High alkaline phosphatase and low intact parathyroid hormone associate with worse clinical outcome in peritoneal dialysis patients.
Alkaline phosphatase (ALP) is used as a biomarker to monitor the chronic kidney disease-mineral bone disorder (CKD-MBD) and high levels of parathyroid hormone (PTH) that were reported to be related to increased mortality in CKD patients. Therefore, we conducted this longitudinal cohort study to evaluate the relations between ALP and intact PTH (iPTH) and the associations with all-cause and cardiovascular mortality in peritoneal dialysis (PD) patients. In 1276 incident PD patients (median age 50 years, 56% males), baseline serum ALP, iPTH, and metabolic biomarkers potentially linked to CKD-MBD were analyzed in relation to mortality during follow-up period of up to 60 months. All-cause and cardiovascular mortality risk of ALP and iPTH were analyzed with competing-risks regression models with transplantation as competing risk adjusting for all covariates. After adjustments for confounders by logistic regression model, older age, higher change level to levels of iPTH, S-albumin, calcium, alanine transaminase (ALT), and lower level of phosphorus were associated with higher ALP level (>79 U/L), and female gender, non-diabetes mellitus, younger age, lower calcium, higher ALT, total bilirubin, phosphorus, and ALP were associated with higher iPTH level (>300 pg/mL). During 60 months (median 44 months) of follow-up, the all-cause mortality rate was 16%, and 91 (46%) of the 199 deaths were caused by cardiovascular disease. In competing-risks regression analysis, "high ALP + low iPTH" was independently associated with all-cause and cardiovascular mortality after adjustment for age, gender, presence of diabetes, and cardiovascular disease, the calendar year of recruitment and vitamin D therapy in PD patients. The subhazard ratio (sHR) of group "high ALP + low iPTH" was 1.96 times and 3.35 times higher than sHR of group "low ALP + high iPTH" for all-cause mortality and cardiovascular mortality, respectively. The combination of high ALP and low iPTH was independently associated with increased all-cause and cardiovascular mortality in PD patients, suggesting that ALP and iPTH have the potential to predict clinical outcomes and might be useful risk assessment tools in PD patients. Further studies exploring the observed association between combination of ALP with iPTH and mortality are warranted.


Role of auditory-somatosensory corticothalamic circuit integration in analgesia.
Our sensory environment is permeated by a diverse array of auditory and somatosensory stimuli. The pairing of acoustic signals with concurrent or forthcoming tactile cues are abundant in everyday life and various survival contexts across species, thus deeming the ability to integrate sensory inputs arising from the combination of these stimuli as crucial. The corticothalamic system plays a critical role in orchestrating the construction, integration and distribution of the information extracted from these sensory modalities. In this mini-review, we provide a circuit-level description of the auditory corticothalamic pathway in conjunction with adjacent corticothalamic somatosensory projections. Although the extent of the functional interactions shared by these pathways is not entirely elucidated, activation of each of these systems appears to modulate sensory perception in the complementary domain. Several specific issues are reviewed. Under certain environmental noise conditions, the spectral information of a sound could induce modulations in nociception and even induce analgesia. We begin by discussing recent findings by Zhou et al. (2022) implicating the corticothalamic system in mediating sound-induced analgesia. Next, we describe relevant components of the corticothalamic pathway's functional organization. Additionally, we describe an emerging body of literature pointing to intrathalamic circuitry being optimal for controlling and selecting sensory signals across modalities, with the thalamic reticular nucleus being a candidate mechanism for directing cross-modal interactions. Finally, Ca2+ bursting in thalamic neurons evoked by the thalamic reticular nucleus is explored.


Knocking down PML impairs p53 signaling transduction pathway and suppresses irradiation induced apoptosis in breast carcinoma cell MCF-7.
The promyelocytic leukemia (PML) can selectively and dynamically recruit a number of proteins including p53 to form a sub-nuclear multiprotein chamber named PML-NBs. In DNA damage response, p53 is recruited into PML-NBs and modified by phosphorylations and acetylations, which in turn potentiate its transcriptional and pro-apoptotic activities. In contrast, in carcinoma cells, the role of PML in the irradiation induced p53-mediated apoptosis is not precisely understood. In this study, we have used the breast carcinoma cell line, MCF-7, and stably suppressed the expression of PML. Inhibition of PML expression had no detectable effect on the expression of endogenous p53 at the mRNA level; however, a significant decrease of p53 protein was observed. There was also an increase in the p53-MDM2 complexes, which may facilitate p53 protein degradation by the ubiquitin-proteasome pathway, also in irradiation treated cells. The p53 transcriptional activity was attenuated both in unstressed and 10 Gy irradiation treated cells. Moreover, inhibition of PML expression in MCF-7 cells significantly reduced p53 downstream genes, cell cycle arrest gene p21(WAF/cip-1) and pro-apoptotic gene Bax expression, then irradiation-induced apoptosis. These results suggest that PML is a key regulator in the irradiation activated p53 apoptotic pathway in breast carcinoma cells.


Activation of Molecular Oxygen Using Durable Cobalt Encapsulated with Nitrogen-Doped Graphitic Carbon Shells for Aerobic Oxidation of Lignin-Derived Alcohols.
It has long been a challenge for activating O2 by transition-metal nanocatalysts, which might lose activity due to strong tendency for oxidation. Herein, O2 could be activated by durable encapsulated cobalt nanoparticles (NPs) with N-doped graphitic carbon shells (Co@N-C), but not by encapsulated cobalt NPs with graphitic carbon, exposed cobalt NPs supported on activated carbon, or N-doped carbon. Electron paramagnetic resonance, real-time in situ FTIR spectroscopy, and mass spectrometry measurements demonstrated the generation of the highly active superoxide radical, O2.- . This unique ability enables Co@N-C to afford an excellent catalytic performance in model aerobic oxidation of monomeric lignin-derived alcohols. Further analysis elucidated that encapsulated cobalt and nitrogen-doped graphitic carbon might contribute to the capacity through influencing the electronic properties of outer layers. Moreover, through isolation by N-doped graphitic carbon shells, the inner metallic cobalt NPs are inaccessible in term of either alcohols or oxygenated products, and a distinctive resistance to leaching and agglomeration has been achieved.


Bone marrow abnormalities on magnetic resonance imaging are associated with type II collagen degradation in knee osteoarthritis: a three-month longitudinal study.
Using radiography to assess the efficacy of a disease-modifying osteoarthritis (OA) drug on joint structure is challenging. Subchondral bone marrow abnormalities determined by magnetic resonance imaging (MRI) and urinary excretion of C-terminal crosslinking telopeptide of type II collagen (CTX-II) have recently been shown to be predictors of radiographic progression in patients with knee OA, suggesting that these may represent valuable biomarkers with increased sensitivity compared with findings on radiography. The aims of this investigation were to analyze, in patients with knee OA, whether the values associated with these 2 OA biomarkers can change within 3 months, and to investigate the relationships between bone marrow abnormalities and CTX-II. Knee MRI scans were obtained in 377 patients with painful knee OA (76% women, mean age 63 years, mean disease duration 6.6 years) at both baseline and 3 months. The femoral and tibial condyles and the patella were divided into 8 sites for the scoring of bone marrow abnormalities. A bone marrow abnormality was defined as an area of increased signal on T2-weighted images of the subchondral bone. All scans were reviewed centrally and scored by a single trained radiologist using a validated 4-point scoring method. Fasting urine and serum samples were also collected from all patients at baseline, month 1, month 2, and month 3, in order to measure the levels of urinary CTX-II and serum CTX-I, a biochemical marker of bone resorption. At baseline, 82% of patients had MRI evidence of bone marrow abnormalities. Bone marrow abnormality scores correlated significantly with CTX-II levels (P < 0.0001). Within 3 months, the bone marrow abnormality score decreased in 37 patients (9.8%), increased in 71 patients (18.8%), and did not change in the majority of patients (71.4%). Patients with baseline urinary CTX-II levels in the highest tertile had a relative risk of 2.4 (95% confidence interval 1.1-5.0) of worsening bone marrow abnormalities at 3 months compared with patients with levels in the lowest tertile, after adjustment for age, sex, and body mass index. In patients who showed a decrease in the bone marrow abnormality score at 3 months, urinary CTX-II levels decreased significantly (mean -75 ng/mmole creatinine), whereas levels increased (mean +23 ng/mmole creatinine) in patients showing an increase in the bone marrow abnormality score (P = 0.01 between the 2 groups). No significant association between bone marrow abnormalities and serum CTX-I was observed. In patients with painful knee OA, bone marrow abnormalities on MRI can change within only 3 months in approximately 30% of patients. Reduction in the extent of bone marrow abnormalities is associated with a decrease in cartilage degradation.


Impact of site dilution and agent diffusion on the critical behavior of the majority-vote model.
In this work we study a modified version of the majority-vote model with noise. In particular, we consider a random diluted square lattice wherein a site is empty with a probability r. In order to analyze the critical behavior of the model, we perform Monte Carlo simulations on lattices with linear sizes up to L=140. By means of a finite-size scaling analysis we estimate the critical noises qc and the critical ratios β/ν, γ/ν, and 1/ν for some values of the probability r. Our results suggest that the critical exponents are different from those of the original model (r=0), but they are r independent (r>0). In addition, if we consider that agents can diffuse through the lattice, the exponents remain the same, suggesting a new universality class for the majority-vote model with noise. Based on the numerical data, we may conjecture that the values of the exponents in this universality class are β∼0.45, γ∼1.1, and ν∼1.0, which satisfy the scaling relation 2β+γ=dν=2.


Interactions between space-based and feature-based attention.
Although early research suggested that attention to nonspatial features (i.e., red) was confined to stimuli appearing at an attended spatial location, more recent research has emphasized the global nature of feature-based attention. For example, a distractor sharing a target feature may capture attention even if it occurs at a task-irrelevant location. Such findings have been used to argue that feature-based attention operates independently of spatial attention. However, feature-based attention may nonetheless interact with spatial attention, yielding larger feature-based effects at attended locations than at unattended locations. The present study tested this possibility. In 2 experiments, participants viewed a rapid serial visual presentation (RSVP) stream and identified a target letter defined by its color. Target-colored distractors were presented at various task-irrelevant locations during the RSVP stream. We found that feature-driven attentional capture effects were largest when the target-colored distractor was closer to the attended location. These results demonstrate that spatial attention modulates the strength of feature-based attention capture, calling into question the prior evidence that feature-based attention operates in a global manner that is independent of spatial attention.


CON: Should aspirin be used in all women older than 65 years to prevent stroke?
A goal of the Women's Health Study was to evaluate the balance of benefits and risks of low-dose aspirin in the primary prevention of stroke in healthy women. A total of 39,876 female health care professionals aged 45 years and older were randomly assigned to either low-dose aspirin (100 mg every other day) or placebo and followed for an average of 10 years. In the overall study population, aspirin significantly lowered the risk of total and ischemic stroke without affecting the risk of myocardial infarction or death from cardiovascular causes, leading to a nonsignificant finding with respect to the primary end point of total cardiovascular disease. In women aged 65 years or older, aspirin significantly reduced the risk of ischemic stroke, as well as myocardial infarction and total cardiovascular disease. While the findings suggest that aspirin should be considered for primary prevention of stroke in women aged 65 years or older, the balance of benefits and risks would not support recommending aspirin for all women in this age group. The discussion on whether to use aspirin should be had on an individual basis, assessing the net risks and benefits.


The influence of dissolved oxygen on the mitogen responses of mouse lymphocytes.
Mouse spleen cells incubated at either 30 mm Hg dissolved oxygen partial pressure (pO2) or 160 mm Hg did not differ significantly in their survival or in their proliferative response to the mitogens concanavalin A, phytohemagglutinin or bacterial endotoxin in a subsequent static culture. If the mitogen was added prior to exposing the cells to the controlled dissolved oxygen environment the incorporation of thymidine was always substanstially lower in cells held at 160 mm Hg pO2. This toxic effect of oxygen increased with the time of incubation and was not reversed by the inclusion of 2-mercaptoethanol in the medium. Incubation of cells with mitogen in the absence of oxygen had no deleterious effect on the proliferative response. A comparison of DNA, RNA and protein synthesis in Con A stimulated cells indicated that the predominant effect of oxygen was on DNA synthesis.


Aggressive statin treatment, very low serum cholesterol levels and haemorrhagic stroke: is there an association?
To assess the potential association between haemorrhagic stroke and achieving very low serum cholesterol levels with aggressive statin treatment. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study showed a reduction in both fatal and nonfatal stroke but an increase in the risk for haemorrhagic stroke during high-dose atorvastatin treatment. However, post-hoc analyses of this trial showed that this increased risk is primarily observed in elderly men with a history of haemorrhagic stroke. In addition, there was no relationship between baseline or on-treatment low-density lipoprotein cholesterol (LDL-C) levels and haemorrhagic stroke. Existing data suggest that low LDL-C levels during intensive statin treatment are not associated with an increased risk for haemorrhagic stroke, except in patients with a history of intracerebral haemorrhage. In patients with a history of ischaemic stroke, intensive statin treatment substantially reduces the risk for both recurrent ischaemic stroke and for coronary heart disease (CHD) events. Any possible excess of haemorrhagic stroke is greatly outweighed by the protective effect against ischaemic stroke and CHD events.


Derivation of the density functional theory from the cluster expansion.
The density functional theory is derived from a cluster expansion by truncating the higher-order correlations in one and only one term in the kinetic energy. The formulation allows self-consistent calculation of the exchange correlation effect without imposing additional assumptions to generalize the local density approximation. The pair correlation is described as a two-body collision of bound-state electrons, and modifies the electron- electron interaction energy as well as the kinetic energy. The theory admits excited states, and has no self-interaction energy.


Continuous-flow determination of primary bile acids, by bioluminescence, with use of nylon-immobilized bacterial enzymes.
We describe a continuous-flow bioluminescence method for measuring primary bile acid in serum, with nylon as the solid support. 7 alpha-Hydroxysteroid dehydrogenase (EC 1.1.1. 159), a bacterial luciferase (EC 126.96.36.199), and NAD+:FMN oxido-reductase (EC 126.96.36.199) are covalently co-immobilized on a nylon coil (1 m X 1.0 mm i.d.). The assay is highly specific for 7 alpha-hydroxy bile acids. Other bile acids and steroids do not interfere. The continuous-flow light-emitting system, in which the reactor (nylon coil) is placed in front of a photomultiplier tube inside a luminometer, is versatile and simple. The flow is air-segmented, and serum samples (5-50 microL) can be injected directly. Concentration and response are linearly related from 10 to 2500 pmol per assay tube. The precision of the method is satisfactory (CV 5-10%), both inter- and intra-assay. We validated the technique by comparing results with those by RIA, enzyme immunoassay, and "high-performance" liquid chromatography. More than 20 samples an hour can be analyzed, with no carryover. The nylon-immobilized enzymes are stable for more than two months, and greater than 500 samples can be analyzed with use of a few milligrams of enzymes. Normal values for bile acid content of serum ranged from 1 to 2.5 mumol/L, in agreement with those obtained by other methods.


Diagnostic accuracy of noncontrast CT imaging markers in cerebral venous thrombosis.
To assess the added diagnostic value of semiquantitative imaging markers on noncontrast CT scans in cerebral venous thrombosis (CVT). In a retrospective, multicenter, blinded, case-control study of patients with recent onset (<2 weeks) CVT, 3 readers assessed (1) the accuracy of the visual impression of CVT based on a combination of direct and indirect signs, (2) the accuracy of attenuation values of the venous sinuses in Hounsfield units (with adjustment for hematocrit levels), and (3) the accuracy of attenuation ratios of affected vs unaffected sinuses in comparison with reference standard MRI or CT angiography. Controls were age-matched patients with (sub)acute neurologic presentations. We enrolled 285 patients with CVT and 303 controls from 10 international centers. Sensitivity of visual impression of thrombosis ranged from 41% to 73% and specificity ranged from 97% to 100%. Attenuation measurement had an area under the curve (AUC) of 0.78 (95% confidence interval [CI] 0.74-0.81). After adjustment for hematocrit, the AUC remained 0.78 (95% CI 0.74-0.81). The analysis of attenuation ratios of affected vs unaffected sinuses had AUC of 0.83 (95% CI 0.8-0.86). Adding this imaging marker significantly improved discrimination, but sensitivity when tolerating a false-positive rate of 20% was not higher than 76% (95% CI 0.70-0.81). Semiquantitative analysis of attenuation values for diagnosis of CVT increased sensitivity but still failed to identify 1 out of 4 CVT. This study provides Class II evidence that visual analysis of plain CT with or without attenuation measurements has high specificity but only moderate sensitivity for CVT.


What Else Can CD39 Tell Us?
As the rate-limiting enzyme in ATP/ADP-AMP-adenosine pathway, CD39 would be a novel checkpoint inhibitor target in preventing adenosine-triggered immune-suppressive effect. In addition, CD39hi Tregs, but not CD25hi Tregs, exhibit sustained Foxp3 levels and functional abilities, indicating it could represent a new specific marker of Tregs. Similarly, inhibition of CD39 enzymatic function at the surface of tumor cells alleviates their immunosuppressive activity. Far from conclusive, present research revealed that CD39 also dephosphorylated and thus inactivated self- and pathogen-associated phosphoantigens of Vγ9Vδ2 T cells, which may be the most promising subpopulation for cellular vaccine. CD39 is also tightly related to Th17 cells and can be regarded as a Th17 cells marker. In this review, we focus on present research of CD39 ectoenzyme and provide insights into its clinical application.


Continuous Optical-to-Mechanical Quantum State Transfer in the Unresolved Sideband Regime.
Optical-to-mechanical quantum state transfer is an important capability for future quantum networks, quantum communication, and distributed quantum sensing. However, existing continuous state transfer protocols operate in the resolved sideband regime, necessitating a high-quality optical cavity and a high mechanical resonance frequency. Here, we propose a continuous protocol that operates in the unresolved sideband regime. The protocol is based on feedback cooling, can be implemented with current technology, and is able to transfer non-Gaussian quantum states with high fidelity. Our protocol significantly expands the kinds of optomechanical devices for which continuous optical-to-mechanical state transfer is possible, paving the way toward quantum technological applications and the preparation of macroscopic superpositions to test the fundamentals of quantum science.


Hippocampus and amygdala volumes in elderly schizophrenic patients as assessed by magnetic resonance imaging.
Reduced size of the hippocampus and amygdala has been one of the more consistent morphological findings in schizophrenia, but the question of medial temporal abnormalities in elderly schizophrenia patients has been inadequately addressed. We examined 20 elderly subjects with a DSM-III-R diagnosis of schizophrenia, five of whom had a late-onset schizophrenia (LOS), and compared them with 20 healthy volunteers on magnetic resonance imaging (MRI) and neuropsychological parameters. Hippocampus and amygdala volumes were obtained by manual tracing on T1-weighted 1.5 mm thick contiguous coronal slices perpendicular to the long axis of the hippocampus. Patients had smaller left hippocampal and right amygdala volumes than comparison subjects, the mean differences being 9.7 and 11.1%, respectively, but the right amygdala volumes were not significantly different after Bonferroni correction. The hippocampus-amygdala volumes together were smaller in the schizophrenia group bilaterally. In a pilot analysis, the LOS subjects had non-significantly smaller hippocampus-amygdala volumes than did the early-onset schizophrenia (EOS) subjects. For the schizophrenia group, there were significant correlations between amygdala and hippocampus volumes and some neuropsychological performance indices. The findings are consistent with those reported in younger schizophrenics, and are of the same order of magnitude, suggesting that they are not likely to be progressive. This pilot analysis in LOS subjects argues against the condition being secondary to Alzheimer's disease.


Ultrafast decay of superexcited c 4Σu- nlσg v=0,1 states of O2 probed with femtosecond photoelectron spectroscopy.
Neutral superexcited states in molecular oxygen converging to the O(2)(+) c (4)Σ(u)(-) ion state are excited and probed with femtosecond time-resolved photoelectron spectroscopy to investigate predissociation and autoionization relaxation channels as the superexcited states decay. The c (4)Σ(u)(-) 4sσ(g) v=0, c (4)Σ(u)(-) 4sσ(g) v=1, and c (4)Σ(u)(-) 3dσ(g) v=1 superexcited states are prepared with pulsed high-harmonic radiation centered at 23.10 eV. A time-delayed 805 nm laser pulse is used to probe the excited molecular states and neutral atomic fragments by ionization; the ejected photoelectrons from these states are spectrally resolved with a velocity map imaging spectrometer. Three excited neutral O* atom products are identified in the photoelectron spectrum as 4d(1) (3)D(J)°, 4p(1) (5)P(J)° and 3d(1) (3)D(J)° fragments. Additionally, several features in the photoelectron spectrum are assigned to photoionization of the transiently populated superexcited states. Using principles of the ion core dissociation model, the atomic fragments measured are correlated with the molecular superexcited states from which they originate. The 4d(1) (3)D(J)° fragment is observed to be formed on a timescale of 65 ± 5 fs and is likely a photoproduct of the 4sσ(g) v = 1 state. The 4p(1) (5)P(J)° fragment is formed on a timescale of 427 ± 75 fs and correlated with the neutral predissociation of the 4sσ(g) v = 0 state. The timescales represent the sum of predissociation and autoionization decay rates for the respective superexcited state. The production of the 3d(1) (3)D(J)° fragment is not unambiguously resolved in time due to an overlapping decay of a v = 1 superexcited state photoelectron signal. The observed 65 fs timescale is in good agreement with previous experiments and theory on the predissociation lifetimes of the v = 1 ion state, suggesting that predissociation may dominate the decay dynamics from the v = 1 superexcited states. An unidentified molecular state is inferred by the detection of a long-lived depletion signal (reduction in autoionization) associated with the B (2)Σ(g)(-) ion state that persists up to time delays of 105 ps.


A South African family with oculopharyngeal muscular dystrophy: Clinical and molecular genetic characteristics.
Autosomal dominantly inherited oculopharyngeal muscular dystrophy (OPMD) is caused by a trinucleotide repeat expansion in exon 1 of the polyadenylate binding protein nuclear 1 (PABPN1) gene on chromosome 14q. A large family with OPMD was recently identified in Pretoria, South Africa (SA). Molecular studies revealed a (GCG)11(GCA)3GCG or (GCN)15 mutant allele. The (GCN)15 mutation detected in this family has been described previously in families from Uruguay and Mexico as a founder effect. To our knowledge, this is the first report of an SA Afrikaner family with molecularly confirmed OPMD. The proband, a 64-year-old woman, presented to the neurology outpatient department at Steve Biko Academic Hospital, Pretoria. A sibship of 18 individuals was identified, of whom eight had OPMD. Four patients were interviewed and examined clinically, and electromyographic studies were performed. Molecular analysis of the PABPN1 gene was performed by polymerase chain reaction amplification and direct sequencing of exon 1 in three of the patients. Patients presented with ptosis, external ophthalmoplegia, dysphagia, dysarthria and mild proximal weakness. High foot arches and absent ankle reflexes raised the possibility of peripheral neuropathy, but electromyography showed only mildly low sensory amplitudes, and myopathic units in two patients.


Flies and humans share a motion estimation strategy that exploits natural scene statistics.
Sighted animals extract motion information from visual scenes by processing spatiotemporal patterns of light falling on the retina. The dominant models for motion estimation exploit intensity correlations only between pairs of points in space and time. Moving natural scenes, however, contain more complex correlations. We found that fly and human visual systems encode the combined direction and contrast polarity of moving edges using triple correlations that enhance motion estimation in natural environments. Both species extracted triple correlations with neural substrates tuned for light or dark edges, and sensitivity to specific triple correlations was retained even as light and dark edge motion signals were combined. Thus, both species separately process light and dark image contrasts to capture motion signatures that can improve estimation accuracy. This convergence argues that statistical structures in natural scenes have greatly affected visual processing, driving a common computational strategy over 500 million years of evolution.


Symmetric and asymmetric solitons in linearly coupled Bragg gratings.
We demonstrate that a symmetric system of two linearly coupled waveguides, with Kerr nonlinearity and resonant grating in both of them, gives rise to a family of symmetric and antisymmetric solitons in an exact analytical form, a part of which exists outside of the bandgap in the system's spectrum, i.e., they may be regarded as embedded solitons (ES's, i.e., the ones partly overlapping with the continuous spectrum). Parameters of the family are the soliton's amplitude and velocity. Asymmetric ES's, unlike the regular (nonembedded) gap solitons (GS's), do not exist in the system. Moreover, ES's exist even in the case when the system's spectrum contains no bandgap. The main issue is the stability of the solitons. We demonstrate that some symmetric ES's are stable, while all the antisymmetric solitons are unstable; an explanation is given to the latter property, based on the consideration of the system's Hamiltonian. We produce a full stability diagram, which comprises both embedded and regular solitons, quiescent and moving. A stability region for ES's is found around the point where the constant of the linear coupling between the two cores is equal to the Bragg-reflectivity coefficient accounting for the linear conversion between the right- and left-traveling waves in each core, i.e., the ES's are the "most endemic" solitary solitons in this system. The stability region quickly shrinks with the increase of the soliton's velocity c, and completely disappears when c exceeds half the maximum velocity. Collisions between stable moving solitons of various types are also considered, with a conclusion that the collisions are always quasielastic.


Strongly aligned molecules inside helium droplets in the near-adiabatic regime.
Iodine (I2) molecules embedded in He nanodroplets are aligned by a 160 ps long laser pulse. The highest degree of alignment, occurring at the peak of the pulse and quantified by ⟨cos2𝜃2D⟩, is measured as a function of the laser intensity. The results are well described by ⟨cos2𝜃2D⟩ calculated for a gas of isolated molecules each with an effective rotational constant of 0.6 times the gas-phase value and at a temperature of 0.4 K. Theoretical analysis using the angulon quasiparticle to describe rotating molecules in superfluid helium rationalizes why the alignment mechanism is similar to that of isolated molecules with an effective rotational constant. A major advantage of molecules in He droplets is that their 0.4 K temperature leads to stronger alignment than what can generally be achieved for gas phase molecules-here demonstrated by a direct comparison of the droplet results to measurements on a ∼1 K supersonic beam of isolated molecules. This point is further illustrated for a more complex system by measurements on 1,4-diiodobenzene and 1,4-dibromobenzene. For all three molecular species studied, the highest values of ⟨cos2𝜃2D⟩ achieved in He droplets exceed 0.96.


Rapid and Economic Synthesis of a Li7PS6 Solid Electrolyte from a Liquid Approach.
Solid electrolytes are the key to realize future solid-state batteries that show the advantages of high energy density and intrinsic safety. However, most solid electrolytes require long time and energy-consuming synthesis conditions of either extended ball milling or high-temperature solid-state reactions, impeding practical applications of solid electrolytes for large-scale systems. Here, we report a new and rapid liquid-based synthetic method for preparing a high-purity Li7PS6 solid electrolyte through the stoichemical reaction of Li3PS4 and Li2S. This method relies on facile and low-cost solution-based soft chemistry to complete chemical reaction in extensively short time (2 h). The prepared Li7PS6 solid electrolyte shows a high phase purity, an impressive ionic conductivity (0.11 mS cm-1), and a reasonable electrochemical stability with a metallic lithium anode. Our results highlight the use of an economic and nontoxic solvent to quickly synthesize a Li7PS6 solid electrolyte, which would promote the development of solid-state batteries for next-generation energy storage systems.


Herpes Simplex Virus Latency: The DNA Repair-Centered Pathway.
Like all herpesviruses, herpes simplex virus 1 (HSV1) is able to produce lytic or latent infections depending on the host cell type. Lytic infections occur in a broad range of cells while latency is highly specific for neurons. Although latency suggests itself as an attractive target for novel anti-HSV1 therapies, progress in their development has been slowed due in part to a lack of agreement about the basic biochemical mechanisms involved. Among the possibilities being considered is a pathway in which DNA repair mechanisms play a central role. Repair is suggested to be involved in both HSV1 entry into latency and reactivation from it. Here I describe the basic features of the DNA repair-centered pathway and discuss some of the experimental evidence supporting it. The pathway is particularly attractive because it is able to account for important features of the latent response, including the specificity for neurons, the specificity for neurons of the peripheral compared to the central nervous system, the high rate of genetic recombination in HSV1-infected cells, and the genetic identity of infecting and reactivated virus.


Advanced nurse practitioner-led abdominal therapeutic paracentesis.
Liver disease is a common cause of death in England and Wales, and ascites is associated with a 50% mortality rate. Most patients who present with ascites have underlying liver cirrhosis, and often require therapeutic paracentesis for symptomatic relief. This article describes a competency framework that was developed to enable advanced nurse practitioners to perform therapeutic paracentesis in an ambulatory care unit.


Associations Between Cardiac Troponin, Mechanism of Myocardial Injury, and Long-Term Mortality After Noncardiac Vascular Surgery.
The time-sensitive hazard of perioperative cardiac troponin T (cTnT) elevation and whether long-term mortality differs by mechanism of myocardial injury are poorly understood. In this observational study of 12 882 patients who underwent noncardiac vascular surgery, patients were assessed for cTnT sampling within 96 hours postoperatively. Mortality out to 5-years was stratified by cTnT level and mechanism of myocardial injury. During a median follow-up of 26.9 months, there were 2149 (16.7%) deaths. By multivariable Cox proportional hazards analysis, there was a graded increase in mortality with any detectable cTnT compared to <0.01 ng/mL; cTnT 0.01 to 0.029 ng/mL hazard ratio (HR) 1.54 (95% CI 1.18-2.00, P=0.002), 0.03 to 0.099 ng/mL HR 1.86 (95% CI 1.49-2.31, P<0.001), 0.10 to 0.399 ng/mL HR 1.83 (95% CI 1.46-2.31, P<0.001), ≥0.40 ng/mL HR 2.62 (95% CI 2.06-3.32, P<0.001). Mortality for each mechanism of injury was greater than for patients with normal cTnT; baseline cTnT elevation HR 1.71 (95% CI 1.31-2.24; P<0.001), Type 2 myocardial infarction HR 1.88 (95% CI 1.57-2.24; P<0.001), Type 1 MI HR 2.56 (95% CI 2.56, 1.82-3.60; P<0.001). On Kaplan-Meier analysis, long-term survival did not differ between mechanisms. The hazard of mortality was greatest within the first 10 months postsurgery. Consistent results were obtained in confirmatory propensity-score matched analyses. Any detectable cTnT ≥0.01 ng/mL is associated with increased long-term mortality after vascular surgery. This risk is greatest within the first 10 months postoperatively. While short-term mortality is greatest with Type 1 myocardial infarction, long-term mortality appears independent of the mechanism of injury.


Children's Divorce and their Financial Support to Older Parents in Rural China.
This study examined how adult children's divorce affected their financial support to older parents in rural China and how that relationship was dependent on children's gender. The sample was from rural Anhui Province and the working sample included 1629 older parents who reported their interactions with 6210 children across six waves of observations in 14 years (2001-2015). Generalized Estimating Equations showed that divorced sons provided less financial support to their parents than married sons. In contrast, divorced daughters did not necessarily provide less financial support than married daughters. This gender difference was statistically significant. The findings were discussed in the context of changing rural Chinese families, where the norm of filial piety is still strong but patrilineal tradition and gender ideology have experienced desynchronized changes.


[Lymphocyte subpopulations in the adenoids analyzed by flow cytometry].
Adenoid hypertrophy is a common problem of childhood. The peak occurrence of adenoid hypertrophy correlates with the onset of serous otitis media. The aim of the study was to evaluate the lymphocyte subpopulations in the adenoids of children with serous otitis media. The adenoids obtained from 65 children at the age of 1 to 17 years were examined. Two groups were studied: 1) children with persistent effusion in the middle ear, 2) children with adenoid hypertrophy without a history of otitis media. The percentage of the lymphocytes B in the adenoids was similar in both groups. However, the percentage of lymphocytes T (p < 0.04), and CD4+ (p < 0.005) was significantly lower in adenoids of children with serous otitis media. The percentage of lymphocytes T HLA-DR+ was slightly higher in this group, but the percentage of lymphocytes T CD25+ was the same in both groups. The quantitative differences in the lymphocyte subpopulations of adenoids may be the predisposing factor in serous otitis media.


Induction and Elimination of Prophages Using CRISPR Interference.
Prophages are widely spread among bacterial genomes, and they can have positive or negative effects on their hosts. A key aspect in the study of prophages is the discovery of their induction signals. Prophage induction can occur by inactivating a phage transcriptional repressor, which is responsible for maintaining the lysogenic state. This repressor can be inactivated through the bacterial SOS response. However, the induction signals for numerous prophages do not involve the SOS system, and therefore significant efforts are needed to identify these conditions. Similarly, curing bacterial strains of inducible prophages is a tedious process, requiring the screening of several colonies. Here, we investigated whether transcriptional silencing of a prophage repressor using CRISPR interference (CRISPRi) would lead to prophage induction. Using Escherichia coli phages λ and P2 as models, we demonstrated the efficiency of CRISPRi for prophage induction and for curing lysogenic strains of their prophages.


Peripheral Teflon catheters: factors determining incidence of phlebitis and duration of cannulation.
Catheter-related phlebitis is a frequent problem in the clinical setting. Risk factors for catheter-related phlebitis were assessed at a single tertiary-care institution where no routine change policy for peripheral intravenous catheters is in place. In a nonrandomized, observational trial, peripheral intravenous Teflon catheters were inserted in patients with a diagnosis of leukemia, lymphoma, solid tumor, acquired immunodeficiency syndrome, other serious infection, or autoimmune disorder. Underlying disease, age, white blood cell count at the time of insertion, physician placing the catheter, catheter bore, duration of cannulation, reason for removal of the catheter, and visual inspection of the insertion site were recorded. Four hundred twelve catheters were inserted in 175 patients. The number of catheterizations per episode varied between 1 and 7. Three hundred sixty-four (88.3%) catheter placements were evaluable. The mean duration of cannulation was 4.2 days. The overall incidence of phlebitis was 12.9%. Catheters in leukopenic patients showed a longer duration of cannulation compared with catheters in nonleukopenic patients, but no difference regarding the phlebitis rate. Findings in this study partly contrast with data reported in the literature. In particular, leukopenia, female gender, prolonged duration of cannulation, antibiotics, and choice of insertion site could not be shown to be risk factors.


[Ultrasonics and computerized tomography in the diagnosis of large cavernous hemangiomas of the liver].
Cavernous haemangiomas of the liver often pose problems in the differential diagnosis on ultrasound because of the complex echo pattern. Some typical features of their sonomorphology are exemplified by the data obtained in 4 patients. In combination with the almost pathognomonic delayed contrast enhancement on computed tomography, additional angiography seems to be no longer necessary for an accurate diagnosis in most cases.


Association of delayed adequate antimicrobial treatment and organ dysfunction in pediatric bloodstream infections.
Bloodstream infections (BSIs) are associated with significant mortality and morbidity, including multiple organ dysfunction. We explored if delayed adequate antimicrobial treatment for children with BSIs is associated with change in organ dysfunction as measured by PELOD-2 scores. We conducted a multicenter, retrospective cohort study of critically ill children <18 years old with BSIs. The primary outcome was change in PELOD-2 score between days 1 (index blood culture) and 5. The exposure variable was delayed administration of adequate antimicrobial therapy by ≥3 h from blood culture collection. We compared PELOD-2 score changes between those who received early and delayed treatment. Among 202 children, the median (interquartile range) time to adequate antimicrobial therapy was 7 (0.8-20.1) hours; 124 (61%) received delayed antimicrobial therapy. Patients who received early and delayed treatment had similar baseline characteristics. There was no significant difference in PELOD-2 score changes from days 1 and 5 between groups (PELOD-2 score difference -0.07, 95% CI -0.92 to 0.79, p = 0.88). We did not find an association between delayed adequate antimicrobial therapy and PELOD-2 score changes between days 1 and 5 from detection of BSI. PELOD-2 score was not sensitive for clinical effects of delayed antimicrobial treatment. In critically ill children with bloodstream infections, there was no significant change in organ dysfunction as measured by PELOD-2 scores between patients who received adequate antimicrobial therapy within 3 h of their initial positive blood culture and those who started after 3 h. Higher PELOD-2 scores on day 1 were associated with larger differences in PELOD-2 scores between days 1 and 5 from index positive blood cultures. Further study is required to determine if PELOD-2 or alternative measures of organ dysfunction could be used as primary outcome measures in trials of antimicrobial interventions in pediatric critical care research.


A device for studying fluid-induced cracks under mixed-mode loading conditions using x-ray tomography.
We introduce an innovative instrument designed to investigate fluid-induced fractures under mixed loading conditions, including uniaxial tension and shear stress, in gels and similar soft materials. Equipped with sensors for measuring force, torque, and fluid pressure, the device is tailored for compatibility with x-ray tomography scanners, enabling non-invasive 3D analysis of crack geometries. To showcase its capabilities, we conducted a study examining crack-front segmentation in a hydrogel subjected to air pressure and a combination of tension and shear stress.


Phylogenomic analyses reveals gene flow between populations of the freshwater shrimp Potimirim brasiliana (Caridea, Atyidae) along its wide distribution.
Potimirim is one of the 40 genera of Atyidae restricted to America, which occurs in coastal freshwater habitats and questions about population status and variability have been emerging. Potimirim brasiliana occurs in Brazil from the northeastern to southeastern region. In order to evaluate the hypothesis of genetic structure among populations, we performed molecular analyses with specimens from all known limit of distribution of the species. The molecular markers used were COI and 28S. Phylogenetic trees were obtained by maximum likelihood and Bayesian analyses, and a haplotype network was obtained based only on COI. We found clear separation between P. brasiliana, P. potimirim, P. glabra and Potimirim sp 2. No pattern of structuration was found among P. brasiliana, but the haplotype network showed geographic pattern of structuration for the congener P. potimirim. The lack of genetic structuration among P. brasiliana can be explained by its life cycle that requires brackish water to complete their larval development. The larvae and juvenile in contact with these habitats can spread through oceanic currents, especially in higher rainfall seasons, maintaining the gene flow. The explanation for the geographical pattern found among P. potimirim is still missing and aspects about its lifecycle and larval development should be investigated.


The immunohistochemistry of gastrointestinal stromal tumors. Evidence supporting an origin from smooth muscle.
To study the histogenesis of gastrointestinal stromal tumors, 79 cases were evaluated for desmin (DES), vimentin (VIM), and S-100 protein immunoreactivity by the avidin-biotin immunoperoxidase procedure on paraffin-embedded, Bouin's-fixed tissue sections. All tumors showed weak vimentin positivity. Trapped non-neoplastic smooth muscle and nerve twigs were often noted, particularly at the tumor periphery. Significant tumor S-100 positivity was not identified in our series. Similarly, glial fibrillary acidic protein (GFAP) immunoreactivity (performed in 11 desmin-negative tumors) was not detected within either gastrointestinal stromal tumors or enteric glial cells. Fifty-three percent (53%) of all gastrointestinal stromal tumors (GIST) displayed positive tumor cell desmin immunoreactivity. All 10 esophageal and all four colorectal tumors were diffusely desmin positive and unequivocal smooth muscle lesions. In contrast, only 17 of 37 (46%) benign and six of nine (67%) malignant gastric tumors were desmin positive. Similarly, four of 10 (40%) benign and one of nine (11%) malignant small-bowel tumors expressed desmin. Several gastric neoplasms with prominent nuclear palisading resembling schwannian Antoni A regions were nonetheless desmin positive. Epithelioid gastric tumors were more frequently desmin positive than nonepithelioid tumors; however, this positivity did not attain statistical significance. Two gastrointestinal stromal tumors that were desmin negative in paraffin-embedded material had detectable antigen in frozen sections. Gastric and small-bowel tumors measuring less than 3 cm were significantly more often desmin positive than those 3 cm or greater. We conclude that the method of fixation, tissue preparation, and immunostaining may significantly affect the expression of desmin. Although the histogenesis of gastrointestinal stromal tumors remains controversial, most of these tumors show evidence of smooth muscle differentiation.


Impact of the acquired immunodeficiency syndrome epidemic on the practice of laryngology.
In only 10 years, the acquired immunodeficiency syndrome epidemic has already had an enormous impact on many aspects of the practice of medicine. The practice of laryngology typifies the changes that have occurred. Heightened clinical vigilance has been required as the laryngologist encounters new and unusual manifestations of the disease and must take more extensive histories regarding social, behavioral, and sexual practices than were previously necessary. The performance of physical examinations and surgical procedures has also changed as a result of experience with the lethal human immunodeficiency virus. Numerous legal, ethical, and social issues have also been raised by the epidemic and have had a major influence on how medicine is practiced and regulated. In this paper we review the laryngeal and pharyngeal manifestations of acquired immunodeficiency syndrome and discuss illustrative patient examples that demonstrate the impact of the disease. We also consider the diverse groups of issues that attend this epidemic and that continue to modify practice patterns.


Poly(ADP-ribose) polymerase-2 contributes to the fidelity of male meiosis I and spermiogenesis.
Besides the established central role of poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 in the maintenance of genomic integrity, accumulating evidence indicates that poly(ADP-ribosyl)ation may modulate epigenetic modifications under physiological conditions. Here, we provide in vivo evidence for the pleiotropic involvement of Parp-2 in both meiotic and postmeiotic processes. We show that Parp-2-deficient mice exhibit severely impaired spermatogenesis, with a defect in prophase of meiosis I characterized by massive apoptosis at pachytene and metaphase I stages. Although Parp-2(-/-) spermatocytes exhibit normal telomere dynamics and normal chromosome synapsis, they display defective meiotic sex chromosome inactivation associated with derailed regulation of histone acetylation and methylation and up-regulated X- and Y-linked gene expression. Furthermore, a drastically reduced number of crossover-associated Mlh1 foci are associated with chromosome missegregation at metaphase I. Moreover, Parp-2(-/-) spermatids are severely compromised in differentiation and exhibit a marked delay in nuclear elongation. Altogether, our findings indicate that, in addition to its well known role in DNA repair, Parp-2 exerts essential functions during meiosis I and haploid gamete differentiation.


IBR and BVD control: the key to successful herd management.
Control of IBR and BVD should be possible in Europe. Effective vaccines and reliable tools for monitoring are available. Systematic approach and strict implementation of control measures are essential. Voluntary or mandatory programs are ongoing on regional or national level in a lot of countries. Successful programs put pressure on surrounding regions/countries to initiate control program as well.


Some cautionary comments on the use of retrospective designs to evaluate treatment efficacy.
This article contrasts the true experimental approach with nonexperimental alternatives, such as retrospective designs, for research on treatment efficacy. The potential problems and limitations of the nonexperimental approach are highlighted so that when deviations from the more desirable experimental methodology are necessary, they can be undertaken with full knowledge of the hazards to be expected. Important issues are illustrated through discussion of a specific type of retrospective design, the case-control design.


Skeletal muscle capillary responses to insulin are abnormal in late-stage diabetes and are restored by angiotensin-converting enzyme inhibition.
Acute physiological hyperinsulinemia increases skeletal muscle capillary blood volume (CBV), presumably to augment glucose and insulin delivery. We hypothesized that insulin-mediated changes in CBV are impaired in type 2 diabetes mellitus (DM) and are improved by angiotensin-converting enzyme inhibition (ACE-I). Zucker obese diabetic rats (ZDF, n = 18) and control rats (n = 9) were studied at 20 wk of age. One-half of the ZDF rats were treated with quinapril (ZDF-Q) for 15 wk prior to study. CBV and capillary flow in hindlimb skeletal muscle were measured by contrast-enhanced ultrasound (CEU) at baseline and at 30 and 120 min after initiation of a euglycemic hyperinsulinemic clamp (3 mU.min(-1).kg(-1)). At baseline, ZDF and ZDF-Q rats were hyperglycemic and hyperinsulinemic vs. controls. Glucose utilization in ZDF rats was 60-70% lower (P < 0.05) than in controls after 30 and 120 min of hyperinsulinemia. In ZDF-Q rats, glucose utilization was impaired at 30 min but similar to controls at 120 min. Basal CBV was lower in ZDF and ZDF-Q rats compared with controls (13 +/- 4, 7 +/- 3, and 9 +/- 2 U, respectively). With hyperinsulinemia, CBV increased by about twofold in control animals at 30 and 120 min, did not change in ZDF animals, and increased in ZDF-Q animals only at 120 min to a level similar to controls. Anatomic capillary density on immunohistology was not different between groups. We conclude that insulin-mediated capillary recruitment in skeletal muscle, which participates in glucose utilization, is impaired in animals with DM and can be partially reversed by chronic ACE-I therapy.


Binding of transcription factors and creation of a large nucleoprotein complex on the human cytomegalovirus enhancer.
The effect of the human cytomegalovirus immediate early region 1 enhancer on transcription was studied in vitro with HeLa cell nuclear extract. Stimulation of in vitro transcription mediated by the enhancer element involves its recognition by specific trans-acting factors present in the nuclear extract. DNase I protection analysis was used to determine at the nucleotide level those enhancer sequences that interact with nuclear factors. At least nine sites of protein-DNA interaction were detected over approximately 400 base pairs of enhancer sequence. The regions of nuclease protection are associated with 21-, 19-, 18-, and 17-base-pair repeat elements as well as with a unique sequence, creating a large nucleoprotein complex. The relationship between the protein binding and the activity of the immediate early region 1 enhancer is discussed.


Content-Based Audio Classification and Retrieving Using Modified Bacterial Foraging Optimization Algorithm.
Audio classification and retrieval has been recognized as a fascinating field of endeavor for as long as it has existed due to the topic of identifying and choosing the most useful audio attributes. The categorization of audio files is significant not only in the area of multimedia applications but also in the disciplines of medicine, sound analysis, intelligent homes and cities, urban informatics, entertainment, and surveillance. This study introduces a new algorithm called the modified bacterial foraging optimization algorithm (MBFOA), which is based on a method that retrieves and classifies audio data. The goal of this algorithm is to reduce the computational complexity of existing techniques. Along with the combination of the peak estimated signal, the enhanced mel-frequency cepstral coefficient (EMFCC) and the enhanced power normalized cepstral coefficients (EPNCC) are used. These are then optimized using the fitness function utilizing MBFOA. The probabilistic neural network is used to differentiate between a music signal and a spoken signal from an audio source (PNN). It is next necessary to extract and list the characteristics that correspond to the class that was arrived at as a consequence of the categorization. When compared to other approaches that are somewhat similar, MBFOA demonstrates superior levels of sensitivity, specificity, and accuracy.


Screening for domestic violence in the pediatric office: a multipractice experience.
The purpose of our study was to screen for domestic violence (DV) in 4 different pediatric practice settings. Women who accompanied their children to well-child visits were eligible. The women were screened with a 6-question tool previously piloted by our group, which included questions on partner abuse, child abuse, and pet abuse. Over a 1-year period, 435 women were screened. Of these women, 95 (22%) described DV at some point in their lives. Sixty-nine (16%) reported abuse longer than 2 years before the screen and 26 (6%) reported more recent abuse. While 11 of 117 women screened in the more affluent private practice reported a history of past abuse, no women in that group reported DV occurring within 24 months. The proportion of women reporting violence did not differ significantly by site, but the proportion of patients reporting new violence was significantly lower at the private practice site by Chi-square analysis. In conclusion, women screened in a variety of pediatric settings will disclose DV. Recent abuse is more likely to be reported in settings with indigent patients. All pediatricians should be screening for DV and have protocols in place to offer women the services they need if DV is revealed.


Heterogeneous red blood cell adhesion and deformability in sickle cell disease.
We present a microfluidic approach that allows simultaneous interrogation of RBC properties in physiological flow conditions at a single cell level. With this method, we studied healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS) containing RBCs using whole blood samples from twelve subjects. We report that HbS-containing RBCs are heterogeneous in terms of adhesion and deformability in flow.


Orexin activation counteracts decreases in nonexercise activity thermogenesis (NEAT) caused by high-fat diet.
Overweight and obesity result from an imbalance between caloric intake and energy expenditure, including expenditure from spontaneous physical activity (SPA). Changes in SPA and resulting changes in non-exercise activity thermogenesis (NEAT) likely interact with diet to influence risk for obesity. However, previous research on the relationship between diet, physical activity, and energy expenditure has been mixed. The neuropeptide orexin is a driver of SPA, and orexin neuron activity can be manipulated using DREADDs (Designer Receptors Exclusively Activated by Designer Drugs). We hypothesized that HFD decreases SPA and NEAT, and that DREADD-mediated activation of orexin neuron signaling would abolish this decrease and produce an increase in NEAT instead. To test these ideas, we characterized behaviors to determine the extent to which access to a high-fat diet (HFD) influences the proportion and probability of engaging in food intake and activity. We then measured NEAT following access to HFD and following a DREADD intervention targeting orexin neurons. Two cohorts of orexin-cre male mice were injected with an excitatory DREADD virus into the caudal hypothalamus, where orexin neurons are concentrated. Mice were then housed in continuous metabolic phenotyping cages (Sable Promethion). Food intake, indirect calorimetry, and SPA were automatically measured every second. For cohort 1 (n=8), animals were given access to chow, then switched to HFD. For cohort 2 (n=4/group), half of the animals were given access to HFD, the other access to chow. Then, among animals on HFD, orexin neurons were activated following injections of clozapine n-oxide (CNO). Mice on HFD spent significantly less time eating (p<0.01) and more time inactive compared to mice on chow (p<0.01). Following a meal, mice on HFD were significantly more likely to engage in periods of inactivity compared to those on chow (p<0.05). NEAT was decreased in animals on HFD, and was increased to the NEAT level of control animals following activation of orexin neurons with DREADDs. Food intake (kilocalories) was not significantly different between mice on chow and HFD, yet mice on chow expended more energy per unit of SPA, relative to that in mice consuming HFD. These results suggest that HFD consumption reduces SPA and NEAT, and increases inactivity following a meal. Together, the data suggest a change in the efficiency of energy expenditure based upon diet, such that SPA during HFD burns fewer calories compared to SPA on a standard chow diet.


A preliminary evaluation of diagnostic odds in lung scan reporting.
Reporting of lung scans for pulmonary embolism (PE) using a descriptive probability notation is tried and tested. Subjectivity in interpretation of this jargon can be a problem for internists. Parallel descriptive and numerical probability reporting has been recommended, but the numerical probability scale is less precise than likelihood ratios expressed as odds. We therefore assessed internists' intuitive understanding of lung scan reports in the odds format compared to the descriptive probability notation. A questionnaire was sent to Scotland's 217 internists to assess their intuitive understanding of odds reporting and to compare their management strategies when confronted by lung scan reports in both an odds and a descriptive probability notation. There was a broad understanding of numerical odds. Internists used 'normal' and '100:1 against PE' identically; similarly, 'low probability' and '10:1 against PE'. There was a statistically significant preference for the diagnosis of PE when internists were given the '1:1 evens' report compared with the 'indeterminate' report. There does appear to be a greater awareness of the risk of PE when non-diagnostic lung scans are reported in numerical odds as compared with the descriptive probability format.


Disulfiram administration affects substance P-like immunoreactive and monoaminergic neural systems in rodent brain.
The biosynthetic enzyme peptidylglycine alpha-amidating monooxygenase catalyzes the formation of a variety of biologically active alpha-amidated peptides from respective COOH-terminal glycine-extended peptide precursors. Peptidylglycine alpha-amidating monooxygenase activity is dependent on copper, ascorbate, and molecular oxygen and is inhibited by the relatively selective copper chelator N,N-diethyldithiocarbamate or its disulfide dimer disulfiram (Antabuse). In the present study, chronic disulfiram treatment (100 mg/kg/day, for 12-25 days) resulted in significant changes in several neurochemical parameters in the mouse central nervous system, including levels of substance P-like, unamidated substance P-Gly-like, and protease-generated substance P-Gly-Lys-like immunoreactivities (SP-LI, SP-G-LI, and SP-G-K-LI, respectively). Combined high performance liquid chromatography/radioimmunoassay analyses of the extracted SP-LI, SP-G-LI, and SP-G-K-LI species indicated very similar chromatographic and immunochemical behavior as demonstrated for chemically authentic peptide standards. Additionally, changes in levels of monoamines and their metabolites were observed after drug administration. Complementary immunohistochemical analyses using affinity-purified anti-SP-G sera localized these drug-induced changes in levels of immunoreactive unamidated precursor to neural elements that normally express SP. As a functional corollary to alterations in neurochemical parameters, we observed significant disulfiram-induced increases in pain thresholds, potentiated by capsaicin treatment. Overall, our results indicate that the observed changes in steady state levels of immunoreactive SP and of the immature COOH-terminal extended forms of SP may reflect compensatory biosynthetic and posttranslational processing events in SP-containing neural systems after pharmacological challenge.


Self-derogation and psychopathology.
To test empirically the oft-repeated clinical hypothesis of a relationship between the self-derogation component of low self-esteem and severity of psychopathology across the entire range of pathology, including nondepressive disorders, the present study examined this relationship in two samples of Ss. The first were 152 patients and expatients from two community mental health catchment areas followed up two years after their first functional-disorder psychiatric admission. The second group were 97 outpatients from the same catchment areas beginning therapy at a community mental health clinic. Within each sample self-derogation was related significantly to severity of diagnosis, overall health-sickness, numerous indices of symptomatology severity, and a measure of difficulty in social/employment functioning. These findings point to the need to recognize and treat self-derogation in psychopathological states other than depression. In addition, they raise the important question of direction of causality between self-derogation and observed psychopathology.


Hasanuddinia maxomyos n. gen., n. sp. and Heligmonoides musseri n. sp. (Nematoda: Heligmonellidae) collected from endemic murines of Sulawesi, Indonesia.
Two new nematodes belonging to the subfamily Nippostrongylinae (Nematoda: Trichostrongyloidea: Heligmonellidae) are described based on specimens from endemic murines of Sulawesi, Indonesia: Hasanuddinia maxomyos n. gen., n. sp. from Maxomys musschenbroekii and Eropeplus canus, and Heligmonoides musseri n. sp. from M. musschenbroekii, E. canus, and Margaretamys elegans. Hasanuddinia is closest to Rattusstrongylus of Malaysian rats in lacking a carene and in having a lateromedian gradient in the size of the synlophe ridges in the ventral side of the midbody but is distinguished in that the dorsal ray is divided in the distal half. Heligmonoides musseri most resembles H. bulbosus of Maxomys whiteheadi of Malaysia in having a carene supported by slender ridges of which the proximal portion is not thickened but is distinguished in having longer externodorsal rays and longer spicules. The ancestors of the present Sulawesi nematodes seem to have originated on the southeast Asian continent, were introduced to Sulawesi with the dispersal of some murines, and subsequently speciated.


Acute macular neuroretinopathy as the first stage of SARS-CoV-2 infection.
To report two cases of Acute Macular Neuroretinopathy (AMN) presented as the first stage of SARS-CoV-2 infection in two European countries during the third wave of pandemic viral infection in the early months of 2021. A unilateral case of type 1 AMN in a man and a bilateral case of type 2 AMN in an otherwise heathy patients were reported. Sudden onset of paracentral scotoma characterized the cases with no systemic symptoms. Structural optical coherence tomography (OCT) shows multifocal middle and inner retinal hyperreflective infarctions. OCT-Angiography showed the presence of hypoperfusion of the deep capillary plexus (DCP) corresponding to the hyperreflective lesions visible on structural OCT, confirming the diagnosis. Type 1 and type 2 AMN may be the first stage of SARS-CoV-2 infection. We suggest testing all patients with AMN for SARS-CoV-2. In our cases, the natural history of AMN associated with SARS-CoV-2 infection was similar to already described cases of AMN.


Role of APLP2 in the prognosis and clinicopathology of renal cell carcinoma.
Identifying diagnostic and prognostic biomarkers is crucial for improved guidance of the treatment of renal cell carcinoma (RCC). Amyloid β precursor-like protein 2 (APLP2) has been determined to serve an important role in the progression of a number of cancer types. However, the expression and significance of APLP2 in RCC remains unknown. In the present study, it was determined that the expression of APLP2 protein (n=10) and mRNA (n=8) expression was significantly decreased in clear cell RCC (CCRCC) tissues compared with that in matched normal renal tissues. The expression level of APLP2 was significantly associated with high Fuhrman grade, high pT stage, and presence of distant metastasis and lymph node metastasis (P<0.05). Multivariate analysis demonstrated that the expression of APLP2 was a significant independent predictor of disease-specific survival in renal cell carcinoma (P=0.026). Notably, APLP2 expression was significantly associated with disease-specific survival (P<0.001). APLP2 may be used to potentially predict patient prognosis, and to guide clinical diagnosis and treatment in CCRCC.


Establishment and Evaluation of an Internal Quality Control Method for ESR Relays.
This study establish and evaluate an internal quality control system for erythrocyte sedimentation rate (ESR) by a "relay" mode based on samples from relevant patients. The method for establishing a new internal quality control system for ESR by a "relay" mode based on patient's samples was executed from February 2021 to July 2021. In this paper, a total of 219 outpatients were recruited for ESR determination, and their blood samples were stored at 4 °C or room temperature for 24 h. Subsequently, the samples were re-measured for ESR, and the re-measured values were compared with the initial values. The patient samples (15±1mm/h and 50±3mm/h) were selected after the TEST1 ESR analyzer was calibrated, and were stored overnight at 4 °C and measured again the following day. The percentage deviation was determined and entered into the quality control management module for internal quality control. Next, we analyzed the median distribution trend of the patients' ESR values measured by our laboratory every day over five months, as well as the external quality assessment (EQA) results for ESR obtained from the National Center for Clinical Laboratories (NCCL). The ESR of the room temperature samples after 24 h of storage had significantly decreased (P=0.001), while there was no noticeable difference for those stored at 4 °C (P=0.197). Results of the internal quality control in March were satisfactory, and there was no significant deviation in the median ESR relay results within five months. Besides, the EQA results for the ESR data obtained from NCCL were excellent. As a precise and practical new method, the ESR relay internal quality control method can be used to scientifically determine the stability and accuracy of the TEST1 ESR analyzer.


Hematological malignancies in East Africa-Which cancers to expect and how to provide services.
Sub-Saharan Africa (SSA) has an increasing non-communicable disease burden. Tanzania has an incidence of more than 35,000 cancer cases per year with an 80% mortality rate. Hematological malignancies account for 10% of these cases. The numbers will double within the next 10 years due to demographic changes, better diagnostic capabilities and life style changes. Kilimanjaro Christian Medical Centre established a Cancer Care Centre (CCC) in December 2016 for a catchment area of 15 million people in Northern Tanzania. This article aims to display the hematological diagnosis and characteristics of the patients as well as to describe the advancements of hematologic services in a low resource setting. A cross-sectional analysis of all hematological malignancies at CCC from December 2016 to May 2019 was performed and a narrative report provides information about diagnostic means, treatment and the use of synergies. A total of 209 cases have been documented, the most common malignancies were NHL and MM with 44% and 20%. 36% of NHL cases, 16% of MM cases and 63% of CML cases were seen in patients under the age of 45. When subcategorized, CLL/SLL cases had a median age was 56.5, 51 years for those with other entities of NHL. Sexes were almost equally balanced in all NHL groups while clear male predominance was found in HL and CML. Malignancies occur at a younger age and higher stages than in Western countries. It can be assumed that infections play a key role herein. Closing the gap of hematologic services in SSA can be achieved by adapting and reshaping existing infrastructure and partnering with international organizations.


Imaging the pneumoconioses: a multidisciplinary approach.
The initial early reaction of pulmonary tissue to inorganic dust inhalation is a fibrosing macrophagic alveolitis. This initial pulmonary lesion can be detected by an enhanced gallium 67 pulmonary uptake and analyses of bronchoalveolar lavage. These two techniques can document not only the increased proliferation of macrophages, but also the activation of macrophages to produce excessive amounts of fibronectin and other factors of fibroblastic growth implicated in the pathogenesis of the pneumoconioses. Of equal clinical interest is the development of computed tomography, which has permitted better characterization of the early stages of fibrosis in the pneumoconioses. These refinements in disease recognition will contribute to the earlier detection of pneumoconioses before they become incapacitating. Newer therapeutic methods are also under investigation that could permit inactivation of either the dust itself or the pulmonary macrophage. The coupling of these new diagnostic and therapeutic developments will bring in a new era in occupational pulmonary medicine.


Tamoxifen-induced non-alcoholic steatohepatitis: where are we now and where are we going?
Tamoxifen is a cheap and effective estrogen-receptor antagonist, used as the adjuvant hormonal treatment of choice in women with estrogen-receptor-positive breast cancer. Tamoxifen-induced non-alcoholic steatohepatitis (NASH) may increase the demand on oncologists, not only with regard to screening for diabetes, but also for the suggested link of NASH with high incidence of coronary heart disease. At present, there is no guideline for treatment of hyperlipidaemia associated with tamoxifen-induced NASH. However, exemstane (and other aromatase inhibitors) has been shown to lower triglyceride and have a neutral effect on low-denisty lipoprotein and cholesterol levels. These may be alternative agents if severe progressive liver disease or hyperlipidaemia were encountered with tamoxifen administration. Other lipid-lowering medications may have potential benefits in the treatment of tamoxifen-induced NASH and is discussed in this article.


Recurrence of Crohn's disease in the neoterminal ileum after ileal resection: is prevention therapy possible?
Crohn's recurrence is the appearance of objective signs--defined radiologically, endoscopically or pathologically--of Crohn's disease in the bowel of a patient who has previously had a resection of all macroscopically diseased tissue. New lesions can be visualized endoscopically within weeks to months after ileal resection and ileocolonic anastomosis in the neoterminal ileum. The evolution of these lesions mimics the natural history of ileal Crohn's disease at the onset. If we are able to prevent recurrence of early lesions, we could probably interrupt the natural course of the disease. Metronidazole decreases the severity of early recurrence without totally preventing it. The data on 5-ASA are conflicting. Claversal seems to have little effect whereas Asacol was found to prevent not only endoscopic but also clinical recurrence. Pentasa prevented the development of severe recurrence. New therapies including topically acting glucocorticosteroids and immune suppression should be studied.


Provision of extended producer responsibility system for products packaging: A case study of Iran.
A powerful legal tool in evolving solid waste management (SWM) systems is extended producer responsibility (EPR). It is a mechanism that shifts the responsibility of a product to manufacturers/importers at the 'end-of-life' stage. Yet, implementation of the EPR concept has faced difficulties in developing countries. In Iran, as one such country, the principle of EPR system was issued in executive regulation of SWM in 2005, however, so far, it has been limited to a voluntary scheme. The problem merits further investigation. Therefore, this study aims to shed light on the obstacles in the path of developing EPR system for product packaging. The research examines the current SWM systems in four functional classified frameworks: legal, institutional, financial and technical. The strengths, weaknesses, opportunities and threats of the system are elaborated through semi-structured interviews with a senior executive in the Ministry of Interior (MoI). Then, viable methods to increase resource efficiency and sustainable waste treatment are suggested. The change in the financing mechanism in the Budget Law 2020 forces the manufacturers/importers of products containing recyclable components to pay the revenue from one in 1000 products to MoI for developing recycling facilities and incinerators through partnerships with the private sector. This new strategy would promote proper management of product packaging, create more jobs and a market for international cooperation. However, poor source-separation of wet/dry waste, informal sector activities, exclusive focus on the economic aspect of waste management, lack of expertise and public awareness campaigns are the barriers in this regard.


Emerging roles of nodal and Cripto-1: from embryogenesis to breast cancer progression.
Breast carcinoma cells and embryonic progenitors similarly implement stem cell-associated signaling pathways to sustain continued growth and plasticity. Indeed, recent studies have implicated signaling pathways, including those associated with the Notch, and Transforming Growth Factor-Beta (TGF-beta) superfamilies, as instrumental to both embryological development and breast cancer progression. In particular, Nodal, an embryonic morphogen belonging to the TGF-beta superfamily, and its co-receptor, Cripto-1, are requisite to both embryogenesis and mammary gland maturation. Moreover, these developmental proteins have been shown to promote breast cancer progression. Here, we review the role of Nodal and its co-receptor Cripto-1 during development and we describe how this signaling pathway may be involved in breast cancer tumorigenesis. Moreover, we emphasize the potential utility of this signaling pathway as a novel target for the treatment and diagnosis of breast cancer.


Dietary acrylamide exposure from traditional food products in Lesser Poland and associated risk assessment.
Acrylamide (AA) is a carcinogenic and genotoxic food contaminant occurring in carbohydrate-rich foods produced at high cooking temperatures. The aim of the study was to determine the importance of AA exposure with respect to traditional food and to assess the associated risks. 165 food samples were collected from local markets in Lesser Poland. The participants enrolled in the study were 500 residents: (males - 179, females - 321) who had purchased food from local markets. Exposure of the participants to AA was assessed by combining the analytical AA results with data on the individual consumption of traditional foods. Risk assessment of AA exposure from traditional foods was estimated and the margin of exposure (MOE) values were calculated. The highest mean AA level was measured in pretzels (92 µg kg -1), followed by bagels (74.81 µg kg-1) and pork paté (59.56 µg kg-1). The average and 95th percentile values of AA exposure were 0.213 and 0.458 [µg kg-1 body weight (BW) day-1]. The calculated values of MOE for the average [798 and 2,019 for both benchmark dose lower confidence limit (BMDL) 0.17 and 0.43 mg kg-1 BW day-1] and 95th percentile AA exposure values (371 and 939 for both BMDL 0.17and 0.43 mg kg -1 BW day-1) suggest that there is a health concern with respect to adult residents. The results of the study confirm the general recommendation to the consumers, especially certain population groups, to eat a balanced healthy diet and to limit the amount of baked cereal products and fried products.


The brinker repressor system regulates injury-induced nociceptive sensitization in Drosophila melanogaster.
Chronic pain is a debilitating condition affecting millions of people worldwide, and an improved understanding of the pathophysiology of chronic pain is urgently needed. Nociceptors are the sensory neurons that alert the nervous system to potentially harmful stimuli such as mechanical pressure or noxious thermal temperature. When an injury occurs, the nociceptive threshold for pain is reduced and an increased pain signal is produced. This process is called nociceptive sensitization. This sensitization normally subsides after the injury is healed. However, dysregulation can occur which results in sensitization that persists after the injury has healed. This process is thought to perpetuate chronic pain. The Hedgehog (Hh) signaling pathway has been previously implicated in nociceptive sensitization in response to injury in Drosophila melanogaster. Downstream of Hh signaling, the Bone Morphogenetic Protein (BMP) pathway has also been shown to be necessary for this process. Here, we describe a role for nuclear components of BMP's signaling pathway in the formation of injury-induced nociceptive sensitization. Brinker (Brk), and Schnurri (Shn) were suppressed in nociceptors using an RNA-interference (RNAi) "knockdown" approach. Knockdown of Brk resulted in hypersensitivity in the absence of injury, indicating that it normally acts to suppress nociceptive sensitivity. Animals in which transcriptional activator Shn was knocked down in nociceptors failed to develop normal allodynia after ultraviolet irradiation injury, indicating that Shn normally acts to promote hypersensitivity after injury. These results indicate that Brk-related transcription regulators play a crucial role in the formation of nociceptive sensitization and may therefore represent valuable new targets for pain-relieving medications.


Thrombin induces expression of FGF-2 via activation of PI3K-Akt-Fra-1 signaling axis leading to DNA synthesis and motility in vascular smooth muscle cells.
To understand the mechanisms by which thrombin induces vascular smooth muscle cell (VSMC) DNA synthesis and motility, we have studied the role of phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR)-S6K1 signaling. Thrombin stimulated the phosphorylation of Akt and S6K1 in VSMC in a sustained manner. Blockade of PI3K-Akt-mTOR-S6K1 signaling by LY-294002, and rapamycin suppressed both thrombin-induced VSMC DNA synthesis and migration. Adenovirus-mediated expression of dominant-negative Akt also inhibited thrombin-induced VSMC DNA synthesis and migration. Furthermore, thrombin induced the expression of Fra-1 in a sustained PI3K-Akt-dependent and mTOR-independent manner in VSMC. Suppression of Fra-1 by its small interfering RNA attenuated both thrombin-induced VSMC DNA synthesis and migration. Thrombin also induced the expression of FGF-2 in a PI3K-Akt-Fra-1-dependent and mTOR-independent manner, and neutralizing anti-FGF-2 antibodies inhibited thrombin-stimulated VSMC DNA synthesis and motility. In addition, thrombin stimulated the tyrosine phosphorylation of EGF receptor (EGFR), and inhibition of its kinase activity significantly blocked Akt and S6K1 phosphorylation, Fra-1 and FGF-2 expression, DNA synthesis, and motility induced by thrombin in VSMC. Together these observations suggest that thrombin induces both VSMC DNA synthesis and motility via EGFR-dependent stimulation of PI3K/Akt signaling targeting in parallel the Fra-1-mediated FGF-2 expression and mTOR-S6K1 activation.


Childhood sexual abuse: a gender perspective on context and consequences.
Literature on gender and child sexual abuse (CSA) has highlighted patterns of similarity and difference among survivors and the need for further research. This study relied on gender analysis of 128 women and 69 men, obtained through an examination of childhood hospital records, to further examine gender differences in mental health outcomes among abuse survivors and correlates of mental health outcomes including professional help seeking, family environment, and other trauma exposure. Overall, men and women were similar in the context and consequences of CSA. The role of the characteristics of CSA and contextual variables in explaining variance in mental health for 106 male victims and nonvictims was also examined. Among male participants, number of incidents of sexual abuse, injury at the hands of a caregiver, and exposure to other traumas significantly explained higher levels of an array of mental health symptoms. Implications for future research are discussed.


Near-Infrared Artificial Synapses for Artificial Sensory Neuron System.
The computing based on artificial neuron network is expected to break through the von Neumann bottleneck of traditional computer, and to greatly improve the computing efficiency, displaying a broad prospect in the application of artificial visual system. In the specific structural layout, it is a common method to connect the discrete photodetector with the artificial neuron in series, which enhances the complexity of signal recognition, conversion and storage. In this work, organic small molecule IR-780 iodide is inserted into the memory device as both the charge trapping layer and near-infrared (NIR) photoresponsive film. Through electrical and optical regulation, artificial synaptic functions including short-term plasticity, long-term plasticity, and spike rate dependence are realized. In the established artificial sensory neuron system, NIR optical pulses can significantly improve the spiking rate. Moreover, the spiking neural networks are further constructed by simulation for handwritten digit classification. This research may contribute to the development of light driven neural robots, optical signal encryption, and neural computing.


Through the looking glass: primary epithelioid angiosarcoma in the left atrium, a unique site for a rare malignancy.
Malignant cardiac tumours occurring on the left side are vanishingly rare entities. We describe a case of a 73-year-old male who underwent surgery for a left-sided cardiac tumour following initial presentation with transient ischaemic attacks. In addition to the unusual presentation and subsequent metastatic pattern to the femur, the tumour's pathological diagnosis was that of an epithelioid variant of an angiosarcoma which has not been previously described in this anatomical location.


Kinesin family members KIF11 and KIF23 as potential therapeutic targets in malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is a rare and aggressive form of cancer commonly associated with asbestos exposure that stems from the thoracic mesothelium with high mortality rate. Currently, treatment options for MPM are limited, and new molecular targets for treatments are urgently needed. Using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and an RNA interference-based screening, we screened two kinesin family members as potential therapeutic targets for MPM. Following in vitro investigation of the target silencing effects on MPM cells, a total of 53 MPMs were analyzed immunohistochemically with tissue microarray. KIF11 and KIF23 transcripts were found to be overexpressed in the majority of clinical MPM samples as well as human MPM cell lines as determined by quantitative RT-PCR. Gene knockdown in MPM cell lines identified growth inhibition following knockdown of KIF11 and KIF23. High expression of KIF11 (KIF11-H) and KIF23 (KIF23-H) were found in 43.4 and 50.9% of all the MPM cases, respectively. Patients who received curative resection with tumors displaying KIF23-H showed shorter overall survival (P=0.0194). These results provide that inhibition of KIF11 and KIF23 may hold promise for treatment of MPMs, raising the possibility that kinesin-based drug targets may be developed in the future.


A randomized trial of intravitreal bevacizumab vs. ranibizumab for myopic CNV.
The aim was to compare the efficacy of intravitreal therapy with bevacizumab and ranibizumab for choroidal neovascularization (CNV) in pathologic myopia (PM). This was a prospective multicenter randomized nonblinded trial. In seven centers, 78 eyes were randomized 1:1 to treatment with bevacizumab (group B, 40 eyes) or ranibizumab (group R, 38 eyes) given with an "on demand" regimen (PRN). The mean follow-up was 19 months (SD 2, range 12-24). The mean BCVA at baseline was 0.60 logMAR (20/80 Snellen equivalent, Seq) and 50 letter score (ls). Mean final BCVA was 0.51 LogMAR (20/63 Seq) and 57 ls (p = 0.0009 and p = 0.0002, respectively). In group B, mean basal BCVA was 0.52 logMAR (20/63 Seq) and 54 ls, and final BCVA was 0.51 logMar (20/63 Seq) and 57 ls. In group R, mean basal BCVA was 0.62 logMAR (20/80 Seq) and 45 ls, and the final values were 0.50 logMAR (20/63 Seq) and 58 ls. Statistical comparison of the two groups showed no significant difference (logMAR p = 0.90 and letters p = 0.78). Multivariate analysis showed no influence of age or previous photodynamic treatment (PDT) on final visual changes. The mean number of treatments in the first year was 2.7 in group B and 2.3 in group R (p = 0.09). Myopic CNV equally benefits from on-demand intravitreal injection of either bevacizumab or ranibizumab; the therapeutic effect is independent of previous PDT and age.


Assessment of gray and white matter structural alterations in migraineurs without aura.
Migraine constitute a disorder characterized by recurrent headaches, and have a high prevalence, a high socio-economic burden and severe effects on quality of life. Our previous fMRI study demonstrated that some brain regions are functional alterations in migraineurs. As the function of the human brain is related to its structure, we further investigated white and gray matter structural alterations in migraineurs. In current study, we used surface-based morphometry, voxel-based morphometry and diffusion tensor imaging analyses to detect structural alterations of the white matter and gray matter in 32 migraineurs without aura compared with 32 age- and gender-matched healthy controls. We found that migraineurs without aura exhibited significantly increased gray matter volume in the bilateral cerebellar culmen, increased cortical thickness in the lateral occipital-temporal cortex, decreased cortical thickness in the right insula, increased gyrification index in left postcentral gyrus, superior parietal lobule and right lateral occipital cortex, and decreased gyrification index in the left rostral middle frontal gyrus compared with controls. No significant change in white matter microstructure was found in DTI analyses. The significantly altered gray matter brain regions were known to be associated with sensory discrimination of pain, multi-sensory integration and nociceptive information processing and were consistent with our previous fMRI study, and may be involved in the pathological mechanism of migraine without aura.


Bushen Jianpi Formula Combined with Entecavir for the Treatment of HBeAg-Negative Chronic Hepatitis B: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.
Bushen Jianpi formula (BSJPF, also known as Lingmao formula) is a traditional Chinese medicine for chronic hepatitis B (CHB). The previous study has suggested that the treatment combination of BSJPF and entecavir (ETV) can achieve a significant loss of hepatitis B e antigen (HBeAg) and a significant decrease in serum level of hepatitis B virus (HBV) DNA in HBeAg-positive CHB patients with mildly elevated alanine aminotransferase. This study aimed to evaluate the efficacy and safety of BSJPF combined with ETV for treating HBeAg-negative CHB patients. A total of 640 patients were assigned randomly to the treatment group (receiving BSJPF combined with ETV for 96 weeks) or the control group (receiving a placebo combined with ETV for 96 weeks) in a 1 : 1 ratio. The primary endpoints are the rate of loss of hepatitis B surface antigen (HBsAg). The secondary outcomes included the rate of decrease in the HBsAg concentration to ≥1 lg·IU/mL, the HBV DNA suppression, the decline of the level of covalently closed circular DNA (cccDNA) in the liver, histological improvements, and the rate of ALT normalization. The rate of HBsAg loss in the treatment group was significantly higher than that of the control group (5.5% versus 1.8%, P=0.031). There were 11.1% of patients in the treatment group who recorded a reduction in HBsAg ≥1 lg·IU/mL, which is better than 5.9% of patients in the control group (P=0.043). There was no significant difference between the two groups with regard to the rate of HBV DNA clearance, the reduction in intrahepatic cccDNA, and the rate of ALT normalization (P > 0.05). The rate of liver fibrosis improvement in the treatment group was better than that of the control group (35.5% versus 11.8%, P=0.031), but there was no difference in necroinflammatory improvement (P > 0.05). The adverse events (AEs) were similar between the two groups, except for the abnormal kidney function, with 2.2% in the control group and 0.0% in the treatment group (P=0.028). The combination of BSJPF and ETV can increase the rate of HBsAg loss and the rate of histological fibrosis improvement without serious adverse events in CHB patients. Trial Registration. This trial is registered with ChiCTR-IOR-16009880 on November 16, 2016-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=16836.


Lumateperone: A Novel Antipsychotic for Schizophrenia.
To provide a concise review of the new Food and Drug Administration (FDA)-approved antipsychotic, lumateperone, for use in schizophrenia. A literature search of PubMed was performed (January 2000 to May 2020) using the following key terms: lumateperone, Caplyta, and ITI-007. Abstracts from conferences, review articles, clinical trials, and drug monographs were reviewed. Relevant English-language monographs and studies conducted in humans were considered. Lumateperone was FDA approved for the treatment of schizophrenia in December 2019 based on 2 published randomized, double-blind, placebo-controlled trials. Lumateperone's pharmacology is consistent with that of other second-generation antipsychotics in that it has a higher affinity for the serotonin (5-HT2A) receptors compared with dopamine (D2) receptors but with lower affinities for α-1 and histaminergic receptors. In addition, it serves as a presynaptic dopamine partial agonist, serotonin reuptake inhibitor, and an indirect modulator of glutamatergic systems. Based on the 4-week clinical trials, lumateperone was well tolerated. Most common treatment-emergent adverse events were headache, somnolence, and dizziness. At this time, lumateperone had a statistically significant reduction in Positive and Negative Syndrome Scale when compared with placebo and was not significantly associated with the extrapyramidal symptoms (EPS) and metabolic adverse effects commonly seen with other antipsychotics. Lumateperone has the potential to benefit individuals with schizophrenia who are intolerant to the EPSs or metabolic adverse effects of other antipsychotics. However, further head-to-head trials with commercially available antipsychotics are still required to assist in establishing its role in treatment.


Hemoglobin Lepore Boston in a Turkish Family.
An abnormal hemoglobin was detected in a Balkan immigrant Turkish family. Erythrocyte morphology was similar to ß-thalassemia trait. Molecular analysis showed that the abnormal hemoglobin was Hemoglobin LeporeBoston. All affected family members were in heterozygote state and asymptomatic.


The bacterial flora of fruits and vegetables in Lebanon and the effect of washing on the bacterial content.
Washed and unwashed vegetables and fruit specimens including radish, lettuce, mint, carrots, parsley, strawberries, green almond, akadinya, green-gages, cherries, plums, peaches, pears, and apples were investigated for their bacterial content. Tested specimens had a high content of bacteria belonging to the genera Enterobacter, Citrobacter, Klebsiella, Proteus, Pseudomonas, Providencia, Escherichia, Staphylococcus, and Salmonella. The washing procedure followed was effective in reducing the number of bacteria, but did not eliminate them. Enterobacter agglomerans was present in most specimens tested, and 11 out of 28 E. coli isolates were serotypable and may be enterotoxigenic or enteropathogenic. These findings are of concern in view of the fact that food-borne illnesses including "Traveler's diarrhea" are common in Lebanon.


Genome-wide association study of blast resistance in indica rice.
Rice blast disease is one of the most serious and recurrent problems in rice-growing regions worldwide. Most resistance genes were identified by linkage mapping using genetic populations. We extensively examined 16 rice blast strains and a further genome-wide association study based on genotyping 0.8 million single nucleotide polymorphism variants across 366 diverse indica accessions. Totally, thirty associated loci were identified. The strongest signal (Chr11_6526998, P =1.17 × 10-17) was located within the gene Os11g0225100, one of the rice Pia-blast resistance gene. Another association signal (Chr11_30606558) was detected around the QTL Pif. Our study identified the gene Os11g0704100, a disease resistance protein containing nucleotide binding site-leucine rich repeat domain, as the main candidate gene of Pif. In order to explore the potential mechanism underlying the blast resistance, we further examined a locus in chromosome 12, which was associated with CH149 (P =7.53 × 10-15). The genes, Os12g0424700 and Os12g0427000, both described as kinase-like domain containing protein, were presumed to be required for the full function of this locus. Furthermore, we found some association on chromosome 3, in which it has not been reported any loci associated with rice blast resistance. In addition, we identified novel functional candidate genes, which might participate in the resistance regulation. This work provides the basis of further study of the potential function of these candidate genes. A subset of true associations would be weakly associated with outcome in any given GWAS; therefore, large-scale replication is necessary to confirm our results. Future research will focus on validating the effects of these candidate genes and their functional variants using genetic transformation and transferred DNA insertion mutant screens, to verify that these genes engender resistance to blast disease in rice.


[Arc welder's lung].
Pneumoconiosis of electric arc welder or siderotic pneumoconiosis was described by Doig and McLaughlin in 1936 as a lung disease caused by chronic inhalation of iron fumes in electric arc welders. We present a case report of electric arc welder siderosis associated with high levels of ferritin, without findings of iron deposit in any other organ.


Direct metal laser sintering titanium dental implants: a review of the current literature.
Statement of Problem. Direct metal laser sintering (DMLS) is a technology that allows fabrication of complex-shaped objects from powder-based materials, according to a three-dimensional (3D) computer model. With DMLS, it is possible to fabricate titanium dental implants with an inherently porous surface, a key property required of implantation devices. Objective. The aim of this review was to evaluate the evidence for the reliability of DMLS titanium dental implants and their clinical and histologic/histomorphometric outcomes, as well as their mechanical properties. Materials and Methods. Electronic database searches were performed. Inclusion criteria were clinical and radiographic studies, histologic/histomorphometric studies in humans and animals, mechanical evaluations, and in vitro cell culture studies on DMLS titanium implants. Meta-analysis could be performed only for randomized controlled trials (RCTs); to evaluate the methodological quality of observational human studies, the Newcastle-Ottawa scale (NOS) was used. Results. Twenty-seven studies were included in this review. No RCTs were found, and meta-analysis could not be performed. The outcomes of observational human studies were assessed using the NOS: these studies showed medium methodological quality. Conclusions. Several studies have demonstrated the potential for the use of DMLS titanium implants. However, further studies that demonstrate the benefits of DMLS implants over conventional implants are needed.