diagnostic modalities. A total of 17 studies were reviewed. The MRI had a pooled sensitivity of 0.88, specificity of 0.68, AUC of 0.897, and Q*index of 0.828, whereas for MIBI, the corresponding values were 0.98, 0.90, 0.991, and 0.962, respectively, and for bone scan, they were 066, 0.83, 0.805, and 0.740, respectively. The corresponding values of MIBI were 0.98, 0.90, 0.991, and 0.962, respectively. For PET and PET/CT, the values were 0.91, 0.69, 0.927 and 0.861, respectively. Statistically significant differences were not found in the sensitivity, specificity, AUC, and Q* index between MRI, scintigraphy, FDG-PET and PET/CT. On the condition that X ray is taken as a reference in our study, we suggested that FDG-PET, PTE/CT, MRI and scintigraphy are all associated with high detection rate of bone disease in patients with MM. Thus, in clinical practice, it is recommended that we could choose these tests according to the condition of the patient.


Structural studies of EcoRII methylase: exploring similarities among methylases.
EcoRII methyltransferase (M.EcoRII) is a cytosine-C5 DNA methylating enzyme. A model of its three-dimensional structure is proposed on the basis of homology modeling. Crystal structures of two members of the same family of enzymes, HaeIII and HhaI methyltransferases (M.HaeIII and M.HhaI respectively), were used as template molecules. Molecular dynamics was used to ensure sampling of conformationally stable structures. The final model has good geometry. The DNA and cofactor binding residues are in expected positions and form proper interactions. M.EcoRII is 147 amino acids longer than the template molecules, and hence the model contains several loops that are significantly longer than those in M.HaeIII and M.HhaI. The model provides a framework for interpretation and designing site-directed mutants that have a potential to improve crystallization experiments of this enzyme, and possibly other similar enzymes.


Impact of Superantigen-Producing Bacteria on T Cells from Tonsillar Hyperplasia.
Staphylococcus aureus and Group A Streptococcus (GAS) are common occupants of the tonsils and many strains produce potent exotoxins (mitogens) that directly target T cells, which could be a driver for tonsillar hyperplasia. Tonsil tissues from 41 patients were tested for these bacteria in conjunction with profiling of B and T cells by flow cytometry. S. aureus and GAS were detected in tonsil tissue from 44% and 7%, respectively, of patients by bacteriological culture; immuno-histology showed bacteria in close proximity to both B and T lymphocytes. The presence of tonsillar S. aureus did not alter B or T cell populations, whereas peripheral blood mucosal-associated invariant T (MAIT) cells were significantly increased in S. aureus culture positive individuals (p < 0.006). Alterations of tonsil CD4+ TCR Vβ family members relative to peripheral blood were evident in 29 patients. Three patients had strong TCR Vβ skewing indicative of recent exposure to superantigens, their tonsils contained mitogenic bacteria, and supernatants from these bacteria were used to partially recapitulate the skewing profile in vitro, supporting the notion that superantigens can target tonsillar T cells in situ. Tonsils are a reservoir for superantigen-producing bacteria with the capacity to alter the composition and function of key immune cells.


Non-standard numerical methods applied to subsurface biobarrier formation models in porous media.
Biofilm forming microbes have complex effects on the flow properties of natural porous media. Subsurface biofilms have the potential for the formation of biobarriers to inhibit contaminant migration in groundwater. Another example of beneficial microbial effects is the biotransformation of organic contaminants to less harmful forms, thereby providing an in situ method for treatment of contaminated groundwater supplies. Mathematical models that describe contaminant transport with biodegradation involve a set of coupled convection-dispersion equations with non-linear reactions. The reactive solute transport equation is one for which numerical solution procedures continue to exhibit significant limitations for certain problems of groundwater hydrology interest. Accurate numerical simulations are crucial to the development of contaminant remediation strategies. A new numerical method is developed for simulation of reactive bacterial transport in porous media. The non-standard numerical approach is based on the ideas of the 'exact' time-stepping scheme. It leads to solutions free from the numerical instabilities that arise from incorrect modeling of derivatives and reaction terms. Applications to different biofilm models are examined and numerical results are presented to demonstrate the performance of the proposed new method.


Group A streptococcal genotypes from throat and skin isolates in the United Arab Emirates.
The bacterium Streptococcus pyogenes causes a variety of human diseases that range from relatively mild skin infections to severe invasive diseases, such as acute rheumatic fever, glomerulonephritis, puerperal sepsis, necrotizing fasciitis, meningitis, and streptococcal toxic shock syndrome. Accurate identification and typing of group A hemolytic streptococci (GAS) is essential for epidemiological and pathogenetic studies of streptococcal diseases. For this reason, The genetic diversity of group A streptococcal (GAS) isolates from subjects in the United Arab Emirates with streptococcal disease was studied using emm gene sequence analysis. The emm typing system which is based on sequence analysis of PCR products of the N-terminal hypervariable region of the M protein gene, concurs with M serotyping almost 1:1. A total of 38 GAS isolates were analyzed, including 35 isolates from throat and 3 from skin. Among the 38 isolates, a total of 25 different emm/st types were detected: 20 isolates (53%) belonged to 16 validated standard reference emm types and 18 isolates (47%) belonged to 9 recognized sequence types. This is the first emm typing study in the United Arab Emirates to demonstrate the heterogeneity of the GAS population.


Neuropsychological symptom presentation after electrical injury.
This study explored the relationship of neuropsychological complaints to accident- and injury-related characteristics, affective state, and work status in a group of electrical injury (EI) patients. Sixty-three EI patients and 22 electricians with no history of electrical shock completed the Neuropsychological Symptom Checklist and the Beck Depression Inventory as part of an extensive neuropsychological evaluation. The EI group endorsed significantly more physical, cognitive, and emotional symptoms than did the controls. Symptom complaints were not related to injury parameters or litigation status. Only the time interval between injury and assessment accounted for differences in symptom presentation, with patients in the postacute stages of recovery showing the most cognitive and emotional complaints. The neuropsychological syndrome of electrical injury survival includes physical, cognitive, and emotional complaints. Considering that most electrically injured patients are treated within the acute medical setting, greater attention needs to be directed early in the course of treatment toward addressing neuropsychologic and psychiatric issues.


Can technology assessment control health spending?
Because medical technology is the most important controllable component of health spending growth, the success of strategies for limiting spending growth depends upon their impact on technology dissemination. Technology assessment is fundamental to any strategy for controlling the adoption of medical technologies. Cost-effectiveness analysis holds particular promise as a method for evaluating alternative health care technologies because it explicitly incorporates costs. This paper describes how the widespread adoption of health insurance promoted the dissemination of medical technologies and how technology dissemination fueled spending growth. It then describes approaches to technology assessment and the ways in which technology assessment, in the form of cost-effectiveness analysis, can be applied to help control spending growth.


[Vulnerability: concept analysis in the clinical practice of nurses from outpatient HIV/AIDS].
This is a reflective article, which aims to discuss the concept of vulnerability and its implications for clinical nursing. Were discussed theoretical concept and how this fits into the area of health as possible to prevent AIDS. We realized that to understand the forms of illness of the subjects, we must understand them as well as biological aspects and take into account cultural, psychological, socio-economic and political, that is, any kind of situation which results in susceptibility to illness. We propose the use of the concept of vulnerability as a useful tool in nursing consultation. This should be at an opportune time for an exchange of knowledge and narrowing of the ties.


Nursing education and international health in the United States, Latin America, and the Caribbean.
To identify international health activities in United States, Latin American, and Caribbean schools of nursing. In the international community, nurses face challenges similar to those in related professions, but without the benefit of a long tradition. There is little research about how nursing education and associated activities prepare nurses to deal with international health, and little information about the extent of international health activities in U.S. schools of nursing. Descriptive. Using a questionnaire with 16 items, a survey was conducted in 1995 on a random sample of representatives from 100 university schools of nursing in the United States plus 15 schools with known international activities (10 from the United States and 5 from Latin America and the Caribbean). International health as a program topic was found in one-third of U.S. schools of nursing. However, nursing curriculums do not integrate international health with other subjects. Also, partnerships with foreign institutions are incipient and international health activities are usually individual initiatives with little institutional support. For nurses to become major contributors to international health, nursing curriculum content must shift from "international nursing" to "international health." Programs of nursing education should include study of social, economic, and political factors that affect health care systems. Schools should develop partnership agreements.


Label-Free Detection of Post-translational Modifications with a Nanopore.
Post-translational modifications (PTMs) of proteins play key roles in cellular processes. Hence, PTM identification is crucial for elucidating the mechanism of complex cellular processes and disease. Here we present a method for PTM detection at the single-molecule level using FraC biological nanopores. We focus on two major PTMs, phosphorylation and glycosylation, that mutually compete for protein modification sites, an important regulatory process that has been implicated in the pathogenic pathways of many diseases. We show that phosphorylated and glycosylated peptides can be clearly differentiated from nonmodified peptides by differences in the relative current blockade and dwell time in nanopore translocations. Furthermore, we show that these PTM modifications can be mutually differentiated, demonstrating the identification of phosphorylation and glycosylation in a label-free manner. The results represent an important step for the single-molecule, label-free identification of proteoforms, which have tremendous potential for disease diagnosis and cell biology.


[Lesions of the posterior visual pathways: clinical presentation and mechanisms of functional restoration].
The present paper begins with a brief discussion of general clinical features found in patients with lesions of the posterior visual pathways. The author goes on to discuss various mechanisms of restitution of function in the central nervous system, including activation of neural pathways subserved by spared neurons, metabolic modulations, and neural plasticity.


Clinical applications of the auditory middle latency response.
The auditory middle latency response (AMLR) was first reported 30 years ago. For a variety of reasons, the AMLR was relatively slow to gain clinical acceptance. However, renewed investigational efforts into the nature of the response is leading to a better understanding of the AMLR's characteristics, limitations, and appropriate clinical applications. This paper reviews the current status of the AMLR with regard to clinical utilization and proposes anticipated directions of clinical endeavors.


[Visual acuity loss, the initial sympton of a spinal cord neoplasm].
A 46-year-old woman, who presented with right visual acuity loss, was found to have papilledema, and subsequently shown to have ventricular dilatation in a cerebral Magnetic Resonance Imaging (MRI) assessment. Elevated protein levels were found in the cerebrospinal fluid. Spinal MRI revealed the presence of a spinal cord neoplasm. After surgical removal of the tumor, which turned out to be a neurilemmoma, the patient's visual acuity was restored. The ocular presentation and the relationship between intracranial hypertension and spinal tumors are discussed. Likewise, the importance of considering the various causes of papilledema is emphasized.


Feelings About Fracking: Using the Affect Heuristic to Understand Opposition to Coal Seam Gas Production.
The rapid expansion of coal seam gas (CSG) extraction across Australia has polarized public opinion about the risks, benefits, and the future of the industry. We conducted a randomized controlled experiment to assess the impact of CSG messaging on opposition to the CSG industry. Residents of a major Australian city (N = 549), aged between 21 and 87 years, were randomly assigned to view one of three brief video messages (pro-CSG, anti-CSG, or a neutral control) sourced from the Internet. They then completed measures assessing CSG affective associations, perceived risks and benefits of CSG, and degree of opposition to the CSG industry. A subsample of 317 participants also completed the measures of affect, risks, benefits, and opposition two weeks following the initial message presentation. Message type significantly predicted message effects in a pattern consistent with the affect heuristic model, although overall, the message effects were modest in magnitude. Respondents who viewed the anti-CSG video (relative to the control) reported more negative affective responses to CSG, perceived higher risks, fewer benefits, and greater opposition to the CSG industry. Those who viewed the pro-CSG video (relative to the control) reported stronger positive affective responses to CSG, perceived more CSG benefits and fewer risks, and expressed less opposition to the industry. The effects persisted over a two-week interval for the anti-CSG message, but not for the pro-CSG message. Our findings suggest that people's risk perceptions and views about the acceptability of CSG are malleable by messaging that targets affective pathways.


Nasolacrimal duct obstruction in children: outcome of primary intubation.
To evaluate the outcome of nasolacrimal intubation as a primary treatment of congenital nasolacrimal duct obstruction (NLDO) in children up to 4 years of age. During the 3 years period from July 2008 to June 2011, in the Paediatric Ophthalmology Department. Alshifa Trust Eye Hospital, Rawalpindi, 65 eyes of 59 children, aged 12 to 48 months with congenital NLDO and no prior Nasolacrimal duct surgery were enrolled. After written informed consent, all nasolacrimal intubations using olive tip silicon tube were performed under general anaesthesia. The planned tube retention was at least 3 months. The study outcome visit was timed 1 month after tube removal and treatment success was analyzed. Intra operative and post operative complications were also noted. Data were analyzed by SPSS 16. Frequencies and percentages were calculated for categorical variables. Mean +/- SD were computed for age and duration of intubation. Chi-square test was used to compare proportion of outcomes in different age groups and duration. The overall success rate of Nasolacrimal intubation as a primary treatment of congenital NLDO was 89% in children between 12 to 48 months age (mean 25.8 +/- 9.8 months). The success was 92% in children under 2 years of age (P < 0.0001) and 90% in children between 2-3 years of age (P < 0.0001). The procedure remained less successful in children between 3-4 years of age (P < 0.2860) as compared to children under 3 years of age. The success rate was consistently high (92.3%) when the tube was left in situ for more than 3-6 months (P < 0.0001). Nasolacrimal intubation with Olive tip silicon intubation tube is a successful procedure as a primary treatment of Nasolacrimal duct obstruction in children under 4 years of age.


A 16-Year-old Boy with Combined Volatile and Alcohol Dependence: A Case Report.
Substance abuse has been defined as the use of chemical substances for non medical purposes in order to achieve alterations in psychological functioning. The substances commonly abused in India include nicotine, alcohol, cannabis and opioids. However, the use of solvents and propellants is also on the rise as these are inexpensive, legally available household, industrial, office and automobile products; which are more commonly available to children and adolescents. We hereby describe a 16-year-old boy with combined volatile and alcohol abuse; who presented with increasing ataxia, visual and hearing disturbances.


In vivo gene delivery. Efficient transfection of T lymphocytes in adult mice.
We have demonstrated that a single intraperitoneal injection of cationic liposomes complexed to a chloramphenicol acetyltransferase (CAT) gene expression plasmid can transfect the majority of splenic Thy 1.2+ T lymphocytes, as well as significant numbers of bone marrow-derived hematopoietic cells, in adult mice. CAT activity was detected in the spleen for at least 2 weeks, and there was no evidence of treatment-related toxicity. Some degree of tissue-specific transgene expression was achieved by varying the cationic lipid used.


The animal models of dementia and Alzheimer's disease for pre-clinical testing and clinical translation.
Dementia is a clinical syndrome with abnormal degree of memory loss and impaired ability to recall events from the past often characterized by Alzheimer's disease. The various strategies to treat dementia need validation of novel compounds in suitable animal models for testing their safety and efficacy. These may include novel anti-amnesic drugs derived from synthetic chemistry or those derived from traditional herbal sources. Multiple approaches have been adopted to create reliable animal models ranging from rodents to non-human primates, where the animals are exposed to a predetermined injury or causing genetic ablation across specific regions of brain suspected to affect learning functions. In this review various animal models for Alzheimer's disease and treatment strategies in development of anti dementia drugs are discussed and an attempt has been made to provide a comprehensive report of the latest developments in the field.


Vγ9Vδ2 T lymphocytes activation in osteoporotic patients treated with bisphosphonates.
Treatment with bisphosphonates induces differentiation and activation of Vγ9Vδ2 T lymphocytes obtained from peripheral blood showing also an antitumoral effect in both in vitro and in vivo models. Aim of the present study was to determine in vivo the effect of BPs treatment in patients affected with osteoporosis on Vγ9Vδ2 T lymphocytes. We have studied Vγ9Vδ2 T lymphocytes expansion and differentiation from PBMC obtained from osteoporotic patients treated with one of the following bisphosphonates zoledronate, alendronate, neridronate or risedronate. We have found that zoledronic acid, followed by alendronate was the most effective on reducing CM population (100%) and increasing TEM and TEMRA γδ population. Our results indicate that in vivo treatment with BPs induces Vγ9Vδ2 cells to mature toward the effector phenotype, which may induce more antiresorptive responses.


[Syndrome of inappropriate secretion of antidiuretic hormone and neurotoxicity induced by vincristine and alkylating agents during chemotherapy for malignant lymphoma of thyroid gland].
We report a syndrome of inappropriate secretion of antidiuretic hormone (SIADH), neurotoxicity and facial erythema induced by several anti-cancer drugs in a case of malignant lymphoma of thyroid gland. A 68-year-old male was admitted, complaining of neck tumor and dyspnea. On admission, he was treated with vincristine (VCR) for bronchostenosis due to malignant lymphoma. Neck tumor and mediastinal lymph node swelling reduced. On the ninth day after chemotherapy of VCR, a consciousness disturbance was found and he was diagnosed as having SIADH. Following chemotherapy of cyclophosphamide, SIADH was also induced so he was treated with irradiation for neck and mediastinal field, instead of chemotherapy. During irradiation, however, enlargement of systemic lymph nodes appeared, and the chemotherapy was resumed. He achieved partial remission, but somnolence after ifosfamide and facial erythema after ranimustine were observed. In spite of the difference in the chemical structure of these anti-cancer drugs, several side effects occurred. It is suggested that the direct effects of drugs on the nervous system were SIADH and neurotoxicity.


A KASP Genotyping Method to Identify Northern Watermilfoil, Eurasian Watermilfoil, and Their Interspecific Hybrids.
The invasive aquatic plant Eurasian watermilfoil (Myriophyllum spicatum L.) can hybridize with the related North American native species northern watermilfoil (M. sibiricum Kom.). Hybrid watermilfoil (M. spicatum × M. sibiricum) populations have higher fitness and reduced sensitivity to some commonly used aquatic herbicides, making management more difficult. There is growing concern that management practices using herbicides in lakes with mixed populations of watermilfoil species may further select for hybrid individuals due to the difference in herbicide sensitivity. Accurate and cost-effective identification of rare hybrid individuals within populations is therefore critical for herbicide management decisions. Here we describe KASP assays for three SNPs in the ITS region to genotype individuals from both parental watermilfoil species and their hybrid, using synthesized plasmids containing the respective sequences as positive controls. Using KASP we genotyped 16 individuals from one lake and 23 individuals from a second lake, giving a highly accurate picture of Myriophyllum species distribution dynamics. We identified one hybrid individual among 16 samples from one lake, a discovery rate of <10%. Discriminant analysis showed that while a single SNP was generally sufficient for genotyping an individual, using multiple SNPs increased the reliability of genotyping. In the future, the ability to genotype many samples will provide the ability to identify the presence of rare individuals, such as a less common parental species or the inter-specific hybrid. Lakes with complex species distribution dynamics, such as a low proportion of hybrids, are where herbicide application must be carefully chosen so as not to select for the more vigorous and less herbicide-sensitive hybrid individuals.


Asthma--something old, something new ....
Asthma is an inflammatory disease characterized by infiltration of the airways by eosinophils and ensuing bronchial hyperresponsiveness. The activation of eosinophils and their recruitment to the airways are strongly influenced by T-lymphocytes and their products. There is now evidence that successful therapy of asthma results in changes in the ratios of helper and suppressor T-lymphocytes both in the circulation and in bronchoalveolar lavage fluid. Theophylline, a drug which has been used in asthma therapy for many years, provides additional benefit for patients already treated with effective doses of beta-agonists and/or corticosteroids. The effects of theophylline on lymphocyte traffic and function have not been studied extensively. However, there is evidence from studies conducted in renal transplant recipients and patients with asthma that theophylline increases the numbers and activity of suppressor T-lymphocytes in the peripheral circulation. This property of theophylline may provide a therapeutic benefit in the treatment of asthma, one that is distinct from its activity as a bronchodilator.


Multipotent mesenchymal stromal cells are sensitive to thermic stress - potential implications for therapeutic hyperthermia.
Purpose: Hyperthermia demonstrated clinical efficacy in multimodal cancer treatment. Multipotent mesenchymal stromal cells (MSCs) as part of the tumor-supporting stroma modulate tumor response and tissue regeneration after hyperthermia. We aimed to investigate the effects of hyperthermia on the survival, stem cell characteristics and heat shock expression of human MSCs.Materials and methods: Human MSCs and normal human dermal fibroblasts (NHDFs) were exposed to temperatures between 37 °C and 44 °C for 60 min, and hyperthermic sensitivity was examined by clonogenicity, proliferation and viability assays. The influence of 42 °C hyperthermia on the MSCs' adhesion potential, migratory capacity, surface marker expression and multi-lineage differentiation capability was investigated. Cell cycle distribution, apoptosis and senescence after 42 °C hyperthermia were determined by flow cytometry and β-galactosidase staining. Heat shock protein expression was determined by Western Blots.Results: MSCs exhibited decreased clonogenic survival after 40 °C and 42 °C hyperthermia compared to NHDFs, while proliferative activity and viability were comparable after hyperthermia up to 44 °C. MSC adhesion was reduced after 42 °C hyperthermia, while the characteristic surface marker expression and the migratory ability remained unaffected in 42 °C hyperthermia-exposed MSCs. 42 °C hyperthermia diminished the adipogenic differential potential of all tested MSC samples. A pronounced G2/M arrest was found after 42 °C hyperthermia and was associated with increased apoptosis and senescence levels in MSCs. MSCs exhibited slightly lower heat shock protein levels compared to NHDFs.Conclusion: Human MSCs exhibit a thermosensitive phenotype which reduced the multipotent cells' regenerative abilities, resulting in impaired tissue regeneration after hyperthermia treatment or thermal injuries. On the other hand, tumor-associated MSCs may be efficiently targeted by hyperthermia treatment.


Remote access perfusion for minimally invasive cardiac surgery: to clamp or to inflate?
Endoaortic balloon occlusion (EBO) and aortic transthoracic clamping (TTC) are the dominant methods of remote access perfusion (RAP) in minimally invasive cardiac surgery. The aim of the study was to compare the two methods in terms of feasibility, success and complications. From June 2001 to November 2011, 307 (median age; range) (57; 16-77 years) and 460 (62; 11-88 years) patients underwent minimally invasive CABG, ASD and mitral valve surgery using EBO and TTC, respectively. Perioperative procedure feasibility, success and postoperative complications were recorded. Overall 30-day mortality was 0 and 2 (0.43%) for the EBO and TTC groups, respectively (P = 0.52). Overall and RAP-associated conversions were noted in 21 (6.8%) and 4 (1.3%) patients in the EBO and in 9 (2%) and 6 (1.3%) patients in the TTC groups (P < 0.001, P = 1.00, respectively). Incidence of major complications, including aortic dissection, major vessel perforation, injury of intrapericardial structures, limb ischaemia, myocardial infarction and neurologic events, was similar [EBO: 12 (4%); TTC: 11 (2.4%); P = 0.23]. Minor complications such as minor vessel injury, groin bleeding or lymphatic fistula were noted in 31 (10.1%) and 35 (7.6%), respectively (P = 0.23). Successful RAP procedures defined as absence of RAP-associated conversions and major complications were equal [EBO: 295 (96%); TTC: 449 (97.6%); P = 0.23]. Complications detected during follow-up included pain: 30 of 249 (12%) and 13 of 279 (4.7%) (P = 0.002); sensational disturbances: 60 of 249 (24.1%) and 40 of 278 (14.4%) (P = 0.005) and wound-healing complications: 49 of 249 (19.7%) and 42 of 277 (15.2%) (P = 0.172) for EBO and TTC, respectively. RAP can be successfully and safely implemented in minimally invasive cardiac surgery. EBO and transthoracic clamping of the ascending aorta are performing equally in terms of feasibility and procedural success.


Effect of dietary electrolyte balance on growth and acid-base status in swine.
The effect of dietary electrolyte balance on pigs fed lysine- or tryptophan-adequate or tryptophan-deficient diets was investigated in four experiments using 8- to 12-wk-old pigs. Electrolyte balance, expressed as Na+K-Cl in meq/kg of diet, was varied by altering dietary levels of Na and Cl while holding all other minerals constant. In two experiments in which the basal diet contained a balance of 135 meq/kg, simple lysine or tryptophan deficiences caused depressed growth, feed intake and efficiency of feed utilization, but none of these responses was altered by dietary supplementation with NaHCO3. In one experiment in which the electrolyte balance of the basal diet was 61 meq/kg and in which both lysine and tryptophan were limiting. NaHCO3 supplementation significantly increased growth and feed intake. This did not occur if the diet was also supplemented with tryptophan. A final experiment was conducted to determine the response of pigs to a range of electrolyte balance (-85 to 341 meq/kg) in a practical corn-soy diet containing adequate levels of all amino acids. Growth and feed intake appeared to be maximal for balances of 0 to 341 meq/kg Na+K-Cl, but were decreased at -85 meq/kg (P less than .05). Acid-base balance was adversely affected at 0 meq/kg. The results suggest that the response of lysine-deficient pigs to sodium bicarbonate is dependent upon the electrolyte balance of the diet, and also is influenced by other dietary amino acids.


Inhibition of the adrenocorticotropin response to surgery in humans: interaction between dexamethasone and fentanyl.
We examined the plasma ACTH and cortisol responses to surgery in 25 patients with atherosclerotic heart disease undergoing myocardial revascularization. The patients were all premedicated with diazepam, and general anesthesia was induced with thiopental. They were randomly assigned to one of four groups: I) no dexamethasone (DEX), enflurane anesthesia, II) 40 mg DEX, iv, 45-60 min before sternotomy, enflurane anesthesia, III) no DEX, fentanyl [N-(1-phenethyl-4-piperidyl)propionanilide] anesthesia (50-100 micrograms/kg), and IV) DEX, fentanyl anesthesia. Isokalemic hemodilution of significant magnitude occurred during cardiopulmonary bypass. All groups had significant increases in plasma ACTH during surgery, which returned to control levels 22 h after the bypass. Group I (no DEX, no fentanyl) and group III (no DEX, fentanyl) patients had large similar increases in plasma ACTH, which peaked 2-4 h postbypass [400 +/- 83 (+/- SEM) pg/mL; 88 +/- 18 pmol/L]. The group II (DEX, no fentanyl) patients also had large increases in ACTH which were similar to those in groups I and III, except 2-4 h postbypass (183 +/- 91 pg/mL; 40 +/- 20 pmol/L). The group IV (DEX, fentanyl) patients had a significantly attenuated ACTH response to surgery; the mean plasma ACTH level 2-4 h postbypass was only 54 +/- 21 pg/mL (12 +/- 5 pmol/L). Therefore, although DEX or fentanyl alone had a minimal effect on the ACTH response to surgery, a significant attenuation occurred when DEX and fentanyl were used in combination. We conclude that glucocorticoids and morphine agonists exert interactive inhibitory effects on ACTH release in humans, probably by virtue of their suppression of CRH release from the hypothalamus.


Management of nonresponsive hepatitis C.
More than 50% of hepatitis C virus (HCV)-infected patients do not respond to the classical pegylated interferon (PEG-IFN)/ribavirin combination therapy. However, failing to respond to one course of treatment is not synonymous of therapy failure and retreatment is often beneficial. Alternative retreatment strategies include repeating the classical standard of care with an optimized drug regimen and adherence, including ribavirin serum concentration adjustment, correcting, if at all possible, comorbidities, and the addition of new specific anti-HCV molecules to the backbone of pegylated interferon/ribavirin. Options of retreatment should include consensus and natural interferons. For patients with advanced disease exposed to a high risk of lethal complications, customized maintenance therapy could be an effective option since it may slow down complications in some patients. Since low-dose interferon monotherapy is not sufficient, such a maintenance therapy remains to be verified via clinical trials. New possibilities of noninvasive assessment of fibrosis and the use of genetic tests to predict fibrosis progression and responsiveness to interferon are major emerging opportunities that run parallel to the revolution of the pharmacologic armentarium.


Functional evidence for increased sodium permeability in aortas from DOCA hypertensive rats.
We studied the role of increased Na+ permeability on the increased responsiveness to ouabain and to K+-free solution in aortas from DOCA hypertensive rats. Helically cut strips from DOCA hypertensive and normotensive control rats were mounted in a muscle bath for recording isometric force. In response to ouabain, aortas from DOCA hypertensive rats were significantly more sensitive and developed a greater maximal force than aortas from control rats. The rate of force development in response to K+-free solution was significantly faster in aortas from DOCA hypertensive rats as compared to those from control rats. Monensin (10(-5)M), a Na+ ionophore, increased the contractile response to ouabain and the rate of force development in response to K+-free solution in both DOCA hypertensive and control aortas. Amiloride (3 X 10(-5) M), a Na+ channel blocker, decreased the contractile response to ouabain and the rate of force development to a K+-free solution in both the DOCA hypertensive and control aortas, but the magnitude of decrease was greater in aortas from DOCA hypertensive rats. Thus, a Na+ ionophore causes the control aortas to perform like those from DOCA hypertensive rats, and a Na+ channel blocker causes aortas from DOCA hypertensive rats to perform like those from control rats. It is concluded that the difference between the two is that the smooth muscle of aortas from DOCA hypertensive rats is more permeable to Na+ than is that from control rats.


Enhancing cognitive-behavioural therapy for recurrent headache: design of a randomised controlled trial.
We have argued against the traditional approach of counselling avoidance of all triggers of headaches and migraine. Problems with this approach include the impossibility of avoiding all triggers and the high costs associated with trying to do so, and that avoidance could lead to reduced tolerance for the triggers. We have developed an alternative approach called Learning to Cope with Triggers (LCT) that encourages avoidance of triggers that are detrimental to health and wellbeing, but uses exposure to other triggers to desensitise headache sufferers to the triggers. This approach has been shown to be more effective than advising avoidance of all triggers. Trigger management is only one component of a comprehensive treatment program and the current study is designed to evaluate a new approach to treating headaches in which LCT has been integrated into an established cognitive-behavioural therapy (CBT) package (LCT/CBT). A target sample of 120 adult participants who suffer from migraine or tension-type headache, at least six days per month, and have done so for at least 12 months will be recruited. Participants will be randomly assigned to one of three groups: LCT/CBT; Avoid/CBT (CBT combined with instructions to avoid all triggers); and waiting-list control. Measures will include: daily diaries for recording headaches, triggers and medication consumption; headache disability and quality of life; trigger avoidance; locus of control and self-efficacy; and coping strategies. Treatment will involve 12 60-minute sessions scheduled weekly. Assessment will be completed before and after treatment, and at 4 and 12 month follow-up. The data will be analysed to determine which approach is most effective, and predictors of response to treatment. Migraine and tension-type headache are common and can be disabling. CBT has been demonstrated to be an efficacious treatment for both disorders. However, there is room for improvement. This study aims to increase the efficacy of behavioural approaches and identify factors predictive of a positive response. Australian and New Zealand Clinical Trials Registry ACTRN12614000435684 .


Psychological State of Camp Counselors with Type 1 Diabetes who Have Attended Diabetes Camp.
By 2050, more than 580,000 children in the United States will be diagnosed with type 1 diabetes (T1D). Management of T1D requires careful and continuous intervention, and children with T1D experience unique challenges in disease management compared to their adult counterparts. Diabetes camps are designed to help those with T1D learn diabetes management skills while experiencing summer camp. Psychological aspects are not addressed explicitly in diabetes camps located in Kansas. The purpose of this study was to evaluate the psychological state of past campers and camp counselors from one diabetes camp in Kansas. Campers and counselors, all of whom had T1D, and attended diabetes camp from 2015 to 2019 in Kansas were recruited to complete a survey about diabetes-related stress, diabetes management self-efficacy, and symptoms of depression. A link to the online survey was distributed to previous campers and counselors by email and through Facebook. A total of 24 camp counselors and 10 campers were surveyed, 100% of whom reported having T1D and attending camp at least once. One-third of respondents (n = 8) reported having severe diabetes-related stress, and 100% (n = 34) reported high levels of diabetes management self-efficacy. Most participants reported moderate levels of depression, and 9% (n = 3) reported a past suicide attempt. These results suggested a relatively high prevalence in signs of psychological distress from former campers and camp counselors with T1D. This study suggested that campers and counselors with T1D have high levels of diabetes-related stress, high diabetes management self-efficacy, and many signs of depression.


Incidence of deep vein thrombosis following vascular surgery.
The incidence of deep vein thrombosis (DVT) has been well documented in general and orthopaedic surgery but there have been few reports of the incidence of DVT following vascular surgery. Our aim was to perform a prospective study of the incidence of DVT in patients managed on the Vascular Unit at our institution. One hundred and forty two consecutive patients presenting for repair of abdominal aortic aneurysm, reconstruction of lower extremity arterial occlusive disease or amputation were studied. Venous duplex ultrasound examination was performed preoperatively and between day seven to 10 postoperatively. All patients received standard DVT prophylaxis of 5,000 units of unfractionated heparin subcutaneously three times daily and intraoperative sequential compression devices. Fourteen patients (9.8%) were found to have postoperative DVT with one patient (0.7%) having a documented pulmonary embolism. The incidence of DVT following reconstructive surgery was 9.1% and 14.3% following amputation. In patients having vascular reconstructive surgery and, in particular, amputation, there is still a moderate risk of DVT despite the application of standard prophylactic measures. There may be a role for newer modalities of prophylaxis such as low molecular weight heparin especially in the higher risk amputation group.


[Influence of some extrinsic factors on the stability of water-soluble carboxymethyl chitosan].
Water-soluble carboxymethyl chitosan was prepared from dried shrimp shells. The intrinsic viscosities of its samples were measured to evaluate the stability of carboxymethyl chitosan. The influential factors of stability, such as heat, pH, ionic strength, ultraviolet radiation, and sterilization were studied. The results demonstrate that the intrinsic viscosities of water-soluble chitosan will be influenced, to a certain extent, by the change of pH and ionic strength. Ultraviolet radiation and sterilized processes not only exept influence on the degradation of chitosan, but also have prominent effects on the molecular structure of it. Besides, temperature will also affect the speed of degradation, and chitosan can be stored at a temperature as low as 2 degrees C-8 degrees C.


Graphene-like BN/gelatin nanobiocomposites for gas barrier applications.
We report a simple, effective and green way for the fabrication of gelatin-graphene-like BN nanocomposites for gas barrier applications. The reinforcement effect of graphene-like BN on the gelatin properties is discussed. The obtained graphene-like BN nanocomposites show good dispersion in the gelatin matrix and remarkable capability to improve the crystallinity and the barrier properties of gelatin. The barrier properties of gelatin/BN nanocomposites have been enhanced by a factor of 500 at 2 bar compared to a gelatin film without graphene-like BN. The greatly improved performance and the high stability of these nanocomposites may lead exciting materials for their implantation in gas barrier applications.


[The step-cut shortening osteotomy of the shaft of the ulna, technique and results].
Step-cut shortening osteotomy of the ulna for impingment of the distal ulna relies on the principles enunciated by Desanfans 1953. We recommend the plate be placed on either the palmar or the dorsal aspect of the ulna. Used since 1990 this technique has enabled primarily bony healing by 6 months in all the 18 cases operated upon. A significant clinical improvement as measured by the scoring system of Chun and Palmer was noted at a median follow-up of 95.7 months. Shortening did not unfortunately, appear to stabilize the distal ulna and those patients with residual clinical radioulnar instability had significantly worse results. We conclude that the technique presented gives reliable bone healing. It is a versatile and simple technique that requires no special instrumentation but does demand skill and precision.


An orthograde labelling study of axons of the dorsal motor nucleus of the vagus to rat cardiac ganglia as demonstrated by autoradiography.
Central organization of the cardiac vagus has not been clarified. Retrograde changes produced in medulla oblongata neurons after section of vagal branches has favored the dorsal motor nucleus of the vagus (DMNX). Current information concerning the origin, course, and termination of vagal preganglionic fibers within cardiac ganglia is conflicting. The explicit purpose of this study was to determine if vagal fibers originated specifically within the DMNX proper. Fibers within the cardiac ganglia were labelled with 3H-leucine following injection into the DMNX. 12 adult albino rats were studied. DMNX were injected with 25 microCi 3H-leucine reconstituted to microliter. Animals were sacrificed by transcardial perfusion following a 4-day survival period. Serial cross-sections of the caudal pons, medulla oblongata, and thoracic viscera were processed for autoradiography. DMNX possessed a heavy incorporation of the radiochemical. Label was observed within the axons of the vagi. Cardiac ganglia contained labelled vagal fibers in close proximity to the postganglionic somata. Cardiac ganglia containing labelled preganglionic vagal axons were located in the cardiac plexuses and in the epicardium. Results show a labelled vagal preganglionic input to cardiac ganglia from the DMNX.


Secondary calcification in the foraminiferal genus globorotalia.
Populations of four species of the planktonic foraminiferal genus Globorotalia from sediments in the Gulf of Mexico show the effects of secondary thickening of the test. Quantitative tabulation of the distribution of thin- and thick-walled specimens illustrates an abrupt and separate depth at which the thickening takes place for each species.


Activation of cannabinoid receptor 2 protects rat hippocampal neurons against Aβ-induced neuronal toxicity.
Alzheimer's disease (AD) is a dementing, neurodegenerative disorder characterized by increased accumulation of beta-amyloid peptides (Aβ), degeneration of hippocampal neurons and the gradual development of learning and memory deficits. Therapeutically, there are still no ideal medicines available and this represents an urgent need for the development of new strategies to treat AD. Emerging lines of evidence suggest that modulation of the cannabinoid system exhibits neuroprotective effects in various neurological diseases, including AD. However, a consensus is yet to emerge as to the impact of hippocampal cannabinoid receptor 2 (CB2R) in protection of hippocampal neurons against Aβ induced neuronal toxicity. Here, we report that chronic treatment of primary hippocampal neuronal cultures with 100 nM Aβ1-42 oligomers for 7 days results in neurotoxicity, which includes increases in lactate dehydrogenase (LDH) levels, suggesting an Aβ1-42 -induced neuron apoptosis. Further, chronic Aβ1-42 reduces the ratio of phosphorylated Akt (pAkt)/Akt, in turn decreases neuronal Bcl-2/Bax ratio, and leads to an increase of caspase-3, which likely underlines the signal pathway of chronic Aβ1-42-induced neuron apoptosis. Interestingly, pre-treatments of CB2R agonist (JWH133, 10 μM) with Aβ1-42 prevents Aβ1-42-induced the decrease of pAkt/Akt ratio, the decrease of Bcl-2/Bax ratio, and the increase of caspase-3, and protects hippocampal neurons against Aβ1-42-induced apoptosis. All neuroprotective effects of JWH133 are abolished by a selective CB2R antagonist, AM630. Taken together, the activation of hippocampal CB2Rs protects neurons against Aβ1-42 toxicity, and the CB2R-mediated enhancement of the pAkt signaling is likely involved in the protection of hippocampal neurons against Aβ1-42-induced neuronal toxicity.


Experimental Analysis of Bragg Reflection Peak Splitting in Gratings Fabricated Using a Multiple Order Phase Mask.
We performed an experimental analysis of the effect of phase mask alignment on the Bragg grating reflection spectra around the wavelength of λB = 1560 nm fabricated in polymer optical fiber by using a multiple order phase mask. We monitored the evolution of the reflection spectra for different values of the angle ϕ by describing the tilt between the phase mask and the fiber. We observed that the peak at λB is split into five separate peaks for the nonzero tilt and that separation of the peaks increases linearly with ϕ. Through comparison with theoretical data we were able to identify the five peaks as products of different grating periodicities, which are associated with the interference of different pairs of diffraction orders on the phase mask.


Development of a real-time and quantitative thrombus sensor for an extracorporeal centrifugal blood pump by near-infrared light.
We developed an optical thrombus sensor for a monopivot extracorporeal centrifugal blood pump. In this study, we investigated its quantitative performance for thrombus detection in acute animal experiments of left ventricular assist using the pump on pathogen-free pigs. Optical fibers were set in the driver unit of the pump. The incident light at the near-infrared wavelength of 810 nm was aimed at the pivot bearing, and the resulting scattered light was guided to the optical fibers. The detected signal was analyzed to obtain the thrombus formation level. As a result, real-time and quantitative monitoring of the thrombus surface area on the pivot bearing was achieved with an accuracy of 3.6 ± 2.3 mm2. In addition, the sensing method using the near-infrared light was not influenced by changes in the oxygen saturation and the hematocrit. It is expected that the developed sensor will be useful for optimal anticoagulation management for long-term extracorporeal circulation therapies.


AutoML accurately predicts endovascular mechanical thrombectomy in acute large vessel ischemic stroke.
Automated machine learning or autoML has been widely deployed in various industries. However, their adoption in healthcare, especially in clinical settings is constrained due to a lack of clear understanding and explainability. The aim of this study is to utilize autoML for the prediction of functional outcomes in patients who underwent mechanical thrombectomy and compare it with traditional ML models with a focus on the explainability of the trained models. A total of 156 patients of acute ischemic stroke with Large Vessel Occlusion (LVO) who underwent mechanical thrombectomy within 24 h of stroke onset were included in the study. A total of 34 treatment variables including clinical, demographic, imaging, and procedure-related data were extracted. Various conventional machine learning models such as decision tree classifier, logistic regression, random forest, kNN, and SVM as well as various autoML models such as AutoGluon, MLJAR, Auto-Sklearn, TPOT, and H2O were used to predict the modified Rankin score (mRS) at the time of patient discharge and 3 months follow-up. The sensitivity, specificity, accuracy, and AUC for traditional ML and autoML models were compared. The autoML models outperformed the traditional ML models. For the prediction of mRS at discharge, the highest testing accuracy obtained by traditional ML models for the decision tree classifier was 74.11%, whereas for autoML which was obtained through AutoGluon, it showed an accuracy of 88.23%. Similarly, for mRS at 3 months, the highest testing accuracy of traditional ML was that of the SVM classifier at 76.5%, whereas that of autoML was 85.18% obtained through MLJAR. The 24-h ASPECTS score was the most important predictor for mRS at discharge whereas for prediction of mRS at 3 months, the most important factor was mRS at discharge. Automated machine learning models based on multiple treatment variables can predict the functional outcome in patients more accurately than traditional ML models. The ease of clinical coding and deployment can assist clinicians in the critical decision-making process. We have developed a demo application which can be accessed at https://mrs-score-calculator.onrender.com/.


Effectiveness of electronic dental anesthesia for restorative care in children.
The effectiveness of electronic dental anesthesia (EDA) for pain control during restorative procedures was compared with local anesthetic injection (LA) in 32 children aged 6 to 12 years. Each child selected had two antimere primary or permanent molars requiring similar-sized Class I or Class II restorations. The pain levels during restorative treatment were assessed using a visual analogue scale. Heart rates and behavior were also recorded. A crossover design was used with each child acting as his/her own control. The results showed that overall, EDA was less effective than LA for cavity preparation. The reported pain scores for EDA were higher in permanent teeth for the deeper cavities, and with one of the operators. The pre- or post-treatment anxiety scores were not found to differ significantly between the two restorative appointments. However, children with the highest pretreatment scores were more likely to report higher pain scores with EDA. Despite this, 63% of the children preferred EDA to LA. Dental anxiety, cavity depth, the tooth being treated, and operator attitude may also be important factors in determining the success of EDA.


Genome-wide analysis of carbohydrate-active enzymes in Pyramimonas parkeae (Prasinophyceae).
The wall-less green flagellate Pyramimonas parkeae is classified in clade I of the prasinophytes, a paraphyletic assemblage representing the last common ancestor of Viridiplantae, a monophyletic group composed of the green algae and land plants. Consequently, P. parkeae and other prasinophytes illuminate early-evolved Viridiplantae traits likely fundamental in the systems biology of green algae and land plants. Cellular structure and organellar genomes of P. parkeae are now well understood, and transcriptomic sequence data are also publically available for one strain of this species, but corresponding nuclear genomic sequence data are lacking. For this reason, we obtained shotgun genomic sequence and assembled a draft nuclear genome for P. parkeaeNIES254 to use along with existing transcriptomic sequence to focus on carbohydrate-active enzymes. We found that the P. parkeae nuclear genome encodes carbohydrate-active protein families similar to those previously observed for other prasinophytes, green algae, and early-diverging embryophytes for which full nuclear genomic sequence is publically available. Sequences homologous to genes related to biosynthesis of starch and cell wall carbohydrates were identified in the P. parkeae genome, indicating molecular traits common to Viridiplantae. For example, the P. parkeae genome includes sequences clustering with bacterial genes that encode cellulose synthases (Bcs), including regions coding for domains common to bacterial and plant cellulose synthases; these new sequences were incorporated into phylogenies aimed at illuminating the evolutionary history of cellulose production by Viridiplantae. Genomic sequences related to biosynthesis of xyloglucans, pectin, and starch likewise shed light on the origin of key Viridiplantae traits.


A one-dimensional manganese(III)-porphyrin coordination polymer: crystal structure and photophysical properties.
A novel manganese(III)-porphyrin complex, namely, catena-poly[[chloridomanganese(III)]-μ2-5,10,15,20-tetrakis(pyridin-3-yl)-21H,23H-porphinato(2-)-κ5N21,N22,N23,N24:N5], [MnCl(C40H24N8)]n, 1, was prepared by the hydrothermal reaction of manganese chloride with 5,10,15,20-tetrakis(pyridin-3-yl)-21H,23H-porphine. The crystal structure was determined by single-crystal X-ray diffraction. The porphyrin macrocycle exhibits a saddle-like distortion geometry. The MnIII atom has a six-coordination geometry. Each porphyrin unit links to two neighbouring units to yield a one-dimensional coordination polymer. These chains are further interlinked by hydrogen bonds to form a two-dimensional network. The complex shows red photoluminescence emission bands in ethanol solution, which can be attributed to ligand-to-ligand charge transfer (LLCT) accompanied by partial metal-to-ligand charge transfer (MLCT), as revealed by TDDFT calculations.


[The comparative evaluation of level of security culture in medical organizations].
The study was carried out on the basis of clinic "Medicine" in 2014-2015 concerning security culture. The sampling included 465 filled HSPSC questionnaires. The comparative analysis of received was implemented. The "Zubovskaia district hospital" Having no accreditation according security standards and group of clinics from USA functioning for many years in the system of patient security support were selected as objects for comparison. The evaluation was implemented concerning dynamics of security culture in organization at implementation of strategies of security of patients during 5 years and comparison of obtained results with USA clinics was made. The study results demonstrated that in conditions of absence of implemented standards of security in medical organization total evaluation of security remains extremely low. The study of security culture using HSPSC questionnaire is an effective tool for evaluating implementation of various strategies of security ofpatient. The functioning in the system of international standards of quality, primarily JCI standards, permits during several years to achieve high indices of security culture.


NSAIDs-Related Pyloroduodenal Obstruction and Its Endoscopic Management.
Endoscopic balloon dilatation (EBD) has important role in the management of benign gastric outlet obstruction. Although there are many reports on the role of EBD in the management of corrosive-induced and peptic benign GOO, there is scanty data on its role in the management of NSAID-induced GOO. We report 10 cases of NSAID-induced pyloroduodenal obstruction and their endoscopic management. The most common site of involvement was duodenum (5/10) followed by both pylorus and duodenum (4/10) and pylorus (1/10). Most of the strictures were short web-like, and the mean (SD) number of stricture was 2.0 (0.94). Endoscopic balloon dilatation was successful in 90% (9/10) cases requiring mean (SD) of 2.0 (1.6) sessions of dilatation to achieve target diameter of 15 mm and mean (SD) of 5.3 (2.7) sessions to maintain it over a treatment period of 4.5 months (IQR 2-15 months). There was no procedure-related complication or mortality.


Protein acetylation affects acetate metabolism, motility and acid stress response in Escherichia coli.
Although protein acetylation is widely observed, it has been associated with few specific regulatory functions making it poorly understood. To interrogate its functionality, we analyzed the acetylome in Escherichia coli knockout mutants of cobB, the only known sirtuin-like deacetylase, and patZ, the best-known protein acetyltransferase. For four growth conditions, more than 2,000 unique acetylated peptides, belonging to 809 proteins, were identified and differentially quantified. Nearly 65% of these proteins are related to metabolism. The global activity of CobB contributes to the deacetylation of a large number of substrates and has a major impact on physiology. Apart from the regulation of acetyl-CoA synthetase, we found that CobB-controlled acetylation of isocitrate lyase contributes to the fine-tuning of the glyoxylate shunt. Acetylation of the transcription factor RcsB prevents DNA binding, activating flagella biosynthesis and motility, and increases acid stress susceptibility. Surprisingly, deletion of patZ increased acetylation in acetate cultures, which suggests that it regulates the levels of acetylating agents. The results presented offer new insights into functional roles of protein acetylation in metabolic fitness and global cell regulation.


Tiagabine: efficacy and safety in partial seizures - current status.
Tiagabine hydrochloride (TGB) is a selective gamma-aminobutyric acid (GABA) reuptake inhibitor. TGB is effective as an add-on medication in adults and children 12 years and older in the treatment of partial seizures. Results of nonrandomized add-on trials with TGB show treatment success with seizure reduction of at least 50% in 33% to 46% of patients. In newly diagnosed patients with partial epilepsy, TGB monotherapy was as effective as carbamazepine. Comedication with TGB elevates the risk of nonconvulsive status (7.8% vs 2.7% without TGB). The most common side effects include dizziness/lightheadedness, asthenia/lack of energy and somnolence. TGB has no negative effects on cognition; it does not increase the risk of fractures or rash. TGB may interfere with color perception. TGB presents an intermediate risk for depression in patients with epilepsy (approximately 4%). Regarding the risk of overdose, 96-680 mg TGB (mean 224 mg) caused seizures or coma. TGB is an antiepileptic drug exhibiting a specific anticonvulsive mechanism of action, the efficacy of which is relatively low when used in comedication. Critical side effects, such as the induction of nonconvulsive status epilepticus, further limit its use.


[Vasculo-Behçet's disease].
Vasculo-Behçet's disease is a type of Behçet's disease with clinical features based on vasculitis of the arteries or deep veins, and is frequently life threatening. Early diagnosis and treatment are essential for the management of vasculo-Behçet's disease. Recent advances in the diagnosis of vasculo-Behçet's disease have been brought about by the use of radionuclide venography for deep vein thrombosis and computed tomography for arterial lesions. In the treatment of vasculo-Behçet's disease, anticoagulants and fibrinolytic agents are beneficial in controlling deep vein thrombosis. Operative therapy is often recommended for the management of arterial aneurysm because rupture of arterial aneurysm is the leading cause of death in patients with Behçet's disease.


Efficacy and Safety of Cyclin-Dependent Kinases 4 and 6 Inhibitors in HR+/HER2- Advanced Breast Cancer.
To assess the efficacy and safety of cyclin-dependent kinases 4 and 6 inhibitors (CDKi) combined with endocrine therapy (ET) in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) and compare the efficacy of different CDKi (palbociclib, ribociclib, or abemaciclib). This study based on randomized Phase 2 or 3 trials of CDKi plus ET compared with placebo plus ET for women with HR+/HER2-ABC and identify relevant randomized clinical trials (RCTs) published prior to February 2020. The primary endpoint was progression-free survival (PFS), the secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit response (CBR) and safety. The PROSPERO registry number is 42018081105. The results from eight trials including 4580 participants were pooled. Evidence indicated that the PFS of CDKi group was significantly prolonged (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.50-0.60, P < 0.01) compared with placebo group. The ORR and CBR were better (risk ratio [RR] 1.47, 95% CI 1.30-1.67, P < 0.01; 1.24, 95% CI 1.15-1.35, P < 0.01) in the CDKi group. The OS of CDKi group (HR 0.75, 95% CI 0.67-0.85, P < 0.01) was significantly longer than ET alone. Subgroup analyses confirmed that the benefit was consistent across most subgroups. Subgroup analyses showed no statistically significant difference of PFS among three CDKi: palbociclib vs ribociclib (HR 0.55, 95% CI 0.49-0.60, P = 0.34), palbociclib vs abemaciclib (HR 0.53, 95% CI, 0.47-0.59, P = 0.61), and ribociclib vs abemaciclib (HR 0.56, 95% CI, 0.51-0.62, P = 0.72). Treatment-related grade 3 or 4 hematologic adverse events (AEs) were more frequently in CDKi group. CDKi combined with ET can significantly prolong PFS and improve the ORR, CBR and OS in patients with HR+/HER2- ABC. However, the advantage of different CDKi has not been established.


Matrine regulates Th1/Th2 cytokine responses in rheumatoid arthritis by attenuating the NF-κB signaling.
To investigate the efficacy and mechanisms of matrine, a component derived from Sophora flavescens in treatment of rheumatoid arthritis (RA), a rat model of RA was established. Compared to control rats, matrine significantly mitigated inflammation and severity of RA (paw volume and articular index (AI) score). Using either mice splenic T cells stimulated with PMA/ionomycin or rat splenic T cells, the levels of Th1 and Th2 responses were determined by flow cytometry, quantitative RT-PCR, and ELISA. Furthermore, the levels of NF-κBp65 (RelA), IκBα, and phosphor-IκBα in T cells were determined by Western blot. Our study found that matrine modulated the imbalance of Th1 and Th2 cytokine responses in rats with RA by reducing the levels of Th1 cytokines (IFN-γ, TNF-α, IL-1β), but increasing Th2 cytokine (IL-4 and IL-10) through attenuating the NF-κB signaling in T cells, suggesting matrine as a promising drug for intervention of RA.


Imprinted genes in mouse placental development and the regulation of fetal energy stores.
Imprinted genes, which are preferentially expressed from one or other parental chromosome as a consequence of epigenetic events in the germline, are known to functionally converge on biological processes that enable in utero development in mammals. Over 100 imprinted genes have been identified in the mouse, the majority of which are both expressed and imprinted in the placenta. The purpose of this review is to provide a summary of the current knowledge regarding imprinted gene function in the mouse placenta. Few imprinted genes have been assessed with respect to their dosage-related action in the placenta. Nonetheless, current data indicate that imprinted genes converge on two key functions of the placenta, nutrient transport and placental signalling. Murine studies may provide a greater understanding of certain human pathologies, including low birth weight and the programming of metabolic diseases in the adult, and complications of pregnancy, such as pre-eclampsia and gestational diabetes, resulting from fetuses carrying abnormal imprints.


Role of reversible dimerization in reactions of amphoteric aziridine aldehydes.
Unprotected aziridine aldehydes belong to the amphoteric class of molecules by virtue of their dual nucleophilicity/electrophilicity. The dimeric nature of these molecules, brought together by a weak and reversible aminal "connection", was found to be an important element of reactivity control. We present evidence that reversible dimer dissociation is instrumental in aziridine aldehyde transformations. We anticipate further developments that will unveil other synthetic consequences of remote control of selectivity through forging reversible covalent interactions.


The utility of screening laboratory studies in pediatric patients with sickle cell pain episodes.
The purpose of this study was to determine whether blood counts discriminate between sickle cell pain episodes that lead to successful discharge from the emergency department (ED) and those that result in complications. This retrospective review compared the hemoglobin, reticulocyte count, and white blood cell count with differential during complicated and uncomplicated ED visits. Complicated visits were pain episodes followed by admission, by readmission within 48 hours, by acute chest syndrome, by an aplastic crisis, or by the administration of blood or antibiotics. There were 2 statistically important differences between complicated and uncomplicated pain episodes. Children successfully discharged were younger than those experiencing a complicated visit (8.9 v 11.2, P = 0.04). At a difference of 0.4 g/dL, the change in hemoglobin from baseline among children with complicated versus uncomplicated pain crises was not clinically useful. Routinely performed blood counts do not reliably identify the course of sickle cell pain crises.


[A look at pharmaceutical and cosmetic advertising in "Comoedia Illustré" at the time of the Ballets Russes].
The author analyses the pharmaceutical and cosmetic advertising in Comoedia Illustré, a very famous French cultural magazine at the beginning of the century. He emphasizes the relation between pharmacists and the development of cosmetics.


Eicosapentaenoic acid and docosahexaenoic acid modulate MAP kinase enzyme activity in human T-cells.
In order to investigate the implication of docosahexacnoic acid (DHA) and eicosapentaenoic acid (EPA) in T signalling, we assessed their effects on the activation of two mitogen activated protein (MAP) kinases, i.e. extracellularly-regulated kinases 1 and 2 (ERK1/ERK2) in Jurkat T-cells. The n-3 polyunsaturated fatty acids (PUFAs) alone failed to induce MAP kinase (MAPK) enzyme activity. To elucidate whether DHA and EPA act via protein kinase C (PKC) dependent and independent pathways, we employed their respective activators, i.e. phorbol 12-myristate 13-acetate (PMA) and antiCD3 antibodies. We observed that U0126, an inhibitor of MAPK kinase-ERK kinase 1/2 (MEK1/2), abolished the actions of these two agents on MAPK activation, suggesting that they act upstream of MEK1/2. Further EPA and DHA diminished both the PMA- and antiCD3 antibodies-induced enzyme activity of ERK1/ERK2 in Jurkat T-cells. Interestingly, okadaic acid (OA), a phosphatase inhibitor seems to act downstream of MEK1/2 as U0126 failed to inhibit the OA-induced MAPK activation. It is noteworthy that EPA and DHA not only failed to curtail the OA-induced MAPK activity but also these n-3 PUFAs at 20 microM potentiated the action of OA. Therefore, EPA and DHA seem to modulate MAPK activation upstream and downstream of MEK1/2. On the hand, arachidonic acid, an n-6 PUFA potentiated the MAPK enzyme activity. In conclusion, our study shows that EPA and DHA may regulate T-cells functions by modulating MAPK enzyme activity.


First report of Colletotrichum fioriniae causing anthracnose on the fruit of omija (schisandra) in South Korea.
Omija or Schisandra (Schisandra chinensis Baillon) is one of Korea's most unique fruits and have been used in herbal medicine. It is also used for making cold drinks during summer and hot tea during winter. Among the different diseases, anthracnose poses great threat for omija production as it reduces the yield and market quality of fruits. In September 2021, severe anthracnose symptoms were observed in some commercial farmer fields (36°36'14.9"N 127°59'31.3"E) in Mungyeong and disease incidence was approximately 30 to 35%. The symptoms on fruits were manifested as small sunken lesions. The presumed fungi were isolated from necrotic tissues on potato dextrose agar (PDA) and purified using the single spore isolation technique (Cai et al. 2009; Hassan et al.2019). A total of 20 morphological similar isolates were obtained from 18 sampled fruits. The cultures were incubated at 25°C in the dark for 5 to 7 days. The colonies were pink with white aerial mycelium on the upper side and pink with black zones on the reverse. All the colonies produced fusiform conidia measuring 12.7 to 17.5 × 4.7 to 7.4 μm (n=50). The appressoria were brown, globose to ellipsoid and measuring 6.3 to 12 × 5.9 to 9.7 μm (n=30). Morphological characteristics of present isolates were in concordance with that of Colletotrichum acutatum sensu lato (Damm et al., 2012). For molecular identification, genomic DNA of five representative isolates was extracted for sequencing of target markers and the phylogenetic tree was constructed. For amplification and sequencing of internal transcribed spacers (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT) chitin synthase-1 (CHS-1), histone 3 (HIS3) and beta-tubulin (TUB2), the primer pairs ITS1/ITS4, GDF1/GDR1, ACT-512F/ACT-783R, CHS1-79F/CHS-1-354R, CYLH3F /CYLH3R and BT2a /BT2b were used respectively (Damm et al., 2012). The resulting sequences were deposited in GenBank with accession numbers LC680890 to LC680914 and LC687627 to LC687631. The maximum likelihood tree based on concatenated sequences of the five genes shows that present isolates were grouped in the C. fioriniae. Pathogenicity on red schisandra fruits was confirmed using the two isolates OR1 and O59. Fruit clusters (20-30 fruits/ cluster) were surface sterilized by dipping them in 1% NaOCl for 3 minutes, rinsing in sterile distilled water, and placing them in a sterile plastic box containing moist paper tissues. All the fruits in each cluster were inoculated with 10 μl of 106 conidia/ml suspensions of each isolate by following either the wounded or un- wounded method (Hassan et al.2019). Fruit clusters treated with sterile distilled water served as a control. Three fruit clusters were inoculated per isolate for each method. With the wounding method, all the inoculated fruits showed typical anthracnose symptoms after 4 days of incubation at 25 ± 1°C in the dark, while the control and un- wounded fruits remained symptomless. This test was repeated twice. The species C. fioriniae were reisolated from the infected fruit. The morphology and ITS sequences of the reisolated fungi were consistent with the original one, fulfilling Koch's postulates. The species C. fioriniae have been described as a causal agent of anthracnose of numerous hosts worldwide including South Korea (Damm et al., 2012; Hassan et al.2019; Oo et al. 2016; Lee et al. 2020). To our knowledge, this is the first report of C. fioriniae as causal agent of omija anthracnose in South Korea. As this disease results in deterioration of fruits quality, management practices should be tailored to address C. fioriniae management. Acknowledgments This research was supported by Kyungpook National University Research Fund, 2021. References Cai, L., et al. 2009. Fungal Divers. 39:183. Damm, U., et al. 2012. Stud. Mycol. 73:37. Hassan, O., et al. 2019. Sci. Rep. 9:12089. Lee, D., et al. 2020. Mycobiology. 48: 210. Oo, M.M., et al. 2016. Mycobiology. 44: 325.


The effect of caerulein induced pancreatitis on the hepatic microvasculature.
A three-dimensional morphological study of the hepatic microvasculature in caerulein induced oedematous pancreatitis was performed using scanning electron microscopy (SEM) vascular casts and transmission electron microscopy (TEM) of hepatocytes and hepatic sinusoids. TEM studies provided ultrastructural evidence of hepatocellular damage while SEM views demonstrated gross irregularity of the sinusoidal outline with abruptly terminating sinusoidal buds and extravasation of cast material, findings which were similar to those previously reported in the pancreas itself using the same model and which were supported by TEM cross-sectional views of the hepatic sinusoids. The results suggest that caerulein induced pancreatitis is associated with extrapancreatic microvascular damage which may be an important factor in the pathogenesis of extrapancreatic organ impairment associated with acute pancreatitis.


[Hypercoagulability during pregnancy: evidences for a thrombophilic state].
The development of thrombotic disorders is a major threat for young women during pregnancy. It is one of the main causes of pregnancy-related disorders, which may also result in harm for the conceptus. Successful pregnancies require an even balance of coagulation and fibrinolysis, in order to secure stabilization of the basal plate as well as adequate placental perfusion. Broad spectrum assays which measure a range of thrombin/fibrin formation in serum have become an established means of identifying activation of blood coagulation and/or fibrinolysis. There is considerable interest in the application of these assays to the diagnosis of other hypercoagulable states, such as thrombophilia during pregnancy. We investigated coagulation/fibrinolysis parameters for significant differences between pregnant women during their gestation (first, second and third trimester) with or without pregnancy loss and healthy nonpregnant women. Thirty-nine pregnant women, aged 24-39 years, were studied. They were subdivided according to pregnancy trimester: 15 patients in the first trimester; 13 in the second and 11 in the third. The selection of patients was carried out in cooperation with the Transfusion Center of the Second University of Naples in order to obtain a homogeneous sample group. The control group included 400 healthy patients. Biochemical and blood coagulation tests were performed for each patient and the results obtained were compared with the control group. A decrease in free protein S (PS) and fibrinolysis (t-PA/PAI-1) activities and an increase in Factor VII, Factor VIII, prothrombin fragment 1+2 (F1+2), D-dimer (D-dimer) were observed in pregnant women during the follow-up of gestation. However, there were statistical differences between the groups of women with one or more pregnancy loss where it was found the lowest values in t-PA and PAI and the highest values in FVII and F1+2. Among subjects with more than one abortion, coagulation/fibrinolysis derangements before the partum were more prominent. A significant association exists between consecutive recurrent abortions and pregnancy complications such as placental abruption, hypertensive disorders and CS. This association persists after controlling for variables considered to coexist with recurrent abortions. These findings suggest that an excessive hypercoagulable state is associated with the termination of pregnancy resulting into a moderate risk for thrombosis during the different trimesters of pregnancy. The follow-up of fibrinolytic markers could represent a useful diagnostic tool for termination of pregnancy.


The initial manifestations of acute myocardinal infarction.
A review of 132 consecutive patients 65 years of age and older who had a myocardial infarction showed that two-thirds of them experienced pain at onset. Pain was the only symptom leading to bedside diagnosis in one-fourth of the patients. Pain at onset combined with sudden or increased dyspnea was present in one-fifth of the patients and pain associated with other symptoms in one-sixth. Dyspnea unaccompanied by pain heralded onset of infarction in one-fifth of the patients, and in almost 7 percent, onset was marked only by other symptoms. Cerebral symptoms dominated onset in one-tenth of the patients. Preexisting coronary heart disease, hypertension, or diabetes was not predictive of painless infarction. To avoid pitfalls and facilitate bedside diagnosis of infarction, physicians should be aware of the different clinical presentations of painless infarction in the aged, which occurred in over one-third of the patients in this cohort. They also should suspect the possibility of myocardial infarction in any patient in whom symptoms are not clear, even when they are mild and unobtrusive. Questioning of the elderly patient, his family, or others around him as early as possible after the onset of an acute attack is likely to elicit a history of pain, which may lead to the correct diagnosis.


Ligand-free sub-5 nm platinum nanocatalysts on polydopamine supports: size-controlled synthesis and size-dictated reaction pathway selection.
Noble metal nanoparticles exhibit intriguing size-dependent catalytic activities toward a plethora of important chemical reactions. A particularly interesting but rarely explored scenario is that some catalytic molecule-transforming processes may even inter-switch among multiple reaction pathways when the dimensions of a metal nanocatalyst are deliberately tuned within specific size windows. Here, we take full advantage of the adhesive surface properties of polydopamine to kinetically maneuver the surface-mediated nucleation and growth of Pt nanocrystals, which enables us to synthesize polydopamine-supported sub-5 nm Pt nanocatalysts with precisely tunable particle sizes, narrow size distributions, ligand-free clean surfaces, and uniform dispersion over the supports. The success in precisely tuning the particle size of ligand-free Pt nanocatalysts within the sub-5 nm size window provides unique opportunities for us to gain detailed, quantitative insights concerning the intrinsic particle size effects on the pathway selection of catalytic molecular transformations. As exemplified by Pt-catalyzed nitrophenol reduction by ammonia borane, catalytic transfer hydrogenation reactions may inter-switch between two fundamentally distinct bimolecular reaction pathways, specifically the Langmuir-Hinshelwood and the Eley-Rideal mechanisms, as the size of the Pt nanocatalysts varies in the sub-5 nm regime.


[Evaluation of correlation between pulmonary function testing and high resolution computed tomography in pulmonary alveolar proteinosis].
Pulmonary alveolar proteinosis (PAP) is a rare respiratory disorder featured by lipoproteinaceous material accumulation within alveoli. Pulmonary function testing (PFT) and quantitative high resolution computed tomography (HRCT) are used in evaluation of the severity, development and treatment effects of PAP. Seventeen patients (10 males, 7 females), aged from 15 to 51 years old, with PAP histopathologically proven by positive periodic acid Schiff reaction were studied in our institute from 2004 to 2007. PFTs and HRCT were performed in all patients. The quantitative parameters of HRCT included total lung volume (TLV), total lung mass (TLM), air-filling lung volume (AFLV), averaged lung density (ALD) and the ratio of air-filling lung volume to total lung volume (AFLV/TLV). The parameters of PFT included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC, diffusion capacity of carbon monoxide (D(L)CO), the ratio of D(L)CO to alveolar volume (D(L)CO/V(A)), total lung capacity (TLC), residual volume (RV), RV/TLC. A total of 24 dataset of the PFT and HRCT were collected. The correlation and regression between PFTs and HRCT were analyzed. PFT and HRCT parameters were compared before and after treatment with whole lung lavage in 6 of these patients. The data were expressed with mean +/- standard deviation and analyzed with SPSS 13.0 software. Restrictive ventilation function disorder and diffusion function disorder were found in patients with PAP, with more significant decline in D(L)CO (46.1% of predicted and abnormal rate 94.1%). Correlation between PFTs and HRCT parameters were found, with significance in ALD and FVC (r = -0.469, P = 0.021), TLM and FEV1 (r= -0.482, P = 0.017), AFLV/TLV and PEF (r = 0.511, P = 0.011), D(L)CO and D(L)CO/V(A) (r = 0.659, 0.692, P = 0.000, respectively). The highest correlation was found between D(L)CO/V(A) and AFLV (r = 0.525; P < 0.05). D(L)CO was markedly improved after the treatment of whole lung lavage, simultaneously found with varied improvement of quantitative parameters of HRCT measurements. Pulmonary function was impaired and correlated with abnormal appearance in HRCT in patients with PAP. Quantitative HRCT may be helpful in prediction of pulmonary function changes. Both techniques are important for the prognosis, outcome and follow-up studies of the disease.


[Modeling of acute thromboembolic stroke in mice].
To evaluate the controllability and reproducibility of a acute thromboembolic cerebral ischemia model for studying molecular imaging and thrombolysis in mice by 7.0 Tesla magnetic resonance imaging (MRI). Twenty-four male C57BL/6J mice were randomly divided into embolic group (n = 14) and sham-operated group (n = 10). To prepare rich fibrin and optimal length of clots and measure diameters of clots under microscope, the clots were injected into internal carotid artery via a microcatheter inserted from external carotid artery to bifurcation of common carotid artery in embolic group. In sham-operated group, phosphate-buffered saline containing bovine serum albumin was injected similarly. At 1, 3 or 24 h after injection of clots or phosphate-buffered saline containing bovine serum albumin, mice underwent 7.0 Tesla magnetic resonance imaging including sequences of magnetic resonance angiography (MRA), diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) by arterial spin labeling technology (ASL) and T(2) weighted imaging (T(2)WI) so as to evaluate the occlusive rate of middle cerebral artery (MCA) and the change of relative cerebral blood flow (rCBF) and lesion volumes. Triphenyl tetrazolium chloride (TTC) stain was performed at 24 h. The diameters of clots were 162 ± 14 µm. In embolic group at 1, 3 or 24 h after injection of clots, the occlusive rate of MCA was 78.6%, 71.4% and 57.1% respectively. And the values of rCBF decrease in mice showing occlusion of MCA in MRA images. The percents of rCBF value in embolic group were 26% ± 10% at 1 h and 26% ± 15% at 3 h respectively. They were significantly lower than the percents of rCBF value in sham-operated group at the same time points. The percents of infarct volumes at 24 h were 30% ± 4% from T(2)WI images and 30% ± 16% from TTC images. In sham-operated groups, both MRI and TTC images were negative. A murine model of acute thromboembolic cerebral ischemia has been successfully established. The improved method is both stable and feasible. It may be readily evaluated from multi-parameter imaging by 7.0 Tesla magnetic resonance imaging.


Nutritional epigenetics with a focus on amino acids: implications for the development and treatment of metabolic syndrome.
Recent findings from human and animal studies indicate that maternal undernutrition or overnutrition affects covalent modifications of the fetal genome and its associated histones that can be carried forward to subsequent generations. An adverse outcome of maternal malnutrition is the development of metabolic syndrome, which is defined as a cluster of disorders including obesity, hyperglycemia, hyperinsulinemia, hyperlipidemia, hypertension and insulin resistance. The transgenerational impacts of maternal nutrition are known as fetal programming, which is mediated by stable and heritable alterations of gene expression through covalent modifications of DNA and histones without changes in DNA sequences (namely, epigenetics). The underlying mechanisms include chromatin remodeling, DNA methylation (occurring at the 5'-position of cytosine residues within CpG dinucleotides), histone modifications (acetylation, methylation, phosphorylation, ubiquitination and sumoylation) and expression and activity of small noncoding RNAs. The enzymes catalyzing these reactions include S-adenosylmethionine-dependent DNA and protein methyltransferases, DNA demethylases, histone acetylase (lysine acetyltransferase), general control nonderepressible 5 (GCN5)-related N-acetyltransferase (a superfamily of acetyltransferase) and histone deacetylase. Amino acids (e.g., glycine, histidine, methionine and serine) and vitamins (B6, B12 and folate) play key roles in provision of methyl donors for DNA and protein methylation. Therefore, these nutrients and related metabolic pathways are of interest in dietary treatment of metabolic syndrome. Intervention strategies include targeting epigenetically disturbed metabolic pathways through dietary supplementation with nutrients (particularly functional amino acids and vitamins) to regulate one-carbon-unit metabolism, antioxidative reactions and gene expression, as well as protein methylation and acetylation. These mechanism-based approaches may effectively improve health and well-being of affected offspring.