Native Mitral Valve Endocarditis Caused by a Non-HACEK Gram-Negative Pathogen in a Hemodialysis Patient.
Infective endocarditis (IE) due to non-HACEK (species other than Hemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) bacteremia accounts for less than 2% of all IE cases but is proven to be associated with higher mortality, even more so in hemodialysis (HD) patients. Few data are available in the literature concerning non-HACEK Gram-negative (GN) IE in this immunocompromised population with multiple comorbidities. We report the atypical clinical presentation of an elderly HD patient diagnosed with a non-HACEK GN IE, namely E. coli, successfully treated with intravenous (IV) antibiotics. The objective of this case study and related literature was to highlight the limited applicability of the modified Duke criteria in the HD population, as well as the frailty of HD patients that increases their susceptibility to IE due to unexpected microorganisms that could have fatal consequences. The need for a multidisciplinary approach of an IE in HD patients is therefore imperative.


Highly Efficient Computationally Derived Novel Metagenome α-Amylase With Robust Stability Under Extreme Denaturing Conditions.
α-Amylases are among the very critical enzymes used for different industrial purposes. Most α-amylases cannot accomplish the requirement of industrial conditions and easily lose their activity in harsh environments. In this study, a novel α-amylase named PersiAmy1 has been identified through the multistage in silico screening pipeline from the rumen metagenomic data. The long-term storage of PersiAmy1 in low and high temperatures demonstrated 82.13 and 71.01% activities after 36 days of incubation at 4 and 50°C, respectively. The stable α-amylase retained 61.09% of its activity after 180 min of incubation at 90°C and was highly stable in a broad pH range, showing 60.48 and 86.05% activities at pH 4.0 and pH 9.0 after 180 min of incubation, respectively. Also, the enzyme could resist the high-salinity condition and demonstrated 88.81% activity in the presence of 5 M NaCl. PersiAmy1 showed more than 74% activity in the presence of various metal ions. The addition of the detergents, surfactants, and organic solvents did not affect the α-amylase activity considerably. Substrate spectrum analysis showed that PersiAmy1 could act on a wide array of substrates. PersiAmy1 showed high stability in inhibitors and superb activity in downstream conditions, thus useful in detergent and baking industries. Investigating the applicability in detergent formulation, PersiAmy1 showed more than 69% activity after incubation with commercial detergents at different temperatures (30-50°C) and retained more than 56% activity after incubation with commercial detergents for 3 h at 10°C. Furthermore, the results of the wash performance analysis exhibited a good stain removal at 10°C. The power of PersiAmy1 in the bread industry revealed soft, chewable crumbs with improved volume and porosity compared with control. This study highlights the intense power of robust novel PersiAmy1 as a functional bio-additive in many industrial applications.


Single-molecule analysis of translational dynamics.
Decades of extensive biochemical and biophysical research have outlined the mechanism of translation. Rich structural studies have provided detailed snapshots of the translational machinery at all phases of the translation cycle. However, the relationship between structural dynamics, composition, and function remains unknown. The multistep nature of each stage of the translation cycle results in rapid desynchronization of individual ribosomes, thus hindering elucidation of the underlying mechanisms by conventional bulk biophysical and biochemical methods. Single-molecule approaches unsusceptible to these complications have led to the first glances at both compositional and conformational dynamics on the ribosome and their impact on translational control. These experiments provide the necessary link between static structure and mechanism, often providing new perspectives. Here we review recent advances in the field and their relationship to structural and biochemical data.


'Intentional' signaling in Animal communication.
The problem of 'intentional' signaling is of interest to evolutionary biologists concerned with animal conflicts and to cognitive ethologists attempting to determine whether nonhuman animals exhibit evidence of complex mental states. Recent theoretical and empirical advances in this area have led to a number of important insights concerning the nature of competitive social interactions. Specifically, and in contrast to earlier claims, individuals involved in social conflicts often produce displays that predict their-subsequent behavior, and such predictive displays occur even when repeated social interactions are infrequent. Moreover, studies on a taxonomically diverse set of organisms show that deception, in the form of withholding information, is prevalent. Deception through concealment of information may be widespread because it is more difficult to detect than active falsification of information.


Undifferentiated Endometrial Sarcoma of the Ovary: A Case Report with Review of Recent Literature and Discussion of Lacking Specificity of CD10 Immunoreactivity.
Undifferentiated endometrial sarcomas (UESs) of the ovary are very rare tumors. This paper presents a case of a 56-year-old patient with a history of hysterectomy and bilateral salpingectomy seven years ago for uterine leiomyomata. Intraoperatively, a tumor originating from the left ovary, adherent to the sigmoid colon, with infiltration of the small intestine and the vaginal apex was found. Histologically, the tumor was composed of pleomorphic round and oval to spindled cells with polymorphous vesicular nuclei with coarse chromatin and large nucleoli. Mitotic activity was brisk. There were large necrotic areas. Adjacent to the tumor tissue endometrium-like glands surrounded by fibrous stroma with macrophages corresponding to ovarian endometriosis were noted. Tumor cells showed diffuse strong immunoreactivity for vimentin and patchy strong staining for CD10; no reactivities were found for AE1/AE3, desmin, S-100, LCA, CD20, c-kit, and CD31. The patient died of her neoplastic disease four months postoperatively. CD10 is frequently expressed in different gynecopathological as well as other lesions, and, thus, nonspecific without relevance to the classification of this case. Morphological features, extensive sampling, and appropriate immunohistochemistry including markers for cytokeratins and myogenic differentiation are mandatory to arrive at the correct diagnosis.


Does ridge preservation following tooth extraction improve implant treatment outcomes: a systematic review: Group 4: Therapeutic concepts & methods.
(1) Primary focused question (Q1): to evaluate the effect of alveolar ridge preservation (ARP) on implant outcomes (implant placement feasibility, need for further augmentation, survival/success rates, marginal bone loss) compared with unassisted socket healing (USH) and (2) secondary focused question (Q2): to estimate the size effects (SE) of these outcomes in three different interventions (GBR, socket filler, socket seal). Electronic (MEDLINE, EMBASE, Cochrane Central Register LILACS; Web of Science) and hand search was conducted up to July 2014. Randomised controlled trials (RCT), controlled clinical trials (CCT) and prospective cohort studies with USH as controls were eligible in the analysis for Q1. RCTs, CCTs and prospective case series, with or without USH as control, were eligible for Q2. Ten (8 RCTs, 2 CCTs) and 30 studies (21 RCTs, 7 CCTs, 2 case series) were included in the analysis for Q1 and Q2, respectively. The risk for bias was unclear or high in most of them. Q1: Implant placement was feasible in ARP-treated and USH sites. These implants presented similar survival/success rates and marginal bone levels. The need for further augmentation decreased when ARP was performed (Relative risk: 0.15, 95% CI: 0.07-0.3). Q2: The SE for implant placement feasibility was 98.5% (95% CI: 96.4-99.6) in GBR and 96.2 (95% CI: 93.1-98.2) in socket filler group. The SE for need for further augmentation was 11.9 (95% CI: 5.6-19.9) for GBR and 13.7% (95% CI: 5.0-25.6) for socket filler groups. GBR and socket filler presented similar SE for survival/success rates and average marginal bone loss. Limited data were available for implant-related outcomes in sites treated with socket seal. There is limited evidence to support the clinical benefit of ARP over USH in improving implant-related outcomes despite a decrease in the need for further ridge augmentation during implant placement. Similar implant placement feasibility, survival/success rates and marginal bone loss should be anticipated following ARP or USH. Currently, it is not clear which type of ARP intervention has a superior impact on implant outcomes.


Controlled formation of closed-edge nanopores in graphene.
Dangling bonds at the edge of a nanopore in monolayer graphene make it susceptible to back-filling at low temperatures from atmospheric hydrocarbons, leading to potential instability for nanopore applications, such as DNA sequencing. We show that closed edge nanopores in bilayer graphene are robust to back-filling under atmospheric conditions for days. A controlled method for closed edge nanopore formation starting from monolayer graphene is reported using an in situ heating holder and electron beam irradiation within an aberration-corrected transmission electron microscopy. Tailoring of closed-edge nanopore sizes is demonstrated from 1.4-7.4 nm. These results should provide mechanisms for improving the stability of nanopores in graphene for a wide range of applications involving mass transport.


Sensory function and albumin excretion according to diagnostic criteria for diabetes.
The purpose of this study was to examine sensory function and albumin excretion according to categories of glucose tolerance in individuals undergoing screening for diabetes. Sensory function and albumin excretion measurements were obtained in 636 individuals at the time of screening for diabetes according to American Diabetes Association glucose tolerance criteria. Sensory thresholds were measured by forced-choice techniques. Albumin-to-creatinine ratios were calculated from spot urine samples. Of 90 individuals whose glucose levels were in the range for diabetes, 65 had fasting glucose values >or=126 mg/dl, whereas 25 had 2-h glucose values >or=200 mg/dl, with fasting glucose values <126 mg/dl. In covariance analyses, those with fasting glucose levels >or=126 mg/dl had higher vibration (P < 0.01) and thermal (P < 0.05 for cool and warm) thresholds than those with normal glucose tolerance. This pattern was also evident for albumin-to-creatinine ratios (P < 0.001). In contrast, those with 2-h glucose values >or=200 mg/dl and fasting glucose values <126 mg/dl had sensory threshold and albumin-to-creatinine ratio values similar to those of the normal group. Individuals with fasting glucose levels >or=126 mg/dl had higher vibration threshold and albumin-to-creatinine ratio values (<0.05 and <0.01, respectively) than those with levels <126 mg/dl. Sensory threshold and albumin excretion values already tend to be greater than normal at screening in individuals with fasting glucose levels >or=126 mg/dl, but not in those with levels <126 mg/dl. A reliance on fasting glucose levels >or=126 mg/dl for screening might not be sufficient for early intervention and the optimal prevention of diabetes complications.


How do introgression events shape the partitioning of diversity among breeds: a case study in sheep.
From domestication to the current pattern of differentiation, domestic species have been influenced by reticulate evolution with multiple events of migration, introgression, and isolation; this has resulted in a very large number of breeds. In order to manage these breeds and their genetic diversity, one must know the current genetic structure of the populations and the relationships among these. This paper presents the results of a genetic diversity analysis on an almost exhaustive sample of the sheep breeds reared in France. Molecular characterization was performed with a set of 21 microsatellite markers on a collection of 49 breeds that include five breed types: meat, hardy meat, dairy, high prolificacy and patrimonial breeds. Values of expected heterozygosity ranged from 0.48 to 0.76 depending on the breed, with specialized meat breeds exhibiting the lowest values. Neighbor-Net, multidimensional analysis or clustering approaches revealed a clear differentiation of the meat breeds compared to the other breed types. Moreover, the group that clustered meat breeds included all the breeds that originated from the United Kingdom (UK) and those that originated from crossbreeding between UK breeds and French local breeds. We also highlighted old genetic introgression events that were related to the diffusion of Merino rams to improve wool production. As a result of these introgression events, especially that regarding the UK breeds, the breeds that were clustered in the 'meat type cluster' exhibited the lowest contribution to total diversity. That means that similar allelic combinations could be observed in different breeds of this group. The genetic differentiation pattern of the sheep breeds reared in France results from a combination of factors, i.e. geographical origin, historic gene flow, and breed use. The Merino influence is weaker than that of UK breeds, which is consistent with how sheep use changed radically at the end of 19(th) century when wool-producing animals (Merino-like) were replaced by meat-producing breeds. These results are highly relevant to monitor and manage the genetic diversity of sheep and can be used to set priorities in conservation programs when needed.


LINC01936 inhibits the proliferation and metastasis of lung squamous cell carcinoma probably by EMT signaling and immune infiltration.
To discover the biological function and potential mechanism of LINC01936 in the development of lung squamous cell carcinoma (LUSC). Transcriptome data of LUSC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the differentially expressed lncRNAs in LUSC and normal tissues by R "DEseq2", "edgeR" and "limma" packages. The subcellular localization of LINC01936 was predicted by lncLocator. Cell proliferation and apoptosis were measured by CCK-8, MTT assay and Hoechst fluorescence staining. The migration and invasion were detected by Transwell assay. The function and pathway enrichment analysis were performed by Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene set variation analysis (GSVA). The downstream targets of LINC01936 were predicted using RNA-Protein Interaction Prediction (RPISeq) program. The effect of LINC01936 on tumor immune infiltration was analyzed using Pearson Correlation Analysis using R "ggpubr" package. Based on the gene expression data of LUSC from TCGA database, 1,603, 1,702 and 529 upregulated and 536, 436 and 630 downregulated lncRNAs were obtained by DEseq2, edgeR and limma programs, respectively. For GSE88862 dataset, we acquired 341 differentially expressed lncRNAs (206 upregulated and 135 downregulated). Venn plot for the intersection of above differential expressed lncRNAs showed that there were 29 upregulated and 23 downregulated genes. LINC01936 was one of downregulated lncRNAs in LUSC tissues. The biological analysis showed that the overexpression of LINC01936 significantly reduced proliferation, migration and invasion of LUSC cells, and promoted cell apoptosis. The knockdown of LINC01936 promoted cell proliferation and metastasis. Pathway and GSVA analysis indicated that LINC01936 might participated in DNA repair, complement, cell adhesion and EMT, etc. LINC01936 was predicted to interact with TCF21, AOC3, RASL12, MEOX2 or HSPB7, which are involved in EMT and PI3K-AKT-MTOR pathway, etc. The expression of LINC01936 was also positively correlated with the infiltrating immune cells in LUSC. LINC01936 is downregulated in LUSC. LINC01936 affected proliferation, migration and invasion of LUSC cells probably by EMT and immune infiltration, which might serve as a new target for the treatment of LUSC.


Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP.
As cancer cells traverse collagen-rich extracellular matrix (ECM) barriers and intravasate, they adopt a fibroblast-like phenotype and engage undefined proteolytic cascades that mediate invasive activity. Herein, we find that fibroblasts and cancer cells express an indistinguishable pericellular collagenolytic activity that allows them to traverse the ECM. Using fibroblasts isolated from gene-targeted mice, a matrix metalloproteinase (MMP)-dependent activity is identified that drives invasion independently of plasminogen, the gelatinase A/TIMP-2 axis, gelatinase B, collagenase-3, collagenase-2, or stromelysin-1. In contrast, deleting or suppressing expression of the membrane-tethered MMP, MT1-MMP, in fibroblasts or tumor cells results in a loss of collagenolytic and invasive activity in vitro or in vivo. Thus, MT1-MMP serves as the major cell-associated proteinase necessary to confer normal or neoplastic cells with invasive activity.


Type II diabetic subjects with secondary failure: treatment with prebreakfast mixed ultralente and regular insulin with a sulfonylurea.
Combination therapy with sulfonylurea and insulin is reported to be effective in several recent reports on the management of non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to sulfonylurea. Most of these studies used insulin twice daily, however, and hence failed to offer a significant practical advantage over insulin therapy alone. Since a subcutaneous injection of Ultralente insulin exerts its peak effect between 16 and 18 hours after injection, its prebreakfast administration is likely to inhibit overnight hepatic glucose production, which is a primary modulator of fasting plasma glucose, a major determinant of diurnal glycemia in NIDDM: Moreover, the simultaneous administration of regular insulin tends to improve glycemia during the premeal and immediate postmeal period before the onset of sulfonylurea-induced insulin secretion. We assessed the efficacy of a prebreakfast subcutaneous injection of mixed Ultralente and regular insulin in conjunction with prior sulfonylurea therapy in 20 NIDDM subjects after precise documentation of secondary failure to these agents initially for the period of 3 months, followed by a long-term evaluation for up to 2 years. Metabolic control improved significantly as reflected by a decline in fasting plasma glucose (FPG) and HbA1c concentrations (FPG, 14.4 mmol/L +/- 0.4 vs 79 mmol/L +/- 0.3 mM/L; HbA1c, 11.7% +/- 0.3% vs 8.8% +/- 0.1%; P less than .001 for both comparisons). Serum cholesterol and triglycerides decreased as well, although the change was significant for triglycerides alone. Body weights and blood pressure remained unaltered. Furthermore, metabolic control appeared to remain in the same range during the long-term follow-up period. Adjuvant therapy with sulfonylurea and a single prebreakfast subcutaneous injection of mixed Ultralente and regular insulin may be an effective and practical therapeutic option in the management of NIDDM with secondary failure to sulfonylurea.


The Empirical Fluctuation Pattern of E. coli Division Control.
In physics, it is customary to represent the fluctuations of a stochastic system at steady state in terms of linear response to small random perturbations. Previous work has shown that the same framework describes effectively the trade-off between cell-to-cell variability and correction in the control of cell division of single E. coli cells. However, previous analyses were motivated by specific models and limited to a subset of the measured variables. For example, most analyses neglected the role of growth rate variability. Here, we take a comprehensive approach and consider several sets of available data from both microcolonies and microfluidic devices in different growth conditions. We evaluate all the coupling coefficients between the three main measured variables (interdivision times, cell sizes and individual-cell growth rates). The linear-response framework correctly predicts consistency relations between a priori independent experimental measurements, which confirms its validity. Additionally, the couplings between the cell-specific growth rate and the other variables are typically non zero. Finally, we use the framework to detect signatures of mechanisms in experimental data involving growth rate fluctuations, finding that (1) noise-generating coupling between size and growth rate is a consequence of inter-generation growth rate correlations and (2) the correlation patterns agree with a near-adder model where the added size has a dependence on the single-cell growth rate. Our findings define relevant constraints that any theoretical description should reproduce, and will help future studies aiming to falsify some of the competing models of the cell cycle existing today in the literature.


Management challenges for chronic dysimmune neuropathies during the COVID-19 pandemic.
Since March 2020, the COVID-19 pandemic has led to the need to re-think the delivery of services to patients with chronic dysimmune neuropathies. Telephone/video consultations have become widespread but have compounded concerns about objective evaluation. Therapeutic decisions need, more than ever before, to be considered in the best interests of both patients, and society, while not denying function-preserving/restoring treatment. Immunoglobulin therapy and plasma exchange, for those treated outside of the home, expose patients to the hazards of hospital or outpatient infusion centers. Steroid therapy initiation and continuation pose increased infectious risk. Immunosuppressant therapy similarly becomes highly problematic, with the risks of treatment continuation enhanced by uncertainties regarding duration of the pandemic. The required processes necessitate considerable time and effort especially as resources and staff are re-deployed to face the pandemic, but are essential for protecting this group of patients and as an integral part of wider public health actions.


Mammography in New Zealand: radiation dose and image quality.
The mean glandular doses to the breast, image quality and machine performance have been determined for all mammographic x-ray facilities in New Zealand, during 1988-89. For 30 mm and 45 mm phantoms the mean doses per film were 1.03 +/- 0.56 mGy and 1.97 +/- 1.06 mGy. These doses are within international guide-lines. Image quality (detection of simulated microcalcifications, and contrast-detail performance) was found to depend on focal spot size/FFD combination, breast thickness, and film processing. The best machines could resolve 0.2 mm aluminium oxide specks with the contact technique. The use of a grid improved image quality as did magnification. Extended cycle film processing reduced doses, but the claimed improvement in image quality was not apparent from our data. The machine calibration parameters kVp, HVL and timer accuracy were in general within accepted tolerances. Automatic exposure controls in some cases gave poor control of film density with changing breast thickness.


A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons.
From a systematic screening of animal venoms, we isolated a new toxin (APETx2) from the sea anemone Anthopleura elegantissima, which inhibits ASIC3 homomeric channels and ASIC3-containing heteromeric channels both in heterologous expression systems and in primary cultures of rat sensory neurons. APETx2 is a 42 amino-acid peptide crosslinked by three disulfide bridges, with a structural organization similar to that of other sea anemone toxins that inhibit voltage-sensitive Na+ and K+ channels. APETx2 reversibly inhibits rat ASIC3 (IC50=63 nM), without any effect on ASIC1a, ASIC1b, and ASIC2a. APETx2 directly inhibits the ASIC3 channel by acting at its external side, and it does not modify the channel unitary conductance. APETx2 also inhibits heteromeric ASIC2b+3 current (IC50=117 nM), while it has less affinity for ASIC1b+3 (IC50=0.9 microM), ASIC1a+3 (IC50=2 microM), and no effect on the ASIC2a+3 current. The ASIC3-like current in primary cultured sensory neurons is partly and reversibly inhibited by APETx2 with an IC50 of 216 nM, probably due to the mixed inhibitions of various co-expressed ASIC3-containing channels.


Oral contraceptives and breast disease.
Epidemiologic data support the hypothesis that the types of OCs used before the mid-1970s protected against most forms of benign breast disease. It is unclear whether current low-dose progestogen OCs will confer the same protection. Further studies are necessary to clarify this. For breast cancer, the relationship is more complex. It is possible that prolonged use of high-dose OCs exert a small increased risk for breast cancer development in women before age 45. Furthermore, prolonged use before a first term pregnancy may result in a small increase in risk for breast cancer before age 45. Studies evaluating the effect of current low-dose OCs are necessary to elucidate what, if any, effect they may have on breast cancer development. Furthermore, as our population ages, studies will be able to determine what effect, if any, may be present in women over age 60, those women with the highest underlying risk of breast cancer. And finally, more research of basic breast tissue physiology and the effect of endogenous and exogenous hormones on this complex organ is needed.


LncRNA XIST sponges miR-199a-3p to modulate the Sp1/LRRK2 signal pathway to accelerate Parkinson's disease progression.
In vitro and in vivo models of Parkinson's disease were established to investigate the effects of the lncRNA XIST/miR-199a-3p/Sp1/LRRK2 axis. The binding between XIST and miR-199a-3p as well as miR-199a-3p and Sp1 were examined by luciferase reporter assay and confirmed by RNA immunoprecipitation analysis. Following the Parkinson's disease animal behavioural assessment by suspension and swim tests, the brain tissue injuries were evaluated by hematoxylin and eosin, TdT-mediated dUTP-biotin nick end labelling, and tyrosine hydroxylase stainings. The results indicated that miR-199a-3p expression was downregulated, whereas that of XIST, Sp1 and LRRK2 were upregulated in Parkinson's disease. Moreover, miR-199a-3p overexpression or XIST knockdown inhibited the cell apoptosis induced by MPP+ treatment and promoted cell proliferation. The neurodegenerative defects were significantly recovered by treating the cells with shXIST or shSp1, whereas miR-199a-3p inhibition or Sp1 and LRRK2 overexpression abrogated these beneficial effects. Furthermore, the results of our in vivo experiments confirmed the neuroprotective effects of shXIST and miR-199a-3p against MPTP-induced brain injuries, and the Parkinson's disease behavioural symptoms were effectively alleviated upon shXIST or miR-199a-3p treatment. In summary, the results of the present study showed that lncRNA XIST sponges miR-199a-3p to modulate Sp1 expression and further accelerates Parkinson's disease progression by targeting LRRK2.


G-protein coupled receptor-mediated nutrient sensing and developmental control in Aspergillus nidulans.
Nutrient sensing and utilisation are fundamental for all life forms. As heterotrophs, fungi have evolved a diverse range of mechanisms for sensing and taking up various nutrients. Despite its importance, only a limited number of nutrient receptors and their corresponding ligands have been identified in fungi. G-protein coupled receptors (GPCRs) are the largest family of transmembrane receptors. The Aspergillus nidulans genome encodes 16 putative GPCRs, but only a few have been functionally characterised. Our previous study showed the increased expression of an uncharacterised putative GPCR, gprH, during carbon starvation. GprH appears conserved throughout numerous filamentous fungi. Here, we reveal that GprH is a putative receptor involved in glucose and tryptophan sensing. The absence of GprH results in a reduction in cAMP levels and PKA activity upon adding glucose or tryptophan to starved cells. GprH is pre-formed in conidia and is increasingly active during carbon starvation, where it plays a role in glucose uptake and the recovery of hyphal growth. GprH also represses sexual development under conditions favouring sexual fruiting and during carbon starvation in submerged cultures. In summary, the GprH nutrient-sensing system functions upstream of the cAMP-PKA pathway, influences primary metabolism and hyphal growth, while represses sexual development in A. nidulans.


Persistent SARS-CoV-2 infection in patients with B-cell deficiency: a case series of successful antiviral treatment of four patients.
Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunocompromised patients remains a major medical challenge. Diagnosing the syndrome is difficult as symptoms may mimic other diseases and treatment guidelines are lacking. We describe a case series of four patients with persistent SARS-CoV-2 infection that all had an underlying B-cell deficiency due to rituximab treatment (in one case in combination with epcoritamab). In all four patients, it was initially difficult to recognize the persistent disease, leading to a duration of illness between 45 and 242 days. Two patients were only positive for SARS-CoV-2 by polymerase chain reaction (PCR) in the nasopharynx at the beginning of the disease but were later repeatedly negative. However, when bronchoalveolar lavage was performed, a positive SARS-CoV-2 PCR was revealed from the lower airways in both patients. The difficulties establishing diagnosis contributed to these two patients' long disease course. The longest disease duration was in the patient treated with rituximab and epcoritamab, who also responded poorly to single standard antiviral treatment. This patient ultimately cleared the infection after administering a combination treatment with remdesivir and nirmatrelvir/ritonavir. After a confirmed diagnosis, the other three patients cleared the infection when they were finally treated with antivirals. Increasing clinicians' awareness of this condition is important as it might be treatable once diagnosed. Further studies are warranted to define the condition and treatment strategy with greater precision.


Probing the size dependence on the optical modes of anatase nanoplatelets using STEM-EELS.
Anatase titania nanoplatelets with predominantly exposed {001} facets have been reported to have enhanced catalytic properties in comparison with bulk anatase. To understand their unusual behaviour, it is essential to fully characterize their electronic and optical properties at the nanometer scale. One way of assessing these fundamental properties is to study the dielectric function. Valence electron energy-loss spectroscopy (EELS) performed using a scanning transmission electron microscope (STEM) is the only analytical method that can probe the complex dielectric function with both high energy (<100 meV) and high spatial (<1 nm) resolution. By correlating experimental STEM-EELS data with simulations based on semi-classical dielectric theory, the dielectric response of thin (<5 nm) anatase nanoplatelets was found to be largely dominated by characteristic (optical) surface modes, which are linked to surface plasmon modes of anatase. For platelets less than 10 nm thick, the frequency of these optical modes varies according to their thickness. This unique optical behaviour prompts the enhancement of light absorption in the ultraviolet regime. Finally, the effect of finite size on the dielectric signal is gradually lost by stacking consistently two or more platelets in a specific crystal orientation, and eventually suppressed for large stacks of platelets.


Extended pathoanatomical studies point to a consistent affection of the thalamus in spinocerebellar ataxia type 2.
The involvement of the thalamus during the course of the currently known polyglutamine diseases is still a matter of debate. While it is well-known that this diencephalic nuclear complex undergoes neurodegeneration in some polyglutamine diseases such as Huntington's disease (HD), it has remained unclear whether and to what extent the thalamus is also involved in spinocerebellar ataxia type 2 (SCA2) patients. Encouraged by our recent post-mortem findings in one German SCA2 patient and the results of a recent nuclear magnetic resonance (NMR) study, we extended our pathoanatomical analysis to serial thick sections stained for lipofuscin granules and Nissl substance through the thalami of four additional German and Cuban SCA2 patients. According to this analysis the thalamus is consistently affected by the destructive process of SCA2. In particular, during our study we observed a consistent involvement of the lateral geniculate body, the lateral posterior, ventral anterior, ventral lateral, ventral posterior lateral, and ventral posterior medial thalamic nuclei as well as the extraterritorial reticular nucleus. In four of the SCA2 cases studied additional damage was seen in the inferior and lateral nuclei of the pulvinar, whereas in the minority of the patients a subset of the limbic nuclei of the thalamus (i.e. anterodorsal, anteroprincipal, laterodorsal, fasciculosus, mediodorsal, central lateral, central medial, cucullar, and paracentral nuclei, medial nucleus of the pulvinar) underwent neurodegeneration. These interindividual differences in the distribution pattern of thalamic neurodegeneration indicate that the thalamic nuclei differ in their proclivities to degenerate in SCA2 and may suggest that they become involved at different phases in the evolution of the underlying degenerative process.


On the relationship between personal experience, affect and risk perception: The case of climate change.
Examining the conceptual relationship between personal experience, affect, and risk perception is crucial in improving our understanding of how emotional and cognitive process mechanisms shape public perceptions of climate change. This study is the first to investigate the interrelated nature of these variables by contrasting three prominent social-psychological theories. In the first model, affect is viewed as a fast and associative information processing heuristic that guides perceptions of risk. In the second model, affect is seen as flowing from cognitive appraisals (i.e., affect is thought of as a post-cognitive process). Lastly, a third, dual-process model is advanced that integrates aspects from both theoretical perspectives. Four structural equation models were tested on a national sample (N = 808) of British respondents. Results initially provide support for the "cognitive" model, where personal experience with extreme weather is best conceptualized as a predictor of climate change risk perception and, in turn, risk perception a predictor of affect. Yet, closer examination strongly indicates that at the same time, risk perception and affect reciprocally influence each other in a stable feedback system. It is therefore concluded that both theoretical claims are valid and that a dual-process perspective provides a superior fit to the data. Implications for theory and risk communication are discussed. © 2014 The Authors. European Journal of Social Psychology published by John Wiley & Sons, Ltd.


Formation of a complex between nucleolin and replication protein A after cell stress prevents initiation of DNA replication.
We used a biochemical screen to identify nucleolin, a key factor in ribosome biogenesis, as a high-affinity binding partner for the heterotrimeric human replication protein A (hRPA). Binding studies in vitro demonstrated that the two proteins physically interact, with nucleolin using an unusual contact with the small hRPA subunit. Nucleolin significantly inhibited both simian virus 40 (SV-40) origin unwinding and SV-40 DNA replication in vitro, likely by nucleolin preventing hRPA from productive interaction with the SV-40 initiation complex. In vivo, use of epifluorescence and confocal microscopy showed that heat shock caused a dramatic redistribution of nucleolin from the nucleolus to the nucleoplasm. Nucleolin relocalization was concomitant with a tenfold increase in nucleolin-hRPA complex formation. The relocalized nucleolin significantly overlapped with the position of hRPA, but only poorly with sites of ongoing DNA synthesis. We suggest that the induced nucleolin-hRPA interaction signifies a novel mechanism that represses chromosomal replication after cell stress.


The passive surveillance of ticks using companion animal electronic health records.
Ticks represent a large global reservoir of zoonotic disease. Current surveillance systems can be time and labour intensive. We propose that the passive surveillance of companion animal electronic health records (EHRs) could provide a novel methodology for describing temporal and spatial tick activity. A total of 16 58 857 EHRs were collected over a 2-year period (31 March 2014 and 29 May 2016) from companion animals attending a large sentinel network of 192 veterinary clinics across Great Britain (the Small Animal Veterinary Surveillance Network - SAVSNET). In total, 2180 EHRs were identified where a tick was recorded on an animal. The relative risk of dogs presenting with a tick compared with cats was 0·73 (95% confidence intervals 0·67-0·80). The highest number of tick records were in the south central regions of England. The presence of ticks showed marked seasonality with summer peaks, and a secondary smaller peak in autumn for cats; ticks were still being found throughout most of Great Britain during the winter. This suggests that passive surveillance of companion animal EHRs can describe tick activity temporally and spatially in a large cohort of veterinary clinics across Great Britain. These results and methodology could help inform veterinary and public health messages as well as increase awareness of ticks and tick-borne diseases in the general population.


Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome.
High level microsatellite instability (MSI-H) occurs in about 15% of colorectal cancer (CRCs), either as sporadic cancers or in the context of hereditary non-polyposis cancer or Lynch syndrome. In MSI-H CRC, mismatch repair deficiency leads to insertion/deletion mutations at coding microsatellites and thus to the translation of frameshift peptides (FSPs). FSPs are potent inductors of T cell responses in vitro and in vivo. The present study aims at the identification of FSP-specific humoral immune responses in MSI-H CRC and Lynch syndrome. Sera from patients with history of MSI-H CRC (n = 69), healthy Lynch syndrome mutation carriers (n = 31) and healthy controls (n = 52) were analyzed for antibodies against FSPs using peptide ELISA. Reactivities were measured against FSPs derived from genes frequently mutated in MSI-H CRCs, AIM2, TGFBR2, CASP5, TAF1B, ZNF294, and MARCKS. Antibody reactivity against FSPs was significantly higher in MSI-H CRC patients than in healthy controls (P = 0.036, Mann-Whitney) and highest in patients with shortest interval between tumor resection and serum sampling. Humoral immune responses in patients were most frequently directed against FSPs derived from mutated TAF1B (11.6%, 8/69) and TGFBR2 (10.1%, 7/69). Low level FSP-specific antibodies were also detected in healthy mutation carriers. Our results show that antibody responses against FSPs are detectable in MSI-H CRC patients and healthy Lynch syndrome mutation carriers. Based on the high number of defined FSP antigens, measuring FSP-specific humoral immune responses is a highly promising tool for future diagnostic application in MSI-H cancer patients.


Regional left ventricular systolic function in patients with segmental early relaxation and single-vessel coronary artery disease.
The purpose of this study was to determine whether systolic function is compromised in segments of the left ventricle that manifest early relaxation and are supplied by a diseased coronary artery. Regional fractional area of shortening (FAS) was evaluated from resting ventriculograms of 24 patients. Nine patients had no cardiac disease or segmental early relaxation (SER) and served as controls. Fifteen patients had single-vessel coronary artery disease (60% to 95% diameter stenosis of the left anterior descending coronary artery). Among these 15 patients, seven had no evidence of SER and eight had SER localized to the anterior wall. In patients with coronary disease and SER, and FAS of the anterolateral segment, 1.30 +/- 0.08, was greater than either controls, 1.07 +/- 0.12 (p less than 0.01) or patients with coronary disease but no SER, 1.03 +/- 0.19 (p less than 0.01). Among patients with coronary disease and SER, the FAS of the anterolateral segment was greater than the corresponding diaphragmatic segment (1.30 +/- 0.08 vs 0.97 +/- 0.12) (p less than 0.001). There was no difference in the FAS between these two segments in either controls or in patients with coronary disease, but without SER. These results indicate that SER of the anterior wall in patients with disease of the left anterior descending coronary artery is associated with enhanced systolic function of the anterolateral region. This observation is incompatible with the concept that ischemia is an underlying mechanism of SER.


Long-term effects of glucose on insulin release and glucose oxidation by mouse pancreatic islets maintained in tissue culture.
Rates of glucose oxidation and insulin release in response to a wide range of glucose concentrations were studied in short-term experiments in isolated mouse pancreatic islets maintained in tissue culture for 6 days at either a physiological glucose concentration (6.7mm) or at a high glucose concentration (28mm). The curves relating glucose oxidation or insulin release to the extracellular glucose concentration obtained with islets cultured in 6.7mm-glucose displayed a sigmoid shape similar to that observed for freshly isolated non-cultured islets. By contrast islets that had been cultured in 28mm-glucose showed a linear relationship between the rate of glucose oxidation and the extracellular glucose concentration up to about 8mm-glucose. The maximal oxidative rate was twice that of the non-cultured islets and the glucose concentration associated with the half-maximal rate considerably decreased. In islets cultured at 28mm-glucose there was only a small increase in the insulin release in response to glucose, probably due to a depletion of stored insulin in those B cells that had been cultured in a high-glucose medium. It is concluded that exposure of B cells for 6 days to a glucose concentration comparable with that found in diabetic individuals causes adaptive metabolic alterations rather than degeneration of these cells.


Spectroscopic and genetic evidence for two heme-Cu-containing oxidases in Rhodobacter sphaeroides.
It has recently become evident that many bacterial respiratory oxidases are members of a superfamily that is related to the eukaryotic cytochrome c oxidase. These oxidases catalyze the reduction of oxygen to water at a heme-copper binuclear center. Fourier transform infrared (FTIR) spectroscopy has been used to examine the heme-copper-containing respiratory oxidases of Rhodobacter sphaeroides Ga. This technique monitors the stretching frequency of CO bound at the oxygen binding site and can be used to characterize the oxidases in situ with membrane preparations. Oxidases that have a heme-copper binuclear center are recognizable by FTIR spectroscopy because the bound CO moves from the heme iron to the nearby copper upon photolysis at low temperature, where it exhibits a diagnostic spectrum. The FTIR spectra indicate that the binuclear center of the R. sphaeroides aa3-type cytochrome c oxidase is remarkably similar to that of the bovine mitochondrial oxidase. Upon deletion of the ctaD gene, encoding subunit I of the aa3-type oxidase, substantial cytochrome c oxidase remains in the membranes of aerobically grown R. sphaeroides. This correlates with a second wild-type R. sphaeroides is grown photosynthetically, the chromatophore membranes lack the aa3-type oxidase but have this second heme-copper oxidase. Subunit I of the heme-copper oxidase superfamily contains the binuclear center. Amino acid sequence alignments show that this subunit is structurally very highly conserved among both eukaryotic and prokaryotic species. The polymerase chain reaction was used to show that the chromosome of R. sphaeroides contains at least one other gene that is a homolog of ctaD, the gene encoding subunit I of the aa3-type cytochrome c oxidase.(ABSTRACT TRUNCATED AT 250 WORDS)


Patterns of failure and toxicity profile following proton beam therapy for pediatric bladder and prostate rhabdomyosarcoma.
Bladder and prostate are unfavorable sites for rhabdomyosarcoma (B/P-RMS), and represent a challenging location for radiotherapy. Nineteen patients with B/P-RMS were enrolled on a prospective registry protocol (2008-2017) and treated with chemotherapy, proton beam therapy (PBT), and surgical resection (n = 8; 42%). Emphasis was given to treatment technique, disease-related outcomes, and toxicity associated with PBT. The majority of patients had bladder RMS (74%) of embryonal histology (95%), Group III (68%), and intermediate-risk disease by Children's Oncology Group (COG) risk stratification (89%). Seven patients (37%) had primary tumors >5 cm in size. All patients were treated according to COG protocols. With a median follow-up of 66.2 months, 5-year overall survival (OS) and progression-free survival (PFS) were 76%. Four patients (21%) experienced disease relapse, all presenting with local failure. The 5-year local control (LC) rate was 76%. Tumor size predicted LC, with 5-year LC for patients with >5 cm tumors being 43% versus 100% for those with ≤5 cm tumors (P = .006). Univariate analysis demonstrated an effect of tumor size on OS (tumor >5 cm, hazard ratio [HR] 17.7, P = .049) and PFS (HR 17.7, P = .049). Acute grade 2 toxicity was observed in two patients (11%, transient proctitis). Late grade 2+ toxicity was observed in three patients (16%; n = 1 grade 2 skeletal deformity; n = 3 transient grade 2 urinary incontinence; one patient experienced both). PBT for B/P-RMS affords promising disease-related outcomes with an acceptable toxicity profile. Higher local failure rates were observed for larger tumors, supporting dose-escalation components of ongoing RMS clinical trials.


[The lithotripsy of salivary stones].
Salivary lithotripsy may be performed with lithotriptors used for crushing urinary concrements. In some cases the method helps escape removal of the salivary gland if the stone is localized inside the gland. Further modifications of the method are needed.


A comparison of 'anaerobic' components of O2 debt and the Wingate test.
This study compared measurements which were considered traditionally to reflect alactacid and lactacid components of anaerobic metabolism. Subjects (men (N = 9) and women (N = 5)) on one occasion performed an exhaustive cycle ergometer ride at VO2 max and had peak lactate and O2 debt (fast and slow components) determined. On a second occasion, they performed a Wingate test. All data were normalized for body weight. Very few correlations were found between O2 debt or peak lactate and the peak power, mean power and power decrease of the Wingate test. In particular, both peak lactate and the fast O2 debt component had low, nonsignificant correlations with either peak or mean power. The study failed to support the traditional assumptions that both tests are quantifying the same anaerobic energy systems.


Superparamagnetic iron oxides as MPI tracers: A primer and review of early applications.
Magnetic particle imaging (MPI) has recently emerged as a non-invasive, whole body imaging technique that detects superparamagnetic iron oxide (SPIO) nanoparticles similar as those used in magnetic resonance imaging (MRI). Based on tracer "hot spot" detection instead of providing contrast on MRI scans, MPI has already proven to be truly quantitative. Without the presence of endogenous background signal, MPI can also be used in certain tissues where the endogenous MRI signal is too low to provide contrast. After an introduction to the history and simplified principles of MPI, this review focuses on early MPI applications including MPI cell tracking, multiplexed MPI, perfusion and tumor MPI, lung MPI, functional MPI, and MPI-guided hyperthermia. While it is too early to tell if MPI will become a mainstay imaging technique with the (theoretical) sensitivity that it promises, and if it can successfully compete with SPIO-based 1H MRI and perfluorocarbon-based 19F MRI, it provides unprecedented opportunities for exploring new nanoparticle-based imaging applications.


Inhibition of xanthine oxidase by some Chinese medicinal plants used to treat gout.
The enzyme xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and then to uric acid, which plays a crucial role in gout. A total of 122 traditional Chinese medicinal plants, selected according to the clinical efficacy and prescription frequency for the treatment of gout and other hyperuricemia-related disorders, have been evaluated for the enzyme inhibitory activity. Among the 122 methanol extracts derived from these species, 69 were shown to be inhibitory at 100 microg/ml, with 29 having greater than 50% inhibition. As to the equal amount of water extracts, 40 were disclosed to be active at 100 microg/ml, with 13 possessing more than 50% inhibition. At 50 microg/ml, 58 methanol and 24 water extracts exhibited inhibitory activity, with 15 of the former and two of the latter showing greater than 50% inhibition. The most active was the methanol extract of the twig of Cinnamomum cassia (Lauraceae) (IC(50), 18 microg/ml), which was followed immediately by those of the flower of Chrysanthemum indicum (Asteraceae) (IC(50), 22 microg/ml) and the leaves of Lycopus europaeus (Lamiatae) (IC(50), 26 microg/ml). Among the water extracts, the strongest inhibition of the enzyme was observed with that of the rhizome of Polygonum cuspidatum (Polygonaceae) (IC(50), 38 microg/ml). The IC(50) value of allopurinol used as a positive control was 1.06 microg/ml. The study demonstrated that the effects for these medicinal plants used for the gout treatment were based, at least in part, on the xanthine oxidase inhibitory action.


Expression of Sucrose Transporter cDNAs Specifically in Companion Cells Enhances Phloem Loading and Long-Distance Transport of Sucrose but Leads to an Inhibition of Growth and the Perception of a Phosphate Limitation.
Sucrose (Suc) is the predominant form of carbon transported through the phloem from source to sink organs and is also a prominent sugar for short-distance transport. In all streptophytes analyzed, Suc transporter genes (SUTs or SUCs) form small families, with different subgroups evolving distinct functions. To gain insight into their capacity for moving Suc in planta, representative members of each clade were first expressed specifically in companion cells of Arabidopsis (Arabidopsis thaliana) and tested for their ability to rescue the phloem-loading defect caused by the Suc transporter mutation, Atsuc2-4. Sequence similarity was a poor indicator of ability: Several genes with high homology to AtSUC2, some of which have phloem-loading functions in other eudicot species, did not rescue the Atsuc2-4 mutation, whereas a more distantly related gene, ZmSUT1 from the monocot Zea mays, did restore phloem loading. Transporter complementary DNAs were also expressed in the companion cells of wild-type Arabidopsis, with the aim of increasing productivity by enhancing Suc transport to growing sink organs and reducing Suc-mediated feedback inhibition on photosynthesis. Although enhanced Suc loading and long-distance transport was achieved, growth was diminished. This growth inhibition was accompanied by increased expression of phosphate (P) starvation-induced genes and was reversed by providing a higher supply of external P. These experiments suggest that efforts to increase productivity by enhancing sugar transport may disrupt the carbon-to-P homeostasis. A model for how the plant perceives and responds to changes in the carbon-to-P balance is presented.


Transmitting the energy: interdomain cross-talk in Pdr5.
ABC (ATP-binding cassette) transporters are ubiquitous integral membrane proteins catalyzing the active export or import of structurally and functionally unrelated compounds. In humans, these proteins are clinically and economically important, as their dysfunction is responsible for a number of diseases. In the case of multidrug resistance (MDR) ABC exporters, they particularly confer resistance to a broad spectrum of toxic compounds, placing them in the focus of clinical research. However, ABC-mediated drug resistance is not only restricted to humans. In yeast for example, MDR is called pleiotropic drug resistance (PDR). Important and well-studied members of the PDR subfamily of ABC transporters are Pdr5 from Saccharomyces cerevisiae and its homolog Cdr1 from Candida albicans. Mutational studies of these two transporters provided many insights into the complexity and conceivable mechanism of the interdomain cross-talk that transmits the energy gained from ATP hydrolysis to the substrate translocation process across the membrane. In this review, we summarize and discuss our current knowledge of the interdomain cross-talk as well as new results obtained for asymmetric ABC transporters and derive possible structural and functional implications for Pdr5.


Primary prevention of periodontitis: managing gingivitis.
Periodontitis is a ubiquitous and irreversible inflammatory condition and represents a significant public health burden. Severe periodontitis affects over 11% of adults, is a major cause of tooth loss impacting negatively upon speech, nutrition, quality of life and self-esteem, and has systemic inflammatory consequences. Periodontitis is preventable and treatment leads to reduced rates of tooth loss and improved quality of life. However, successful treatment necessitates behaviour change in patients to address lifestyle risk factors (e.g. smoking) and, most importantly, to attain and sustain high standards of daily plaque removal, lifelong. While mechanical plaque removal remains the bedrock of successful periodontal disease management, in high-risk patients it appears that the critical threshold for plaque accumulation to trigger periodontitis is low, and such patients may benefit from adjunctive agents for primary prevention of periodontitis. The aims of this working group were to systematically review the evidence for primary prevention of periodontitis by preventing gingivitis via four approaches: 1) the efficacy of mechanical self-administered plaque control regimes; 2) the efficacy of self-administered inter-dental mechanical plaque control; 3) the efficacy of adjunctive chemical plaque control; and 4) anti-inflammatory (sole or adjunctive) approaches. Two meta-reviews (mechanical plaque removal) and two traditional systematic reviews (chemical plaque control/anti-inflammatory agents) formed the basis of this consensus. Data support the belief that professionally administered plaque control significantly improves gingival inflammation and lowers plaque scores, with some evidence that reinforcement of oral hygiene provides further benefit. Re-chargeable power toothbrushes provide small but statistically significant additional reductions in gingival inflammation and plaque levels. Flossing cannot be recommended other than for sites of gingival and periodontal health, where inter-dental brushes (IDBs) will not pass through the interproximal area without trauma. Otherwise, IDBs are the device of choice for interproximal plaque removal. Use of local or systemic anti-inflammatory agents in the management of gingivitis has no robust evidence base. We support the almost universal recommendations that all people should brush their teeth twice a day for at least 2 min. with fluoridated dentifrice. Expert opinion is that for periodontitis patients 2 min. is likely to be insufficient, especially when considering the need for additional use of inter-dental cleaning devices. In patients with gingivitis once daily inter-dental cleaning is recommended and the adjunctive use of chemical plaque control agents offers advantages in this group.


Beam profile measurement of a solar-pumped iodine laser.
Beam profile measurements have been made as a function of time within the laser pulse and C2F5I pressure. Measurements indicate that the profile is determined directly by the optical excitation volume, produced by the solar simulator, and that media distortion plays a minor role compared to the build up of quenching species during the lasing pulse.


Prognostic value of tumor burden measurement using the number of tumors in non-surgical patients with non-small cell lung cancer.
No study to test the feasibility and prognostic value of the number of primary tumors, the number of positive lymph nodes, and the total number of tumors in the whole body as tumor burden measurements on FDG PET/CT imaging has been reported. To determine whether the number of tumors seen in 18F-FDG PET scans can be a prognostic factor in non-surgical patients with non-small cell lung cancer (NSCLC). One hundred and forty patients with histologically proven NSCLC and baseline 18F-FDG PET scan before therapy were identified in this retrospective analysis. The total number of tumors (TTn) in the whole body, the number of primary tumors (Tn), positive lymph nodes (Nn), and distant metastases (Mn), along with the maximum standardized uptake values (SUV(max)) of the tumors were measured. Inter-observer variability of the total number of tumors, counted by two radiologists, was assessed. Survival analyses were performed to determine the prognostic value of the number of tumors. Concordance correlation coefficients for the TTn, Tn, Nn, and Mn were all greater than 0.85. TTn and Nn were strong prognostic factors of NSCLC patients' overall survival (OS). In univariate Cox regression models, gender, stage, TTn, Nn, and Mn were statistically significant factors (P = 0.016, 0.032, <0.001, <0.001, and 0.006, respectively). In multivariate Cox regression models, TTn and Nn remained as statistically significant predictors for survival with hazard ratios (HR) of 1.06 (P = 0.001) and 1.11 (P = 0.002), respectively, after adjusting for clinical stage based 7th edition of TNM staging system, age, gender, and SUV(max). Patients with a TTn ≤4 (cutpoint based on median value) had a median OS of 15.2 months compared with 9.0 months for those with TTn >4. Measuring the number of tumors on FDG PET imaging is easy to perform with minimal inter-observer variability. The total number of tumors and number of nodal metastases, as metabolic tumor burden measurements in 18F-FDG PET/CT, are prognostic markers independent of clinical stage, age, gender, and SUV measurement in non-surgical patients with NSCLC.


Screening for Parkinson syndrome in a Chinese rural population: re-examination of a historic questionnaire.
Standardized screening tools for Parkinson syndrome have not been developed for non-western populations. This study aimed to validate the Copiah County questionnaire (CCQ) as a screening instrument in a Chinese rural population. All participants of a previously reported prevalent study were interviewed using CCQ. The participants who answered yes to at least one item on CCQ were defined as positive. The Parkinson's disease (PD) diagnosis was established using United Kingdom Parkinson's disease Brain Bank Clinical diagnosis criteria (UKPDBBC) and served as a gold standard to determine the sensitivity, specificity, and positive and negative predictive values (PPV, NPV) for the questionnaire. Among 16 130 participants, 2872 (17.8%) were screened positive for CCQ and 13 258 negative (82.2%). Among the 697 participants diagnosed as having Parkinson syndrome, 605 were positive for CCQ, and 92 were negative, leading to a sensitivity of 86.8%. Out of the 15 433 non-Parkinson syndrome participants, 13 166 were negative to CCQ, giving a specificity of 85.3%. Among the 2872 participants screened positive, 605 were diagnosed with Parkinson syndrome, and their PPV was 21.1%. For the 13 258 participants screened negative on CCQ, 92 were diagnosed with Parkinson syndrome and 13 166 did not have Parkinson syndrome, leading to a NPV of 99.3%. CCQ appeared to have satisfactory statistical parameters to serve as a screening instrument for Parkinson syndrome in this rural Chinese population. Further studies may prove the utility of this short questionnaire in Parkinson syndrome screening among Chinese populations including those residing in rural areas.


A novel potassium channel in photosynthetic cyanobacteria.
Elucidation of the structure-function relationship of a small number of prokaryotic ion channels characterized so far greatly contributed to our knowledge on basic mechanisms of ion conduction. We identified a new potassium channel (SynK) in the genome of the cyanobacterium Synechocystis sp. PCC6803, a photosynthetic model organism. SynK, when expressed in a K(+)-uptake-system deficient E. coli strain, was able to recover growth of these organisms. The protein functions as a potassium selective ion channel when expressed in Chinese hamster ovary cells. The location of SynK in cyanobacteria in both thylakoid and plasmamembranes was revealed by immunogold electron microscopy and Western blotting of isolated membrane fractions. SynK seems to be conserved during evolution, giving rise to a TPK (two-pore K(+) channel) family member which is shown here to be located in the thylakoid membrane of Arabidopsis. Our work characterizes a novel cyanobacterial potassium channel and indicates the molecular nature of the first higher plant thylakoid cation channel, opening the way to functional studies.


[Charles Bonnet syndrome: report of three cases].
Charles Bonnet syndrome is characterized by the presence of visual hallucinations associated with loss of vision. We report three patients aged 74, 84 and 80 years (two women) with a severe loss of vision due to ocular diseases and silent visual hallucinations, that they recognized as unreal. Two patients felt that the hallucinations were ominous. Years later, two suffered a probable Alzheimer's disease (AD). One of them had a mild cognitive impairment when the syndrome appeared, that evolved into an AD with psychosis. This syndrome is not uncommon in older patients with loss of vision and it is probably underdiagnosed. Its pathogenesis is probably a cortical deafferentation. The content of the visual hallucinations (faces, landscaped, and so on) coincides with the activation of different areas of the visual association cortices.


Allergy and Venous Thromboembolism: A Casual or Causative Association.
Allergic diseases are very frequent conditions worldwide. The pathogenesis of allergic reactions and venous thromboembolism (VTE) shares several risk factors and predisposing conditions. In particular, the concentration of immunoglobulin E (IgE) is considerably increased in patients with allergic diseases, and this immunoglobulin exert many prothrombotic and antifibrinolytic activities, especially through interaction with mast cells. Therefore, this narrative review is aimed to provide an overview of the current scientific evidence supporting a potential relationship between allergy and the risk of VTE. Although no prospective studies have been published so far, the evidence provided by six large cross-sectional studies and several case reports support the existence of an unquestionable epidemiological association between different allergic diseases (especially atopy, asthma, and celiac disease) and venous thrombosis. Two additional investigations reported that the concentration of IgE might predict the onset of severe complications of pulmonary embolism such as pulmonary infarction and pleural fluid accumulation. Therefore, the existence of a convincing epidemiologic link between allergy and VTE paves the way to future investigations aimed to establish whether the prevention or treatment of allergic diseases might be regarded as an effective measure to lower the risk of VTE.


Saturation analysis of cellular retinoid binding proteins: application to retinoic acid resistant human neuroblastoma cells and to human tumors.
A method for saturation analysis of cellular retinoic acid and retinol binding proteins, CRABP and CRBP, respectively, in cultured cells and human tumor samples, and its application to a retinoic acid resistant subline of the human neuroblastoma LA-N-5 cell line is described. Assessment of retinoid binding was accomplished by incubation of cytosols with increasing concentrations of [3H]retinoid (28-43 Ci/mmol; 1 Ci = 37 GBq) for 24 h. Bound retinoid was separated from free retinoid by adsorption with dextran-coated charcoal. Nonspecific binding was quantitated in parallel incubations which had been treated with p-chloromercuribenzene sulfonate (PCMBS), resulting in selective elimination of sulfhydryl-dependent ligand binding to both CRABP and CRBP. Quantitation was accomplished by Scatchard analysis of specific (PCMBS sensitive) binding. Employing this technique, specific retinoid binding was attributed to the presence of 2S macromolecules which displayed the known properties of CRABP and CRBP, namely ligand specificity, saturability, high ligand affinity, and PCMBS sensitivity. The apparent dissociation constants (Kd) for retinoic acid binding in cytosols prepared from murine 3T6 fibroblasts, rat testes, and a human ovarian tumor were 7, 11, and 35 nM, respectively. These preparations also bound retinol with high affinity, exhibiting Kds of 12, 26, and 48 nM, respectively. A retinoic acid resistant subline of LA-N-5 cells designated LA-N-5-R9 was established by long-term culture in the presence of 10(-6) M retinoic acid. This subline is resistant to the effects of retinoic acid in that it requires a 10-fold higher concentration of retinoic acid for 50% inhibition of growth than the parent line and displays no retinoic acid induced morphologic differentiation. Saturation analysis of CRABP in the parent and resistant subline reveal no significant alteration in either CRABP content or affinity. These results indicate that resistance to retinoic acid induced differentiation in LA-N-5-R9 occurs distal to CRABP binding or that CRABP does not mediate this response to retinoic acid.


Optimal Scene Time to Achieve Favorable Outcomes in Out-of-hospital Cardiac Arrest: How Long Is Too Long?
Background Despite advances in resuscitation science and public health, out-of-hospital cardiac arrest (OOHCA) cases have an average survival rate of only 12% nationwide, compared to 24.8% of cases occurring in hospital. Many factors, including resuscitation interventions, contribute to positive patient outcomes and have, therefore, been studied in attempts to optimize emergency medical services (EMS) protocols to achieve higher rates of return of spontaneous circulation (ROSC) in the field. However, no consensus has been met regarding the appropriate amount of time for EMS to spend on scene. Aim A favorable outcome is defined as patients that achieved the combination of ROSC and a final disposition of "ongoing resuscitation in the emergency department (ED)." The primary purpose of this preliminary study was to determine the scene time interval (STI) in which American urban EMS systems achieved the highest rates of favorable outcomes in non-traumatic OOHCAs. Methods All EMS-related data, including demographics, presenting rhythm, airway management, chemical interventions, and ROSC were recorded using a standardized EMS charting system by the highest-ranking EMS provider on the ambulance. The reports were retrospectively collected and analyzed. Conclusion Our data suggest that the optimal 20-minute STI for OOHCA patients in an urban EMS system is between 41 and 60 minutes. Interestingly, the 10-minute interval within the 41-60 minute cohort that provided the highest rate of ROSC was between 41 and 50 minutes. Generally, the longer the STI, the greater the percentage of favorable outcomes up to the 50-minute mark. Once past 50 minutes, a phenomenon of diminishing return was observed and the rates of favorable outcomes sharply declined. This suggests a possible "sweet spot" that may exist regarding the optimal scene time in a cardiac arrest encounter. Significant differences between the average number of interventions per patient were found, however, many confounding factors and the limited data set make the results difficult to generalize.


Tobacco control efforts in the Gulf Cooperation Council countries: achievements and challenges.
This paper reports a review into the current state of tobacco use, governance and national commitment for control, and current intervention frameworks in place to reduce the use of tobacco among the populations of the Gulf Cooperation Council (GCC) member states and Yemen. It further reviews structured policy-oriented interventions (in line with the MPOWER package of 6 evidence-based tobacco control measures) that represent government actions to strengthen, implement and manage tobacco control programmes and to address the growing epidemic of tobacco use. Our findings show that tobacco control in the GCC countries has witnessed real progress over the past decades. These are still early days but they indicate steps in the right direction. Future investment in implementation and enforcement of the Framework Convention on Tobacco Control, production of robust tobacco control legislation and the establishment of universally available tobacco cessation services are essential to sustain and strengthen tobacco control in the GCC region.


The association between school exam grades and subsequent development of bipolar disorder.
Prior studies have indicated that both high and low school grades are associated with development of bipolar disorder (BD), but these studies have not adjusted for parental history of mental disorder, which is a likely confounder. Furthermore, the association between school grades and bipolar I disorder (BD-I) has not been studied. Therefore, we aimed to study the association between school exam grades and subsequent development of BD and BD-I while adjusting for parental history of mental disorder. We conducted a register-based nationwide cohort study following 505 688 individuals born in Denmark between 1987 and 1995. We investigated the association between school exam grades and development of BD or BD-I with a Cox model adjusting for family history of mental disorder and other potential confounders. During follow-up, 900 individuals were diagnosed with BD and 277 of these with BD-I. The risk for BD and BD-I was significantly increased for individuals not having completed the exams at term [adjusted hazard ratio (aHR) for BD (aHR=1.71, 95% CI: 1.43-2.04) and for BD-I (aHR=1.57, 95% CI: 1.13-2.19)]. Also, having low exam grades in mathematics was associated with increased risk of both BD (aHR=2.41, 95% CI: 1.27-4.59) and BD-I (aHR=2.71, 95% CI: 1.41-5.21). Females with very high exam grades in Danish (percentile group>97.7) had a significantly increased risk of BD-I (aHR=2.49, 95% CI: 1.19-5.23). The potential to develop BD seems to affect the school results of individuals negatively even before BD is diagnosed - with females having the potential to develop BD-I as a possible exception.


Stability of carotenoids and tocopherols in ready-to-eat baby-leaf lettuce and salad rocket during low-temperature storage.
Minimally processed ready-to-eat baby-leaf vegetables (BLVs) are the most convenient source to include the health beneficial bioactive in the daily diet. In the present study, the visual quality and storage stability of carotenoids, tocopherols were investigated in lettuce (green and red romaine) and salad rocket BLVs. The commercially packed samples of BLVs were stored at 0 °C and 4 °C in dark conditions and analyzed after 0, 2, 4, 8 and 12 days of storage. All the studied samples were found in better visual quality up to eight days of storage at both the temperatures. In most cases, the quality was correlated with the chlorophyll contents. The highest significant (p < 0.05) positive changes in total carotenoids and tocopherols were observed in samples stored at 4 °C. Also, carotenoids and tocopherols are maximum stable in green and red romaine lettuce, respectively.


Effect of temperature and protein concentration on the protein types within the ultracentrifugation supernatant of liquid micellar casein concentrate.
Liquid micellar casein concentrate (MCC) is an ideal milk-based protein ingredient for neutral-pH ready-to-drink beverages. The texture and mouthfeel of liquid MCC-based beverages depend on the beverage protein content as well as the composition of soluble proteins in the aqueous phase around the casein micelle. The objective of this study was to determine the composition of soluble proteins in the aqueous phase around the casein micelles in skim milk and liquid MCC containing 7.0 and 11.6% protein content. Skim milk was pasteurized and concentrated to 7% protein content by microfiltration and then to 18% protein content by ultrafiltration. The 18% MCC was then serially diluted with distilled water to produce 11.6 and 7.0% protein MCC. Skim milk, 7.0% MCC, and 11.6% MCC were ultracentrifuged at 100,605 x g for 2 h at 4, 20 and 37°C. The ultracentrifugation supernatants were collected to represent the aqueous phase around the casein micelle in MCC solutions. The supernatants were analyzed by Kjeldahl to determine the crude protein, casein, and casein as a percentage of crude protein content, and by sodium dodecyl sulfate PAGE to determine the composition of the individual proteins. Most of the proteins in MCC supernatant (about 45%) were casein proteolysis products. The remaining proteins in the MCC supernatant consisted of a combination of intact αs-, β-, and κ-caseins (about 40%) and serum proteins (14 to 18%). Concentrations of αs-casein and β-casein in the supernatant increased (P < 0.05) with decreasing temperature, especially at higher protein concentrations. Temperature and interaction between temperature and protein explained about 80% of the variation in concentration of supernatant αs- and β-caseins. Concentration of supernatant κ-casein, casein proteolysis products, and serum protein increased (P < 0.05) with increasing MCC protein concentration, and MCC protein concentration explained most of the variation in supernatant κ-casein, casein proteolysis products, and serum protein concentrations. Predicted MCC apparent viscosity was positively associated with the dissociation of αs- and β-caseins. Optimal beverage viscosity could be achieved by controlling the dissociation of these proteins in MCC.


The efficacy of bromocriptine in patients with ovulatory dysfunction and normoprolactinemic galactorrhea.
The response to bromocriptine therapy of 12 infertile women with ovulatory dysfunction and euprolactinemic galactorrhea was studied. Four of the subjects had anovulation, four had oligo-ovulation, and four had delayed ovulation. Serum PRL levels in all 12 subjects were less than 20 ng/ml. Normal ovulation occurred at least once in all of the patients on bromocriptine therapy and in 38 of 41 (92%) of the cycles. Seven patients (58%) conceived promptly with bromocriptine therapy, and all subjects had cessation of galactorrhea within 1 month of the onset of therapy. The seven pregnancies included five normal term vaginal deliveries, one premature vaginal delivery, and one tubal pregnancy. The results of this study should be considered preliminary but suggest that the presence of euprolactinemic galactorrhea in patients with ovulatory dysfunction may still represent a covert disorder of PRL physiologic factors. The prompt correction of these ovulation disturbances gives supporting evidence for this hypothesis and suggests that a short trial of bromocriptine therapy may be warranted after minimal blood sampling. The differential outcome between our group of patients produces further evidence that variable mechanisms may be operative.


Strategy to Enhance the Luminescence of Lanthanide Ions Doped MgWO4 Nanosheets through Incorporation of Carbon Dots.
Highly fluorescent nanomaterials have shown great potential application in optics area. However, further improving their fluorescence properties especially for nanomaterials still remains a challenge. Specifically, luminescence of lanthanide (Ln) ions doped two-dimensional (2D) nanosheets is seldom studied. Herein, MgWO4:Ln3+ (Ln = Eu, Tb) nanosheets were successfully synthesized via a simple hydrothermal method, and the luminescence properties of these nanosheets are obviously improved through incorporation of fluorescent carbon dots (CDs) onto the surface of MgWO4:Ln3+ (CDs@MgWO4:Ln3+) nanosheets. The obtained MgWO4:Ln3+ samples have a 2D nanosheet morphology with triclinic phase, and the morphology and phase structure can be maintained after incorporating CDs onto the nanosheets' surface. Under the excitation of UV light, the obtained MgWO4:Ln3+ nanosheets exhibit the characteristic emission of the doping ions, and the emission intensity of CDs@MgWO4:Eu3+ and CDs@MgWO4:Tb3+ nanosheets increases 2- and 7-fold compared to the corresponding samples without incorporation of CDs, respectively. This luminescent enhancement mechanism might be due to the capturing electrons by CDs and energy transfer from CDs to luminescent Ln3+. The fluorescence enhancement through incorporation of CDs provides a simple and environment-friendly strategy for further improving luminescence property of other lanthanide ions doped nanomaterials.


Premalignant alterations in the lipid composition and fluidity of colonic brush border membranes of rats administered 1,2 dimethylhydrazine.
Dimethylhydrazine (DMH) is a potent procarcinogen with selectivity for the colon. To determine whether alterations in the lipid composition and fluidity of rat colonic brush border membranes existed before the development of DMH-induced colon cancer, rats were injected s.c. with this agent (20 mg/kg body weight per wk) or diluent for 5, 10, and 15 wk. Animals were killed at these time periods and brush border membranes were prepared from proximal and distal colonocytes of each group. The "static" and "dynamic" components of fluidity of each membrane were then assessed, by steady-state fluorescence polarization techniques using limiting hindered fluorescence anisotropy and order parameter values of the fluorophore 1,6 diphenyl-1,3,5-hexatriene (DPH) and fluorescence anisotropy values of DL-2-(9-anthroyl) stearic acid and DL-12-(9-anthroyl) stearic acid, respectively. Membrane lipids were extracted and analyzed by thin-layer chromatography and gas-liquid chromatography. Phospholipid methylation activity in these membranes was also measured using S-adenosyl-L-methionine as the methyl donor. The results of these studies demonstrate that: the lipid composition and both components of fluidity of proximal DMH-treated and control membranes and their liposomes were similar at all time periods examined; at 5, 10, and 15 wk the "dynamic component of fluidity" of distal DMH-treated membranes and their liposomes was found to be higher, similar, and lower, respectively, than their control counterparts; the "static component of fluidity" of distal DMH-treated membranes and their liposomes, however, was similar to control preparations at all three time periods; and alterations in the lipid composition and phospholipid methylation activities appeared to be responsible for these differences in the "dynamic component of fluidity" at these various time periods.


Incommensurate diffusion in confined systems.
Molecular simulations corroborate the existence of the disputed window effect, i.e., an increase in diffusion rate by orders of magnitude when the alkane chain length increases so that the shape of the alkane is no longer commensurate with that of a zeolite cage. This window effect is shown to be characteristic for molecular sieves with pore openings that approach the diameter of the adsorbate. Furthermore, the physical compatibility between the adsorbate and the adsorbent has a direct effect on the heat of adsorption, the Henry coefficients, the activation energy, and the frequency factors.


Advancement in Polymer-based Carrier for DNA Vaccine.
A novel strategy that has the potential to solve the drawbacks of the present conventional vaccines is the development of DNA vaccines. DNA vaccines offer a versatile and adaptable platform for treating a wide variety of diseases, as immunization targets may be easily adjusted by altering the gene sequences encoded in the plasmid DNA delivered. Due to their ability to elicit both humoral and cellular immune responses, their stability, and the ease with which they may be produced, plasmid DNA vaccines are quickly becoming the vaccine of choice, they are frequently safer than conventional vaccinations. Despite the highly encouraging outcomes of ongoing clinical trials, these vaccines' immunogenicity is compromised by a few factors. The use of various vaccine delivery techniques, the use of various polymer-based carriers, and the use of adjuvants are some of the several approaches that might be examined to better the immunogenicity of DNA vaccines made from plasmids. These advancements taken together might allow plasmid DNA vaccines to be successfully used in clinical settings.


Prevalence of High-Risk Human Papillomavirus Genotypes among Young Women in Puerto Rico; a retrospective longitudinal study.
Background: Human Papillomavirus (HPV) is the most common sexually transmitted infection. High-risk HPV types are the main cause of cervical cancer. Annually, cervical cancer is among the top 10 cancers in Puerto Rican women, with 22% of these cases ending in death. The purpose of this study was to establish the prevalence of high-risk HPV genotypes in a large cohort of young women living in Puerto Rico. Methods: A retrospective longitudinal analysis was performed with a sample of 5,749 HPV results obtained from a clinical database of women ages 21 to 29 from 2014-2016. Results: Outcomes indicate that among those with a positive HPV result, about one-third (35.2%) had a high-risk HPV infection. Women between the ages of 21 to 23 showed the highest prevalence (40.6%) of high-risk HPV. Among genotypes HPV 16 and 18, genotype 16 was the most prevalent. Interestingly, 85.4% of results were positive for other high-risk HPV types other than 16 or 18. Of the 458 women who had at least two tests completed, 217 had an initial positive result for HPV and only 108 (49.7%) resolved the infection. Conclusions: This study confirms the high prevalence of several genotypes of high-risk HPV in young women in a large Puerto Rican sample.


Cell mechanics: principles, practices, and prospects.
Cells generate and sustain mechanical forces within their environment as part of their normal physiology. They are active materials that can detect mechanical stimulation by the activation of mechanosensitive signaling pathways, and respond to physical cues through cytoskeletal re-organization and force generation. Genetic mutations and pathogens that disrupt the cytoskeletal architecture can result in changes to cell mechanical properties such as elasticity, adhesiveness, and viscosity. On the other hand, perturbations to the mechanical environment can affect cell behavior. These transformations are often a hallmark and symptom of a variety of pathologies. Consequently, there are now a myriad of experimental techniques and theoretical models adapted from soft matter physics and mechanical engineering to characterize cell mechanical properties. Interdisciplinary research combining modern molecular biology with advanced cell mechanical characterization techniques now paves the way for furthering our fundamental understanding of cell mechanics and its role in development, physiology, and disease. We describe a generalized outline for measuring cell mechanical properties including loading protocols, tools, and data interpretation.We summarize recent advances in the field and explain how cell biomechanics research can be adopted by physicists, engineers, biologists, and clinicians alike.


Identification of molecular biomarkers associated with non-small-cell lung carcinoma (NSCLC) using whole-exome sequencing.
Significant progress has been made in the treatment of patients with pulmonary adenocarcinoma (ADCA) based on molecular profiling. However, no such molecular target exists for squamous cell carcinoma (SQCC). An exome sequence may provide new markers for personalized medicine for lung cancer patients of all subtypes. The current study aims to discover new genetic markers that can be used as universal biomarkers for non-small cell lung cancer (NSCLC). WES of 19 advanced NSCLC patients (10 ADCA and 9 SQCC) was performed using Illumina HiSeq 2000. Variant calling was performed using GATK HaplotypeCaller and then the impacts of variants on protein structure or function were predicted using SnpEff and ANNOVAR. The clinical impact of somatic variants in cancer was assessed using cancer archives. Somatic variants were further prioritized using a knowledge-driven variant interpretation approach. Sanger sequencing was used to validate functionally important variants. We identified 24 rare single-nucleotide variants (SNVs) including 17 non-synonymous SNVs, and 7 INDELs in 18 genes possibly linked to lung carcinoma. Variants were classified as known somatic (n= 10), deleterious (n= 8), and variant of uncertain significance (n= 6). We found TBP and MPRIP genes exclusively associated with ADCA subtypes, FBOX6 with SQCC subtypes and GPRIN2, KCNJ18 and TEKT4 genes mutated in all the patients. The Sanger sequencing of 10 high-confidence somatic SNVs showed 100% concordance in 7 genes, and 80% concordance in the remaining 3 genes. Our bioinformatics analysis identified KCNJ18, GPRIN2, TEKT4, HRNR, FOLR3, ESSRA, CTBP2, MPRIP, TBP, and FBXO6 may contribute to progression in NSCLC and could be used as new biomarkers for the treatment. The mechanism by which GPRIN2, KCNJ12, and TEKT4 contribute to tumorigenesis is unclear, but our results suggest they may play an important role in NSCLC and it is worth investigating in future.


Spectral phase based medical image processing.
To exploit the spectral phase characteristics of digital or digitized mammograms for early detection of microcalcifications, shape, and sizes of suspected lesions and to demonstrate its use for training radiologists to discriminate signal features in different spatially varying backgrounds. We propose two algorithms: in the phase-only image (POI) reconstruction algorithm the spectral phase of the digital mammogram is extracted from its Fourier spectrum. This is coupled with unit magnitude and inverse Fourier transformed to reconstruct the POI thus enhancing the features of interest such as microcalcifications, shape, and sizes of suspected lesions. In the algorithm for image reconstruction from a priori phase-only information, spectral phase is used to extract signal features of the digital mammogram and then this is combined with spectral magnitude that is extracted and averaged over an ensemble of unrelated digital mammograms. The results for several digital phantoms and mammograms show that POI reconstructs only high spatial frequencies related to the features such as microcalcifications, shape, and size of masses like cysts and tumors. The results on image reconstruction from a priori phase-only information demonstrate the changes in the visibility of signal features when buried in a wide variety of real world mammogram backgrounds with different densities. The POI can aid radiologists in early detection of microcalcifications, lesions, and other masses of interest in digital mammograms. This reconstruction method is self-adaptive to changes in the background. The image reconstruction from a priori phase-only information can help the radiologist as a training tool in his decision-making process. Preliminary experiments indicate the potential of the techniques for early diagnosis of breast cancer. Clinical studies on these algorithm procedures are in progress for application as a diagnostic CAD tool in digital mammography. These methods can in general be applied to other medical images such as CT and MRI images.


Levels of cyclic GMP and cyclic AMP in regenerating forelimbs of adult newts following denervation.
The effect of short-term denervation (0, 12, 24, and 72 hours) on the levels of cyclic 3'5'-guanosine monophosphate (cGMP) and cyclic 3'5'-adenosine monophosphate (cAMP) in adult newt (Notophthalmus viridescens) forelimbs at 15, 22, and 35 days of regeneration was investigated. Regenerate blastema and stump cyclic nucleotide levels were compared with those of the contralateral intact forelimb and hindlimb, with levels in the normally regenerating blastema, and with levels measured in the forelimbs of intact, nonoperated animals. Variations in cyclic nucleotide levels occurred according to regeneration stage and tissue type. Changes in level were noted immediately upon denervation and subsequently at other sample times in all regenerate and control series. Parallel fluctuations occurred in regenerate stump and contralateral intact forelimbs. Our results from nonamputated denervated and sham-denervated animals indicate that short-term, denervation-associated cyclic nucleotide fluctuations cannot be attributed solely to the loss of innervation.


Primary DQ effect in the association between HLA and neurological syndromes with anti-GAD65 antibodies.
The primary cause of neurological syndromes with antibodies against glutamic acid decarboxylase 65 (GAD65-Ab) is unknown, but genetic predisposition may exist as it is suggested by the co-occurrence in patients and their relatives of other organ-specific autoimmune diseases, notably type 1 diabetes mellitus (T1DM), and by the reports of a few familial cases. We analyzed the human leukocyte antigen (HLA) in 32 unrelated patients and compared them to an ethnically matched sample of 137 healthy controls. Four-digit resolution HLA alleles were imputed from available Genome Wide Association data, and full HLA next-generation sequencing-based typing was also performed. HLA DQA1*05:01-DQB1*02:01-DRB1*03:01 was the most frequent class II haplotype in patients (13/32, 41%). DQB1*02:01 was the only allele found to be significantly more common in patients than in controls (20/137, 15%, corrected p = 0.03, OR 3.96, 95% CI [1.54-10.09]). There was also a trend towards more frequent DQA1*05:01 among patients compared to controls (22/137, 16%; corrected p = 0.05, OR 3.54, 95% CI [1.40-8.91]) and towards a protective effect of DQB1*03:01 (2/32, 6% in patients vs. 42/137, 31% in control group; corrected p = 0.05, OR 0.15, 95% CI [0.02-0.65]). There was no significant demographic or clinical difference between DQ2 and non-DQ2 carriers (p > 0.05). Taken together, these findings suggest a primary DQ effect on GAD65-Ab neurological diseases, partially shared with other systemic organ-specific autoimmune diseases such as T1DM. However, it is likely that other non-HLA loci are involved in the genetic predisposition of GAD65-Ab neurological syndromes.


Recent developments in peptide stereoisomer separations by capillary electromigration techniques.
The stereochemistry of peptides determines their physicochemical and biological activities. Thus, analytical methods that are able to discriminate between peptide stereoisomers are important. As peptides are typically hydrophilic compounds, many methods for the separation of peptide diastereomers and enantiomers have been developed by capillary electromigration techniques. Moreover, peptide enantiomers displayed unique migration behavior such as a pH-dependent change of the enantiomer migration order in CD-mediated enantioseparations in CE making them ideal compounds to study mechanistic effects of enantioseparations. The present short review summarizes recent developments in the separation of stereoisomers of peptide and peptidomimetics by capillary electromigration techniques. Moreover, recent NMR and molecular modeling studies as well as investigation on the effect of buffer additives on complex formation will be discussed as attempts to understand mechanistic aspects of peptide enantioseparations and to analyze the structure of peptide-CD complexes.


Establishment of a predictive model for short-term efficacy of transcatheter arterial chemoembolization treatment in hepatocellular carcinoma and its clinical application.
This study aimed to establish a predictive model for the presence of transcatheter arterial chemoembolization (TACE) resistance in hepatocellular carcinoma (HCC) Barcelona Clinic Liver Cancer classification stage B or stage C4 (BCLC B/C) and further verify its accuracy, enabling clinicians to accurately predict the efficacy of TACE and propose individualized therapy to further optimize multidisciplinary team plans. A retrospective database review was performed, including 191 patients (39 females and 152 males; aged 50-76 years with a mean age of 55 ± 10 years) who received three consecutive TACE sessions for treating HCC (BCLC B/C) in 1 month apart, for a total of 3 months. After three TACE treatments, a total of 95 patients among the 191 patients showed TACE resistance, 112 cases were randomly selected to build the modeling group, and the remaining 79 cases formed a verification group. Some prognostic risk factors were obtained through clinical observation. Then, univariate and multivariate analyses were performed using the logistic proportional hazard regression model. Based on multivariate analysis results, a risk-index model was established and its effects on predicting the incidence of TACE resistance of those patients were evaluated. Based on the results of the multivariate analysis, to show that were four-independent factors affecting a prognosis of patients with TACE resistance after three consecutive TACE treatment in 3 months, which were red blood cell (RBC), neutrophil count (NC), model for end-stage liver disease (MELD), and Apoprotein A1. The risk index model established according to the above factors was expressed as a predictive indice (PI), and PI = -3.79 + 4.916 × RBC - 1.547 × NC - 4.142 × MELD + 10.789 × ApoA1. The area under the receiver operating characteristic curves (AUROC) of PI of the modeling group was 0.986, which was significantly higher than that of each component index in the equation. The specificity of the modeling group was 86.3%, and the sensitivity was 70.4%, and 43 of 61 patients with PI ≤ 5.36 (70.5%) had a good outcome 3 months after consecutive TACE. From of the PI, among 51 patients with TACE resistance after consecutive TACE, 32 (62.7%) had a PI > 5.36, and only 19 patients were misidentified as having TACE resistance because of their PI > 5.36. The accuracy was 82.1%. The specificity of the validation group was 85.9%, and the sensitivity was 77.9%. The disease was under control in 29 of the 35 patients with PI ≤ 5.36 (82.9%) after consecutive TACE. According to PI, among the 44 patients with TACE resistence after consecutive TACE, 38 (86.4%) had PI > 5.36, and only 6 patients were misidentified as TACE resistance due to their PI > 5.36, with an accuracy of 87.3%, respectively. According to the PI of this study, we investigated the risk factors and protective factors to estimate the presence of TACE resistance after three consecutive TACE treatment, so as it could help doctors to evaluate the patientet condition and choose more reasonable treatment methods.


Liquid chromatography electrospray mass spectrometry with variable fragmentor voltages gives simultaneous elemental and molecular detection of arsenic compounds.
A single quadrupole high performance liquid chromatography electrospray mass spectrometry system with a variable fragmentor voltage facility was used in the positive ion mode for simultaneous recording of elemental and molecular mass spectral data for arsenic compounds. The method was applicable to the seven organoarsenic compounds tested: four arsenic-containing carbohydrates (arsenosugars), a quaternary arsonium compound (arsenobetaine), dimethylarsinic acid, and dimethylarsinoylacetic acid. It was not suitable for the two inorganic arsenic species arsenite and arsenate. In the case of arsenosugars, qualifying ion data for a characteristic common fragment (m/z 237) was also simultaneously obtained. The method was used to identify and quantify the major arsenosugars in crude extracts of two brown algae.