Effects of perampanel on cognitive behavior and GluR1 expression in immature mice of temporal lobe epilepsy.
Temporal lobe epilepsy (TLE) has a low antiepileptic drug (AED) treatment response rate, and about 70% of patients eventually progress to refractory epilepsy. Perampanel (PER) is a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist, which is used clinically for the treatment of partially refractory epilepsy, but its mechanism of action is not completely clear. In this study, kainic acid (KA) was successfully used to induce TLE in 3-week-old C57BL/6 immature mice, and the effects of PER on the cognitive behavior of the epileptic mice were characterized using the Morris water maze paradigm. To determine the mechanism underlying the therapeutic effects of PER, the morphological evolution of the hippocampus and the expression of AP-1 and GluR1 were systematically evaluated. Compared to control TLE mice, escape latency was reduced and the number of target platform crossings was increased in the Morris water maze by treatment with PER. The therapeutic effects of PER were mediated mainly via inhibition of the expression of AP-1 and GluR1, as the TLE mice showed significantly improved learning and memory and decreased seizure frequency after treatment with PER.


Development of an alert system for subjects with paroxysmal atrial fibrillation.
Knowledge of the onset of atrial fibrillation (AF) episodes in patients with paroxysmal atrial fibrillation (PAF) will enable them to better manage this condition. Current advances in mobile technology allow RR interval data to be obtained in real time. An analysis technique using RR interval data is presented with a view to alert a subject before a PAF episode. The method is based on a time series of standard deviation and 0.99 quantile values of the spectral entropy, constructed from RR data. The RR data are taken from three time periods. The first time period has no occurrences of AF for 45 min to either side of the time period. The second time period just precedes an AF attack. Both of these are of thirty minutes duration. The third time period of approximately 5 min follows the second, and is when AF occurs. Twenty-two PAF subjects were studied and in all cases there was a steady increase in the values of these indices as the onset of the AF attack approached. This method of analysis of RR interval data shows potential use to alert a PAF subject before the onset of an AF episode.


Rethinking the visceral innervation --- Peek into the emerging field of molecular dissection of neural signals.
Communication between the nervous system and the viscera, comprising the afferent and efferent pathways, is a fundamental part of maintaining homeostasis. The cellular and molecular properties of the visceral innervation have long been obscure. Emerging techniques applied in neuroscience including single-cell RNA sequencing approaches prove us with powerful tools to tackle the unsolved puzzles. This perspective aims to derive and inspire new insights into the integrative roles of the nervous system based on the latest research progress.


Differential treatment of hypertension by primary care providers and hypertension specialists in a barber-based intervention trial to control hypertension in Black men.
Black men have less physician contact than other groups and thus lower rates of hypertension treatment and control. In the Barber-Assisted Reduction in Blood Pressure among Ethnic Residents trial, hypertension control in 8 active-intervention barbershops where barbers offered blood pressure (BP) checks with haircuts and motivated black male patrons with high BP to seek provider follow-up showed a small improvement over that in 7 comparison shops where patrons received hypertension pamphlets but not barber-BP checks. Undertreatment of hypertension, which is common in primary care, may have impacted the outcomes. Thus, in patrons with a baseline systolic BP of ≥140 mm Hg and 10-month follow-up including BP and medication data, we performed post hoc comparison of systolic BP reduction between comparison-arm patrons (n = 68) treated by primary care providers (PCPs) with (1) intervention-arm patrons (n = 37) treated by PCPs or (2) intervention-arm patrons (n = 33) who lacked access to PCPs and were treated by hypertension specialist physicians serving as safety net providers. The latter group had higher baseline systolic BP than the others (162 ± 3 vs 155 ± 2 and 154 ± 2 mm Hg, respectively, p <0.01). After adjustment for baseline systolic BP and other covariates, systolic BP reduction was 21 ± 4 mm Hg greater than in the comparison group (p <0.0001), when barbers referred patrons to hypertension specialists but was no different when they referred to PCPs (4 ± 4 mm Hg, p = 0.31). Specialist-treated patrons received more BP medication and different classes of medication than PCP-treated patrons. In conclusion, the barber-based intervention-if connected directly to specialty-level medical care-could have a large public health impact on hypertensive disease in black men.


ALG2 inhibits the epithelial-to-mesenchymal transition and stemness of ovarian granulosa cells through the Wnt/β-catenin signaling pathway in polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects fertility in women of reproductive age, and a leading cause of anovulatory infertility. Ovarian granulosa cells are a major functional cell type in the ovary that undergo epithelial-to-mesenchymal transition (EMT) to initiate ovulation. Protein glycosylation, catalyzed by specific glycosyltransferases, has been implicated in reproductive events, such as embryo implantation, endometrial receptivity, and decidualization, etc. However, the relationship between glycosylation and EMT-mediated ovulation in PCOS is not well understood. To clarify the role of cobalt chloride (CoCl2) and α-1,3/1,6-mannosyltransferase (ALG2) in PCOS, transwell assay, Real-time PCR, Western blot, immunofluorescence, and sphere formation assay were applied to assess cell migration, invasion, EMT, and stemness of ovarian granulosa cells. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the serum level of ALG2 in PCOS patients. We found that CoCl2 promoted the migration, invasion, EMT, and stemness of ovarian granulosa cells by downregulating the expression of ALG2. Upregulation of ALG2 rescued the effects of CoCl2 partially, and inhibited the EMT and stemness of ovarian granulosa cells by inactivating the Wnt/β-catenin signaling pathway. Moreover, the serum level of ALG2 was increased in patients with PCOS. Elevated ALG2, in combination with testosterone, represented better diagnostic value for PCOS as a multimarker than ALG2 or testosterone alone as a single marker. Thus, ALG2, downregulated by CoCl2, was increased in PCOS patients which inhibited the EMT and stemness of ovarian granulosa cells by deactivating the Wnt/β-catenin signaling pathway. The combination of ALG2 and testosterone might thus act as a novel but promising biomarker for PCOS detection.


The Diabetic Foot as a Proxy for Cardiovascular Events and Mortality Review.
This article reviewed very recent papers (2016) discussing or bringing clinical evidences of the possible common pathways leading to diabetic foot syndrome (DFS) and increased mortality rates. Diabetic patients with diabetic foot syndrome have a mortality rate greater than twofold when compared with non-ulcerated diabetics. In addition, the 5-year mortality rate following amputation is estimated at 39-68%, a life expectancy comparable to aggressive types of cancer or advanced congestive heart failure. The majority of patients with diabetic foot ulcer also present insulin resistance, central obesity, dyslipidemia, and hypertension that characterize the metabolic syndrome that, in turn, is associated with an elevated risk of major cardiovascular events. Sensory neuropathy is the primary cause of more the 60% of diabetic foot ulcer. Diabetic peripheral neuropathy is a microvascular complication of diabetes mellitus and in type 2 diabetes, not only hyperglycemia but also other metabolic alterations and persistent inflammatory status due to adiposity play a major role in axon injury. Elevated triglycerides have been showed to be an independent risk factor for lower extremity amputation in diabetic patients. Also, toxic adiposity, oxidative stress, mitochondrial dysfunction, activation of the polyol pathway, accumulation of advanced glycation end products (AGEs), and elevation of inflammatory markers are also implicated in diabetic vascular disease and neuropathy. The hypotheses that the association between DFS and increased rates of mortality reflects the progression of micro- and macrovascular complications are reinforced by the additional association of DFU to renal failure and retinopathy.


Transmission dynamics model and the coronavirus disease 2019 epidemic: applications and challenges.
Since late 2019, the beginning of coronavirus disease 2019 (COVID-19) pandemic, transmission dynamics models have achieved great development and were widely used in predicting and policy making. Here, we provided an introduction to the history of disease transmission, summarized transmission dynamics models into three main types: compartment extension, parameter extension and population-stratified extension models, highlight the key contribution of transmission dynamics models in COVID-19 pandemic: estimating epidemiological parameters, predicting the future trend, evaluating the effectiveness of control measures and exploring different possibilities/scenarios. Finally, we pointed out the limitations and challenges lie ahead of transmission dynamics models.


Hollow Prussian Blue nanocubes as peroxidase mimetic and enzyme carriers for colorimetric determination of ethanol.
The peroxidase-like activity of hollow Prussian Blue nanocubes (hPBNCs) is used, in combination with the enzyme alcohol oxidase (AOx), in a colorimetric ethanol assay. Different from other nanozymes, the large cavity structure of the hPBNCs provides a larger surface and more binding sites for AOx to be bound on their surface or in the pores. This extremely enhances the sensitivity of the assay system. In the presence of ethanol, AOx is capable of catalyzing the oxidation of alcohols to aldehydes, accompanied by the generation of hydrogen peroxide (H2O2). The hPBNCs act as peroxidase mimics and then can catalyze the oxidation of 3,3'5,5'-tetramethylbenzidine (TMB) by H2O2, resulting in a color change of the solution from colorless to blue with a strong absorption at 652 nm. The lower detection limit for ethanol is 1.41 μg∙mL-1. Due to the high catalytic activity of hPBNCs in weakly acidic and neutral solutions, the system was successfully applied to the determination of ethanol in mice blood. This is critically important for studying the alcohol consumption and monitoring the ethanol toxicokinetics. Graphical abstract Schematic representation of hollow Prussian Blue nanocubes (hPBNCs) used as both a peroxidase mimetic and as a carrier for alcohol oxidase. Utilizing hPBNCs along with the ethanol conversion enzyme, a sensitive colorimetric assay for ethanol was developed and applied to blood samples with satisfactory results.


Evidence that the p53 negative / Bcl-2 positive phenotype is an independent indicator of good prognosis in colorectal cancer: a tissue microarray study of 460 patients.
Advances in our understanding of the molecular biology of colorectal cancer have fuelled the search for novel molecular prognostic markers to complement existing staging systems. Markers assessed in combination may perform better than those considered individually. Using high-throughput tissue microarray technology, we describe the prognostic value of combined p53 / Bcl-2 status in colorectal cancer. Tumour samples from 462 patients who underwent elective surgery to resect a primary colorectal cancer between 1994 and 2000 (mean follow-up of 75 months) were assembled in tissue microarray format. Clinico-pathological data including tumour grade, stage, vascular invasion status along with disease specific survival data has been collected prospectively. Immunohistochemical analysis of p53 and Bcl-2 expression was performed using antibodies DO-7 (p53) and 124 (Bcl-2), and results correlated with known clinico-pathological variables and outcomes. Abnormal nuclear p53 accumulation and Bcl-2 overexpression were detected in 221/445 (49.6%) and199/437 (45.5%) tumours respectively, with a significant inverse correlation between the two markers (p = 0.023). On univariate analysis no correlations were found between either marker and standard clinico-pathological variables, however nuclear p53 expression was associated with a significantly reduced survival (p = 0.024). Combined analysis of the two markers indicated that 112/432 (24.2%) cases displayed a p53(-)/Bcl-2(+) phenotype, this occurring more frequently in earlier stage tumours. Kaplan-Meier analysis revealed a significant survival advantage in these p53(-)/Bcl-2(+) tumours compared with the remaining cases (p = 0.0032). On multivariate analysis using the Cox proportional hazards model, neither p53 expression nor Bcl-2 expression alone were of independent prognostic significance, however the combined p53(-)/Bcl-2(+) phenotype was significantly associated with a good prognosis in this series (HR 0.659, 95%CI 0.452-0.959, p = 0.029). Patient stratification by combined p53 / Bcl-2 phenotype provides stage-independent prognostic information in colorectal cancer. Specifically, that up to a quarter of patients display a good prognosis p53(-)/Bcl-2(+) phenotype. This may indicate a more clinically indolent phenotype and a subset of patients for whom less aggressive adjuvant treatment appropriate.


An unexpected cause for cavitary pneumonia and empyema.
Tularemia is an emerging zoonotic disease mainly of the Northern Hemisphere caused by the Gram-negative coccobacillus Francisella tularensis. It is affecting a wide range of animals and causes human disease after insect and tick bites, skin contact, ingestion and inhalation. A 66-year-old man presented to our clinic with cavitary pneumonia and distinct pleural effusion. After failure of empiric antibiotic therapy, thoracoscopic assisted decortication and partial excision of the middle lobe were conducted. Conventional culture methods and broad-range bacterial PCR including RipSeqMixed analysis were performed from the excised biopsies. Culture results remained negative but broad-range PCR targeting the first half of the 16S rRNA gene revealed F. tularensis DNA. This result was confirmed by F. tularensis-specific PCR and by serology. The source of infection could not be explored. To conclude, we report the rare clinical picture of a community-acquired pneumonia followed by pleural effusion and empyema due to F. tularensis. Broad range bacterial PCR proved to be a powerful diagnostic tool to detect the etiologic organism.


Different apoptotic activity and p21(WAF1/CIP1), but not p27(Kip1), expression in serrated adenomas as compared with traditional adenomas and hyperplastic polyps of the colorectum.
Serrated adenomas (SAs), which include a wide spectrum of lesions, can be broadly divided into two subtypes: type I, closely mimicking hyperplastic polyps (HPs), and type II, unequivocal adenomatous tumor. Our preliminary findings showed clinicopathologic differences between them. The present study was conducted to investigate apoptotic activity and expression of the cell cycle regulator proteins p21(WAF1/CIP1) and p27(Kip1) in type I and II SAs, as compared with traditional adenomas (TAs) and HPs. Apoptotic activity was estimated in hematoxylin-eosin stained specimens, and p21(WAF1/CIP1) or p27(Kip1) immunoreactivity was determined in 62 SAs (19 type I and 43 type II), 50 TAs and 19 HPs. The numbers (percentages) of apoptotic or immunoreactive cells were counted per 1,000 epithelial cells in equally separated crypt zones (upper, middle, and lower thirds). The apoptotic activity in the middle, but not the upper or lower crypt zone was higher in type II SAs (median 0.2%, interquartile range 0.1-0.5%) than in HPs (0.1%, 0.1-0.2%, P<0.01), whereas it was lower in type I SAs (0.2%, 0.1-0.3%) than in TAs (0.5%, 0.2-0.6%, P<0.001). P21(WAF1/CIP1) expression in the lower crypt zone was higher in both type I and type II SAs (19.8%, 7.0-33.2% and 20.4%, 3.9-47.8%, P<0.0001) than in TAs (1.2%, 0.6-5.2%), and a similar tendency was also observed for the middle crypt zone. p27(Kip1) expression did not vary among the groups. The differences in apoptotic activity and p21(WAF1/CIP1) expression between SAs and TAs or HPs indicate that SA should be considered as a distinct subtype of colorectal neoplasm. The two subtypes of SA do not differ in these parameters despite specific clinicopathological features.


The effect of simplifying assumptions in the bidomain model of cardiac tissue: application to ST segment shifts during partial ischaemia.
In this study various electrical conductivity approximations used in bidomain models of cardiac tissue are considered. Comparisons are based on epicardial surface potential distributions arising from regions of subendocardial ischaemia situated within the cardiac tissue. Approximations studied are a single conductivity bidomain model, an isotropic bidomain model and equal and reciprocal anisotropy ratios both with and without fibre rotation. It is demonstrated both analytically and numerically that the approximations involving a single conductivity bidomain, an isotropic bidomain or equal anisotropy ratios (ignoring fibre rotation) results in identical epicardial potential distributions for all degrees of subendocardial ischaemia. This result is contrary to experimental observations. It is further shown that by assuming reciprocal anisotropy ratios, epicardial potential distributions vary with the degree of subendocardial ischaemia. However, it is concluded that unequal anisotropy ratios must be used to obtain the true character of experimental observations.


Isolation, purification, and characterization of a mouse plasmacytoma cell surface glycoprotein involved in the resistance of the tumor cells to immune destruction.
Cells of a subline of the mouse plasmacytoma LPC-1 are resistant to lysis by cytotoxic T-lymphocytes, probably as a result of the blocking of the major histocompatibility gene complex-encoded cell surface antigens by a trypsin-sensitive glycoprotein of approximately 160 kilodaltons. This glycoprotein (gp 160) was extracted from LPC-1 cells with 1.5 M urea and was further purified by ammonium sulfate precipitation and Sephacryl S-300 gel filtration. The gp 160 consists of a single peptide chain rich in sialic acid residues (10% of total molecular weight) and has an acidic isoelectric point. The amino acid composition of gp 160 is compatible with the linkage of carbohydrates (galactose, glucosamine, and sialic acid) to the protein portion. The apparent weak attachment of gp 160 to the cell membrane could explain the finding that LPC-1 cells easily revert from the resistant to the sensitive to the immune lysis phenotype.


Salvage radiotherapy is effective in patients with PSMA-PET-negative biochemical recurrence- results of a retrospective study.
The present study aimed to assess whether SRT to the prostatic fossa should be initiated in a timely manner after detecting biochemical recurrence (BR) in patients with prostate cancer, when no correlate was identified with prostate-specific membrane antigen positron emission tomography (PSMA-PET). This retrospective, multicenter analysis included 1222 patients referred for PSMA-PET after a radical prostatectomy due to BR. Exclusion criteria were: pathological lymph node metastases, prostate-specific antigen (PSA) persistence, distant or lymph node metastases, nodal irradiation, and androgen deprivation therapy (ADT). This led to a cohort of 341 patients. Biochemical progression-free survival (BPFS) was the primary study endpoint. The median follow-up was 28.0 months. The 3-year BPFS was 71.6% in PET-negative cases and 80.8% in locally PET-positive cases. This difference was significant in univariate (p = 0.019), but not multivariate analyses (p = 0.366, HR: 1.46, 95%CI: 0.64-3.32). The 3-year BPFS in PET-negative cases was significantly influenced by age (p = 0.005), initial pT3/4 (p < 0.001), pathology scores (ISUP) ≥ 3 (p = 0.026), and doses to fossa > 70 Gy (p = 0.027) in univariate analyses. In multivariate analyses, only age (HR: 1.096, 95%CI: 1.023-1.175, p = 0.009) and PSA-doubling time (HR: 0.339, 95%CI: 0.139-0.826, p = 0.017) remained significant. To our best knowledge, this study provided the largest SRT analysis in patients without ADT that were lymph node-negative on PSMA-PET. A multivariate analysis showed no significant difference in BPFS between locally PET-positive and PET-negative cases. These results supported the current EAU recommendation to initiate SRT in a timely manner after detecting BR in PET negative patients.


Health-related predictors of falls and fractures in women over 40.
A longitudinal study of women aged 40-80 predicted single falls from a previous fall history and deficient vestibular integration. Multiple falls were predicted by a fall history, low activity levels, more medical conditions and deficient vestibular integration. Low bone mineral density, more medical conditions and fall history predicted fractures. The purpose of this study was to identify potentially modifiable health-related factors predicting falls and fractures, focussing on women over 40. Four hundred and forty-nine women aged 40-80 years from the Longitudinal Assessment of Women study participated. Demographic information (age, BMI, medications, medical conditions and activity level), balance assessments (including timed up & go and modified clinical test for sensory interaction of balance) and measurements of bone mineral density and body composition were collected in 2001; fall and fracture data were gathered in 2003, 2005, 2007, 2008 and 2010 to determine incidence. Multinomial logistic regression revealed that single falls could be predicted by a history of previous falls (OR 3.08) and being unsteady in bipedal stance on foam with eyes closed (OR 1.99). Multiple falls were predicted by a history of falls at baseline (OR 4.69), low levels of activity (OR 2.17), greater number of medical conditions (OR 1.12) and being unsteady in bipedal stance on foam with eyes closed (OR 4.21). Low bone mineral density (OR 3.13), greater number of medical conditions (OR 1.32) and a history of falls (OR 3.04) were predictive of fractures. Poor health, decreased balance, and inactivity are predictive of falls and low bone mineral density, low activity level and poor health predictive fractures. Results suggest failing the balance test bipedal stance on foam with eyes closed in the presence of low activity and poor health is a valid quick screening tool for detecting potential fallers for referral for in-depth balance assessment and intervention.


Evaluation of the antiviral effect of new compounds by using cellular cultures.
Replication Kinetics of HIV was studied under single-growth cycle conditions in C8166 lymphoblastoid cells by back-titrating released and cell-associated infectious virus et each time point. Under these conditions HIV seemed to replicate faster than previously estimated. The amount cell-associated virus always exceeded that detectable in the medium. In these conditions the replication curve of HIV is completed at 24 h post infection. At lower multiplicity of infection, virus yield peaks at approximately 72 h post-infection, and the virus released in the medium is negligible with respect to that which remains cell-associated. The method based on back-titration of virus in cryolysates of C8166 cells infected with HIV and treated with antiviral compounds has been used to evaluate HIV sensitivity to some agents. This method allows a precise and quick determination of the degree of activity of antiviral drugs.


Archaeon Pyrococcus kodakaraensis KOD1: application and evolution.
Archaea is the third domain which is phylogenetically differentiated from the other two domains, bacteria and eucarya. Hyperthermophile within the archaea domain has evolved most slowly retaining many ancestral features of higher eukaryotes. Pyrococcus kodakaraensis KOD1, which grows at 95 degrees C optimally, is a newly isolated hyperthermophilc archaeon. The KOD1 strain possesses a circular genome, whose size is estimated to be approximately 2,036 kb. KOD1 enzymes involved in the genetic information processing system, such as DNA polymerase, Rec protein, aspartyl tRNA synthetase and molecular chaperonin, share features of eukaryotic enzymes. Rapid and accurate PCR method by KOD1 DNA polymerase and enzyme stabilization system by KOD1 chaperonin are also introduced in this article.


Cognitive processes of apathy in Huntington's disease show high sensitivity to disease progression.
Disease-modifying treatments for Huntington's disease (HD) are entering clinical trials: there is a pressing need for objective outcome measures of disease progression. Our previous work showed an association between 2 novel, objective cognitive tasks and apathy - a core feature of disease progression in HD. Evaluate the longitudinal validity and sensitivity of the novel Persistence and Maze tasks to assess their utility as clinical outcome measures in HD. 83 participants positive for the HD gene and 54 controls performed a battery of established and novel tools, at baseline and 12 month follow up. The Maze task was found to be the most sensitive measure of change at 12 months, including the current gold-standard measure (the composite disease progression score). The Maze task has potential as a novel outcome measure of disease progression in HD and may have utility in other major neurodegenerative diseases.


Increase in ibotenate-stimulated phosphatidylinositol hydrolysis in slices of the amygdala/pyriform cortex and hippocampus of rat by amygdala kindling.
Hydrolysis of membrane phospholipid phosphoinositides following ibotenate stimulation of an excitatory amino acid receptor subtype has recently been demonstrated to be a receptor-mediated biochemical response. The present study examined ibotenate-stimulated phosphoinositides hydrolysis, determined as accumulation of [3H]inositol 1-phosphate, in amygdala/pyriform cortical and hippocampal slices of amygdala-kindled rats which exhibited fully developed kindled seizures on 20 consecutive days. Animals which underwent a sham operation were used as controls. Ibotenate (10(-3) M)-stimulated accumulation of [3H]inositol 1-phosphate increased significantly by 191% in the amygdala/pyriform cortex (P less than 0.01) and by 59% in the hippocampus (P less than 0.05) of the amygdala-kindled rats killed 24 h after the last seizure. One week after the last seizure, a similar magnitude of significant increase (by 171%, P less than 0.05) was maintained in the amygdala/pyriform cortex of the amygdala-kindled rats. In contrast, the increase in the hippocampus had attenuated by this time, although accumulation of [3H]inositol 1-phosphate increased significantly (P less than 0.05) when stimulated by 10(-4) M ibotenate. These results suggest that enhancement of ibotenate-stimulated phosphoinositides hydrolysis in the amygdala/pyriform cortex may be associated with the long-lasting seizure susceptibility of amygdala-kindled rats.


Enzyme-aided alkaline extraction of oligosaccharides and polymeric xylan from hardwood kraft pulp.
In this paper we describe the effect of enzyme treatments on the production of polymeric xylan, oligosaccharides and hemicellulose lean pulp by alkaline extraction of bleached hardwood kraft pulp. Enzyme treatments were carried out before one or in between two subsequent alkaline extractions by purified Trichoderma reesei xylanase and endoglucanase II (Cel 5a) as well as by a commercial monocomponent endoglucanase (FibreCareR). Without enzyme pre-treatment 61% and 7% of the pulp xylan was extracted in high purity in the first and second alkaline stage, respectively. Higher molecular mass xylan was obtained in the second than in the first alkaline extraction. Xylanase treatment before alkaline extraction hydrolyzed up to 12% of xylan to xylooligosaccharides. According to our results, preparation of polymeric xylan, and/or oligosaccharides as well as hemicellulose lean pulp with cellulose content of 93-94%, is possible by enzyme-aided alkaline extraction process.


Ion-neutral reactions in the ion source of a mixture of CO2/CH3OH, CO2/C2H5OH, and CO2/2-C3H7OH by packed capillary supercritical fluid chromatography-mass spectrometry (SFC-MS).
Ion neutral reactions in the gas phase in mixtures of ROH/CO(2), R = CH(3), C(2)H(5), and 2-C(3)H(7) were studied by supercritical fluid chromatography-mass spectrometry (SFC-MS). Three main reaction series were found for this system; ionization followed by alpha-cleavage, formation of clusters, and formation of protonated dialkyl ethers from the corresponding alcohol. The ion chemistries were similar for the three alcohols, but that of 2-propanol was somewhat more complex.


Large divalent cations and electrostatic potentials adjacent to membranes. Experimental results with hexamethonium.
A simple extension of the Gouy-Chapman theory predicts that the ability of a divalent cation to screen charges at a membrane-solution interface decreases significantly if the distance between the charges on the cation is comparable with the Debye length. We tested this prediction by investigating the effect of hexamethonium on the electrostatic potential adjacent to negatively charged phospholipid bilayer membranes. The distance between the two charges of an extended hexamethonium molecule is approximately 1 nm, which is the Debye length in the 0.1 M monovalent salt solutions used in these experiments. Six different experimental approaches were utilized. We measured the electrophoretic mobility of multilamellar vesicles to determine the zeta potential, the line width of the 31P nuclear magnetic resonance (NMR) signal from sonicated vesicles to calculate the change in potential at the phosphodiester moiety of the lipid, and the conductance of planar bilayer membranes exposed to either carriers (nonactin) or pore formers (gramicidin) to estimate the change in potential within the membrane. We also measured directly the effect of hexamethonium on the potential above a monolayer formed from negative lipids, and attempted to calculate the change in the surface potential of a bilayer membrane from capacitance measurements. With the exception of the capacitance calculations, each of the techniques gave comparable results: hexamethonium exerts a smaller effect on the potential than that predicted by the classic screening theory. The results are consistent with the predictions of the extended Gouy-Chapman theory and are relevant to the interpretation of physiological and pharmacological experiments that utilize hexamethonium and other large divalent cations.


Multiple-factor classification of a human-modified forest landscape in the Hsuehshan Mountain Range, Taiwan.
Human actions drive landscape heterogeneity, yet most ecosystem classifications omit the role of human influence. This study explores land use history to inform a classification of forestland of the Tayal Mrqwang indigenous people of Taiwan. Our objectives were to determine the extent to which human action drives landscape heterogeneity. We used interviews, field sampling, and multivariate analysis to relate vegetation patterns to environmental gradients and human modification across 76 sites. We identified eleven forest classes. In total, around 70 % of plots were at lower elevations and had a history of shifting cultivation, terrace farming, and settlement that resulted in alder, laurel, oak, pine, and bamboo stands. Higher elevation mixed conifer forests were least disturbed. Arboriculture and selective harvesting were drivers of other conspicuous forest patterns. The findings show that past land uses play a key role in shaping forests, which is important to consider when setting targets to guide forest management.


LRP1 Regulates Retinal Angiogenesis by Inhibiting PARP-1 Activity and Endothelial Cell Proliferation.
We recently demonstrated that low-density lipoprotein receptor-related protein 1 (LRP1) is required for cardiovascular development in zebrafish. However, what role LRP1 plays in angiogenesis remains to be determined. To better understand the role of LRP1 in endothelial cell function, we investigated how LRP1 regulates mouse retinal angiogenesis. Depletion of LRP1 in endothelial cells results in increased retinal neovascularization in a mouse model of oxygen-induced retinopathy. Specifically, retinas in mice lacking endothelial LRP1 have more branching points and angiogenic sprouts at the leading edge of the newly formed vasculature. Increased endothelial proliferation as detected by Ki67 staining was observed in LRP1-deleted retinal endothelium in response to hypoxia. Using an array of biochemical and cell biology approaches, we demonstrate that poly(ADP-ribose) polymerase-1 (PARP-1) directly interacts with LRP1 in human retinal microvascular endothelial cells. This interaction between LRP1 and PARP-1 decreases under hypoxic condition. Moreover, LRP1 knockdown results in increased PARP-1 activity and subsequent phosphorylation of both retinoblastoma protein and cyclin-dependent kinase 2, which function to promote cell cycle progression and angiogenesis. Together, these data reveal a pivotal role for LRP1 in endothelial cell proliferation and retinal neovascularization induced by hypoxia. In addition, we demonstrate for the first time the interaction between LRP1 and PARP-1 and the LRP1-dependent regulation of PARP-1-signaling pathways. These data bring forth the possibility of novel therapeutic approaches for pathological angiogenesis.


Participatory antimicrobial stewardship: fostering patient and public engagement to counter antimicrobial resistance.
International governments defined antimicrobial stewardship (AS) as an essential ally against antimicrobial resistance (AMR). Patient and public engagement (PPE) in AS was pointed out as an imperative requirement to be embraced. We discuss PPE state of the art in AS and methodological reflections on how to achieve its effective implementation.


Mood, Th-1/Th-2 cytokine profile, and autonomic activity in older adults with acute/decompensated heart failure: preliminary observations.
In order to assess the relationships among mood, peripheral autonomic output and circulating immunoinflammatory mediators in older individuals with decompensated heart failure (CHF), 20 consecutive patients (78+/-7 years, 35% women) admitted to the coronary care unit with a clinical diagnosis of acute/decompensated CHF of coronary origin were examined. Mood was evaluated by the 21-item Hamilton Depression Scale (HAM-D). Four patients met the criteria for major depression. Heart rate variability (HRV) analysis and the levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-6 and IL-10 were measured within 24-72 h of admission. A significant positive relationship between score in HAM-D and serum IL-6 levels was detected with a similar trend as far as IL-2 levels. Circulating IL-2 levels were strongly associated with the HRV L/H quotient, an index of increased sympathetic and/or decreased parasympathetic thoracic activity. A negative correlation between vagal activity (as assessed by HRV) and IL-4 occurred. Neither TNF-alpha nor IL-10 were detectable in this group of elderly patients. The results add to the concept that mood and autonomic unbalance are associated with increased systemic inflammation in old patients with decompensated CHF, a potential mechanism for mood-related worsened prognosis of heart failure at an advanced age.


Coexistence in a fluctuating environment by the effect of relative nonlinearity: a minimal model.
The minimal model of the "relative nonlinearity" type fluctuation-maintained coexistence is investigated. The competing populations are affected by an environmental white noise. With quadratic density dependence, the long-term growth rates of the populations are determined by the average and the variance of the (fluctuating) total density. At most two species can coexist on these two "regulating" variables; competitive exclusion would ensue in a constant environment. A numerical study of the expected time until extinction of any of the two species reveals that the criterion of mutual invasibility predicts the parameter range of long-term coexistence correctly in the limit of zero extinction threshold. However, any extinction threshold consistent with a realistic population size will allow only short-term coexistence. Therefore, our simulations question the biological relevance of mutual invasibility, as a sufficient condition of coexistence, for large density fluctuations. We calculate the average and the variance of the fluctuating density of the coexisting populations analytically via the moment-closure approximation; the results are reasonably close to the simulated behavior. Based on this treatment, robustness of coexistence is studied in the limit of infinite population size. We interpret the results of this analysis in the context of necessity of niche segregation with respect to the regulating variables using a framework theory published earlier.


Long COVID and psychological distress in young adults: Potential protective effect of a prior mental health diagnosis.
Although young adulthood is a period characterized by marked psychological vulnerability, young adults are typically considered to be in good physical health and are therefore understudied with respect to the effects of COVID-19 infection and long COVID. The present study examined associations between post-acute sequelae of COVID-19 (PASC) and serious psychological distress during young adulthood, and tested whether prior mental health diagnosis moderated this association. Participants were 44,652 young adults who completed the Spring 2022 administration of the American College Health Association-National College Health Assessment III (ACHA-NCHA). Blockwise logistic regressions tested the odds of meeting the clinical threshold for serious psychological distress. PASC was associated with 53 % increased likelihood of meeting the clinical threshold for serious psychological distress. Among young adults with a prior mental health diagnosis, PASC predicted 36 % increased odds of serious psychological distress; among those without a diagnosis, PASC predicted 81 % increased odds. PASC was assessed using a single self-report item rather than a clinical diagnosis of specific symptomatology. The analyses were cross-sectional and relied on concurrent reports of PASC and psychological distress which precluded us from making claims regarding directionality of the associations. The outcome of generalized psychological distress limited us from generating targeted treatment recommendations. PASC may confer elevated psychological distress among young adults. The association of PASC to serious psychological distress was stronger in young adults without a mental health diagnosis than those with a diagnosis. Prior experience with mental illness may mitigate the psychological burden of long-term symptomatology.


Sources of energy for the brain and susceptibility to audiogenic seizures.
The onset of susceptibility to audiogenic seizures (AGS) coincides with the draining of the ear canal at about 14 to 16 days of age. This is also when the mouse brain has almost attained its maximal size and weight, and also about the time of weaning from the dam's high-fat milk to the beginning of dietary self-sufficiency. During suckling, the brain is primarily dependent on ketone-body utilization as a source for brain energy; weaned mice use glucose. It is suggested that in AGS-prone mice, there may be a developmental lag in the onset of a sufficient rate of glycolysis in brain to provide adequate immediately available energy reserves to last through a brief period of an external-stimulus-induced large energy expediture until energy repletion processes can begin. As a results, ATP levels might fall below an hypothesized lower limit to subserve organized neural activity in some inhibitory area of the brain, resulting in the onset of an AGS.


What Role Expectations Do Primary Care Physicians in Japan Hold for Physical Therapists Regarding Primary Care?
This study aimed to clarify what primary care physicians (PCPs) in Japan understand of the role of physical therapists (PTs) through the experience of working with PTs in hospitals, and what roles PCPs expect for PTs in future primary care. Semi-structured interviews were conducted individually with 9 purposively sampled PCPs with sufficient experience of collaboration with PTs. Interview data were analyzed by theme analysis focusing on "What does the PCP understand about the role of PTs through the experience of working with PTs in hospitals?" and "What roles and purposes does the PCP wish for PTs in primary care settings?" PCPs viewed PTs as providers of rehabilitation in the traditional medical model, and understood their role as an occupation having a mono-causal viewpoint, namely a specific and well-defined outcome for individual patients, and intervening with patients within a short clinical course with the aim of improvement or maintenance of the patient's condition. With regard to future primary care, PCPs expected that PTs would interpret various factors related to patient lives from the viewpoint of causal interactions; become important stakeholders in the community; and respond flexibly to patients and the environmental factors around them with continued support to the individual. PCPs understood the role of PTs in hospitals as "Rehabilitation in the traditional medical model," and expected the future role of PTs in primary care as "Rehabilitation in integrated community care."


All-cause mortality attributable to sitting time and physical inactivity in chilean adults.
Evidence on all-cause mortality attributable to joint sitting time and physical inactivity is lacking. In this study, we estimated the proportion and number of deaths attributable to sitting time and physical inactivity in Chilean adults. A sample of 5834 adults aged 20-96 years from a 2016-2017 Chilean National Health Survey was included to describe the prevalence of 16 joint categories of sitting time and physical activity. Relative risks for the joint association of sitting time and physical inactivity were obtained from a meta-analysis of individual participant data. We retrieved the number of deaths in adults ≥ 20 years in 2019 from the Chilean Ministry of Health. Participants with high sitting time (> 8 h/day) and low physical activity (< 2.5 MET-hour/week) were more likely to be women, 20-64 years, non-indigenous ethnicity, lived in the urban areas, had middle education level and monthly household income, and had public health insurance. Reducing sitting time and increasing physical activity to a theoretical minimum risk exposure level could prevent up to 11,470 deaths or 10.4% of all deaths. Increasing physical activity to >35.5 MET-hour/week and maintaining sitting time could prevent approximately 10,477 deaths or 9.5% of all deaths. Reducing sitting time to < 4 h/day and maintaining physical activity would not reduce the number of deaths (-3.4% or 38 deaths). Reducing sitting time may be ancillary for preventing mortality. Therefore, increasing physical activity should be the primary focus of interventions and policies in Chile.


Hemimegalencephaly: signal changes suggesting abnormal myelination on MRI.
We reviewed the MRI of 17 patients with hemimegalencephaly to investigate abnormal myelination in this condition. On images of seven patients aged 18 months or less, the white matter on the affected side suggested advanced myelination for the age. On T1-weighted images of three patients aged 1 month, the anterior limb of the internal capsule in the affected hemisphere was myelinated, and T1 shortening was not clearly seen in the pre- and postcentral gyri. The cortical grey matter and subcortical white matter was isointense in two patients. Images of two patients aged 4 to 5 months and of five patients aged 8-18 months showed myelination that extended more peripherally in the white matter of the affected hemisphere.


Impact of intensive physical activity on selenium status.
Various biomarkers were used to assess selenium (Se) status during 3 months of basic military training in a group of recruits. Samples of whole blood and plasma or serum were taken from a group of conscripts three times: at the beginning (n = 15), in the middle immediately after a severely stressful physical activity (n = 15) and at the end of military training (n = 13). Selenium was determined in diet samples, blood, plasma and plasma protein fractions as selenoprotein P (SelP) and glutathione peroxidase (eGPx). Selenium was determined by hydride generation-atomic fluorescence spectrometry and fractionation of proteins performed by affinity chromatography. Total serum glutathione, erythrocyte and serum GPx activity were followed as well. The average Se intake was calculated according to meal consumption questionnaires and Se determined in composite diet samples, giving an assessed intake of 48 ± 10 μg/day. At all three samplings, the average blood Se concentration was within the framework of adequate supply (87 ± 12, 94 ± 15 and 80 ± 13 ng/g). Plasma Se was between 70 and 80 ng/g (71 ± 10, 79 ± 9 and 76 ± 10 ng/g), which is believed to enable the full expression of plasma GPx. The average shares of plasma Se proteins were 61 ± 6%, 58 ± 6% and 54 ± 9% for SelP and 27 ± 4%, 34 ± 7% and 29 ± 5% for GPx. Although the observed tendency of the increases of serum and erythrocyte GPx activities at the second and third samplings with respect to the first was statistically insignificant, it is still indicative of some protection against oxidative stress, while the decreasing SelP levels during training suggest a slowly decreasing biologically active selenium pool.


Hair cortisol: A new tool for evaluating stress in programs of stress management.
Longitudinal and experimental studies have shown that chronic stress contributes to the onset and progression of different diseases. Although it is not possible to eliminate stress completely, people can learn to manage it by participating in different kinds of stress management interventions. This study examined the effectiveness of stress management interventions on neuroendocrine responses in stressed students and health professionals, by measuring hair cortisol in comparison to salivary cortisol. Salivary and hair cortisol measurements were performed in 37 subjects (31women, 6 men; mean age 34.0±10.6) who attended to a Coping Stress and Quality of Care Program at the University of Buenos Aires. Cortisol was measured at the beginning and at the end of the program. The State-Trait Anxiety Inventory STAI was used to evaluate state and trait anxiety. In subjects who completed the program, no differences were observed in salivary cortisol levels between the first and the last session. However, in these subjects, hair cortisol obtained in the last session was significantly lower than hair cortisol in the first session. Hair cortisol appears to be a better biomarker than salivary cortisol for evaluation of the effectiveness of a stress reduction program and it seems to be a better indicator of stress system dysregulation as well.


Acceleration of Drosophila melanogaster acetylcholinesterase methanesulfonylation: peripheral ligand D-tubocurarine enhances the affinity for small methanesulfonylfluoride.
D-Tubocurarine, a reversible peripheral inhibitor of cholinesterases accelerates methanesulfonylation of Drosophila melanogaster wild type and W359L mutant. The kinetic evaluation of the process was performed in a step-by-step analysis. The second order overall sulfonylation rate constants, determined from classical residual activity measurements, were used in the subsequent analysis of progress curves. The latter were obtained by measuring the hydrolysis of acetylthiocholine in a complex reaction system of enzyme, substrate, irreversible and reversible inhibitor. The underlying kinetic mechanisms, from such a complex data, could only be untangled by targeted inspection and successive incorporation of reaction steps for which experimental evidence existed. The study showed that the peripheral ligand D-tubocurarine, by binding at the entrance into the active site of the two investigated enzymes (Golicnik et al., Biochemistry 40 (2001) 1214), enhances the affinity for small methanesulfonylfluoride, rather to speeding up the formation of a stable covalent enzyme-inhibitor complex. The specific arrangements at the rim of the active site of each individual enzyme dictate the actual events which can be detected by kinetic means.


[Prevalence of urinary incontinence in pregnant women with prenatal care at the National Institute of Perinatology Isidro Espinosa de los Reyes].
Urinary incontinence during pregnancy is relatively frequent and is seen in some cases as a normal event. Several authors estimate a prevalence of urinary incontinence during pregnancy of 58.1%. To determine the prevalence of urinary incontinence in women at the National Institute of Perinatology Isidro Espinosa de los Reyes from March to May 2008. We also assessed the type, severity and frequency of involuntary loss of urine. longitudinal study to determine the prevalence of urinary incontinence before and during pregnancy, by quarter, type, frequency and severity. The prevalence of urinary incontinence during pregnancy was 58.2% and before pregnancy was 34.7%. The odds ratio for the association of multiparity and incontinence before pregnancy was 1.7 (95% CI 1.2-2.5) and 2.0 (95% CI 1.4-2.9) to manifest during pregnancy. Patients under 26 years have an odds ratio for urinary incontinence of 0.67 (95% CI 0.4-0.9). The prevalence of urinary incontinence increases during pregnancy, multiparity is a risk factor for urinary incontinence and age under 26 is a protective factor.


Immunoglobulins G from patients with ANCA-associated vasculitis are atypically glycosylated in both the Fc and Fab regions and the relation to disease activity.
Anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against myeloperoxidase (MPO) and proteinase 3 (PR3) are pathogenic in ANCA-associated vasculitis (AAV). The respective role of IgG Fc and Fab glycosylation in mediating ANCA pathogenicity is incompletely understood. Herein we investigate in detail the changes in Fc and Fab glycosylation in MPO-ANCA and Pr3-ANCA and examine the association of glycosylation aberrancies with disease activity. Total IgG was isolated from serum or plasma of a cohort of 30 patients with AAV (14 MPO-ANCA; 16 PR3-ANCA), and 19 healthy control subjects. Anti-MPO specific IgG was affinity-purified from plasma of an additional cohort of 18 MPO-ANCA patients undergoing plasmapheresis. We used lectin binding assays, liquid chromatography, and mass spectrometry-based methods to analyze Fc and Fab glycosylation, the degree of sialylation of Fc and Fab fragments and to determine the exact localization of N-glycans on Fc and Fab fragments. IgG1 Fc glycosylation of total IgG was significantly reduced in patients with active AAV compared to controls. Clinical remission was associated with complete glycan normalization for PR3-ANCA patients but not for MPO-ANCA patients. Fc-glycosylation of anti-MPO specific IgG was similar to total IgG purified from plasma. A major fraction of anti-MPO specific IgG harbor extensive glycosylation within the variable domain on the Fab portion. Significant differences exist between MPO and PR3-ANCA regarding the changes in amounts and types of glycans on Fc fragment and the association with disease activity. These differences may contribute to significant clinical difference in the disease course observed between the two diseases.


Traumatic rupture of the aorta and paraplegia.
During the past 10 years, 15 traumatic ruptures of the aorta isthmus have been diagnosed. The most likely mechanism is that of a brutal deceleration. Three patients developed a complete mid-thoracic flaccid paraplegia. One died in a few hours of a complete rupture, the second after a few days from renal insufficiency, the third 12 days after, having been operated upon on the same day of the accident. All had associated lesions. Diagnosis can be very difficult in these patients, especially in the first few hours. Paraplegia is here considered as an aggravation ischaemic symptom with anuria and loss of blood circulation in the lower limbs. In delayed cases the vascular mechanism of the infarction of the spinal cord is discussed, either by compression of the intercostal arteries or by direct compression of the aorta itself. In our cases, the most likely mechanism is that of an obstruction of the lumen of the aorta by a torn inner coat. These patients must be transferred as quickly as possible to a cardiovascular surgical unit and operated upon immediately. Three cases of preoperative, rapidly progressive paraplegia with neurological recovery after the operation, have been reported in the literature.


The contribution of the reflex hypoxic drive to the hyperpnoea of exercise.
Oxygen breath tests have been applied to six normal subjects at rest and during steady state exercise on a bicycle ergometer (200, 400 and 600 kpm) to estimate the contribution of the reflex hypoxic drive to total ventilation. The subjects were changed without their knowledge from air to 100% oxygen for 4--5 breaths, the fall in ventilation was recorded and expressed as a percentage of total ventilation (hypoxic drive). The average reflex hypoxic drive was 16.2% (SE +/- 2.6; n = 35) this remianed unaltered during all levels of steady state exercise. The maximum fall in ventilation occurred earlier in exercise (P less than 0.0005). At rest the maximum fall occurred on average 31.2 s (SE +/- 2.6) from the start of the first breath of oxygen. During the first level of steady state exercise the maximum fall occurred 19.4 s (SE +/- 0.5) from the start of the first breath of oxygen. It is concluded that the contribution of the reflex hypoxic drive to the total ventilation is unaltered by exercise although a substantial part of the hyperpnoea can be accounted for by the presence of this drive.


Subcutaneous nodules in rheumatic fever.
Acute rheumatic fever is described in a six year old Ethiopian male child who first presented with subcutaneous nodules and later developed carditis.


Caspase-specific and nonspecific in vivo protein processing during Fas-induced apoptosis.
We generated a comprehensive picture of protease substrates in anti-Fas-treated apoptotic human Jurkat T lymphocytes. We used combined fractional diagonal chromatography (COFRADIC) sorting of protein amino-terminal peptides coupled to oxygen-16 or oxygen-18 differential labeling. We identified protease substrates and located the exact cleavage sites within processed proteins. Our analysis yielded 1,834 protein identifications and located 93 cleavage sites in 71 proteins. Indirect evidence of apoptosis-specific cleavage within 21 additional proteins increased the total number of processed proteins to 92. Most cleavages were at caspase consensus sites; however, other cleavage specificities suggest activation of other proteases. We validated several new processing events by immunodetection and by an in vitro assay using recombinant caspases and synthetic peptides containing presumed cleavage sites. The spliceosome complex appeared a preferred target, as 14 of its members were processed. Differential isotopic labeling further revealed specific release of nucleosomal components from apoptotic nuclei.


Pharmacodynamic studies in normal volunteers with MDL-899, a new arteriolar vasodilator.
We conducted pharmacodynamic studies with a new vasodilator, MDL-899. Following initial dose-ranging studies we studied eight male normotensive volunteers, each of whom received, orally, 10 mg MDL-899 or placebo in double-blind random order. MDL-899 significantly lowered standing blood pressure, the maximal effect occurring 3-6 h following drug administration. There was a significant increase in heart rate in both supine and standing positions, maximal 6-8 h postdose. Supine plasma noradrenaline concentrations were greater following MDL-899, with the greatest difference present 4 h after drug administration. Plasma renin concentrations were greater following MDL-899. Six of our subjects were also given 10 mg MDL-899 together with 100 mg atenolol, in an additional study. Atenolol increased the hypotensive effect and attenuated the tachycardia following MDL-899 alone. Side effects following MDL-899 administration included headache, lightheadedness, and tachycardia. These were reduced following atenolol coadministration. The haemodynamic profile of MDL-899 suggests that this drug acts as a direct arteriolar vasodilator in man. The observed increase in heart rate is likely mediated by reflex activation of the sympathetic nervous system.


Incidence and severity of retinopathy in low birth weight infants monitored by TCPO2.
The incidence and severity of retinopathy of prematurity (ROP) were studied in 561 survivors of low birth weight infants (LBWIs) weighing under 2,000g. They were the survivors out of 604 LBWIs admitted to Okayama National Hospital during the five years from January 1981 to December 1985. The tcPO2 of all the LBWIs on the respirator or under oxygen administration was monitored using an Oxymonitor SM 361. The upper limit of tcPO2 was maintained between 50 to 80 torr. The ophthalmologic funduscopy was continued until 12 months of age. The early active stages of ROP were recorded by "the International Classification 1984". The cicatricial change of retina was classified by the criteria of the Joint Committee for the Study of Retrolental Fibroplasia in Japan. In the survivors, 55 cases of active ROP were found. (Stage 1:29 cases, 2:17, 3:9, and 4:0) In the survivors, 27 cases of cicatricial ROP were found, (Grade I:27 cases, II:0, III:0, IV:0) None of them developed blinding retinopathy. Neither the artificial ventilation nor the duration of oxygen administration influenced the incidence of ROP with statistical significance. The incidence and severity of ROP in this study seems to be one of the lowest among those hitherto published. Though our study is not a controlled one, it can be concluded that tcPO2 monitoring eliminates the blinding ROP.


Altering the swelling pressures within in vitro engineered cartilage is predicted to modulate the configuration of the collagen network and hence improve tissue mechanical properties.
Prestress in the collagen network has a significant impact on the material properties of cartilaginous tissues. It is closely related to the recruitment configuration of the collagen network which defines the transition from lax collagen fibres to uncrimped, load-bearing collagen fibres. This recruitment configuration can change in response to alterations in the external environmental conditions. In this study, the influence of changes in external salt concentration or sequential proteoglycan digestion on the configuration of the collagen network of tissue engineered cartilage is investigated using a previously developed computational model. Collagen synthesis and network assembly are assumed to occur in the tissue configuration present during in vitro culture. The model assumes that if this configuration is more compact due to changes in tissue swelling, the collagen network will adapt by lowering its recruitment stretch. When returned to normal physiological conditions, these tissues will then have a higher prestress in the collagen network. Based on these assumptions, the model demonstrates that proteoglycan digestion at discrete time points during culture as well as culture in a hypertonic medium can improve the functionality of tissue engineered cartilage, while culture in hypotonic solution is detrimental to the apparent mechanical properties of the graft.


Improving the assessment of RDE dynamics through vehicle-specific power analysis.
Vehicles are an important source of air pollutants and greenhouse gases. Their emissions have been controlled since the 1970s by laboratory tests but there are often found divergences to real-world emissions. Real driving emissions procedure is in implementation in many countries, for evaluating vehicles closer to actual operation. In order to reduce the dispersion of the results, some dynamic parameters, such as speed, acceleration, and CO2 emissions, are controlled; however, sometimes they are into the limits but divergences remain. This paper has the goal of applying VSP as an additional parameter for improving the evaluation of the vehicle dynamics, because it can better represent the engine power required for running as well as the road grade influence.


Stattic ameliorates the cecal ligation and puncture-induced cardiac injury in septic mice via IL-6-gp130-STAT3 signaling pathway.
Sepsis-induced cardiac dysfunction is the leading cause of higher morbidity and mortality with poor prognosis in septic patients. Our recent previous investigation provides evidence of the hallmarks of signal transducer and activator of transcription3 (STAT3) activation in sepsis and targeting of STAT3 with Stattic, a small-molecule inhibitor of STAT3, has beneficial effects in various septic tissues. We investigated the possible cardioprotective effects of Stattic on cardiac inflammation and dysfunction in mice with cecal ligation and puncture (CLP)-induced sepsis. A polymicrobial sepsis model was induced by CLP in mice and Stattic (25 mg/kg) was intraperitoneally given at one and twelve hours after CLP operation. The cecum was exposed in sham-control mice without CLP. After 18 h of surgery, electrocardiogram (ECG) for anaesthized mice was registered followed by collecting of samples of blood and tissues for bimolecular and histopathological assessments. Myeloperoxidase, a marker of neutrophil infiltration, was assessed immunohistochemically. CLP profoundly impaired cardiac functions as evidenced by ECG changes in septic mice as well as elevation of cardiac enzymes, and inflammatory markers with myocardial histopathological and immunohistochemical alterations. While, Stattic markedly reversed the CLP-induced cardiac abnormalities and restored the cardiac function by its anti-inflammatory activities. Stattic treatment had potential beneficial effects against sepsis-induced cardiac inflammation, dysfunction and damage. Its cardioprotective effects were possibly attributed to its anti-inflammatory activities by targeting STAT3 and downregulation of IL-6 and gp130. Our investigations suggest that Stattic could be a promising target for management of cardiac sepsis and inflammation-related cardiac damage.


Use of therapeutic ultrasound to restore failed trabeculectomies.
We treated 20 recently postoperative eyes with nonfunctioning trabeculectomies at the site of the failed bleb with two to four ultrasound applications, each of five seconds duration, at an intensity level of 10 kW/cm2. Fifteen of the eyes demonstrated a long-term decrease in intraocular pressure to 21 mm Hg or below. The mean intraocular pressure of all patients fell from a preultrasound mean (+/- S.D.) of 32 +/- 8 mm Hg to 20 +/- 10 mm Hg at a mean time of 236 +/- 204 days postultrasound. Complications included an immediate postultrasound rise in pressure over 10 mm Hg in 13 eyes, and the immediate development of a cataract in one patient.


European Resuscitation Council and European Society of Intensive Care Medicine 2015 guidelines for post-resuscitation care.
The European Resuscitation Council and the European Society of Intensive Care Medicine have collaborated to produce these post-resuscitation care guidelines, which are based on the 2015 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. Recent changes in post-resuscitation care include: (a) greater emphasis on the need for urgent coronary catheterisation and percutaneous coronary intervention following out-of-hospital cardiac arrest of likely cardiac cause; (b) targeted temperature management remains important but there is now an option to target a temperature of 36 °C instead of the previously recommended 32-34 °C; (c) prognostication is now undertaken using a multimodal strategy and there is emphasis on allowing sufficient time for neurological recovery and to enable sedatives to be cleared; (d) increased emphasis on rehabilitation after survival from a cardiac arrest.


Insights into mustard gas keratopathy: Characterizing corneal layer-specific changes in mice exposed to nitrogen mustard.
Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various corneal disorders that are collectively referred to as mustard gas keratopathy (MGK). In this study, we aimed to develop a mouse model of MGK by using ocular NM exposure, and describe the subsequent structural changes analyzed across the different layers of the cornea. A 3 μL solution of 0.25 mg/mL NM was applied to the center of the cornea via a 2-mm filter paper for 5 min. Mice were evaluated prior to and after exposure on days 1 and 3, and weekly for 4 weeks using slit lamp examination with fluorescein staining. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) tracked changes in the epithelium, stroma, and endothelium of the cornea. Histologic evaluation and immunostaining were used to examine corneal cross-sections collected at the completion of follow-up. A biphasic ocular injury was observed in mice exposed to NM, most prominent in the corneal epithelium and anterior stroma. Following exposure, mice experienced central corneal epithelial erosions and thinning, accompanied by a decreased number of nerve branches in the subbasal plexus and increased activated keratocytes in the stroma. The epithelium was recovered by day 3, followed by exacerbated punctuate erosions alongside persistent stromal edema that arose and continued onward to four weeks post-exposure. The endothelial cell density was reduced on the first day after NM exposure, which persisted until the end of follow-up, along with increased polymegethism and pleomorphism. Microstructural changes in the central cornea at this time included dysmorphic basal epithelial cells, and in the limbal cornea included decreased cellular layers and p63+ area, along with increased DNA oxidization. We present a mouse model of MGK using NM that successfully replicates ocular injury caused by SM in humans who have been exposed to mustard gas. Our research suggests DNA oxidation contributes to the long-term effects of nitrogen mustard on limbal stem cells.


Neuroglobin is an endogenous neuroprotectant for retinal ganglion cells against glaucomatous damage.
Neuroglobin (NGB), a newly discovered member of the globin superfamily, may regulate neuronal survival under hypoxia or oxidative stress. Although NGB is greatly expressed in retinal neurons, the biological functions of NGB in retinal diseases remain largely unknown. We investigated the role of NGB in an experimental model of glaucoma, a neurodegenerative disorder that usually involves elevation of intraocular pressure (IOP). Elevated IOP is thought to induce oxidative stress in retinal ganglion cells (RGCs), thereby causing RGC death and, eventually, blindness. We found that NGB plays a critical role in increasing RGC resistance to ocular hypertension and glaucomatous damage. Elevation of IOP stimulated a transient up-regulation of endogenous NGB in RGCs. Constitutive overexpression of NGB in transgenic mice prevented RGC damage induced by glutamate cytotoxicity in vitro and/or by chronic IOP elevation in vivo. Moreover, overexpression of NGB attenuated ocular hypertension-induced superoxide production and the associated decrease in ATP levels in mice, suggesting that NGB acts as an endogenous neuroprotectant to reduce oxidative stress and improve mitochondrial function, thereby promoting RGC survival. Thus, NGB may modulate RGC susceptibility to glaucomatous neural damage. Manipulating the expression and bioactivity of NGB may represent a novel therapeutic strategy for glaucoma.


Quantitative characterizations of the cholesterol-related pathways in the retina and brain of hamsters.
The retina and brain are separated from the systemic circulation by the anatomical barriers, which are permeable (the outer blood-retinal barrier) and impermeable (the blood-brain and inner blood-retina barriers) to cholesterol. Herein we investigated whether whole-body cholesterol maintenance affects cholesterol homeostasis in the retina and brain. We used hamsters, whose whole-body cholesterol handling is more similar to those in humans than in mice, and conducted separate administrations of deuterated water and deuterated cholesterol. We assessed the quantitative significance of the retinal and brain pathways of cholesterol input and compared the results with those from our previous studies in mice. The utility of the measurements in the plasma of deuterated 24-hydroxycholesterol, the major cholesterol elimination product from the brain, was investigated as well. We established that despite a sevenfold higher serum LDL to HDL ratio and other cholesterol-related differences, in situ biosynthesis remained the major source of cholesterol for hamster retina, although its quantitative significance was reduced to 53% as compared to 72%-78% in the mouse retina. In the brain, the principal pathway of cholesterol input was also the same, in situ biosynthesis, accounting for 94% of the total brain cholesterol input (96% in mice); the interspecies differences pertained to the absolute rates of the total cholesterol input and turnover. We documented the correlations between deuterium enrichments of the brain 24-hydroxycholesterol, brain cholesterol, and plasma 24-hydroxycholesterol, which suggested that deuterium enrichment of plasma 24-hydroxycholesteol could be an in vivo marker of cholesterol elimination and turnover in the brain.


Vaccine hesitancy communication: What counts as evidence.
The evidence base for vaccine hesitancy communication is generally confined to research focused on the content of the message rather than the process of communication. This has important consequences, because shifting focus to encompass the process of communicating, and not just on the content of content message being conveyed; opens the possibility of greater insight and understanding regarding the conversation health care workers have with those who are vaccine hesitant, creating increased chances of acceptance.


Intra-tendinous gout in a repaired flexor digitorum profundus.
A patient presented with decreased flexion and triggering following a zone IIc flexor digitorum profundus repair 7 years previously. Chalky-white deposits, confirmed histologically as gout, were present at the repair site.


Retreatment with argon laser trabeculoplasty.
Forty eyes in 37 patients that had previously successful 360 degrees argon laser trabeculoplasty were again found to have uncontrolled intraocular pressure (IOP) on maximally tolerated medical therapy and were retreated with argon laser trabeculoplasty to 180 degrees of the trabecular circumference. Successful retreatment was considered a decrease in IOP of 3 mmHg or more and sufficient to avoid further laser therapy or invasive glaucoma surgery. Laser trabeculoplasty retreatment was successful in 13 of the eyes treated (32%). Retreatment failed to control IOP in 27 of the retreated eyes (68%): either the IOP was not lowered by at least 3 mmHg (4 eyes) or the eyes required further laser therapy or surgery (23 eyes). The probability of successful IOP control 1 year after retreatment was 33% and only 14% after 1.75 years. No IOP elevations greater than 6 mmHg were recognized in the postlaser period. Although retreatment with argon laser trabeculoplasty can safely be used to control the IOP in some glaucomatous eyes, the likelihood of success is low.


High-dose gallium imaging in lymphoma.
The role of gallium-67 imaging in the management of patients with lymphoma, traditionally assessed using low tracer doses and the rectilinear scanner, was assessed when using larger doses (7 to 10 mCi) and a triple-peak Anger camera. Gallium scan results in 51 patients with non-Hodgkin's lymphoma and 21 patients with Hodgkin's disease were compared with simultaneous radiologic, clinical, and histopathologic reports. Subsequent disease course was also evaluated in light of radionuclide findings. Sensitivity and specificity of the scans were 0.90 or greater for both non-Hodgkin's lymphoma and Hodgkin's disease, and overall accuracy by site was 96 percent. Although there are insufficient numbers of pretreatment scans to allow any conclusions, our data suggest that newer approaches to gallium scanning in treated patients are (1) highly specific in all lymphomas and most sensitive in high-grade non-Hodgkin's lymphoma and Hodgkin's disease; (2) valuable in assessing the mediastinum in both non-Hodgkin's lymphoma and Hodgkin's disease; and (3) helpful adjuncts to computed tomographic scanning and ultrasonography in assessing abdominal node disease.


[Maternal-fetal transmission of HIV: preventive measures and prenatal care].
HIV can be transmitted to foetus during pregnancy, labour, and breastfeeding. An estimated 600,000 newborns acquired HIV each year through mother to fetus transmission. Without preventive interventions, approximately 25% of infants born to HIV positive mothers contract the virus. Elective delivery by caesarean section at 38th weeks, before labor and rupture of membrane, decreased the fetal risk. Anniotomy and long-standing rupture of the membranes should be avoided, as should breastfeeding. As well based on the review of literature the authors provide an overview of vertically acquired of HIV infection, preventive measures and perinatal car are discussed.


Reconstructing avian mercury concentrations through time using museum specimens from New York State.
We examined how variation in MeHg concentrations through time is reflected in birds, a taxon commonly used as a biological indicator of ecosystem health. Using museum specimens collected from 1880 to 2016, we measured feather MeHg concentrations in six species of birds that breed in New York State and have distinct dietary and habitat preferences. We predicted that MeHg concentrations in feathers would mirror Hg emission patterns in New York State and increase through time until 1980 then decrease thereafter in response to increased regulation of anthropogenic Hg emissions. We found that MeHg concentrations increased with δ15N, and that MeHg feather concentrations for some individuals from four of the six species examined exceeded concentrations known to cause negative sublethal effects in birds. In contrast to our prediction, MeHg concentrations in feathers did not parallel global or local Hg emissions through time and varied by species, even after controlling for possible changes in diet and habitat. MeHg concentrations varied substantially within species and individual specimens, suggesting that high within-individual variation in feather MeHg concentrations caused by spatiotemporal variation in molt, environmental Hg exposure, or mobility decoupling Hg uptake from breeding sites, may obscure trends in MeHg through time. Our study provides a unique assessment of feather MeHg in six species not typically analyzed using this retrospective approach.


LPS-induced inflammation potentiates the IL-1β-mediated reduction of LH secretion from the anterior pituitary explants.
Acting at the level of the brain, interleukin- (IL-)1 β is considered to be one of the most potent downregulators of reproduction processes during immune/inflammatory challenge. IL-1 β suppresses gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus resulting in the inhibition of the luteinizing hormone (LH) release from the anterior pituitary (AP). However, the presence of IL-1 β receptors in the AP suggests the possible direct action of this cytokine on LH secretion. The study was designed to determine the effect of IL-1 β on the LH secretion from the AP explants collected from saline and LPS-treated ewes in the follicular phase. It was found that IL-1 β suppressed (P ≤ 0.01) GnRH-stimulated LH release and LH β gene expression in AP explants in both groups. However, IL-1 β action was more potent in the explants collected from LPS-treated animals. Pituitaries from LPS-treated animals were characterized by increased (P ≤ 0.01) IL-1 type I receptor and decreased (P ≤ 0.01) GnRH receptor gene expression level compared to the saline-treated group. IL-1 β also affected the GnRH-R gene expression in explants collected from LPS-treated animals. Our results show that direct action of IL-1 β on the pituitary gonadotropes could be one of the reasons of the reproductive processes disorders accompanying an inflammatory state.


Interference with the function of leukocyte adhesion molecules by monoclonal antibodies: a new approach to burn injury.
Monoclonal antibody to intercellular adherence molecule-1 (ICAM-1) was used to inhibit leukocyte adherence in two models of burn injury. The antibodies to ICAM-1 had significant effects in preserving microvascular blood flow in burn wounds, and in modulating the systemic response to major burn injury. These results suggest a central role for leukocytes in the pathophysiologic response to burn injury.


[Experimental study of therapy effects of anti -VEGF antibody on osteosarcoma].
To investigate the effect of anti-VEGF antibody on angiogenesis induced by osteosarcoma OS-732 cell line and tumor growth. With a tumor model on the chick embryo chorioallantoic membrane (CAM), the inhibition of angiogenesis and tumor growth by anti-VEGF antibody were observed under a stero-microscope and a light microscope. Furthermore, the proliferation and apoptosis in tumor cells and endothelial cells (EC) were studied by TdT-mediated duTP nick and labeling (TUNEL) and immunohistochemical staining using proliferating cell nuclear antigen (PCNA) monoclonal antibody. VEGF polyclonal antibody administration in tumor-bearing chick embryo resulted in growth arrest of xenografts and a markedly reduction in the new capillaries which converged upon the tumor. The tumor cell apoptotic index was higher in the anti-VEGF antibody treated group than the negative control group, but the proliferation index was not significantly different between them. At the same time, increased apoptosis and decreased proliferation in EC were also noted. VEGF polyclonal antibody is able to inhibit the angiogenesis induced by OS-732 obviously, probably by the mechanism of inhibition of EC proliferation and promotion of their apoptosis, furtherly, which may contribute to the apoptosis of tumor cells and result in suppression of tumor growth.


Foraging behavior as a determinant of asymmetric competitive interaction between two ant species in a tropical agroecosystem.
This work is concerned with elucidating competitive interactions between two neotropical ants, Solenopsis geminata and Pheidole radoszkowskii, focusing on their foraging behavior. When released from competition from P. radoszkowskii, S. geminata increased its foraging activity. On the other hand, when released from competition from S. geminata, P. radoszkowskii did not respond, demonstrating asymmetric competition between the two species. Foraging experiments showed that P. radoszkowskii is more efficient at finding food resources, whereas S. geminata is better at defending the resources once they are encountered. These differences in foraging behavior appear to permit the coexistence of these two species. The practical implications of the results for the management of ant communities in tropical agroecosystems is discussed with respect to the potential use of ants as natural enemies.


Prospective outcome assessment of occupational rhinitis after removal from exposure.
To conduct a prospective evaluation of clinical and quality of life (QOL) outcomes of occupational rhinitis (OR) after cessation of exposure. We assessed changes in nasal symptoms, disease-specific QOL, nasal patency, and nasal inflammation in 20 subjects with confirmed OR. Olfactory function was assessed cross-sectionally at follow-up. At follow-up, a significant decrease in the number of nasal symptoms and a significant improvement in QOL were observed. There were no significant differences in nasal patency outcomes. A not significant decrease in neutrophils number in nasal fluid and a significant decrease in macrophages were observed. As a group, study subjects showed a mild olfactory dysfunction at follow-up. We showed that cessation of exposure to causal agent improved QOL in patients with OR, leading to relief of rhinitis-associated symptoms and improvement in well-being.


Correlation of ultrasonic and endocrinologic assessment of human follicular development.
Human ovarian follicular development measured by peripheral plasma hormone levels and ovarian follicular growth assessed by ultrasonic visualization of the ovary were compared and contrasted in apparently normally menstruating women. The linear correlation coefficient between the mean values for plasma estradiol and follicular diameter on day -5 to day 0 of 15 normal cycles was r = 0.968. When the individual paired data were subjected to multiple linear regression analyses (on days -5 to 0), r = 0.771. These good correlations show that ultrasound measurements of follicular diameter are valuable in the assessment of follicular growth and development. Observations on apparently abnormal cycles are also discussed. Ultrasound measurement of follicular diameter offers an additional technique for the study of ovarian function.


The 18 O-signal transfer from water vapour to leaf water and assimilates varies among plant species and growth forms.
The 18 O signature of atmospheric water vapour (δ18 OV ) is known to be transferred via leaf water to assimilates. It remains, however, unclear how the 18 O-signal transfer differs among plant species and growth forms. We performed a 9-hr greenhouse fog experiment (relative humidity ≥ 98%) with 18 O-depleted water vapour (-106.7‰) on 140 plant species of eight different growth forms during daytime. We quantified the 18 O-signal transfer by calculating the mean residence time of O in leaf water (MRTLW ) and sugars (MRTSugars ) and related it to leaf traits and physiological drivers. MRTLW increased with leaf succulence and thickness, varying between 1.4 and 10.8 hr. MRTSugars was shorter in C3 and C4 plants than in crassulacean acid metabolism (CAM) plants and highly variable among species and growth forms; MRTSugars was shortest for grasses and aquatic plants, intermediate for broadleaf trees, shrubs, and herbs, and longest for conifers, epiphytes, and succulents. Sucrose was more sensitive to δ18 OV variations than other assimilates. Our comprehensive study shows that plant species and growth forms vary strongly in their sensitivity to δ18 OV variations, which is important for the interpretation of δ18 O values in plant organic material and compounds and thus for the reconstruction of climatic conditions and plant functional responses.


Volume targeted versus pressure support non-invasive ventilation in patients with super obesity and chronic respiratory failure: a randomised controlled trial.
Automatic titration modes of non-invasive ventilation, including average volume assured pressure support (AVAPS), are hybrid technologies that target a set volume by automated adjustment of pressure support (PS). These automated modes could offer potential advantages over fixed level PS, in particular, in patients who are super obese. Consecutive patients with obesity hypoventilation syndrome were enrolled in a two-centre prospective single-blind randomised controlled trial of AVAPS versus fixed-level PS using a strict protocolised setup. The primary outcome was change in daytime arterial PCO(2) (PaCO(2)) at 3 months. Body composition, physical activity (7-day actigraphy) and health-related quality of life (severe respiratory insufficiency questionnaire, SRI) were secondary outcome measures. 50 patients (body mass index 50±7 kg/m(2); 55±11 years; 53% men) were enrolled with a mean PaCO(2) of 6.9±0.8 kPa and SRI of 53±17. 46 patients (23 AVAPS and 23 PS) completed the trial. At 3 months, improvements in PaCO(2) were observed in both groups (AVAPS 0.6 kPa, 95% CI 0.2 to 1.1, p<0.01 vs PS 0.6 kPa, 95% CI 0.1 to 1.1, p=0.02) but no between-group difference (-0.1 kPa, 95% CI -0.7 to 0.6, p=0.87). SRI also improved in both groups (AVAPS 11, 95% CI 6 to 17, p<0.001 vs PS 7, 95% CI 1 to 12, p=0.02; between groups 5, 95% CI -3 to 12, p=0.21). Secondary analysis of both groups combined showed improvements in daytime physical activity that correlated with reduction in fat mass (r=0.48; p=0.01). The study demonstrated no differences between automated AVAPS mode and fixed-level PS mode using a strict protocolised setup in patients who were super obese. The data suggest that the management of sleep-disordered breathing may enhance daytime activity and promote weight loss in super-obese patients.


Inhibition of pyruvate oxidation in rat islets by alpha-cyano-4-hydroxycinnamate. Differential effects on insulin secretion and inositol lipid metabolism.
The oxidation of 14C-pyruvate by isolated rat pancreatic islets was inhibited competitively and in a concentration-dependent manner by alpha-cyano-4-hydroxycinnamate. A similar, though less marked inhibition was observed of U-14C-glucose oxidation, although oxidation of 1-14C-glucose was slightly enhanced in the presence of the drug. The rate of glycolysis, as estimated by the utilisation of 5-[3H]-glucose and levels of ATP in islets were unaffected by alpha-cyano-4-hydroxycinnamate. The inhibition of pyruvate oxidation by alpha-cyano-4-hydroxycinnamate was accompanied by an inhibition of insulin secretion in response to glucose, but not to a combination of Ba2+ and theophylline. In contrast, glucose-stimulated inositol lipid breakdown was not affected by the drug. Thus, mitochondrial oxidation of pyruvate appears to be a prerequisite for glucose-stimulated insulin secretion, but not enhanced inositol lipid metabolism.


Glaucoma detection using image processing techniques: A literature review.
The term glaucoma refers to a group of heterogeneous diseases that cause the degeneration of retinal ganglion cells (RGCs). The degeneration of RGCs leads to two main issues: (i) structural changes to the optic nerve head as well as the nerve fiber layer, and (ii) simultaneous functional failure of the visual field. These two effects of glaucoma may lead to peripheral vision loss and, if the condition is left to progress it may eventually lead to blindness. No cure for glaucoma exists apart from early detection and treatment by optometrists and ophthalmologists. The degeneration of RGCs is normally detected from retinal images which are assessed by an expert. These retinal images also provide other vital information about the health of an eye. Thus, it is essential to develop automated techniques for extracting this information. The rapid development of digital images and computer vision techniques have increased the potential for analysis of eye health from images. This paper surveys current approaches to detect glaucoma from 2D and 3D images; both the limitations and possible future directions are highlighted. This study also describes the datasets used for retinal analysis along with existing evaluation algorithms. The main topics covered by this study may be enumerated as follows.


First trimester uterine artery Doppler in women with previous pre-eclampsia.
To assess the role of first trimester uterine artery Doppler in pregnancies previously complicated by pre-eclampsia. Case-control study in two tertiary referral hospitals. A total of 56 singleton pregnancies in women with a previous pregnancy complicated by pre-eclampsia (Group 1). For each case, two parous controls (Group 2) and two nulliparous controls (Group 3) with normal pregnancy outcome were matched. Doppler examination of the uterine arteries at 11-14 weeks' gestation. Mean uterine artery resistance index (UtARI) and notching. Pregnancy outcome. UtARI did not vary significantly between the three groups (0.73, 0.70 and 0.71, respectively). Women in Group 1 had a significantly higher prevalence of uterine artery notching than those in Group 2 (73 vs 57%, p=0.04). In Group 1, the UtARI and prevalence of notching was not significantly increased when pregnancies were subsequently complicated by pre-eclampsia (p=0.60 and 0.61, respectively). However, in 12 pregnancies requiring delivery before 37 weeks due to pre-eclampsia, fetal growth restriction, abruption or intrauterine fetal death, the UtARI was significantly higher than in the 44 pregnancies with normal outcome (p=0.04). A combination of UtARI and notching showed sensitivities up to 75% and negative predictive values up to 88% for adverse outcome before 37 weeks. In pregnancies following a previous gestation complicated by pre-eclampsia, first trimester uterine artery Doppler findings are similar to those observed in nulliparous women. In these high-risk women, a combination of UtARI and notching can predict the risk of adverse outcome before 37 weeks.


Tissue carnitine concentrations after total parenteral nutrition with and without L-carnitine supplementation.
The concentrations (mumoles/g dry weight) of total carnitine (TC), free carnitine (FC) and acylcarnitine (AC) were determined in skeletal muscle, heart, liver, kidney and brain cortex of male mini pigs (4000-5000 g) after seven days of total parenteral nutrition (TPN) with amino acids 5% (3.0g/kg/d), glucose (25g/kg/d) and lipids 20% (4g/kg/d). This regime was administered with L-carnitine supplementation (1.5 mg/kg/d; n = 7) (group 1) and without it (n = 5) (group 2). Orally alimented animals (n = 5) served as controls (group 3). (Average carnitine intake: 3 mg/d) Carnitine free TPN affected only the concentrations in muscle. TC was markedly reduced (3.6 +/- 0.8) when compared with oral controls (5.8 +/- 0.7) (p<0.01). This decrease was exclusively due to AC, whereas FC concentrations remained almost unchanged. In group 1 the concentrations of TC in skeletal muscle, heart and brain cortex were higher than in both the other groups. The increase was mainly due to AC and FC remained unchanged in heart and brain. The concentrations in liver and kidney were not affected by either carnitine free or carnitine supplemented TPN. AC, determined as described, consists almost entirely of acid soluble acetyl-carnitine, the major product of fatty acid oxidation. Since the AC concentrations were almost exclusively altered by the two TPN-regimes we conclude that the observed changes reflect regulatory changes of fatty acid oxidation. Thus the decrease of muscle TC in group 2 is considered a consequence of an insulin induced down regulation (plasma insulin: mean 20 muU/ml; maximum: 60 muU/ml) of fatty acid oxidation in consequence of high glucose intake (25 g/kg/d). The increased TC concentrations after carnitine supplemented TPN are discussed to reflect an enhancement of oxidative degradation of fatty acids as a pharmacological effect of L-carnitine.


Systems pharmacology, proteomics and in vivo studies identification of mechanisms of cerebral ischemia injury amelioration by Huanglian Jiedu Decoction.
Huanglian Jiedu Decoction (HLJDD) has the effect of clearing heat and detoxifying, and has been considered as an effective prescription for cerebral ischemia (CI) for thousands of years in traditional Chinese medicine (TCM). It can improve the quality of life of patients with ischemic stroke, but its pharmacological mechanism remains unclear. The study aimed to explore the pharmacological action and potential mechanism of HLJDD against CI by systems pharmacology, proteomics and in vivo experiments. In this study, databases such as TCMIP V2.0 and Genecards were used to predict compounds, targets and CI related targets, and network topology criteria of protein-protein interaction (PPI) network was used to screen core targets. The Database for Annotation, Visualization and Integrated Discovery database (DAVID) was used to discover biological processes and pathways. In addition, molecular docking was performed between the screened core biological active compounds and targets to verify the binding activity. Finally, proteomics and Western blot were performed on cerebral cortex tissues of middle cerebral artery occlusion (MCAO) model rats with HLJDD intervention to further verify the predicted results. 77 compounds and 308 targets of HLJDD were identified, 54 of which were predicted to be associated with cerebral ischemia. PPI network and enrichment results showed that 8 targets, including AKT1, PTGS2 and TLR4, were core targets of HLJDD in CI. And 19 signaling pathways, including Rap1 signaling pathway, cAMP signaling pathway and arachidonic acid metabolism, were identified as key pathways to the therapeutic activity of HLJDD in CI. Combined with proteomics studies, we identified that Rap1 signaling pathway and upstream and downstream targets were the key mechanisms. Molecular biology experiments showed that RAP1A and AKT expression levels were significantly up-regulated in middle cerebral artery occlusion (MCAO) rats treated with HLJDD (P < 0.0001), GRIN1 expression level was significantly down-regulated (P < 0.0001). However, ACTB expression level was slightly down-regulated (P > 0.05), which may be related to the biological function. This study confirms the pharmacological effect of HLJDD on cerebral ischemia. These results indicate that HLJDD mediates various pathways such as inhibition of apoptosis, regulation of oxygen balance, inhibition of excitatory toxicity and maintenance of basic cell functions to improve CI by regulating Rap1 signaling pathway.


Perceived barriers and enablers of physical activity in postpartum women: a qualitative approach.
Postpartum women's recovery from birth can be assisted through increased physical activity (PA). However, women face substantial barriers to participating in exercise and require support to enable them to benefit from increased PA. This study sought to explore women's beliefs about and experiences of PA and exercise during the 6 weeks to 12 months postpartum period. A cohort of 14 postpartum women from a survey study of the barriers and enablers to exercise participation agreed to take part in interview sessions to provide an in-depth understanding of the women's perceptions of the postpartum period and their physical activity during this time. Findings are presented with reference to the social ecological framework and indicate postpartum women face substantial personal and environmental barriers to PA and exercise participation: fatigue, a lack of motivation and confidence, substantial time constraints, lack of access to affordable and appropriate activities and poor access to public transport. In contrast, enablers such as possessing greater social support, in particular partner support, improved PA and exercise participation. The findings encourage facilitation of exercise through mothers' groups, mothers' exercise clubs or postnatal classes suggesting behavioral and social change is needed. Interaction between individuals, community, organizations and policy makers is required. In addition, the provision of specifically tailored and appropriate exercise programs could potentially enable increased PA in postpartum women, thereby improving their health.


Pulsing electromagnetic field stimulation of the in vitro growth plate.
Specific pulsing electromagnetic fields (PEMFs) have been used to stimulate growth and repair of osteogenic tissues; however, the basis for this specificity is unknown. Previously, we determined the relevant electromagnetic field parameters of the clinically used PEMF and independently verified the beneficial effects of PEMFs on the rabbit fibula fracture healing model. The goal of the present study was to develop an in vitro model that would permit the effectiveness of various electric and magnetic field components of the PEMF to be determined. The costochondral junction (CCJ) of the 21-day-old rat was exposed in vitro to PEMFs with various electric and magnetic field component amplitudes. Response of this model to PEMFs was determined by nondestructive macrophotographic measurement of CCJ growth. Preliminary data indicated that temperature effects were present in this in vitro system. Subsequent experiments designed to separate the effects of temperature and PEMFs on the growth of CCJs in tissue culture were performed. Results indicate that accurate and frequent temperature measurements must be made for in vitro models being used to study effects of PEMFs. Small temperature differences induced by the coils used to produce PEMFs in the CCJ experimental system can have significant stimulatory effects, and the combined effects of temperature and PEMFs are not linearly additive in this model. Furthermore, our results suggest that thermal and PEMF stimuli could affect macrophotographically measured growth of the CCJ by separate mechanisms or could have a synergistic effect. Therefore, PEMF stimulation experiments should be performed under strictly "athermal" conditions.