Intracellular QX-314 causes depression of membrane potential oscillations in lamprey spinal neurons during fictive locomotion.
Spinal neurons undergo large cyclic membrane potential oscillations during fictive locomotion in lamprey. It was investigated whether these oscillations were due only to synaptically driven excitatory and inhibitory potentials or if voltage-dependent inward conductances also contribute to the depolarizing phase by using N-(2,6-dimethylphenyl carbamoylmethyl)triethylammonium bromide (QX-314) administered intracellularly during fictive locomotion. QX-314 intracellularly blocks inactivating and persistent Na+ channels, and in some neurons, effects on certain other types of channels have been reported. To detail the effects of QX-314 on Na+ and Ca2+ channels, we used dissociated lamprey neurons recorded under whole cell voltage clamp. At low intracellular concentrations of QX-314 (0.2 mM), inactivating Na+ channels were blocked and no effects were exerted on Ca2+ channels (also at 0.5 mM). At 10 mM QX-314, there was, however a marked reduction of I(Ca). In the isolated spinal cord of the lamprey, fictive locomotion was induced by superfusing the spinal cord with Ringer's solution containing N-methyl-D-aspartate (NMDA), while recording the locomotor activity from the ventral roots. Simultaneously, identified spinal neurons were recorded intracellularly, while infusing QX-314 from the microelectrode. Patch electrodes cannot be used in the intact spinal cord, and therefore "sharp" electrodes were used. The amplitude of the oscillations was consistently reduced by 20-25% in motoneurons (P < 0.05) and unidentified spinal neurons (P < 0.005). The onset of the effect started a few minutes after impalement and reached a stable level within 30 min. These effects thus show that QX-314 causes a reduction in the amplitude of membrane potential oscillations during fictive locomotion. We also investigated whether QX-314 could affect glutamate currents by applying short pulses of glutamate from an extracellular pipette. No changes were observed. We also found no evidence for a persistent Na+ current in dissociated neurons, but these cells have a much-reduced dendritic tree. The results indicate that there is an inward conductance, which is sensitive to QX-314, during membrane potential oscillations that "boosts" the synaptic drive during fictive locomotion. Taken together, the results suggest that inactivating Na+ channels contribute to this inward conductance although persistent Na+ channels, if present on dendrites, could possibly also contribute to shaping the membrane potential oscillations.


Factors contributing to home deliveries by women attending post-natal care at a selected clinic in Rundu District, Kavango East Region, Namibia.
In 2016, almost 31 million births in low- and middle-income countries occurred without a qualified birth attendant. 90% were in South Asia and sub-Saharan Africa. In sub-Saharan Africa, where Namibia is located, 50% of births are unattended. This study aimed at identifying factors contributing to home births in Rundu District, Kavango East Region. This study was quantitative cross-sectional. Postnatal moms who gave birth at home completed a self-administered questionnaire with closedended questions. 27.2% of respondents were 33 to 38. Most responders (83.3%) were unmarried and 38.6% were "other" religious. Participants were mostly unemployed (79.8%). 49.1% of respondents were uneducated. 8.8% of employed people were in the public sector, 6.1% in private, and 1.8% self-employed. Most (93.9%) visited antenatal clinics once (25.4%), twice (20.2%), or three times (40%) before delivery. 81% picked where to deliver on their own, and 71% had previously delivered at home. No one explained this behavior. The majority of women in this study had given delivery at home. Education, religion, and delivery location were correlated. These findings inform the community and government about the present trend of home births, which may harm mother and newborn outcomes.


The effects of propranolol HCl in hippocampal-lesioned rats.
Experiments were conducted to determine the effects of propranolol administration in rats lesioned in the hippocampal area. Chronic oral administration of propranolol to intact rats produced a significant decrease in mean systolic blood pressure. No significant changes in blood pressure were produced with propranolol treatment in rats lesioned in the septal or anterior hypothalamic areas, whereas, in rats lesioned in the hippocampal area, a significant elevation of blood pressure was observed. These findings confirm previous results that suggest that the hypotensive effects observed with chronic propranolol administration are mediated via the hippocampus.


A study on changes in lung function, neutralizing antibodies, and symptoms of adult patients hospitalized with COVID-19.
To identify changes in symptoms and pulmonary sequelae in patients with coronavirus disease 2019 (COVID-19). Patients with COVID-19 hospitalized at seven university hospitals in Korea between February 2020 and February 2021 were enrolled, provided they had ≥ 1 outpatient follow-up visit. Between January 11 and March 9, 2021 (study period), residual symptom investigations, chest computed tomography (CT) scans, pulmonary function tests (PFT), and neutralizing antibody tests (NAb) were performed at the outpatient visit (cross-sectional design). Additionally, data from patients who already had follow-up outpatient visits before the study period were collected retrospectively. Investigation of residual symptoms, chest CT scans, PFT, and NAb were performed in 84, 35, 31, and 27 patients, respectively. After 6 months, chest discomfort and dyspnea persisted in 26.7% (4/15) and 33.3% (5/15) patients, respectively, and 40.0% (6/15) and 26.7% (4/15) patients experienced financial loss and emotional distress, respectively. When the ratio of later CT score to previous ones was calculated for each patient between three different time intervals (1-14, 15-60, and 61-365 days), the median values were 0.65 (the second interval to the first), 0.39 (the third to the second), and 0.20 (the third to the first), indicating that CT score decreases with time. In the high-severity group, the ratio was lower than in the low-severity group. In COVID-19 survivors, chest CT score recovers over time, but recovery is slower in severely ill patients. Subjects complained of various ongoing symptoms and socioeconomic problems for several months after recovery.


Popular Views on Addictions and on Prospects for Recovery in Poland.
Popular views of addictive substances and behaviors constitute an important research topic because these views have an impact upon the functioning of treatment systems and societal responses to substance use disorders. The analysis is based on a random sample of N = 1000 telephone interviews collected in Poland in 2013. Questionnaire measures targeted such issues as the perceived risks of addictions and beliefs about potential recovery from various types of addictions. First, a coherent view of the addiction potential of various addictive substances and/or behaviors emerges, distinguishing licit drugs and types of behavior from illicit drugs. Second, treatment optimism proves to be quite high independent of the type of addictive behavior, while chances of recovery without treatment are considered less likely. Third, chances for assisted change (change with treatment) and self-change are considered largely independent of perceived addiction-related risks and are not perceived as contradictory. The results point to the persistence of the disease model of addiction in Poland, placing responsibility for addiction on the individual and pairing it with the expectation of undergoing specialized treatment. This individualistic approach was applied as a framework for addiction problems in the 1950s to deflect from the shortcomings of the ''new socialist society.'' Neo-liberal market reform and socioeconomic changes have provided reinforcement for this individualistic framework.


Echinocystic Acid Inhibits Inflammation and Exerts Neuroprotective Effects in MPTP-Induced Parkinson's Disease Model Mice.
Parkinson's disease (PD), the second primary neurodegenerative disease affecting human health, is mainly characterized by dopaminergic neuron damage in the midbrain and the clinical manifestation of movement disorders. Studies have shown that neuroinflammation plays an important role in the progression of PD. Excessively activated microglia produce several pro-inflammatory mediators, leading to damage to the surrounding neurons and finally inducing neurodegeneration. Echinocystic acid (EA) exhibits an anti-inflammatory effect in peripheral tissues. However, whether it inhibited neuroinflammation remains unclear. Therefore, the current study investigates the effect of EA on neuroinflammation and whether it can improve PD symptoms through inhibiting neuroinflammation. In our experiments, we discovered that EA inhibited the production of pro-inflammatory mediators in LPS-exposed BV2 cells. Further mechanism-related studies revealed that EA inhibited inflammation by activating PI3K/Akt and inhibiting NF-κB and MAPK signal pathways in LPS-induced BV2 cells. Research revealed that EA eases microglia-mediated neuron death in SN4741 and SHSY5Y cells. In in vivo studies, the results demonstrated that EA improves weight loss and behavioral impairment in MPTP-induced mice. Further studies have revealed that EA inhibited dopaminergic neuron damage and inflammation in the mice midbrain. In conclusion, our study demonstrated that EA inhibits neuroinflammation and exerts neuroprotective effects by activating PI3K/Akt and inhibiting NF-κB and MAPK signal pathways in vivo and in vitro.


CTAB-PAGE.
Although SDS-PAGE is the method of choice for most denaturing gel electrophoresis procedures, the anionic detergent SDS still presents some drawbacks. For example, SDS forms crystals at low temperatures and, in some cases, causes proteins to aggregate or precipitate. In addition, some proteins are not well-resolved in SDS gels or may migrate anomalously. In these situations, the use of a cationic detergent for PAGE offers an alternative approach. The system described in this protocol uses the cationic detergent cetyltrimethyl ammonium bromide (CTAB) and includes a stacking gel based on the zwitterion arginine (used as a stacking agent) and tricine (N-tris[hydroxymethyl]-methylglycine) used as a counterion and buffer. Some proteins separated on the CTAB electrophoresis system retain their native enzymatic activity, provided the samples are prepared without boiling and without the addition of a reducing agent.


Two-photon imaging of immune cells in neural tissue.
To develop new therapeutic strategies for many central nervous system (CNS) diseases, it is essential to observe the motility and function of immune cells within neural tissue. Two-photon laser-scanning microscopy is an outstanding technique for imaging these phenomena under in vivo-like conditions. To gain deeper insight into the pathological phenomena that occur during chronic neuroinflammation of the CNS, we use it to view acute murine hippocampal slices cocultured with different subpopulations of immune cells and to view in vivo the brain stem of anesthetized transgenic mice affected by experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. This protocol describes the preparation of cocultures of acute hippocampal slices with antigen-specific T helper 17 (Th17) cells migrating into the parenchyma, and the preparation of anesthetized mice for imaging the brain stem. We also discuss technical aspects of dual-color, two-photon laser-scanning microscopy that is used to image these samples and that allows for greater flexibility in the choice of fluorophores.


The stretch reflex and the contributions of C David Marsden.
The stretch reflex or myotatic reflex refers to the contraction of a muscle in response to its passive stretching by increasing its contractility as long as the stretch is within physiological limits. For ages, it was thought that the stretch reflex was of short latency and it was synonymous with the tendon reflex, subserving the same spinal reflex arc. However, disparities in the status of the two reflexes in certain clinical situations led Marsden and his collaborators to carry out a series of experiments that helped to establish that the two reflexes had different pathways. That the two reflexes are dissociated has been proved by the fact that the stretch reflex and the tendon reflex, elicited by stimulation of the same muscle, have different latencies, that of the stretch reflex being considerably longer. They hypothesized that the stretch reflex had a transcortical course before it reached the spinal motor neurons for final firing. Additionally, the phenomenon of stimulus-sensitive cortical myoclonus lent further evidence to the presence of the transcortical loop where the EEG correlate preceded the EMG discharge. This concept has been worked out by later neurologists in great detail, and the general consensus is that indeed, the stretch reflex is endowed with a conspicuous transcortical component.


Boundaries of anion/naphthalenediimide interactions: from anion-π interactions to anion-induced charge-transfer and electron-transfer phenomena.
The recent emergence of anion-π interactions has added a new dimension to supramolecular chemistry of anions. Yet, after a decade since its inception, actual mechanisms of anion-π interactions remain highly debated. To elicit a complete and accurate understanding of how different anions interact with π-electron-deficient 1,4,5,8-naphthalenediimides (NDIs) under different conditions, we have extensively studied these interactions using powerful experimental techniques. Herein, we demonstrate that, depending on the electron-donating abilities (Lewis basicity) of anions and electron-accepting abilities (π-acidity) of NDIs, modes of anion-NDI interactions vary from extremely weak non-chromogenic anion-π interactions to chromogenic anion-induced charge-transfer (CT) and electron-transfer (ET) phenomena. In aprotic solvents, electron-donating abilities of anions generally follow their Lewis basicity order, whereas π-acidity of NDIs can be fine-tuned by installing different electron-rich and electron-deficient substituents. While strongly Lewis basic anions (OH(-) and F(-)) undergo thermal ET with most NDIs, generating NDI(•-) radical anions and NDI(2-) dianions in aprotic solvents, weaker Lewis bases (AcO(-), H(2)PO(4)(-), Cl(-), etc.) often require the photoexcitation of moderately π-acidic NDIs to generate the corresponding NDI(•-) radical anions via photoinduced ET (PET). Poorly Lewis basic I(-) does not participate in thermal ET or PET with most NDIs (except with strongly π-acidic core-substituted dicyano-NDI) but forms anion/NDI CT or anion-π complexes. We have looked for experimental evidence that could indicate alternative mechanisms, such as a Meisenheimer complex or CH···anion hydrogen-bond formation, but none was found to support these possibilities.


Association of Revised WIC Food Package With Perinatal and Birth Outcomes: A Quasi-Experimental Study.
The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) serves more than one-quarter of pregnant and postpartum women. In October 2009, the WIC food package underwent revisions to improve nutritional content. No studies have investigated the downstream effects of this revision on maternal and infant health. To investigate whether the revised WIC food package improved perinatal and birth outcomes among recipients. We conducted a quasi-experimental difference-in-differences analysis, comparing WIC recipients (the treatment group) before and after the package revisions while accounting for temporal trends among nonrecipients (the control group). Multivariable linear regressions were adjusted for sociodemographic covariates. This study was conducted using linked birth certificate and hospital discharge data from California from January 2007 to December 2012. Analysis began July 2018. Whether pregnant women received the revised WIC package, which included more whole grains, fruit, vegetables, and low-fat milk. Measures of maternal and infant health, including maternal preeclampsia, gestational diabetes, and gestational weight gain as well as infant gestational age, birth weight, and hospitalizations. The sample included 2 897 537 infants born to 2 441 658 mothers. WIC recipients were more likely to be Hispanic, less educated, of greater parity, and younger than nonrecipients. The revised WIC food package was associated with reductions in maternal preeclampsia (-0.6% points; 95% CI, -0.8 to -0.4) and more than recommended gestational weight gain (-3.2% points; 95% CI, -3.6 to -2.7), increased likelihood of as recommended (2.3% points; 95% CI, 1.8 to 2.8) and less than recommended (0.9% points; 95% CI, 0.5 to 1.2) gestational weight gain, and longer gestational age (0.2 weeks; 95% CI, 0.001 to 0.034). Among infants, an increased likelihood of birth weight that was appropriate for gestational age was observed (0.9% points; 95% CI, 0.5 to 1.3). Although birth weight itself was reduced (-0.009 SDs; 95% CI, -0.016 to -0.001), this was accompanied by reductions in small for gestational age (-0.4% points; 95% CI, -0.7 to -0.1), large for gestational age (-0.5% points; 95% CI, -0.8 to -0.2), and low-birth-weight infants (-0.2% points; 95% CI, -0.4 to -0.004), suggesting that the revised food package improved distributions of birth weight. The revised WIC food package, intended to improve women's nutrition during pregnancy, was associated with beneficial impacts on maternal and child health. This suggests that WIC policy may be an important lever to reduce health disparities among high-risk women and children at a critical juncture in the life course.


Analysis of CD4+ T-helper-associated hub gene signature and immune dysregulation via RNA-sequencing data in a mouse tail model of lymphedema.
T-helper cells play an essential role in the progression of lymphedema. This study aimed to explore the biological significance of T-helper cell-associated genes (THAGs) in a mouse tail model of lymphedema by RNA-sequencing (RNA-seq) data. The expression profiles of a murine model of secondary lymphedema were obtained from European Nucleotide Archive (ENA) database. Differentially expressed genes (DEGs) were screened and the enrichment analysis of DEGs was conducted. THAGs were constructed by crossing the T-helper-related gene sets obtained from Molecular Signatures Database with DEGs. Protein-protein interaction (PPI) network analysis was utilized to establish T-helper-associated hub genes (THAHGs). Single-sample gene set enrichment analysis (ssGSEA) was employed to decipher differences in immune cell infiltration. The correlation between THAHGs and immune infiltration was calculated by Pearson correlation analysis. Receiver operating characteristic (ROC) curves of THAHGs were drawn to evaluate their diagnostic properties. Additionally, potential drugs and upstream transcription factors (TFs) were predicted based on THAHGs. Enrichment analysis showed that lymphedematous tissue presented higher activation of biological process (BP) of T-helper 1 (Th1), T-helper 2 (Th2), T-helper 17 (Th17). The immune infiltration analysis further calculated that the relative immune abundance of follicular B cells, memory B cells, M1 macrophage, and CD4+ Tm cells was significantly elevated while the relative immune abundance of neutrophils and plasma cells were down-regulated in lymphedema. We established a list of THAHGs consisting of eight hub genes, compassing Cd4, Foxp3, Irf4, Ccr6, Il12rb1, Batf, Il1b, Cd74. THAHGs were shown to be significantly interrelated and related to immune infiltration by Pearson correlation analysis. ROC curves showcased that the area under curve (AUC) values of THAHGs were larger than 0.70. Gata3 was the most potential TF and thalidomide might be the immunoregulatory drug for lymphedema based on THAHGs. Biological pathways associated with T-helpers were significantly enriched in mouse lymphedema tissue. The relative immune infiltration abundance of M1 macrophage, CD4+ Tm cells, and T-helper cells was higher in the lymphedema group. Besides, we identified the THAHGs containing eight genes, namely, Cd4, Foxp3, Irf4, Ccr6, Il12rb1, Batf, Il1b, and Cd74. The THAHGs were closely correlated with immune infiltration results and with good diagnostic properties.


Breaking of time-reversal symmetry for a particle in a parabolic potential that is subjected to Lévy noise: Theory and an application to solar flare data.
The noise in nonequilibrium systems commonly contains more outliers as compared to equilibrium systems and is often best described with a Lévy distribution. Many systems in which there are fluctuations around a steady-state throughput can be modeled as a Lévy-noise-subjected particle in a parabolic potential. We consider an overdamped particle in a parabolic potential that is subjected to noise. Microscopic reversibility and time-reversal symmetry apply if the particle is subject to Gaussian distributed noise, but are violated if the noise is Lévy. A parameter to detect this violation is formulated. We, furthermore, develop an understanding for how the time-reversal asymmetry depends on the time Δt between the sample points and on the stability index, α, of the Lévy noise. With solar flare data it is shown how the time-reversal asymmetry parameter of a signal can be used to obtain the α of the underlying noise.


Effects of oestradiol and progesterone on the concentration of alpha 2-macroglobulin in the sera of injured male and female rats.
The effects of ovarian hormones on the synthesis of alpha 2-macroglobulin in response to injury were investigated. After injection of turpentine to provoke synthesis of alpha 2-macroglobulin, the mean concentrations of this protein in serum were lower in intact female than in male rats. Sera from injured ovariectomized rats contained levels of alpha 2-macroglobulin similar to those of injured male animals. Administration to ovariectomized animals of oestradiol or oestradiol plus progesterone substantially reduced the levels of alpha 2-macroglobulin produced in response to injury. Administration of progesterone only resulted in a small increase in the response of ovariectomized animals to injury. Oestradiol and progesterone had no effect on the response of male rats to injury. These findings suggest that only in the female rat can these steroid hormones, especially oestradiol, regulate the synthesis of alpha 2-macroglobulin in response to tissue injury.


Arginine Promotes the Expression of Aquaporin-3 and Water Transport in Porcine Trophectoderm Cells Through NO- and cAMP-Dependent Mechanisms.
Dietary supplementation with L-arginine (Arg) has been shown to increase the volume of fetal fluids in gestating swine. Aquaporins (AQPs), known as water channel proteins, are essential for embryonic growth and development. It was not known if Arg mediates water transport through AQPs in porcine conceptus trophectoderm (pTr2) cells. pTr2 cells derived from pregnant gilts on day 12 of gestation were cultured in customized Arg-free Dulbecco's modified Eagle's Ham medium (DMEM) supplemented with either 0.00, 0.25, or 0.50 mM Arg. Arg treatment increased water transport and the expression of AQP3, which was abundantly expressed in pTr2 cells at both the mRNA and protein levels. Arg also increased the expression of iNOS and the synthesis of nitric oxide (NO) in pTr2 cells. The presence of Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME; an inhibitor of NO synthase) significantly attenuated the Arg-induced expression of AQP3. Furthermore, 0.50 mM Arg increased the concentrations of cAMP and the abundances of phosphorylated cAMP-dependent protein kinase A (PKA), phosphorylated PKA α/β/γ, and phosphorylated CREB. These effects of Arg were mimicked by Forskolin (a cell-permeable activator of adenylyl cyclase), but inhibited by H-89 (an inhibitor of cAMP-dependent protein kinase). The results of this study demonstrate that Arg regulates AQP3 expression and promotes water transport in pTr2 cells through NO- and cAMP-dependent signaling pathways.


There is little experience and limited data to support policy making on integrated care for dual eligibles.
Coordinating care for the nine million elderly or disabled and low-income people who are dually eligible for Medicare and Medicaid is a pressing policy issue. To support the debate over this issue, we synthesized public data on how services are provided to dual eligibles receiving covered benefits in both programs. Our analysis confirmed that most dual-eligible beneficiaries receive benefits separately for each program through fee-for-service arrangements. Their enrollment in Medicare and Medicaid managed care is growing but still low, with highly uneven experiences across states. Few states or health plans have experience with coordinating care for dual eligibles within an integrated plan. These findings reinforce the need for caution in considering policies that would rapidly give states the responsibility for coordinating dual eligibles' care and coverage. We also found data gaps that warrant prompt attention in order to provide national-level oversight and improve the evidence base for debating and tracking policy changes.


Epidemiologic data on adult glaucomas. Data from the Hospital Discharge Registry and the Registry of Right to Free Medication.
The prevalence of glaucoma was studied using material from the Registry of Right to Free Medications, completed by the Social Insurance Institution of Finland in 1985. A total of 31,981 patients (10,022 males and 21,959 females) received free medication for glaucoma in 1985. Total crude glaucoma prevalence in Finland in 1985 was 0.67%, calculated for the total population (all glaucomas) according to data from this registry. The crude prevalence for those of 40 years of age and over, was 1.7% and for those of age 70 years and older, 6.1%. Age adjusted prevalence showed a female excess of cases with a male-female ratio of 1/1.3. The incidence of different types of glaucoma was studied using the Hospital Discharge Registry for the years 1973-1982. For this 10-year period, a total of 48,864 patients with glaucoma and 10,614 glaucoma suspects were found in a compilation based on an International Classification of Diseases (8th edn.) code number. Of all adult glaucomas, 67% were primary glaucomas, while 33% were secondary glaucomas. An increase in the incidence of glaucoma was noted during the 10-year period, especially for the chronic simple and capsular glaucoma groups. Females were at higher risk for chronic simple, acute angle-closure, capsular and chronic angle-closure glaucoma; whereas, males were at greater risk for other types of secondary glaucomas. The patients with secondary glaucoma were the youngest (mean age 53.5 years in males, and 60.3 years in females), while the patients with capsular glaucoma were the oldest (mean age 71.9 years in males, and 72.8 in females).


Patient Perspectives on Artificial Intelligence in Radiology.
There are two major areas for patient engagement in radiology artificial intelligence (AI). One is in the sharing of data for AI development; the second is the use of AI in patient care. In general, individuals support sharing deidentified data if used for the common good, to help others with similar health conditions, or for research. However, there is concern with risk to privacy including reidentification and use for other than intended purposes. Lack of trust is mentioned as a barrier for data sharing. Individuals want to be involved in the data-sharing process. In the use of AI in medical care, patients generally support AI as an assist to the radiologist but lack trust in unsupervised AI. Patients worry about liability in case of bad outcomes. Patients are concerned about loss of the human connection and the loss of empathy during a vulnerable time in their lives. Patients expressed concern about risk of discrimination due to bias in AI algorithms. Building trust in AI requires transparency, explainability, security, and privacy protection. Radiologists can take action to prepare their patients to become more trusting of AI. Developing and implementing data-sharing agreements allows patients to voluntarily help in the algorithm development process. Developing AI disclosure guidelines and having AI use disclosure discussions with patients will help them understand the use of AI in their care. As the use of AI increases, there is an opportunity for radiologists to develop and maintain close relationships with their patients and to become more involved in their care.


Light Weight, Flexible and Ultrathin PTFE@Ag and Ni@PVDF Composite Film for High-Efficient Electromagnetic Interference Shielding.
Dopamine was used to modify polytetrafluoroethylene (PTFE) in order to obtain functional polydopamine (PDA) surface-modified PTFE microporous film (PTFE@PDA). Ag was deposited on the surface of PTFE@PDA using electroless plating in order to obtain Ag-wrapped PTFE@PDA film (PTFE@Ag). A liquid-phase chemical reduction method was employed to prepare nickel nanochains. A Ni@PVDF cast film was obtained by mechanically blended nickel nanochains and polyimide (PVDF). The above two films were hot pressed to give a flexible, ultra-thin, and highly effective electromagnetic shielding composite film with a "3+2" layered structure. IR, XRD, and TEM results showed the PTFE@PDA film surface was coated by a tight plating layer of Ag particles with a particle size of 100~200 nm. PTFE@Ag+Ni@PVDF composite film exhibited excellent electromagnetic shielding effectiveness, with the conductivity of 7507.5 S/cm and the shielding effectiveness of 69.03 dB in the X-band range. After a 2000-cycle bending, this value still remained at 51.90 dB. Furthermore, the composite film presented excellent tensile strength of 62.1 MPa. It has great potential for applications in flexible and wearable intelligent devices.


Partial purification and properties of neutral PTHase from the cytosolic fraction of rat renal cortex.
A possible new enzyme, a cytosolic neutral PTH-degrading enzyme previously described by us, was purified by ammonium sulfate fractionation, Sephadex G-200 column chromatography and DEAE cellulose column chromatography from the 100,000 x g supernatant of rat kidney. Three active peaks (designated P-I, P-II and P-III) were obtained through a DEAE cellulose chromatographic column. These three activity peaks were interchangeable on rechromatography. Further characterization of the major P-II fraction was attempted. When PTH was used as the substrate, this enzyme preparation (P-II) was inhibited by Ca2+, ATP and glutathione (GSH), but not by trypsin inhibitor, PMSF, E-64, leupeptin, chymostatin or pepstatin. This enzyme preparation could hardly hydrolyze several synthetic analogs containing MCA but not Leu-MCA and Z-Phe-Arg-MCA. When Z-Phe-Arg-MCA was used as the substrate, this enzyme preparation was activated by ATP and GSH, while no activation was induced when PTH was used. These results indicate that the neutral PTH-degrading enzyme seems to represent a new PTHase capable of specifically splitting PTH at certain locations.


Brain Metabolite Changes After Anodal Transcranial Direct Current Stimulation in Autism Spectrum Disorder.
Previous research has provided evidence that transcranial direct current stimulation (tDCS) can reduce severity of autism spectrum disorder (ASD); however, the exact mechanism of this effect is still unknown. Magnetic resonance spectroscopy has demonstrated low levels of brain metabolites in the anterior cingulate cortex (ACC), amygdala, and left dorsolateral prefrontal cortex (DLPFC) in individuals with ASD. The aim of this study was to investigate the effects of anodal tDCS on social functioning of individuals with ASD, as measured by the social subscale of the Autism Treatment Evaluation Checklist (ATEC), through correlations between pretreatment and posttreatment concentrations of brain metabolites in the areas of interest (DLPFC, ACC, amygdala, and locus coeruleus) and scores on the ATEC social subscale. Ten participants with ASD were administered 1 mA anodal tDCS to the left DLPFC for 20 min over five consecutive days. Measures of the ATEC social subscale and the concentrations of brain metabolites were performed before and immediately after the treatment. The results showed a significant decrease between pretreatment and immediately posttreatment in the ATEC social subscale scores, significant increases in N-acetylaspartate (NAA)/creatine (Cr) and myoinositol (mI)/Cr concentrations, and a decrease in choline (Cho)/Cr concentrations in the left DLPFC and locus coeruleus after tDCS treatment. Significant associations between decreased ATEC social subscale scores and changed concentrations in NAA/Cr, Cho/Cr, and mI/Cr in the locus coeruleus were positive. Findings suggest that beneficial effects of tDCS in ASD may be due to changes in neuronal and glia cell activity and synaptogenesis in the brain network of individuals with ASD. Further studies with larger sample sizes and control groups are warranted.


Bronchiolitis obliterans after bone marrow transplantation: the effect of preconditioning.
While half of all patients receiving bone marrow transplantation (BMT) for malignancies and related diseases may achieve prolonged disease-free survival, 2-10% of patients undergoing allogeneic transplantation develop bronchiolitis obliterans (BrOb). We have hypothesized that total body irradiation (TBI) which has been used for pretreatment may influence the subsequent development of BrOb in patients undergoing allogeneic BMT. Since 1976, we have treated 104 patients undergoing allogeneic BMT with non-TBI preconditioning. Of 60 patients that survived and were evaluable for chronic graft versus host disease (GVHD) 26 developed chronic GVHD (43%). Four of 104 patients (3.9%) developed BrOb by clinical and/or pathologic findings. Four of 4 patients (100%) with BrOb had chronic GVHD. Two of these 4 patients (50%) were alive at the end of 2 years. These data demonstrate that chronic GVHD is a risk factor for BrOb in patients receiving non-TBI preconditioning regimens. The similar incidence of BrOb in this population compared to other studies using TBI suggest that the preconditioning regimen is not a factor in the development of BrOb. Further study is needed to confirm these findings. Allogeneic bone marrow transplantation (BMT) has revolutionized the therapeutic approach toward acute and chronic leukemias, aplastic anemia and rare immunodeficiency disorders. Half of all patients that undergo BMT achieve long-term disease-free survival but a similar number develop significant complications [1].(ABSTRACT TRUNCATED AT 250 WORDS)


Folliculin promotes substrate-selective mTORC1 activity by activating RagC to recruit TFE3.
Mechanistic target of rapamycin complex I (mTORC1) is central to cellular metabolic regulation. mTORC1 phosphorylates a myriad of substrates, but how different substrate specificity is conferred on mTORC1 by different conditions remains poorly defined. Here, we show how loss of the mTORC1 regulator folliculin (FLCN) renders mTORC1 specifically incompetent to phosphorylate TFE3, a master regulator of lysosome biogenesis, without affecting phosphorylation of other canonical mTORC1 substrates, such as S6 kinase. FLCN is a GTPase-activating protein (GAP) for RagC, a component of the mTORC1 amino acid (AA) sensing pathway, and we show that active RagC is necessary and sufficient to recruit TFE3 onto the lysosomal surface, allowing subsequent phosphorylation of TFE3 by mTORC1. Active mutants of RagC, but not of RagA, rescue both phosphorylation and lysosomal recruitment of TFE3 in the absence of FLCN. These data thus advance the paradigm that mTORC1 substrate specificity is in part conferred by direct recruitment of substrates to the subcellular compartments where mTORC1 resides and identify potential targets for specific modulation of specific branches of the mTOR pathway.


Measuring the Interaction Force Between a Droplet and a Super-hydrophobic Substrate by the Optical Lever Method.
The goal of this paper is to investigate the interaction force between droplets and super-hydrophobic substrates in the air. A measurement system based on an optical lever method is designed. A millimetric cantilever is used as a force sensitive component in the measurement system. Firstly, the force sensitivity of the optical lever is calibrated using electrostatic force, which is the critical step in measuring interaction force. Secondly, three super-hydrophobic substrates with different grid fractions are prepared with nanoparticles and copper grids. Finally, the interaction forces between droplets and super-hydrophobic substrates with different grid fractions are measured by the system. This method can be used to measure the force on the scale of sub-micronewton with a resolution on the scale of nanonewton. The in-depth study of the contact process of droplets and super-hydrophobic structures can help to improve the production efficiency in coating, film and printing. The force measurement system designed in this paper can also be used in other fields of microforce measurement.


Effect of cooking methods on the formation of heterocyclic aromatic amines in chicken and duck breast.
Heterocyclic aromatic amines (HAAs), potent mutagens/carcinogens, are pyrolysis formed during the cooking of meat and fish. In the present study, the effects of various cooking methods, pan-frying, deep-frying, charcoal grilling and roasting on the formation of HAAs in chicken breast and duck breast were studied. The various HAAs formed during cooking were isolated by solid-phase extraction and analyzed by high-performance liquid chromatography (HPLC). Results showed that chicken breast cooked by charcoal grilling contained the highest content of total HAAs, as high as 112 ng/g, followed by pan-fried duck breast (53.3 ng/g), charcoal grilled duck breast (32 ng/g), pan-fried chicken breast (27.4 ng/g), deep-fried chicken breast (21.3 ng/g), deep-fried duck breast (14 ng/g), roasted duck breast (7 ng/g) and roasted chicken breast (4 ng/g). For individual HAA, the most abundant HAA was 9H-pyrido-[4,3-b]indole (Norharman), which was detected in charcoal grilled chicken breast at content as high as 32.2 ng/g, followed by 1-methyl-9H-pyrido[4,3-b] indole (Harman) and 2-amino-1-methyl-6-phenylimidazo[4,5-f]pyridine(PhIP) at 32 and 31.1 ng/g in charcoal grilled chicken breast, respectively. The content of PhIP in pan-fried duck and chicken breast were 22 and 18.3 ng/g, respectively. Generally, the type and content of HAAs in cooked poultry meat varies with cooking method and cooking conditions.


Students explore livable communities.
In 2006 and 2007, undergraduate and certificate students in gerontology at the University of Massachusetts Boston investigated the elder livability of seven area communities. Elder "livability" refers to features of a local community that support residents who wish to age in place--characteristics such as the availability of appropriate services, transportation options, and affordable housing. A survey developed by AARP guided the research and facilitated its completion within a single academic semester. With its potential to benefit both students and researched cities and towns, the Livable Communities project is recommended to gerontology educators and action researchers as a meaningful, real-world inquiry into factors affecting the ability of older adults to age in place.


Role of water oxidation in the photoreduction of graphene oxide.
By means of a H218O labeling experiment in combination with mass spectrometry tracking, we studied GO photoreduction. Observation of 18O labeled O2 provides direct evidence to confirm that water oxidation occurs during GO photoreduction. In combination with DFT calculations, we propose a mechanism for O2 and CO2 evolution in the photoreduction of GO.


Assignment of the contribution of the tryptophan residues to the circular dichroism spectrum of human carbonic anhydrase II.
The circular dichroism (CD) spectrum of human carbonic anhydrase II (HCAII) has been investigated using various mutants of the enzyme in which tryptophans have been replaced by site-directed mutagenesis. HCAII contains seven tryptophans which are believed to significantly contribute to the CD spectrum in both the near- and far-UV regions. By substituting the tryptophans one at a time, the spectral effects of the individual tryptophans were studied. The near-UV spectrum of HCAII is very complex, with multiple Cotton effects. This complexity has been attributed to aromatic amino acids, especially tryptophans, located in asymmetric aromatic clusters in the molecule. CD spectra of the individual tryptophans were calculated as difference spectra between the CD spectrum of HCAII and those of the tryptophan mutants. These spectra showed that the tryptophans contributed to the CD spectrum in almost the entire wavelength region investigated (180-310 nm). Summation of the individual tryptophan CD spectra in the near-UV region yielded a spectrum that was qualitatively very similar to that of HCAII, showing that the tryptophans are the major determinant for this part of the CD spectrum. Since tryptophans were also demonstrated to contribute significantly in the far-UV region, tryptophans can interfere considerably with the assignment of changes in CD bands to changes in secondary structure content during folding reactions. Moreover, because of this substantial interference, predictions of the amount of various types of secondary structure from CD data from the far-UV region are made more difficult. These findings are probably of general importance for proteins that, like HCAII, contain several tryptophans.(ABSTRACT TRUNCATED AT 250 WORDS)


Allele-Specific Inhibition of Rhodopsin With an Antisense Oligonucleotide Slows Photoreceptor Cell Degeneration.
To preserve photoreceptor cell structure and function in a rodent model of retinitis pigmentosa with P23H rhodopsin by selective inhibition of the mutant rhodopsin allele using a second generation antisense oligonucleotide (ASO). Wild-type mice and rats were treated with ASO by intravitreal (IVT) injection and rhodopsin mRNA and protein expression were measured. Transgenic rats expressing the murine P23H rhodopsin gene (P23H transgenic rat Line 1) were administered either a mouse-specific P23H ASO or a control ASO. The contralateral eye was injected with PBS and used as a comparator control. Electroretinography (ERG) measurements and analyses of the retinal outer nuclear layer were conducted and correlated with rhodopsin mRNA levels. Rhodopsin mRNA and protein expression was reduced after a single ASO injection in wild-type mice with a rhodopsin-specific ASO. Transgenic rat eyes that express a murine P23H rhodopsin gene injected with a murine P23H ASO had a 181 ± 39% better maximum amplitude response (scotopic a-wave) as compared with contralateral PBS-injected eyes; the response in control ASO eyes was not significantly different from comparator contralateral eyes. Morphometric analysis of the outer nuclear layer showed a significantly thicker nuclear layer in eyes injected with murine P23H ASO (18%) versus contralateral PBS-injected eyes. Allele-specific ASO-mediated knockdown of mutant P23H rhodopsin expression slowed the rate of photoreceptor degeneration and preserved the function of photoreceptor cells in eyes of the P23H rhodopsin transgenic rat. Our data indicate that ASO treatment is a potentially effective therapy for the treatment of retinitis pigmentosa.


[Pediatric one-lung anesthesia with a Fogarty catheter].
One-lung anesthesia using a Fogarty catheter in pediatric patients is presented. Case 1 is an 8 year old male with coarctation of the aorta scheduled for coarctectomy. Case 2 is a 13 year old female with metastatic lung tumor scheduled for partial resection of the left upper lobe under thoracoscopic surgery. One-lung anesthesia was successfully established with a Fogarty catheter in both patients and no hypoxic episode was encountered during the one-lung anesthesia. Postoperatively, there was no evidence of atelectasis of the lung or barotrauma to the trachea or bronchus. Thus, the Fogarty catheter appears useful for pediatric one-lung anesthesia, especially when the double lumen endobronchial tubes or endobronchial blockers of smaller sizes are not available.


Red blood cell 2,3-diphosphoglycerate concentration and in vivo P50 during early critical illness.
To measure red blood cell 2,3-diphosphoglycerate (RBC 2,3-DPG) concentrations in early critical illness; to investigate factors associated with high or low RBC 2,3-DPG levels; to calculate in vivo P50 in patients with early critical illness; and to explore the relationship between RBC 2,3-DPG and intensive care mortality. Prospective cohort study. General medical-surgical intensive care unit (ICU) of a major Scottish teaching hospital. One-hundred eleven critically ill patients during the first 24 hrs in the ICU with no history of chronic hematologic disorders or RBC transfusion within 24 hrs and 34 age- and sex-matched healthy reference subjects. None. We measured RBC 2,3-DPG concentration, plasma biochemistry values, and arterial blood gas parameters. On average, RBC 2,3-DPG was lower among critically ill patients than controls (mean [sd], 14.1 [6.3] vs. 16.7 [3.7] mumol/g hemoglobin; p = .004) and had a wider range of values (patients, 3.2-32.5 mumol/g hemoglobin; reference group, 9.1-24.3). Regression analysis indicated a strong independent association between plasma pH and RBC 2,3-DPG (B, 32.15 [95% confidence interval, 19.07-46.22], p < .001) and a weak association with plasma chloride (B, -0.196 [95% confidence interval, -0.39 to -0.01], p = .044) but not with hemoglobin or other measured biochemical parameters. The mean calculated in vivo P50 level was normal (3.8 kPa) but varied widely among patients (range, 2.0-5.5 kPa). RBC 2,3-DPG concentration was similar for ICU survivors and nonsurvivors. RBC 2,3-DPG concentrations vary widely among critically ill patients. Acidosis is associated with lower RBC 2,3-DPG concentrations, but anemia is not associated with a compensatory increase in RBC 2,3-DPG early in critical illness. Lower RBC 2,3-DPG concentrations during the first 24 hrs of intensive care are not associated with higher ICU mortality.


Treatment of Hoffa fracture of femoral condyle with anchor combined with auxiliary fixation.
A Hoffa fracture is an unstable intra-articular break that is generally treated with surgery. To evaluate the feasibility and clinical outcomes of using a suture anchor combined with auxiliary fixation for the treatment of a lateral femoral condyle Hoffa fracture. The study retrospectively reviewed 8 patients (5 males and 3 females) with a lateral femoral condyle Hoffa fracture who had been treated by combining a suture anchor with auxiliary fixation between January 2016 and April 2020. The mean age of patients was 37.5 years (ranging from 23 to 45). According to Letenneur's classification, there were 4 cases of type I, 2 cases of type II, and 2 cases of type III fractures. The clinical outcomes were assessed using Letenneur's functional assessment. The follow-up duration ranged between 14-24 months. All patients achieved primary healing of the incision and fracture union, as well as normal flexion and extension of the knee joint, with 7 cases showing excellent outcomes and 1 case showing a good outcome. No postoperative complications, such as fracture displacement, anchor loosening, or fracture malunion, occurred in this series. Our results indicated that a suture anchor, combined with external fixation, was an effective treatment for a lateral femoral condyle Hoffa fracture. Accordingly, this procedure is worthy of wider clinical application.


ZnI2-Directed Stereocontrolled α-Glucosylation.
Here we report a glucosylation strategy mediated by ZnI2, a cheap and mild Lewis acid, for the highly stereoselective construction of 1,2-cis-O-glycosidic linkages using easily accessible and common 4,6-O-tethered glucosyl donors. The versatility and effectiveness of the α-glucosylation strategy were demonstrated successfully with various acceptors, including complex alcohols. This approach demonstrates the feasibility of the modular synthesis of various α-glucans with both linear and branched backbone structures.


Diabetes mellitus attenuates the repolarization reserve in mammalian heart.
In diabetes mellitus several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models changes in these parameters were reported, but no such data are available in other mammalian species including the dog. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and its underlying transmembrane ionic currents and channel proteins in canine hearts. Diabetes was induced by a single injection of alloxan, a subgroup of dogs received insulin substitution. After the development of diabetes (8 weeks) electrophysiological studies were performed using conventional microelectrodes, whole cell voltage clamp, and ECG. Expression of ion channel proteins was evaluated by Western blotting. The QTc interval and the ventricular action potential duration in diabetic dogs were moderately prolonged. This was accompanied by significant reduction in the density of the transient outward K+ current (I(to)) and the slow delayed rectifier K+ current (I(Ks)), to 54.6% and 69.3% of control, respectively. No differences were observed in the density of the inward rectifier K+ current (I(K1)), rapid delayed rectifier K+ current (I(Kr)), and L-type Ca2+ current (I(Ca)). Western blot analysis revealed a reduced expression of Kv4.3 and MinK (to 25+/-21% and 48+/-15% of control, respectively) in diabetic dogs, while other channel proteins were unchanged (HERG, MiRP1, alpha(1c)) or increased (Kv1.4, KChIP2, KvLQT1). Insulin substitution fully prevented the diabetes-induced changes in I(Ks), KvLQT1 and MinK, however, the changes in I(to), Kv4.3, and Kv1.4 were only partially diminished by insulin. It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization, attenuates the repolarization reserve by decreasing I(to) and I(Ks) currents, and thereby may markedly enhance the risk of sudden cardiac death.


COLOR POLYMORPHISM IN PACIFIC TREE FROGS.
Crosses between green and non-green Hyla regilla suggest that green color is determined by genes at two loci; each loci must have a dominant gene. Red is the result of a recessive gene and brown a dominant gene. The frequency of frogs with each color varies in different populations.


Occupational radiation exposure in health care facilities.
Radiation, which is used extensively to diagnose and treat human diseases, poses an occupational health risk for the concerned health workers. Personal dosimetry is an important tool to monitor occupational radiation exposures. This study was conducted to reveal and to describe the situation of occupational radiation exposure monitoring among staffs in different health care facilities in Nepal. A cross-sectional study was performed among the 35 Health Care Facilities. Information about types and number of X-ray procedures performed, types and number of personnel involved, workload and the availability of personal dosimetry service were collected. Six Health Care Facilities had personal dosimetry service available for a total of 149 personnel. Of a total of nearly one million X-ray procedures performed in the 35 Health Care Facilities in 2007, 76 percent was performed by non-monitored personnel. The majority of the facilities performing high dose procedures, like catheterisation, angiography and intestinal barium procedures did not offer personal dosimetry for the involved personnel. There are a limited number of personnel being monitored with personal dosimetry. There are no regulatory dose limits for occupationally exposed staff. Thus, there is an urgent need to establish a national radiation protection authority to regulate the use of radiation in Nepal.


Beneficial effects of a nitric oxide donor on recovery of contractile function following brief hypoxia in isolated rat heart.
Brief myocardial hypoxia causes both systolic and diastolic dysfunction, the latter often persisting during re-oxygenation. The underlying mechanisms may involve cytosolic Ca2+ overload as well as altered myofilament properties. Recent studies show that nitric oxide enhances myocardial relaxation via a cGMP-induced reduction in myofilament response to Ca2+. We studied the effects of pretreatment with a nitric oxide donor, sodium nitroprusside (0.1-1 microM) on the response to 5 min hypoxia in isovolumic rat hearts perfused at constant coronary flow. Left ventricular relaxation was assessed by an exponential time constant of pressure fall. Sodium nitroprusside reduced the depression of peak left ventricular pressure and peak dP/dt during hypoxia, and improved left ventricular relaxation both during hypoxia and re-oxygenation. Similar results were observed with a Ca2+ antagonist, nicardipine (10 nM). However, adenosine (400 nM), which reduced coronary perfusion pressure to a similar extent as the other two drugs, failed to improve left ventricular function. Addition of sodium nitroprusside or nicardipine at re-oxygenation did not improve relaxation, but instead impaired recovery of peak left ventricular pressure. These results suggest that exogenous nitric oxide improves LV contractile function, in particular relaxation, during brief hypoxia-re-oxygenation independent of changes in coronary flow or coronary perfusion pressure. Its failure to be protective if administered only during re-oxygenation suggests that its action does not involve an anti-oxidant effect.


Enhanced Gas Uptake in a Microporous Metal-Organic Framework via a Sorbate Induced-Fit Mechanism.
Physical adsorption of gas molecules in microporous materials is an exothermic process, with desorption entropy driving a decrease in uptake with temperature. Enhanced gas sorption with increasing temperature is rare in porous materials and is indicative of sorbate initiated structural change. Here, sorption of C2H6, C3H6, and C3H8 in a flexible microporous metal-organic framework (MOF) {Cu(FPBDC)]·DMF}n (NKU-FlexMOF-1) (H2FPBDC = 5-(5-fluoropyridin-3-yl)-1,3-benzenedicarboxylic acid) that increases with rising temperature over a practically useful temperature and pressure range is reported along with other small molecule and hydrocarbon sorption isotherms. Single X-ray diffraction studies, temperature-dependent gas sorption isotherms, in situ and variable temperature powder X-ray diffraction experiments, and electronic structure calculations were performed to characterize the conformation-dependent sorption behavior in NKU-FlexMOF-1. In total, the data supports that the atypical sorption behavior is a result of loading-dependent structural changes in the flexible framework of NKU-FlexMOF-1 induced by sorbate-specific guest-framework interactions. The sorbates cause subtle adaptations of the framework distinct to each sorbate providing an induced-fit separation mechanism to resolve chemically similar hydrocarbons through highly specific sorbate-sorbent interactions. The relevant intermolecular contacts are shown to be predominantly repulsion and dispersion interactions. NKU-FlexMOF-1 is also found to be stable in aqueous solutions including toleration of pH changes. These experiments demonstrate the potential of this flexible microporous MOF for cost and energy efficient industrial hydrocarbon separation and purification processes. The efficacy for the separation of C3H6/C3H8 mixtures is explicitly demonstrated using NKU-FlexMOF-1a (i.e., activated NKU-FlexMOF-1) for a particular useful temperature range.


Bias annealing: a method for obtaining transition paths de novo.
Computational studies of dynamics in complex systems require means for generating reactive trajectories with minimum knowledge about the processes of interest. Here, we introduce a method for generating transition paths when an existing one is not already available. Starting from biased paths obtained from steered molecular dynamics, we use a Monte Carlo procedure in the space of whole trajectories to shift gradually to sampling an ensemble of unbiased paths. Application to basin-to-basin hopping in a two-dimensional model system and nucleotide-flipping by a DNA repair protein demonstrates that the method can efficiently yield unbiased reactive trajectories even when the initial steered dynamics differ significantly. The relation of the method to others and the physical basis for its success are discussed.


Diagnosis and Management of Polycythemia Vera in a Ferret (Mustela putorius furo).
A 5-y-old female ferret (Mustela putorius furo) was evaluated for diarrhea, anorexia, and lethargy for 1 wk. Only mild dehydration was detected on physical examination. CBC analysis revealed marked erythrocytosis with an unremarkable plasma biochemistry panel; follow-up CBC analyses revealed a consistent primary erythrocytosis. Whole-body radiographs and abdominal ultrasonography were unremarkable except for a small nephrolith in the right kidney and a small cyst in the left kidney. The plasma erythropoietin level was 17.0 mIU/mL and considered normal. In light of the diagnostic work-up and consistent erythrocytosis, a diagnosis of polycythemia vera (primary erythrocytosis) was made. The initial presentation of diarrhea resolved after treatment with oral metronidazole (20 mg/kg PO BID for 7 d). Treatment for the polycythemia consisted of a phlebotomy initially followed by chemotherapy with hydroxyurea (10 mg/kg PO BID). During the subsequent 12 mo, the hydroxyurea dose adjusted according to follow-up CBC results, and finding an optimal dosage regimen proved to be challenging. One year after the initial diagnosis, the ferret presented to an emergency clinic for acute and severe hemorrhagic diarrhea and died shortly thereafter. The postmortem diagnosis was acute venous infarction of the small and large intestine. To our knowledge, this report is the first to describe the diagnosis and long-term management of polycythemia vera in a ferret and the use of hydroxyurea for this purpose.


Fractionation and Extraction of Crude Nuclear Proteins From Arabidopsis Seedlings.
The plant nucleus is an important subcellular organelle that contains the genome, ribosomal RNA, and regulatory proteins, and performs a central role in the functioning and metabolism of the cell. Fractionation of intact nuclei is a crucial process to elucidate the function of nuclear proteins. Here, we present a simple method for the fractionation of crude nuclei and extraction of nuclear proteins, based on previously established methods. This protocol provides an easy and quick method to isolate crude nuclei and extract nuclear proteins from Arabidopsis seedlings, which is useful for the research on the nuclear proteins, without requirement for high-purity nuclei. Graphic abstract: Schematic procedure for the isolation of crude nuclei and extraction of nuclear proteins from Arabidopsis seedlings.


Immunohistochemical and topographic studies of dendritic cells and macrophages in human fetal cornea.
To investigate the distribution and phenotype of major histocompatibility complex (MHC) class II-positive dendritic cells and macrophages in normal human fetal cornea in the age range 10 to 25 weeks gestation. Peroxidase and gold immunohistochemistry were used to visualize MHC class II and macrophage antigen (S22) immunoreactive cells. Cell distributions were analyzed quantitatively, and topographic maps were produced. Immunoreactive cells, concentrated centrally, were present at 10 weeks gestation in the corneal epithelium and stroma. Average densities increased steadily up to 25 weeks gestation. Two morphologic forms of MHC class II and S22 immunoreactive cells were observed--large, dendritiform cells and small, rounded cells with short processes. Electron microscopy revealed that most MHC class II-positive cells were morphologically consistent with previous ultrastructural descriptions of corneal Langerhans cells. Immunoreactive cells were more numerous in immunogold-labeled specimens than in peroxidase-labeled specimens of similar ages. However, quantitative analysis of both techniques revealed that S22-positive cells comprised 30% to 50% of MHC class II-positive cells. This study provides a detailed description of heterogeneous populations of MHC class II and S22 immunoreactive cells in the human fetal cornea. In contrast to the adult cornea, which is typically devoid of MHC class II-positive cells, immunoreactive cells in the fetal cornea are concentrated centrally and increase in density up to at least 25 weeks gestation. These results indicate that reduction in Langerhans cell numbers to adult levels must occur after 25 weeks gestation. The presence of dendritic cells and macrophages in the fetal cornea has important implications for the understanding of corneal immunology.


Optomechanical characterization of silicon nitride membrane arrays.
We report on the optical and mechanical characterization of arrays of parallel micromechanical membranes. Pairs of high-tensile stress, 100 nm thick silicon nitride membranes are assembled parallel to each other with separations ranging from 8.5 to 200 μm. Their optical properties are accurately determined using transmission measurements under broadband and monochromatic illuminations, and the lowest vibrational mode frequencies and mechanical quality factors are determined interferometrically. The results and techniques demonstrated are promising for investigations of collective phenomena in optomechanical arrays.


CNS drug design based on principles of blood-brain barrier transport.
Lipid-soluble small molecules with a molecular mass under a 400-600-Da threshold are transported readily through the blood-brain barrier in vivo owing to lipid-mediated transport. However, other small molecules lacking these particular molecular properties, antisense drugs, and peptide-based pharmaceuticals generally undergo negligible transport through the blood-brain barrier in pharmacologically significant amounts. Therefore, if present day CNS drug discovery programs are to avoid termination caused by negligible blood-brain barrier transport, it is important to merge CNS drug discovery and CNS drug delivery as early as possible in the overall CNS drug development process. Strategies for special formulation that enable drug transport through the blood-brain barrier arise from knowledge of the molecular and cellular biology of blood-brain barrier transport processes.


Correlation of capecitabine-induced skin toxicity with treatment efficacy in patients with metastatic colorectal cancer: results from the German AIO KRK-0104 trial.
The AIO KRK-0104 randomised phase II trial investigated the efficacy and safety of two capecitabine-based regimens: combination of capecitabine and irinotecan (CAPIRI) plus cetuximab (CAPIRI-C) and combination of capecitabine with oxaliplatin (CAPOX) plus cetuximab (CAPOX-C) in the first-line treatment of metastatic colorectal cancer (mCRC). Treatment-related skin toxicity (ST) was evaluated separately for capecitabine and cetuximab. The present analysis investigates the correlation of capecitabine-attributed ST (Cape-ST) and parameters of treatment efficacy. Patients with mCRC were randomised to cetuximab (400 mg m(-2), day 1, followed by 250 mg m(-2) weekly) plus CAPIRI (irinotecan 200 mg m(-2), day 1; capecitabine 800 mg m(-2), twice daily, days 1-14, every 3 weeks), or cetuximab plus CAPOX (oxaliplatin 130 mg m(-2), day 1; capecitabine 1000 mg m(-2), twice daily, days 1-14, every 3 weeks). Of 185 recruited patients, 149 (CAPIRI-C, n=78; CAPOX-C, n=71) received study treatment beyond the first tumour assessment and were evaluable for efficacy. Capecitabine-attributed ST, predominantly hand-foot syndrome, was observed in 32.2% of patients. Capecitabine-attributed ST grade 1-3 was associated with a significantly higher disease control rate (DCR) (97.9 vs 86.1%, P=0.038) compared with grade 0 toxicity. Moreover, Cape-ST grade 1-3 related to a markedly longer progression-free survival (PFS) (9.9 vs 5.6 months, P<0.001) and overall survival (OS) (32.8 vs 22.4 months, P=0.008). Separate analyses of treatment arms indicated that the effect of Cape-ST on PFS remained significant for both arms, whereas the effect on OS remained apparent as a strong trend. This analysis supports the hypothesis that for the evaluated regimens, a correlation exists between Cape-ST and treatment efficacy regarding DCR, PFS, and OS.


Measuring the complexity of clinical problems.
Recent studies on clinical problem-solving show that a considerable proportion of the problem-solving strategy employed by doctors and medical students is "case specific" or "system specific." Such studies have failed to consider adequately the starting place of the problem-solving process, that is, the inherent complexity of the problem being considered. In presenting clinical problems to students and writing problem-solving skills assessments, educators have demonstrated no quantifiable ways of grading the complexity of the clinical problems they select for instruction or examination purposes. The author in this study reports on the development and application of a complexity index to 29 clinical problems used in a new graduate curriculum. The index uses five components of problem complexity: symptoms, physical signs and investigations, socioeconomic and behavioral factors, diagnoses, and management plans. A test has been made of its interrater reliability between two observers applying it independently in one application. Trials to establish the validity of the complexity index with various criterion groups of physicians and educators are discussed. Suggestions for further refinement of such an index and its application in research in the quality of care and in medical education are offered.


Synthetic peptides probe folding initiation sites in platelet factor-4: stable chain reversal found within the hydrophobic sequence LIATLKNGRKISL.
Platelet factor-4 (PF4) is a 70-residue protein which contains a 3-stranded antiparallel beta-sheet domain on to which is folded a C-terminal alpha-helix and an aperiodic N-terminal region. In this study, three peptides derived from the beta-sheet (residues 24-46 and 38-57) and helix (residues 57-70) domains have been synthesized and studied in aqueous solution by CD and NMR. While peptides 24-46 and 56-70 demonstrate some weak conformational preferences, peptide 38-57 maintains a relatively well-defined, NOE-rich chain reversal sequence, L45-K46-N47-G48-R49-K50, which apparently is stabilized by hydrophobic side-chain interactions from the flanking sequences L41-L45 and I51-L53. Some helix-like conformational populations are noted in the native PF4 I42-A43-T44-L45 beta-strand segment. NOE-based distance geometry calculations yield native-like conformations within the L45-K50 sequence. Among 40 structures, backbone RMS deviations range from 0.5 to 1.2 A, and compared to the same sequence in native PF4, the average RMS deviation is 1.1 A. These results suggest that beta-sheet/turn residues L41-L53 present a folding initiation site on the PF4 folding pathway.


Effects of a movement and swimming program on vital capacity and water orientation skills of children with cerebral palsy.
Swimming and aquatic exercise are known for their effects on respiration in normal and asthmatic people. The purpose of the present study was to evaluate the effect of a 6-month movement and swimming program on the respiratory function and water orientation skills of children with cerebral palsy (CP). Forty-six kindergarten children aged 5 to 7 years were assigned either to a treatment or control group. The intervention program consisted of swimming sessions twice weekly and sessions of group physical activity in a gym once weekly, each session lasting 30 minutes, for a period of 6 months. Children in the control group were treated (30 minutes, 4 days per week) with Bobath physical therapy. The children in the treatment and control groups had comparable disability types, age, and anthropometric measurements. A 2 x 2 (group x test period) repeated measures ANOVA design confirmed a significant effect of interaction of time with group. The results also confirmed that children with CP have reduced lung function compared with normative data for children in the same age category. The treatment program improved baseline vital capacity results by 65%, while children in the control group improved by only 23%. The movement and swimming exercise program had a better effect than a physical therapy routine implemented in a previous study, consisting of respiratory exercise alone.


A systematic in silico report on iron and zinc proteome of Zea mays.
Zea mays is an essential staple food crop across the globe. Maize contains macro and micronutrients but is limited in essential mineral micronutrients such as Fe and Zn. Worldwide, serious health concerns have risen due to the deficiencies of essential nutrients in human diets, which rigorously jeopardizes economic development. In the present study, the systematic in silico approach has been used to predict Fe and Zn binding proteins from the whole proteome of maize. A total of 356 and 546 putative proteins have been predicted, which contain sequence and structural motifs for Fe and Zn ions, respectively. Furthermore, the functional annotation of these predicted proteins, based on their domains, subcellular localization, gene ontology, and literature support, showed their roles in distinct cellular and biological processes, such as metabolism, gene expression and regulation, transport, stress response, protein folding, and proteolysis. The versatile roles of these shortlisted putative Fe and Zn binding proteins of maize could be used to manipulate many facets of maize physiology. Moreover, in the future, the predicted Fe and Zn binding proteins may act as relevant, novel, and economical markers for various crop improvement programs.


A combination of supplements may reduce the risk of Alzheimer's disease in elderly Japanese with normal cognition.
A number of studies have examined the effect of a single supplement against Alzheimer's disease (AD) with conflicting results. Taking into account the complex and multifactorial nature of AD pathogenesis, multiple supplements may be more effective. Physical activity is another prospect against AD. An open-label intervention study was conducted to explore a potential protective effect of multiple supplements and physical activity. Their interaction was also examined. Participants were community-dwelling volunteers aged 65 or older as of May 2001 in a rural area of Japan. Among 918 cognitively normal participants included in the analyses, 171 took capsules daily for three years that contained n-3 polyunsaturated fatty acid, Ginkgo biloba leaf dry extracts, and lycopene. Two hundred and forty one participants joined the two-year exercise intervention that included a community center-based and a home-based exercise program. One-hundred and forty eight participated in both interventions. A standardized neuropsychological battery was administered at baseline in 2001, the first follow-up in 2004-2005, and the second in 2008-2009. The primary outcome was AD diagnosis at follow-ups. A complementary log-log model was used for survival analysis. A total of 76 participants were diagnosed with AD during follow-up periods. Higher adherence to supplementation intervention was associated with lower AD incidence in both unadjusted and adjusted models. Exercise intervention was also associated with lower AD incidence in the unadjusted model, but not in the adjusted model. We hypothesized that the combination of supplements acted in a complementary and synergistic fashion to bring significant effects against AD occurrence.


GDE2-RECK controls ADAM10 α-secretase-mediated cleavage of amyloid precursor protein.
A disintegrin and metalloprotease 10 (ADAM10) is the α-secretase for amyloid precursor protein (APP). ADAM10 cleaves APP to generate neuroprotective soluble APPα (sAPPα), which precludes the generation of Aβ, a defining feature of Alzheimer's disease (AD) pathophysiology. Reduced ADAM10 activity is implicated in AD, but the mechanisms mediating ADAM10 modulation are unclear. We find that the plasma membrane enzyme glycerophosphodiester phosphodiesterase 2 (GDE2) stimulates ADAM10 APP cleavage by shedding and inactivating reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a glycosylphosphatidylinositol (GPI)-anchored inhibitor of ADAM10. In AD, membrane-tethered RECK is highly elevated and GDE2 is abnormally sequestered inside neurons. Genetic ablation of GDE2 phenocopies increased membrane RECK in AD, which is causal for reduced sAPPα, increased Aβ, and synaptic protein loss. RECK reduction restores the balance of APP processing and rescues synaptic protein deficits. These studies identify GDE2 control of RECK surface activity as essential for ADAM10 α-secretase function and physiological APP processing. Moreover, our results suggest the involvement of the GDE2-RECK-ADAM10 pathway in AD pathophysiology and highlight RECK as a potential target for therapeutic development.


[The non-recurrent inferior laryngeal nerve. Surgical experience].
During the performance of 1018 thyroid operations, 1497 recurrent laryngeal nerves were identified and exposed. Of the 773 visualized nerves on the right side, 2 were found to be non recurrent (0.26%). This abnormality may represent a pitfall during thyroidectomy even for very experienced thyroid surgeons. We emphasize that the exposure and preservation of this vital structure is the standard of care and an essential component of routine dissection in thyroid surgery.


Effects of dental attendance frequency in heavy and low private care-using young adults.
In Finland, adults born in 1961 or later were progressively entitled to subsidies for dental care from private practitioners during 1986-90, while at the same time having access to care in the Public Dental Service. The aim of this study was to compare the effects of attendance frequency of private dental care on treatment costs and treatment spectrum for the heaviest and lowest users over a period. Three separate cohorts of recipients of reimbursements were formed, using the Social Insurance Register. The highest and lowest cost groups in 1986, 1990, and 1994 were followed up to 1997. Initially, the mean numbers of visits were 1.2-1.3 and 5.2-5.6 and cost Euro 48 53 and Euro 358-379 among low users and heavy users, respectively, in all cohorts. Among the heavy users (the high-cost category) infrequent attendance was related to higher and frequent attendance to lower mean annual costs of care. Among the low users (the low-cost category the opposite was true. Those who initially belonged to the high-cost category received in 1997 significantly more (P < 0.01) restorative treatment and, to a lesser extent, more (P < 0.01) preventive and periodontal treatment than those belonging to the low-cost category. Frequent dental care seemed to benefit those who received a lot of care. Frequency of attendance was not associated with being a low or a heavy user, indicating rigid check-up routines. The inclusion of simple oral health data would greatly improve the usefulness of the register as an evaluation tool for health-political decisions.


Endothelial nitric oxide synthase gene single nucleotide polymorphisms and the risk of hypertension: A meta-analysis involving 63,258 subjects.
The endothelial nitric oxide synthase (eNOS) gene plays an important role in regulating vascular tone and blood pressure. Recently, the eNOS G894T and T-786C single nucleotide polymorphisms (SNPs) were intensively studied with regard to their associations with hypertension. However, the results of these studies were inconsistent. Therefore, we conducted the so far largest meta-analysis to better assess the correlations between eNOS SNPs and hypertension. Eligible articles were searched in PubMed, Medline, Embase, Scopus, and CNKI up to April 2016. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential associations between eNOS SNPs and the risk of hypertension. A total of 95 case-control studies involving 29,308 hypertension cases and 33,950 healthy controls were analyzed. The overall meta-analysis results showed that eNOS G894T and T-786C SNPs were both significantly associated with the risk of hypertension, the T allele of G894T SNP (G versus T, P < 0.00001, OR = 0.82, 95% CI 0.76-0.89) and C allele of T-786C SNP (T versus C, P = 0.004, OR = 0.92, 95% CI 0.87-0.97) conferred an increased susceptibility to hypertension. Further subgroup analyses yielded similar positive results for G894T SNP in essential hypertension, gestational hypertension, and Asian ethnicity, and that for T-786C SNP in essential hypertension and Asian population. Overall, our findings suggest that eNOS G894T and T-786C SNPs were both significantly correlated with hypertension. Additionally, the T allele of G894T SNP and C allele of T-786C SNP may serve as potential biological markers for hypertension susceptibility in Asians.


A new AT III-heparin-complex preparation: in vitro and in vivo characterisation.
The in vitro experiments show that the anticoagulant affect of a new AT III-Heparin-complex preparation in plasma is similar to heparin. The in vivo experiments indicate that the thrombin inhibition is even improved by using the complex preparation, because the aPTT values after complex treatment remained stable for more than one hour in the desired range. Bleeding complications are less likely after complex treatment, because much smaller maximum aPTT values are reached. The prolonged half life of the complex preparation possibly allows a reduced and more accurate dosage.


Postoperative complications affect early recurrence of hepatocellular carcinoma after curative resection.
Postoperative recurrence remains the major cause of death after curative resection for hepatocellular carcinoma (HCC). This study was conducted to evaluate the impact of postoperative complications on HCC recurrence after curative resection. The postoperative outcomes of 274 HCC patients who underwent curative resection were analysed retrospectively. Of the 247 HCC patients, 103 (37.6 %) patients developed postoperative complications. The occurrence of postoperative complications was found to be associated with a significantly higher tumor recurrence (76.2 % vs. 56.6 %, P = 0.002) and a lower 5-year overall survival rate (27.7 % vs. 42.1 %; P = 0.037) as compared with those without complications. Regarding the recurrence pattern, early recurrence (≤2 years) was more frequently seen in patients with complications than that in patients without complications (54.5 % vs.38.6 %; P = 0.011). Multivariate analysis indicated that postoperative complications occurrence was an independent risk factor for early recurrence (odds ratio [OR] 2.223; 95 % confidence intervals [95 % CI] 1.161-4.258, P = 0.016) and poor overall survival (OR 1.413; 95 % CI, 1.012-1.971, P = 0.042). The results of the present study indicate that the occurrence of postoperative complications is a predictive factor for HCC recurrence after curative hepatectomy, especially for early recurrence.


Age differences in the last week of life in advanced cancer patients followed at home.
A retrospective analysis of a consecutive sample of patients admitted to a home care program was performed. Data were recorded in the last week through a backward analysis from the day before death as follows: 1 week before dying (-1W), 3 days before death (-3D), and the day before dying (-1D). Data to be collected included the Edmonton Symptom Assessment System (ESAS), background pain intensity, the prevalence of breakthrough pain, the use of opioids in the last week, and the need for palliative sedation, with indications, duration, and drugs used. Patients were distributed according to the following age ranges: adults (<65 years, A) and aged (≥65 years, O). Of the latter group, three subgroups were assessed: old (65-74 years, O1), very old (75-84 years, O2), and the oldest (≥85 years, O3). Four hundred eleven patients were assessed. At -W1, no statistical differences in intensity of ESAS items ≥4 among the age subgroups were found. For ESAS values at -1W, -3D, and -1D, no statistical differences were found unless for anorexia at -1W (p = 0.000) (more likely), depression at -3D (p = 0.000) (less likely), depression (p = 0.000), and dyspnea (p = 0.01) (less likely) at -1D in the oldest group (O3). No differences in pain intensity among the groups were found (p = 0.54). Opioid doses increased in time and were significantly lower in older patients (p = 0.000). The subcutaneous route was more frequently used at -3D and -1D in older patients. No differences in opioid switching were found among the groups (p = 0.56). Adult patients required more often palliative sedation (p = 0.003). Older patients have problems relatively similar to adult patients in the last week of life, unless for some symptoms. Older patients had also a lower opioid consumption, a more frequent use of the subcutaneous route, and a lower need for palliative sedation.


Explorative analysis of IPA-SPECT data through statistical inference for an automated diagnosis of glioma tumor.
The identification of a brain tumor imaged with PET or SPECT is usually performed with visual inspection of an expert medical clinician. However an automated diagnostic of such images hasn't been established or applied. In this study, we explored the possibility of establishing an automated statistical analysis for the diagnosis of glioma by means of IPA-SPECT data. On the basis of a dataset of 100 patients that have undergone MRI and IPA-SPECT acquisition, in this work, we identify an automated workflow. Three different approaches were explored: I. statistical non-parametric mapping analysis (SnPM), II. statistical non-parametric analysis with an increased number of permutations due to sign-flipping function (PALM) and III. statistical parametric analysis (SPM). The automated methods were compared with the visual inspection. The study proved PALM and SPM approaches to have a high diagnostic power. Compared to the parametric methods, the non-parametric method is the mathematically correct approach for the problem in question. If we take the high resolution structural MRI information into account, the diagnostic power of PALM was not significantly inferior to the visual inspection (P = 0.5150), showing an area under the ROC curve (AUC) smaller only by less than 3%. The automated diagnostic method based on statistical inference, here applied to diagnose glioma tumors in IPA-SPECT data, seems to be a promising tool that can support the visual investigation in nuclear medicine. Moreover in the foreseeable future, the presented methodology has a big potential in various application like localization of active tumor tissues in surgical resection or stereotactic radiosurgery.


Pharmacomodulations around the 4-oxo-1,4-dihydroquinoline-3-carboxamides, a class of potent CB2-selective cannabinoid receptor ligands: consequences in receptor affinity and functionality.
CB2 receptor selective ligands are becoming increasingly attractive drugs due to the potential role of this receptor in several physiopathological processes. Thus, the development of our previously described series of 4-oxo-1,4-dihydroquinoline-3-carboxamides was pursued with the aim to further characterize the structure-affinity and structure-functionality relationships of these derivatives. The influence of the side chain was investigated by synthesizing compounds bearing various carboxamido and keto substituents. On the other hand, the role of the quinoline central scaffold was studied by synthesizing several 6-, 7-, or 8-chloro-4-oxo-1,4-dihydroquinolines, as well as 4-oxo-1,4-dihydronaphthyridine and 4-oxo-1,4-dihydrocinnoline derivatives. The effect of these modifications on the affinity and functionality at the CB2 receptor was studied and allowed for the characterization of new selective CB2 receptor ligands.


Ultrastructure of the shoot apex of Chenopodium album and certain other seed plants.
The ultrastructure of cells of the vegetative shoot apices is described for Chenopodium album, Kalanchoë blossfeldiana and K. laxiflora, Bryophyllum daigremontianum, Nicotiana rustica, and N. tabacum (Maryland Mammoth), and Ginkgo biloba. A less intensive study was made of the last three listed. The structures and organelles usually associated with meristematic cells were observed: dictyosomes, plastids (in various stages of development), mitochondria, endoplasmic reticulum (ER), vacuoles, lipid droplets, and plasmalemma. In addition, spherosome-like structures were observed in all zones of the shoot apices. Also, multivesicular bodies were observed in C. album and B. daigremontianum. Ribosome density is greater in cells of the flank meristem. Proplastids, plastids with prolamellar bodies, or grana have a differential distribution in the apex, characteristic for a particular species. Confirmation could not be given to the concept that vacuoles arise as a series of local dilations in long extensions of the so called "smooth ER." The tonoplast and ER are distinguishable at the time of inception of a vacuole, although the tonoplast may arise from the ER. Rapid growth of a vacuole and/or fusion with other vacuoles may result in irregularly shaped prevacuoles. No vacuoles were observed to originate from cisternae of dictyosomes in the species studied.


Promotion of Latina Health: Intersectionality of IPV and Risk for HIV/AIDS.
Latina women in the United States are vulnerable to two intersecting public health concerns: intimate partner violence (IPV) and subsequent risk for HIV/AIDS infection. Examination of the cultural and contextual life factors of this understudied population is crucial to developing culturally relevant HIV interventions. Focus groups with Latinas (15 monolingual; 10 bilingual) who have experienced IPV were conducted. Monolingual and bilingual Latinas endorsed that they were concerned about HIV infection, naming partner infidelity and experiences of forced and coerced sex as primary reasons for their concern. However, monolingual participants had lower levels of HIV knowledge, spending much time discussing myths of HIV infection, whereas bilingual participants spent more time discussing specific prevention techniques, including challenges related to the violence in their relationships. These findings suggest that HIV/AIDS prevention programs for Latinas need to pay close attention to the different historical, contextual, and cultural experiences of this at-risk group of women.


[Spectrum of pathogens for community-acquired pneumonia in children].
To investigate the spectrum of pathogens for community-acquired pneumonia (CAP) in children, and to provide a basis for the diagnosis and treatment of CAP. Respiratory secretions and venous blood samples were collected from 1560 children with CAP aged from one month to 9 years within 2 hours after admission, for detection of multiple pathogens. Respiratory virus antigens in nasopharyngeal swab specimens were detected by immunofluorescence. Sputum was used for bacterial culture. Levels of Mycoplasma pneumoniae (MP)-IgM and Chlamydia pneumoniae (CP)-IgM in venous blood were measured by enzyme-linked immunosorbent assay. A total of 579 strains of bacteria were isolated from all respiratory secretions, including 213 (36.8%) Gram-positive strains and 366 (63.2%) Gram-negative strains. The five most common strains were Haemophilus influenzae (7.50%), Streptococcus pneumoniae (6.73%), Staphylococcus aureus (6.35%), Moraxella catarrhalis (5.19%), and Escherichia coli (3.46%), wherein the beta-lactamase-producing strains accounted for 3.3% of all strains. The non-bacterial pathogens mainly included respiratory syncytial virus (12.88%), MP (7.88%), and CP (8.91%). Mixed infection of pathogens was serious, and the mixed infection of respiratory syncytial virus with Haemophilus influenzae infections were the most common. For most pathogens, the infection rate was higher in children aged under one year than in those aged over one year. Haemophilus influenzae, respiratory syncytial virus, MP and CP are the main pathogens for children with CAP. For most pathogens, the infection rate is higher in children aged under one year than in those aged over one year. Mixed infection rate of pathogens is high.


Biphilic Organophosphorus-Catalyzed Intramolecular Csp2-H Amination: Evidence for a Nitrenoid in Catalytic Cadogan Cyclizations.
A small-ring phosphacycloalkane (1,2,2,3,4,4-hexamethylphosphetane, 3) catalyzes intramolecular C-N bond forming heterocyclization of o-nitrobiaryl and -styrenyl derivatives in the presence of a hydrosilane terminal reductant. The method provides scalable access to diverse carbazole and indole compounds under operationally trivial homogeneous organocatalytic conditions, as demonstrated by 17 examples conducted on 1 g scale. In situ NMR reaction monitoring studies support a mechanism involving catalytic PIII/PV═O cycling, where tricoordinate phosphorus compound 3 represents the catalytic resting state. For the catalytic conversion of o-nitrobiphenyl to carbazole, the kinetic reaction order was determined for phosphetane catalyst 3 (first order), substrate (first order), and phenylsilane (zeroth order). For differentially 5-substituted 2-nitrobiphenyls, the transformation is accelerated by electron-withdrawing substituents (Hammett factor ρ = +1.5), consistent with the accrual of negative charge on the nitro substrate in the rate-determining step. DFT modeling of the turnover-limiting deoxygenation event implicates a rate-determining (3 + 1) cheletropic addition between the phosphetane catalyst 3 and 2-nitrobiphenyl substrate to form an unobserved pentacoordinate spiro-bicyclic dioxazaphosphetane, which decomposes via (2 + 2) cycloreversion giving 1 equiv of phosphetane P-oxide 3·[O] and 2-nitrosobiphenyl. Experimental and computational investigations into the C-N bond forming event suggest the involvement of an oxazaphosphirane (2 + 1) adduct between 3 and 2-nitrosobiphenyl, which evolves through loss of phosphetane P-oxide 3·[O] to give the observed carbazole product via C-H insertion in a nitrene-like fashion.


Conestat alfa for the treatment of angioedema attacks.
Recently, multiple C1 inhibitor (C1-INH) replacement products have been approved for the treatment of hereditary angioedema (HAE). This review summarizes HAE and its current treatment modalities and focuses on findings from bench to bedside trials of a new C1-INH replacement, conestat alfa. Conestat alfa is unique among the other C1-INH replacement products because it is produced from transgenic rabbits rather than derived from human plasma donors, which can potentially allow an unlimited source of drug without any concern of infectious transmission. The clinical trial data generated to date indicate that conestat alfa is safe and effective for the treatment of acute HAE attacks.


Manganese Mineralization of Pathogenic Viruses as a Universal Vaccine Platform.
Biomimetic viral mineralization improves viral vaccine stability and immunogenicity using inorganic metals such as Ca, Al, or Fe. Mn is a metal found in high concentrations in mammalian tissues; however, under natural or laboratory conditions, Mn mineralization by medical viruses has yet to be established. Herein, a single IAV particle is successfully encapsulated with manganese phosphate (MnP) under specific conditions using the human influenza A virus (IAV). MnP-mineralized IAVs (IAV@Mn) exhibited physiochemical and in vitro properties similar to Ca-mineralized IAVs. In animal models, IAV@Mn shows limited replication in immune-competent cells and a significant attenuation compared to naïve cells. Moreover, a single-dose vaccination with IAV@Mn induced robust humoral and cellular immune responses and conferred significant protection against a wild-type IAV challenge in mice. Thus, Mn mineralization in pathogenic viruses provides a rapid and universal strategy for generating an emergency vaccine in response to emerging viruses.


Cobalt-catalyzed C-H cyanation of arenes and heteroarenes.
Carboxylate assistance proved to be the key for the success of efficient cobalt(III)-catalyzed C-H cyanations. Thus, an in situ generated cationic cobalt complex was identified as a versatile catalyst for the site-selective synthesis of various aromatic and heteroaromatic nitriles with ample substrate scope.


[Spatial heterogeneity and forest regeneration].
The research on spatial heterogeneity is meaningful for forest regeneration dynamics, which is a critical part in the forest ecosystem dynamics. Traditionally, forestry scientists are mainly concentrated their attention to the studies on the process of regeneration. However forests are spatiotemporal heterogeneous. In regeneration, there exists an ecological dynamic process at temporal scale, but also a heterogeneous pattern at spatial scale. Almost of the factors influencing forest regeneration, including both botic and abotic environment, both natural and human disturbances, and both characteristics of tree species and response of tree species to different disturbance agents, are spatially heterogeneous. Discussion on spatial heterogeneity and its effect on regeneration is indispensable for the understanding of the pattern, process and mechanism of forest regeneration. Main research contents and viewpoints of spatial heterogeneity in forest regeneration were summarised on the basis of available literature, and sources of spatial heterogeneity in the process of regeneration were analysed. The response of species to spatial heterogeneity, small-scale spatial heterogeneity and regeneration dynamics, spatial heterogeneity of lights in stand and regeneration pattern, and correlative relationships between the scales of soil heterogeneity and regeneration heterogeneity were reviewed.


Long-term effects and quality of life following definitive bile duct reconstruction.
The study covered a cohort of 236 patients with transection of hepatic duct. It aimed to assess the long-term outcome of the reconstruction and a patient's quality of life.The literature contains many controversies over timing of biliary reconstruction and who ought to repair the injury but just few reports on the long-term outcomes and patient's quality of life.The bile duct system was reconstructed by hepaticojejunostomy in 236 patients. Of these, 139 patients were initially repaired at a public hospital and referred because of stricture (Group A, N = 59) or of an anastomosis dehiscence (Group B, N = 80); 97 were unrepaired and referred because of a surgical clip occluding the duct (Group C, N = 39) or bile leakage from an open duct (Group D, N = 58). All patients were surveyed in 2015 for quality of life using WHOQOL-BREF.The mean time of follow-up was 150 months. The time without symptoms amounted to >5 years in 78.6% of patients. The mean time before anastomosis renewal ranged from 8.9 to 4.7 years (P < .04). Multivariate analysis showed infection, failure of reconstruction in public hospital, and female sex as factors responsible for poor long-term outcome.Patients in Group C had better quality of life than the others (P < .001) with respect to physical health (median 67.85) and psychological condition (median 79.16). The overall mortality was 15.2%.The long-term result of reconstruction depends on the cause of referral which, in turn, arises from subsequent intervention taken in local hospitals.


Autoimmune regulator (AIRE) gene is expressed in human activated CD4+ T-cells and regulated by mitogen-activated protein kinase pathway.
The autoimmune regulator (AIRE) gene is a gene responsible for autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Here we show that AIRE is expressed in human peripheral CD4-positive T-cells, and most highly in antigen-and interleukin 2-stimulated T (IL-2T) cells. Mitogen-activated protein kinases (MAPKs), including MAPK kinase (MEK) 1/2 and p38 MAPK, were phosphorylated in IL-2T cells and the expression of the AIRE gene was inhibited by a specific p38 MAPK inhibitor (SB203580), thereby indicating that AIRE gene expression is controlled by the MAPK pathway in IL-2T cells. These data suggested the possible significance of the AIRE gene in the peripheral immune system.


Can countries of the WHO African Region wean themselves off donor funding for health?
More than 20% of total health expenditure in 48% of the 46 countries in the WHO African Region is provided by external sources. Issues surrounding aid effectiveness suggest that these countries ought to implement strategies for weaning off aid dependency. This paper broaches the following question: what are some of the strategies that countries of the region can employ to wean off donor funding for health? Five strategies are discussed: reduction in economic inefficiencies; reprioritizing public expenditures; raising additional tax revenues; increased private sector involvement in health development; and fighting corruption.


[Primary malignant melanoma of the nasal cavity presenting as a large tumor of the cheek].
Malignant melanoma of the nasal cavity is a rare tumor usually causing unilateral nasal obstruction and nasal bleeding. Diagnosis is achieved with immunohistochemistry analysis. Surgery is proposed for curative treatment. We report the case of a 60-year-old man with a malignant melanoma of the nasal cavity revealed by an important tumor of the cheek. Epistaxis and nasal obstructive syndrome occurred later. Because of the tumor stage, palliative chemotherapy was performed but the patient died 4 months after the diagnosis. This clinical presentation of malignant melanoma of the nasal cavity, related to local spreading, is exceptional. CT scan and MRI are essential for tumor staging and therapeutic decision-making. Prognosis remains poor.