The intriguing giant deer from the Bate cave (Crete): could paleohistological evidence question its taxonomy and nomenclature?
The research describes for the first time a possible case of pituitary gigantism in fossil mammals, precisely in deer. The pathology was detected in 2 long bones (tibia and metatarsus) belonging to an individual of an unusual large size found at the Bate cave (Rethymnon, Northern Crete). It formed the basis of Candiacervus major, the largest among the endemic deer species recorded in the Pleistocene-Early Holocene of Crete. Radiological and histomorphological examinations highlighted a reduction in cortical bone thickness and the presence of wide lacunae inside of the bone tissue. The pathological conditions suggest a pituitary gigantism diagnosis also supported by some morphological evidence, such as the extremely elongated distal part of the metatarsal diaphysis, the proportionally small proximal epiphysis, and some bone gracility. The diagnosis of a case of pituitary gigantism as presumed responsible for the extraordinary elongation of the tibia and the metatarsal bone is intriguing as they are, respectively, the paratype and the holotype of the C. major. The species represents a case of a deviation from the "island rule" in Pleistocene large mammals. The new evidence recommends a taxonomic and nomenclatural revision of this species. The main outcomes of this research are as follows: (i) a case of pituitary gigantism is described for the first time in an extinct mammal; (ii) it is underlined that paleohistology may provide interesting clues for disentangling taxonomic and nomenclatural issues; (iii) one of the very few cases of gigantism in insular mammals is being questioned.


The impact of musculoskeletal pain on health-related quality of life in Fort Prajaksilapakom Hospital.
To investigate the prevalence of musculoskeletal pain and its impact on health-related quality of life (HRQoL) in workers of Fort Prajaksilapakom Hospital. A cross-sectional study was conducted. Participants completed self-reported questionnaires requesting demographic data and report ofpain symptoms occurring within the last one month. In addition, the HRQoL questionnaire (Thai SF-36v2) was used to study the SF-36v2 score. Musculoskeletal pain was divided into five groups: (1) no pain, 2) pain at one site, 3) pain at two sites, 4) pain at three sites and 5) pain at four sites. The association between the SF-36v2 score and mnusculoskeletal pain was evaluated using multivariable linear regression analysis. Of 726 hospital workers, 485 (66.8%) participated in the present study. The majority of participants were female (65.3%) and comprised non-health care providers (56.3%) with a mean age of 37 +/- 11.5 years (range: 20-59). The prevalence of musculoskeletal pain during the last one month was 77.0%. Musculoskeletal pain was mostly reported at the lower extremities (50.8%),followed by low back (48.2), the neck (40.5%) and the upper extremities (33.0%). Multiple sites pain (pain at more than one site) was 51%. Each subscale score of the Thai SF-36v2 was significantly lower in participants with pain than in those without pain (physical functioning; p<0.001, physical role; p = 0.001, bodily pain; p<0.001, general health; p<0.001, vitality; p<0.001, social functioning; p = 0.02, emotion role; p = 0.003 and mental health; p<0.001). Multiple pain sites were more likely to be associated with lower HRQoL. The present study showed the high prevalence of musculoskeletal pain and negative impact on HRQoL in workers ofFort Prajaksilapakom Hospital. The number of sites of musculoskeletal pain was associated with a reduction in the quality oflife.


Vulnerability in Children with Celiac Disease: A Scoping Review Protocol.
(1) Background: The scientific literature reports that children with celiac disease (CD) are more susceptible to developing physical, psychological and social problems, conditioning their healthy childhood development. Despite this scientific evidence, the knowledge about determinants of vulnerability for the development of such problems is not consistent. In order to search the literature, a scoping review was conducted to analyse and map the evidence on the sociopsychosomatic vulnerability of children with CD and identify the gaps in this topic. (2) Methods: The methodology proposed by the Joanna Briggs Institute will be adopted and aims to identify studies that meet pre-defined eligibility criteria. The survey will include a range of relevant electronic databases as well as grey literature using related terms such as vulnerability, child and celiac disease. (3) Results: This review will consider any type of quantitative, qualitative and mixed studies and systematic reviews, focusing on dimensions of vulnerability in children with CD. The process of selection of studies, data extraction and analysis will be developed by two independent researchers. A third and fourth researcher will be involved in the study when there is no consensus between the previous researchers, as well as for resolving issues regarding the methodological process. (4) Conclusions: Identifying the determinants of vulnerability in children with CD will help nurses to understand the impact on their childhood development and trace possible gaps. This research is registered on the platform Open Science Framework (OSF).


Phased Array Imaging of Complex-Geometry Composite Components.
Progress in computational fluid dynamics and the availability of new composite materials are driving major advances in the design of aerospace engine components which now have highly complex geometries optimized to maximize system performance. However, shape complexity poses significant challenges to traditional nondestructive evaluation methods whose sensitivity and selectivity rapidly decrease as surface curvature increases. In addition, new aerospace materials typically exhibit an intricate microstructure that further complicates the inspection. In this context, an attractive solution is offered by combining ultrasonic phased array (PA) technology with immersion testing. Here, the water column formed between the complex surface of the component and the flat face of a linear or matrix array probe ensures ideal acoustic coupling between the array and the component as the probe is continuously scanned to form a volumetric rendering of the part. While the immersion configuration is desirable for practical testing, the interpretation of the measured ultrasonic signals for image formation is complicated by reflection and refraction effects that occur at the water-component interface. To account for refraction, the geometry of the interface must first be reconstructed from the reflected signals and subsequently used to compute suitable delay laws to focus inside the component. These calculations are based on ray theory and can be computationally intensive. Moreover, strong reflections from the interface can lead to a thick dead zone beneath the surface of the component which limits sensitivity to shallow subsurface defects. This paper presents a general approach that combines advanced computing for rapid ray tracing in anisotropic media with a 256-channel parallel array architecture. The full-volume inspection of complex-shape components is enabled through the combination of both reflected and transmitted signals through the part using a pair of arrays held in a yoke configuration. Experimental results are provided for specimens of increasing complexity relevant to aerospace applications such as fan blades. It is shown that PA technology can provide a robust solution to detect a variety of defects including porosity and waviness in composite parts.


Fusion of Lateral Calvarial Sutures on Volume-Rendered Computed Tomography Reconstructions in Patients With Known Craniosynostosis.
After treating a child with familial sagittal craniosynostosis, clinocephaly, and bilateral parietomastoid/posterior squamosal suture fusion, the authors wondered if major-suture synostosis and clinocephaly were associated with abnormal fusion of minor lateral calvarial sutures. The authors reviewed all preoperative volume-rendered head computed tomography reconstructions performed for craniosynostosis at their institution from 2010 through 2014 and determined whether the sphenoparietal, squamosal, and parietomastoid sutures were open, partially fused, or fused. The authors determined whether any sutures were abnormally fused based upon a previous study from their center, in which abnormal fusion was defined as either 1 of 3 abnormal fusion patterns or abnormally-early fusion. The authors then determined the rate of abnormal fusion of these sutures and whether abnormal fusion was associated with (1) major-suture craniosynostosis, (2) type of craniosynostosis (sutures involved; single-suture versus multisuture; syndromic versus nonsyndromic), and (3) clinocephaly. In 97 included children, minor lateral sutures were abnormally fused in 8, or 8.2%, which was significantly higher than in children without craniosynostosis from our earlier study. Abnormal minor lateral suture fusion was not associated with the type of single-suture synostosis or with multisuture synostosis but was associated with syndromic synostosis. Four of 8 children with abnormal minor lateral suture fusion had multisuture synostosis and 6 had syndromic synostosis. Lateral sutures were abnormally fused in 1 of 4 subjects with clinocephaly, which was not significant. Abnormal minor lateral calvarial suture fusion is significantly associated with major-suture craniosynostosis, especially syndromic synostosis.


HLA-DR expression in the vascular lesion and circulating T lymphocytes of patients with giant cell arteritis.
Giant cell arteritis (GCA) is a vascular inflammatory disease characterized by accumulations of T lymphocytes and macrophages in the arterial wall. In order to characterize the immune response in GCA, we have analysed temporal artery biopsies using a double-staining immunofluorescence method and studied T lymphocytes in peripheral blood with a fluorescence-activated cell sorter (FACS). HLA-DR was expressed on 28% (range 16-42%) of all T lymphocytes in the wall of the inflamed temporal artery, but only on average on 6% of peripheral blood T lymphocytes, indicating a high degree of local T cell activation in the inflammatory lesion. The proportions of T lymphocytes, T helper/inducer and T suppressor/cytotoxic cells in the blood of GCA patients before treatment with prednisolone did not deviate from those in normal individuals, but there was a minor increase in T helper cells after initiation of steroid therapy. The number of T helper cells expressing HLA-DR antigen and IL-2 receptor was not altered after 6-10 days of treatment with prednisolone. We found no evidence of HLA-DR expression by arterial smooth muscle cells in the GCA lesions, suggesting that these cells do not serve as antigen-presenting cells in GCA.


Ultrasonic detection of calcification in gallstones: "the reverberation shadow".
Observation of reverberations within a gallstone shadow (the "reverberation shadow") resulted in this study. Reverberation shadow was seen in sonograms of 27 patients with gallstones and three patients with milk of calcium bile. Calcification within gallstones was demonstrated by radiography or computed tomography in 22 of the 27 patients with gallstones, associated with the reverberation shadow. Whether the remaining five patients had calcified gallstones remains unknown. This study suggests that the reverberation shadow produced by gallstones indicates the presence of calcification within the gallstones.


ERG Expression in Prostate Needle Biopsy: Potential Diagnostic and Prognostic Implications.
To investigate the prognostic and diagnostic value of ERG immunohistochemistry (IHC) in prostate needle biopsy when combined with AMACR-CK5/6. ERG IHC was assessed in 119 consecutive prostate needle biopsies where the dual-stain AMACR-CK5/6 IHC was ordered and in 16 cases with a Gleason score (GS) ≥7. IHC results were evaluated in prostate carcinoma (PCA), high-grade prostatic intraepithelial neoplasia (HGPIN), HGPIN with adjacent atypical glands (PINATYP), atypical/suspicious (ASAP) foci, and benign PCA mimickers. GS, HGPIN, extraprostatic extension, perineural invasion, bilateralism of PCA, largest percent of core, and the overall percent of tissue involved by PCA were recorded. ERG was detected in 36% of PCA, 27% of HGPIN, 13% of ATYP/PINATYP, and none of benign mimickers. ERG-positive HGPIN was strongly associated with ERG-positive PCA in the same core compared with ERG-negative HGPIN (P<0.0001). Positive ERG expression in PCA was inversely related to GS and showed trends toward association with higher volume and bilateral disease. ERG was more specific for PCA than AMACR (0.87 vs. 0.23), but less sensitive (0.36 vs. 0.95). In conclusion, ERG IHC is of limited additional diagnostic value when added to AMACR and CK5/6. ERG expression is inversely related to GS and is associated with bilateral involvement and higher PCA tumor volume. ERG-positive HGPIN is strongly associated with the presence of PCA in the same core. Studies investigating the prognostic value of ERG in HGPIN should be implemented to address whether patients with ERG-positive HGPIN are at increased risk for subsequent PCA development.


BAG-1L protein enhances androgen receptor function.
BAG-1 is a regulator of heat shock protein (Hsp) 70/Hsc70 family proteins that interacts with steroid hormone receptors. The recently identified BAG-1 long (BAG-1L) protein, an isoform of BAG-1 that arises from translation initiation at a noncanonical CUG codon, was co-immunoprecipitated with androgen receptors (AR) from LNCaP prostate cancer cells and other cell lysates, whereas the shorter originally identified BAG-1 and BAG-1M (RAP 46) proteins were not. BAG-1L, but not BAG-1 or BAG-1M (RAP46), also markedly enhanced the ability of AR to transactivate reporter gene plasmids containing an androgen response element (ARE) in PC3 prostate cancer and other cell lines. A C-terminal region deletion mutant of BAG-1L failed to co-immunoprecipitate with AR and functioned as a trans-dominant inhibitor of BAG-1L, impairing AR-induced transactivation of ARE-containing reporter plasmids. In addition, BAG-1L significantly reduced the concentrations of 5alpha-dihydrotestosterone (DHT) required for AR activity but did not induce ligand-independent transactivation. BAG-1L also markedly improved the ability of AR to transactivate reporter genes when cells were cultured with DHT in combination with the anti-androgen cyproterone acetate. The effects of BAG-1L on AR could not be explained by detectable alterations in the DHT-induced translocation of AR from cytosol to nucleus, nor by BAG-1L-induced increases in the amounts of AR protein. These findings implicate BAG-1L in the regulation of AR function and may have relevance to mechanisms of prostate cancer resistance to hormone-ablative and anti-androgen therapy.


AN1284 attenuates steatosis, lipogenesis, and fibrosis in mice with pre-existing non-alcoholic steatohepatitis and directly affects aryl hydrocarbon receptor in a hepatic cell line.
Non-alcoholic steatohepatitis (NASH) is an aggressive form of fatty liver disease with hepatic inflammation and fibrosis for which there is currently no drug treatment. This study determined whether an indoline derivative, AN1284, which significantly reduced damage in a model of acute liver disease, can reverse steatosis and fibrosis in mice with pre-existing NASH and explore its mechanism of action. The mouse model of dietary-induced NASH reproduces most of the liver pathology seen in human subjects. This was confirmed by RNA-sequencing analysis. The Western diet, given for 4 months, caused steatosis, inflammation, and liver fibrosis. AN1284 (1 mg or 5 mg/kg/day) was administered for the last 2 months of the diet by micro-osmotic-pumps (mps). Both doses significantly decreased hepatic damage, liver weight, hepatic fat content, triglyceride, serum alanine transaminase, and fibrosis. AN1284 (1 mg/kg/day) given by mps or in the drinking fluid significantly reduced fibrosis produced by carbon tetrachloride injections. In human HUH7 hepatoma cells incubated with palmitic acid, AN1284 (2.1 and 6.3 ng/ml), concentrations compatible with those in the liver of mice treated with AN1284, decreased lipid formation by causing nuclear translocation of the aryl hydrocarbon receptor (AhR). AN1284 downregulated fatty acid synthase (FASN) and sterol regulatory element-binding protein 1c (SREBP-1c) and upregulated Acyl-CoA Oxidase 1 and Cytochrome P450-a1, genes involved in lipid metabolism. In conclusion, chronic treatment with AN1284 (1mg/kg/day) reduced pre-existing steatosis and fibrosis through AhR, which affects several contributors to the development of fatty liver disease. Additional pathways are also influenced by AN1284 treatment.


Artifacts During Short-Term Interictal Electroencephalographic Recording in Dogs.
The electroencephalogram (EEG) is an electrodiagnostic technique widely used in both scientific research and clinical medicine. It makes it possible to study the neurophysiology of brain activity by recording real-time changes in electrical potential produced by cortical activation. The importance of EEG in diagnosing canine epilepsy demonstrates its usefulness when the owner's description of crises is not clear or when the episodes cannot be differentiated from behavioral or cardiac disorders. However, EEG recordings also often record electrical activity from sources other than the brain, which may interfere with the clinical event-related signal. This activity is known as artifactual electrical activity, and the signal changes recorded in these cases corrupt the trace when they are superimposed on brain activity or even, in some cases, mimic pathologic abnormalities. The first step in analyzing and interpreting EEG traces is to recognize artifacts and other specific transient events. This retrospective study set out to ascertain whether artifacts comparable to those described in humans are observed in protocols used to perform short-term interictal EEG for canine epilepsy and how these can be classified.


Histologic reporting of malignant melanoma.
The schema for histologic reporting of malignant melanoma outlined above is incomplete. A number of variables, including quantification of tumor cell pigmentation, description of solar degeneration in surrounding stroma, and extent of S-100 protein immunoreactivity by tumor cells, have not been addressed. In addition, it is likely that within the next several years, additional parameters, including those identified by the use of in situ genomic probes (Chapter 3), will become known to confer prognostic information when assessed histologically in biopsy material. Nonetheless, this approach represents a start, an attempt to achieve uniformity in histologic reporting of melanoma. It represents a three-tiered approach. First is the establishment of a malignant melanocytic lesion (malignant melanoma) and the assessment of the anatomic level and extent of invasion of the dermis, which correlates directly with metastatic potential (the vertical growth phase measured in millimeters). Subclassification of the radial growth phase is optional and, by convention, is also reported in this "above the line" portion of the diagnostic assessment. Second, a number of subsidiary diagnostic statements, usually in the form of notes or comments, are recommended. These include assessment of overlying epidermal ulceration, a description of the morphology and mitotic activity of the vertical growth phase nodule, an assessment of the presence or absence of vascular invasion and microscopic satellite formation, a description of the host mononuclear cell response and/or regression, and mention of associated pathology. Finally, an additional narrative statement may be included to describe such things as extent of S-100 immunoreactivity or to modify in a more descriptive manner the database provided above. Although this last category is neither crucial nor mandatory, it serves to add to a collective database from which future determinations concerning the prognostic significance of new histologic parameters may be formulated. Table 6.3 provides a sample report based on the above considerations. This method of histologic reporting is recommended because it includes important diagnostic information as well as parameters for prognosis. Although certain details of less impelling current significance are included, these are of potential future importance as a greater number of patients with malignant melanoma are followed prospectively for prolonged periods of time. These factors may also prove to be significant in the accumulation of a database for research.


Clinical Application of Flexible Endoscopic Evaluation of Swallowing in Stroke.
This article aims to review the use of laryngoscopy to assess swallowing function in the stroke population. Since its inception in 1988, fiberoptic endoscopic evaluation of swallowing (FEES) has become an established procedure with distinct objective findings and practical applications, enabling many to choose it as the primary instrumental tool in evaluating poststroke dysphagia. In this article, we outline the decision-making process of when to use FEES. We highlight considerations for the acute stroke patient and visual signs that guide decision making during a FEES, such as secretions, swallowing frequency, and pharyngeal squeeze elicitation. The application of the ice chip protocol for stroke patients who have been nil per os is discussed, along with common observable events on FEES performed on stroke patients like a delay, penetration/aspiration, and bolus retention. Finally, we briefly review testing interventions and follow-up readiness with FEES.


γ-Secretase fanning the fire of innate immunity.
Innate immunity is the first line of defense against pathogens, alerting the individual cell and surrounding area to respond to this potential invasion. γ-secretase is a transmembrane protease complex that plays an intricate role in nearly every stage of this innate immune response. Through regulation of pattern recognition receptors (PRR) such as TREM2 and RAGE γ-secretase can modulate pathogen recognition. γ-secretase can act on cytokine receptors such as IFNαR2 and CSF1R to dampen their signaling capacity. While γ-secretase-mediated regulated intramembrane proteolysis (RIP) can further moderate innate immune responses through downstream signaling pathways. Furthermore, γ-secretase has also been shown to be regulated by the innate immune system through cytokine signaling and γ-secretase modulatory proteins such as IFITM3 and Hif-1α. This review article gives an overview of how γ-secretase is implicated in innate immunity and the maintenance of its responses through potentially positive and negative feedback loops.


Solid-state pulsed microwave emitter based on Rydberg excitons.
We theoretically demonstrate how the cuprous oxide Cu 2O could be used as a gain medium in a solid-state maser. By taking advantage of radiative microwave transitions between highly excited Rydberg states, one can achieve population inversion and masing in a wide range of wavelengths. In the pulsed emission regime, the considered excitonic system is characterized by intricate and rich dynamics, which are investigated numerically, taking into account several key features of the medium, such as strong Stark shift of energy levels and the presence of the Rydberg blockade effect.


Patient specific 3-d modeling of blood flow in a multi-stenosed left coronary artery.
The current study investigates the effect of multi stenosis on the hemodynamic parameters such as wall pressure, velocity and wall shear stress in the realistic left coronary artery. Patients CT scan image data of normal and diseased left coronary artery was chosen for the reconstruction of 3D coronary artery models. The diseased 3D model of left coronary artery shows a narrowing of more than 70% and 80% of area stenosis (AS) at the left main stem (LMS) and left circumflex (LCX) respectively. The results show that the decrease in pressure was found downstream to the stenosis as compared to the coronary artery without stenosis. The maximum pressure drop was noted across the 80% AS at the left circumflex branch. The recirculation zone was also observed immediate to the stenosis and highest wall shear stress was found across the 80% area stenosis. Our analysis provides an insight into the distribution of wall shear stress and pressure drop, thus improving our understanding on the hemodynamics in realistic coronary artery.


Mechanisms of Immune Evasion and Immune Modulation by Lymphoma Cells.
Targeting cancer cells by modulating the immune system has become an important new therapeutic option in many different malignancies. Inhibition of CTLA4/B7 and PD1/PDL1 signaling is now also being investigated and already successfully applied to various hematologic malignancies. A literature review of PubMed and results of our own studies were compiled in order to give a comprehensive overview on this topic. We elucidate the pathophysiological role of immunosuppressive networks in lymphomas, ranging from changes in the cellular microenvironment composition to distinct signaling pathways such as PD1/PDL1 or CTLA4/B7/CD28. The prototypical example of a lymphoma manipulating and thereby silencing the immune system is Hodgkin lymphoma. Also other lymphomas, e.g., primary mediastinal B-cell lymphoma and some Epstein-Barr virus (EBV)-driven malignancies, use analogous survival strategies, while diffuse large B-cell lymphoma of the activated B-cell type, follicular lymphoma and angioimmunoblastic T-cell lymphoma to name a few, exert further immune escape strategies each. These insights have already led to new treatment opportunities and results of the most important clinical trials based on this concept are briefly summarized. Immune checkpoint inhibition might also have severe side effects; the mechanisms of the rather un(der)recognized hematological side effects of this treatment approach are discussed. Silencing the host's immune system is an important feature of various lymphomas. Achieving a better understanding of distinct pathways of interactions between lymphomas and different immunological microenvironment compounds yields substantial potential for new treatment concepts.


Child neglect and oral health problems in offspring of substance-abusing fathers.
This study examined (1) orodental (OD) problems in 10-19-year-old children of substance use disorder (SUD) (n = 127) and non-SUD fathers (n = 111) and (2) the moderating effect of child's substance use (SU) involvement in the associations of paternal SUD and neglectful parenting with OD problems in the offspring. The results showed that periodontal problems differentiated between groups and the interactions between child's SU involvement and paternal SUD and neglectful parenting were respectively associated with hard/soft tissue lesions and carious lesions in the offspring, indicating that SU involvement increases risk for OD due to paternal SUD and neglectful parenting.


Heterogeneous beta2-adrenoceptor expression and dilation in coronary arterioles across the left ventricular wall.
Previous in vivo studies have shown that beta-adrenoceptor agonists cause a redistribution of coronary flow away from the subendocardium; however, the underlying mechanism remains uncertain. We tested the hypothesis that a heterogeneous distribution of beta-adrenoceptors and their vasomotor responses exists in the coronary microcirculation across the left ventricular wall. Porcine subepicardial and subendocardial arterioles (<100 microm) were isolated from the left ventricle and pressurized for in vitro study of vasodilation to the nonselective beta-adrenoceptor agonist isoproterenol and the selective beta2-adrenoceptor agonist procaterol. Both vessel types developed a similar level of basal tone and dilated to isoproterenol and procaterol. However, subepicardial arterioles exhibited a much higher sensitivity and greater dilation capacity to both agonists. The isoproterenol-induced vasodilations were inhibited by glibenclamide, an ATP-sensitive potassium (K(ATP)) channel blocker. In contrast to isoproterenol, dilations of subepicardial and subendocardial arterioles to pinacidil, a K(ATP) channel opener, were similar. In both vessel types, isoproterenol-induced dilation was inhibited by the beta2-adrenoceptor blocker ICI-118,551 but was insensitive to the beta1-adrenoceptor blocker atenolol. Reverse transcription-polymerase chain reaction and immunohistochemical data revealed that beta2-adrenoceptor mRNA and protein expression, respectively, were markedly greater in subepicardial arterioles. This study demonstrates that selective activation of beta2-adrenoceptors elicits dilation of both subepicardial and subendocardial arterioles through opening of K(ATP) channels. The higher beta2-adrenoceptor expression in subepicardial arterioles may contribute to the greater dilation of these vessels to beta2-adrenoceptor activation.


Involvement of the kidney in catabolism of human leukocyte interferon.
The metabolic fate of human leukocyte interferon (HuIFN-alpha) was studied after intravenous injection into rats and cynomolgus monkeys. At various intervals the animals were sacrificed and the HuIFN-alpha content determined in serum and various tissues. HuIFN-alpha quickly disappeared from the circulation and was found mainly in the kidneys, in which levels were at least 7- to 10-fold higher than in the liver, spleen, lungs, heart, brain and muscles. No interferon was detected in urine. Subcellular fractionation of kidney revealed that the mitochondrial-lysosomal fraction (15 000 g) had a high HuIFN-alpha content. It was also found that HuIFN-alpha was rapidly inactivated by two types of proteinases found in the lysosomal fractions of rat, monkey and human kidneys, with an optimal pH of 3 to 4. The inactivation was partially inhibited by either pepstatin or leupeptin. Inactivation was totally prevented by a mixture of both inhibitors. Since it is known that interferon is scantily excreted in urine, our findings suggest that the kidney serves as a main site for its degradation.


Shear horizontal guided wave modes to infer the shear stiffness of adhesive bond layers.
This paper presents a non-destructive, ultrasonic technique to evaluate the quality of bonds between substrates. Shear-horizontally polarized (SH) wave modes are investigated to infer the shear stiffness of bonds, which is necessarily linked to the shear resistance that is a critical parameter for bonded structures. Numerical simulations are run for selecting the most appropriate SH wave modes, i.e., with higher sensitivity to the bond than to other components, and experiments are made for generating-detecting pre-selected SH wave modes and for measuring their phase velocities. An inverse problem is finally solved, consisting of the evaluation of the shear stiffness modulus of a bond layer at different curing times between a metallic plate and a composite patch, such assembly being investigated in the context of repair of aeronautical structures.


The Effects of Fasting During Ramadan on the Concentration of Serotonin, Dopamine, Brain-Derived Neurotrophic Factor and Nerve Growth Factor.
Neurotransmitters and neurotrophic factors are signaling molecules that play a crucial role in cell proliferation, differentiation, survival and functions of neurons. It is believed that caloric restriction could help the health of the nervous system by affecting the synthesis of neurotrophins and neurotransmitter and oxygen radical metabolism. The objective was to investigate the plasma levels of serotonin, dopamine, brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in 29 healthy fasted subjects (22 women and 7 men) during the month of fasting in Ramadan. The levels of these factors were measured (using ELISA method) three times, 2 days before the fasting month as a control, on the 14th and 29th day of Ramadan as test groups. In addition, these factors were investigated in the group of women only. According to our investigation, the plasma levels of serotonin, BDNF and NGF were significantly increased during fasting month of Ramadan. In detail, the levels of these factors were increased in 14th and 29th day test groups compared to controls (P<0.05). Moreover, these levels were significantly increased on the 29th day compared to the 14th day test groups, but there were no differences between dopamine levels in all groups. Furthermore, the results obtained in women's groups were the same as those obtained in previous groups. Our findings suggest that plasma levels of serotonin, BDNF and NGF were significantly increased during fasting month of Ramadan.


Antibacterial activity of chitooligosaccharides.
The aim of this study was to investigate the antibacterial activity of chitooligosaccharide, prepared by partial acid hydrolysis of chitosan, and of an aminoglycosylated derivative, prepared by reductive alkylation of the chitooligosaccharide, against E. coli and S. aureus.


Atorvastatin efficacy in the primary and secondary prevention of cardiovascular events.
Atorvastatin has been extensively studied in the primary and secondary prevention of cardiovascular events, and may have some clinical advantages over various other statins in these respects. The principal primary prevention study of atorvastatin, ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm), revealed that atorvastatin reduced the relative risk of primary coronary heart disease (CHD) events by 36% (p = 0.0005) compared with placebo in patients with hypertension. Much published data confirm the secondary preventive benefits of atorvastatin in various clinical settings. The IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) and TNT (Treating to New Targets) trials demonstrate the preventive efficacy of atorvastatin in patients with stable CHD. Relative to simvastatin (in the IDEAL trial) and low-dosage atorvastatin (in the TNT trial), intensive atorvastatin therapy (80 mg/day) reduced the risk of nonfatal myocardial infarction (MI) by 17-22% (p < or = 0.02). Furthermore, the ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events) and GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation) trials highlight the benefits of atorvastatin in the 'real world' setting in patients with stable CHD. Compared with 'usual' care, atorvastatin reduced the risk of nonfatal MI by 47-59% (p < or = 0.0002).Moreover, the MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering), PROVE-IT (PRavastatin Or atorVastatin Evaluation and Infection Therapy) and IDEAL-ACS (Acute Coronary Syndromes) studies outline the benefits of high-dosage atorvastatin therapy started within 24-96 hours, 10 days or 2 months, respectively, of an acute coronary syndrome. Relative to placebo, pravastatin and simvastatin, atorvastatin reduced the risk of death or major cardiovascular events by 16-18% (p < or = 0.048). In patients undergoing revascularisation procedures, the AVERT (Atorvastatin VErsus Revascularisation Treatment) study revealed that 18 months' administration of atorvastatin 80 mg/day was at least as effective as angioplasty plus usual care in reducing the risk of ischaemic events in low-risk patients with stable coronary artery disease. Furthermore, the ARMYDA (Atorvastatin for Reduction in MYocardial DAmage during angioplasty) and ARMYDA-3 trials showed that 7 days' administration of atorvastatin 40 mg/day before coronary intervention significantly reduced the risks of periprocedural myocardial damage (ARMYDA), postprocedural MI (p = 0.025; ARMYDA) and atrial fibrillation (p = 0.003; ARMYDA-3) versus placebo. In addition, it has been reported that C-reactive protein levels and the combined incidence of cardiovascular events (death, MI and target segment revascularisation during the 6-month follow-up) were significantly higher in coronaropathic patients undergoing non-surgical revascularisation procedures (stent implantation) not receiving statin therapy compared with those treated with atorvastatin (80mg). Overall, therefore, the marked efficacy of atorvastatin in the primary and secondary prevention of cardiovascular events underscores the pivotal place that this statin has in general cardiovascular disease management, and suggests even greater potential clinical utility for the drug in some clinical settings.


Angiotensin I-converting enzyme insertion-related genotypes and allele are associated with higher susceptibility of endometriosis and leiomyoma.
Endometriosis and leiomyoma display features similar to malignancy, requiring neovascularization to proliferation and growth. Altered vascular-related genes might be related to the development of endometriosis and leiomyoma. Polymorphisms of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) genes have been linked with some vascular diseases. This study investigates whether ACE I/D gene polymorphisms could be used as markers of susceptibility in endometriosis and leiomyoma. Women were divided into three groups: (1) endometriosis (n = 125); (2) leiomyoma (n = 120); (3) normal controls (n = 128). Genomic DNA was obtained from peripheral leukocyte. ACE I/D gene polymorphisms in intron 16 were amplified by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) Genotypes and allelic frequencies in both groups were compared. We observed the genotype distribution and allele frequency of ACE I/D gene polymorphisms in both groups were significantly different. Proportions of ACE*I homozygote/heterozygote/D homozygote in both groups were: (1) 50.4/24/25.6%; (2) 25/23.33/51.67%; (3) 10.2/29.7/60.1%. Proportions of I/D alleles in each group were: (1) 62.4/37.6%; (2) 36.7/63.3%; (3) 25/75%. We concluded that ACE*I/D gene polymorphisms are associated with endometriosis and leiomyoma susceptibilities. ACE*I-related genotypes and allele are strongly related to the occurrence of endometriosis and moderately related to the occurrence of leiomyoma.


A Comparative Study of the Anti-Obesity Effects of Dietary Sea Cucumber Saponins and Energy Restriction in Response to Weight Loss and Weight Regain in Mice.
Dietary supplementation of sea cucumber saponins and calorie restriction have been proved to be effective in alleviating obesity, but the differences of anti-obesity effects between sea cucumber saponins and energy restriction during weight loss and weight regain are still unknown. In the present study, high-fat-induced obesity mice were randomly divided into three groups, including a high-fat diet group (HF), an energy restriction by 40% group (HF-L), and a sea cucumber saponins group (HF-S), to compare the effects of dietary sea cucumber saponins and energy restriction on the weight, glucose, and lipid metabolism of obese mice during weight loss and weight regain. The results showed that dietary 0.06% sea cucumber saponins and limiting energy intake by 40% had the same weight loss effect. Interestingly, sea cucumber saponins could alleviate impaired glucose tolerance and insulin resistance caused by obesity. In addition, the inhibited SREBP-1c mediated lipogenesis might lead to the alleviation of weight regain after resuming the high-fat diet even when sea cucumber saponins were no longer supplemented. In contrast, limiting energy intake tended to promote lipid synthesis in the liver and white adipose tissue after restoring a high-fat diet, and inflammation was also induced. The findings indicated that sea cucumber saponins could replace calorie restriction to prevent obesity and might be used as a functional food or drug to resist obesity and related diseases caused by obesity.


THE PROFITS AND PERILS OF PUBLICITY: ALLGEMEINE LITERATUR- ZEITUNG, THE THURN UND TAXIS POST, AND THE PERIODICAL TRADE AT THE END OF THE EIGHTEENTH CENTURY.
Recent historiography on the growth of periodical publishing has emphasized newspapers and journals as constituents of an emergent communications system in early modern Europe. This system comprised the newspapers, journals and other publications that contributed its content, and also the postal systems that were the principal method of distributing that content. This article describes how the growth of this system in central Europe was supported in large measure by financial incentives that it offered to both constituents. First, in contrast with postal systems in France and the UK, the Thurn und Taxis Reichspost inserted itself as a middleman in the sale of periodicals, which gave the Reichspost an incentive to promote the trade. Second, the financial conditions for periodical publication made their costs depend more heavily on costs that were scalable to circulation than is true today, which resulted in the viability of publications with a lower circulation. The same cost structure also made it possible for certain prominent periodicals of the era to earn considerable profits for their publishers, as illustrated in this article by Allgemeine Literatur-Zeitung, which was published in Jena from 1785.


Improving the Efficiency of Configurational-Bias Monte Carlo: Extension of the Jacobian-Gaussian Scheme to Interior Sections of Cyclic and Polymeric Molecules.
The Jacobian-Gaussian method, which has recently been developed for generating bending angle trials, is extended to the conformational sampling of inner segments of a long chain or cyclic molecule where regular configurational-bias Monte Carlo was found to be very inefficient or simply incapable (i.e., for the cyclic case). For these molecules, a new conformational move would be required where one interior section is relocated while the rest of the molecule, before and after this section, is fixed. Techniques have been developed to extend the regular configurational-bias Monte Carlo to such a fixed-end points case by introducing a biasing probability function. Each trial is weighted by this function to ensure the closure of the molecule by selecting appropriate growth direction. However, the acceptance rate might be reduced significantly due to the incongruity of this weight and the energy weight. In addition, the last steps of closing the molecule include several bending and torsional energies that are coupled to each other. Thus, generating a trial that is acceptable for all energetic terms becomes a difficult problem. The Jacobian-Gaussian method can overcome these two problems with the following two principles: First, basic geometrical constraints must be fulfilled to guarantee molecular closure, which avoids the need of the biasing probability function. Second, the growth variables are transformed into those used explicitly in expressing the various intramolecular energies between fixed points to allow for the trials to be generated directly according to the Boltzmann distributions of these energetic terms, which improves the acceptance rates dramatically. This method has been examined on the growth of inner segments of linear and cyclic alkanes, which proves its higher efficiency over that of traditional methods.


Life after BRCA1/2 testing: family communication and support issues.
The process of genetic testing is often deemed a family affair. Several studies have indicated that individuals undergo BRCA1/2 testing not only to learn about their own cancer risks and options for screening and prevention, but also to gather information for potentially at-risk relatives. However, many individuals are not prepared for the medical and emotional implications that accompany the genetic testing process. This can be complicated by a moral or ethical obligation to disclose result status to other family members. Several characteristics including gender, BRCA1/2 carrier status, and cultural and ethnic background may influence the communication process between the proband and his/her potentially at-risk kin. In addition, the age of family members and their degree of relatedness may affect whether or not they are told the results of their relative's genetic testing. While genetic providers have an obligation to inform individuals of the implications of BRCA1/2 test results for at-risk relatives, they must also strive to respect and maintain autonomy and confidentiality. This paper will examine the characteristics that influence the disclosure of BRCA1/2 test results to relatives. In addition, methods of post-test support and follow-up to facilitate the disclosure process for patients and their family members as well as foster positive communication, will be discussed.


Gadolinium-doped carbon dots as nano-theranostic agents for MR/FL diagnosis and gene delivery.
Nano-theranostic agents play important roles in the development of therapeutic methods for serious diseases. In this study, novel carbon dots (CDs) L-CD/C-CD were prepared from Gd(iii) salt/complexes, cationic polymers and citric acid in the hope that they would combine the abilities of gene delivery and multi-modal (MR/FL) imaging. The CDs inherited the properties of good water-solubility and positive charge from their precursor polymers. In vitro gene transfection results showed that the CDs have good transfection efficiency and anti-serum ability, especially for L-CD, which has 74 times higher transfection efficiency than PEI 25 kDa in the presence of 10% serum. The CDs exhibited bright fluorescence, which was stable for several days under various pH. Confocal laser scanning microscopy revealed that the CDs could image HeLa cells with blue or green fluorescence well, and realize the monitoring of the gene delivery process. Besides, the CDs showed favorable biocompatibility with excellent performance in longitudinal relaxivity rates (r1) of 11.4 mM-1 s-1 for L-CD and 57.6 mM-1 s-1 for C-CD, which were about 3-15 times higher than that of the clinical Gd reagent Gd-DTPA (3.75 mM-1 s-1). Furthermore, the CDs could perform in vivo tumor-specific MR-imaging more clearly than Gd-DTPA, which is attributed to their suitable particle size and their resulting greater accumulation at tumor site via the EPR effect. This study provides a promising strategy for constructing multi-functional CDs for tumor theranostics.


Keratosis lichenoides chronica: report of a new case with partial response to PUVA therapy.
Keratosis lichenoides chronica is a rare disorder characterized by a distinctive seborrheic dermatitis-like facial eruption together with development of asymptomatic verrucosities on the limbs and the trunk, with a partially linear distribution. We report a case of a 35-year-old Syrian woman who presented with keratotic plaques and papules of the limbs for several years, and a seborrheic dermatitis-like facial eruption. A diagnosis of keratosis lichenoides chronica was clinically and histologically. Treatment with isotretinoin was without benefit. She had partial response to PUVA.


Ultrasensitive Magnetic Assisted Lateral Flow Immunoassay Based on Chiral Monoclonal Antibody against R-(-)-Salbutamol of Broad-Specificity for 38 β-Agonists Detection in Swine Urine and Pork.
Screening for ″zero tolerance″ β-agonists requires broad-specificity and sensitivity methods. Herein, R-(-)-salbutamol (SAL) is chirally separated and designed as a hapten, and a monoclonal antibody (mAb) was first prepared with an IC50 of 0.27 ng/mL, which can recognize 38 β-agonists simultaneously. The broad-specificity of chiral mAb was explored by molecular simulation technology. Magnetic nanoparticles (MNPs) were then synthesized and applied as a signal tracer to develop a lateral flow immunoassay (LFIA). The limits of detection of MNPs-LFIA for SAL in swine urine and pork were 0.05 and 0.09 μg/kg, which was (2-125)-fold lower than that of the reported LFIAs. The recoveries were between 95.8 and 116.7%, with the coefficient of variation from 2.7 to 15.4%. Parallel analysis of 44 samples by commercial ELISA kits confirmed the reliability. Therefore, our work not only provides a broad-specificity and ultrasensitive method for β-agonists but also suggests that chirality is the new general theory that guided the rational hapten design.


A framework for health promoting emergency departments.
Since 1986, the World Health Organization (WHO) has been advocating for the health sector to move increasingly in a health promotion direction, beyond its responsibility for providing clinical and curative services (WHO, 1986). Some Emergency Departments (EDs) have partially achieved this through providing patient health information, screening and early intervention programs, injury prevention and asthma education. While EDs are a suitable setting for health promotion, they are grounded in a medical paradigm where most of the staff are educated to think exclusively of relation care. As such, a significant organizational shift is required for EDs to be more inclusive of health promotion principles. Following a comprehensive literature review, a theoretical framework was developed for the Health Promoting Emergency Departments Program (HPEDP). It describes the opportunities for health promotion in EDs through combining the 'strategies for health promotion' with the 'spectrum of health and disease'. This forms a matrix to enable health development, primary prevention and secondary prevention interventions to be planned in EDs. The framework is a tool to support the development of coordinate and comprehensive health promotion programs and to avoid the use of isolated victim-blaming strategies. Beyond EDs, planners in other health care institutions may also find the framework useful-particularly those settings where staff health promotion training and experience is limited.


Oral Health Care: A Missing Pillar of Total Health Care?
Oral health is an important component of overall health, and preventive dental care is essential for maintaining good oral health. However, many patients face significant barriers to preventive dental care. We examined prevalence of and factors associated with no recent preventive dental care in an adult health plan population. For this cross-sectional study, we used data for 19,672 Kaiser Permanente members aged 25-85 who participated in the 2014/2015 or 2017 Member Health Survey (MHS) and 20,329 Medicaid members who completed an intake questionnaire. We estimated percentages of adults with no preventive dental care (teeth cleaning and examination by a dental professional) in the prior 12 months, overall and among four racial groups, by age, sex, education, income, and dental care cost factors. We used logistic regression to model associations of sociodemographic and cost factors with no preventive dental care. We also examined lack of preventive dental care in subgroups at elevated risk for periodontal disease. Overall prevalence of no preventive dental care was 21%, with significant differences by race (non-Hispanic White, 19.6%; African-American/Black, 29.3%; Latinx, 24.9%, Asian American/Pacific Islander, 19.6%). Adults with lower educational attainment and household income and dental care cost barriers were more likely to lack preventive dental care. Racial and socioeconomic factors remained significant in the multivariable models. Lack of preventive dental care was fairly common among adults with diabetes, prediabetes, hypertension, smokers, frequent consumption of sugary beverages, and Medicaid coverage. Oral health care should be better integrated with primary medical care to promote adult total health.


Insight into differential responses of upland and paddy rice to drought stress by comparative expression profiling analysis.
In this study, the drought responses of two genotypes, IRAT109 and Zhenshan 97 (ZS97), representing upland and paddy rice, respectively, were systematically compared at the morphological, physiological and transcriptional levels. IRAT109 has better performance in traits related to drought avoidance, such as leaf rolling, root volumes, the ratio of leaf water loss and relative conductivity. At the transcriptional level, more genes were induced by drought in IRAT109 at the early drought stage, but more genes had dynamic expression patterns in ZS97 at different drought degrees. Under drought conditions, more genes related to reproductive development and establishment of localization were repressed in IRAT109, but more genes involved in degradation of cellular components were induced in ZS97. By checking the expression patterns of 36 drought-responsive genes (located in 14 quantitative trail loci [QTL] intervals) in ZS97, IRAT109 and near isogenic lines (NILs) of the QTL intervals, we found that more than half of these genes had their expression patterns or expression levels changed in the NILs when compared to that in ZS97 or IRAT109. Our results may provide valuable information for dissecting the genetic bases of traits related to drought resistance, as well as for narrowing the candidate genes for the traits.


pH-Responsive Near-Infrared Emitting Gold Nanoclusters.
Near-infrared (NIR) fluorophores with pH-responsive properties suggest merits in biological analyses. This work establishes a general and effective method to obtain pH-responsive NIR emissive gold nanoclusters by introducing aliphatic tertiary amine (TA) groups into the ligands. Computational study suggests that the pH-responsive NIR emission is associated with electronic structure change upon protonation and deprotonation of TA groups. Photo-induced electron transfer between deprotonated TA groups and the surface Au-S motifs of gold nanoclusters can disrupt the radiative transitions and thereby decrease the photoluminescence intensity in basic environments (pH=7-11). By contrast, protonated TA groups curb the electron transfer and restore the photoluminescence intensity in acidic environments (pH=4-7). The pH-responsive NIR-emitting gold nanoclusters serve as a specific and sensitive probe for the lysosomes in the cells, offering non-invasive emissions without interferences from intracellular autofluorescence.


Early Initiation Of Beta Blockers Following Primary Endoscopic Therapy For Bleeding Oesophageal Varices In Cirrhotics.
Beta-blockers provide secondary prophylaxis following endoscopic therapy for variceal bleeding. Guidelines recommend starting beta-blockers 6 days after endoscopy to prevent masking hemodynamic signs of re-bleeding. We aimed to see safety of earlier initiation of betablockers. Cirrhotic patients with upper GI bleed were given intravenous vasoactive agents until undergoing endoscopy. Patients with only oesophageal varices as source of bleed were recruited. Vasoactive agents were discontinued following variceal banding. The patients were observed for 12-18 hours, discharged on oral carvedilol 6.25 mg BID and monitored for 6 weeks for re-bleeding and mortality. Fifty patients were included, 27 (54%) male and 23 (46%) female. Average age was 43±3 years. Aetiology of cirrhosis was HCV in 42 (84%), HBV in 6 (12%), HCV & HBV in 2 (4%) and indeterminate in 1 (2%) patient. Seventeen (34%) patients had Child A, 22 (44%) Child B and 11 (22%) had Child C disease. Hospital stay was under 24 hours in 24 (48%), 24-48 hours in 15 (30%) and 48-72 hours in 11 (22%) patients. Five (10%) patients underwent EGD within 6 hours of admission, 28 (56%) within 12 hours, 14 (28%) within 24 hours and 3 (6%) within 36 hours. No re-bleeding, mortality or drug related adverse effects were noted during 6 weeks after discharge. Our study proves possibility of shorter management of variceal bleeding by having a 12-18 hour monitoring after endoscopic banding, followed by beta-blocker initiation and discharge. This will safely reduce physical and financial burden on health services.


Continuous production of aqueous suspensions of ultra-fine particles of curcumin using ultrasonically driven mixing device.
Developing drug formulations for poorly water-soluble drugs is a major challenge for pharmaceutical industries as the poor water solubility limits bioavailability of these drugs. Production of nanoparticles/microparticles of these drugs is one of the ways to improve dissolution rates by increasing interfacial area for dissolution. Curcumin, a compound obtained from the rhizome of curcuma longa (turmeric roots), is a pharmaceutically viable molecule. However, poor aqueous solubility limits its therapeutic use. In this work, we report studies conducted to continuously produce aqueous suspensions of curcumin nano/micro particles. Influence of process parameters such as ultrasound, additives, and solvent to antisolvent ratio on polymorphic outcome and morphology of precipitated particles has been investigated. Ultrasound was found to greatly influence the polymorphic form and the morphology of precipitated particles. Nucleation rates, mixing time, and solid-liquid interfacial energies were also estimated to understand the effect of various processing parameters on the precipitation process.


Estradiol Alleviates Intervertebral Disc Degeneration through Modulating the Antioxidant Enzymes and Inhibiting Autophagy in the Model of Menopause Rats.
To investigate the effects of menopause on redox balance in the intervertebral disc and to examine whether oxidative stress and autophagy were associated with disc degeneration in menopause rats. Thirty female Sprague-Dawley rats were randomly divided into three groups (sham, ovariectomized with vehicle, and ovariectomized with estrogen). At the end of the 3-month treatment, the rats were examined by 3.0 T MRI. Serum estradiol (E2) level was measured. Redox balance of nucleus pulposus was determined by measuring total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione (GSH), and oxidized glutathione (GSSG). Transmission electron microscopy (TEM), immunohistochemical staining, and Western blot were used to determine the nucleus pulposus autophagy level. At the same time, Spearman's correlation coefficient was used to describe the relationship between intervertebral disc grade, oxidative stress status, serum E2, and autophagy level. The level of serum E2 was significantly decreased by ovariectomy and can be corrected by the estrogen replacement therapy (ERT). In OVX rats, an increased oxidative stress and high level of autophagy were observed in nucleus pulposus tissue. ERT prevented the intervertebral disc degeneration (IVDD), restored the redox balance, and reduced autophagy level. Ovariectomy induced oxidative stress, autophagy, and intervertebral disc degeneration. Autophagy of the intervertebral disc was negatively correlated with oxidative stress, and the level of autophagy can be reduced by ERT through modulating the redox balance and downregulating the autophagy level. Regulating the redox balance of IVD may be a potential therapeutic option for degeneration of the disc in the postmenopausal women.


A prospective evaluation of the heat shock protein 70 gene polymorphisms and the risk of stroke.
Genetic polymorphisms of heat shock protein 70-kD (HSP70) gene family have recently been hypothesized to be risk factors for cerebral ischemia. However, no prospective epidemiological data evaluating this gene family are available. The present investigation was conducted to examine the possible associations between the HSP70-1 nucleotide 190. HSP70-2 nucleotide 1267, and HSP70-hom nucleotide 2437 polymorphisms and the incidence of stroke in a large cohort of initially healthy men. 14916 apparently healthy men were followed over a 12-year period for incident stroke. Employing a nested case-control study design, 338 study participants who developed stroke (cases) and 338 age- and smoking-matched study participants who remained healthy during follow-up (controls) were evaluated. All observed genotype frequencies were in Hardy-Weinberg equilibrium. The allele and genotype distributions of the polymorphisms tested were similar among cases and controls, such that the relative risk of future stroke was 0.89 for HSP70-1 nucleotide 190 (95%CI = 0.70-1.12; p = 0.31), 1.13 for HSP70-2 nucleotide 1267 (95%CI = 0.90-1.42: p = 0.29); and 0.89 for HSP70-hom nucleotide 2437 (95%CI = 0.65-1.21; p = 0.45), assuming an additive model. No evidence of association was observed assuming dominant or recessive mode of inheritance. In this large, prospective study, genetic polymorphisms in the HSP70 genes were not associated with risks of future stroke. Screening for these polymorphisms is unlikely to be a useful tool for risk assessment.


Activities of certain 5-substituted 4'-thiopyrimidine nucleosides against orthopoxvirus infections.
As part of a program to identify new compounds that have activity against orthopoxviruses, a number of 4'-thionucleosides were synthesized and evaluated for their efficacies against vaccinia and cowpox viruses. Seven compounds that were active at about 1 microM against both viruses in human cells but that did not have significant toxicity were identified. The 5-iodo analog, 1-(2-deoxy-4-thio-beta-d-ribofuranosyl)-5-iodouracil (4'-thioIDU), was selected as a representative molecule; and this compound also inhibited viral DNA synthesis at less than 1 microM but only partially inhibited the replication of a recombinant vaccinia virus that lacked a thymidine kinase. This compound retained complete activity against cidofovir- and ST-246-resistant mutants. To determine if this analog had activity in an animal model, mice were infected intranasally with vaccinia or cowpox virus and treatment with 4'-thioIDU was given intraperitoneally or orally twice daily at 50, 15, 5, or 1.5 mg/kg of body weight beginning at 24 to 120 h postinfection and was continued for 5 days. Almost complete protection (87%) was observed when treatment with 1.5 mg/kg was begun at 72 h postinfection, and significant protection (73%) was still obtained when treatment with 5 mg/kg was initiated at 96 h. Virus titers in the liver, spleen, and kidney were reduced by about 4 log(10) units and about 2 log(10) units in mice infected with vaccinia virus and cowpox virus, respectively. These results indicate that 4'-thioIDU is a potent, nontoxic inhibitor of orthopoxvirus replication in cell culture and experimental animal infections and suggest that it may have potential for use in the treatment of orthopoxvirus infections in animals and humans.


Spectrum and Outcome of Prenatally Diagnosed Fetal Primary Cardiomyopathies-A Twenty-Year Overview.
to assess the course and outcome of fetuses affected by primary cardiomyopathy (CM). Retrospective study of 21 cases with prenatal diagnosis of a primary CM in one tertiary center over a period of 20 years. Charts were reviewed for echocardiographic findings, pregnancy outcome, and postnatal course. The utility of prenatal evaluation was discussed. The mean gestational age (GA) at diagnosis was 26.7 (±5.1) weeks. A total of 33.3% (7/21) had associated anomalies. Genetic etiology was confirmed in 50.0% (10/20, with one case lost to follow up). The overall survival rate of the entire study population was 40% (8/20) including termination of pregnancy in 20% (4/20) and an intrauterine mortality rate of 5% (1/20). Of the initial survivors (n = 15), a neonatal and early infant mortality rate of 46.7% (7/15) was calculated. Prenatal isolated right ventricular involvement was the only identified significant parameter for survival (p = 0.035). Four phenotypical groups were identified: 42.9% (9/21) hypertrophic (HCM), 38.1% (8/21) dilated (DCM), 14.3% (3/21) isolated noncompaction (NCCM), and 4.8% (1/21) restrictive CM (RCM). Fetuses assigned to isolated NCCM revealed a 100% survival rate. Prenatal detection is feasible but needs to a introduce classification method for better consulting and management practices. A poor outcome is still observed in many cases, but an increase in examiners' awareness may influence optimal multispecialized care.


The role of SAMM50 in non-alcoholic fatty liver disease: from genetics to mechanisms.
Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation. SAMM50 encodes Sam50, a mitochondrial outer membrane protein involved in the removal of reactive oxygen species, mitochondrial morphology and regulation of mitophagy. Certain single nucleotide polymorphisms of SAMM50 have been reported to be correlated with NAFLD. However, the contribution of SAMM50 polymorphisms to the occurrence and severity of fatty liver in the Chinese Han cohort has rarely been reported. Here, we investigated the association between SAMM50 polymorphisms (rs738491 and rs2073082) and NAFLD in a Chinese Han cohort, as well as the mechanistic basis of this association. Clinical information and blood samples were collected from 380 NAFLD cases and 380 normal subjects for the detection of genotypes and biochemical parameters. Carriers of the rs738491 T allele or rs2073082 G allele of SAMM50 exhibit increased susceptibility to NAFLD [odds ratio (OR) = 1.39; 95% confidence interval (CI) = 1.14-1.71, P = 0.001; OR = 1.31; 95% CI = 1.05-1.62, P = 0.016, respectively] and are correlated with elevated serum triglyceride, alanine aminotransferase and aspartate aminotransferase levels. The presence of the T allele (TT + CT) of rs738491 (P < 0.01) or G allele (AG + GG) of rs2073082 (P = 0.03) is correlated with the severity of fatty liver in the NAFLD cohort. In vitro studies indicated that SAMM50 gene polymorphisms decrease its expression and SAMM50 deficiency results in increased lipid accumulation as a result of a decrease in fatty acid oxidation. Overexpression of SAMM50 enhances fatty acid oxidation and mitigates intracellular lipid accumulation. Our results confirm the association between the SAMM50 rs738491 and rs2073082 polymorphisms and the risk of fatty liver in a Chinese cohort. The underlying mechanism may be related to decreased fatty acid oxidation caused by SAMM50 deficiency.


The n-SET domain of Set1 regulates H2B ubiquitylation-dependent H3K4 methylation.
Past studies have documented a crosstalk between H2B ubiquitylation (H2Bub) and H3K4 methylation, but little (if any) direct evidence exists explaining the mechanism underlying H2Bub-dependent H3K4 methylation on chromatin templates. Here, we took advantage of an in vitro histone methyltransferase assay employing a reconstituted yeast Set1 complex (ySet1C) and a recombinant chromatin template containing fully ubiquitylated H2B to gain valuable insights. Combined with genetic analyses, we demonstrate that the n-SET domain within Set1, but not Swd2, is essential for H2Bub-dependent H3K4 methylation. Spp1, a homolog of human CFP1, is conditionally involved in this crosstalk. Our findings extend to the human Set1 complex, underscoring the conserved nature of this disease-relevant crosstalk pathway. As not all members of the H3K4 methyltransferase family contain n-SET domains, our studies draw attention to the n-SET domain as a predictor of an H2B ubiquitylation-sensing mechanism that leads to downstream H3K4 methylation.


Fulminant BCG Disease in a 7 Month Old Healthy Male Infant.
A seven month old healthy male infant was brought with papular skin lesions all over the body, which became ulcerative with increasing fever and redness within 1 week duration. On examination, Bacilli Calmette Guerin (BCG) scar was ulcerated with discharge; infant was irritable with tachycardia and tachypnea. Investigations revealed pancytopenia, and acid fast bacilli was positive in skin lesions and at BCG scar site. There was progressive worsening of infant's condition, culminating in death.


Quantitative geometric descriptions of the belt iron atoms of the iron-molybdenum cofactor of nitrogenase and synthetic iron(II) model complexes.
Six of the seven iron atoms in the iron-molybdenum cofactor of nitrogenase display an unusual geometry, which is distorted from the tetrahedral geometry that is most common in iron-sulfur clusters. This distortion pulls the iron along one C3 axis of the tetrahedron toward a trigonal pyramid. The trigonal pyramidal coordination geometry is rare in four-coordinate transition metal complexes. In order to document this geometry in a systematic fashion in iron(II) chemistry, we have synthesized a range of four-coordinate iron(II) complexes that vary from tetrahedral to trigonal pyramidal. Continuous shape measures are used for a quantitative comparison of the stereochemistry of the Fe atoms in the iron-molybdenum cofactor with those of the presently and previously reported model complexes, as well as with those in polynuclear iron-sulfur compounds. This understanding of the iron coordination geometry is expected to assist in the design of synthetic analogues for intermediates in the nitrogenase catalytic cycle.


Emotional resemblance: Perception of facial emotion in written English.
Written language is comprised of simple line configurations (i.e., letters) that, in theory, elicit affect by virtue of the concepts they symbolize, rather than their physical features. However, we propose that the line configurations that comprise letters vary in their visual resemblance to canonical features of facial emotion and, through such emotional resemblance, influence affective responses to written language. We first describe our data-driven approach to indexing emotional resemblance in each letter according to its visual signature. This approach includes cross-cultural validation and neural-network modeling. Based on the resulting weights, we examine the extent to which emotional resemblance in Latin letters is incidentally processed in a flanker paradigm (Study 1), shapes unintentional affective responses to letters (Study 2), accounts for affective responses to orthographically controlled letter strings (Study 3), and shapes affective responses to real English words (Study 4). Results were supportive of hypotheses. We discuss mechanisms, limitations, and implications. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Damaged hair retrieval with ceramide-rich liposomes.
Lipids from human hair consist mainly of cholesterol esters, free fatty acids, cholesterol, ceramides, and cholesterol sulfate. They are structured as lipid bilayers in the cell membrane complex (CMC) and make a large contribution to diffusion, cell cohesion, and mechanical strength. The loss of these lipids could impair the integrity of the hair, leading to deterioration in its tensile properties. Internal wool lipids (IWL) resemble those of the membranes of other keratinic tissues such as human hair or stratum corneum. The application of IWL structured as liposomes on pretreated hair samples has been demonstrated to restore the natural properties of the fibers. This study seeks to apply IWL liposomes to untreated hair fibers and to hair fibers subjected to chemical treatment. Differences in the lipidic composition of all chemically treated hairs were found with respect to the untreated ones. Lipid recovery of damaged hair due to the application of IWL liposomes was corroborated by lipid analysis of the hair. A high resistance to break of hair samples post-treated with IWL liposomes was observed. An increase in hydrogen bonds and electrostatic forces and an improvement in the cohesion between matrix and filaments were detected, probably because of some lipid recovery.


Characterization of multidrug-resistant and metallo-beta-lactamase-producing Pseudomonas aeruginosa isolates from a paediatric clinic in China.
In the present study, we characterized multidrug-resistant Pseudomonas aeruginosa (MDRP) clinical isolates from a paediatric facility and investigated the types and features of the metallo-beta-lactamases (MBLs) produced by carbapenem-resistant strains. Four hundred and ninety-eight strains of Pseudomonas aeruginosa were isolated from patients at Beijing Children's Hospital between January 2005 and December 2006. The minimal inhibition concentrations (MICs) of the strains for 13 antibiotics were measured. A combination of the E test and PCR amplification/DNA sequencing was used to define the carbapenem-resistant strains. We found that 24.1% (120/498) of the isolates were MDRP. The frequencies of resistance to imipenem and meropenem were 34.2% and 35.8%, respectively, and the MIC50 and MIC90 values for the two antibiotics were identical at 4 microg/ml and 32 microg/ml, respectively. The detection rate for carbapenem resistance was 49.2% (59/120). Among the 59 carbapenem-resistant Pseudomonas aeruginosa strains, 39 (66.1%) were positive for the MBL genotype; 35 (89.7%) strains carried the bla(IMP) gene and 4 (10.3%) strains carried the bla(VIM) gene. Neither bla(SPM) nor bla(GIM) was amplified from any of the 59 isolates. DNA sequencing revealed that IMP-1 was present in 35 IMP-producing isolates and VIM-2 was detected in four VIM-producing isolates. These MDRP isolates exhibited high frequencies of resistance to carbapenems among clinical isolates from a paediatric facility in Beijing, China. The production of MBL appears to be an important mechanism for carbapenem resistance in Pseudomonas aeruginosa.


Non-point source pollution of glyphosate and AMPA in a rural basin from the southeast Pampas, Argentina.
We measured the occurrence and seasonal variations of glyphosate and its metabolite, aminomethylphosphonic acid (AMPA), in different environmental compartments within the limits of an agricultural basin. This topic is of high relevance since glyphosate is the most applied pesticide in agricultural systems worldwide. We were able to quantify the seasonal variations of glyphosate that result mainly from endo-drift inputs, that is, from direct spraying either onto genetically modified (GM) crops (i.e., soybean and maize) or onto weeds in no-till practices. We found that both glyphosate and AMPA accumulate in soil, but the metabolite accumulates to a greater extent due to its higher persistence. Knowing that glyphosate and AMPA were present in soils (> 93% of detection for both compounds), we aimed to study the dispersion to other environmental compartments (surface water, stream sediments, and groundwater), in order to establish the degree of non-point source pollution. Also, we assessed the relationship between the water-table depth and glyphosate and AMPA levels in groundwater. All of the studied compartments had variable levels of glyphosate and AMPA. The highest frequency of detections was found in the stream sediments samples (glyphosate 95%, AMPA 100%), followed by surface water (glyphosate 28%, AMPA 50%) and then groundwater (glyphosate 24%, AMPA 33%). Despite glyphosate being considered a molecule with low vertical mobility in soils, we found that its detection in groundwater was strongly associated with the month where glyphosate concentration in soil was the highest. However, we did not find a direct relation between groundwater table depth and glyphosate or AMPA detections. This is the first simultaneous study of glyphosate and AMPA seasonal variations in soil, groundwater, surface water, and sediments within a rural basin.


Double crush syndrome in lower extremities.
Retrospective analysis of results of electromyography and nerve conduction velocity was performed in 169 patients with lower back pain, mostly caused by trauma. A total 289 peroneal, 280 posterior tibial and 301 sural nerves were included in statistical analysis. Peripheral entrapment of nerves (tarsal tunnel syndrome and anterior tarsal tunnel syndrome) were found in 5.3% of patients, signs of acute or chronic partial muscle denervation of corresponding muscles of lower extremities in 21.8% of patients, and abnormally prolonged F-wave latency in 12.5% of patients. Combined partial denervation and abnormally prolonged F-wave latency were found in 6.2% of patients, combined partial denervation and peripheral entrapment of nerves in 4.4% of patients, combined abnormally prolonged F-wave latency and peripheral entrapment of nerves in 2.4% of patients and combined partial denervation, abnormally prolonged F-wave latency and peripheral entrapment of nerves in 3.5% of patients. Statistical analysis of these data showed significantly higher than random overlap of peripheral entrapment syndromes and signs of proximal nerve damage of the corresponding nerves (partial muscle denervation or abnormalities of F-wave). This higher than random coincidence of the two conditions strongly suggests cause-and-effect relationship of damage of the proximal stretch of motor nerve fibers and development of peripheral entrapment syndromes in the same nerves rather than a random coincidence of two independent pathologies. Appreciation of this causal relationship is important in the development of comprehensive approach to treatment of peripheral entrapment syndromes. In appropriate cases, simultaneous treatment of the lower back problem should be considered as well.


Significance of unconventional peripheral CD4+CD8dim T cell subsets.
Routine T cells phenotyping occasionally reveals a CD4+CD8dim T cell subset with an apparently homogeneous dot plot. The aim of this study was to elucidate their immunological significance from analysis of 31 healthy donors, 21 elderly and 220 immune deficient patients. CD4+CD8dim T cells expressed reduced levels of CD8 (11-17,000 compared to 96-128,000 mol/cell on CD8+ T Cells). CD4 was expressed at the same level as on CD4+ T cells. The occurrence of raised CD4+CD8dim T cells (> 20 cells/muL) was similar in kidney transplant recipients (28.4%) and healthy donors (26%). It was somewhat lower in HIV+ patients (19.7%) possibly due to virally induced CD4+ T lymphopenia. However, an age effect is possible because the occurrence was raised (33.3%) in 70 volunteers (chi2 test NS). On the other hand, the size of the CD4+CD8dim subset was not correlated with age. CD4+CD8dim T cells did not express the activation markers CD69 (n = 220) or CD25 (n = 10) and expressed the homodimeric (alphaalpha) isoform of CD8, suggesting they are related to mucosal immunity (MALT). We selected 29 patients with unambiguous dot plots. In 26 of them one predominant TCR Vbeta clonotype was expressed on 18 to 94% of CD4+CD8dim T cells and never on more than 10% of conventional T cells. The predominant clonotypes were Vbeta8 (n = 5), Vbeta2 (n = 4), Vbeta13.1 and Vbeta 21 (n = 3 each). Whether this reveals a chronic stimulation or an emerging lymphoproliferative disorder must be elucidated. We propose to name this entity: "Oligoclonal Clonopathy of Undetermined Significance (OCUS)."


New science in plain sight: Citizen scientists lead to the discovery of optical structure in the upper atmosphere.
A glowing ribbon of purple light running east-west in the night sky has recently been observed by citizen scientists. This narrow, subauroral, visible structure, distinct from the traditional auroral oval, was largely undocumented in the scientific literature and little was known about its formation. Amateur photo sequences showed colors distinctly different from common types of aurora and occasionally indicated magnetic field-aligned substructures. Observations from the Swarm satellite as it crossed the arc have revealed an unusual level of electron temperature enhancement and density depletion, along with a strong westward ion flow, indicating that a pronounced subauroral ion drift (SAID) is associated with this structure. These early results suggest the arc is an optical manifestation of SAID, presenting new opportunities for investigation of the dynamic SAID signatures from the ground. On the basis of the measured ion properties and original citizen science name, we propose to identify this arc as a Strong Thermal Emission Velocity Enhancement (STEVE).


Efficacy and safety of eight types Salvia miltiorrhiza injections in the treatment of unstable angina pectoris: A network meta-analysis.
Background: Salvia miltiorrhiza Bunge. [Lamiaceae, danshen] injection classes (SMIC) is widely used in the treatment of unstable angina (UA). However, it is uncertain which SMIC is more effective in terms of UA efficacy. The purpose of this Network Meta-analysis (NMA) was to compare the treatment effects of various SMIC to determine the best SMIC for the treatment of UA. Methods: The China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), Chinese Biomedical Literature Database (CBM), PubMed, Web of Science, and Cochrane Library databases were searched to screen randomized controlled trials (RCTs) of SMIC for UA. The search time frame was all from the establishment of the database to May 2022. RevMan 5.3 and Stata 14.0 software were used for NMA. Results: A total of 148 studies including 14,979 patients, including 7,584 cases in the experimental group and 7,395 cases in the control group were included, and eight SMIC were extracted, namely:Danshen injection, Fufang Danshen injection, Guanxinning injection, Danshenchuanxiongqin injection, Danhong injection, Danshentong IIA Huangsuanna injection, Shenxiong Putaotang injection, and Danshenduofensuanyan injection. The results of NMA showed that, in terms of total effective rate, Shenxiong Putaotang injection and Danshenchuanxiongqin injection have the advantage; In terms of ECG efficiency, Danshentong IIA Huangsuanna injection and Danshen injection have an advantage; Danshenchuanxiongqin injection and Danshenduofensuanyan injection were more effective than other SMIC in improving angina pectoris attacks; Shenxiong Putaotang injection has an advantage in improving hs-CRP; Shenxiong Putaotang injection and Danshentong IIA Huangsuanna injection have advantages in improving TC and TG, respectively. Conclusion: The eight SMIC included in the current study were effective in treating UA, Shenxiong Putaotang injection and Danshentong IIA Huangsuanna injection were both superior in improving all outcome indicators. However, there is still a need for larger samples and high-quality randomized controlled trials for more refined comparisons of various SMIC. Systematic Review Registration: [PROSPERO], identifier [CRD42022350872].


An unusual presentation of Ménétrier's Disease.
Ménétrier's Disease (MD) is a rare acquired hypertrophic gastropathy characterized by giant hypertrophic rugal folds, hypochlorhydria, and hypoproteinemia. The definitive etiology of MD is controversial, although infection with Helicobacter pylori (H. pylori) has been implicated in adults. It presents as a constellation of symptoms including epigastric pain, fatigue, vomiting, weight loss, anorexia, and edema. None of these signs and symptoms is specific for the disease. The gastrointestinal symptoms and the degree of hypoalbuminemia can be profound, the latter resulting from the leakage of protein from the gastric lining. The disease is more common in males. Herein, we report a case of a young woman presenting with the chief complaint of peripheral edema with minimal gastrointestinal symptoms, which was diagnosed as MD on endoscopic evaluation and histopathological examination of gastric biopsy. A high index of suspicion is needed to correctly diagnose this condition for its optimal management.


Isolated pan-pontine posterior reversible encephalopathy syndrome in a patient with uncontrolled hypertension.
Recognition of central variant PRES is key to avoiding detrimental treatment. The pons may be the most vulnerable area in central PRES, and delayed presentation may result in greater damage. CSF reporting may lead to eventual recognition of a common profile, and possible aid in future diagnosis.


[Myocardial infarct. Dimensions of the problem and its local aspects].
World statistics of infarction are given in brief from the viewpoints of incidence, mortality and prevalence. The results of analysing admittances for m.i. to the Imperia Hospital in the period 1960-1972 are then reported. The series is considered from the general and local standpoints, with reference to the organizational and welfare problems created by the high number of admittances and their high annual increment.


Salience-driven overestimation of total somatosensory stimulation.
Psychological characterisation of sensory systems often focusses on minimal units of perception, such as thresholds, acuity, selectivity and precision. Research on how these units are aggregated to create integrated, synthetic experiences is rarer. We investigated mechanisms of somatosensory integration by asking volunteers to judge the total intensity of stimuli delivered to two fingers simultaneously. Across four experiments, covering physiological pathways for tactile, cold and warm stimuli, we found that judgements of total intensity were particularly poor when the two simultaneous stimuli had different intensities. Total intensity of discrepant stimuli was systematically overestimated. This bias was absent when the two stimulated digits were on different hands. Taken together, our results showed that the weaker stimulus of a discrepant pair was not extinguished, but contributed less to the perception of the total than the stronger stimulus. Thus, perception of somatosensory totals is biased towards the most salient element. 'Peak' biases in human judgements are well-known, particularly in affective experience. We show that a similar mechanism also influences sensory experience.


Interdisciplinary Perspectives on Health Literacy Research Around the World: More Important Than Ever in a Time of COVID-19.
As we write our editorial for a health literacy special issue in the midst of the international COVID-19 crisis, we take this opportunity to highlight the importance of individual, community, and population health literacy. We are not only in a "pandemic" but also an "infodemic". Health literacy is more important than ever in the face of these global health threats, which have impacted outcomes across the levels of the socio-ecological model (SEM), including individual health behaviors, family relationships, organizational behavior, state policy-making, national mortality statistics, and the international economy in the span of weeks. Our special issue sought to pull together interdisciplinary threads guided by two principles. The first was defining health literacy as essential skills and situational resources needed for people to find, understand, evaluate, communicate, and use information and services in a variety of forms across various settings throughout their life course to promote health and wellbeing. The second was the idea that enhancing health literacy in populations and systems is critical to achieving health equity. In this time of public health need across traditional borders, the inter-sectoral and international perspectives of special issue articles are more urgent than ever. A greater understanding, appreciation, and application of health literacy can support policy action on multiple levels to address major public health challenges. Health literacy should be built deliberately as a population-level resource and community asset. We have summarized the set of articles in this special issue across the levels of the SEM, hoping their thoughtful considerations and interesting findings will help to support global health and wellness and inspire future research, policy, and practice in this global public health emergency and beyond.


Visual surround suppression in schizophrenia.
Compared to unaffected observers patients with schizophrenia (SZ) show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgments of contrast - a manifestation of weaker surround suppression (SS). To examine the generality of this phenomenon we measured the ability of 24 individuals with SZ to judge the luminance, contrast, orientation, and size of targets embedded in contextual surrounds that would typically influence the target's appearance. Individuals with SZ demonstrated weaker SS compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation SS in SZ may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies.


[40]π Fused and Nonfused Core-Modified Nonaphyrins: Syntheses and Structural Diversity.
The synthesis of fused and nonfused core-modified 40π nonaphyrins are reported. Spectroscopic and X-ray structural studies reveal a twisted figure-eight conformation in the freebase form that is nonaromatic. Structural changes occur, from figure-eight to open extended conformation, upon protonation, thereby adopting 4nπ Hückel antiaromatic character, which is reflected in spectroscopic and theoretical studies. Such a structural change also induces ring inversions of specific heterocyclic rings by 180°.


Investigations on the pathogenesis of venous leg ulcers.
Based on a prospective study of 92 patients with DVT initiated in 1979, including a follow-up every year, the following investigations were performed: phlebography, Doppler-ultrasound, plethysmography (strain gauge and PPG) and foot-volumetry. In ulcer-patients skin blood flow was measured by Laser-Doppler and local oxygen supply by measurement of transcutaneous oxygen. Transcapillary protein-leakage was assessed by isotopic methods, local lymph-drainage by isotopic lymphography and indirect x-ray lymphography. From the results of these investigations the following course of events, which may be of importance for the development of venous ulceration, can be outlined: 1. Venous refluxes penetrating into the venules of the skin. 2. Chronic venous ambulatory hypertension (lack of pressure-fall during walking), waves of high pressure in the capillaries. 3. Protein-rich oedema. 4. Failure of fibrin clearance from the pericapillary space due to inadequate (exhausted?) fibrinolysis and deficient local lymph drainage. 5. Resulting changes in the ground substance, proliferation of fibres. 6. Local hypoxia due to a diffusion block by the impermeable pericapillary cuffs, partially due to a reduction of capillaries in the superficial layers.


Dental interventions in oral antithrombotic therapy.
Dentists commonly encounter patients taking oral antithrombotic agents who require invasive dental procedures. Although antithrombotics can cause an increase in bleeding, there is consensus that treatment regimens with antiplatelet agents, older anticoagulants (warfarin) and direct oral anticoagulants should not be altered before routine dental procedures when the risk of bleeding is low. Thromboembolic risk of their discontinuing likely outweighs potential bleeding complications associated with surgery. Therefore, the risks of stopping or reducing these medications must be weighed against the potential consequences of prolonged bleeding, which can be controlled with local measures such as mechanical pressure, suturing, haemostatic agents or antifibrinolytics. Some patients who are taking antithrombotic medications may have additional comorbid conditions or receive other therapy that can increase the risk of prolonged bleeding after dental treatment. Where a patient is believed to be at high bleeding risk, the dentist should consider a consultation with the patient's physician to discuss temporarily discontinuing the antithrombotic therapy.


Efficient Queries of Stand-off Annotations for Natural Language Processing on Electronic Medical Records.
In natural language processing, stand-off annotation uses the starting and ending positions of an annotation to anchor it to the text and stores the annotation content separately from the text. We address the fundamental problem of efficiently storing stand-off annotations when applying natural language processing on narrative clinical notes in electronic medical records (EMRs) and efficiently retrieving such annotations that satisfy position constraints. Efficient storage and retrieval of stand-off annotations can facilitate tasks such as mapping unstructured text to electronic medical record ontologies. We first formulate this problem into the interval query problem, for which optimal query/update time is in general logarithm. We next perform a tight time complexity analysis on the basic interval tree query algorithm and show its nonoptimality when being applied to a collection of 13 query types from Allen's interval algebra. We then study two closely related state-of-the-art interval query algorithms, proposed query reformulations, and augmentations to the second algorithm. Our proposed algorithm achieves logarithmic time stabbing-max query time complexity and solves the stabbing-interval query tasks on all of Allen's relations in logarithmic time, attaining the theoretic lower bound. Updating time is kept logarithmic and the space requirement is kept linear at the same time. We also discuss interval management in external memory models and higher dimensions.


Evaluation of urinary FOXP3 mRNA as a biomarker of lupus nephritis in Egyptian patients with systemic lupus erythematosus.
Lupus nephritis (LN) is one of the most serious complications of SLE. Tregs (Regulatory T lymphocytes) are thought to play a part in the pathogenesis of SLE. According to recent research, Foxp3, a Treg identification marker, plays a significant role in the pathogenesis of SLE. This study aimed to compare the urinary Foxp3 mRNA levels of patients with active and inactive forms of LN and healthy control subjects to see whether it played a role in disease activity. We measured FOXP3 messenger RNA (mRNA) expression in the urine of 50 people with active LN, 50 people with inactive lupus, and 50 healthy people. We found that the expression level of FOXP3 was significantly higher in urine from patients with active LN than from subjects with inactive lupus and healthy controls (22.93 ± 4.13 vs 5.66 ± 0.47 vs 0.57 ± 0.15copy; P < 0.001).Urinary FOXP3 mRNA level significantly correlated with SLEDAI (0.000057) In the active group, urinary FOXP3 mRNA level also significantly correlated with histological activity index (< 0.00001). We concluded that urinary FOXP3 mRNA is elevated in patients with active LN and that it is linked to the SLEDAI and the severity of the disease. FOXP3 mRNA in urine sediment may be used as a non-invasive biomarker for evaluating the severity of LN and risk stratification.


Acute Eosinophilic Pneumonia Masquerading as a Lung Abscess.
Acute Eosinophilic Pneumonia (AEP) is a rare form of non-infectious pneumonia that is easily missed and misdiagnosed because of its atypical clinical symptoms and misleading laboratory and imaging studies. By reporting a case of an initial diagnosis of lung abscess, which was treated with antibiotics and then CT suggesting that the lesion continued to worsen, it was eventually confirmed to be AEP by lung biopsy, A joint literature analysis was conducted to improve clinicians' understanding of the diagnosis and treatment of AEP. Initially, because of the atypical ancillary findings, we thought the disease was a lung abscess, which was eventually confirmed by pathology as AEP. The presence of AEP needs to be considered when various laboratory findings point to infectious dis-ease, but anti-infection is not effective. Diagnosis can be confirmed by bronchoalveolar lavage and lung tissue biopsy. Prompt treatment can provide rapid relief and reduce the risk of patient death.


A Patient-Centered Understanding of the Referral System in Ethiopian Primary Health Care Units.
Primary healthcare systems in sub-Saharan Africa have undergone substantial development in an effort to expand access to appropriate facilities through a well-functioning referral system. The objective of this study was to evaluate the current patterns of seeking prior care before arriving at a health center or a hospital as a key aspect of the referral system of the primary health care unit (PHCU) in three regions in Ethiopia. We examined what percentage of patients had either sought prior care or had been referred to the present facility and identified demographic and clinical factors associated with having sought prior care or having been referred. We conducted a cross-sectional study using face-to-face interviews in the local language with 796 people (99% response rate) seeking outpatient care in three primary health care units serving approximately 100,000 people each and reflecting regional and ethnic diversity; 53% (N = 418) of the sample was seeking care at hospital outpatient departments, and 47% of the sample was seeking care at health centers (N = 378). We used unadjusted and adjusted logistic regression to identify factors associated with having been referred or sought prior care. Our findings indicated that only 10% of all patients interviewed had been referred to their current place of care. Among those in the hospital population, 14% had been referred; among those in the health center population, only 6% had been referred. Of those who had been referred to the hospital, most (74%) had been referred by a health center. Among those who were referred to the health center, the plurality portion (32%) came from a nearby hospital (most commonly for continued HIV treatment or early childhood vaccinations); only 18% had come from a health post. Among patients who had not been formally referred, an additional 25% in the hospital sample and 10% in the health center sample had accessed some prior source of care for their present health concern. In the adjusted analysis, living a longer distance from the source of care and needing more specialized care were correlated with having sought prior care in the hospital sample. We found no factors significantly associated with having sought prior care in the health center sample. The referral system among health facilities in Ethiopia is used by a minority of patients, suggesting that intended connections between health posts, health centers, and hospitals may need strengthening to increase the efficiency of primary care nationally.


Hyperuricosuria in cystic fibrosis patients treated with pancreatic enzyme supplements. A study of 16 patients in Israel.
Uric acid metabolism was evaluated in 16 Israeli cystic fibrosis patients, all of whom were taking pancreatic enzyme supplements. The findings were compared with those in a recent study of uric acid metabolism in 65 healthy Israeli children. Hyperuricemia of 4.9 +/- 0.2 (SE) mg/dl was found in the cystic fibrosis patients, compared with a normal level of 3.1 +/- 0.2 mg/dl ( P < 0.05). In five patients, 24-h urine collections were assayed and all showed hyperuricosuria. Thirteen patients had high urinary uric acid/creatinine ratios. Hyperuricosuria increased with the age of the patient and when the administered dosage of pancreatic enzyme exceeded 10,000 lipase units/kg body weight. Despite normal levels of serum creatinine and urea, and normal creatinine clearance in the cystic fibrosis patients, risk of future renal damage seems obvious and preventive measures should be considered.