REPRINT OF: The Behavioral Risk Factor Surveys: I. State-Specific Prevalence Estimates of Behavioral Risk Factors.
Editor's Note: This article is a reprint of a previously published article. For citation purposes, please use the original publication details: Marks JS, Hogelin GC, Gentry EM, et al. The Behavioral Risk Factor Surveys: I. State-specific prevalence estimates of behavioral risk factors. Am J Prev Med. 1985;1(6):1-8. The prevalence of most behavioral risk factors varies substantially among states. The prevalence of current cigarette smoking ranges from 22 percent to 38 percent. Estimates of alcohol use show geographic clustering, with lower rates in the southeastern states. The prevalence of sedentary lifestyle, uncontrolled hypertension, overweight, and seatbelt use differs markedly among states. These findings represent an initial step toward the analysis of state-specific baseline risk-factor data for use in developing state programs aimed at reducing the leading causes of death in the United States.


The non-Hodgkin's lymphomas. I. A retrospective clinical and pathologic analysis of 499 cases diagnosed between 1958 and 1969.
A retrospective clinical and histopathological review was made of 499 previously untreated cases of non-Hodgkin's lymphoma with adequate initial biopsy material diagnosed at Memorial Hospital between 1958 and 1969. Three hundred-eighty-four cases (77%) had diffuse, 104 (21%) nodular, nine (2%) nodular and diffuse, and two (less than 1%) unclassifiable histologic types. Overall median survival was 16 months, and 79% of the patients died with lymphoma. For all treatments, survival of responding patients was the same as that of nonresponders, a reflection of the palliative approach. Significant differences in survival were found between patients in the various Ann Arbor stages. Median survival was 42 months for the nodular group and 11.5 months for the diffuse (P less than 0.001). The ten-year survival was 12% for the diffuse and 22% for the nodular patients. The overall difference in survival was due to early deaths in the diffuse group. Long-term follow-up is necessary to appreciate the usual fatal course of patients with all types of non-Hodgkin's lymphomas treated conservatively.


Nonalcoholic fatty liver disease as a complication of insulin resistance.
Nonalcoholic fatty liver disease (NAFLD) refers to a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis, advanced fibrosis, and rarely, progression to cirrhosis. The pathogenesis of NAFLD is thought to be related to insulin resistance and oxidant stress. Truncal obesity, dyslipidema, hypertension, and hyperglycemia are strongly associated with NAFLD; therefore, management of NAFLD entails identification and treatment of metabolic risk factors, improving insulin sensitivity, and increasing antioxidant defenses in the liver. This article briefly summarizes advances in our understanding of the relationship between NAFLD and the insulin resistance (metabolic) syndrome, its prevalence, natural history, and treatment.


Brain vasoactive intestinal peptide: a potent stimulant of gastric acid secretion.
Vasoactive intestinal peptide (VIP) belongs to a rapidly expanding family of cerebrogastrointestinal oligopeptides. This report describes a potent dose-, time- and vagus-dependent stimulation of gastric acid secretion by brain VIP. Physiologic evidence favoring a role of VIP on acid secretion was provided by the finding that immunoneutralization of endogenous brain VIP produced a significant decrease of acid secretion. These and other data contained herein suggest that the mechanism by which central VIP stimulates acid secretion appears to involve peripheral cholinergic pathways.


The functions, oncogenic roles, and clinical significance of circular RNAs in renal cell carcinoma.
Renal cell carcinoma (RCC) is the most common form of malignancy affecting the kidneys. Circular RNAs (circRNAs) are non-coding RNAs that are derived from exonic or intronic sequences through a selective shearing process. There is growing evidence that these circRNAs can influence a range of biological pathways by serving as protein decoys, microRNA sponges, regulators of transcriptional activity, or templates for protein translation. The dysregulation of circRNA expression patterns is a hallmark of RCC and other cancer types, and there is strong evidence that these RNA species can play central roles in the onset and progression of RCC tumors. In the present review, we summarized recent findings on the functional roles and clinical impacts of circRNAs in RCC. Further, we discussed their potential utility as diagnostic biomarkers or targets for therapeutic intervention.


Bioactivity of male (sperm transmitted) mouse mammary tumor virus as influenced by donor, recipient and age at treatment.
The sperm collected from mammary tumor virus (MTV)-carrying mice (C3H, BALB/cfC3H, BALB/cfRIII and RIII) was separately tested for mammary tumor-inducing activity in (BALB/c x C3Hf)F1, (BALB/c x RIIIf) F1, and BALB/c female recipients by i.p., injection of 0.1 ml of the sperm at 1-2 weeks or at 3 months of age. A total of 551 recipents was observed, including control mice. The results may be summarized as follow: 1) mammary tumor incidence in experiments with or without histocompatibility between sperm donor and recipient is the same; 2) bioactivity is related to the type of MTV (C3H, RIII) and to the type of recipient, not to the sperm donor; 3) the activity of RIII MTV released in the sperm appears to be less influenced by the age of recipients than is that of C3H MTV; 4) BALB/c recipients are more susceptible to C3H than to RIII sperm-released MTV; 5) (BALB/c x RIIIf) F1 hybrids are resistant to sperm-released MTV, especially to C3H MTV infection, and show a 34% incidence of late spontneous lymphomas inherited by the RIIf male parent; 6) (BALB/c x C3Hf) F1 hybrids are susceptible to both C3H and RIII sperm-released MTV and show a 30% incidence of late spontaneous mammary tumors due to genetic transmission of MTV by the C3H male parent.


Suitability of the marine prosobranch snail Hydrobia ulvae for sediment toxicity assessment: A case study with the anionic surfactant linear alkylbenzene sulphonate (LAS).
Individuals of the mudsnail Hydrobia ulvae (Pennant) (Mollusca: Prosobranchia) were exposed to sediments spiked with increasing concentrations (1.59-123.13mgkg(-1) dry weight) of the anionic surfactant linear alkylbenzene sulphonate (LAS) which is employed in the formulation of laundry powders and liquids, as well as hand dishwashing products. The suitability of the selected organism, H. ulvae for routine sediment toxicity testing was evaluated by measuring acute toxicity recording survival. Sublethal toxicity was evaluated as total number of produced veliger larvae per treatment throughout the test (9d). Mortality has shown to be a reliable and reproducible indicator of acute toxicity. LC(50) values were comprised between 203.4 (48h) and 94.3mgkg(-1) (9d) dry weight. As sublethal endpoint, the total number of produced larvae showed to be a useful indicator of toxicity for this organism. The number of produced larvae increased at lower exposure concentrations, whereas at the highest LAS concentration, the number of produced larvae decreased. This is the first report of acute and sublethal toxicity of sediment associated LAS for this species.


Outcomes After Atrial Fibrillation Ablation in Patients With Premature Atrial Contractions Originating From Non-Pulmonary Veins.
The aim of this study was to examine the relationship between residual premature atrial contractions (PACs) originating from non-pulmonary veins (PVs), which do not initiate atrial fibrillation (AF), and AF recurrence after ablation. Residual atrial ectopic beats that trigger AF from non-PVs (non-PV AF triggers) after catheter ablation are among the major causes of AF recurrence. However, little is known about the impact of non-PV PACs on AF recurrence. This retrospective study included 565 consecutive patients who underwent first-time AF ablation at our institution. After PV isolation, we infused isoproterenol to provoke non-PV AF triggers and/or non-PV PACs. We excluded 26 patients with non-PV AF triggers and 3 patients who underwent ablation of non-PV PACs, and finally analyzed 536 patients. Non-PV PACs were defined as ectopic beats that were constantly observed with the same intra-atrial activation patterns from non-PVs. Residual non-PV PACs during the procedure were observed in 112 patients (21%). There was no significant difference in the AF recurrence rate between patients with non-PV PACs (35 of 112, 31%) and those without (145 of 424, 34%; log-rank p = 0.69), during a median follow-up of 670 days. Age- and sex-adjusted hazards for AF recurrence were also similar between the 2 groups. The similar AF recurrence rate in patients with and without non-PV PACs suggests that the additional ablation of non-PV PACs has limited effect on AF recurrence.


Progressive spontaneous occlusion of a cerebellar AVM: pathogenetic hypothesis and review of literature.
Cerebral arteriovenous malformation (AVM) is a complex network of vascular channels consisting of arterial feeders, a nidus and enlarged venous drainage. AVMs usually increase in size with time, but may rarely obliterate; spontaneous angiographic regression occurs in less than 1.5% of cerebral AVMs. Several causes of spontaneous regression have been postulated such us hemodynamic alterations due to hemorrhage, hypercoagulability, atherosclerosis, and tromboembolism from associated aneurysms. In this report we describe a case of spontaneous, complete and asymptomatic occlusion of a left cerebellar hemispheric AVM; angiograms clearly demonstrate a progressive decrease in size of the AVM at follow-up. Thrombosis of the dominant-draining vein caused by turbulent blood flow seemed to be the main driver. Possible mechanisms leading to the occlusion are discussed and a review of the literature is reported.


[Access to safe drinking water and sanitation: a case study at the district community, in Douala V (Cameroon)].
Access to drinking water and sanitation has been a long-standing issue between many States. However, it represents a daily struggle for hundreds of thousands of city dwellers who live mainly in the developing countries. The government of Cameroon with the assistance of providers of funds have implemented strategies to make sanitation and access to safe drinking water a reality. We have therefore decided to assess sanitation and access to drinking water in Douala V sub division. We conducted a cross-sectional descriptive study from May to June 2018. We used a two-stage random sampling. Data were collected using a questionnaire. The analysis was conducted using Epi Info Version 18.104.22.168. Our study shows that 22.47% of subjects discharged waters into the natural environment after use. Then, 65,55% (493/752) of households consumed borehole water; 53.69% of households rode between 1 to 5 km, 49.25% walked more than 15 minutes to collect water and 85,50% of households did not use a water treatment method. Only 14.49% of subjects used a water treatment method. No household used solar water disinfection (SODIS); 2/752 households (0.26%) had no latrine. Most of the households (54.52%; 410/752) discharged domestic wastes onto the street. The creation of decentralized units: the drillings, waste disposal systems and water treatment education to meet basic needs are essential.


National Trends and Geographic Variation in Availability of Home Health Care: 2002-2015.
To evaluate national trends and geographic variation in the availability of home health care from 2002 to 2015 and identify county-specific characteristics associated with home health care. Observational study. All counties in the United States. All Medicare-certified home health agencies included in the Centers for Medicare & Medicaid Services Home Health Compare system. County-specific availability of home health care, defined as the number of available home health agencies that provided services to a given county per 100,000 population aged ≥18 years. The study included 15,184 Medicare-certified home health agencies that served 97% of U.S. ZIP codes. Between 2002-2003 and 2014-2015, the county-specific number of available home health agencies per 100,000 population aged ≥18 years increased from 14.7 to 21.8 and the median (inter-quartile range) population that was serviced by at least one home health agency increased from 403,605 (890,329) to 455,488 (1,039,328). Considerable geographic variation in the availability of home health care was observed. The West, North East, and South Atlantic regions had lower home health care availability than the Central regions, and this pattern persisted over the study period. Counties with higher median income, a larger senior population, higher rates of households without a car and low access to stores, more obesity, greater inactivity, and higher proportions of non-Hispanic white, non-Hispanic black, and Hispanic populations were more likely to have higher availability of home health care. The availability of home health care increased nationwide during the study period, but there was much geographic variation.


[Guideline-conform inpatient psychiatric psychotherapeutic treatment of chronic depression: Normative personnel requirements].
Chronic depression is a frequent mental disorder representing a significant subjective and economic burden. Effective disorder-specific treatment of chronic depression presupposes sufficient funding of treatment resources. Definition of normative needs of personnel resources for guideline-compliant and evidence-based inpatient treatment of chronic depression based on treatment duration and intensity. The personnel resources determined were compared to the resources provided on the basis of the existing reimbursement system (Psych-PV) in Germany. Resources determined according to national treatment guidelines and empirical evidence were compared to personnel resources dictated by the German Psych-PV reimbursement algorithm. The current funding algorithm greatly underestimates the resources needed for a guideline-compliant and evidence-based treatment program, even if healthcare providers received 100 % reimbursement of the sum determined by the Psych-PV algorithm. The results clearly show that even in the case of a full coverage of the current German reimbursement algorithm, funding allocation for evidence-based inpatient treatment of chronic depression is insufficient. In addition, the difficulties of specific coding of chronic depression in the ICD-10 system generates a major problem in the attempt to measure the current resources needed for sufficient treatment.


Influence of diamino acid derivatives of protoporphyrin IX on mouse immunological system: preliminary results.
Immunological response related to photodynamic therapy (PDT) is one of the basic elements that influence on the efficiency of this cancer treatment method. Diamino acid derivatives of protoporphyrin IX are promising photosensitizing agents that are intended to be the components of new anti-tumor drug. The influence of three derivatives - PP(Ser)(2)Arg(2), PP(Ala)(2)Arg(2), PP(Phe)(2)Arg(2) and a mixture of these compounds called Sensyphyrine on mouse immunological system was investigated where animals were exposed and unexposed to the laser irradiation. Porphyrins solutions were injected intravenously, mice were irradiated with the red diode laser at lambda=632 nm. Cells and blood samples were taken at time intervals after irradiation. The levels of interleukin-6, interleukin-1beta and the production of reactive forms of nitrogen by macrophages were determined. The results show that all of the diamino acid derivatives of protoporphyrin IX indicate an immunological response when the light is applied. Each of the porphyrin revealed different impact on mice immunological system. The most potent stimulant properties disclosed PP(Phe)(2)Arg(2) derivative for which the highest values of IL-1beta, IL-6 and NO(2)(-) were noticed. The weakest immunological activation revealed PP(Ser)(2)Arg(2) derivative.


AnCF, the CCAAT binding complex of Aspergillus nidulans, contains products of the hapB, hapC, and hapE genes and is required for activation by the pathway-specific regulatory gene amdR.
CCAAT binding factors (CBFs) positively regulating the expression of the amdS gene (encoding acetamidase) and two penicillin biosynthesis genes (ipnA and aatA) have been previously found in Aspergillus nidulans. The factors were called AnCF and PENR1, respectively. Deletion of the hapC gene, encoding a protein with significant similarity to Hap3p of Saccharomyces cerevisiae, eliminated both AnCF and PENR1 binding activities. We now report the isolation of the genes hapB and hapE, which encode proteins with central regions of high similarity to Hap2p and Hap5p of S. cerevisiae and to the CBF-B and CBF-C proteins of mammals. An additional fungus-specific domain present in HapE was revealed by comparisons with the homologs from S. cerevisiae, Neurospora crassa, and Schizosaccharomyces pombe. The HapB, HapC, and HapE proteins have been shown to be necessary and sufficient for the formation of a CCAAT binding complex in vitro. Strains with deletions of each of the hapB, hapC, and hapE genes have identical phenotypes of slow growth, poor conidiation, and reduced expression of amdS. Furthermore, induction of amdS by omega amino acids, which is mediated by the AmdR pathway-specific activator, is abolished in the hap deletion mutants, as is growth on gamma-aminobutyric acid as a sole nitrogen or carbon source. AmdR and AnCF bind to overlapping sites in the promoters of the amdS and gatA genes. It is known that AnCF can bind independently of AmdR. We suggest that AnCF binding is required for AmdR binding in vivo.


The chemical and dynamic distribution characteristics of iron, cobalt and nickel in three different anaerobic digestates: Effect of pH and trace elements dosage.
The enhancement of the bioavailability and process controllability of trace elements (TEs) addition is of significance to improve the anaerobic digestion (AD) performance. In order to understand the bioavailability of TEs, the chemical form distribution patterns of endogenous/exogenous Fe, Ni and Co with different dosage (Fe: 1, 10 and 100 mg/kg; Ni and Co: 0.1, 1 and 10 mg/kg) and different pH condition (6.5; 7.5 and 8.5) were investigated in three different anaerobic digestates. The results showed that the exogenous TEs dosage exerted no obvious effects on the TEs distribution patterns. The chemical fractionation of TEs was more affected by pH, redox potential, AD process and digestate resource. Under pH 6.5 and with redox potential rising, the acid-extractable and reducible fractions and of Fe, Ni and Co were increased while the oxidizable fractions were decreased, which enhanced the bioavailability of TEs.


Undifferentiated gliomas of the brain stem.
Undifferentiated gliomas of the brain stem were confirmed surgically in two young children. The patients were treated by aggressive irradiation of the entire neuraxis, similar to that administered for medulloblastoma. Therapy resulted in a good prognosis and there was no tumor recurrence.


Effects of nocturnal bright light on saliva melatonin, core body temperature and sleep propensity rhythms in human subjects.
Nine healthy male volunteers (mean age of 24) participated in two experimental sessions of random crossover design: a bright light (5000 lux for 5 h from 00:00 to 05:00 h) session and a dim light (10 lux for 5 h from 00:00 to 05:00 h) session. Subsequently participants entered an ultra-short sleep-wake schedule for 26 h, in which a sleep-wake cycle consisting of 10-min sleep EEG recording on a bed and 20-min resting awake on a semi-upright chair were repeated. Saliva melatonin level and core body temperature was measured throughout the experiment. Bright light significantly delayed rhythms of melatonin secretion (01:58 h), core body temperature (01:12 h) and sleep propensity (02:00 h), compared as dim light session. Significant positive correlation was found between bright light-induced phase change in core body temperature and that in sleep propensity rhythm. Light-induced melatonin suppression significantly positively correlated with the phase change in core body temperature and that in sleep propensity rhythm. Assuming that light-induced melatonin suppression represents an acute impact of light on the circadian pacemaker, our results suggest that such an impact may be directly reflected in phase changes of sleep propensity and core body temperature rhythms rather than in melatonin rhythm.


Analytical method development for α-amanitin and β-amanitin in plasma at ultra-trace level by online solid phase extraction-high performance liquid chromatography-triple quadrupole mass spectrometry and its application in poisoning events.
α-Amanitin and β-amanitin are the main fatal mushroom toxins. The toxins metabolize rapidly in blood and are reported hard to be detected 24 h after poisoning. The main challenge is that of developing a highly sensitive method at sub-pg mL-1 level in blood to diagnose intoxication cause and to study the poisoning mechanism and blood toxicity kinetics. An analytical method for α-amanitin and β-amanitin at ultra-trace level was developed in this study by online solid phase extraction-high performance liquid chromatography-triple quadrupole mass spectrometry (online SPE-LC-MS/MS). Simple protein precipitation and liquid-liquid extraction were introduced to resolve the sample preparation problem of the online SPE-LC-MS/MS system with large-volume injection. A quick valve-switching technique with a quantitative loop as interface was used in the online system. This design can ensure the independence of flow path and pressure between the SPE and LC-MS/MS modules and can obtain the precise cleanup of the toxins. The limits of detection for α-amanitin and β-amanitin in plasma were both 0.02 ng mL-1. The linear ranges were 0.05-20 ng mL-1 with a correlation coefficient r >0.99. The average recoveries at three spiking levels were 82.9 %-92.2 % with the relative standard deviations (RSD) of 5.4 %-8.0 % for α-amanitin and 84.5 %-93.9 % with RSDs of 4.5 %-7.8 % for β-amanitin. The composition and concentration of the toxins in plasma from 18 patients in 5 mushroom poisoning events caused by aminitins were studied. The developed method has high positive confirmation ability and can identify toxins in plasma 40 h after poisoning.


Thermally unstable gating of the most common cystic fibrosis mutant channel (ΔF508): "rescue" by suppressor mutations in nucleotide binding domain 1 and by constitutive mutations in the cytosolic loops.
Most cystic fibrosis (CF) cases are caused by the ΔF508 mutation in the CF transmembrane conductance regulator (CFTR), which disrupts both the processing and gating of this chloride channel. The cell surface expression of ΔF508-CFTR can be "rescued" by culturing cells at 26-28 °C and treating cells with small molecule correctors or intragenic suppressor mutations. Here, we determined whether these various rescue protocols induce a ΔF508-CFTR conformation that is thermally stable in excised membrane patches. We also tested the impact of constitutive cytosolic loop mutations that increase ATP-independent channel activity (K978C and K190C/K978C) on ΔF508-CFTR function. Low temperature-rescued ΔF508-CFTR channels irreversibly inactivated with a time constant of 5-6 min when excised patches were warmed from 22 °C to 36.5 °C. A panel of CFTR correctors and potentiators that increased ΔF508-CFTR maturation or channel activity failed to prevent this inactivation. Conversely, three suppressor mutations in the first nucleotide binding domain rescued ΔF508-CFTR maturation and stabilized channel activity at 36.5 °C. The constitutive loop mutations increased ATP-independent activity of low temperature-rescued ΔF508-CFTR but did not enhance protein maturation. Importantly, the ATP-independent activities of these ΔF508-CFTR constructs were stable at 36.5 °C, whereas their ATP-dependent activities were not. Single channel recordings of this thermally stable ATP-independent activity revealed dynamic gating and unitary currents of normal amplitudes. We conclude that: (i) ΔF508-CFTR gating is highly unstable at physiologic temperature; (ii) most rescue protocols do not prevent this thermal instability; and (iii) ATP-independent gating and the pore are spared from ΔF508-induced thermal instability, a finding that may inform alternative treatment strategies.


MR imaging of hepatocellular carcinoma: prospective intraindividual head-to-head comparison of the contrast agents gadoxetic acid and gadoteric acid.
The routine use of dynamic-contrast-enhanced MRI (DCE-MRI) of the liver using hepatocyte-specific contrast agent (HSCA) as the standard of care for the study of focal liver lesions is not widely accepted and opponents invoke the risk of a loss in near 100% specificity of extracellular contrast agents (ECA) and the need for prospective head-to-head comparative studies evaluating the diagnostic performance of both contrast agents. The Purpose of this prospective intraindividual study was to conduct a quantitative and qualitative head-to-head comparison of DCE-MRI using HSCA and ECA in patients with liver cirrhosis and HCC. Twenty-three patients with liver cirrhosis and proven HCC underwent two 3 T-MR examinations, one with ECA (gadoteric acid) and the other with HSCA (gadoxetic acid). Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), wash-in, wash-out, image quality, artifacts, lesion conspicuity, and major imaging features of LI-RADS v2018 were evaluated. Wash-in and wash-out were significantly stronger with ECA compared to HSCA (P < 0.001 and 0.006, respectively). During the late arterial phase (LAP), CNR was significantly lower with ECA (P = 0.005), while SNR did not differ significantly (P = 0.39). In qualitative analysis, ECA produced a better overall image quality during the portal venous phase (PVP) and delayed phase (DP) compared to HSCA (P = 0.041 and 0.008), showed less artifacts in the LAP and PVP (P = 0.003 and 0.034) and a higher lesion conspicuity in the LAP and PVP (P = 0.004 and 0.037). There was no significant difference in overall image quality during the LAP (P = 1), in artifacts and lesion conspicuity during the DP (P = 0.078 and 0.073) or in the frequency of the three major LI-RADS v2018 imaging features. In conclusion, ECA provides superior contrast of HCC-especially hypervascular HCC lesions-in DCE-MR in terms of better perceptibility of early enhancement and a stronger washout.


Sumatriptan and 5-benzyloxytryptamine: contractility of two 5-HT1D receptor ligands in canine saphenous veins.
Sumatriptan and 5-benzyloxytryptamine are ligands with high affinity for 5-HT1D receptors in the caudate nucleus. Both compounds contracted canine saphenous veins, in vitro. Benzyloxytryptamine was less potent as a contractile agonist than sumatriptan which was less potent than serotonin. In high concentrations (greater than 10(-5) M) serotonin-induced contraction resulted, in part, from activation of alpha-adrenoceptors as determined by blockade of contraction with prazosin (10(-6) M) and idazoxan (10(-6) M). Likewise, benzyloxytryptamine but not sumatriptan also activated contractile alpha-receptors in the canine saphenous vein. Furthermore, benzyloxytryptamine antagonized contraction to sumatriptan in an apparently non-competitive fashion. Thus, benzyloxytryptamine, although possessing some alpha-receptor agonist activity, like sumatriptan, can interact with serotonin receptors in canine saphenous veins. Although effects of sumatriptan and benzyloxytryptamine quantitatively differed in canine saphenous veins, both agents showed similar affinity and agonist efficacy at 5-HT1D receptors in brain. These studies may reflect potential differences between the 5-HT1D receptor in brain and the 5-HT1-like receptor in canine saphenous veins.


Human soluble leptin receptor number in healthy normotensive individuals with high normal blood pressure.
High normal blood pressure (BP) seems to be related to increased cardiovascular risk in healthy normotensive subjects, whereas hyperleptinemia enhances both sympathetic tone and arterial BP. The aim of our study was to determine the human soluble leptin receptor number in healthy normotensive subjects with high normal BP and to compare these findings to those of healthy normotensive individuals with normal BP levels. We studied 36 healthy normotensive individuals with high normal BP (19 men and 17 women, mean age 42+/-8 years, body mass index [BMI] 23+/-1.5 kg/m2) and 40 healthy normotensive individuals with normal BP (23 men and 17 women, mean age 43+/-7 years, BMI 23.2+/-1.4 kg/m2). The two groups are matched for age, sex, and BMI. The human soluble leptin receptor number and immunoreactive leptin levels were determined in the study population by enzyme-linked immunoassay and radioimmunoassay, respectively. Mean plasma leptin levels were significantly higher, whereas mean human soluble leptin receptor numbers were lower in the group with high normal BP compared with the normotensive group (10+/-4.8 v 6+/-2.7 ng/mL, P<.001 and 18+/-7 v 27+/-9 IU/mL, P<.001, respectively). Our findings indicate that normotensive individuals with high normal BP have statistically significantly higher plasma leptin levels and lower numbers of human soluble leptin receptors. This observation may play a important role in the pathogenesis of cardiovascular events in this special group of patients and needs further investigation.


Pathways to medical abortion self-use (MASU): results from a cross-sectional survey of women's experiences in Kenya and Uganda.
In Kenya and Uganda, unsafe abortions are a leading cause of maternal mortality. The new WHO policy guidelines on the safe termination of pregnancies up to 9 weeks lack information on women's experiences with self-administered medical abortion (MA), impeding the development of interventions to increase MA use. This study aimed to comprehend women's experiences with MA in Kenyan and Ugandan pharmacies. A cross-sectional mixed-methods survey utilized data from medical registers in 71 purposefully identified pharmacies and clinics dispensing MA drugs between September and October 2021. Forty women who were MA users participated in focus group discussions. The main outcome variables were: sources of MA information, costs of MA services, complications from MA, pain management, follow-up rates, and use of post-MA contraception. Quantitative data were analyzed using Stata 15, while qualitative thematic analysis was conducted using Dedoose qualitative analysis software. 73.6% of 2,366 women got an MA, both in Kenya (79%) and Uganda (21%). Most (59.1%) were walk-in clients. Kenya had significantly more women referred for MA (49.9%) than Uganda (10.1%) (p 0.05). Friends and family members were the main sources of MA information. The median cost of MA was USD 18 (IQR 10-60.5) in Kenya and USD 4.2 (IQR 2-12) in Uganda. Most MA clients received pain management (89.6%), were followed up (81%), and received post-MA contraception (97.6%). Qualitative results indicated a lack of medicines, high costs of MA, complications, stigma, and inadequate training of providers as barriers to MA use. Communities are a valuable information resource for MA, but only if they have access to the right information. A relatively weak health referral system in Uganda highlights the importance of pharmacies and clinicians collaborating to support clients' abortion needs and contraceptive use after medical abortion (MA). Low client follow-up rates show how important it is to make sure pharmacy technicians know how to give MA correctly. Finally, it is crucial to strengthen the supply chain for MA products in order to eliminate cost barriers to access.


Glutamyl-tRNA synthetases of Bacillus subtilis 168T and of Bacillus stearothermophilus. Cloning and sequencing of the gltX genes and comparison with other aminoacyl-tRNA synthetases.
The glutamyl-tRNA synthetase (GluRS) of Bacillus subtilis 168T aminoacylates with glutamate its homologous tRNA(Glu) and tRNA(Gln) in vivo and Escherichia coli tRNA(1Gln) in vitro (Lapointe, J., Duplain, L., and Proulx, M. (1986) J. Bacteriol. 165, 88-93). The gltX gene encoding this enzyme was cloned and sequenced. It encodes a protein of 483 amino acids with a Mr of 55,671. Alignment of the amino acid sequences of four bacterial GluRSs (from B. subtilis, Bacillus stearothermophilus, E. coli, and Rhizobium meliloti) gives 20% identity and reveals the presence of several short highly conserved motifs in the first two thirds of these proteins. Conserved motifs are found at corresponding positions in several other aminoacyl-tRNA synthetases. The only sequence similarity between the GluRSs of these Bacillus species and the E. coli glutaminyl-tRNA synthetase (GlnRS), which has no counterpart in the E. coli GluRS, is in a segment of 30 amino acids in the last third of these synthetases. In the three-dimensional structure of the E. coli tRNA(Gln).GlnRS.ATP complex, this conserved peptide is near the anticodon of tRNA(Gln) (Rould, M. A., Perona, J. J., Söll, D., and Steitz, T. A. (1989) Science 246, 1135-1142), suggesting that this region is involved in the specific interactions between these enzymes and the anticodon regions of their tRNA substrates.


Imaging of cationic multifunctional liposome-mediated delivery of COX-2 siRNA.
Liposomes are a useful means of delivering molecular targeting agents such as small interfering RNA (siRNA) to downregulate specific pathways important in cancer growth and progression. The ability to non-invasively image these carriers is important to ascertain their delivery within the tumor. As cyclooxygenase-2 (COX-2) is an important therapeutic target in cancer, we investigated loading COX-2-specific siRNA into cationic liposomes containing MR contrast agents for imaging delivery in cancer cells and tumors. COX-2 and GAPDH siRNA, as well as Magnevist or Feridex, were loaded directly into the liposomes. These lipoplexes were used for cell transfection of the poorly differentiated and highly metastatic breast cancer cell line MDA-MB-231. PEGylated liposomes loaded with Feridex and fluorescently labeled COX-2 siRNA were used for in vivo delivery of lipoplexes in MDA-MB-231 breast cancer xenografts in female SCID mice. Transient transfection assays demonstrated potent and specific downregulation of the COX-2 protein in cells in culture. Tail vein injections of PEGylated COX-2 lipoplexes resulted in intratumoral delivery of siRNA. Biodistribution studies showed significant localization in the lung, liver and kidney at 24 h. These data demonstrate the feasibility of liposomal-mediated delivery of COX-2-specific siRNA to downregulate COX-2 in cancer cells, and multi-modality imaging of the delivery of specific siRNA in tumors.


Preoperative combination chemotherapy for advanced stage head and neck cancer. Promising early results.
We treated 19 consecutive patients with cisplatin, bleomycin, and methotrexate before definitive surgery or radiation therapy. Fourteen patients (74 percent) had partial or complete tumor regression after chemotherapy. With a minimum follow-up time of 27 months, none of the 4 patients who had a major histologic response relapsed, and only 2 of the remaining 15 patients continued disease-free. The achievement of a complete histologic response after preoperative chemotherapy may correlate with long-term disease-free survival after surgery and radiation therapy for head and neck cancer.


Modulation of the K+ efflux activity of Bacillus subtilis YhaU by YhaT and the C-terminal region of YhaS.
The cation/proton antiporter 2 (CPA2) family is a large family of cation transporters and putative channel proteins that are found in bacteria, archaea as well as eukaryotes. Consistent with a K+ efflux capacity that is found in several other CPA2 proteins, it is shown here that the YhaU protein of Bacillus subtilis greatly increased the concentration of K+ required for growth of a K+ uptake-defective mutant of Escherichia coli. No YhaU-dependent K+(Na+)/H+ antiport activity was found in membrane vesicles. Two genes, yhaS and yhaT, are located upstream of yhaU and form an apparent operon with it. The YhaS protein has no reported homologues while the YhaT protein has sequence similarity to a sub-domain of KTN proteins that are associated with potassium-translocating channels and transporters. YhaT and the C-terminal region of YhaS were shown to modulate the K+ transport capacities of YhaU in complementation experiments. Expression studies, conducted by monitoring the beta-galactosidase levels in pMutin-disrupted mutants of the yhaU locus, indicated that yhaU is strongly induced by alkaline pH- plus salt-induced stress and that there are additional sodium-specific responses of yhaS and yhaT.


Evidence of zinc superoxide formation in the gas phase: comparisons in behaviour between ligated Zn(I/II) and Cu(I/II) with regard to the attachment of O2 or H2O.
Singly and doubly charged atomic ions of zinc and copper have been complexed with pyridine and held in an ion trap. Complexes involving Zn(II) and Cu(I) (3d(10)) display a strong tendency to bind with H(2)O, whilst the Zn(I) (3d(10)4s(1)) complexes exhibit a strong preference for the attachment of O(2). DFT calculations show that this latter result can be interpreted as internal oxidation leading to the formation of superoxide complexes, [Zn(II)O(2)(-)](pyridine)(n), in the gas phase. The calculations also show that the oxidation of Zn(I) to form Zn(II)O(2)(-) is promoted by a mixing of the occupied 4s and vacant 4p orbitals on the metal cation, and that this process is facilitated by the presence of the pyridine ligands.


Elucidation of quorum sensing components and their role in regulation of symbiotically important traits in Ensifer nodulating pigeon pea.
Quorum sensing (QS) in rhizobia regulates diverse processes determining the success and efficiency of association with the legume host. Despite the notable importance of QS as well as the well-known underlying variability in the genomic and metabolic components thereof, its study in rhizobia is largely restricted to few laboratory strains. In this work, QS phenomenon in the rhizobia nodulating pigeon pea- one of the most important legume crops of the global-south, is characterized. Using 16S rRNA and recombinaseA sequencing analysis, the selected QS-positive and host-beneficial isolates were identified to be taxonomically affiliated to the genus Ensifer. Their QS components, including homologues of QS genes, and the repertoire of N-acyl homoserine lactone (AHL) autoinducers were identified. Sequences of the QS homologues showed significant variabilities ranging from 10 to >20% with the known Ensifer sequences. Autoinducer profiling using LC-MS/MS revealed the production of long and short chain AHLs variably by the isolates, including 3-oxo-C12-homoserine lactone (3-O-C12-HSL) and 3-OH-C16-HSL as their first report in Rhizobiaceae. Motility and attachment- two of the most crucial traits for effective establishment on host roots were discovered to be QS dependent in in vitro analysis and the same was confirmed using expression analysis of their regulatory genes using qRT-PCR; both revealing a QS mediated repression of motility and promotion of attachment. This study highlights that Ensifer nodulating pigeon pea, although with significant variance in the anatomy of their QS components, regulate symbiotically crucial cell-processes via QS in a scheme that is conserved in multiple genera.


Further evaluation of the characteristics of Treponema pallidum-specific IgM antibody in syphilis serofast reaction patients.
Syphilis serofast reaction (SSR) is common in clinical work. From June 2005 to May 2009, 1208 syphilis patients were chosen for research by the Xiamen Center of Clinical Laboratory in China. Serologic tests were performed with toluidine red unheated serum test (TRUST) and Treponema pallidum particle agglutination (TPPA). Then, T. pallidum-specific IgM antibody (TP-IgM) was detected with fluorescent treponemal antibody absorption (FTA-Abs) and TPPA. In this study, patients were divided into the following experimental groups according to the results of TRUST and TPPA: (1) the SSR group consisted of 411 cases with (+) TRUST and (+) TPPA, and without clinical manifestations after 1 year of recommended syphilis treatment; (2) the serum cure group, which was further subdivided into group A consisting of 251cases with (-) TRUST and (+) TPPA; (3) group B consisting of 546 cases with (-) TRUST and (-) TPPA; and (4) the blood donor control group which consisted of 100 cases. We demonstrated that a total of 136 cases (33.09%) of 411 SSR patients were TP-IgM positive by TPPA, and this percentage was markedly higher than that in serum cure group A (9.16%). FTA-Abs analyses revealed similar results. All samples in serum cure group B and the control group were TP-IgM negative, which is identical to our previous report. The present study also indicated that the TP-IgM positive rate was not significantly different among patients with different ages, genders, and clinical phases after 1 year of recommended therapy. From the total of 1208 syphilis patients, 289 were randomly selected for TP-DNA detection by fluorescence quantitative polymerase chain reaction, and the positive rate of TP-DNA was 32.53%, which was slightly higher than that of FTA-Abs TP-IgM, and no statistically significant difference by chi-square tests, indicating the TP-DNA result is preferably consistent with FTA-Abs and supporting our deduction that TP-IgM could be used as a serologic marker for the relapse and infection of syphilis.


Genetic Profiling of Diffuse Large B-Cell Lymphoma: A Comparison Between Double-Expressor Lymphoma and Non-Double-Expressor Lymphoma.
Data are limited regarding the genetic profiling of diffuse large B-cell lymphoma (DLBCL) with double expression of MYC and BCL2 proteins without underlying rearrangements (double-expressor lymphoma [DEL]). This study aimed to describe the genetic profiling and determine the prognostic significance in patients with DEL and in those with non-DEL. Capture-based targeted sequencing was performed on 244 patients with de novo DLBCL, not otherwise specified. Immunohistochemistry staining was performed for evaluating the MYC and BCL2 expression. Among 244 patients, 46 patients had DEL, and 198 had non-DEL. KMT2D, CD58, EP300, PRDM1, TNFAIP3 and BCL2 gain or amplification (BCL2GA/AMP) were significantly more frequently altered in the DEL group. Alterations in the BCR/TLR (p = 0.021), B-cell development and differentiation (p = 0.004), and NF-κB (p = 0.034) pathways occurred more frequently in patients with DEL. Thirty-seven DEL patients and 132 non-DEL patients were included for survival analyses. DEL was not significantly associated with progression-free survival (PFS) (p = 0.60) and overall survival (OS) (p = 0.49). In DEL patients, after adjusting for the International Prognostic Index, BCL2 alteration (HR 2.516, 95% CI 1.027-6.161; p = 0.044) remained an independent predictor of inferior PFS. BCL2GA/AMP also predicted poor PFS, but with marginal statistical significance (HR 2.489, 95% CI 0.995-6.224; p = 0.051). There was difference in profiling of altered genes and signaling pathways between the DEL group and the non-DEL group. The presence of DEL alone should not be considered as an adverse prognostic indicator, and BCL2 alteration could define a subset of patients with poor prognosis within DEL.


The effects of probiotic administration on patients with prediabetes: a meta-analysis and systematic review.
This paper aimed to examine the effects of probiotics on eight factors in the prediabetic population by meta-analysis, namely, fasting blood glucose (FBG), glycated haemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and the mechanisms of action are summarized from the existing studies. Seven databases (PubMed, Web of Science, Embase, Cochrane Library, SinoMed, CNKI, and Wanfang Med) were searched until March 2022. Review Manager 5.4 was used for meta-analysis. The data were analysed using weighted mean differences (WMDs) or standardized mean differences (SMDs) under a fixed effect model to observe the efficacy of probiotic supplementation on the included indicators. Seven publications with a total of 460 patients were included. According to the meta-analysis, probiotics were able to significantly decrease the levels of HbA1c (WMD, -0.07; 95% CI -0.11, -0.03; P = 0.001), QUICKI (WMD, 0.01; 95% CI 0.00, 0.02; P = 0.04), TC (SMD, -0.28; 95% CI -0.53, -0.22; P = 0.03), TG (SMD, -0.26; 95% CI -0.52, -0.01; P = 0.04), and LDL-C (WMD, -8.94; 95% CI -14.91, -2.97; P = 0.003) compared to levels in the placebo group. The effects on FBG (WMD, -0.53; 95% CI -2.31, 1.25; P = 0.56), HOMA-IR (WMD, -0.21; 95% CI -0.45, 0.04; P = 0.10), and HDL-C (WMD, 2.05; 95% CI -0.28, 4.38; P = 0.08) were not different from those of the placebo group. The present study clearly indicated that probiotics may fulfil an important role in the regulation of HbA1c, QUICKI, TC, TG and LDL-C in patients with prediabetes. In addition, based on existing studies, we concluded that probiotics may regulate blood glucose homeostasis in a variety of ways. This meta-analysis has been registered at PROSPERO with ID: CRD42022321995.


Role of adipose tissue in determining muscle mass in patients with chronic kidney disease.
Malnutrition is a powerful predictor of mortality in chronic kidney disease (CKD). However, its etiology is unclear. We hypothesized that the adipocyte-derived proteins leptin and adiponectin, inflammation (as measured by C-reactive protein, CRP), and insulin resistance (as measured by homeostasis model assessment, HOMA), implicated in the malnutrition-inflammation complex syndrome commonly seen in maintenance dialysis patients, would be associated with the loss of muscle mass in earlier stages of CKD. Arm muscle area was used as an indicator of muscle mass. The Modification of Diet in Renal Disease Study cohort of people with CKD stages 3 and 4 was used for analysis (N = 780). Regression models were carried out to examine the relationships of leptin, adiponectin, CRP, and HOMA with arm muscle area (the main study outcome). Arm muscle area was 39 +/- 15 cm(2) (mean +/- SD), and adiponectin levels were 13 +/- 7 microg/mL. Median and interquartile range (IQR) concentrations were: 9.0 (13.6) ng/mL for leptin, 2.3 (4.9) mg/L for CRP, and 2.4 (2.0) for HOMA. Higher leptin (beta coefficient and 95% confidence interval, -6.9 [-8.7 to -5.1], P < .001) and higher CRP (beta coefficient and 95% confidence interval, -2.7 [-3.9 to -1.4], P < .001) were associated with lower arm muscle area. There was a trend toward lower arm muscle area with higher adiponectin (P = .07), but no association with HOMA (P = .80). Leptin and CRP were associated with lower muscle mass in subjects with CKD at stages 3 and 4. Further studies are needed to understand the mechanisms underlying these associations, and to develop targeted interventions for this patient population.


A Missed Opportunity: The Impact of Hepatitis C Treatment Prior to Total Knee Arthroplasty on Postoperative Complications.
Hepatitis C (HCV) is undertreated and increasing in prevalence. Its influence on outcomes following total knee arthroplasty (TKA) remains unclear. The purpose of this study is to examine the impact of HCV and prearthroplasty antiviral treatment on postoperative complications following TKA. A retrospective matched cohort study was conducted using an administrative claims database to compare postoperative complication rates following TKA for (1) patients with vs without HCV and (2) among patients with HCV, patients with antiviral treatment before TKA vs no treatment. In total, 6971 patients with HCV were matched 1:4 with 27,884 controls without HCV, and 708 HCV patients with antiviral treatment before TKA were matched 1:2 with 1416 HCV patients without treatment. Rates of joint complications at 1 and 2 years postoperatively were compared via multivariable logistic regression. The HCV cohort exhibited significantly higher risk of prosthetic joint infection (PJI) than controls at both 1 (4.1 vs 2.1%; odds ratio [OR] 1.58) and 2 years (5.0% vs 2.7%; OR 1.55) postoperatively. Rates of revision TKA were also significantly higher for HCV patients at 1 (2.8% vs 1.8%; OR 1.40) and 2 years (4.1% vs 2.9%; OR 1.30). HCV patients with prearthroplasty antiviral treatment exhibited significantly lower risk of PJI at 1 (2.1% vs 4.1%; OR 0.50) and 2 years (2.7% vs 5.1%, OR 0.51) compared to patients without treatment. Patients with HCV have significantly increased risk of PJI and revision arthroplasty following TKA. Antiviral treatment before TKA significantly decreases the risk of PJI postoperatively. Level III.


The effect of calcium hydroxide on the steroid component of Ledermix and Odontopaste.
To investigate the chemical interaction of calcium hydroxide with the corticosteroid triamcinolone acetonide in Ledermix Paste and in Odontopaste, a new steroid/antibiotic paste. Validated methods were developed to analyse the interaction of calcium hydroxide in two forms, Pulpdent Paste and calcium hydroxide powder, with triamcinolone acetonide within Odontopaste and Ledermix Paste. High-performance liquid chromatography (HPLC) was used to analyse the mixed samples of the pastes and calcium hydroxide. The concentration of triamcinolone acetonide within the pastes was determined over 0, 2, 6, 24 and 72-h time-points. All tests with the HPLC involved the testing of the standard with triplicate injections alongside the samples. All samples were tested in duplicate with each injected twice; therefore, four tests were performed for each investigation. Linearity, precision and specificity of the testing procedures and apparatus were validated. Descriptive statistics are provided. In both pastes, there was a marked rapid destruction of the triamcinolone acetonide steroid upon mixing with calcium hydroxide. Odontopaste suffered a lower rate of destruction of the triamcinolone acetonide component than Ledermix Paste, but both pastes showed very similar degrees of steroid destruction after 72 h. When using calcium hydroxide powder with Ledermix Paste, the triamcinolone was destroyed entirely and immediately. The addition of calcium hydroxide to Odontopaste or Ledermix Paste results in the rapid destruction of the steroid.


Biosynthesis of aphid alarm pheromone is modulated in response to starvation stress under regulation by the insulin, glycolysis and isoprenoid pathways.
The mechanism for biosynthesis and molecular regulation of the aphid alarm pheromone (AAP) is still a mystery. Previous studies indicated that the biosynthesis of AAP was directly affected by the terpenoid backbone biosynthesis pathway, and several pathways involved in nutritional metabolism providing the bricks for AAP biosynthesis were up-regulated in response to simulated stimulation. This suggests that AAP biosynthesis might be regulated by complex metabolic pathways. Here the molecular responses of the bird cherry-oat aphid Rhopalosiphum padi to starvation stress were investigated, and the molecular pathways were further analyzed by using RNA interference (RNAi) and protein inhibitor, combined with gas chromatography-mass spectrometry analysis of (E)-β-farnesene (EβF), the major component of the alarm pheromone in R. padi. The results showed that the nutritional stress significantly reduced the weight of aphid and the quantity of EβF, and meanwhile dramatically up-regulated the insulin receptor genes (InsR1/2) and down-regulated the downstream genes encoding the kinases PI3K and Akt, key enzymes in the glycolysis pathway (HK, A6PFK, PK) and the isoprenoid pathway (ACSS, HMGR, FPPS1, FPPS2, GGPPS, DPPS). PI3K inhibitor LY294002 treatment and RNAi-mediated knockdown of InsR1/2 significantly reduced the expression level of downstream genes and the quantity of EβF. Furthermore, knockdown of PK, the rate-limiting enzyme in the glycolysis pathway, down-regulated the genes in the isoprenoid pathway and the production of EβF; knockdown of the genes encoding isoprenyl diphosphate enzymes revealed that FPPS1 and FPPS2 were both required for EβF biosynthesis. Our data suggested that AAP is synthesized via glycolysis and isoprenoid pathways under regulation by the insulin signaling pathway.


Species-specific action of (Pro3)GIP - a full agonist at human GIP receptors, but a partial agonist and competitive antagonist at rat and mouse GIP receptors.
Specific, high potency receptor antagonists are valuable tools when evaluating animal and human physiology. Within the glucose-dependent, insulinotropic polypeptide (GIP) system, considerable attention has been given to the presumed GIP receptor antagonist, (Pro3)GIP, and its effect in murine studies. We conducted a pharmacological analysis of this ligand including interspecies differences between the rodent and human GIP system. Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation and assayed in competition binding using (125) I-human GIP. Using isolated perfused pancreata both from wild type and GIP receptor-deficient rodents, insulin-releasing, glucagon-releasing and somatostatin-releasing properties in response to species-specific GIP and (Pro3)GIP analogues were evaluated. Human (Pro3)GIP is a full agonist at human GIP receptors with similar efficacy (Emax ) for cAMP production as human GIP, while both rat and mouse(Pro3)GIP were partial agonists on their corresponding receptors. Rodent GIPs are more potent and efficacious at their receptors than human GIP. In perfused pancreata in the presence of 7 mM glucose, both rodent (Pro3)GIP analogues induced modest insulin, glucagon and somatostatin secretion, corresponding to the partial agonist activities observed in cAMP production. When evaluating new compounds, it is important to consider interspecies differences both at the receptor and ligand level. Thus, in rodent models, human GIP is a comparatively weak partial agonist. Human (Pro3)GIP was not an antagonist at human GIP receptors, so there is still a need for a potent antagonist in order to elucidate the physiology of human GIP.


Effects of 1-epinephrine on hemodynamics and cardiac function in coronary disease: dose-response studies.
To assess the effects of elevated epinephrine levels on cardiovascular performance in patients with coronary artery disease (CAD), epinephrine was infused intravenously into eight patients with normal coronary anatomy and 22 patients with CAD at dose rates of 0.06, 0.12, 0.18, and 0.24 micrograms/kg/min. Hemodynamic responses to epinephrine were not significantly different between the two groups. However, contractility increased significantly more (P less than 0.05) and end-systolic volume decreased significantly more (P less than 0.025) in normal subjects than in those with CAD. Plasma norepinephrine concentrations increased significantly (P less than 0.05) at 0.24 micrograms/kg/min epinephrine, indicating activation of sympathetic nervous system. Epinephrine ischemic thresholds ranged from 652 to 3362 pg/ml. Patients with CAD compared with normal subjects had more frequent ventricular arrhythmias (55% vs. 25%), chest pain (50% vs. 13%), and ischemic ECG changes (73% vs. 13%). These results indicate that although epinephrine induced myocardial ischemia in CAD, hemodynamics and ventricular pump function were maintained.


Antimicrobial activity of Eupatorium ayapana.
Petroleum ether and methanolic extracts of leaves of Eupatorium ayapana were tested for their antimicrobial activity. The petroleum ether extract showed higher antibacterial and antifungal activity than the methanolic extract.


[Age features of the allergens in allergic rhinitis patients of different age in Hubei area].
To investigate the distribution of positive allergens in patients with allergic rhinitis and the discrepancy among different age group. Skin prick tests were done to 2 808 allergic rhinitis patients, the major allergens of local area were tested with standard allergens. Data was analyzed with age and allergens. Dermatophagoides pteronyssinus and dermatophagoides farinae had the highest positivity among all allergens (91.03%, 86.47%). Other important allergens were cockroach (19.55%), ragweed (15.63%) and mugwort (14.13%) subsequently. The distribution of major allergens was variable among different age group. The positivity of mold mixture I was much higher in 3-9 years old group than other age group. Positive percentage of ragweed and mugwort allergens were increased with age growing. Positive ratio of cockroach which was higher in the elder than that in the younger, was highest in 30-39 years old group. Ratio in patients with single allergen positive decreased with age growing. House dust mite was the most important allergen of the local area, the distribution of positive allergens was variable in different age group.


Andreev reflection at high magnetic fields: evidence for electron and hole transport in edge states.
We have studied magnetotransport in arrays of niobium filled grooves in an InAs/Al(x)Ga(1-x)Sb heterostructure. The critical field of up to 2.6 T permits one to enter the quantum Hall regime. In the superconducting state, we observe strong magnetoresistance oscillations, whose amplitude exceeds the Shubnikov-de Haas oscillations by a factor of about 2, when normalized to the background. Additionally, we find that above a geometry-dependent magnetic field value the sample in the superconducting state has a higher longitudinal resistance than in the normal state. Both observations can be explained with edge channels populated with electrons and Andreev-reflected holes.


Erratum to "Ketamine Administration Reverses Corticosterone-Induced Alterations in Excitatory and Inhibitory Transmission in the Rat Dorsal Raphe Nucleus".
[This corrects the article DOI: 10.1155/2019/3219490.].


The cardiovascular effects of high-dose butorphanol-nitrous oxide anaesthesia before and during operation.
The cardiovascular effects of high doses of butorphanol (0.3-0.45 mg . kg-1) plus 60 per cent N2O anaesthesia were measured at unconsciousness, following tracheal intubation, and immediately before and at one and ten minutes after surgical stimulation in 17 A.S.A. class I and II patients undergoing elective gastric or gall bladder surgery. Butorphanol and N2O produced unconsciousness with only small decreases in heart rate and cardiac output but did not result in sufficient analgesia to block or treat stimulation of the cardiovascular system secondary to tracheal intubation or surgical incision, even when supplemented with additional butorphanol to high cumulative dose levels (1.0 mg . kg-1). The data suggest that even high dose butorphanol - N2O anaesthesia requires supplementation with other anaesthetics or anaesthetic adjuvants to prevent cardiovascular stimulation during general abdominal surgery.


Function of neutral endopeptidase on the cell membrane of human neutrophils.
Intact human neutrophils hydrolyzed N-formyl-Met-Leu-[3H]Phe (fMLP) and released Leu-[3H]Phe, cleaving 45-50% of the peptide within 20 min at 37 degrees C. The dipeptide after its release was then hydrolyzed to free amino acids by a dipeptidase (EC 126.96.36.199). This activity, present in plasma membrane-enriched fractions of neutrophil lysates, was also inhibited over 90% by phosphoramidon, an inhibitor of neutral endopeptidase (NEP, EC 22.214.171.124). Dithiothreitol and EDTA inhibited the activity to a comparable degree, suggesting the requirement for a heavy metal cofactor. Bestatin and amastatin, inhibitors of aminopeptidases (but not human kidney NEP), did not inhibit the rate of fMLP degradation but prevented the production of free phenylalanine and enhanced the accumulation of Leu-Phe. Of other inhibitors, alpha 1-antitrypsin and alpha 2-macroglobulin slightly enhanced the rate of fMLP hydrolysis by neutrophils, and others tested were ineffective. Rabbit antiserum to homogeneous human kidney NEP reacted specifically with a 100-kDa protein present in sodium dodecyl sulfate-solubilized neutrophils. The Mr of this protein was slightly larger than that of the kidney enzyme in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The antiserum incubated with intact cells specifically inhibited the degradation of fMLP over 70%. First, we confirm that NEP present on the plasma membrane cleaves fMLP at the Met-Leu bond; then the dipeptide Leu-Phe is cleaved by a dipeptidase. Finally, inhibition of NEP completely blocks fMLP-mediated chemotaxis. Thus, the enzyme may play an important role in modulating chemotactic responses.


Nitrogen Systemic Signaling: From Symbiotic Nodulation to Root Acquisition.
Plant nutrient acquisition is tightly regulated by resource availability and metabolic needs, implying the existence of communication between roots and shoots to ensure their integration at the whole-plant level. Here, we focus on systemic signaling pathways controlling nitrogen (N) nutrition, achieved both by the root import of mineral N and, in legume plants, through atmospheric N fixation by symbiotic bacteria inside dedicated root nodules. We explore features conserved between systemic pathways repressing or enhancing symbiotic N fixation and the regulation of mineral N acquisition by roots, as well as their integration with other environmental factors, such as phosphate, light, and CO2 availability.


A cephalometric study of fetal alcohol syndrome.
Analysis of cephalometric radiographs of 12 children with fetal alcohol syndrome corroborated the clinical observation of midfacial deficiency described in patients with this disorder. Contrary to previous reports, however, our data show that this abnormality is not caused by true maxillary hypoplasia but by retrusion of the maxilla. We postulate that this abnormal position is secondary to restricted forward growth of the face, resulting from abnormal brain growth and subsequent shortening of the anterior cranial base.


Routine circumcision practice in Western Australia 1981-1999.
Routine neonatal circumcision has declined in most English-speaking countries. The purpose of the present study was to investigate the trends in incidence of routine circumcision in Western Australia and current patterns of the procedure according to sociodemographic factors. Hospital morbidity data were used to conduct a population-based study of all circumcisions performed in Western -Australian hospitals during 1981-1999. Medicare insurance rebate statistics were used to estimate the numbers of circumcisions performed outside of hospital on boys <6 months of age between 1994 and 1999. In 1994, 9.8% of boys were circumcised before reaching 6 months of age, falling to 7.9% by 1999. Boys <6 months of age were 3.3 times more likely to undergo a hospital-performed circumcision if they lived in country areas compared with metropolitan Perth. Middle socioeconomic class families were twice as likely to circumcise a son than those in the higher and lower socioeconomic groups. The decreasing circumcision rate in boys <6 months of age was partly offset by an increase in routine circumcisions in boys older than 6 months of age during 1981-1999. Circumcision remains a relatively common procedure in Western Australia. Based on total routine circumcision rates in 1999, 10.2% of boys will be circumcised by the time they reach 15 years of age. The routine circumcision rate in boys <6 months is falling in contrast to a rising routine circumcision rate in older boys. Risk factors for a circumcision before 6 months of age include living in country areas and a middle socioeconomic status.


Effect of deviant probability and interstimulus/interdeviant interval on the auditory N1 and mismatch negativity in the cat auditory cortex.
In passive oddball paradigm the effects of changes in interstimulus/interdeviant interval (ISI; IDI) and deviant probability were investigated on mismatch negativity (MMN), auditory N1 wave and the exogenous P1 component of the auditory event-related potential in the cat. An epidural electrode matrix was chronically implanted over the auditory fields of the neocortex, and the amplitudes of the aforementioned components were measured in the location of their amplitude maxima. Dependence of the MMN both on the ISI and IDI as well as deviant probability was revealed, while the amplitude of the P1 and N1 showed dependence merely on the ISI. This method can be used for separation of the two negative, often overlapping components in the cat.


Mechanisms of flame retardant tris (2-ethylhexyl) phosphate biodegradation via novel bacterial strain Ochrobactrum tritici WX3-8.
Tris (2-ethylhexyl) phosphate (TEHP) is a common organophosphorus flame retardant analog with considerable ecological toxicity. Here, novel strain Ochrobactrum tritici WX3-8 capable of degrading TEHP as the sole C source was isolated. Our results show that the strain's TEHP degradation efficiency reached 75% after 104 h under optimal conditions, i.e., 30 °C, pH 7, bacterial inoculum 3%, and<initial concentration 100 mg L-1. The biodegradation efficiency of cell and intracellular enzymes were 75-76%. A consistent degradation trend was observed, with the cellular surface hydrophobicity being increased from 21 to 58% after 24 h while the biodegradation efficiency being increased from 29 to 59% after 20 h. The data indicate that TEHP increased the cell surface for better biosorption to enter the cell more easily, which was decomposed via intracellular enzymes. Furthermore, the membrane permeability increased with time from 1.22 to 1.39 during 104 h degradation, supporting that TEHP changed the surface structure of cells to promote entry into cells for degradation. Further metabolic pathway analysis revealed the possible TEHP biodegradation metabolic pathway as: tri (2-ethylhexyl) phosphate → di (2-ethylhexyl) phosphate → mono (2-ethylhexyl) phosphate → phosphoric acid and generated 2-ethylhexanol. Results showed that TEHP was transformed by O-dealkylation. This research suggests the viability of using novel strain WX3-8 for TEHP as a cost-effective and environmentally-friendly strategy for bioremediation applications of TEHP in the environment.


Hemoglobin-based blood substitutes: characterization of five pyridoxal 5'-phosphate derivatives of hemoglobin.
Six fractions (I-VI) of pyridoxal 5'-phosphate (PLP) hemoglobin (Hb), prepared by the method of De Venuto and Zegna [J. Surg. Res., 34 (1983) 205] have been isolated and purified by anion-exchange high-performance liquid chromatography (HPLC). Total phosphate analyses indicate that I is HbA, II and III are double-labelled, IV and V are tetra-labelled and VI contains 6 mol of phosphorus per mol of hemoglobin. The purified components have been resolved into their alpha and beta chains by preparative reversed-phase HPLC using a macroporous C4 support. Phosphate analyses indicate that the beta chains of II, III and IV each contain one phosphate per chain while the beta chains of V and VI each contain two phosphates. The alpha chains of IV and VI were found to be monophosphate-labelled. Reversed phase HPLC analysis of the tryptic peptides of the beta chains indicates that the label is bound exclusively to the 1-valine residue in II, III and IV while both the 1-valine and the 82-lysine are labelled in V and VI. Similarly, modification of the 1-valine residue of the alpha chains of IV and VI was detected. Components II and III have the same molecular formula. Evidence is presented which shows that they are interconvertible and that they correspond to the PLP2-Hb species and component V is Benesch's PLP4-Hb [J. Biol. Chem., 257 (1983) 1320 and references cited therein]. Component IV is III with one additional PLP per alpha chain and similarly VI is V with monolabelled alpha chains.(ABSTRACT TRUNCATED AT 250 WORDS)


Review of outcomes of neonatal screening for cystic fibrosis versus non-screening in Europe.
We reviewed the published results of European prospective cohort and controlled studies and 1 randomized controlled study to assess whether newborn screening (NBS) for cystic fibrosis (CF) leads to an improved prognosis. We used long-term survival, early mortality, nutritional and pulmonary status, and the number of hospital admissions as outcome measures. Effects on reproductive behavior of the parents and relatives were also assessed. In 2 studies, a similar trend for improved long-term survival rate of the screened cohort was observed, whereas in 2 other studies CF NBS appeared to prevent CF-related deaths in infancy and early childhood. Screened patients born in the last 2 decades showed normal growth for height and weight from infancy until late childhood. In most studies, patients who were screened were found to have less lung damage than their non-screened peers. CF NBS significantly reduced the number of affected children who ever required hospitalization. In Brittany, France, a reduction of 15.7% in CF prevalence at birth was attributed to the introduction of a NBS program for CF. We conclude that there is accumulating evidence that CF NBS prevents early CF-related deaths and leads to a substantial and prolonged health gain for patients with CF.


Evaluation of vaccines designed to induce protective cellular immunity against the Plasmodium yoelii circumsporozoite protein: vaccinia, pseudorabies, and Salmonella transformed with circumsporozoite gene.
In an attempt to induce a protective cytotoxic T-cell mediated immunity against sporozoites of Plasmodium yoelii, the gene encoding the P. yoelii circumsporozoite (CS) protein was engineered into three live vectors: vaccinia, attenuated pseudorabies, and attenuated Salmonella typhimurium. Balb/c mice were immunized with 1-4 doses of 10(8) pfu of the vaccinia construct (IP), 3 doses of 10(5), 10(6) or 10(7) pfu of pseudorabies construct (IV), and 3 doses of 10(9) salmonella transformants (orally). In the case of vaccinia and pseudorabies constructs, an excellent immune response was obtained as measured by antibodies to sporozoites. No protection or delay in prepatent period was seen in any of the experimental animals when challenged with 200 (vaccinia, pseudorabies) or 100 (salmonella) sporozoites, although mice immunized with irradiation-attenuated sporozoites were consistently protected against challenge with greater than 10(4) sporozoites. Since other vaccinia, pseudorabies, and salmonella CS constructs have been shown to induce cytotoxic T lymphocytes (CTL) against the CS protein, it is likely that CTL against the CS protein were induced during these studies. It is currently unclear if the vaccines did not induce the appropriate CTL or inadequate numbers of CTL, or if CTL against the P. yoelii CS protein are inadequate to protect against sporozoite challenge.


Substance P alterations in skin and brain of chronically stressed atopic-like mice.
Stress is known to worsen the symptoms of atopic eczema (AE). Substance P is likely to play an important role in the development and pathogenesis of AE. To examine a possible connection between chronic mild stress and changes in the expression of substance P and its receptor (R) neurokinin (NK) 1 in the skin and stress-related brain regions in NC/Nga atopic-like mice. The mice were divided into three groups (eight animals per group): SE (stressed eczematous), NSE (non-stressed eczematous) and SC (stressed control). Ears and brains of the mice were investigated using immunohistochemistry and RT-PCR. In the skin, there was a decrease in the number of substance P immunoreactive nerve fibres in SE compared with SC group. RT-PCR showed a strong tendency to an increase in mRNA for NK1R in the skin of SE compared with NSE mice. There was an increase in the number of mast cells and the degree of their degranulation in the SE compared with both other groups. A decrease in substance P immunoreactivity in medial hippocampus was found in SE compared with NSE animals. In prefrontal cortex and central amygdala, there were no significant differences in substance P immunoreactivity between the three groups. Exposure to chronic mild stress in NC/Nga atopic-like mice may result in altered expression patterns of substance P in the skin and hippocampus.


Muscarinic receptor subtypes: modulation of ion channels.
The discovery of five muscarinic receptor subtypes by molecular genetic techniques has resulted in new approaches to understanding their function. This involves the expression of the individual genes encoding each receptor subtype in isolation, such that their effects and mechanisms of action can be studied. The coupling of the receptors with G-proteins and ion channels is the subject of this review and emphasis is placed upon the assignment of genetically defined receptor subtypes with a given physiological function. Activation of inwardly rectifying potassium conductances by m2 and m4 and inhibition by m1, as well as stimulation of calcium-dependent conductances by m1, m3 and m5 are discussed.


The use of stable isotopes in metabolic investigation.
The use of tracers to define substrate dynamics has been the sine qua non of metabolic investigation in vivo, because static measurements of substrate content alone are inadequate. The judicious use of radioactively labelled compounds remains the principal tracer approach in some adult subjects. However, in certain young adults, in pregnant women and in children, stable isotope tracers offer a practical alternative for answering important metabolic questions. In the last decade, the developmental problems previously associated with employing stable isotope tracers for this purpose have largely disappeared. Furthermore, the use of stable isotopically labelled materials offers certain additional advantages which are either difficult or impossible to achieve using radiotracers. These include the ability to measure simultaneously substrate content and isotopic enrichment with very high specificity and precision, the ability to determine the intramolecular location of the label, the ability to use the mass of the stable isotope substrate as a probe of the metabolite system response to perturbation, and the ability to study simultaneously and repeatedly the same subject with multiple substrate tracers. The practical application of these principles has been amply demonstrated by the expanding use of non-radioactive tracers to study body composition, energy balance, and the inter-organ transport and oxidation of the three major metabolic fuels--glucose, fat and amino acids. Continued development in the organic synthesis of new, stable isotopically labelled biochemicals will allow investigation of additional areas of biomedical importance which have been hitherto inaccessible to this approach, particularly in the pathophysiology of metabolic events in the growing child.


The importance of atrial fibrillation and selected echocardiographic parameters for the effectiveness and safety of thrombolytic therapy in patients with stroke.
The efficacy and safety of thrombolytic therapy in stroke depend on multiple factors. The aim of this study was to evaluate the significance of atrial fibrillation the prognosis in terms of the functional status in patients with stroke treated with intravenous thrombolysis. An additional aim was also to assess the potential significance of reduced ejection fraction (EF) and enlarged left atrium (LA) of the heart for the prognosis in patients with stroke who underwent thrombolytic therapy. A prospective study involved enrollment of 222 patients, mean age of 72 years with first-in-life ischemic stroke. In all participants there were realized procedures as follows: neurological status before administering rt-PA (NIHSS), selected echocardiographic parameters, functional status on the 14th day from the onset (mRankin scale) and analysis the bleeding events. Atrial fibrillation was significantly more frequent in women than men; females had higher CHA2DS2VASc scores and heavier neurological conditions on day 1 of stroke. Two independent factors for poor prognosis (3-5 points by mRankin) were found: the NIHSS score and the CHA2DS2VASc score ≥3. We identified 2 independent factors for death within 14 days from the onset: the result by NIHSS and the EF. The NIHSS score turned out to be the only independent predictor of hemorrhage during hospitalization: RR 1.19; CI [1.06-1.33]; p=0.003; p for model=0.0025. The presence of atrial fibrillation worsens the patient's prognosis in terms of the functional status and survival during the acute period of stroke in patients treated with intravenous thrombolysis. Higher NIHSS and CHA2DS2VASc scores and reduced EF in patients with stroke treated with thrombolysis are the predictors of unfavorable short-term prognosis.


Antipsychotic medication prescribing trends in children and adolescents.
The Food and Drug Administration has approved the use of antipsychotic medications in some children and adolescents with severe emotional and behavioral disorders. However, recent national data show a dramatic rise in off-label and Food and Drug Administration-approved uses of these medications. Of particular note is a twofold to fivefold increase in the use of antipsychotic medications in preschool children, despite little information on their long-term effects. This article describes the trend in pediatric antipsychotic medication use, possible explanations for the increase, implications for children's health, and recommendations for pediatric providers who work with parents of children and adolescents who seek or receive antipsychotic medication treatments.


Towards a humanized PPARγ reporter system for in vivo screening of obesogens.
Overeating and lack of exercise are major contributors to the current obesity epidemic, but environmental contaminants, or obesogens, are also considered to be potential actors. A common obesogen target is the Peroxisome Proliferator Activated Receptor Gamma (PPARγ). Screening for exogenous obesogens requires in vivo systems as many xenobiotics exert their effects through metabolites. We thus developed a humanized in vivo PPARγ reporter model, using Xenopus laevis larvae, a species possessing metabolic capacities comparable to mammals. A somatic transgenesis approach was used to co-express an expression vector for the human PPARγ protein simultaneously with one of a series of reporter vectors, each containing a PPARγ Response Element (PPRE)-eGFP sequence. Treatment of tadpoles with PPARγ agonists, antagonists or candidate obesogens, significantly modulated eGFP expression. Thus, the system provides a promising proof of principle for a sensitive and reliable humanized in vivo tool to screen both novel PPARγ drug ligands and potential endocrine disruptors or obesogens targeting this receptor.


Structural characterization of bioactive pectic polysaccharides from elderflowers (Sambuci flos).
Elderflowers have traditionally been used and are still used for its anti-inflammatory property. Traditionally elderflowers were used as remedies against cold, flu and diuretic. The aim of this study was to relate the structure of pectic-polysaccharides from elderflowers to immunomodulating properties. Purified fractions obtained by gelfiltration and ion exchange chromatography of 50% ethanol, 50°C water and 100°C water extracts exhibited strong complement fixating activity and macrophage stimulating activity. Reduced bioactivity was observed after removal of arabinose and 1,3,6-Gal linkages by weak acid hydrolysis. Enhanced bioactivity was observed after removal of estergroups by NaOH. Relating linkage analysis to the results of the bioactivity tests, led to the assumption that the branched moieties of the arabinogalactans linked to rhamnogalacturonan region, is important for the immunomodulating activity seen in elderflowers. No cytotoxity was observed.


Effects of albendazole combined with TSII-A (a Chinese herb compound) on optic neuritis caused by Angiostrongylus cantonensis in BALB/c mice.
Angiostrongylus cantonensis (A. cantonensis) infection can lead to optic neuritis, retinal inflammation, damage to ganglion cells, demyelination of optic nerve and visual impairment. Combined therapy of albendazole and dexamethasone is a common treatment for the disease in the clinic, but it plays no role in vision recovery. Therefore, it has been necessary to explore alternative therapies to treat this disease. Previous studies reported the neuro-productive effects of two constituents of Danshen (a Chinese herb)-tanshinone II-A (TSII-A) and cryptotanshinone (CPT), and this study aims to evaluate the impacts of TSII-A or CPT combined with albendazole on optic neuritis caused by A. cantonensis infection in a murine model. To assess the effects of TSII-A or CPT combined with albendazole on optic neuritis due to the infection, mice were divided into six groups, including the normal control group, infection group and four treatment groups (albendazole group, albendazole combined with dexamethasone group, albendazole combined with CPT group and albendazole combined with TSII-A group). The infection group and treatment groups were infected with A. cantonensis and the treatment groups received interventions from 14 dpi (days post infection), respectively. At 21 dpi, the visual acuity of mice in each group was examined by visual evoked potential (VEP). The pathologic alteration of the retina and optic nerve were observed by hematoxylin and eosin (H&E) staining and transmission electronic microscopy (TEM). Infection of A. cantonensis caused prolonged VEP latency, obvious inflammatory cell infiltration in the retina, damaged retinal ganglions and retinal swelling, followed by optic nerve fibre demyelination and a decreasing number of axons at 21 dpi. In treatment groups, albendazole could not alleviate the above symptoms; albendazole combined with dexamethasone lessened the inflammation of the retina, but was futile for the other changes; however, albendazole combined with CPT and albendazole combined with TSII-A showed obvious effects on the recovery of prolonged VEP latency, destruction and reduction of ganglion cells, optic nerve demyelination and axon loss. Compared with albendazole-CPT compound, albendazole combined with TSII-A was more effective. The current study demonstrates that albendazole combined with TSII-A plays a more effective role in treating optic neuritis caused by A. cantonensis in mice than with dexamethasone, as applied in conventional treatment, indicating that albendazole combined with TSII-A might be an alternate therapy for this parasitic disease in the clinic.


Natural Course of Cerebral Cavernous Malformations in Children: A Five-Year Follow-Up Study.
The purpose of this study was to investigate the natural course of cerebral cavernous malformations (CCM) in the pediatric population, with special emphasis on the risk of first and recurrent bleeding over a 5-year period. Our institutional database was screened for patients with CCM treated between 2003 and 2020. Patients ≤18 years of age with complete magnetic resonance imaging data set, clinical baseline characteristics, and ≥1 follow-up examination were included. Surgically treated individuals were censored after CCM removal. We assessed the impact of various parameters on first or recurrent intracerebral hemorrhage (ICH) at diagnosis using univariate and multivariate logistic regression adjusted for age and sex. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for (re)hemorrhage. One hundred twenty-nine pediatric patients with CCM were analyzed. Univariate logistic regression identified brain stem CCM (odds ratio, 3.15 [95% CI, 1.15-8.63]; P=0.026) and familial history of CCM (odds ratio, 2.47 [95% CI, 1.04-5.86]; P=0.041) as statistically significant predictors of ICH at diagnosis. Multivariate logistic regression confirmed this correlation (odds ratio, 3.62 [95% CI, 1.18-8.99]; P=0.022 and odds ratio, 2.53 [95% CI, 1.07-5.98]; P=0.035, respectively). Cox regression analysis identified ICH as mode of presentation (hazard ratio, 14.01 [95% CI, 1.80-110.39]; P=0.012) as an independent predictor for rehemorrhage during the 5-year follow-up. The cumulative 5-year risk of (re)bleeding was 15.9% (95% CI, 10.2%-23.6%) for the entire cohort, 30.2% (20.2%-42.3%) for pediatric patients with ICH at diagnosis, and 29.5% (95% CI, 13.9%-51.1%) for children with brain stem CCM. Pediatric patients with brain stem CCM and familial history of CCM have a higher risk of ICH as mode of presentation. During untreated 5-year follow-up, they revealed a similar risk of (re)hemorrhage compared to adult patients. The probability of (re)bleeding increases over time, especially in cases with ICH at presentation or brain stem localization.


Structural basis for the EBA-175 erythrocyte invasion pathway of the malaria parasite Plasmodium falciparum.
Erythrocyte binding antigen 175 (EBA-175) is a P. falciparum protein that binds the major glycoprotein found on human erythrocytes, glycophorin A, during invasion. Here we present the crystal structure of the erythrocyte binding domain of EBA-175, RII, which has been established as a vaccine candidate. Binding sites for the heavily sialylated receptor glycophorin A are proposed based on a complex of RII with a glycan that contains the essential components required for binding. The dimeric organization of RII displays two prominent channels that contain four of the six observed glycan binding sites. Each monomer consists of two Duffy binding-like (DBL) domains (F1 and F2). F2 more prominently lines the channels and makes the majority of the glycan contacts, underscoring its role in cytoadherence and in antigenic variation in malaria. Our studies provide insight into the mechanism of erythrocyte invasion by the malaria parasite and aid in rational drug design and vaccines.


The benefits of sacubitril-valsartan in patients with acute myocardial infarction: a systematic review and meta-analysis.
We aimed to investigate whether sacubitril-valsartan could further improve the prognosis, cardiac function, and left ventricular (LV) remodelling in patients following acute myocardial infarction (AMI). We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) from inception to 10 May 2021 to identify potential articles. Randomized controlled trials (RCTs) meeting the inclusion criteria were included and analysed. Thirteen RCTs, covering 1358 patients, were analysed. Compared with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), sacubitril-valsartan did not significantly reduced the cardiovascular mortality [risk ratio (RR) 0.65, 95% confidence interval (CI) 0.22 to 1.93, P = 0.434] and the rate of myocardial reinfarction (RR 0.65, 95% CI 0.29 to 1.46, P = 0.295) of patients following AMI, but the rate of hospitalization for heart failure (HF) (RR 0.48, 95% CI 0.35 to 0.66, P < 0.001) and the change of LV ejection fraction (LVEF) [weighted mean difference (WMD) 5.49, 95% CI 3.62 to 7.36, P < 0.001] were obviously improved. The N-terminal pro-brain natriuretic peptide (NT-ProBNP) level (WMD -310.23, 95% CI -385.89 to -234.57, P < 0.001) and the LV end-diastolic dimension (LVEDD) (WMD -3.16, 95% CI -4.59 to -1.73, P < 0.001) were also significantly lower in sacubitril-valsartan group than in ACEI/ARB group. Regarding safety, sacubitril-valsartan did not increase the risk of hypotension, hyperkalaemia, angioedema, and cough. This meta-analysis suggests that early administration of sacubitril-valsartan may be superior to conventional ACEI/ARB to decrease the risk of hospitalization for HF, improve the cardiac function, and reverse the LV remodelling in patients following AMI.


Stimulation of mono (ADP-ribosyl)ation by reduced extracellular calcium levels in human fibroblasts.
Lowering extracellular calcium in cultures of human diploid fibroblast-like cells caused a rapid depletion of NAD pools. This loss of NAD was reversed by restoring extracellular Ca2+ and was inhibited by 3-aminobenzamide, an inhibitor of ADP-ribosyl transfer reactions. The concentrations of 3-aminobenzamide needed to inhibit the loss of NAD were consistent with those required to inhibit cellular mono(ADP-ribosyl) rather than poly(ADP-ribosyl) reactions. Calcium depletion did not inhibit the biosynthesis of NAD. These results suggest that mono(ADP-ribosyl)ation is involved in the regulation of cellular Ca2+ levels.


Variations in erythrocyte uroporphyrinogen I synthetase activity in non porphyrias.
The activity of erythrocyte uroporphyrinogen I synthetase has been measured in various cases of non-porphyric affections. The results indicate a diminution of this activity in some of the studied cases of chronic renal insufficiency and chronic polyarthritis. This modulation in activity mitigates against its use as a diagnostic criterion of acute intermittent porphyria. On the other hand, an increase in urosynthetase activity has been noted in acute and especially chronic hepatic affections. This increase seems to be connected with the severity of the hepatic affection. The relationship is illustrated particularly in the case of viral hepatitis associated to an AIP, where the increasing activity of the urosynthetase masks for many weeks the congenital deficiency peculiar to this AIP. Our study thus indicates that the diagnosis of AIP based on the activity of the urosynthetase must take into account the pathological context in which the investigation is realised.


Thymidine kinase genes and the induction of anti-viral responses by interferon.
A mouse fibroblast cell-line deficient in thymidine kinase (Ltk(-) aprt(-)) fails to show an anti-viral response when treated with interferon. After introduction of a viral tk gene into these cells the resultant clones showed normal responses to interferon. However, one such tk-containing clone (C6) spontaneously lost its ability to respond to interferon by inducing an antiviral state although it retained its ability to induce the enzyme oligo(2'-5' A)-synthetase. This sub-clone (6A) still expressed thymidine kinase activity but restriction endonuclease analysis indicated an alteration in the sequences flanking the exogenous viral tk gene. Our results suggest that a modification in the exogenous viral DNA sequences led to a loss of interferon sensitivity.


Immunosenescence evaluation of peripheral blood lymphocyte subsets in 957 healthy adults from 20 to 95 years old.
Immunosenescence is characterized by an age-related decline in immune system function. Major efforts have been made to identify changes in peripheral blood lymphocyte subsets accompanying immunosenescence in elderly adults. However, the change trends of some lymphocyte subsets with age are still controversial, and populations of advanced ages, such as people in their 80s or 90s, have not yet been thoroughly investigated. To provide further insight, we recruited 957 healthy donors without certain diseases with ages ranging from 20 to 95 years. Peripheral lymphocyte subsets, including T cells, CD4 T cells, CD8 T cells, B cells and NK cells, and the CD4/CD8 ratio were measured by flow cytometry. Additionally, regulatory CD4 T cells with inhibitory functions marked by CD3+CD4+CD25hi and the expression of the costimulatory molecule CD28 on CD8 T cells were evaluated. Sex was considered at the same time. The data indicated that in elderly people, peripheral T (p < 0.001), CD4 T (p < 0.001) and B (p < 0.001) lymphocyte subsets decreased, but the NK cell population (p < 0.001) increased. More regulatory CD4 T cells may imply stronger inhibition in the elderly population. The decreased CD28 expression with age in females verified CD28 to be an immunosenescence marker and the sharply decreased CD28 expression after 75 years in males indicated a rapid immunosenescence at the late life span of the male populations. In addition, our study established reference values for peripheral lymphocyte subsets at different age stages in males and females, which are urgently needed for the clinical management and treatment of geriatric diseases.


Understanding the penetrance of intrinsic protein disorder in rotavirus proteome.
Rotavirus is a major cause of severe acute gastroenteritis in the infants and young children. The past decade has evidenced the role of intrinsically disordered proteins/regions (IDPs)/(IDPRs) in viral and other diseases. In general, (IDPs)/(IDPRs) are considered as dynamic conformational ensembles that devoid of a specific 3D structure, being associated with various important biological phenomena. Viruses utilize IDPs/IDPRs to survive in harsh environments, to evade the host immune system, and to highjack and manipulate host cellular proteins. The role of IDPs/IDPRs in Rotavirus biology and pathogenicity are not assessed so far, therefore, we have designed this study to deeply look at the penetrance of intrinsic disorder in rotavirus proteome consisting 12 proteins encoded by 11 segments of viral genome. Also, for all human rotaviral proteins, we have deciphered molecular recognition features (MoRFs), which are disorder based binding sites in proteins. Our study shows the wide spread of intrinsic disorder in several rotavirus proteins, primarily the nonstructural proteins NSP3, NSP4, and NSP5 that are involved in viral replication, translation, viroplasm formation and/or maturation. This study may serve as a primer for understanding the role of IDPs/MoRFs in rotavirus biology, design of alternative therapeutic strategies, and development of disorder-based drugs.


Tuberculosis in a general hospital: high incidence of extrapulmonary disease.
Twenty six patients with tuberculosis were admitted between 1979 and 1982 to the Tel Aviv Medical Center. Most were immigrants from Eastern Europe. In contrast to previous studies, patients were relatively young (mean age 57 years) and lacked predisposing medical illness. Eighteen (69%) had extrapulmonary infections, half of which involved the genitourinary tract. Two instances of miliary tuberculosis were diagnosed at autopsy.


The Effect of ACP₁-ADA₁ Genetic Interaction on Human Life Span.
Acid phosphatase (ACP₁) is a polymorphic enzyme that catalyzes the conversion of flavin-mononucleotide (FMN) to riboflavin and regulates the cellular concentration of flavin-adenine-dinucleotide (FAD) and, consequently, energy metabolism. Its activity is modulated by adenosine deaminase locus 1 (ADA₁) genotype. The aim of our work is to verify whether individuals with a high proportion of ACP₁ f-isozyme and carrying the ADA₁*2 allele, displaying the highest phosphatase activity, may have a higher life expectancy. Genomic DNA was extracted from the peripheral blood of 569 females and 509 males (18 to 106 years of age) randomly recruited from Central Italy. These samples were subdivided into three sex-specific age groups (the ages of women are in square bracket): Class 1: age <66 [<73]; Class 2: ages 66 to 88 [73 to 91]; Class 3: age >88 [>91]. ACP₁and ADA₁ singlenucleotide polymorphisms (SNPs) were genotyped by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) methods and statistical analyses were performed with SPSS 14.0. The results showed a larger proportion of Class 3 individuals displaying high ACP₁ f-isozyme concentration and carrying the ADA₁*2 allele than those individuals of Class 2 and Class 2 plus Class 1. Thus, we postulate that in Class 3 individuals the high phosphatase activity, resulting from the combined presence of high ACP₁ f-isozyme concentration and the ADA₁*2 allele, lowers the rate of glycolysis that may reduce the amount of metabolic calories and, in turn, activate Sirtuin genes that protect cells against age-related diseases.


Prevalence of Haemophilus influenzae with resistant genes isolated from young children with acute lower respiratory tract infections in Nha Trang, Vietnam.
Our study was undertaken to investigate the characteristics of Haemophilus influenzae in young children with acute lower respiratory tract infections in Nha Trang, Vietnam. The study population consisted of 116 children less than 5 years of age admitted to Khanh Hoa General Hospital due to acute lower respiratory tract infections between July 2004 and April 2005. Organisms could be detected from nasopharyngeal swabs (NP) in 72 (62.1%) of the 116 children. Haemophilus influenzae was the most common organism, and 39 strains were isolated from 39 children aged 2 to 60 months (mean age, 16 months). We examined 37 of these 39 H. influenzae strains. The serotypes of the 37 isolates were all nontypeable, and 22 strains (59.5%) were beta-lactamase producing. Polymerase chain reaction (PCR) analysis to identify resistance genes revealed that 17 strains had the TEM-1-type beta-lactamase gene alone, 6 strains had the ftsI gene with the same substitution as that in g low-beta-lactamase-negative ampicillin-resistant (g low-BLNAR) strains, and 6 strains had both the TEM-1-type beta-lactamase gene and the ftsI gene with the same substitution as that in g beta-lactamase-producing amoxicillin clavulanic acid-resistant (g BLPACR I) strains, although no BLNAR strains were found. Molecular typing by pulsed-field gel electrophoresis (PFGE) showed that the 6 g low-BLNAR strains had five PFGE patterns and the 6 g BLPACR I strains had four PFGE patterns. Our results indicate that BLNAR strains are still not prevalent, but that g low-BLNAR and g BLPACR I strains are potentially spreading in Nha Trang, Vietnam.


Direct synthesis of dialkylarylvinylsilane derivatives: metathesis of dialkylaryl-iso-propenylsilane and its application to tetracyclic silacycle dye synthesis.
The metathesis of dialkylarylvinylsilane, which has not been accomplished to date, is achieved using dialkylaryl-iso-propenylsilane as a substrate. In addition, we discovered that the reason why the metathesis of a ruthenium carbene complex and dialkylarylvinylsilane is difficult is the formation of a carbide complex.