Validation of a Predictive Scoring System for Ventriculoperitoneal Shunt Insertion After Aneurysmal Subarachnoid Hemorrhage.
Hydrocephalus is a frequently encountered complication in the context of aneurysmal subarachnoid hemorrhage (aSAH). Here, we performed an external validation of the recently proposed postsubarachnoid shunt scoring (PS3) system, which aims to stratify patients presenting with aSAH based on their relative risk of requiring ventriculoperitoneal (VP) shunt insertion. A retrospective review of all patients presenting with aSAH to our institution between July 2007 and December 2016, who underwent computed tomography imaging at the time of hospital admission, was performed. A total of 242 patients (66.1% women) with aSAH were included in the analysis with a mean age of 55.6 years. Sixty-four (26.4%) patients had a Hunt and Hess grade of 4 or 5 on admission. An external ventricular drain (EVD) was placed in 130 (53.7%) patients during the hospital admission. EVD placement was found to correlate with an increased rate of VP shunt placement (P < 0.001), and a trend toward an association between a high Hunt and Hess grade and VP shunt placement was observed (P = 0.05). The area under the receiver operating characteristic curve for the PS3 system was found to be 0.845. The system reliably predicted shunt-dependent chronic hydrocephalus in our patient cohort (odds ratio, 3.36; 95% confidence interval, 2.31-4.89; P < 0.001). Data from this study validated the previously proposed PS3 system, which was found to more accurately predict shunt-dependent chronic hydrocephalus in patients with aSAH compared with other such systems in the neurosurgical literature, such as the chronic hydrocephalus ensuing from SAH score, Barrow Neurological Institute, and shunt dependency in aSAH systems.


Stable-isotope dilution analysis of D- and L-2-hydroxyglutaric acid: application to the detection and prenatal diagnosis of D- and L-2-hydroxyglutaric acidemias.
A stable-isotope dilution assay has been developed for quantitation of D- and L-2-hydroxyglutaric acids in physiologic fluids. D- and L-2-hydroxyglutaric acids are separated as the O-acetyl-di-(D)-2-butyl esters. The method uses D,L-[3,3,4,4-2H4]-2-hydroxyglutaric acid as internal standard with ammonia chemical ionization, selected ion monitoring gas chromatography-mass spectrometry. For 13 patients with L-2-hydroxyglutaric aciduria, the concentrations of L-2-hydroxyglutaric acid were urine, 1283 +/- 676 mmol/mol creatinine (range, 332-2742; n = 12 patients); plasma, 47 +/- 13 mumol/L (range, 27-62; n = 8); cerebrospinal fluid, 62 +/- 30 mumol/L (range, 34-100; n = 6). In a child with D-2-hydroxyglutaric aciduria, the levels of D-2-hydroxyglutaric acid were urine, 1565 +/- 847 mmol/mol creatinine (range, 729-2668; n = 4); plasma, 61 +/- 14 mumol/L (range, 46-73; n = 3); cerebrospinal fluid, 15 and 25 mumol/L (n = 2). Control concentrations of D- and L-2-hydroxyglutaric acids were (D:L): urine (n = 18), 6.0 +/- 3.6 mmol/mol creatinine (range, 2.8-17): 6.0 +/- 5.4 (range, 1.3-19); plasma (n = 10), 0.7 +/- 0.2 mumol/L (range, 0.3-0.9): 0.6 +/- 0.2 (range, 0.5-1.0); cerebrospinal fluid (n = 10), 0.1 +/- 0.1 mumol/L (range, 0.07-0.3): 0.7 +/- 0.6 (range, 0.3-2.3). Investigation of control amniotic fluid (n = 10) revealed the following values (D:L): 1.2 +/- 0.4 mumol/L (range, 0.6-1.8): 4.0 +/- 0.7 (range, 3.1-5.2), suggesting the feasibility of prenatal diagnosis in families at risk.


Cats and Apples: Semantic Fluency Performance for Living Things Identifies Patients with Very Early Alzheimer's Disease.
Reduced semantic memory performance is a known neuropsychological marker of very early Alzheimer's disease (AD), but the task format that best predicts disease status is an open question. The present study aimed to identify the semantic fluency task and measure that best discriminates early-stage AD patients (PATs) from cognitively healthy controls. Semantic fluency performance for animals, fruits, tools, and vehicles was assessed in 70 early-stage AD PATs and 67 cognitively healthy participants. Logistic regressions and receiver operating characteristics were calculated for five total score semantic fluency measures. Compared with all other measures, living things (i.e., total correct animals + total correct fruits) achieved highest z-statistics, highest area under the curve and smallest difference between the upper and lower 95% confidence intervals. Living things total correct is a powerful tool to detect the earliest signs of incipient AD.


Transmembrane nuclease NUMEN/ENDOD1 regulates DNA repair pathway choice at the nuclear periphery.
Proper repair of DNA damage lesions is essential to maintaining genome integrity and preventing the development of human diseases, including cancer. Increasing evidence suggests the importance of the nuclear envelope in the spatial regulation of DNA repair, although the mechanisms of such regulatory processes remain poorly defined. Through a genome-wide synthetic viability screen for PARP-inhibitor resistance using an inducible CRISPR-Cas9 platform and BRCA1-deficient breast cancer cells, we identified a transmembrane nuclease (renamed NUMEN) that could facilitate compartmentalized and non-homologous end joining-dependent repair of double-stranded DNA breaks at the nuclear periphery. Collectively, our data demonstrate that NUMEN generates short 5' overhangs through its endonuclease and 3'→5' exonuclease activities, promotes the repair of DNA lesions-including heterochromatic lamina-associated domain breaks as well as deprotected telomeres-and functions as a downstream effector of DNA-dependent protein kinase catalytic subunit. These findings underline the role of NUMEN as a key player in DNA repair pathway choice and genome-stability maintenance, and have implications for ongoing research into the development and treatment of genome instability disorders.


Mobile phones and seizures: drug-resistant epilepsy is less common in mobile-phone-using patients.
Epilepsy is a condition where patients have seizures due to abnormal nerve impulses in the brain. The effect of mobile phone radiation on patients with seizures is not known. To compare the seizure profile of patients not using mobile phones with that of their peers using mobile phones. In a retrospective cohort study performed at the neurology outpatient department of Guntur Medical College Hospital, Guntur, India from September 2014 to September 2015, we included 178 consecutive epileptic patients aged 16-65 years, who had had seizure disorder for 1 year or more. On the basis of their possession and usage of mobile phones, patients were divided into three groups: no mobile group (NMG), home mobile group (HMG) and personal mobile group (PMG). We obtained data on seizure frequency and recorded details of mobile phone usage and their antiepileptic drug (AED) treatment. 107 NMG, 3 HMG and 68 PMG patients were finalised for the analysis. There was no significant difference in the number of seizures in the past year between the three groups. The PMG (3.7%) contained a clinically significant lower proportion of patients with drug-resistant epilepsy than the NMG (28.2%). Patients with drug-responsive epilepsy were 7.4 (95% CI 1.4 to 39.9) (p=0.01) times more likely to be found in the PMG than in the NMG after adjustment for differences in sex and occupation. Although the experimental data remain inconclusive, our clinical study suggests that patients who use mobile phones are less likely to have drug-resistant epilepsy.


Synaptogenesis in the basilar papilla of the chick.
Synaptogenesis was studied in the basilar papilla of chicken embryos from days 7--21 of incubation. On the 9th day of incubation differentiating hair cells first appeared and a few growing nerve tips made contact with them, although no membrane specializations were apparent at this stage. Synaptic bodies associated with presynaptic membrane specializations were first observed on the 10th day. They lay opposite either supporting cells or afferent nerve processes; in the latter site slight membrane thickenings were occasionally found. During subsequent stages synaptic bodies and the surrounding vesicles increased in number. Synaptic bodies associated with presynaptic membrane specializations, but devoid of contact with afferent nerve endings, were often observed on the 14th day, whereas almost all the synaptic bodies associated with presynaptic specializations were in contact with afferent nerve processes by the 21st day. The efferent synapses were first recognized on the 14th day. These results suggest that in the hair cells of chicken basilar papilla the synaptic bodies and presynaptic membrane specializations appear first and after the synaptic sites are determined by the position of the synaptic bodies, the growing nerve tips seek out and establish synaptic contact at the pre-existing synaptic sites.


Challenges of evidence-informed offshore decommissioning: an environmental perspective.
Many offshore artificial structures are at or nearing their ends of life, and society faces the considerable challenge that is decommissioning. Current scientific evidence of the ecological and environmental consequences of decommissioning is insufficient to reliably and accurately inform decision-making and policy development. Thus, we must strengthen the scientific basis for evidence-informed decommissioning.


Evaluating the effect of alpha-mangostin on neural toxicity induced by acrylamide in rats.
Acrylamide (ACR) is known to be a neurotoxic agent for humans and animals that has many applications in industry. Alpha-mangostin is a natural antioxidant that is extracted from mangosteen. This study aimed to investigate the protective effects of alpha-mangostin against ACR-induced neurotoxicity in rats and PC12 cells. Male Wistar rats were used in this investigation for 11 days, divided into 8 groups: 1. control group (normal saline), 2. ACR (50 mg/kg, i.p.), 3-6. ACR + alpha-mangostin (20, 40, 60 mg/kg, p.o.), 7. ACR + vitamin E (200 mg/kg, i.p., every other day) 8. alpha-mangostin (60 mg/kg, p.o.). On the last day of the study, the behavioral test was performed. The amounts of malondialdehyde (MDA) and glutathione (GSH) were measured. Also, the effects of ACR and alpha-mangostin were assessed by MTT assay on PC12 cells, and the levels of reactive oxygen species (ROS), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved caspase-3 proteins were measured by Western blotting. Receiving ACR caused motor disorders in animals, increased MDA, and decreased GSH levels of the cerebral cortex versus the control group. Alpha-mangostin (60 mg/kg) reduced ACR motility disorders, MDA amounts, and augmented GSH levels. The concurrent administration of vitamin E and ACR reduced gait score, MDA level, and amplified GSH content versus the ACR group. In the in vitro section, alpha-mangostin (1.25 µM, 24 h) increased cell viability, attenuated ROS, Bax/Bcl-2, and cleaved caspase-3 levels versus the ACR group. Alpha-mangostin reduced the toxicity of ACR by inhibiting oxidative stress and apoptosis. Therefore, it could be a promising compound for managing ACR-induced neurotoxicity.


Correction to: Severe Cardiomyopathy as the Isolated Presenting Feature in an Adult with Late-Onset Pompe Disease: A Case Report.
[This corrects the article DOI: 10.1002/jmd2.8904.].


Purified RNA polymerase III accurately and efficiently terminates transcription of 5S RNA genes.
RNA polymerase III was purified to about 90% homogeneity from ovarian tissue of Xenopus laevis. The enzyme accurately initiates and terminates transcription of 5S RNA synthesis in isolated nuclei, but not when naked 5S DNA is used as a template. A sensitive hybridization technique was used to demonstrate that the purified polymerase, even when supplemented with a transcription factor that binds specifically to the 5S RNA gene internal control region, is unable to initiate synthesis at the start site of the 5S RNA gene. However, the polymerase alone terminates transcription at precisely the same site that is recognized in vivo and in complete transcription extracts. The purified polymerase distinguishes between weak and strong terminator sequences with the same relative efficiency as the enzyme in complete extracts. We conclude that the pure enzyme can recognize the simple consensus sequence found at the end of genes transcribed by RNA polymerase III.


Lifespan Analysis of Dystrophic mdx Fast-Twitch Muscle Morphology and Its Impact on Contractile Function.
Duchenne muscular dystrophy is caused by the absence of the protein dystrophin from skeletal muscle and is characterized by progressive cycles of necrosis/regeneration. Using the dystrophin deficient mdx mouse model, we studied the morphological and contractile chronology of dystrophic skeletal muscle pathology in fast-twitch Extensor Digitorum Longus muscles from animals 4-22 months of age containing 100% regenerated muscle fibers. Catastrophically, the older age groups lost ∼80% of their maximum force after one eccentric contraction (EC) of 20% strain with the greatest loss of ∼92% recorded in senescent 22-month-old mdx mice. In old age groups, there was minimal force recovery ∼24% after 120 min, correlated with a dramatic increase in the number and complexity of branched fibers. This data supports our two-phase model where a "tipping point" is reached when branched fibers rupture irrevocably on EC. These findings have important implications for pre-clinical drug studies and genetic rescue strategies.


Social and economic factors and black-white disparities in cardiovascular health: A decomposition analysis.
Cardiovascular health (CVH) in Black adults, and particularly in Black women, has lagged behind White adults for decades and contributes to higher mortality rates for Black adults. We quantified the contribution of five social and economic factors to observed racial disparities in CVH by gender. We analyzed data from N = 8,019 adults aged ≥20 years free of cardiovascular disease assessed in the National Health and Nutrition Examination Survey, 2011-2018. Social and economic factors included self-reported education, income, employment, food security, and marital status. CVH was measured using eight behavioral and clinical indicators. We utilized Kitagawa-Blinder-Oaxaca decomposition to quantify gendered racial differences in CVH accounted for by these factors. Black women (mean CVH = 79.3) had a lower age-adjusted CVH score compared to White women (mean CVH = 82.3) (mean difference [MD] = -3.01; 95% CI: -5.18, -0.84). Social and economic factors accounted for a 3.26-point disadvantage (95% CI: -4.12, -2.40) and a 0.25-point CVH score advantage due to factors not accounted for in the model. In women, income had the largest coefficient associated with CVH score (b = -1.48; 95% CI: -2.04, -0.92). Among men, social and economic factors accounted for a 2.27-point disadvantage (95% CI: -2.97, -1.56) with educational attainment being the largest coefficient associated with CVH score (b = -1.55; 95% CI: -2.03, -1.06). However, the disadvantage in men was offset by a 1.99 CVH score advantage that was not accounted for by factors in the model resulting in no racial difference in age-adjusted CVH score (MD = -0.28; 95% CI: -3.78, 3.22). Racial differences in social and economic factors may contribute a large portion to the observed disparity in CVH between U.S. Black and White women.


AcP and EsD polymorphisms in Central Sardinia.
A sample of the population from Central Sardinia was studied with respect to acid phosphatase (AcP) and esterase D (EsD) enzymes. The gene frequencies were: AcPA = 0.322, AcPB = 0.617, AcPC = 0.061 and EsD1 = 0.892. The results were compared with those of other Italian populations.


Diversity and morphology of abdominal glands in workers of the ant genus Myopias (Formicidae, Ponerinae).
Histological examination of serial sections through the abdomen of workers of three species of Myopias ants revealed the presence of several exocrine glands. These include the common venom and Dufour glands as well as the pygidial gland, but also more specific sternal glands and glands associated with the sting base and the gonostyli. Two of these glands have not been reported previously among ants: one is the paired oblong plate gland, that occurs next to the oblong plate and may have a pheromonal function. The other novel gland is the paired sting shaft gland, that occurs at the dorsal side in the proximal region of the sting shaft. A remarkable characteristic of these Myopias ants is that all glands of class-3 show ducts with gradually widening internal diameter. Myopias emeryi shows a clearly more simple variety of abdominal glands than Myopias maligna and M. sp.1.


Tips for a freestanding center to survive a Joint Commission survey.
Achieving accreditation for a freestanding facility is no different from achieving accreditation for a hospital. "Our standards do not drop because we work in a freestanding facility," Phillips said.


Current status of viability assessment with positron tomography.
Accurate detection of reversible myocardium has great clinical importance, especially in patients being considered for interventional therapy. Positron emission tomography (PET) with fluorine 18-labeled fluorodeoxyglucose (FDG) has been used for this purpose, based on the residual metabolic activity in reversible ischemic areas. Although thallium imaging has been widely used for the evaluation of tissue viability in clinical cardiology, PET-FDG may provide independent values and thus may enhance the accuracy of studies for identifying ischemic myocardium. This review considers the advantages of PET technique, the clinical value of PET-FDG for assessing tissue viability, and the development of other new PET techniques.


Orthotopic transplantation of pig hearts harvested after 30 min of normothermic ischemia: controlled reperfusion with blood cardioplegia containing the Na+-H+-exchange inhibitor HOE 642.
The aim of our study was to develop a surgical technique for a successful transplantation of hearts harvested after 30 min of normothermic ischemia without donor pretreatment. Successful transplantation of ischemic compromised hearts could help to expand the severely limited donor pool. We used the pig model because this species is very susceptible to myocardial ischemia. Na+-H+-exchange (NHE) inhibitors have shown excellent protective properties in several in vitro and in vivo models of myocardial ischemia and reperfusion. In group I (n=12) hearts were harvested after 30 min of normothermic ischemia following cardiac arrest induced by exsanguination. Hearts were perfused with warm blood cardioplegia and transplanted orthotopically. In group II (n=9) controlled reperfusion with cold leucocyte-depleted blood cardioplegia was performed after 30 min of normothermic ischemia. In group III (n=8) the same procedure was performed as in group II but blood cardioplegia contained 1 mmol/l HOE 642. In group I massive myocardial oedema was observed and none of the animals could be weaned from cardiopulmonary bypass (CPB). In contrast, all animals in groups II and III could be weaned from CPB with low dose inotropic support. In groups II and III the contractility of the hearts, expressed as maximal left and right ventricular stroke work index was significantly impaired after transplantation as compared with the preoperative value. Supplementation of blood cardioplegia with HOE 642 resulted in a significantly better recovery of the LVSWImax (Group II vs. III). Successful transplantation of pig hearts is possible after 30 min of normothermic ischemia without donor pretreatment if a controlled reperfusion with cold leucocyte-depleted blood cardioplegia is performed. HOE 642 given during reperfusion only improves posttransplant left ventricular function.


Clinical perspectives on the age-related increase of immunosuppressive activity.
The aging process is associated with a remodeling of the immune system involving chronic low-grade inflammation and a gradual decline in the function of the immune system. These processes are also called inflammaging and immunosenescence. The age-related immune remodeling is associated with many clinical changes, e.g., risk for cancers and chronic infections increases, whereas the efficiency of vaccination and immunotherapy declines with aging. On the other hand, there is convincing evidence that chronic inflammatory states promote the premature aging process. The inflammation associated with aging or chronic inflammatory conditions stimulates a counteracting immunosuppression which protects tissues from excessive inflammatory injuries but promotes immunosenescence. Immunosuppression is a driving force in tumors and chronic infections and it also induces the tolerance to vaccination and immunotherapies. Immunosuppressive cells, e.g., myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), and type M2 macrophages, have a crucial role in tumorigenesis and chronic infections as well as in the tolerance to vaccination and immunotherapies. Interestingly, there is substantial evidence that inflammaging is also associated with an increased immunosuppressive activity, e.g., upregulation of immunosuppressive cells and anti-inflammatory cytokines. Given that both the aging and chronic inflammatory states involve the activation of immunosuppression and immunosenescence, this might explain why aging is a risk factor for tumorigenesis and chronic inflammatory states and conversely, chronic inflammatory insults promote the premature aging process in humans.


Are there allelopathic interactions in zooplankton? Laboratory experiments with Daphnia.
Daphnia hyalina and Daphnia cucullata were kept in flow-through chambers in lake water (I), water from mass cultures of D. hyalina (II) and water from mass cultures of D. cucullata (III). A good correlation between body length and clutch size of the Daphnia was found in all cases. The regression lines of the different treatments were compared with respect to different slopes and different intercepts. D. hyalina showed the same reaction to medium II and III, but a lower regression coefficient and higher intercept in medium I. In contrast D. cucullata showed the same reaction to medium I and II, but a higher regression coefficient in medium III.


A multi-criteria decision model for assessing health and self-care ability.
Population ageing together with the greater prevalence of multimorbidity add to the need for and complexity of healthcare services. This makes it important to encourage and empower patients with chronic diseases to take care of themselves. An associated goal of such efforts is to significantly reduce the burden on healthcare systems and positively impact patients' health outcomes and quality of life. The paper presents a multi-criteria decision model for assessing the health and self-care of patients with chronic diseases in the home environment. The model is based on the DEX methodology and was tested on ten cases. The model assists with the timely recognition of relevant symptoms and signs in decision-making about health and self-care. It can be used to promote patients taking on an active role with respect to caring for their health and well-being. The model could be integrated into self-care processes. It might also serve as a basis for an interprofessional approach to supporting older patients with chronic diseases living as fully and independently as possible in the environment in which they feel most comfortable.


Identification of genetic elements that autonomously determine DNA methylation states.
Cytosine methylation is a repressive, epigenetically propagated DNA modification. Although patterns of DNA methylation seem tightly regulated in mammals, it is unclear how these are specified and to what extent this process entails genetic or epigenetic regulation. To dissect the role of the underlying DNA sequence, we sequentially inserted over 50 different DNA elements into the same genomic locus in mouse stem cells. Promoter sequences of approximately 1,000 bp autonomously recapitulated correct DNA methylation in pluripotent cells. Moreover, they supported proper de novo methylation during differentiation. Truncation analysis revealed that this regulatory potential is contained within small methylation-determining regions (MDRs). MDRs can mediate both hypomethylation and de novo methylation in cis, and their activity depends on developmental state, motifs for DNA-binding factors and a critical CpG density. These results demonstrate that proximal sequence elements are both necessary and sufficient for regulating DNA methylation and reveal basic constraints of this regulation.


Alkaline hydrolysis to remove potentially infectious viral RNA contaminants from DNA.
Diagnostics and research of high-consequence animal disease agents is often limited to laboratories with a high level of biosecurity that restrict the transport of biological material. Often, sharing of DNA with external partners is needed to support diagnostics, forensics, or research. Even in the absence of virus, RNA from positive-sense single stranded RNA (+ssRNA) viruses that may contaminate otherwise purified DNA preparations continues to pose a threat due to its potential to be infectious via direct translation to yield viral proteins. While the risk of animal infection or accidental reconstitution and release of a virus from RNA is very low, the high impact of an animal disease event associated with the accidental release of some + ssRNA viruses, such as classical swine fever or foot-and-mouth disease viruses, necessitates the precaution of having procedures to ensure the complete inactivation of viruses and + ssRNA viral genomes. RNA and DNA are differentially susceptible to enzymatic degradations; however, such procedures are susceptible to unintended DNA damage and/or failure due to enzyme or cofactor instabilities. Therefore, we describe the development and verification of a robust and simple chemical and physical method to selectively degrade RNA from purified DNA preparations. The procedure employs incubation of DNA in 0.25 N sodium hydroxide at 65 °C for 1 h followed by neutralization and boiling for 10 min to hydrolyze contaminating RNA and inactivate animal disease viruses from DNA preparations. Additional critical quality control elements include use of a synthetic control RNA (SCR) and an SCR-specific real-time RT-PCR to track effectiveness of the procedure in a parallel treated control sample, and a pH check of reagents to ensure proper neutralization of alkaline conditions. The new procedure reduced intact RNA beyond the limit of detection by realtime RT-PCR and inactivated viruses by in vitro culture infectivity assays. Treated DNA, while denatured, remains suitable for most common molecular biology procedures including PCR, transformation of E. coli, and molecular sequencing. The procedure ensures not only the inactivation of a variety of viruses but also the degradation through hydrolysis of potentially contaminating infectious + ssRNA viral genomes.


Intercellular adhesiveness of H-2 identical and H-2 disparate cells.
Using a 2 X 2 design, the collection rates of cells from radioactively labelled single-cell suspensions on cell-coated collecting surfaces were tested for a possible H-2 effect on intracellular adhesiveness. By a statistical procedure, the undesirable variability in the suspension and/or in the collecting surface could be eliminated, and the H-2 specific net effect estimated. In this way it was possible to detect (even on the background of a large non-specific variability) significant reductions of the allogeneic collection rates (i.e. between cells which differed only in their H-2 haplotypes) as compared to the syngeneic standards. It is concluded that cells of a given H-2 haplotype have preferential adhesiveness to syngeneic cells.


The influence of gut microbiome on progression of overactive bladder symptoms: a community-based 3-year longitudinal study in Aomori, Japan.
To assess the influence of gut microbiome on overactive bladder (OAB) symptoms progression. This was a 3-year longitudinal study, Hirosaki in Japan. We assessed OAB symptoms and reviewed the medication records of each subject in 2016. We extracted 16S rRNA genes from fecal samples and analyzed gut microbiomes via next-generation sequencing. We evaluated the changes in urinary urgency (UU) and/or urgent urinary incontinence (UUI) from 2016 to 2019. We defined UU/UUI-progression as exacerbation of UU and/or UUI. We compared the clinical backgrounds and microbiota structure between UU/UUI-progression subjects and non-progression (controls). We assessed the impact of gut microbiome on the UU/UUI-progression via multivariate logistic regression analyses. Of 669 subjects, 126 were UU/UUI-progression subjects. These subjects had a higher age and prevalence of proton pump inhibitor (PPI) use (14% vs. 5.4%, P = 0.003), irritable bowel syndrome, sleep disturbance, and metabolic syndrome than those without. We found the different microbiota structures between subjects with UU/UUI-progression and those without. A higher relative abundance of genus Streptococcus (harmful bacterial genus for human health) appeared in UU/UUI-progression subjects (3.8% vs. 2.3%, P < 0.001). Multivariate analysis revealed that age ≥ 65 years, current smoking, sleep disturbance, metabolic syndrome, and genus Streptococcus (Odds ratio: 1.05, P = 0.029) were independent risk factors for UU/UUI-progression. PPI use turned to be a significant risk factor on a multivariate analysis without including genus Streptococcus. Gut microbiome might be associated with a risk for OAB symptoms progression. PPI use might cause gut dysbiosis and increase this risk.


Mitigation of Fe(0) nanoparticles toxicity to Trichosporon cutaneum by humic substances.
Zero-valent iron nanoparticles (nZVI) are a relatively new option for the treatment of contaminated soil and groundwater. However, because of their apparent toxicity, nZVI in high concentrations are known to interfere with many autochthonous microorganisms and, thus, impact their participation in the remediation process. The effect of two commercially available nZVI products, Nanofer 25 (non-stabilized) and Nanofer 25S (stabilized), was examined. Considerable toxicity to the soil yeast Trichosporon cutaneum was observed. Two chemically different humic substances (HSs) were studied as a possible protection agent that mitigates nZVI toxicity: oxidized oxyhumolite X6 and humic acid X3A. The effect of addition of HSs was studied in different phases of the experiment to establish the effect on cells and nZVI. SEM and TEM images revealed an ability of both types of nZVI and HSs to adsorb on surface of the cells. Changes in cell surface properties were also observed by zeta potential measurements. Our results indicate that HSs can act as an electrosteric barrier, which hinders mutual interaction between nZVI and treated cell. Thus, the application of HS seems to be a promising solution to mitigating the toxic action of nZVI.


Antigens of tissue plasminogen activator and plasminogen activator inhibitor 1: correlates in nonsmoking Japanese and Caucasian men and women.
We reported in a 1987 preliminary study that tissue plasminogen activator antigen was significantly higher in American Caucasian men than in Japanese men. To further examine possible differences in fibrinolytic activity between the two races, an expanded study was conducted in a total of 300 nonsmoking men and women aged 47-69 years in two population-based samples: rural Japanese living in Akita and Caucasians living in Minneapolis-St. Paul, MN. Antigens of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) were measured. Mean t-PA antigen was 2.3 ng/ml higher in Caucasian men than in Japanese men (P < 0.001), but no race difference was seen for women (P = 0.59). Mean PAI-1 was higher in Caucasians than in Japanese for both sexes, and the race difference in mean was 1.8 ng/ml for men (P = 0.07) and 4.4 ng/ml for women (P < 0.001). Both t-PA and PAI-1 were associated positively with body mass index and blood triglycerides for all sex-race groups, and positively with alcohol intake for Japanese and Caucasian men. Compared to Japanese, Caucasians of both sexes had higher levels of body mass index and blood triglycerides, and lower average intake of alcohol among men. Even when adjusted for body mass index, triglycerides, alcohol and other cardiovascular risk factors, the race difference in mean t-PA antigen persisted for men (P < 0.001), as did the difference in mean PAI-1 for men (P = 0.03) and women (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Inability of real-time reverse transcriptase PCR assay to detect subtype H7 avian influenza viruses isolated from wild birds.
We report a failure of the real-time reverse transcriptase PCR H7 subtyping protocol currently used in national avian influenza surveillance programs. Significant substitutions in primer and probe target sequences were identified, especially in wild bird viruses. The protocol, originally designed for detecting H7 influenza viruses in poultry, is not reliable for wild bird surveillance.


Progesterone metabolism by guinea pig intrauterine tissues.
Progesterone metabolism by guinea pig amnion, chorion, myometrium, and endometrium was studied at the following gestational stages. Day 45 represents mid-gestation, about 5 days before strong chorion interaction between the entire surface of the chorion and the uterus; days 57-58, 1-2 days after chorion attachment, and 2-3 days before the onset of pubic symphysis relaxation; days +1-+6, 1-6 days after the onset of pubic symphysis relaxation, i.e. within 1 week of parturition. The high metabolic activity of chorion exceeded that by amnion at all stages. Metabolism by endometrium and myometrium was always low. Conversion of progesterone by amnion significantly decreased (P < 0.05) between days 57-58 and days +1-+6. Progesterone metabolites produced by chorion and amnion were identified by TLC, HPLC, and capillary GC/MS. Both tissues converted progesterone to three major products during 60-min incubations. These were 5 alpha-pregnane-3,20-dione, 3 alpha-hydroxy-5 alpha-pregnan-20-one, and 3 beta-hydroxy-5 alpha-pregnan-20-one. The metabolite pattern differed between the two tissues. Three-minute incubations with chorion resulted in a significantly higher proportion of 3 alpha-hydroxy-4-pregnen-20-one (P < 0.01) and 5 alpha-pregnane-3,20-dione (P < 0.025) than at 60 min. The production of 3 beta-hydroxy-5 alpha-pregnen-20-one by chorion decreased (P < 0.05) between days 50-51 and 57-58. The ratio of 3 alpha-hydroxy-5 alpha-pregnan-20-one to 3 beta-hydroxy-5 alpha-pregnan-20-one increased (P < 0.05) between days 45 post-relaxation. The marked conversion of progesterone by chorion, or the formation of one or more of its metabolites, may serve to influence uterine function prior to delivery.


Cross-resistance profiles of malaria mosquito P450s associated with pyrethroid resistance against WHO insecticides.
Extensive use of pyrethroids for malaria control in Africa has led to widespread pyrethroid resistance in the two major African vectors of malaria An. gambiae and An. funestus. This is often associated with constitutively elevated levels of cytochrome P450s involved with pyrethroid metabolism and detoxification. P450s have the capacity to metabolise diverse substrates, which raises concerns about their potential to cause cross-resistance. A bank of seven recombinant P450s from An. gambiae (CYPs 6M2, 6P2, 6P3, 6P4, 6P5, 9J5) and An. funestus (CYP6P9a) commonly associated with pyrethroid resistance were screened against twelve insecticides representing the five major classes of insecticides recommended by WHO for malaria control; permethrin, etofenprox and bifenthrin (type I pyrethroids), deltamethrin, lambda cyhalothrin and cypermethrin (type II pyrethroids), DDT (organochlorine), bendiocarb (carbamate), malathion, pirimiphos methyl and fenitrothion (organophosphates) and pyriproxyfen (juvenile hormone analogue). DDT was not metabolised by the P450 panel, while bendiocarb was only metabolised by CYP6P3. Pyrethroids and pyriproxyfen were largely susceptible to metabolism by the P450 panel, as were organophosphates, which are activated by P450s. Primiphos-methyl is increasingly used for malaria control. Examination of the pirimiphos-methyl metabolites generated by CYP6P3 revealed both the active pirimiphos-methyl-oxon form and the inactive oxidative cleavage product 2-diethylamino-6-hydroxy-4-methylpyrimidine. The inhibition profile of CYPs 6M2, 6P2, 6P3, 6P9a and 9J5 was also examined using diethoxyfluorescein (DEF) as the probe substrate. Bendiocarb was the weakest inhibitor with IC50 > 100 μM across the P450 panel, while CYP6M2 showed strongest inhibition by malathion (IC50 0.7 μM). The results suggest that P450s present at elevated levels in two major Anopheline vectors of malaria in Africa have the capacity to metabolise a diverse range of pyrethroid and organophosphate insecticides as well as pyriproxyfen that could impact vector control.


Redox and zinc signalling pathways converging on protein tyrosine phosphatases.
Zinc ions, though redox-inert, have either pro-antioxidant or pro-oxidant functions at critical junctures in redox metabolism and redox signalling. They are released from cells and in cells, e.g. from metallothionein, a protein that transduces redox signals into zinc signals (1). The released zinc ions inhibit enzymes such as protein tyrosine phosphatases (PTPs), key regulatory enzymes of cellular phosphorylation signalling. The Ki(Zn) value for inhibition of receptor PTPB is 21pM (2). The binding is about as tight as the binding of zinc to zinc metalloenzymes and suggests tonic zinc inhibition. PTP1-B (PTPN1), an enzyme regulating the insulin and leptin receptors and involved in cancer and diabetes pathobiochemistry, has a Ki(Zn) value of about 5nM (3). Zinc ions bind to the enzyme in the closed conformation when additional metal-binding ligands are brought into the vicinity of the active site. In contrast, redox reactions target cysteines in the active sites of PTPs in the open conformation. This work provides a molecular basis how hydrogen peroxide and free zinc ions generated by growth factor signalling stimulate phosphorylation signalling differentially. (Supported by the Biotechnology and Biological Sciences Research Council UK, grant BB/K001442/1.).


Rapid polymerase chain reaction-based detection of epidermal growth factor receptor gene mutations in lung adenocarcinomas.
Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in lung adenocarcinomas that respond to the EGFR inhibitors gefitinib and erlotinib. Two types of mutations account for approximately 90% of mutated cases: short in-frame deletions in exon 19 and a specific point mutation in exon 21 at codon 858 (L858R). Screening for these mutations has been based mainly on direct sequencing. We report here the development and validation of polymerase chain reaction-based assays for these two predominant types of EGFR mutations. The assay for exon 19 mutations is based on length analysis of fluorescently labeled polymerase chain reaction products, and the assay for the exon 21 L858R mutation is based on a new Sau96I restriction site created by this mutation. Using serial dilutions of DNAs from lung cancer cell lines harboring either exon 19 or 21 mutations, we detected these mutations in the presence of up to approximately 90% normal DNA. In a test set of 39 lung cancer samples, direct sequencing detected mutations in 25 cases whereas our assays were positive in 29 cases, including 4 cases in which mutations were not apparent by sequencing. These assays offer higher sensitivity and ease of scoring and eliminate the need for sequencing, providing a robust and accessible approach to the rapid identification of most lung cancer patients likely to respond to EGFR inhibitors.


Patient satisfaction with cataract surgery.
Measuring the patient satisfaction is a very important issue that will help very much in improving the service provided to patients and improve the level of satisfaction. To evaluate patient satisfaction with the cataract surgery service and identify any areas for improvement, determination of patient satisfaction with referral, out-patient consultation, pre-assessment clinic, surgery and post-operative care, also to report patients' comments relating to improvement in service provision. A retrospective study was undertaken for 150 patients underwent cataract surgery at Barrow General Hospital, UK, the survey sample was by postal questionnaires. We collected our data from the theatre lists for a period of 4 month. This study included 150 patients; the response rate was (72%) 108 patients, Most patients were referred from their general practitioner 86.1%, 93 (86.1%) patients were happy with the time interval from seeing their GP to eye clinic. In the eye out patient department many factors significantly affected the level of patient satisfaction, in general the more information provided for the patient the more the satisfaction. Patient satisfaction is on important health outcome old understanding both the domains of satisfaction as well as their relative importance to patients is necessary to improve the overall quality of patient care. Meeting the doctor, presenting all relevant information and giving printed information are very important factors in improving the patient's satisfaction with cataract surgery.


Time trends in the levels and patterns of polycyclic aromatic hydrocarbons (PAHs) in pine bark, litter, and soil after a forest fire.
Forest fires are known as an important natural source of polycyclic aromatic hydrocarbons (PAHs), but time trends of PAH levels and patterns in various environmental compartments after forest fires have not been thoroughly studied yet. In this study, 16 US-EPA priority PAHs were analyzed for pine bark, litter, and soil samples collected one, three, five, and seven months after a forest fire in Pohang, South Korea. At the first sampling event, the highest levels of ∑16 PAHs were measured for the three types of samples (pine bark: 5,920 ng/g, litter: 1,540 ng/g, and soil: 133 ng/g). Thereafter, there were apparent decreasing trends in PAH levels; the control samples showed the lowest levels (pine bark: 124 ng/g, litter: 75 ng/g, and soil: 26 ng/g). The levels of PAHs in the litter and soil samples normalized by organic carbon (OC) fractions also showed decreasing trends, indicating a direct influence of the forest fire. Among the 16 target PAHs, naphthalene was a dominant compound for all types of samples. Light PAHs with 2-4 rings significantly contributed to the total concentration, and their contribution decreased in the course of time. Runoff by heavy precipitation, evaporation, and degradation of PAHs in the summer were probably the main reasons for the observed time trends. The results of principal component analysis (PCA) and diagnostic ratio also supported that the forest fire was indeed an important source of PAHs in the study area.


Morphological architecture and distribution of blood capillaries and elastic fibres in the human skin.
This study was undertaken to clarify the morphological features in the blood capillary and elastic fibre distribution of the human skin in terms of susceptibility to pressure sore development. Skin tissues were obtained from bony areas: the sacrum and ischial tuberosity and non-bony area: the centre of the gluteus maximus of 5 aged subjects post mortem for examination using light and scanning electron microscopy. It was observed that the sacral skin had finger-like papillae and underneath the blood capillary loops were most numerous. In the ischial skin the dermal papillae consisted of a combination of finger-like and trapezoid shapes having moderate density of blood capillaries. In contrast, the dermal papillae in the gluteal skin were almost flat, so that the blood capillaries were scattered. The size of elastic bundles in the papillary layer of the sacral, ischial and gluteal skin ranged from 2 to 3 microns, 5 to 10 microns, and 3 to 5 microns, respectively. The elastic fibres were densely distributed in the ischial skin while less so in the sacral skin.


A novel breast cancer detection architecture based on a CNN-CBR system for mammogram classification.
This paper presents a novel framework for breast cancer detection using mammogram images. The proposed solution aims to output an explainable classification from a mammogram image. The classification approach uses a Case-Based Reasoning system (CBR). CBR accuracy strongly depends on the quality of the extracted features. To achieve relevant classification, we propose a pipeline that includes image enhancement and data augmentation to improve the quality of extracted features and provide a final diagnosis. An efficient segmentation method based on a U-Net architecture is used to extract Regions of interest (RoI) from mammograms. The purpose is to combine deep learning (DL) with CBR to improve classification accuracy. DL provides accurate mammogram segmentation, while CBR gives an explainable and accurate classification. The proposed approach was tested on the CBIS-DDSM dataset and achieved high performance with an accuracy (Acc) of 86.71 % and a recall of 91.34 %, outperforming some well-known machine learning (ML) and DL approaches.


Investigating the correlation between hospital of primary treatment and the survival of women with breast cancer.
To understand the relation between hospital of initial treatment and the survival of women with breast cancer, the authors investigated the characteristics of the treatment center that were related most to outcome. The authors selected women from 5 regions of Quebec, Canada, who were diagnosed with lymph node-negative breast cancer between 1988 and 1994. Data were collected by chart review, queries to physicians, and linkage with administrative data bases. Overall survival to the end of 1999 was analyzed using the Kaplan-Meier method and Cox proportional hazards models. The study population included 1727 women with a median follow-up of 6.8 years. The 7-year survival rate was 82% (95% confidence interval [95%CI], 80-84%). Compared with women who were treated in centers with > or = 100 new cases per year, the hazard ratio (HR) of death from any cause was 1.80 (95%CI, 1.23-2.63), 1.44 (95%CI, 1.03-2.03), and 1.30 (95%CI, 0.96-1.76) among women who were treated in hospitals with < 25 new cases, 25-49 new cases, and 50-99 new cases per year after adjusting for case mix and characteristics of the attending physician. However, the significance of caseload disappeared after adjusting for the type of hospital. By contrast, women who were treated in centers with either on-site radiotherapy, research activity, or teaching status had significantly better outcomes, even after adjusting for caseload (HR, 0.68; 95%CI, 0.50-0.92). These associations were independent of primary treatment received, which was a strong determinant of outcome. Primary treatment of early-stage breast cancer in larger hospitals was associated with improved survival. This relation was mediated by factors related to proficiency of care, which tended to cluster within institutions.


The induction of heme oxygenase-1 modulates bismuth oxide-induced cytotoxicity in human dental pulp cells.
The aim of this study was to investigate the cytotoxic and nitric oxide (NO)-inducing effects of bismuth oxide (Bi(2)O(3))-containing Portland cement (BPC) on human dental pulp cells. We also assessed whether heme oxygenase-1 (HO-1) is involved in BPC-induced cytotoxicity in dental pulp cells. Cytotoxicity and NO production induced by BPC were higher than those induced by Portland cement at 12 and 24 hours, and the former gradually decreased to the level observed for PC. HO-1 and inducible nitric oxide synthase messenger RNA expressions in the BPC group showed maximal increase at 24 hours, and it gradually decreased with increasing cultivation time. Hemin treatment reversed the BPC-induced cytotoxicity, whereas zinc protoporphyrin IX treatment increased the cytotoxicity. These results suggested that NO production by BPC correlates with HO-1 expression in dental pulp cells. Moreover, BPC-induced HO-1 expression in dental pulp cells plays a protective role against the cytotoxic effects of BPC.


Use of the Portuguese version of the educational material "your pelvic floor" among Brazilian teenagers.
To evaluate the use of the Portuguese version of the booklet "Your Pelvic Floor" as educational material, among Brazilian teenagers. The original version in English, directed to teenage audience, was developed by members of the Association for Continence Advice, in 2009. This quasi-experimental study was carried out at a non-governmental organization (NGO, São Paulo, Brazil) that develops continuing education programs for low-income girls aged eight to eighteen years old. A questionnaire with five questions was developed and validated by experts to measure the efficacy of the booklet "Your Pelvic Floor" on the learning of teenagers. After this, teenagers underwent three steps: pre-test, reading educational material and post-test, using the developed questionnaire to evaluate the knowledge about pelvic floor before and after reading the booklet. Sixteen teenagers volunteered to participate. The number of correct answers to the questionnaire was significantly higher (P < 0.01) after reading the educational material, in all questions. The educational material "Your pelvic floor" was shown to be effective in teaching teenagers about the pelvic floor. Neurourol. Urodynam. 36:62-64, 2017. © 2015 Wiley Periodicals, Inc.


Chronic hepatitis: pathogenesis and treatment.
Current therapies for chronic viral hepatitis, autoimmune "lupoid" chronic active hepatitis, and drug-induced chronic hepatitis are discussed in the context of recent advances in our understanding of the pathophysiology of chronic active liver disease. Accurate diagnosis is the cornerstone of proper treatment; the limitations and pitfalls of conventional techniques are discussed. Current theories of the pathogenesis of chronic hepatitis B are reviewed to provide a framework for the use of antiviral drugs. Data from the early results of therapy with adenine arabinoside, acyclovir, and immunomodulatory agents are reviewed, and the theoretical basis for the use of alpha-interferon as well as preliminary data supporting its efficacy is presented. Strategies for the treatment of chronic delta hepatitis and chronic non-A, non-B viral hepatitis are discussed as well. The immunological changes associated with autoimmune chronic active hepatitis are described to help define those patients with chronic active hepatitis who are likely to respond to immunosuppressive therapy. The recognized hazards of long-term corticosteroid therapy are indicated and guidelines for the management of these patients are suggested. Chronic drug-induced liver disease will usually improve with cessation of the offending agent. An approach to the patient with suspected drug-induced chronic hepatitis is indicated. Finally, the role of liver transplantation is mentioned as the ultimate treatment modality available for endstage liver disease.


New strategies for cardiopulmonary resuscitation.
Sudden death claims hundreds of thousands of lives each year in the United States. Emergency resuscitation efforts are successful in only about 6% of all out-of-hospital arrests. In light of the poor survival rate, innovative research is reexamining the practice of cardiopulmonary resuscitation. Basic life support (BLS), with its stepwise management of airway, breathing, circulation, and defibrillation, is far from a rudimentary procedure. Each step has been challenged and changed in recent years, reflecting ongoing resuscitation research into the mechanisms, efficacy, and practical aspects of delivery of these interventions. Recommended modifications to BLS techniques have resulted in increased survival rates. Therefore, health professionals need to stay current with the latest guidelines through literature reviews and frequent recertification.


Internalized heterosexism, alcohol use, and alcohol-related problems among lesbians and gay men.
Research regarding internalized heterosexism in relation to alcohol use and alcohol-related problems has suffered from methodological problems. Moreover, the results of the research have been mixed. The purpose of the current study was to examine internalized heterosexism in relation to alcohol use and alcohol-related problems among a sample of 335 lesbians and gay men recruited through lesbian and gay events, listserves, and friendship networks. Females completed the Lesbian Internalized Homophobia Scale [Szymanski, D. M., & Chung, Y. B. (2001). The internalized homophobia scale for lesbians: A rational/theoretical approach. Journal of Homosexuality, 41(2), 37-52.]; males completed the Internalized Homonegativity Inventory [Mayfield, W. (2001). The development of an internalized homonegativity inventory for gay men. Journal of Homosexuality, 41(2), 53-76.]. Items from the National Household Survey on Drug Abuse [Substance Abuse and Mental Health Services Administration. (2000). National household survey on drug abuse: main findings 1998. Rockville, MD: Author.] measured alcohol consumption. The Michigan Alcoholism Screening Test [Selzer, M. L. (1971). The Michigan Alcoholism Screening Test: the quest for a new diagnostic instrument. American Journal of Psychiatry, 127, 89-94.] and the Drinker Inventory of Consequences [Miller, W. R., Tonigan, J. S., & Longabaugh, R. (1995). The drinker inventory of consequences (DrInC): An instrument for assessing adverse consequences of alcohol abuse test manual. National institute on alcohol abuse and alcoholism project match monograph series volume 4. Rockville, MD: U.S. Department of Health and Human Services.] measured alcohol-related problems. The hypothesis that a positive relationship exists was partially supported for lesbians, but generally not supported for males.


Activation and priming of the human neutrophil oxidase response by substance P: distinct signal transduction pathways.
The undecapeptide substance P (SP), both activates and 'primes' the neutrophil NADPH-oxidase response. In this paper we investigate the roles of Ca2+ and actin polymerisation in both the activation and 'priming' of the neutrophil oxidase response by the non-oxidisable SP-analog norleucine-SP (n-SP). We demonstrate that by binding to receptors which were distinct from the formylated peptide receptor, n-SP (100 nM-400 microM) directly triggered the NADPH-oxidase response, elevated cytosolic free Ca2+, and caused the polymerisation of G-actin. However at lower concentrations (1-100 nM), in the absence of these phenomena, n-SP primed the oxidase response to the peptide f-Met-Leu-Phe. We propose that occupancy of SP-activatable receptors on neutrophils triggers two different signal transduction pathways, one being responsible for the generation of signals for oxidase activation and the second, which is independent of Ca2+ and actin signalling, being responsible for priming.


Pathogenic and non-pathogenic Naegleria and Acanthamoeba spp.: a new autochthonous isolate from an Italian thermal area.
We performed an epidemiological survey of 17 thermal baths and the same number of mud-basins. This study aimed to ascertain the presence and incidence of small free-living amoebae, particularly species and/or strains of Naegleria and Acanthamoeba spp., occasional etiological agents of fatal meningoencephalitis and/or ocular infections in man. Over 51 samples of water and mud incubated at 37 degrees C and at 45 degrees C, 34 (66.7%) became positive at 37 degrees C and 33 (64.7%) at 45 degrees C. We isolated 7 (6%) strains of Naegleria spp., 6 (5.2%) of Acanthamoeba spp., 39 (33.6%) of Vahlkampfia spp., 28 (24.1%) of Hartmannella spp. and 36 (31.1%) strains of other species of free-living amoebae. 4 strains of Naegleria spp. and 6 of Acanthamoeba spp. proved pathogenic both in vivo, after experimental infection (meningoencephalitis) in the albino mouse, and in vitro, having previously contaminated monolayers of Vero cell line (cytopathic effect). Within the isolated pathogenic strains of Naegleria spp., a new strain of N. australiensis s.sp. italica was typified from an immunochemical point of view. This should be added to previous isolations reported by us.


Exploring the pharmacological mechanism of Shengjing capsule on male infertility by a network pharmacology approach.
Shengjing capsule (SJC) is a traditional Chinese medicine (TCM) and has gained widespread clinical application for the treatment of male infertility (MI). However, the pharmacological mechanism of SJC against MI remains vague to date. The active ingredients of SJC and their targets were identified from the database, and MI-related genes were retrieved from several databases. Protein-protein interaction (PPI) data were obtained to construct the PPI networks. The candidate targets of SJC against MI were identified through topological analysis of the PPI network. Functional enrichment analysis of candidate targets was performed, and the key target genes were identified from the gene-pathway network. We identified 154 active ingredients and 314 human targets of SJC, as well as 564 MI-related genes. Eight pharmacological network diagrams illustrating the interactions among herbs, active ingredients, targets, and pathways, were constructed. The four dominating network maps included a compound-target network of SJC, a compound-anti-MI targets network, a candidate targets PPI network, a pathway-gene network, and a drug-key compounds-hub targets-pathways network. Systematic analysis indicated that the targets of SJC in the treatment of MI mainly involved RPS6, MAPK1, MAPK3, MDM2, and DDX5. Pathway enrichment analysis showed that SJC had the potential to impact multiple biological pathways, such as cancer-related pathways, viral/bacterial infection-related pathways, and signal transduction-related pathways. Our results preliminarily revealed the pharmacological basis and molecular mechanism SJC in treating MI, but further experimental research is required to verify these findings.


Occurrence of Cryptosporidium spp. and Cystoisospora belli among adult patients with diarrhoea in Maputo, Mozambique.
Infections with Cryptosporidium spp. and Cystoisospora belli are important causes of diarrhoea in HIV patients. Nevertheless, information concerning these two parasites is scarce in many African countries, including Mozambique. In this study occurrence of Cryptosporidium spp. and C. belli was investigated by microscopy of stool specimens from 108 adult diarrhoeal patients, most with a confirmed HIV diagnosis. The Cryptosporidium isolates were further characterized by molecular methods. Cryptosporidium and C. belli oocysts were found in 8.3% (9/108), and 25.0% (27/108) of the study participants, respectively. Species identification was possible for all Cryptosporidium isolates with available DNA. The following Cryptosporidium species were detected (number of cases within parentheses): C. parvum (3), C. hominis (3), C. felis (1), and C. hominis/C. parvum (1). Subtyping targeting the gp60 gene revealed two C. hominis isolates with subtype IaA23R3, one C. parvum isolate with IIcA5G3d, and one with IIeA12G1. In summary the occurrence of C. hominis and anthroponotic subtypes of C. parvum indicates that the main route of Cryptosporidium transmission in the present study population was human to human (direct or via food and water). The high prevalence of C. belli highlights the need for early diagnosis of this parasite, for which a treatment exists.


Multidimensional immune profiling in Gastric Cancer Multiplex Immunohistochemistry Atlas from Peking University Cancer Hospital project informs PD-1/PD-L1 blockade efficacy.
Immunotherapy has resulted in impressive objective response rates and durable tumour remission, but only in a subset of gastric cancer (GC) patients. The PD-L1 combined positive score is the most widely used tissue-based biomarker for anti-PD-1/PD-L1 therapy; however, this unidimensional method has limitations. Next-generation exploration of tissue-based biomarkers for GC requires characterisation of various cellular markers and key immunoregulatory molecule expression in situ. Thus, a complete, stepwise solution covering the entire process from staining samples to cross-site utilisation of pathomics data is urgently needed. With the advanced multispectral imaging analysis method, web-based data repository, and interactive sharing technology, we conducted a project entitled Gastric Cancer Multiplex Immunohistochemistry Atlas from Peking University Cancer Hospital (GMAP). We propose a standard pipeline covering sample collection, staining, scanning multispectral images, constructing a spectral library, identifying and phenotyping cells, positioning each element, and quantitatively extracting immune features. We designed an open-access relational database to explore tissue-based biomarkers to determine PD-1/PD-L1 blockade efficacy. The GMAP project detected the functional status and spatial location of more than 50 million cells using 15 markers in 80 GC patients, based on which billions of cell pairs were recognised, highlighting the rich spatial arrangement information and the fine tumour microenvironment structure. We generated a tumour-immune atlas using the count and spatial features of 65 immune cell types. We eventually selected the indicators and built a comprehensive risk-scoring system. Patients with higher risk score showed superior immunotherapy-related progression-free survival (irPFS) (hazard ratio [HR]: 3.19; P < 0.001; median irPFS: 4.87 versus 19.87months, respectively) and immunotherapy-related overall survival (HR: 3.10; P = 0.001; median irPFS: 10.03 versus 24.87months, respectively) compared with lower risk patients, demonstrating their potential for guiding anti-PD-1/PD-L1-based immunotherapy. Importantly, an easy-to-use and versatile web server was built to promote tissue-based biomarker exploration in GC. The GMAP project highlighted the clinical value of tissue-based immune features as biomarkers for immunotherapeutic decision-making. We present a well-designed, detailed workflow for the orderly generation and use of a high-quality, spatially resolved pathological database.


Effect of arterial proteoglycans on the interaction of LDL with human monocyte-derived macrophages.
The effect of human arterial proteoglycans (PG1) on the interaction of low density lipoprotein (LDL) with cultured human monocyte-derived macrophages (HMDM) was studied. LDL was insolubilized by treatment with chondroitin-6-sulfate-rich, partially purified PG1. The LDL, resolubilized in culture medium, was added to HMDM. The PG1 pretreated LDL induced lipid accumulation in the HMDM, converting them into foam cells. Mass determination of lipids by spectrophotometric and chromatographic procedures showed a 2-4-fold accumulation of triglycerides, phospholipids, unesterified cholesterol and cholesterol esters in 48 h, in the HMDM incubated with PG pretreated LDL, when compared to those incubated with native LDL. Incorporation of [14C]oleic acid into the HMDM lipid esters correlated with the accumulation. Association of 125I-labeled LDL and of fluorescent labeled LDL (3,3-octadecyl indocarbocyanine) to HMDM also indicated that the PG1-pretreatment of LDL increased its uptake. Density gradient centrifugation, isoelectric focusing and electron microscopy showed that, when added to the cells, the PG1 pretreated LDL was not aggregated or altered in its surface charge. However, controlled trypsin treatment and polypeptide pattern analysis indicate that the accessibility of apoB has been altered. The results suggest that changes in the surface of LDL, induced by the arterial PG1, lead to increased endocytosis of the lipoprotein and stimulation of lipid synthesis in the macrophages. The possibility that a similar process may cause lipid accumulation in arterial macrophages is discussed.


An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19.
The worldwide outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to countering the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human coronavirus antiviral activity and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro antiviral cell potency in a phase 1 clinical trial in healthy human participants.


Polarity in filamentous fungi: moving beyond the yeast paradigm.
Filamentous fungi grow by the polar extension of hyphae. This polar growth requires the specification of sites of germ tube or branch emergence, followed by the recruitment of the morphogenetic machinery to those sites for localized cell wall deposition. Researchers attempting to understand hyphal morphogenesis have relied upon the powerful paradigm of bud emergence in the yeast Saccharomyces cerevisiae. The yeast paradigm has provided a useful framework, however several features of hyphal morphogenesis, such as the ability to maintain multiple axes of polarity and an extremely rapid extension rate, cannot be explained by simple extrapolation from yeast models. We discuss recent polarity research from filamentous fungi focusing on the position of germ tube emergence, the relaying of positional information via RhoGTPase modules, and the recruitment of morphogenetic machinery components including cytoskeleton, polarisome and ARP2/3 complexes, and the vesicle trafficking system.


Global distribution of ustiloxins in rice and their male-biased hepatotoxicity.
Ustiloxins, a group of bioactive metabolites produced by the pathogen of rice false smut (RFS), have emerged as ubiquitous contaminants in RFS-occurred paddy fields and could accumulate in rice. Nevertheless, the prevalence of ustiloxins in rice and exposure risks of humans are limited. In this study, concentrations of ustiloxin A (UA) and ustiloxins B (UB), which are two predominant ustiloxins, were measured in 240 rice samples from China and 72 rice samples from 12 other counties. The detection rates (DRs) of UA and UB were 82.1% and 49.3%, respectively, and their concentrations in rice ranged from below detection limit (LOD: 0.22 μg/kg) to 85.96 μg/kg dw. Furthermore, for the first time, we reported the occurrence of UA (DR = 22.8%) in urine collected from residues of Enshi city, China. Urinary UA were significantly correlated with the activities of alanine aminotransferase in male, and this male-biased hepatotoxicity was further confirmed in mice exposure experiment. This study for the first time reported the widespread geographical distribution of ustiloxins in rice, as well as emphasized the occurrence of internal exposure and potential health risk in humans.


In Situ Formation of CoP/Co3 O4 Heterojunction for Efficient Overall Water Splitting.
Electrochemical water splitting is an environmentally friendly and effective energy storage method. However, it is still a huge challenge to prepare non-noble metal based electrocatalysts that possess high activity and long-term durability to realize efficient water splitting. Here, we present a novel method of low-temperature phosphating for preparing CoP/Co3 O4 heterojunction nanowires catalyst on titanium mesh (TM) substrate that can be used for oxygen evolution reaction (OER), hydrogen evolution reaction (HER), and overall water splitting. CoP/Co3 O4 @TM heterojunction showed an excellent catalytic performance and long-term durability in 1.0 M KOH electrolyte. The overpotential of CoP/Co3 O4 @TM heterojunction was only 257 mV at 20 mA cm-2 during the OER process, and it could work stably more than 40 h at 1.52 V versus reversible hydrogen electrode (vs. RHE). During the HER process, the overpotential of CoP/Co3 O4 @TM heterojunction was only 98 mV at -10 mA cm-2 . More importantly, when used as anodic and cathodic electrocatalyst, they achieved 10 mA cm-2 at 1.59 V. The Faradaic efficiencies of OER and HER were 98.4 % and 99.4 %, respectively, outperforming Ru/Ir-based noble metal electrocatalysts and other non-noble metal electrocatalysts for overall water splitting.


Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis Syndrome Diagnosis in Adolescent and Isotretinoin as a Possible Serious Exacerbating Factor.
Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare auto-inflammatory condition involving cutaneous and osteoarticular manifestations. This study presents a case where a 16-year-old male with glucose-6-phosphate dehydrogenase (G6PD) deficiency presented with severe nodulocystic acne after three weeks of isotretinoin therapy. In addition to worsening acne, the patient had bone and joint pain with movement restriction. The patient's workup showed elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), bilateral symmetrical sacroiliitis on magnetic resonance imaging (MRI), and multiple bony lesions on bone scintigraphy. A diagnosis of SAPHO syndrome possibly induced by isotretinoin was made. Isotretinoin discontinuation, analgesia, topical acne medications, prednisolone, and adalimumab yielded considerable clinical improvement.


Characteristics of HCN channels and their participation in neuropathic pain.
Neuropathic pain is induced by the injury to nervous systems and characterized by hyperalgesia, allodynia and spontaneous pain. The underlying mechanisms include peripheral and central sensitization resulted from neuronal hyperexcitability. A number of ion channels are considered to contribute to the neuronal hyperexcitability. Here, we particularly concentrate on an interesting ion channel, hyperpolarization-activated cyclic nucleotide gated (HCN) channels. We overview its biophysical properties, physiological functions, followed by focusing on the current progress in the study of its role in the development of neuropathic pain. We attempt to provide a comprehensive review of the potential valuable target, HCN channels, in the treatment of neuropathic pain.


[Ischemia of the extremity as a rare complication of alloplastic joint replacement].
Two cases of extremity ischemia after alloplastic knee and hip joint replacement are presented. In both cases early operative intervention led to complete recovery. The mechanisms of iatrogenic vascular injury following arthroplastic operations on the hip and knee joint are demonstrated. In particular, the importance of preexisting vascular occlusive disease is stressed. Diagnostic procedures and implications for treatment are discussed.


A randomized study of combined spinal-epidural analgesia versus intravenous meperidine during labor: impact on cesarean delivery rate.
Combined spinal-epidural (CSE) analgesia produces rapid-onset pain relief and allows ambulation in early labor. Epidural local anesthetics may contribute to an increase in operative deliveries by decreasing perineal sensation and causing motor weakness. Operative delivery rates might be reduced with CSE, by avoiding or delaying administration of local anesthetics. This study compares the operative delivery rates associated with a CSE technique and those associated with intravenous meperidine for labor analgesia. Healthy parturients at full term were assigned randomly to receive CSE or intravenous meperidine analgesia. The CSE group received 10 microg intrathecal sufentanil, followed by epidural bupivacaine and fentanyl at their next request for analgesia. Parturients receiving intravenous meperidine had 50 mg on demand (maximum, 200 mg in 4 h). Labor and delivery outcomes in both groups were recorded and compared. An intent-to-treat analysis of 1,223 women indicated that CSE does not increase the rate of cesarean delivery for dystocia in nulliparous and parous women (CSE, 3.5% vs. intravenous meperidine, 4; P=not significant) or in nulliparous women alone (CSE, 7% vs. intravenous meperidine, 8%; P=not significant). Profound fetal bradycardia that necessitated emergency cesarean delivery within 1 h of the time the mother received sufentanil occurred in 8 of 400 parturients (compared with 0 of 352 who received meperidine; P < 0.01). However, the method of fetal monitoring differed between the two groups. Despite this, neonatal outcomes were similar overall. Combined spinal-epidural analgesia during labor does not increase the cesarean delivery rate for dystocia in healthy parturient patients at full term, regardless of parity. However, an unexpected increase in the number of cesarean deliveries for profound fetal bradycardia after intrathecal sufentanil was observed. Further investigation is warranted.


Reference intervals of urinary steroid metabolites using gas chromatography-mass spectrometry in Chinese adults.
Urinary steroid profiling by GC or GC-MS are established clinical tools to complement other biochemical tests in the diagnosis and investigation of a wide range of adrenocortical disorders, but normative data on adults using the more specific GC-MS are lacking. Our objective was to set up the reference intervals of commonly detected urinary steroid metabolites as well as marker metabolites seen in disease states. Apparently healthy adult Chinese males and females were recruited by completing health questionnaires. A 24-h urine specimen was collected from all the participants for urinary steroid profiling by GC-MS in cyclic scan mode. The analyzer was calibrated by using authentic steroid standards. Statistical methods recommended by the National Committee for Clinical Laboratory Standards were followed for setting up the reference intervals of various steroid metabolites. After outliers were excluded, the data were tested for the necessity to partition into sex-, menopausal status- and age-specific reference intervals. 83 males and 89 females were recruited for the study. Necessity to partition into sex-specific reference intervals was demonstrated for almost all steroid metabolites. Menopausal status and age also had a significant impact on steroid metabolite excretion, making separate reference intervals necessary. We have set up the normative data on the levels of urinary steroid metabolite excretion in Chinese adults for future reference in patient management and research in steroid metabolism.


Programmable thermal emissivity structures based on bioinspired self-shape materials.
Programmable thermal emissivity structures based on the bioinspired self-shape anisotropic materials were developed at macro-scale, and further studied theoretically at smaller scale. We study a novel concept, incorporating materials that are capable of transforming their shape via microstructural rearrangements under temperature stimuli, while avoiding the use of exotic shape memory materials or complex micro-mechanisms. Thus, programmed thermal emissivity behaviour of a surface is achievable. The self-shape structure reacts according to the temperature of the surrounding environment or the radiative heat flux. A surface which incorporates self-shape structures can be designed to quickly absorb radiative heat energy at low temperature levels, but is simultaneously capable of passively controlling its maximum temperature in order to prevent overheating. It resembles a "game" of colours, where two or more materials coexist with different values of thermal emissivity/ absorptivity/ reflectivity. The transformation of the structure conceals or reveals one of the materials, creating a surface with programmable - and therefore, variable- effective thermal emissivity. Variable thermal emissivity surfaces may be developed with a total hemispherical emissivity ratio (εEff_H/εEff_L) equal to 28.


Penicillin Allergy Assessment in Pregnancy: Safety and Impact on Antibiotic Use.
Penicillin and other beta-lactam antibiotics are recommended for group B Streptococcus and cesarean section prophylaxis, but approximately 10% of pregnant patients report a penicillin allergy. To assess the safety and impact of penicillin allergy evaluation in pregnant patients. In this retrospective study of obstetrician-ordered Allergy/Immunology (AI) electronic consultations (e-consults) from September 20, 2017 through December 31, 2019, we reviewed the electronic health record for e-consult recommendation; patient demographic, obstetric, and allergy histories; and peripartum antibiotic utilization with indication. For patients whose electronic consultation recommended an in-person AI evaluation, testing outcomes were determined, and multivariable logistic regression models were used to compare antibiotic use between patients who did and did not receive an in-person AI evaluation. Of 389 obstetrician-ordered e-consults, 363 (93%) recommended an in-person AI evaluation; of these, 222 (61%) patients received an in-person AI evaluation. Of 220 (99%) patients skin tested, 209 (95%) had their penicillin allergy label safely removed. Compared with patients who did not receive an in-person AI evaluation despite it being recommended (n = 141), patients with in-person AI evaluation (n = 222) had reduced peripartum vancomycin (adjusted odds ratio [aOR], 0.07; 95% CI, 0.01-0.33), clindamycin (aOR, 0.17; 95% CI, 0.08-0.34), and gentamicin (aOR, 0.39; 95% CI, 0.19-0.78) use and increased penicillin (aOR, 18.0; 95% CI, 6.30-51.2) use. The fully AI evaluated patients had increased first-line antibiotic prophylaxis for group B Streptococcus (aOR, 26.9; 95% CI, 6.32-114) and cesarean section (aOR, 1.94; 95% CI, 1.06-3.52). In a sample of 220 pregnant patients with penicillin allergy histories and in-person AI evaluation, penicillin allergy testing was safe and associated with significantly reduced broad-spectrum antibiotic use and increased first-line beta-lactam antibiotic use.


Evidence for a single common Na+-dependent transport system for alanine, glutamine, leucine and phenylalanine in brush-border membrane vesicles from bovine kidney.
The characteristics of the Na+-dependent transport of alanine, glutamine, leucine and phenylalanine were studied in bovine renal brush-border membrane vesicles. Inhibition of the transport of any one of these amino acids by any other was mutually competitive. The Ki value for the inhibition of alanine transport by leucine was similar to the Km for leucine transport; similar interrelationships existed for the other amino acids. Each amino acid was shown to exchange with each of the other amino acids across the membrane. From these and other results it is concluded that the Na+-dependent transport of these four amino acids is catalysed by a single common transport system.


Fatty acid composition and biogenic amines in acidified and fermented fish silage: a comparison study.
In the presented study, ensiling of discard fish by acidification or fermentation was evaluated. Klunzinger's ponyfish which is a discard fish was used for the production of fish silage by acidification (3% formic acid for Method FA; 1.5% formic and 1.5% sulphuric acid for Method FASA) and fermentation (Lactobacillus plantarum for Method LP and Streptococcus thermophilus for Method ST). The chemical, microbiological and nutritional properties of the differently preserved fish silages were estimated during a storage period of 60 d at ambient temperature. Compared to the raw material, a slight increase in saturated fatty acids and a slight decrease in polyunsaturated fatty acids were observed in all silages. At the end of the storage period, the aerobic bacteria counts after applying Methods FA, FASA, LP and ST amounted to 2.35, 2.39, 5.77 and 5.43 log cfu/g, respectively. The analysis of thiobarbituric acid revealed that acidification of silages accelerated the lipid oxidation. Nine biogenic amines were found in raw fish and different silages. The initial histamine concentration in raw fish was 0.17 mg/100 g and in all silages it remained at low levels during the storage period. The initial tyramine content was found to be 1.56 mg/100 g in raw fish and increased significantly in all silages. The increase of the tyramine content in fermented silages was considerably higher than in acidified silages (23-48 mg/100 g and 5-10 mg/100 g, respectively). It can be concluded that acidified or fermented fish silage should be considered as potential feed component for animals because of its high nutritional value and appropriate microbiological and chemical quality.


The human neuroprotective placental protein composition suppressing tinnitus and restoring auditory brainstem response in a rodent model of sodium salicylate-induced ototoxicity.
The effect of neuroprotective placental protein composition (NPPC) on the suppression of tinnitus and the restoration of the auditory brainstem response (ABR) characteristics was explored in tinnitus-induced rats. The animals were placed into two groups: (1) the study group, rats received sodium salicylate (SS) at the dose of 200 mg/kg twice a day for two weeks, and then 0.4 mg of the NPPC per day, between the 14th and 28th days, (2) the placebo group, rats received saline for two weeks, and then the NPPC alone between the 14th and 28th days. The gap pre-pulse inhibition of the acoustic startle (GPIAS), the pre-pulse inhibition (PPI), and the ABR assessments were performed on animals in both groups three times (baseline, day 14, and 28). The GPIAS value declined after 14 consecutive days of the SS injection, while NPPC treatment augmented the GPIAS score in the study group on the 28th day. The PPI outcomes revealed no significant changes, indicating hearing preservation after the SS and NPPC administrations. Moreover, some changes in ABR characteristics were observed following SS injection, including (1) higher ABR thresholds, (2) lowered waves I and II amplitudes at the frequencies of 6, 12, and 24 kHz and wave III at the 12 kHz, (3) elevated amplitude ratios, and (4) prolongation in brainstem transmission time (BTT). All the mentioned variables returned to their normal values after applying the NPPC. The NPPC use could exert positive therapeutic effects on the tinnitus-induced rats and improve their ABR parameters.


Unearthing the Rosetta Stone of public antibody responses.
Comprehensive profiling of humoral responses to viruses reveals that germline-encoded V gene motifs govern the emergence of recurrent antibody epitopes across individuals.


Changes in plasma and urinary 11-dehydrothromboxane B2 in healthy subjects produced by oral CS-518, a novel thromboxane synthase inhibitor.
When 50 mg CS-518, a novel thromboxane (TX) A2 synthase inhibitor, was orally administered to healthy male volunteers, the plasma concentration of CS-518 peaked after 0.5 h and then decreased with a half-life of 0.44 h. There was no significant change in the plasma concentration of circulating TXB2, whereas that of circulating 11-dehydrothromboxane B2 (11-dhTXB2), an enzymatic metabolite of TXB2, was significantly decreased from 0.5 h to 24 h after administration; the maximal decrease to about 25% of the pre-dose value was found at 6 h. After CS-518 100 mg b.d. for 4.5 days, plasma 11-dhTXB2 was suppressed to the same extent as after the single dose of 50 mg from 6 h after the initial dose throughout the administration period. The urinary excretion of 11-dhTXB2 corrected for the creatinine level was significantly decreased by 70-84% throughout the treatment. These results suggest that CS-518 causes long-lasting inhibition of TXA2 synthase despite its rapid elimination from plasma, and that circulating 11-dhTXB2 in plasma and its urinary excretion can serve as a quantitative index of TXA2 synthase inhibition in vivo by CS-518.


Evaluation of iron overload by single voxel MRS measurement of liver T2.
To overcome the difficulty of poor signal-to-noise ratio of magnetic resonance imaging (MRI) in evaluating heavy iron overload by using a single voxel magnetic resonance spectroscopy (MRS) technique. A single voxel STEAM pulse sequence with a minimum TE of 1.5 msec and a sampling volume of 36.6 cm(3) was developed and applied to 1/T2 measurement of the liver in 14 patients with thalassemia whose liver iron concentration was determined through biopsy. The iron level ranged from 0.23 to 37.15 mg Fe/g dry tissue with a median value of 18.06. In all cases, strong MR signals were obtained. 1/T2 was strongly correlated with the liver iron concentration (r = 0.95, P < 0.00005). The single voxel MRS measurement of T2 in liver iron overload overcomes the difficulty of lack of detectable signals in conventional MRI when the iron level is high. There is an excellent correlation between the iron level and 1/T2.


"Police Wouldn't Give You No Help": Female Offenders on Reporting Sexual Assault to Police.
Sexual assault remains one of the most underreported violent crimes. When victims report, they often are dissatisfied with the police response. The factors influencing one's decision to invoke the law have been widely examined. However, less research examines (a) how the victim's criminality affects this decision and (b) women offenders' characterization of their reporting decisions. We use mixed methods to explore the factors related to an offender's decision to report sexual victimization to police and consider their descriptions of police response when they do report the crime. Our findings provide insight into the gendered relations between offenders and police.


A tetrahydro beta-carboline trisaccharide from Palicourea coriacea (Cham.) K. Schum.
A new tetrahydro beta-carboline alkaloid that has an oligosaccharide unit was isolated from the root extracts of the Palicourea coriacea. The structure was elucidated using spectral methods, including 2D NMR: COSY, HMQC, HMBC and NOESY.


Sequence of the signal peptide for rat liver mitochondrial aldehyde dehydrogenase.
The cDNA coding for the signal peptide of rat liver mitochondrial aldehyde dehydrogenase was sequenced. The deduced amino acid sequence of the signal peptide was MLRAALSTARRGPRLSRLL. From this sequence an amphiphilic helix which had a high hydrophobic moment could be constructed. A comparison to the published cDNA sequence of human mitochondrial aldehyde dehydrogenase revealed great sequence identity and allowed us to make some predictions regarding the primary structure of the human signal peptide.


Synthesis of Multifunctionalized 2-Carbonylpyrrole by Rhodium-Catalyzed Transannulation of 1-Sulfonyl-1,2,3-triazole with β-Diketone.
A facile rhodium-catalyzed transannulation of 1-sulfonyl-1,2,3-triazoles with β-diketones was realized, and a series of multisubstituted 2-carbonylpyrroles were synthesized efficiently (up to 94% yield). The protocol features several advantages, such as readily available materials, mild reaction conditions, a concise operating procedure, a broad reaction scope, and excellent regioselectivity when benzoylacetone derivatives were used.


Study on timing sequence control fracture blasting excavation of deep rock masses with filled joints.
During the blasting excavation of deep underground caverns, the effects of the structural surface on crack propagation are usually considered in addition to the clamping effects of high in situ stress. Based on the notched borehole and timing sequence control (TSC) fracture blasting method, this paper studies the effects of different borehole shapes on the degree of damage of the surrounding rock and profile flatness of the rock anchor beams and the effects of different filled joint characteristics on the blasting crack propagation rules. The results show that the damage depth of the surrounding rocks by round hole smooth blasting is approximately twice that by notched hole smooth blasting, by which the profile formed is flatter. The notched primary borehole (PBH) remains a strong guidance for crack propagation in a rock mass with filled joints, while the stress concentration effects of the round target borehole (TBH) cannot fully guide the cracks until they fall within a certain distance between the PBH and TBH. It is favourable for cracks to propagate along the lines between boreholes with larger filled joint strengths and larger angles between boreholes.


Life without RNase P.
The universality of ribonuclease P (RNase P), the ribonucleoprotein essential for transfer RNA (tRNA) 5' maturation, is challenged in the archaeon Nanoarchaeum equitans. Neither extensive computational analysis of the genome nor biochemical tests in cell extracts revealed the existence of this enzyme. Here we show that the conserved placement of its tRNA gene promoters allows the synthesis of leaderless tRNAs, whose presence was verified by the observation of 5' triphosphorylated mature tRNA species. Initiation of tRNA gene transcription requires a purine, which coincides with the finding that tRNAs with a cytosine in position 1 display unusually extended 5' termini with an extra purine residue. These tRNAs were shown to be substrates for their cognate aminoacyl-tRNA synthetases. These findings demonstrate how nature can cope with the loss of the universal and supposedly ancient RNase P through genomic rearrangement at tRNA genes under the pressure of genome condensation.


The potential of computed tomography in visualising structures inside the metal cup in surface-replacement total hip arthroplasty.
Computed tomography (CT) was employed to evaluate the femoral component of the prosthesis in surface-replacement total hip arthroplasty in seven patients suffering from rheumatoid arthritis. Image reconstruction using the high frequency filter resulted in an image of the cement-bone interface inside the cup which allowed the detection of bone resorption. This new application of CT could prove to be a valuable complement to conventional methods in the radiological assessment of metal cup arthroplasties.


Herbarium macroalgae specimens reveal a rapid reduction of thallus size and reproductive effort related with climate change.
Understanding and forecasting the effects of climate changes on vulnerable species are leading concerns for ecologists and conservation biologists. Herbaria are invaluable for use in long-term data series, and one of the few available methods for quantifying biodiversity changes over large periods of time. Gelidium canariense is an endemic and habitat-forming macroalga of the Canary Islands that coexists with two other habitat-forming Gelidiales: G. arbuscula and Pterocladiella capillacea. This study assesses long-term changes in thallus size and reproductive effort of all specimens deposited in the Herbarium of Universidad de La Laguna of these three Gelidiales species. Also assessed were the effects of seawater temperature and increased incident light on net primary production (NPP), and the effects of extreme desiccation conditions on the relative water content and NPP of the three Gelidiales species. The length of the thallus of the endemic species G. canariense was halved during the past 40 years. The shortening of the thallus coincided with a significant decrease in the number of reproductive structures in both Gelidium species. These morphological changes coincide with a significant increase of the sea surface temperature, air temperature above sea surface and ultraviolet radiation in the studied area. The experiments have revealed the deleterious effects of extreme desiccation and extreme irradiance on all three species. Hence, these results suggest that air temperature and irradiance are related with these morphological changes over time in the habitat-forming Gelidium species and that are most likely compromising the survival of their populations which are already declining.


Pain Management and Opioid Therapy: Persistent Knowledge Gaps Among Primary Care Providers.
Given the opioid epidemic in the US, it is vital that clinicians who prescribe opioids for pain management to do so in an evidence-based manner, eg considering all pharmacologic and non-pharmacologic options, assessing risk of opioid use disorder prior to initiating opioids. Continuing education regarding the evidence-based prescribing of opioids is now required for US healthcare providers who prescribe opioids. A "blueprint" of the content to be included in continuing education programs was developed by the US Food and Drug Administration and updated in 2018. To understand the baseline knowledge and confidence of healthcare professionals in prescribing opioids for pain management, we posed 27 unique knowledge-based questions and 1 confidence question to clinician participants before or during 2 continuing educational programs that were based respectively on the 2016 and 2018 FDA Risk Evaluation and Mitigation Strategy (REMS) educational blueprints for pain management. Overall, 5571 clinicians completed these programs, including 1925 physicians (1516 [79%] identifying as primary care), 1181 physician assistants, 737 advanced practice nurses, 719 nurses, and 479 pharmacists. Responses to pretest questions in both programs indicated profound and persistent gaps in knowledge, particularly in definitions and mechanisms of pain, general principles of pharmacologic analgesic therapy, and specific aspects of opioid analgesic therapy and addiction. Participants in both programs also expressed limited confidence in their abilities to incorporate patient engagement techniques into pain management or develop a treatment plan for a patient with chronic pain. These data support an ongoing need for comprehensive clinician-based education as outlined in the FDA REMS educational blueprint, especially given recent data of escalating overdose deaths during the COVID-19 pandemic.


[Interventional treatment of thoracic aortic dissection with stent-graft placement guided by transesophageal echocardiography].
To evaluate the effect and safety of transfemoral stent-graft placement in combination with transesophageal echocardiography (TEE) in treating DeBakey IIIb aortic dissecting aneurysm. Eight male patients [mean age (55.8 +/- 10.2) years, range 28-71 years] with DeBakey IIIb aortic dissection were diagnosed and confirmed by magnetic resonance angiography (MRA). With TEE and fluoroscopy monitoring, transfemoral stent-grafts placement was performed with resulting close of the proximal or both proximal and distal ruptures of aortic dissection. The immediate and follow-up results were assessed. Eleven stent-grafts were placed successfully in the 8 patients, the mean diameter of stents was 29.4 (22-38) mm. Three patients had a mild endoleak and 2 patients had a tiny shunt immediately after operation. Ascending aortic dissection occurred in 1 patient after balloon dilation. The mean stay in hospital was 9 days. All the eight patients were followed up and the mean time of follow-up was 10.5 (6-18) months, 4 residual shunts disappeared. No stents displacement or new endoleak occurred. Transfemoral stent-graft placement in combination with TEE for the treatment of DeBakey IIIb aortic dissection is a promising method, which is safe, effective and with little injury. Its recent and middle term result is satisfactory, but further observation is needed for long term result.


Use of laser capture microdissection together with in situ hybridization and real-time PCR to study distribution of latent herpes simplex virus genomes in mouse trigeminal ganglia.
The herpes simplex virus (HSV) frequently establishes a latent state in neurons, which can then be reactivated from the infected neurons. Quantifying the single-cell viral load is essential for understanding latency and reactivation of this virus. In this chapter the methods of laser capture microdissection and quantitative real-time polymerase chain reaction with in situ hybridization have been combined to determine the HSV copy number per neuron in latently infected trigeminal ganglia. The distribution of latent herpes simplex genomes at the individual cell level has been deteremined and the relationship of the number of latent genomes to the expression of latency-associated transcripts established.


MRI assessment of the effects of acetazolamide and external lumbar drainage in idiopathic normal pressure hydrocephalus.
The objective was to identify changes in quantitative MRI measures in patients with idiopathic normal pressure hydrocephalus (iNPH) occurring in common after oral acetazolamide (ACZ) and external lumbar drainage (ELD) interventions. A total of 25 iNPH patients from two clinical sites underwent serial MRIs and clinical assessments. Eight received ACZ (125-375 mg/day) over 3 months and 12 underwent ELD for up to 72 hours. Five clinically-stable iNPH patients who were scanned serially without interventions served as controls for the MRI component of the study. Subjects were divided into responders and non-responders to the intervention based on gait and cognition assessments made by clinicians blinded to MRI results. The MRI modalities analyzed included T1-weighted images, diffusion tensor Imaging (DTI) and arterial spin labelling (ASL) perfusion studies. Automated threshold techniques were used to define regions of T1 hypo-intensities. Decreased volume of T1-hypointensities and decreased mean diffusivity (MD) within remaining hypointensities was observed after ACZ and ELD but not in controls. Patients responding positively to these interventions had more extensive decreases in T1-hypointensites than non-responders: ACZ-responders (4,651 ± 2,909 mm(3)), ELD responders (2,338 ± 1,140 mm(3)), ELD non-responders (44 ± 1,188 mm(3)). Changes in DTI MD within T1-hypointensities were greater in ACZ-responders (7.9% ± 2%) and ELD-responders (8.2% ± 3.1%) compared to ELD non-responders (2.1% ± 3%). All the acetazolamide-responders showed increases in whole-brain-average cerebral blood flow (wbCBF) estimated by ASL (18.8% ± 8.7%). The only observed decrease in wbCBF (9.6%) occurred in an acetazolamide-non-responder. A possible association between cerebral atrophy and response was observed, with subjects having the least cortical atrophy (as indicated by a positive z-score on cortical thickness measurements) showing greater clinical improvement after ACZ and ELD. T1-hypointensity volume and DTI MD measures decreased in the brains of iNPH patients following oral ACZ and ELD. The magnitude of the decrease was greater in treatment responders than non-responders. Despite having different mechanisms of action, both ELD and ACZ may decrease interstitial brain water and increase cerebral blood flow in patients with iNPH. Quantitative MRI measurements appear useful for objectively monitoring response to acetazolamide, ELD and potentially other therapeutic interventions in patients with iNPH.