The impact of a filariasis control program on Lihir Island, Papua New Guinea.
Annual mass drug administration (MDA) over five years is the WHO's recommended strategy to eliminate lymphatic filariasis (LF). Some experts, however, consider that longer periods of treatment might be necessary in certain high prevalence and transmission environments based upon past unsuccessful field experience and modelling. To evaluate predictors of success in a LF control program we conducted an ecological study during a pre-existing MDA program. We studied 27 villages in Lihir Island, Papua New Guinea, from two areas with different infection rates before MDA. We undertook surveys to collect information on variables potentially having an influence on the outcome of the program, including epidemiological (baseline prevalence of infection, immigration rate), entomological (vector density) and operational (treatment coverage, vector control strategies) variables. The success in a village was defined using variables related to the infection (circulating filarial antigenemia prevalence < 1%) and transmission (antigenemia prevalence < 1 in 1000 children born since start of MDA). 8709 people were involved in the MDA program and average coverage rates were around 70%. The overall prevalence of filariasis fell from an initial 17.91% to 3.76% at round 5 (p < 0.001). Viewed on a village by village basis, 12/27 (44%) villages achieved success. In multivariate analysis, low baseline prevalence was the only factor predicting both success in reducing infection rates (OR 19,26; CI 95% 1,12 to 331,82) and success in preventing new infections (OR 27,44; CI 95% 1,05 to 719,6). Low vector density and the use of an optimal vector control strategy were also associated with success in reducing infection rates, but this did not reach statistical significance. Our results provide the data that supports the recommendation that high endemic areas may require longer duration MDA programs, or alternative control strategies.


The clinical relevance of epithelial-mesenchymal transition and its correlations with tumorigenic immune infiltrates in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a cancer with extremely high mortality. Epithelial-mesenchymal transition (EMT) may play an important role in the occurrence, invasion and prognosis of HCC; however, its relationship with immunity in HCC has not yet been studied. Therefore, we investigated the diagnostic and prognostic values of EMT and explored its potential connections with tumorigenic immune infiltrates in HCC. We first proposed a quantitative metric of EMT activity, the EMT score. After applying this metric to 20 datasets from the Integrative Molecular Database of Hepatocellular Carcinoma, the Cancer Genome Atlas, and the Gene Expression Omnibus, we explored the ability of the EMT score to stratify across sample types. We then applied the EMT score for survival analysis and to differentiate patients with/without vascular invasion to test its prognostic value. We also collected and calculated data on the abundance of immune cells and immune cell markers in HCC and investigated their correlations with EMT scores. Finally, we synthesized and analyzed 20 datasets and constructed an EMT-gene-immune linkage network. The results showed higher EMT scores in HCC samples than in cirrhotic and normal livers. The cases with higher EMT scores also showed poorer performance in terms of prognostic factors such as vascular invasion and overall survival time. Our research demonstrated a broad correlation between EMT and the tumor immune microenvironment, and we uncovered multiple potential linkers associated with both EMT and immunity. Studying EMT has clinical relevance and high diagnostic and prognostic value for HCC.


Primary Central Nervous System Lymphoma Revealed by 68Ga-FAPI and 18F-FDG PET/CT.
A 67-year-old woman presented with left limb weakness, facial paralysis, and unsteady gait for 1 month. Brain MRI detected a mass in the right frontal lobe with prominent peritumoral edema, suggesting a malignant brain tumor. In 18F-FDG PET/CT, the mass was very FDG avid, and 68Ga-FAPI PET/CT showed the mass had heterogeneously mild to moderate increased uptake of the tracer. Histopathological examination after surgical resection of the mass confirmed the diagnosis of diffuse large B-cell lymphoma. The current case indicated the existence of fibrosis in the lymphoma lesion to some extent.


[Autism spectrum disorder and genes for synaptic proteins].
Autism spectrum disorder (ASD) is characterized by impaired social interaction and communication, and restricted interests. It is generally accepted that ASD is caused by abnormalities in the structure or functions of the brain. Recent genome-wide analyses have identified copy number variations (CNVs) of neuronal genes in the genomes of ASD patients. CNV is a commonly observed phenomenon in human beings. During the first cell division of meiosis, irregular crossing over between homologous chromosomes results in loss or duplication of a segment. From 2007 to 2010, several groups performed a large-scale virtual screening of CNVs in ASD genomes. Genes affected by CNV, de novo CNVs, and rare CNVs were more prevalent in ASD. The results highlighted the CNVs of many neuronal genes associated with ASD. A fraction of these genes was previously identified in ASD but some were newly identified in each study. The CNVs implicated in ASD include neuronal genes belonging to 4 classes. These genes encode (1) neural adhesion molecules, including cadherins, neuroligin, and neurexin; (2) scaffold proteins such as SHANK3; (3) protein kinases and other intracellular signaling molecules; and (4) proteins that regulate protein syntheses. In general, these proteins play a role in synapse of glutamatergic neurons. The CNVs detected in the ASD patient genomes of imply a link between the synaptic proteins and pathological characteristics of ASD. Altered protein dosage by the CNVs may alter the functional quality of ASD patient's synapses, and may consequently affect their development of language and communication skills. There are 2 types of ASD, one is sporadic and, the other is familial. According to some reports, de novo CNVs are more frequently observed in sporadic-type ASD. However, it is generally understood that a combination of particular CNVs and other possible mutations underlie the pathology of ASD regardless of ASD type. The major symptoms of ASD are often curable with behavioral intervention during early childhood. An early diagnosis, followed by early start of treatment is crucial for language development and communication skills. Further and broader research on genomes will eventually provide information on the biological characteristics of ASD, as well as on specific ASD genotypes, thus aiding in the establishment of optimal treatment and medication to meet the biological conditions of each patient.


The cerebellum in Alzheimer's disease: evaluating its role in cognitive decline.
The cerebellum has long been regarded as essential only for the coordination of voluntary motor activity and motor learning. Anatomical, clinical and neuroimaging studies have led to a paradigm shift in the understanding of the cerebellar role in nervous system function, demonstrating that the cerebellum appears integral also to the modulation of cognition and emotion. The search to understand the cerebellar contribution to cognitive processing has increased interest in exploring the role of the cerebellum in neurodegenerative and neuropsychiatric disorders. Principal among these is Alzheimer's disease. Here we review an already sizeable existing literature on the neuropathological, structural and functional neuroimaging studies of the cerebellum in Alzheimer's disease. We consider these observations in the light of the cognitive deficits that characterize Alzheimer's disease and in so doing we introduce a new perspective on its pathophysiology and manifestations. We propose an integrative hypothesis that there is a cerebellar contribution to the cognitive and neuropsychiatric deficits in Alzheimer's disease. We draw on the dysmetria of thought theory to suggest that this cerebellar component manifests as deficits in modulation of the neurobehavioural deficits. We provide suggestions for future studies to investigate this hypothesis and, ultimately, to establish a comprehensive, causal clinicopathological disease model.


[Vein of Galen aneurysmal malformation in a Neonate: a case report].
The aneurysm of the Galen vein is a rare and complex congenital intracerabral vascular malformation. We report a case suspected by the obstetric ultrasound in the third trimester and confirmed by the transfontanellar Doppler ultrasound and brain CT-Scan in the asymptomatic 11-day old baby born at term.


Significant Factors Influencing the Effectiveness of Cranial Remolding Orthoses in Infants With Deformational Plagiocephaly.
Infants with deformational plagiocephaly may be indicated for a cranial remolding orthosis (CRO) depending on the severity of deformation. Studies have found torticollis and prematurity to be risk factors for the development of deformational plagiocephaly and indicate younger infants have faster and greater correction. However, clinical decisions about which infants should be recommended for CRO treatment differ among healthcare providers and insurance coverage criteria vary. In order to provide insight into treatment recommendations, this study aims to examine the influence of 4 specific factors on CRO treatment time and the infant's resultant posttreatment head shape. Results indicate that presenting age, presenting severity, and the presence of torticollis significantly influence treatment duration. Presenting age and severity were found to significantly influence final head shape. The presence of prematurity was not found to be significant when infants were categorized by their corrected postpartum ages.


Two genetically separable steps in the differentiation of thymic epithelium.
The development of the thymus depends initially on epithelial-mesenchymal and subsequently on reciprocal lympho-stromal interactions. The genetic steps governing development and differentiation of the thymic microenvironment are unknown. With the use of a targeted disruption of the whn gene, which recapitulates the phenotype of the athymic nude mouse, the WHN transcription factor was shown to be the product of the nude locus. Formation of the thymic epithelial primordium before the entry of lymphocyte progenitors did not require the activity of WHN. However, subsequent differentiation of primitive precursor cells into subcapsular, cortical, and medullary epithelial cells of the postnatal thymus did depend on activity of the whn gene. These results define the first genetically separable steps during thymic epithelial differentiation.


Rapid axonal sprouting and pruning accompany functional reorganization in primary visual cortex.
The functional architecture of adult cerebral cortex retains a capacity for experience-dependent change. This is seen following focal binocular lesions, which induce rapid changes in receptive field size and position. To follow the dynamics of the circuitry underlying these changes, we imaged the intrinsic long-range horizontal connections within the lesion projection zone (LPZ) in adult macaque primary visual cortex. To image the same axons over time, we combined viral vector-mediated EGFP transfer and two-photon microscopy. The lesion triggered, within the first week, an approximately 2-fold outgrowth of axons toward the center of the LPZ. Over the subsequent month, axonal density declined due to a parallel process of pruning and sprouting but maintained a net increase relative to prelesion levels. The rate of turnover of axonal boutons also increased. The axonal restructuring recapitulates the pattern of exuberance and pruning seen in early development and correlates well with the functional changes following retinal lesions.


Preoperative Optimization Before Elective Total Joint Replacement.
The identification and preoperative optimization of modifiable risk factors is proposed to be an effective method to decrease complications and improve the value of elective total joint arthroplasty. It is important to highlight the best practices as well as controversies in the preoperative evaluation and treatment of patients undergoing total joint arthroplasty.


Cost-effectiveness of strategies for detecting diabetic retinopathy.
A computer model has been developed to determine cost-effectiveness of screening and treatment for diabetic retinopathy from a societal viewpoint. This model was used to evaluate biannual and annual screening programs using ophthalmoscopy, fundus photography with a "nonmydriatic camera," and photography with a "mydriatic camera." Computations were performed for three subpopulations formed by patients with younger onset diabetes (age at diagnosis less than 30 years) of 5 years or more duration, with older onset diabetes (age at diagnosis greater than or equal to 30 years) who are taking insulin, and with older onset diabetes not taking insulin. Population characteristics are from a well-described southern Wisconsin population where data are available, but the computer model may be specialized to other population. Generally costs of screening programs appear to be recovered by avoided costs of blindness in the population subgroups taking insulin; however, the cost of screening programs generally are not recovered by avoiding costs of blindness in the older onset population subgroup not taking insulin. It was estimated that supplying annual examination with mydriatic fundus photography as a screening program to a cohort of 1,000 diabetics from the younger onset population who have been diagnosed at least 5 years and who are currently not receiving care might save 319 sight years over the lifetime of the cohort. This program will save 62 sight years in an older onset cohort who are taking insulin, and 21 sight years in the older onset population not taking insulin (all benefits are presented as present values computed with an annual discount rate of 5%). Other programs achieve slightly lower savings in each subpopulation.


Discrimination is not just Black and White in romantic relationships: A consideration of perspective taking and self-expansion.
Interracial relationships can satisfy our human need for interpersonal bonds, but face adversity due to racial discrimination. This adversity is not parallel for the involved partners, however, in ways that have implications for relationship outcomes. As such, in the current research, we considered that discrimination may provide an avenue for positive self-expansion for a White partner, insofar as they use it to learn more about their partner's worldview and experience. This is important, as facing racial discrimination could be a reason White partners think about ending their relationship. Thus, identifying processes that mitigate adversity for the White partner could bolster relationship outcomes for both partners and enhance persistence in interracial relationships. Specifically, we tested whether White partners engaging in perspective taking could buffer against the negativity of discrimination. In Study 1 (N = 260), we found that perspective taking was associated with feeling the relationship expanded one's worldview for White partners in interracial relationships (but not for Black or non-White Hispanic partners). In Studies 2-4 (N = 531), we found that partners who engaged in perspective taking when discrimination was salient experienced greater positive self-expansion, which in turn led to greater reports of relationship quality. Collectively, these results suggest that perspective taking provides one process by which interracial relationships can be fortified against the adversity of racial discrimination. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Expression and significance of c-met protein in papillary thyroid carcinoma.
The c-met protein, encoded by the c-met oncogene and its ligand, the hepatocellular growth factor/scatter factor, are known to be responsible for the motility and mitogenesis of epithelial cells including cancer cells. Recent studies have reported the prognostic significance of the c-met protein in malignant tumors. Papillary thyroid carcinoma, the most common histological type of thyroid carcinoma, can easily metastasize to regional lymph nodes, reflecting the activated motility and invasiveness of the carcinoma cells. We examined the expression of c-met protein in papillary thyroid carcinomas to assess its significance. Immunohistochemical staining of the c-met protein was performed on archival materials. The c-met protein was expressed in 10 cases of papillary thyroid carcinoma with recurrence, and in 5 of 10 cases without recurrence. Normal thyroids were negative for c-met protein. Expression of the c-met protein was statistically associated with recurrence of the thyroid carcinoma (p = 0.016). It is suggested that expression of the c-met protein plays a role in the recurrence of papillary thyroid carcinoma.


Evaluation of standard pyrethroid based LNs (MiraNet and MagNet) in experimental huts against pyrethroid resistant Anopheles gambiae s.l. M'bé, Côte d'Ivoire: Potential for impact on vectorial capacity.
There is evidence from experimental hut and household studies that the entomological efficacy of long lasting pyrethroid treated nets (LLINs) is compromised in areas of pyrethroid resistance. The rapid increase in resistance intensity in African malaria vectors could further undermine the performance of these nets. The pyrethroid resistance intensity in Anopheles gambiae s.l. M'bé from central Côte d'Ivoire is reported to be high (> 1700 fold). Whether this translates into an increase in entomological indicators of malaria transmission needs investigation. The efficacy of two long lasting insecticidal nets (LN) MiraNet and MagNet, both alpha-cypermethrin based was evaluated in experimental huts against pyrethroid resistant Anopheles gambiae in M'bé, central Côte d'Ivoire. All nets were deliberately holed to simulate wear-and-tear and were tested unwashed and after 20 standardized washes. The entry rates of An. gambiae s.l. into huts with insecticide treated nets were 62-84% lower than entry into huts with untreated nets (p < 0.001). Exit rates of An. gambiae s.l. with unwashed MiraNet and MagNet LNs were significantly greater than with untreated nets (50-60% vs 26%) and this effect after washing 20 times nets did not decrease. Blood-feeding with both nets was significantly inhibited relative to the untreated reference net (31-55%) (p < 0.001). Washing MiraNet LN 20 times had no significant impact on protection against An. gambiae s.l. bites but it did cause a significant fall by 40% in protection with MagNet LN (p < 0.001). All insecticide treated nets induced higher mortality of An. gambiae s.l. than the untreated net (p < 0.05). The impact though significant was limited (14-30%). The personal protection against An. gambiae s.l. bites derived from all treatments was high (75-90%). The overall insecticidal effect was compromised by pyrethroid resistance and was not detectable in some treatments. In this area of high pyrethroid resistance intensity (over 1700 fold), both MiraNet and MagNet LNs still conferred appreciable personal protection against mosquito bites despite inducing only slightly greater mortality of pyrethroid resistant Anopheles mosquitoes than untreated nets. The impact is comparable to moderately intense Benin resistance area (207 fold) and Burkina Faso (over 1000 fold). This preserved level of protection plus the small but sensitive killing of mosquitoes may continue to impact vectorial capacity despite high intensity of resistance. Nevertheless, there is an obvious need for strategies and nets with novel mode of action to enhance vector control.


Committee report: publication guidelines and recommendations for studies using electroencephalography and magnetoencephalography.
Electromagnetic data collected using electroencephalography (EEG) and magnetoencephalography (MEG) are of central importance for psychophysiological research. The scope of concepts, methods, and instruments used by EEG/MEG researchers has dramatically increased and is expected to further increase in the future. Building on existing guideline publications, the goal of the present paper is to contribute to the effective documentation and communication of such advances by providing updated guidelines for conducting and reporting EEG/MEG studies. The guidelines also include a checklist of key information recommended for inclusion in research reports on EEG/MEG measures.


[Surgical treatment for Pancoast tumor].
Pancoast tumor has been considered to be associated with a poor prognosis in the presence of severe chest pain and brachial and/or antebrachial pain because of brachial plexus infiltration. However, the treatment outcome was markedly improved by the introduction of trimodality therapy comprising advanced surgical resection, chemotherapy, and radiotherapy. Surgical resection after preoperative concurrent chemoradiotherapy has now been established as the standard treatment strategy. Pancoast tumor invades the surrounding tissues of the thoracic inlet area where important blood vessels and nerves run, making the surgical procedure difficult. However, there have been many advances in radical resection aiming for an improved outcome. Thus, it is possible for surgeons to select the proper surgical approach according to the location of the tumor mass. We should be careful regarding oversurgery after induction chemoradiotherapy. Therefore, the selection of patients who may benefit from surgery and improvement of surgical techniques for reduced invasiveness and complications are necessary.


Electrophoretic deposition polymerization of diacetylenes with tunable structure.
Serial novel chiral polydiacetylenes (PDAs) are efficiently prepared at room temperature by the controllable electrophoretic deposition of diacetylenes with tunable structure as designed from easily available starting materials. The colorimetrically reversible properties of PDAs in the range between 25 and 85 °C are influenced by the different amino acid moiety in the PDAs as anticipated. The PDA containing aromatic ring is much better for the colorimetrically reversible properties, while irreversible thermochromism is displayed for the PDA with the structure of the longer methylene units in the main chain of amino acid moiety.


Sensory quality of functional beverages: bitterness perception and bitter masking of olive leaf extract fortified fruit smoothies.
Olive leaf extract (OLE) contains high amounts of oleuropein and hydroxytyrosol. The antioxidant capacity of these polyphenols makes OLE a promising ingredient for functional food. OLE causes very strong bitterness perception and can therefore only be formulated in low concentrations. In this research, bitter detection and recognition thresholds of OLE-fortified fruit smoothies were determined by a trained sensory panel (n = 11). Masking of the OLE's bitter taste was investigated with addition of sodium cyclamate, sodium chloride, and sucrose by means of a standardized ranking method and a scale test. Detection (5.78 mg/100 g) and recognition thresholds (8.05 mg/100 g) of OLE polyphenols confirmed the low formulation limits when bitterness was not masked by other substances. At higher polyphenol levels of 20 mg/100 g, sodium cyclamate and sucrose were able to reduce bitter taste perception by 39.9% and 24.9%, respectively, whereas sodium chloride could not effectively mask bitterness. Practical Application: Development of functional food poses new challenges for the food industry. A major problem in this field is the high bitterness of natural polyphenol-containing extracts with potential health benefits. This research was conducted to understand the sensory impact of olive leaf extract (OLE), a novel food ingredient with very bitter taste. In product development, the data of this research can be considered for formulation limits and the general sensory quality of OLE-fortified food and beverages.


Clinical diagnosis of internal resorption: an exception to the rule.
This paper describes a case in which the radiographic appearance of a resorptive lesion in a mandibular incisor tooth posed difficulty in the diagnosis of its origin. The lesion did not conform to the normally accepted criteria for diagnosis of internal resorption. Clinical examination did not support the diagnosis of external cervical resorption. Serial histological section of the extracted tooth subsequently confirmed the diagnosis of internal resorption. The criteria for differential diagnosis of resorptive lesions with smooth outlines in the cervical regions of teeth are discussed together with the rationale for their management.


New Onset Multiple Sclerosis Post-COVID-19 Vaccination and Correlation With Possible Predictors in a Case-Control Study.
Various inflammatory diseases have been associated with the administration of various vaccines. Several reports have associated vaccine administration with the demyelinating diseases of the central nervous system (CNS). However, no clear or strong scientific evidence exists to support the association of vaccine administration with the onset of demyelinating diseases. Some CNS demyelination diseases such as acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica spectrum disorders (NMOSD) were reported following the administration of COVID-19 vaccines. In this study, new onset multiple sclerosis (MS) following COVID-19 vaccine administration was reported. In this longitudinal observational case-control study, a total of 65 participants were studied, who were divided into two groups. Group A included 32 MS patients who were diagnosed post-COVID-19 vaccine administration and group B included 33 participants who received COVID-19 vaccines and did not develop MS. Group B was used as a control. The Chi-square test and logistic regression analysis were carried out using Statistical Product and Service Solutions (SPSS) (IBM SPSS Statistics for Windows, Armonk, NY) software. Univariate and multivariate logistic regression analysis was performed and a significant correlation between the risk factors and the development of MS post-COVID-19 vaccination was identified. The risk factors, identified in this study, can be used as significant independent predictors for developing MS post-COVID-19 vaccinations.


Proteins in the enamel fluid of immature porcine teeth.
The fluid was separated from the immature soft enamel of porcine permanent teeth in the secretory stage according to procedures reported previously (Aoba and Moreno, 1987). The protein content of the fluid was about 2.8% w/v; its amino-acid composition was characterized by high contents of Pro, Glx, Leu, and His, showing composition similar to that of the 20 kilo-dalton (kd) amelogenin or its C-terminal segments. The two major protein species in the fluid had apparent molecular weights of 13 kd and 11 kd, as determined by SDS electrophoresis; the N-terminal residue of the former was Leu, while that of the latter was Ala. The C-terminal sequence of both of them was -Met-Phe-Ser. By comparison with the published sequence of 20-kd porcine amelogenin, it is concluded that the main fluid constituents were derived by cleavages of N-terminal segments from the 20-kd amelogenin.


An oligodeoxyribonucleotide that supports catalytic activity in the hammerhead ribozyme domain.
A study of the activity of deoxyribonucleotide-substituted analogs of the hammerhead domain of RNA catalysis has led to the design of a 14mer oligomer composed entirely of deoxyribonucleotides that promotes the cleavage of an RNA substrate. Characterization of this reaction with sequence variants and mixed DNA/RNA oligomers shows that, although the all-deoxyribonucleotide oligomer is less efficient in catalysis, the DNA/substrate complex shares many of the properties of the all-RNA hammerhead domain such as multiple turnover kinetics and dependence on Mg2+ concentration. On the other hand, the values of kinetic parameters distinguish the DNA oligomer from the all-RNA oligomer. In addition, an analog of the oligomer having a single ribonucleotide in a strongly conserved position of the hammerhead domain is associated with more efficient catalysis than the all-RNA oligomer.


Optimized Orbitrap HCD for quantitative analysis of phosphopeptides.
Despite the tremendous commercial success of radio frequency quadrupole ion traps for bottom-up proteomics studies, there is growing evidence that peptides decorated with labile post-translational modifications are less amenable to low-energy, resonate excitation MS/MS analysis. Moreover, multiplexed stable isotope reagents designed for MS/MS-based quantification of peptides rely on accurate and robust detection of low-mass fragments for all precursors. Collectively these observations suggest that beam-type or tandem in-space MS/MS measurements, such as that available on traditional triple quadrupole mass spectrometers, may provide beneficial figures of merit for quantitative proteomics analyses. The recent introduction of a multipole collision cell adjacent to an Orbitrap mass analyzer provides for higher energy collisionally activated dissociation (HCD) with efficient capture of fragment ions over a wide mass range. Here we describe optimization of various instrument and post-acquisition parameters that collectively provide for quantification of iTRAQ-labeled phosphorylated peptides isolated from complex cell lysates. Peptides spanning a concentration dynamic range of 100:1 are readily quantified. Our results indicate that appropriate parameterization of collision energy as a function of precursor m/z and z provides for optimal performance in terms of peptide identification and relative quantification by iTRAQ. Using this approach, we readily identify activated signaling pathways downstream of oncogenic mutants of Flt-3 kinase in a model system of human myeloid leukemia.


Purification and characterization of serine acetyltransferase from Escherichia coli partially truncated at the C-terminal region.
Incubation of serine acetyltransferase (SAT) from Escherichia coli at 25 degrees C in the absence of protease inhibitors yielded a truncated SAT. The truncated SAT was much less sensitive to feedback inhibition than the wild-type SAT. Analyses of the N- and C-terminal amino acid sequences found that the truncated SAT designated as SAT delta C20 was a resultant form of the wild-type SAT cleaved between Ser 253 and Met 254, deleting 20 amino acid residues from the C-terminus. Based on these findings, we constructed a plasmid containing an altered cysE gene encoding the truncated SAT. SAT delta C20 was produced using the cells of E. coli JM70 transformed with the plasmid and purified to be homogeneous on an SDS-polyacrylamide gel. Properties of the purified SAT delta C20 were investigated in comparison with those of the wild-type SAT and Met-256-Ile mutant SAT, which was isolated by Denk and Böck but not purified (J. Gen. Microbiol., 133, 515-525 (1987)). SAT delta C20 was composed of four identical subunits like the wild-type SAT and Met-256-Ile mutant SAT. Specific activity, optimum pH for reaction, thermal stability, and stability to reagents for SAT delta C20 were similar those for the wild-type SAT and Met-256-Ile mutant SAT. However, SAT delta C20 did not form a complex with O-acetylserine sulfhydrylase-A (OASS-A), a counterpart of the cysteine synthetase and did not reduce OASS activity in contrast to the wild-type SAT and Met-256-Ile mutant SAT.


Inactivation of a heterocyst-specific invertase indicates a principal role of sucrose catabolism in heterocysts of Anabaena sp.
Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that carries out N(2) fixation in specialized cells called heterocysts, which exchange nutrients and regulators with the filament's vegetative cells that perform the photosynthetic fixation of CO(2). The Anabaena genome carries two genes coding for alkaline/neutral invertases, invA and invB. As shown by Northern analysis, both genes were expressed monocistronically and induced under nitrogen deprivation, although induction was stronger for invB than for invA. Whereas expression of an InvA-N-GFP fusion (green fluorescent protein [GFP] fused to the N terminus of the InvA protein [InvA-N]) was homogeneous along the cyanobacterial filament, consistent with the lack of dependence on HetR, expression of an InvB-N-GFP fusion upon combined nitrogen deprivation took place mainly in differentiating and mature heterocysts. In an hetR genetic background, the InvB-N-GFP fusion was strongly expressed all along the filament. An insertional mutant of invA could grow diazotrophically but was impaired in nifHDK induction and exhibited an increased frequency of heterocysts, suggesting a regulatory role of the invertase-mediated carbon flux in vegetative cells. In contrast, an invB mutant was strongly impaired in diazotrophic growth, showing a crucial role of sucrose catabolism mediated by the InvB invertase in the heterocysts.


A new nerve pedicle for finger sensibility: the dorsal digital sensory nerve.
Restoration of sensibility to the traumatized finger can be a difficult problem. Two patients with insensibility to the volar distal finger after trauma underwent delayed digital nerve repair. In the first patient, the dorsal branch of the radial proper digital nerve was approximated to the distal stump as a pedicle to span a 12-mm gap resulting from neuroma excision. The second patient had a 14-mm defect after scar-tissue excision 8 months following primary neurorrhaphy after trauma. Reconstruction was performed by approximating the dorsal branch of the radial proper digital nerve to the distal stump. Both patients had fingertip sensibility restored 1 year postoperatively, as documented by two-point discrimination. Anatomic dissections of 12 fresh cadaver fingers revealed a consistent pattern. Of the 24 proper digital nerves dissected, 23 had a distal dorsal sensory branch arising at the midportion of the proximal phalanx. The dorsal branch-vascularized pedicle of the proper digital nerve has not been described previously as a method for restoring finger sensibility in cases not amenable to primary neurorrhaphy. We believe this technique should be added to the repertoire of the practicing hand surgeon.


The Effect of Female Orgasm Frequency on Female Mate Selection: A Test of Two Hypotheses.
Female orgasm has been a mystery that psychologists have been attempting to understand for decades. Many have contended that female orgasm is a functionless by-product of male orgasm, while others have argued that female orgasm may be an adaptation in its own right, offering several adaptationist accounts of female orgasm. In the current research, we tested predictions derived from two hypotheses regarding adaptive functions of female orgasm: female orgasm indicates partner mate value or female orgasm promotes long-term, pair bonding. 199 female undergraduates participated in an experiment where they imagined themselves as a member of a romantic relationship provided in a scenario. Within these scenarios, the relationships varied between either short- or long-term and the frequency that the female experienced orgasm during intercourse varied between never, occasionally, and almost always. Participants answered questions regarding relationship satisfaction and perceptions of the fictional relationship. A series of analysis of variance (ANOVAs) indicated that females assigned to conditions of experiencing more frequent orgasms reported greater relationship satisfaction, across both short- and long-term relationships. The relationship between female orgasm frequency and relationship satisfaction was fully mediated by the female's perceived love for her hypothetical partner but not by perceptions of her hypothetical partner's commitment. Taken together, this study provides preliminary support for the hypothesis that female orgasm evolved as a mate-selection tool for females and promotes long-term, pair bonding but does not provide support for the hypothesis that female orgasm evolved as an indicator of male value.


Effects of rTMS and tDCS on neuropathic pain after brachial plexus injury: a randomized placebo-controlled pilot study.
Neuropathic pain after brachial plexus injury (NPBPI) is a highly disabling clinical condition and is increasingly prevalent due to increased motorcycle accidents. Currently, no randomized controlled trials have evaluated the effectiveness of non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in patients suffering from NPBPI. In this study, we directly compare the efficacy of 10-Hz rTMS and anodal 2 mA tDCS techniques applied over the motor cortex (5 daily consecutive sessions) in 20 patients with NPBPI, allocated into 2 parallel groups (active or sham). The order of the sessions was randomised for each of these treatment groups according to a crossover design and separated by a 30-day interval. Scores for "continuous" and "paroxysmal" pain (primary outcome) were tabulated after the last stimulation day and 30 days after. Secondary outcomes included the improvement in multidimensional aspects of pain, anxiety state and quality of life from a qualitative and quantitative approach. Active rTMS and tDCS were both superior to sham in reducing continuous (p < 0.001) and paroxysmal (p = 0.002; p = 0.02) pain as well as in multidimensional aspects of pain (p = 0.001; p = 0.002) and anxiety state (p = < 0.001; p = 0.005). Our results suggest rTMS and tDCS are able to treat NPBPI with little distinction in pain and anxiety state, which may promote the use of tDCS in brachial plexus injury pain management, as it constitutes an easier and more available technique.Clinical Trial Registration: http://www.ensaiosclinicos.gov.br/, RBR-5xnjbc - Sep 3, 2018.


Spatial relations between the vertebral body and the thoracic aorta in adolescent idiopathic scoliosis.
An analysis of computed tomography images of patients with adolescent idiopathic scoliosis. To evaluate the spatial relations between the vertebral body and the thoracic aorta and to verify the safety of anterior instrumentation surgery. Recent studies have suggested that the aorta is positioned more laterally and posteriorly in patients with idiopathic scoliosis than in normal patients; however, no study used rib heads as references in the analysis. Computed tomography images of the whole thoracic spine of 10 patients with adolescent idiopathic scoliosis were analyzed. A line that passed the anterior edge of the bilateral rib heads was regarded as the virtual passage of the screw used for anterior instrumentation surgery. Whether this line crossed the aorta was investigated. A distance between the vertebral body and the aorta was measured along this line. The aorta was located more posteriorly between T6 and T9. At these levels, the virtual passage of the screw crossed the aorta in 33 of 40 vertebrae (83%). At seven vertebrae in 5 patients, this passage crossed the aorta and the distance was less than 2 mm. Of these, four were T6, two T7, and one T8. In some patients with adolescent idiopathic scoliosis, the aorta can be located in the direction of the screw passage and close to the vertebral body. Accordingly, when planning anterior instrumentation surgery for right thoracic curve, surgeons should pay attention to these spatial relations.


Convergent extension analysis in mouse whole embryo culture.
Mutations have been identified in a non-canonical Wnt signalling cascade (the planar cell polarity pathway) in several mouse genetic models of severe neural tube defects. In each of these models, neurulation fails to be initiated at the 3-4 somite stage, leading to an almost entirely open neural tube (termed craniorachischisis). Studies in whole embryo culture have identified a defect in the morphogenetic process of convergent extension during gastrulation, preceding the onset of neural tube closure. The principal defect is a failure of midline extension, both in the neural plate and axial mesoderm. This leads to an abnormally wide neural plate in which the elevating neural folds are too far apart to achieve closure. In this chapter, we provide details of several experimental methods that can be used to evaluate convergent extension in cultured mouse embryos. We describe analytical methods that can reveal the abnormalities that characterise neurulation-stage embryos with defective planar cell polarity signalling, in particular the loop-tail (Lp; Vangl2) mutant.


Clarification of the Position of Linum stelleroides Planch. within the Phylogeny of the Genus Linum L.
The phylogeny of members of the family Linaceae DC. ex Perleb has not been adequately studied. In particular, data on the phylogenetic relationship between Linum stelleroides Planch. and other representatives of the blue-flowered flax are very controversial. In the present work, to clarify this issue, we obtained DNA sequences of three nuclear loci (IGS and ITS1 + 5.8S rDNA + ITS2 of the 35S rRNA gene and the 5S rRNA gene) and eight chloroplast loci (rbcL, the trnL-trnF intergenic spacer, matK, the 3' trnK intron, ndhF, trnG, the psbA-trnH intergenic spacer, and rpl16) of 10 Linum L. species (L. stelleroides, L. hirsutum, L. perenne, L. leonii, L. lewisii, L. narbonense, L. decumbens, L. grandiflorum, L. bienne (syn. L. angustifolium), and L. usitatissimum) using high-throughput sequencing data. The phylogenetic analysis showed that L. stelleroides forms a basal branch in the blue-flowered flax clade. Previously found inconsistencies in the position of L. stelleroides and some other species in the Linaceae phylogenetic tree resulted from the erroneous species identification of some of the studied plant samples.


The Development of 18F Fluorthanatrace: A PET Radiotracer for Imaging Poly (ADP-Ribose) Polymerase-1.
Fluorine 18 (18F) fluorthanatrace (18F-FTT) is a PET radiotracer for imaging poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1), an important target for a class of drugs known as PARP inhibitors, or PARPi. This article describes the stepwise development of this radiotracer from its design and preclinical evaluation to the first-in-human imaging studies and the initial validation of 18F-FTT as an imaging-based biomarker for measuring PARP-1 expression levels in patients with breast and ovarian cancer. A detailed discussion on the preparation and submission of an exploratory investigational new drug application to the Food and Drug Administration is also provided. Additionally, this review highlights the need and future plans for identifying a commercialization strategy to overcome the major financial barriers that exist when conducting the multicenter clinical trials needed for approval in the new drug application process. The goal of this article is to provide a road map that scientists and clinicians can follow for the successful clinical translation of a PET radiotracer developed in an academic setting. Keywords: Molecular Imaging-Cancer, PET, Breast, Genital/Reproductive, Chemistry, Radiotracer Development, PARPi, 18F-FTT, Investigational New Drug © RSNA, 2022.


A Systematic Review on the Prevalence of Overweight and Obesity, in Iranian Children and Adolescents.
Obesity has now become a common health problem worldwide. To gain insight into the epidemiology of the problem in Iran, we systematically reviewed all available studies on the prevalence of overweight and obesity in the Iranian pediatric population. We systematically searched PubMed, ISI, SCOPUS, as well as Iranmedex, Irandoc, and Scientific Information Database (SID) databases.All studies on mean and standard deviation or percentile categories of BMI, WC, WHR, or WHtR or prevalence of obesity/overweight in Iranian child and adolescence, were performed from January 1990 to the end of December 2013. Refining processes were conducted by two independent reviewers. Quality assessment and data extraction followed based on validated form. As, these data were heterogeneous, meta-analysis was not performed. From 3253 records, through three refining steps, 129 articles were found related to our study. In Iran, national studies are limited and nearly there is no comprehensive study for sub-national trends. Different age and sex groups had large variations in the prevalence of obesity and overweight (from 1% up to 16.1% and from 4.4% up to 42.3% respectively for obesity and overweight). Related data are very scattered or limited to some specific subgroups in some living areas. For comparing, aggregating, and imputing the information we need more modern practical statistical methods.


Lattice energies of molecular solids from the random phase approximation with singles corrections.
We use the random phase approximation (RPA) method with the singles correlation energy contributions to calculate lattice energies of ten molecular solids. While RPA gives too weak binding, underestimating the reference data by 13.7% on average, much improved results are obtained when the singles are included at the GW singles excitations (GWSE) level, with average absolute difference to the reference data of only 3.7%. Consistently with previous results, we find a very good agreement with the reference data for hydrogen bonded systems, while the binding is too weak for systems where dispersion forces dominate. In fact, the overall accuracy of the RPA+GWSE method is similar to an estimated accuracy of the reference data.


Motor and nonmotor heterogeneity of LRRK2-related and idiopathic Parkinson's disease.
Parkinson's disease (PD) associated with LRRK2 mutations has been described as similar to idiopathic PD with minor clinical differences. No study has compared the clinical features of LRRK2-associated PD due to different mutations. The objective of this study was to compare LRRK2-associated PD due to G2019S and G2385R mutations and to compare each to idiopathic PD. Sites within the international LRRK2 Cohort Consortium undertook family-based, community-based, or clinic-based studies to gather clinical data on manifesting carriers and patients with idiopathic PD. Five hundred sixteen PD patients with the G2019S mutation, 199 with the G2385R mutation, and 790 patients with idiopathic PD were included in the data set. Adjusted for age, sex, disease duration, and levodopa-equivalent daily dose, mean MDS-UPDRS part II or III scores and the frequency of motor fluctuations were higher in the G2385R mutation carriers than in either the G2019S mutation carriers or idiopathic PD patients. G2019S mutation carriers had significantly lower UPDRS part III scores than idiopathic PD patients. Both G2019S and G2385R mutation carriers had a higher proportion of the postural instability gait disorder phenotype compared with idiopathic PD patients. LRRK2 G2019S PD patients had better UPSIT scores and lower Geriatric Depression Scale scores than idiopathic PD patients in adjusted analyses. G2385R and G2019S PD appear to have motor differences that may be explained by contrasting local treatment or measurement practices or differences in the biology of the disease. Longitudinal studies should evaluate whether progression is faster in G2385R mutation carriers compared with G2019S PD or idiopathic PD. © 2016 International Parkinson and Movement Disorder Society.


[The value of serum tumor marker CA125 and CEA in the diagonosis of non-small cell lung cancer.].
Tumor marker cancer antigen 125(CA125) and carcinoembryonic antigen (CEA) all are the tumor markers found early. It was reported that the positive rate of CEA was highly in adenocarcinoma, after being analyzed all the case reports of non-small cell lung cancer (NSCLC) in recent 3 years, it was found that positive rate of CA125 was much higher in NSCLC than that of literatures. So, it's necessary to evaluate the value of serum CA125 and CEA measurement for NSCLC. The level of CA125 and CEA were detected with chemiluminescence in 136 NSCLC patients, 42 patients with respiratory diseases and 50 cases of normal control. The levels of serum CA125 in NSCLC patients were significantly higher than that of patients with respiratory diseases and normal control (except mixed cell lung cancer) (P<0.0001). The levels of serum CEA in adenocarcinoma and squamous patients were significantly higher than that of patients with respiratory diseases and normal control(P<0.0001). No difference between patients with respiratory diseases and normal control. The positive rates of CA125 were 92.3% in large-cell lung cancers, 80.2% in adenocarcinoma, 54.8% in squamous cancer, 50% in mixed cell lung cancer, respectively. The positive rates of CEA were 67.4% in large-cell lung cancers, 25.8% in squamous cancer, 0 in adenocarcinoma and mixed cell lung cancer, respectively. Combined measurement of CA125 and CEA positive rates was higher only in adenocarcinoma. The positive rates of CA125 and CEA were 86.9%and 63.6% in advanced NSCLC, respectively. The positive rates of CA125 were 90.9% in advanced adenocarcinoma. The positive rates of CA125 is higher than that of CEA in NSCLC patients, especially in large-cell lung cancers and advanced adenocarcinoma. CA125 is more useful than CEA in diagnosis of NSCLC.


Developmental Dyspraxia in Children With Learning Disorders: Four-Year Experience in a Referred Sample.
The term apraxia is clearly understood in adult behavioral neurology, with assessment of gesture central to the diagnosis. In contrast, the concept of "developmental dyspraxia" has been more problematic. In an effort to better specify its potential significance, we describe preliminary practice-based evidence for understanding developmental dyspraxia acquired within a theoretical framework informed by both adult behavioral neurology and a neuroconstructivist appreciation of neurodevelopmental disorders. Specifically, we describe the experience of a diagnostic clinic for children with learning disorders that adopted this framework and compare clinical characteristics of children diagnosed with dyspraxia with those of children diagnosed with dyslexia during the same time period. The dyspraxia diagnosis was based on the presence of impaired gesture and/or cognitive problems with planning. Over the target period, 71 children were diagnosed with dyspraxia and 114 children were diagnosed with dyslexia. Twenty-nine of the 71 children with dyspraxia were also diagnosed with dyslexia. Domains assessed included early developmental milestones, neurologic findings, cognition, speech and language, academic skills, and psychosocial functioning. Compared to the dyslexia group, children with dyspraxia (with or without dyslexia) had more problems with speech and language planning and planning in everyday life. Children with dyspraxia without dyslexia had more frequent early motor delays and deficits in visuospatial production than the other groups. The dyslexia groups predictably demonstrated poorer single word reading and phonologic processing compared to the dyspraxia only group (all P < .01). A neurologic finding of impaired gesture in children with learning disorders may signal a broader neurodevelopmental profile of developmental dyspraxia with both theoretical relevance and meaningful implications for evaluation and treatment. Cognitive problems with planning are particularly relevant.


Management of retroperitoneal liposarcoma: A case report and review of the literature.
Retroperitoneal liposarcoma is a rare tumor with an incidence of 2.5 per million individuals. Early diagnosis is difficult as there is an absence of specific clinical presentations. The present case study reports a patient diagnosed with retroperitoneal liposarcoma who was treated by complete surgical resection and relapsed 3 months following the surgery. In addition, the clinical data of 14 patients with retroperitoneal liposarcoma were reviewed and analyzed. The mean age of the 14 patients at presentation was 54.1 (range, 36-73 years) and 5/14 patients experienced recurrence, ranging between 1 and 10 times. Of the 12 cases that reported histological subtypes, 7 were well-differentiated liposarcoma, 2 were dedifferentiated liposarcoma, 2 were myxoid liposarcoma and 1 was mixed subtype. All the patients underwent complete resection and 5 received combined multiple organs resection (3 nephrectomy, 1 sigmoid colon and 1 multiple visceral organs). However, no patients received chemotherapy or radiotherapy. In conclusion, retroperitoneal liposarcoma is a rare disease with a high rate of recurrence. Complete resection is the predominant treatment and combined resection of adjacent organs is occasionally necessary.


Paragonimus heterotremus infection in Nagaland: A new focus of Paragonimiasis in India.
To determine the prevalence of paragonimiasis among the patients who were attending the tuberculosis (TB) clinics at the Community Health Centre, Pfutsero, Phek District, Nagaland. To determine the species of Paragonimus that cause infection in humans and the crustacean host that acts as the infectious source for humans. Sputum specimens were examined microscopically for Paragonimus eggs and acid fast bacilli. Blood samples were tested by microenzyme-linked immunosorbant assay for Paragonimus-specific immunoglobulin G antibodies. Crab extracts prepared by digestion with artificial gastric juice were examined for Paragonimus metacercariae under a stereoscopic microscope. The species identification of the parasite was based on morphological and molecular characterizations of eggs and metacercariae employing polymerase chain reaction and DNA sequencing. Seven out of the 14 patients tested seropositive for paragonimiasis and Paragonimus eggs were detected in sputum of two out of the seven seropositive patients, indicating a prevalence of 50% and an egg detection rate of 14%, respectively. The prevalence was highest in the 10-30 year age group. More males got the infection than females, the ratio being 5:2. P. heterotremus was identified as the causative agent of human paragonimiasis and Potamiscus manipurensis as the crab host. The study revealed that paragonimiasis has been endemic in Pfutsero, Nagaland, and half of the patients attending the TB clinic were actually suffering from pulmonary paragonimiasis. This is the first confirmed report of an endemic focus of paragonimasis and description of P. heterotremus as the causative agent in Nagaland, India.


The value of whole-brain CT perfusion imaging combined with dynamic CT angiography in the evaluation of pial collateral circulation with middle cerebral artery occlusion.
Middle cerebral artery (MCA) occlusion is extremely common, especially unilateral artery, which can result in a significant incidence of cerebral infarction. To assess the value of whole-brain computed tomography perfusion (CTP) imaging combined with dynamic CT angiography (dCTA) in the evaluation of pial collateral circulation in patients with MCA occlusion. Whole-brain CTP and dCTA images were acquired in 58 patients with unilateral MCA occlusion. All patients were divided into three groups according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral score (by CTA). The CTP parameters were analysed, including relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), relative mean transit time (rMTT), and relative time to peak (rTTP). Patients were followed up with the modified Rankin scale (mRS). All cases in this study were confirmed by DSA. The CTP parameters of the MCA blood supply area on the affected side of patients with different degrees of stenosis were significantly different from those on the unaffected side. There are significant differences in the CTP parameters and openings of the Willis circle in patients with different degrees of stenosis. Significant differences were found in the number of patients with good prognosis. Whole-brain CT perfusion combined with dynamic CTA can structurally and functionally evaluate the establishment of pial collateral circulation and its effect on cerebral hemodynamic changes.


Draft Genome Sequence of an Atypical Highly Virulent Rabbit Staphylococcus aureus Strain.
Rabbit staphylococcosis is one of the most important diseases in industrial rabbit production. We report here the draft genome sequence of Staphylococcus aureus strain 380/11, an atypical highly virulent (aHV) rabbit Staphylococcus aureus strain.


[Characteristics and significance of criteria for obesity disease in Japan 2011].
The Committee of Japan Society for the Study of Obesity reported the new criteria for 'obesity disease' for Japanese in 2011. 1) Obesity: This is judged by body mass index (BMI) at initial screening and defined as a BMI > or = 25. 2) Definition of 'obesity disease': obesity disease is a clinical designation based on the presence of associated complications or their likely occurrence. A person in this situation needs to reduce their weight for medical reasons. 3) Criteria for'obesity disease': a) obesity with complications that require weight reduction for their improvement or elimination. b) high-risk obesity as specified by an excess of visceral fat confirmed by CT scan (visceral fat obesity).


[Determination of absolute configuration of a new triterpenic acid in leaves of Ilex hainanensis].
This study aimed to explore the triterpenic acid components in leaves of Ilex hainanensis. Alkaline water extraction, macroporous resin adsorption, and high performance liquid chromatography were used to separate and purify the triterpenic acid components in leaves of I. hainanensis. The physical and chemical property analysis, MS, NMR spectroscopy, and literature comparison were performed to identify the structures, and a new triterpene acid compound was discovered:(3S, 4R, 5R, 8R, 9R, 10R, 14S, 17S, 18S, 19R)-3,19-dihydroxyursa-12,20(30)-diene-24,28-dioic-acid, and named ilexhainanin F. In addition, according to its structural characteristics, the ~(19)F-NMR Mosher method was further employed to study its absolute configuration. By comparison of the ~(19)F-NMR chemical shifts of Mosher esters, it was determined that the absolute configuration of the 3-position chiral center of the compound was the S configuration.


Multiple brain metastases are associated with poor survival in patients treated with surgery and radiotherapy.
A retrospective analysis was performed to evaluate the role of surgery in the management of patients with solitary and multiple brain metastases. Between 1980 and 1990, 46 patients underwent surgical resection of brain metastases at the University of Colorado Health Sciences Center. All but two patients received postoperative whole-brain radiotherapy to a median total dose of 30 Gy (range, 11.4 Gy to 50.0 Gy). Lung was the most common (56%) primary site and adenocarcinoma was the most common (46%) tumor histology. Twenty-eight of 46 patients (61%) had solitary metastases, while the remaining 18 patients had two or more foci. The median survival of all 46 patients was 11 months, and the 1- and 2-year survival rates were 40% and 12%, respectively. Moderately severe to severe neurologic impairment at the time of diagnosis and the presence of multiple brain metastases were associated with a significantly poorer survival. In patients with solitary metastasis, gross total resection and adenocarcinoma tumor histology significantly prolonged survival, whereas primary tumor site, the presence of active extracranial disease, and radiation dose had no significant effect on survival. These results are consistent with a recent randomized study supporting the role of surgery and whole-brain radiation therapy in the management of patients with solitary brain metastases. We would caution against the generalization of this concept to patients with two or more brain metastases.


Novel Ti3C2Tx MXene nanozyme with manageable catalytic activity and application to electrochemical biosensor.
In this work, Ti3C2Tx MXene was identified as efficient nanozyme with area-dependent electrocatalytic activity in oxidation of phenolic compounds, which originated from the strong adsorption effect between the phenolic hydroxyl group and the oxygen atom on the surface of Ti3C2Tx MXene flake. On the basis of the novel electrocatalytic activity, Ti3C2Tx MXene was combined with alkaline phosphatase to construct a novel cascading catalytic amplification strategy using 1-naphthyl phosphate (1-NPP) as substrate, thereby realizing efficient electrochemical signal amplification. Taking advantage of the novel cascading catalytic amplification strategy, an electrochemical biosensor was fabricated for BCR/ABL fusion gene detection, which achieved excellent sensitivity with linear range from 0.2 fM to 20 nM and limit of detection down to 0.05 fM. This biosensor provided a promising tool for ultrasensitive fusion gene detection in early diagnosis of chronic myelogenous leukemia and acute lymphocytic leukemia. Moreover, the manageable catalytic activity of MXene broke a path for developing nanozymes, which possessed enormous application potential in not only electrochemical analysis but also the extensive fields including organic synthesis, pollutant disposal and so on.


Nuclear roles and regulation of chromatin structure by the stress-dependent MAP kinase Sty1 of Schizosaccharomyces pombe.
Microorganisms are invariably exposed to abrupt changes in their environment, and consequently display robust, high plasticity gene programmes to respond to stresses. In fission yeast, the Sty1 pathway is activated in response to diverse stress conditions, such as osmotic and oxidative stress, heat shock or nitrogen deprivation. The MAP kinase Sty1 and its substrate, the transcription factor Atf1, regulate diverse processes mainly at the nucleus. For instance, Sty1, Atf1 and its heterodimeric partner Pcr1 participate in promoting recombination at some hot spots, and in the assembly of heterochromatin at the mating locus. Their main role, however, is to engage a wide gene expression programme aimed to allow cellular survival by decreasing and repairing the damage exerted. Once Sty1 and Atf1 are activated by stress, they are recruited to promoters of up to 5-10% of the coding genes and regulate their transcription. Even though there is no simple, global relationship establishing RNA polymerase II occupancy, nucleosome architecture and transcriptional activity in eukaryotes, we discuss within this review the current knowledge and future perspectives of how activation of Sty1 and Atf1 affect chromatin architecture of a large fraction of the Schizosaccharomyces pombe genome to trigger the cellular response to environmental stress.


Spatial distribution and risk factors for equine infectious anaemia in the state of Mato Grosso, Brazil.
The prevalence of equine infectious anaemia (EIA) in the three biomes of the state of Mato Grosso (Amazon, Cerrado and Pantanal) was estimated. Serum samples were collected from 3,858 equines in 1,067 herds between Septemberand December 2014. The agar gel immunodiffusion (AGID) assay was used to detect EIA virus antibodies, and if a herd contained a seropositive animal itwas classified as a focus. The prevalence rates were 17.2% (95% confidence interval [CI]: 14.9-19.8%) for herds and 6.6% (95% CI: 5.8-7.5%) for animals. The Pantanal region showed the highest prevalence rates: 36.1% (95% CI: 30.8-41.7%) for herds and 17.0% (95% CI: 14.7-19.6%) for animals. The spatial distribution of relative risk was calculated according to the kernel density, which revealed three major clusters with the highest prevalence rates occurring in the north-western(Amazon biome), north-eastern (Cerrado biome) and southern (Pantanal biome)regions. A high spatial correlation was found among ranches, with high intra-herd prevalence rates located in the Amazon and Cerrado biomes, but the highest spatial correlation with EIA foci was found in the Pantanal biome. Variables related to ranch management, reflecting human influence, were associated with positive equines. Based on the results, it can be concluded that EIA is present in all biomes of the state, and that the risk factors are associated with human interference in the transmission process. Given this situation, the EIA control programme should be re-evaluated and more prophylactic measures should be adopted to control the disease.


Capitation in IPA-HMOs. Dealing with financial risks and ethical dilemmas.
Capitation, a relatively new method of payment, is being used increasingly for primary care physicians in independent practice association (IPA) model HMOs. The author explains the actual payment method, including the various amounts withheld, and the financial risks and rewards inherent in this system. He then confronts the sensitive ethical issues posed by capitation. Finally, he offers five sound suggestions for physicians who contemplate joining an HMO that employs capitation.


Numerical experiments in modeling diffraction phenomena.
Diffraction has been numerically modeled using a Monte Carlo statistical analysis. The Heisenberg uncertainty principle has been applied to attain this goal. Example solutions have been studied and are presented to illustrate the utility and accuracy of the technique.


Design, Synthesis, and Activity Evaluation of Novel N-benzyl Deoxynojirimycin Derivatives for Use as α-Glucosidase Inhibitors.
To obtain α-glucosidase inhibitors with high activity, 19 NB-DNJDs (N-benzyl-deoxynojirimycin derivatives) were designed and synthesized. The results indicated that the 19 NB-DNJDs displayed different inhibitory activities towards α-glucosidase in vitro. Compound 18a (1-(4-hydroxy-3-methoxybenzyl)-2-(hydroxymethyl) piperidine-3,4,5-triol) showed the highest activity, with an IC50 value of 0.207 ± 0.11 mM, followed by 18b (1-(3-bromo-4-hydroxy-5-methoxybenzyl)-2-(hydroxymethyl) piperidine-3,4,5-triol, IC50: 0.276 ± 0.13 mM). Both IC50 values of 18a and 18b were significantly lower than that of acarbose (IC50: 0.353 ± 0.09 mM). According to the structure-activity analysis, substitution of the benzyl and bromine groups on the benzene ring decreased the inhibition activity, while methoxy and hydroxyl group substitution increased the activity, especially with the hydroxyl group substitution. Molecular docking results showed that three hydrogen bonds were formed between compound 18a and amino acids in the active site of α-glucosidase. Additionally, an arene‒arene interaction was also modelled between the phenyl ring of compound 18a and Arg 315. The three hydrogen bonds and the arene‒arene interaction resulted in a low binding energy (-5.8 kcal/mol) and gave 18a a higher inhibition activity. Consequently, compound 18a is a promising candidate as a new α-glucosidase inhibitor for the treatment of type Ⅱ diabetes.


Probabilistic quantification of tsunami current hazard using statistical emulation.
In this paper, statistical emulation is shown to be an essential tool for the end-to-end physical and numerical modelling of local tsunami impact, i.e. from the earthquake source to tsunami velocities and heights. In order to surmount the prohibitive computational cost of running a large number of simulations, the emulator, constructed using 300 training simulations from a validated tsunami code, yields 1 million predictions. This constitutes a record for any realistic tsunami code to date, and is a leap in tsunami science since high risk but low probability hazard thresholds can be quantified. For illustrating the efficacy of emulation, we map probabilistic representations of maximum tsunami velocities and heights at around 200 locations about Karachi port. The 1 million predictions comprehensively sweep through a range of possible future tsunamis originating from the Makran Subduction Zone (MSZ). We rigorously model each step in the tsunami life cycle: first use of the three-dimensional subduction geometry Slab2 in MSZ, most refined fault segmentation in MSZ, first sediment enhancements of seabed deformation (up to 60% locally) and bespoke unstructured meshing algorithm. Owing to the synthesis of emulation and meticulous numerical modelling, we also discover substantial local variations of currents and heights.


Underreporting of psychopathology on the MMPI-2: a meta-analytic review.
Meta-analytic techniques were applied to studies of the MMPI-2 in which participants given standard instructions were compared with participants instructed or believed to have been underreporting. Traditional and supplementary indices of underreporting yielded a mean effect size of 1.25, suggesting that underreporting respondents differ from those responding honestly by a little more than 1 standard deviation, on the average, on these scales. Analyses of classification accuracy suggested that several scales are moderately effective in detecting underreporting, although accuracy decreases if participants have been coached about validity scales. Base rates of defensive responding in relevant populations are reviewed, and methodological issues, including research designs, coaching, and incremental validity of supplementary underreporting scales, are discussed.


HLA-B27 associated reactive spondyloarthropathies in a Dutch military hospital.
Forty-two male patients with reactive spondyloarthropathies in a Dutch military hospital are described with mean age of onset 21.9 years. Peripheral arthritis or sacroiliitis was present in all, eye symptoms in 21 (50%), and genitourinary disease in 15 (35.7%). Evidence of antecedent sexually acquired or enterocolitic infection was found only in three (7.2%). HLA-B27 antigen was detected in 34 (81%) of 42 patients. Additional data suggest that reactive spondyloarthropathies are the most common form of inflammatory arthritis in young men.


Total Versus Subtotal Gastrectomy for Signet Ring Cell Carcinoma of the Stomach.
To determine the adequate surgery type for the treatment of signet ring cell of stomach in terms of postoperative complications and survival. Comparative analytical study. Baskent University Adana Teaching and Research Center, Adana, Turkey, between 2006 and 2015. Atotal of 46 patients with the diagnosis of gastric signet ring cell, who underwent total or subtotal gastrectomy, were enrolled in this study. Patients were compared according to age, gender, tumor location, TNM stage, survival and mortality rates, operation time, complication and recurrence. Comparisons between groups were performed by using Mann-Whitney U-test for the data not normally distributed. The categorical data were analyzed by using the Chisquare test or Fisher's exact test, where applicable. Kaplan-Meier test was used for survival curve and Long-rank test was used for survival differences between groups. Values of p < 0.05 were considered statistically for all tests. Of the 46 patients, 29 (63.0%) were male. The mean age was 56.6 ±13.2 years. The median tumor size was 5.0 cm (IQR: 3.0-6.6). Twenty-six (56.5%) patients were in total gastrectomy, whereas 20 (43.5%) were in subtotal gastrectomy group. Five-year cumulative survival rate was 0.487. Five-year overall survival rate for early and advanced signet ring cell carcinoma was 0.830 and 0.164, respectively (p<0.001). Five-year overall survival rate for total and subtotal gastrectomy groups were 0.422 and 0.582, respectively (P=0.417). Complications were observed in 17.4% (n=8) of all 46 patients. Subtotal gastrectomy can be performed safely for patients with gastric signet ring cell carcinoma and is equal to total gastrectomy with respect to prognosis and complication rates.


Peripheral blood counts in workers exposed to synthetic fibres.
Acrylonitrile is an intermediary with possible adverse health effects in the synthesis of organic products, such as acrylic fibres. This investigation was undertaken to determine the possible changes in the peripheral blood counts in workers of a polyacrylic fibres plant. The study involved 218 workers exposed to acrylonitrile at low doses and a control group of 200 unexposed workers. The chosen subjects underwent blood tests in order to check their haematological parameters. There were no statistically significant differences between the two groups in terms of the red blood cells, haemoglobin and total number of leukocytes. An increase in the neutrophils associated with a reduction of lymphocytes, both statistically significant, was observed. The authors hypothesized that the neutrophils are influenced by the exposure to acrylonitrile at low doses.


Free microvascular muscle flaps with skin graft reconstruction of extensive defects of the foot: a clinical and gait analysis study.
Over the past 4 years at the Massachusetts General Hospital 18 patients have been treated for extensive defects (mean size 130 cm2) of the foot at or below the medial and lateral malleoli. These patients have been treated with free muscle flaps covered with thick split-thickness skin grafts. Full muscle flap survival has been seen in each patient, and all patients are currently ambulatory. A subgroup of nine patients are weight-bearing directly upon their skin grafts covering transferred muscle. All patients are walking without chronic breakdown over a mean follow-up of over 19 months with the exception of a single patient who has had breakdown in a region of redundant improperly tailored muscle flap. None of the skin grafted muscles has significant cutaneous sensibility. Detailed gait analysis of these patients has confirmed the weight-bearing capabilities of free muscle flaps with skin grafts and has proven to be an excellent method of foot reconstruction evaluation. It would appear from this study that cutaneous sensibility may not be necessary for successful reconstruction of the weight-bearing surface of the foot. This method of reconstruction should be considered when local tissues are not suitable for plantar foot reconstruction.


Quantitative analysis of vascularization and cytochrome oxidase following fetal transplantation in the contused rat spinal cord.
In the normal adult central nervous system, a coupling between energy consumption and vascular density is well established. Likewise, the survival of fetal neural tissue grafts is highly dependent on the establishment of functional vascular integration with the host. However, to what degree graft vascularization and tissue metabolism influence the normal host response to traumatic injury has not been extensively studied. In the present report, embryonic day 14 fetal spinal cord suspension grafts were made into the lesion epicenter of subchronic (10 days) contusion-injured rats. Three months later, intraspinal transplants were analyzed using correlative cytochrome oxidase histochemistry and vascular morphometric analysis. The same approaches were applied to the host spinal cord and injured, non-transplanted animals in order to determine the ability of a graft to alter the level of post-injury vascularization and/or metabolism. In general, graft vascular density was increased over that measured in normal or injured gray matter. Vascular density in gray matter near the host/graft interface was markedly increased when compared to either gray matter of the same spinal level in injured non-grafted animals or normal control spinal gray matter. Vascular changes were not noted in gray matter 3 mm distal to the lesion epicenter (rostral or caudal) in all groups analyzed. Cytochrome oxidase was up-regulated at this time in the graft and gray matter at the host/graft interfaces when compared to either gray matter of the same spinal level in injured, non-grafted animals or that of uninjured controls. These data indicate that an intraspinal transplant placed into the contused adult rat spinal cord reaches a metabolic capacity that is likely to be associated with high levels of oxidative metabolism in the well-vascularized graft neuropil. In addition, transplantation chronically alters vascularization and metabolic patterns of adjacent spinal gray matter following contusion injury.


Ethanol-induced growth inhibition of erythroleukemia stem cells. Cell cycle effects.
Friend erythroleukemia stem cells are strongly growth inhibited by 60 mM ethanol. The expression of this inhibition requires several days to develop fully, and is not relieved by washing into new ethanol-containing medium even in the presence of excess folic acid. Removal of the fully inhibited cells from ethanol results in rapid growth recovery, with the onset of recovery occurring within a few hours. Cell cycle analysis reveals a G1 delay which is evident within a few hours after initial ethanol exposure. Bivariate RNA-DNA analysis indicates that this G1 delay results from restriction in late G1. It is unclear at present whether this delay can account for all the observed growth inhibition.


Hemoregulatory peptide (HP5b) dimer effects on normal and malignant cells in culture.
The dimer of the hemoregulatory peptide HP5b has been investigated for biological effects on various cell types in culture including mouse granulocyte-macrophage colony forming units (CFU-GM) from agar and murine long-term bone marrow culture (LTBMC). While CFU-GM were significantly stimulated in both systems, mitogen activation of mouse T, B and natural killer (NK) cells was not affected. Peptide treated mouse 3T3 fibroblasts reached a higher saturation density than controls; otherwise no effect was seen. A series of malignant cell lines was also tested. On a human glioblastoma cell line (GaMg) and rat glioma cell line (BT5C) a slight but significant stimulatory effect was found, while human mammary carcinoma cells (MCF7) were not affected. On SC1 mouse lymphoma cells a slight stimulation of cell growth was seen during the first part of exponential growth. Since HP5b acts as a stimulator for stromal cell secretion of other growth factors, supernatants from a human bone marrow stromal cell line stimulated with HP5b were tested on various cell lines. The effects of the supernatants on cell growth of the tested cell lines were not affected by HP5b treatment. Taken together with available in vivo data, the results indicate that the hemoregulatory peptide is a selective stimulator of myelopoiesis.


Regulation of steady state pyruvate dehydrogenase complex activity in plant mitochondria : reactivation constraints.
The requirements for reactivation (dephosphorylation) of the pea (Pisum sativum L.) leaf mitochondrial pyruvate dehydrogenase complex (PDC) were studied in terms of magnesium and ATP effects with intact and permeabilized mitochondria. The requirement for high concentrations of magnesium for reactivation previously reported with partially purified PDC is shown to affect inactivation rather than reactivation. The observed rate of inactivation catalyzed by pyruvate dehydrogenase (PDH) kinase is always greater than the reactivation rate catalyzed by PDH-P phosphatase. Thus, reactivation would only occur if ATP becomes limiting. However, pyruvate which is a potent inhibitor of inactivation in the presence of thiamine pyrophosphate, results in increased PDC activity. Analysis of the dynamics of the phosphorylation-dephosphorylation cycle indicated that the covalent modification was under steady state control. The steady state activity of PDC was increased by addition of pyruvate. PDH kinase activity increased threefold during storage of mitochondria suggesting that there may be an unknown level of regulation exerted on the enzyme complex.


Self-Assembled, Adjuvant/Antigen-Based Nanovaccine Mediates Anti-Tumor Immune Response against Melanoma Tumor.
Malignant melanoma is a highly aggressive type of cancer that requires radical treatment strategies to inhibit the cancer cell progression and metastasis. In recent years, preclinical research and clinical trials on melanoma treatment have been considerably focused on the adjuvant-based immunotherapy for enhancing the immune response of innate immune cells against cancer cells. However, the clinical outcome of these adjuvant-based treatments is inadequate due to an improper delivery system for these immune activators to reach the target site. Hence, we developed a vaccine formulation containing tumor lysate protein (TL) and poly I:C (PIC) complexed with positively charged poly (sorbitol-co-polyethylenimine (PEI) (PSPEI). The resulting ionic PSPEI-polyplexed antigen/adjuvant (PAA) (PSPEI-PAA) nanocomplexes were stable at the physiological condition, are non-toxic, and have enhanced intracellular uptake of antigen and adjuvant in immature dendritic cells leading to dendritic cell maturation. In the murine B16F10 tumor xenograft model, PSPEI-PAA nanocomplexes significantly suppressed tumor growth and did not exhibit any noticeable sign of toxicity. The level of matured dendritic cells (CD80+/CD86+ cells) in the tumor draining lymph node of PSPEI-PAA treated tumor mice were enhanced and therefore CD8+ T cells infiltration in the tumor were enriched. Additionally, the cytotoxic T lymphocytes (CTLs) assay involving co-culturing of splenocytes isolated from the PSPEI-PAA-treated mice with that of B16F10 cells significantly revealed enhanced cancer killing by the TL-reactivated CTLs compared to untreated control mice bearing tumor. Therefore, we strongly believe that PSPEI-PAA nanocomplexes could be an efficient antigen/adjuvant delivery system and enhance the antitumor immune response against melanoma tumor in the future clinical trials.


Potato tuber callus: validation as a biochemical tool.
Callus was initiated from explants of tubers of the Norchip cultivar of Solanum tuberosum L. and grown on medium with a single carbon source and without addition of coconut milk, protein hydrolysate, or amino acid. Callus samples were harvested at intervals and compared to mature tubers for which there was good biochemical knowledge.The amino acid spectrum, the glycoalkaloid content, and the properties of the isolated invertase and sucrose synthetase were similar in callus and in tuber. Significantly the level of sucrose synthetase varied with the age of the developing callus just as it did with the age of the developing tuber. Of greater significance, levels of reducing sugars and invertase varied with the age of developing callus and also with time and temperature of storage after the callus has ceased growth. Similar changes occur in intact tubers.Callus and tuber biochemistry differed in the amount of deposited starch and in the absence of potato invertase inhibitor.


Predisposing Factors of Difficult Tracheal Intubation Among Adult Patients in Aliabad Teaching Hospital in Kabul, Afghanistan - A Prospective Observational Study.
Airway management may be a considerable challenge for anesthesiologists. Currently used preoperative screening tests are known to lack sufficient specificity and sensitivity. Nevertheless, preoperative screenings and the combination of various tests are highly recommended to reduce the risk of unexpected difficult or failed airway management. This study aims to determine if socio-demographic characteristics can predict difficult intubation among adult patients scheduled for elective surgeries under general anesthesia in Aliabad Teaching Hospital, Kabul, Afghanistan. A total of 341 patients were selected based on consecutive sampling method. Informed consent forms were obtained before inclusion in the study. Data were collected using a data collection form. Age, gender, ASA physical status and ethnicity were recorded for each participant. Airway assessment tests such as mouth opening (MO), thyromental distance (TMD), and Mallampati classes, inability to prognath (AP) and neck mobility and size (NM) category were conducted by research team. Data were initially entered into an Excel data sheet and then exported to SPSS Statistics version 22 for analysis. From 28 October 2018 to 30 January 2019, a total of 341 patients included in the study. Of these, 193 (56.6%) were male and 148 (43.4%) were female. The mean age of the subjects was 36.98 ± 15.048 years. More than half (54.5%) of the study population were Tajiks. Patients from the Hazara ethnicity, female patients, older patients and those suffering from systemic diseases found to be more difficult to intubate. We recognized that, Mallampati classes ≥3, small MO, short TMD, AP, reduced NM were also associated with difficult intubation. Multiple logistic regression analysis of the associated factors determined that increased age more than 40 years, AP and small MO were independent predictors of difficult intubation. The study findings show that Hazara ethnicity, female patients, increasing age and systemic disease have significant associations with difficult intubation. Mallampati classes III and IV, MO ≤4 cm, TMD ≤6 cm, and reduced NM had higher risks of difficult intubation. Multiple logistic regression analysis determined that increased age, AP and MO were independent predictors for difficult intubation.


[Causes of re-emergence of Oncomelania snails in hardened ditches].
To understand the impact factors of the re-emergence of Oncomelania snails in hardened ditches so as to find out the measures to improve the effect of snail eradication. Thirteen infected townships from Jingmen City were randomly selected and investigated with the retrospective method and the field survey. All the data were analyzed for evaluating the effect of the hardened ditches on snail eradication and finding out the causes of the re-emergence of snails in hardened ditches After on-site investigation of 151 hardened ditches, the eradication rate of snail areas was 78.79%, and 71 ditches were founded with snails and the re-emergence rate was 47.02%. The major factors of the snail re-emergence were the spread of the snails from the upstream, the dilapidation of the hardened ditches, no using molluscicides before the hardened ditches, and the snails being brought by the engineering construction. The only hardened ditches can not eradicate the snails. We should manage an overall plan when processing the ditches hardening project, implementation with molluscicides before the project and strengthen the maintenance of the hardened ditches.


Long-Term Subjective and Objective Assessment of Smell and Taste in COVID-19.
Among the first clinical symptoms of the SARS-CoV-2 infection is olfactory−gustatory deficit; this continues for weeks and, in some cases, can be persistent. We prospectively evaluated 162 patients affected by COVID-19 using a visual analogue scale (VAS) for nasal and olfactory−gustatory symptoms. Patients were checked after 7, 14, 21, 28, 90, and 180 days. A total of 118 patients (72.8%) reported an olfactory VAS < 7 at baseline (group B), and 44 (27.2%) reported anosmia (VAS ≥ 7) (group A) and underwent the Brief Smell Identification Test (B-SIT) and Burghart Taste Strips (BTS) to quantify the deficit objectively and repeated the tests to confirm the sense recovery. Group A patients showed B-SIT anosmia and hyposmia in 44.2% and 55.8% of cases, respectively. A total of 88.6% of group A patients reported ageusia with VAS ≥ 7, and BTS confirmed 81.8% of ageusia and 18.2% of hypogeusia. VAS smell recovery was recorded starting from 14 days, with normalization at 28 days. The 28-day B-SIT score showed normosmia in 90.6% of group A patients. The mean time for full recovery (VAS = 0) was shorter in group B (22.9 days) than in group A (31.9 days). Chemosensory deficit is frequently the first symptom in patients with COVID-19, and, in most cases, recovery occurs after four weeks.


Ambulatory blood pressure in patients with systemic lupus erythematosus: Association with markers of immune activation.
Objectives: Ambulatory blood pressure monitoring measures 24-hour blood pressure, night-time blood pressure, and impaired dipping of nocturnal blood pressure, parameters that better predict cardiovascular risk than standard office blood pressure measurements. Systemic lupus erythematosus is characterized by immune system hyperactivity, elevated cardiovascular risk and high prevalence of hypertension; however, little is known about ambulatory blood pressure in lupus patients and its relationship to immune activation. Methods: We studied 26 patients with lupus and 26 control subjects. We obtained ambulatory 24-hour blood pressure measurements and report plasma concentrations of 77 markers of immune activation using a multiplex immunoassay and assessed their association with blood pressure measurements. Results: Despite similar office blood pressure measurements in patients with lupus and controls, lupus patients had higher 24-hour systolic [median (interquartile range) 129 (113 - 140) vs. 116 (111 - 121) mmHg, p = 0.03] and diastolic blood pressure [80 (69 - 86) vs. 72 (64 - 75) mmHg, p = 0.006] as well as less nocturnal dipping [7.8% (5.1 - 14.2%) vs. 12.0% (8.1 20.0%)] p = 0.03], compared to controls. In patients with lupus, markers of the innate (monocyte chemotactic protein-3) and adaptive immune systems [CUB domain-containing protein-1 and Interleukin-15 receptor subunit-α,] were associated with nocturnal blood pressure measurements and attenuated nocturnal dipping. In conclusion, 24-hour systolic and diastolic blood pressure was higher and nocturnal blood pressure dipping was attenuated in patients with lupus compared to control subjects. Conclusion: In patients with SLE, nocturnal blood pressure and attenuated nocturnal blood pressure dipping were significantly associated with several innate and adaptive immune system biomarkers.


Leukemic cells growth fraction in the central nervous system in blastic phase of chronic myelogenous leukemia.
Clinical and neuropathological investigations were carried out in 6 patients, deceased due to blastic phase of chronic myelogenous leukemia (BPCML). Growth fraction of leukemic cells in peripheral blood, cerebrospinal fluid and in the central nervous system (CNS) was studied, using mitotic index and immunohistochemical staining technique with the monoclonal antibody antiproliferating cell nuclear antigen (anti-PCNA). The results suggest that in BPCML the proliferative activity of leukemic cells is low both in peripheral blood, cerebrospinal fluid, cerebral leukostasis and within the leptomeningeal and intracerebral infiltrates, even in cases with a very high white blood cells count. It can confirm the opinion that in BPCML, accumulation rather than proliferation of leukemic cells plays an important role in the development of the CNS leukemia.


Respirator leakage in the pharmaceutical industry of northwest England.
Field qualitative fit tests were conducted at 10 separate companies in the Northwest of England to determine the proportion of leaking respirators in a cross-section of pharmaceutical manufacturing industries. The 3 M FT-10 Qualitative Fit Test Apparatus was used to test a total of 211 half-face particulate respirator wearers. Participants wore their own respirators and were asked to don them as they would normally. In all cases, no specific intervention had occurred prior to testing. Results indicated a failure rate of 69% (of the 211 subjects tested, 145 respirators were leaking). Successful results were not associated with the frequency of use (p = 0.71) or years of experience wearing respirators (p = 0.59). Similarly, successful results were not associated with respirator training in the current job (p = 0.38) or training in previous jobs (p = 0.49). Leakage was not consistent across the 10 companies, with two companies exhibiting a 100% failure rate while another company had 26 successful tests in 50 wearers (52% pass rate). Only 35 of the 211 participants performed a negative pressure test. Of these, 80% successfully passed the test, which was significantly greater than the 22% pass rate among those who had not performed the pressure test (p < 0.001).


Deletion of the transmembrane transporter ABCG1 results in progressive pulmonary lipidosis.
We show that mice lacking the ATP-binding cassette transmembrane transporter ABCG1 show progressive and age-dependent severe pulmonary lipidosis that recapitulates the phenotypes of different respiratory syndromes in both humans and mice. The lungs of chow-fed Abcg1(-/-) mice, >6-months old, exhibit extensive subpleural cellular accumulation, macrophage, and pneumocyte type 2 hypertrophy, massive lipid deposition in both macrophages and pneumocytes and increased levels of surfactant. No such abnormalities are observed at 3 months of age. However, gene expression profiling reveals significant changes in the levels of mRNAs encoding key genes involved in lipid metabolism in both 3- and 8-month-old Abcg1(-/-) mice. These data suggest that the lungs of young Abcg1(-/-) mice maintain normal lipid levels by repressing lipid biosynthetic pathways and that such compensation is inadequate as the mice mature. Studies with A-549 cells, a model for pneumocytes type 2, demonstrate that overexpression of ABCG1 specifically stimulates the efflux of cellular cholesterol by a process that is dependent upon phospholipid secretion. In addition, we demonstrate that Abcg1(-/-), but not wild-type macrophages, accumulate cholesterol ester droplets when incubated with surfactant. Together, these data provide a mechanism to explain the lipid accumulation in the lungs of Abcg1(-/-)mice. In summary, our results demonstrate that ABCG1 plays essential roles in pulmonary lipid homeostasis.


[Anorexia-cachexia frequency and its gastrointestinal symptoms association in paliative patients at the Instituto Nacional de Cancerología, México].
Anorexia-cachexia is a frequent syndrome among cancer patients, specially in late stages: the global prevalence of para-neoplastic anorexia-cachexia ranges between 20-40% in the diagnostic stage and between 70-80% in the late stage of the disease. The co-existence of functional or structural digestive abnormalities is frequently observed among cancer patients; this is a consequence of the tumor growth and of those systemic phenomena related to metabolism, which are affected by the relationship tumor-host specific to anorexia- cachexia. This study aimed at establishing the frequency of anorexia-cachexia, as well as its relationship to GI symptoms in the context of palliative care patients at the Instituto Nacional de Cancerología, México City. Analytic cross-sectional study including 100 patients diagnosed with late-stage cancer, age range 18-80, and a Karnofsky score > 50, as well as an ECOG <2; patients with a bad general health status were not allowed in the study. After reviewing inclusion and exclusion criteria, participants fulfilled the FAACT questionnaire, as well as the EGS. Patients recruitment was carried out by the Instituto Nacional de Cancerología. Results and discussion: Results show that 61% (n=61)of the patients had anorexia-cachexia, and 39% (n=39)did not. 56% of the sample participants (n=34) were women, and 44% (n=27) were men. GI symptoms associated with anorexia-cachexia were: nausea (p= 0.0001), vomiting (p=0.004), early satiety (p=0.0005), dysgeusia(p=0.0005) and dysphagia (p=0.001). Anorexia and cachexia are among the most devastating and frequent symptoms in late-stage cancer patients and they are also associated with GI symptoms affecting the physical, psychosocial and existential aspects of the patient's life. Data from this research validate the importance of an early nutrition support in palliative patients so that they can achieve a better quality of life.


Evaluating the fate of metals in air pollution control residues from coal-fired power plants.
Changes in emissions control at U.S. coal-fired power plants will shift metals content from the flue gas to the air pollution control (APC) residues. To determine the potential fate of metals that are captured through use of enhanced APC practices, the leaching behavior of 73 APC residues was characterized following the approach of the Leaching Environmental Assessment Framework. Materials were tested over pH conditions and liquid-solid ratios expected during management via land disposal or beneficial use. Leachate concentrations for most metals were highly variable over a range of coal rank, facility configurations, and APC residue types. Liquid-solid partitioning (equilibrium) as a function of pH showed significantly different leaching behavior for similar residue types and facility configurations. Within a facility, the leaching behavior of blended residues was shown to follow one of four characteristic patterns. Variability in metals leaching was greater than the variability in totals concentrations by several orders of magnitude, inferring that total content is not predictive of leaching behavior. The complex leaching behavior and lack of correlation to total contents indicates that release evaluation under likely field conditions is a better descriptor of environmental performance than totals content or linear partitioning approaches.


Eosinophil apoptosis as a therapeutic target in allergic asthma.
Asthma is a chronic inflammatory disease of the airways manifesting in many different phenotypes. Allergic asthma, comprising approximately half of patients with asthma, is characterized by the accumulation of eosinophils into the lungs. Eosinophils release factors that damage the surrounding cells and participate in the maintenance and exacerbation of inflammation. In the absence of any inflammatory survival-prolonging factors, eosinophils die by apoptosis in few days but in inflamed airways, eosinophil survival is thought to be prolonged due to the surrounding pro-inflammatory factors such as IL-5, IL-3 and GM-CSF. Resolution of eosinophilic inflammation is an important goal in the treatment of allergic asthma. Apoptosis is a physiological and non-inflammatory way to eliminate these harmful cells, and development of drugs targeting eosinophil apoptosis is one possible strategy for the therapy of allergic asthma. Importance of this strategy is supported by the fact that promotion of eosinophil apoptosis is a property of many anti-asthmatic agents such as glucocorticoids, the current main anti-inflammatory therapy of asthma, theophylline and leukotriene modifiers. β2 agonists have been shown to modulate eosinophil longevity by increasing survival. Also, anti-IL-5 antibody mesolizumab has shown efficacy in reducing asthma exacerbations in patients with severe eosinophilic asthma. Many potential future anti-asthmatic agents, such as Siglec-8 activating antibody and novel humanized anti-IL-5 antibody MEDI-563, have the property of inducing eosinophil apoptosis. This MiniReview aims to present eosinophil apoptosis as a therapeutic target in the treatment of allergic asthma. We summarize the effects and mechanisms of current and potential future anti-asthmatic drugs on eosinophil apoptosis and additionally, discuss the potential factors that promote eosinophil longevity in the lungs.