Outbreak of chickenpox in a Union Territory of North India.
Primary infection with a varicella-zoster virus (VZV) leads to chickenpox. Though the incidence of the disease has decreased in many developed countries due to the introduction of the varicella vaccine, outbreaks continue to occur in developing countries. The present study reports an outbreak of varicella in an urbanised village in the vicinity of Chandigarh City in North India in November 2013. The outbreak was confirmed by the detection of VZV IgM antibodies in serum samples of clinically suspected patients. Vesicular fluid samples were collected from 8 patients with active lesions and tested for VZV DNA by polymerase chain reaction. Blood samples were also collected from 17 healthy controls residing in the same locality and tested for the presence of VZV IgM and IgG antibodies. A total of 18 cases occurred, and the majority of them (67%) were <15 years of age. Of 17 samples collected from patients with the clinically suspected disease, 13 (76.5%) showed the presence of VZV IgM antibodies. Of the healthy controls, 6 were VZV IgM positive and 4 of them developed symptomatic disease on follow-up. VZV DNA was positive in 5/8 (62.5%) of the patients. In one patient, VZV DNA was detected in the absence of an IgM antibody response. The introduction of varicella vaccine in the universal immunisation programme of India may help to prevent these outbreaks; however, the cost-benefit analysis needs to be carried out before making such policies.


Abnormal pinocytosis and valence-variable behaviors of cerium suggested a cellular mechanism for plant yield reduction induced by environmental cerium.
The environmental safety of cerium (Ce) applications in many fields has been debated for almost a century because the cellular effects of environmental Ce on living organisms remain largely unclear. Here, using new, interdisciplinary methods, we surprisingly found that after Ce(III) treatment, Ce(III) was first recognized and anchored on the plasma membrane in leaf cells. Moreover, some trivalent Ce(III) was oxidized to tetravalent Ce(IV) in this organelle, which activated pinocytosis. Subsequently, more anchoring sites and stronger valence-variable behavior on the plasma membrane caused stronger pinocytosis to transport Ce(III and IV) into the leaf cells. Interestingly, a great deal of Ce was bound on the pinocytotic vesicle membrane; only a small amount of Ce was enclosed in the pinocytotic vesicles. Some pinocytic vesicles in the cytoplasm were deformed and broken. Upon breaking, pinocytic vesicles released Ce into the cytoplasm, and then these Ce particles self-assembled into nanospheres. The aforementioned special behaviors of Ce decreased the fluidity of the plasma membrane, inhibited the cellular growth of leaves, and finally, decreased plant yield. In summary, our findings directly show the special cellular behavior of Ce in plant cells, which may be the cellular basis of plant yield reduction induced by environmental Ce.


Should Esmarch bandages be used for exsanguination in knee arthroscopy and knee replacement surgery? A prospective trial of Esmarch exsanguination versus simple elevation.
In order to compare the adequacy of exsanguination produced by Esmarch bandages with that produced by simple elevation for 2 min, a blind randomized prospective trial was undertaken in 50 patients undergoing total knee replacement surgery and 50 patients undergoing knee arthroscopy surgery. The mean blood loss during total knee replacement was significantly greater in the group exsanguinated by elevation (P < 0.01). The haematocrit of samples of the arthroscopy drainage fluid was consistently less than 1%, irrespective of the method of exsanguination used. None of the operating surgeons reported that they considered that either knee replacement surgery or arthroscopic knee surgery had been made any more difficult by the use of elevation as a means of exsanguination. In view of the established risks of using Esmarch bandages, we would suggest that the use of this method of exsanguination in these fields of orthopaedic surgery is not justified.


Asymmetrical linear structures including three-electron hemibonds or other interactions in the (ABA)-type triatomic cations: Ne3+, (He-Ne-He)+, (Ar-Ne-Ar)+, (Ar-O-Ar)+, (He-O-He)+, and (Ar-He-Ar)+.
By the counterpoise geometry optimization at the level of CCSD(T)aug-cc-pVDZ, the asymmetrical linear structures with all the real frequencies were obtained for the triatomic cations of (ABA)+ type: Ne3+, (He-Ne-He)+, (Ar-Ne-Ar)+, (Ar-He-Ar)+, (He-O-He)+, and (Ar-O-Ar)+. The validity of this optimization method is confirmed by comparing with the method of the potential-energy surface for the calculations of Ne3+ and (He-Ne-He)+. Using the molecular-orbital theory, it is found that the interaction within the triatomic cations is dominated by the contribution from the first two atoms while the contribution from the third atom is small. This result is justified as a direct consequence of forming an asymmetrical linear structure. Specifically, four types of interaction within the triatomic cations are identified: three-electron sigma-type hemibond, three-electron pi-type hemibond, two-electron sigma bond, and the attraction between cation and atoms. For Ne3+, (He-Ne-He)+, and (He-O-He)+ clusters, it is shown that the electron correlation effect supports the asymmetry.


Limbs anthropometry of singleton Chinese newborns of 28-42 weeks' gestation.
Abnormalities of limbs are important features of some syndromes recognizable at birth. The purpose of this study was to establish normal standards of limbs including arm length, arm circumference, upper arm length, lower arm length, leg length, thigh circumference, upper leg length, and lower leg length. 10,226 infants (5,422 males, 4,804 females) with gestation 28-42 weeks from 12 hospitals were included. The LMS method using maximum penalized likelihood was used to perform model fitting of the anthropometric centiles for these parameters. This study provided the first set of references for the limbs of the infants by gestation and gender. Racial differences were found when comparing with other populations. The parameters are useful for evaluation of morphologic disorders involving the limbs.


A comparison of roxatidine and ranitidine for the acute treatment of duodenal ulcer.
Roxatidine acetate is a new histamine H2-antagonist of about twice the potency of ranitidine on a weight-for-weight basis. Two hundred and thirty-two patients participated in a double-blind randomized trial of duodenal ulcer healing comparing 300 mg ranitidine nocte with 150 mg roxatidine nocte. Endoscopy was repeated fortnightly to 4 weeks in each of four participating centres. Usual exclusion criteria applied but NSAID users were allowed. There were no important demographic differences between treatment recipients. Three analyses were used: protocol (dropouts and violators not included), intention-to-treat I (dropouts considered failures), and intention-to-treat II (dropouts considered failures, but violators outcome included). Healing rates differed markedly (but not significantly) with each analysis. After 2 weeks of treatment ulcers had healed in 51% versus 45% using the intention to treat I analysis with roxatidine and ranitidine, respectively; by the protocol analysis the healing proportions were 60% and 55%. These differences between treatments were not significant. After 4 weeks of treatment healing rates ranged from 71% to 83% on roxatidine and between 69% and 84% on ranitidine depending on the analysis. Differential healing proportions of smokers and non-smokers were non-significant (83% vs. 79%). Both drugs were well tolerated and adverse events were similar with each agent. Roxatidine should prove as effective as ranitidine for acute duodenal ulcer treatment.


Nonlinear Exceptional Points with a Complete Basis in Dynamics.
Exceptional points (EPs) are special spectral singularities at which two or more eigenvalues, and their corresponding eigenvectors, coalesce and become identical. In conventional wisdom, the coalescence of eigenvectors inevitably leads to the loss of completeness of the eigenbasis. Here, we show that this scenario breaks down in general at nonlinear EPs (NEPs). As an example, we realize a fifth-order NEP (NEP_{5}) within only three coupled resonators with both a theoretical model and simulations in circuits. One stable and another four auxiliary steady eigenstates of the nonlinear Hamiltonian coalesce at the NEP_{5}, and the response of eigenfrequency to perturbations demonstrates a fifth-order root law. Intriguingly, the biorthogonal eigenbasis of the Hamiltonian governing the system dynamics is still complete, and this fact is corroborated by a finite Petermann factor instead of a divergent one at conventional EPs. Consequently, the amplification of noise, which diverges at other EPs, converges at our NEP_{5}. Our finding transforms the understanding of EPs and shows potential for miniaturizing various key applications operating near EPs.


The in vivo and in vitro phase I metabolism of FYL-67, a novel oxazolidinone antibacterial drug, studied by LC-MS/MS.
In our previous study, FYL-67, a novel linezolid analogue with the morpholinyl ring replaced by a 4-(pyridin-2-yl)-1H-pyrazol-1-yl group, was demonstrated to own an excellent activity against Gram-positive organisms,such as methicillin-resistant Staphylococcus aureus (MRSA). However, metabolic biotransformation was not investigated. This study was performed to identify the phase I metabolites of FYL-67 using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The chemical structures were confirmed by comparison with corresponding chemical standards obtained internal. Primary elucidation of the metabolic pathway of FYL-67 in vitro was performed using liver preparations (microsomes and hepatocytes) from rats and humans, and SD (Sprague Dawley, rat, rattus norvegicus) rats were used for the study of in vivo approach. To the end, two metabolites (M1 and M2 ) were detected after in vitro as well as in vivo experiments. Based on LC-MS/MS analyses, the metabolites were demonstrated to be 5-(aminomethyl)-3-(3-fluoro-4-(4-(pyridin-2-yl)-1H-pyrazol-1-yl)phenyl)oxazolidin-2-one (M1 ) and 3-(3-fluoro-4-(4-(pyridin-2-yl)-1H-pyrazol-1-yl)phenyl)-5-(hydroxymethyl)oxazolidin-2-one (M2 ). Amide hydrolysis at acetyl group of FYL-67 leading to the formation of M1 was observed and suggested to play a major role in both in vivo and in vitro phase I metabolism of FYL-67. M1 was demonstrated to undergo a further oxidation to form M2 . In addition, the results indicated no species difference existing between rats and humans. The outcomes of our research can be utilized for the development and validation of the analytical method for the quantification of FYL-67 as well as its metabolites in biological samples. Furthermore, it is helpful to conduct studies of pharmacodynamics and toxicodynamics. Copyright © 2015 John Wiley & Sons, Ltd.


Natriuretic peptide regulation of endochondral ossification. Evidence for possible roles of the C-type natriuretic peptide/guanylyl cyclase-B pathway.
The natriuretic peptide family consists of three structurally related endogenous ligands: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). The biological actions of natriuretic peptides are thought to be mediated through the activation of two guanylyl cyclase (GC)-coupled receptor subtypes (GC-A and GC-B). In this study, we examined the effects of ANP and CNP, which are endogenous ligands for GC-A and GC-B, respectively, on bone growth using an organ culture of fetal mouse tibias, an in vitro model of endochondral ossification. CNP increased the cGMP production much more potently than ANP, thereby resulting in an increase in the total longitudinal bone length. Histological examination revealed an increase in the height of the proliferative and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP. The natriuretic peptide stimulation of bone growth, which was mimicked by 8-bromo-cGMP, was inhibited by HS-142-1, a non-peptide GC-coupled natriuretic peptide receptor antagonist. The spontaneous increase in the total longitudinal bone growth and cGMP production was also inhibited significantly by HS-142-1. CNP mRNA was expressed abundantly in fetal mouse tibias, where no significant amounts of ANP and BNP mRNAs were detected. A considerable amount of GC-B mRNA was present in fetal mouse tibias. This study suggests the physiologic significance of the CNP/GC-B pathway in the process of endochondral ossification.


Freud's "analytic pact": the standard therapeutic alliance.
Freud's "analytic pact," as the final therapeutic model he evolved (1937, 1940), places the fundamental rule in a two-person structural framework that operates in a continuum between the inner reality and outer reality of both patient and analyst as these come to center in the analytic situation. To Freund's basic definition of psychoanalysis as related to resistance and transference, a third component is added, the collaboration that has been a feature of the treatment since the beginning. The alliance postulated by the pact relates a helpful physician to a sufferer in a carefully regulated operational field and atmosphere suitable for a particular technique and therapeutic goal. Actually the alliance may be described from the aspect of component combinations as described in different frameworks--structural, topographic, developmental, realistic, adaptive, etc. In diverse forms of analytic or analytically oriented forms of therapy, selected aspects of the alliances receive greater prominence--but a fully informed analytic therapy retains contact with all the elements involved. Organizational aspects of the fundamental rule with respect to the flow of associations and the transient and structured interactions of patient and physician are examined with regard to their dynamic and linguistic features.


Astrocyte development and heterogeneity.
Astrocytes have many roles within the brain parenchyma, and a subpopulation restricted to germinal niches functions as neural stem cells (NSCs) that produce various types of neuronal progeny in relation to spatiotemporal factors. A growing body of evidence supports the concept of morphological and molecular differences between astrocytes in different brain regions, which might relate to their derivation from regionally patterned radial glia. Indeed, the notion that astrocytes are molecularly and functionally heterogeneous could help explain how the central nervous system (CNS) retains embryonic positional information into adulthood. Here, we discuss recent evidence for regionally encoded functions of astrocytes in the developing and adult CNS to provide an integrated concept of the origin and possible function of astrocyte heterogeneity. We focus on the regionalization of NSCs in the ventricular-subventricular zone (V-SVZ) of the adult mammalian brain and emerging evidence for a segmental organization of astrocytes in the developing spinal cord and forebrain. We propose that astrocytes' diversity will provide fundamental clues to understand regional brain organization and function.


MUC5AC and a Glycosylated Variant of MUC5B Alter Mucin Composition in Children With Acute Asthma.
Diffuse airway mucus obstruction is an important feature of severe and fatal asthma. MUC5AC and MUC5B are the principal gel-forming mucins found in airway mucus. The mucin composition of airway mucus likely affects its functional properties. We quantified the principal airway mucins MUC5AC and MUC5B in the sputum of age-matched children with acute and stable asthma and healthy control subjects by using Western blotting. Sputum samples from 38 children (13 with acute asthma, 15 with stable asthma, 10 control subjects) were obtained. Sputum MUC5AC concentrations were 7.6 μg/mL in control subjects, 22.4 μg/mL in those with stable asthma (P = .17), and 44.7 μg/mL in those with acute asthma (P < .05). MUC5B concentrations showed less variation, with 238.5, 208.4 and 165.9 μg/mL in control subjects, those with stable asthma, and those with acute asthma, respectively. The greater MUC5AC concentration in those with acute asthma resulted in a significantly altered MUC5B:MUC5AC ratio between control subjects and those with acute asthma (P < .05). Significant differences in MUC5B glycoforms were present between the groups, with the low-charge-only glycoform being found uniquely in those with acute asthma. Increased MUC5AC and the presence of a low-charge-only MUC5B glycoform significantly altered mucin composition in children with acute asthma. These changes may be important contributory factors to the airway mucus obstruction observed during acute asthma.


An approach to postembedding staining of protein (immunoglobulin) antigen embedded in plastic: prerequisites and limitations.
A method is described for performing postembedding staining of protein (immunoglobulin) antigen embedded in styrene-methacrylate resin. Fixation of specimens in a combination of 4% paraformaldehyde and 0.2% picric acid and washing in buffer containing 7% sucrose, followed by abrupt dehydration with absolute acetone in the cold preserved the antigenicity, although in a masked form. The masked antigenicity could be reexposed by treatment with nonspecific protease. Staining with fluorescent-, peroxidase-, or ferritin-labeled antibodies on semi- and ultrathin sections resulted in specific localization of the antigen. We applied this technique to the localization of rabbit immunoglobulin in specimens of renal tissue obtained from rats with anti-glomerular basement membrane nephritis; we also localized human IgG in a renal biopsy specimen. The prerequisites for recovery of antigenicity are such that preservation of tissue structure at the light microscopic level is good, but relatively poor at the electron microscopic level.


[Effect of oxygen-increased respirator on SaO2 and heart rate under plateau environment].
To study effects of oxygen-increased respirator on blood oxygen saturation (SaO2) and heart rate under altitude hypoxic environment. Nine subjects were carried to the plateau of 3700 m by air for the first time, and then four trials were carried out two hours later. First, SaO2 and heart rate were examined during rest without oxygen-increased respirators, and then the examination was repeated by using the respirators. Second, the examinations were repeated during loaded exercise test without respirators. After rest for one hour, test of using the respirators during motion was carried out finally. During rest, after using respirators, the level of SaO2 increased significantly while heart rate decreased notably (P<0.05) than those without respirators. During loaded-bicycle exercise, after using respirators, the level of SaO2 increased significantly (P<0.05) than that without respirators, while heart rate didn't show significant difference (P>0.05). But, the recoveries of heart rate after three minutes and fives minutes were better than those without respirators (P<0.05). Oxygen-increased respirator can improve the capacity of workload under altitude hypoxic environment. It can promote the acclimation to high altitude.


Human immunological response to mouse monoclonal antibodies in the treatment or diagnosis of malignant diseases.
An overview of the literature is presented concerning the formation, detection, incidence and effect of the human immunoglobulin response on immunoscintigraphy. The following conclusions are drawn. The production of human anti-mouse antibodies (HAMAs) is associated with a diminished therapeutic response; adequate prevention of HAMA production is not yet possible; high HAMA titres give rise to rapid clearance of MoAb into the liver and marked reduction of tumour uptake which results in reduced image quality on immunoscintigraphy; alteration of antibody biodistribution is likely to be related to the in vivo formation of antibody-antibody complexes which could interfere with image quality when sequential imaging is carried out.


Control of neural stem cell adhesion and density by an electronic polymer surface switch.
Adhesion is an essential parameter for stem cells. It regulates the overall cell density along the carrying surface, which further dictates the differentiation scheme of stem cells toward a more matured and specified population as well as tissue. Electronic control of the seeding density of neural stem cells (c17.2) is here reported. Thin electrode films of poly(3,4-ethylenedioxythiophene) (PEDOT):Tosylate were manufactured along the floor of cell growth dishes. As the oxidation state of the conjugated polymer electrodes was controlled, the seeding density could be varied by a factor of 2. Along the oxidized PEDOT:Tosylate-electrodes, a relatively lower density of, and less tightly bonded, human serum albumin (HSA) was observed as compared to reduced electrodes. We found that this favors adhesion of the specific stem cells studied. Surface analysis experiments, such as photoelectron spectroscopy, and water contact angle measurements, were carried out to investigate the mechanisms responsible for the electronic control of the seeding density of the c17.2 neural stem cells. Further, our findings may provide an opening for electronic control of stem cell differentiation.


Dynamics in the p53-Mdm2 ubiquitination pathway.
The tumor suppressor p53 is highly regulated under various states of cellular stress. p53 stability is predominantly regulated through the ubiquitin-proteasomal pathway by the E3 ligase Mdm2. p53 ubiquitination is a dynamic process with Mdm2 capable of catalyzing both mono- and polyubiquitination. Additionally, deubiquitination is an important step occurring in p53 and Mdm2 stabilities. Factors such as HAUSP, p14(ARF), and MdmX play important regulatory roles in p53 ubiquitination/deubiquitination and their interplay with Mdm2 and p53 compound layers of complexity for regulating this important pathway.


The transradial approach. An increasingly used standard for coronary diagnosis and interventions.
In the 20 years since its introduction, radial access for diagnostic and interventional coronary procedures has been well validated in countless scientific studies. Nevertheless, the use of this access route varies greatly among--and even within--countries. Fear of the unknown may make some experienced interventionalists hesitant to adopt the transradial approach in spite of its proven advantages. In our review, we describe practical aspects of the transradial access, such as the role of Allen's test in patient selection and considerations on the optimal puncture technique of the radial artery. Catheter selection, anatomic variations which may complicate access, as well as strategies to avoid and/or manage possible complications are outlined. Finally, we review the literature on the reduction of access site complications by adopting the transradial approach. Even in interventions for acute myocardial infarction, transradial access can be used safely and effectively. In addition to a reduced rate of access site complications, a reduction in overall in-hospital major adverse cardiac events has been demonstrated. The advantage regarding access site complications could be seen even when closure devices were utilized for transfemoral procedures.


Methods for measuring the citations and productivity of scientists across time and discipline.
Publication statistics are ubiquitous in the ratings of scientific achievement, with citation counts and paper tallies factoring into an individual's consideration for postdoctoral positions, junior faculty, and tenure. Citation statistics are designed to quantify individual career achievement, both at the level of a single publication, and over an individual's entire career. While some academic careers are defined by a few significant papers (possibly out of many), other academic careers are defined by the cumulative contribution made by the author's publications to the body of science. Several metrics have been formulated to quantify an individual's publication career, yet none of these metrics account for the collaboration group size, and the time dependence of citation counts. In this paper we normalize publication metrics in order to achieve a universal framework for analyzing and comparing scientific achievement across both time and discipline. We study the publication careers of individual authors over the 50-year period 1958-2008 within six high-impact journals: CELL, the New England Journal of Medicine (NEJM), Nature, the Proceedings of the National Academy of Science (PNAS), Physical Review Letters (PRL), and Science. Using the normalized metrics (i) "citation shares" to quantify scientific success, and (ii) "paper shares" to quantify scientific productivity, we compare the career achievement of individual authors within each journal, where each journal represents a local arena for competition. We uncover quantifiable statistical regularity in the probability density function of scientific achievement in all journals analyzed, which suggests that a fundamental driving force underlying scientific achievement is the competitive nature of scientific advancement.


Bronchoscopic needle aspiration biopsy.
Bronchoscopic needle aspiration biopsy, which encompasses transbronchial needle aspiration, transtracheal needle aspiration, and endobronchial needle aspiration, is a minimally invasive technique used to diagnose mediastinal and pulmonary masses and to stage lung cancer patients with mediastinal lymphadenopathy. Since it is safe, accurate, and potentially cost-efficient, its use may increase in the coming years. It is important that pathologists who examine cytology specimens understand this procedure, its limitations, and ways that it may be optimized.


[Epilepsy, society and rights].
Although from the medical point of view epilepsy is considered to be a neurological disorder, this has not always been so. It was once included in the group of psychiatric disorders by the medical profession and others. In the case law of the Supreme Court, epilepsy is defined as a typical endogenous psychosis, and therefore as insanity. This would lead to its inclusion in the grounds for exoneration from criminal responsibility and has therefore been invoked as grounds for immunity from prosecution by many offenders. This has proved to be a two-edged sword, since the concept of insanity has led to these patients suffering social rejection. Medicine and Law have never found it easy to understand each other. However, now more than ever, some degree of mutual understanding is necessary when passing judgement on a person, since the Law progresses more slowly than Medicine does. Thus, today we would question a series of offences referred to in this paper, which used to be classified as insanity due to epilepsy. From a legal point of view we advocate a clear classification of epilepsy as a neurological disorder. This would doubtless lead to epileptics being more socially acceptable.


Small range distributions in the high Andes: two new species of Liaghinella (Hemiptera: Heteroptera: Reduviidae: Emesinae) from Colombia.
Liaghinella Wygodzinsky, 1966 (Hemiptera: Heteroptera: Reduviidae: Emesinae: Metapterini), is an endemic Neotropical genus with two described species, one from Jamaica and one from Colombia. In this paper we describe two additional new species from the high Andes in Colombia, Liaghinella heldamariae sp. nov from Monserrate and Villa de Leyva, and L. tuberculata sp. nov. from Chicaque Natural Park, both in the Eastern Cordillera. The new species were collected very close to the type locality of the previously known Colombian species, L. andina Forero, 2007. These two new species differ from L. andina by having both a pair of conspicuous tubercles on the posterior margin of the pronotum, and by the structure of the male and female genitalia. Species diagnosis and descriptions, digital macrophotographies, and a key to separate the species of Liaghinella are presented. A discussion on the small range distributions exhibited by the high Andean species of Liaghinella is provided.


[Causal agents of onychomycosis].
The results obtained with 307 specimens from putatively immunocompetent patients between May 1991 and May 1992 were reviewed, to determine the frequency of isolation of fungal species causing onychomycoses. Sixty eight percent of the specimen were positive for microscopic examination and/or cultures. Onychomycoses occurred with double frequency in women than in men (Table 1), and 77% of cases were diagnosed in patients aged between 30 and 70 years (Figure 1). Out of 182 patients with positive cultures, 60% were affected by dermatophytes and 39% by yeasts; molds (Aspergillus spp.) were isolated in only two cases (Table 3). Neither Corynebacterium spp., nor Malasezzia furfur were detected. In toe nails Trichophyton rubrum predominated over yeasts being isolated in 72.9% of the cases; yeasts other than Candida albicans were isolated in 12.3%, Trichophyton mentagrophytes in 10%, while Aspergillus spp., C. albicans and Epidermophyton floccosum in only 1.6%. On the other hand, in finger nails yeasts predominated: C. albicans was isolated in 46.7% of cases, other yeasts in 43.3%; and T. rubrum in the remaining 10%. Out of 41 isolations of yeasts other than C. albicans, 42% were C. parapsilosis, 16% Debaryomyces hansenii, 6% C. pulcherrima, 6% Trichosporum cutaneum and 6% C. famata (Figure 2).


Metformin exerts anti-AR-negative prostate cancer activity via AMPK/autophagy signaling pathway.
Encouraged by the goal of developing an effective treatment strategy for prostate cancer, this study explored the mechanism involved in metformin-mediated inhibition of AR-negative prostate cancer. Cell behaviors of DU145 and PC3 cells were determined by CCK8 test, colony formation experiment and scratch test. Flow cytometry was used to detect cell cycle distribution. Cell autophagy was induced with metformin, and an autophagy inhibitor, 3-MA, was used to assess the level of autophagy. Detection of LC3B by immunofluorescence was conducted to determine autophagy level. Cell proliferation, autophagy and cell cycle were examined by performing Western blot. DU145 and PC3 cell lines were transfected with AMPK siRNA targeting AMPK-α1 and AMPK-α2. Tumor formation experiment was carried out to evaluate the anti-prostate cancer effect of metformin in vivo. The inhibitory effect of metformin on the proliferation of prostate cancer cell lines was confirmed in this study, and the mechanism of such an effect was related to autophagy and the block of cell cycle at G0/G1 phase. Metformin also induced the activation of AMPK, markedly promoted expression of LC3II, and down-regulated the expression of p62/SQSTM1. Animal experiments showed that the tumor volume of metformin group was smaller, meanwhile, the levels of p-AMPK (Thr172) and LC3B were up-regulated and the Ki-67 level was down-regulated, without abnormalities in biochemical indicators. This study found that autophagy induction might be the mechanism through which metformin suppressed the growth of AR-negative prostate cancer. Moreover, the activation of AMPK/autophagy pathway might be a therapeutically effective for treating AR-negative prostate cancer in the future.


A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors.
The amino acid sequence of a major human epididymis-specific protein was deduced from the nucleotide sequence of its cloned cDNA. The encoded product showed characteristics of a secretory protein, with a signal peptide followed by a small (approximately 10-kDa), acidic (pI 4.3), and cysteine-rich polypeptide. The positions of half-cysteines suggested that it was a two-domain member of the family of 'four-disulfide core' proteins to which a number of proteinase inhibitors belong. Southern blot analyses of human genomic DNA showed that the transcripts originated from a single copy gene. Northern blot and in situ transcript hybridization specifically localized the HE4 (human epididymis gene product) mRNA to the epithelial cells of the epididymal duct, predominantly within the distal sections. A possible function in sperm maturation as indicated by amino acid similarities to extracellular proteinase inhibitors of genital tract mucous secretions is discussed in the context of its tissue-specific transcription.


Fate of Deepwater Horizon oil in Alabama's beach system: understanding physical evolution processes based on observational data.
The impact of MC252 oil on northern Gulf of Mexico (GOM) beaches from the 2010 Deepwater Horizon (DWH) catastrophe was extensive along Alabama's beaches. While considerable amount of cleanup has occurred along these beaches, as of August 2014, DWH oil spill residues continue to be found as surface residual balls (SRBs), and also occasionally as submerged oil mats (SOMs). Four years of field observations informing the fate and transport of DWH SRBs in Alabama's beach system are presented here, along with a conceptual framework for describing their physical evolution processes. The observation data show that SRBs containing MC252 residues currently remain in Alabama's beach system, although their relationship to SOMs is not fully known. Based on our field observations we conclude that small DWH SRBs are likely to persist for several years along the Alabama shoreline.


Cloning and analysis of the promoter region of CCR5, a coreceptor for HIV-1 entry.
The chemokine receptor CCR5 is a cofactor for cellular entry of macrophage-tropic strains of HIV-1. Expression of CCR5 is restricted to T cells, macrophages, and certain cell lines; however, the mechanisms controlling its expression remain largely unknown. To delineate these mechanisms, approximately 1.0 kb of DNA from the immediate 5' upstream region of CCR5 was cloned and characterized. CCR5 promoter activity was up-regulated by PMA, and a region spanning -417 to +61 relative to the transcription start site was sufficient for the basal and induced activity. DNase I footprinting assays demonstrated several protected areas within this region, and gel shift assays determined binding sites for transcriptional factors Oct-1, Oct-2, T cell factor 1alpha, and GATA1. CCR5 promoter activity was also induced by IL-2 or anti-CD3 Ab, while stimulation with anti-CD28 Ab markedly reduced CD3-mediated up-regulation of the CCR5 promoter. Flow cytometry confirmed the findings at the level of cell surface expression. Further delineation of the regulation of the CCR5 promoter will be important for a more comprehensive understanding of the pathogenesis of HIV disease.


[Doctor Anglas' observations on the presence of cytomegalic cells in macerated fetal tissues].
Early in this century, Anglas had observed in the renal tubules of a macerated fetus unusual giant structures, which turned out to be cytomegalic inclusion cells. But since he omitted to distinguish them by a suggestive term from previously known giant cells, his observation felt into oblivion. Yet, it constituted the first report on the occurrence of cytomegaly in France, and in general, the first indication of the histogenic origin of these cells, as well as of their resistance to autolysis.


Systematic psychosocial screening in a paediatric cardiology clinic: clinical utility of the Pediatric Symptom Checklist 17.
To examine the clinical utility of the Pediatric Symptom Checklist 17 for identifying psychosocial concerns and improving access to psychology services within a paediatric cardiology clinic. Parents of 561 children (aged 4-17 years) presenting for follow-up of CHD, acquired heart disease, or arrhythmia completed the Pediatric Symptom Checklist 17 as part of routine care; three items assessing parental (1) concern for learning/development, (2) questions about adjustment to cardiac diagnosis, and (3) interest in discussing concerns with a behavioural healthcare specialist were added to the questionnaire. A psychologist contacted the parents by phone if they indicated interest in speaking with a behavioural healthcare specialist. Percentages of children scoring above clinical cut-offs for externalising (10.5%), attention (8.7%), and total (9.3%) problems were similar to a "normative" primary-care sample, whereas fewer children in this study scored above the cut-off for internalising problems (7.8%; p<0.01). Sociodemographic, but not clinical, characteristics were associated with Pediatric Symptom Checklist 17 scores. 17% of the parents endorsed concerns about learning/development, and 20% endorsed questions about adjustment to diagnosis. History of cardiac surgery was associated with increased concern about learning/development (p<0.01). Only 37% of the parents expressing psychosocial concerns reported interest in speaking with a psychologist. The Pediatric Symptom Checklist 17 may not be sensitive to specific difficulties experienced by this patient population. A questionnaire with greater focus on learning/development and adjustment to diagnosis may yield improved utility. Psychology integration in clinics serving high-risk cardiac patients may decrease barriers to behavioural healthcare services.


Comparing staging by positron emission tomography with contrast-enhanced computed tomography and by pathology in head and neck squamous cell carcinoma.
This study aimed to evaluate the ability of positron emission tomography with contrast-enhanced computed tomography to correctly stage head and neck squamous cell carcinomas, in comparison with pathological staging. Positron emission tomography computed tomography was used to determine the tumour-node-metastasis classification and overall cancer stage in 85 head and neck squamous cell carcinoma patients who underwent pre-operative imaging using this modality and primary surgery between July 2010 and January 2013. Staging by positron emission tomography computed tomography was retrospectively compared with staging using pathological specimens. Agreement between imaging stage and pathological stage was examined by univariate and multivariate analysis both overall and for each primary tumour site. This imaging modality was 87.5 per cent sensitive and 44.8 per cent specific in identifying regional cervical metastases, and had false positive and false negative rates of 18.8 per cent and 8.2 per cent, respectively. The positive predictive and negative predictive values were 75.4 per cent and 65.0 per cent, respectively. Univariate and multivariate analyses revealed a significant agreement between positron emission tomography computed tomography and pathological node classification in older patients and for the oral cavity primary tumour site. There was significant agreement between both methods in the overall classification only for tumours classified as T3 or greater. Positron emission tomography computed tomography should be used with caution for the pre-operative staging of head and neck cancers because of its high false positive and false negative rates.


Experimental study on the statistic characteristics of a 3x3 RF MIMO channel over a single conventional multimode fiber.
Based on the observed random fluctuation phenomenon of speckle pattern across multimode fiber (MMF) facet and received optical power distribution across three output ports, we experimentally investigate the statistic characteristics of a 3×3 radio frequency multiple-input multiple-output (MIMO) channel enabled by mode division multiplexing in a conventional 50 µm MMF using non-mode-selective three-dimensional waveguide photonic lanterns as mode multiplexer and demultiplexer. The impacts of mode coupling on the MIMO channel coefficients, channel matrix, and channel capacity have been analyzed over different fiber lengths. The results indicate that spatial multiplexing benefits from the greater fiber length with stronger mode coupling, despite a higher optical loss.


Gender differences in the association between functional limitation and depressive symptoms: the salience of food insecurity.
The present study evaluated gender differences in the associations of functional limitation with food insecurity and depressive symptoms. Using data from 3,624 respondents ages 18to 80 years from two pooled cross-sectional cycles (2011-2012 and 2013-2014) of the National Health and Nutrition Examination Survey (NHANES), a structural equation model was estimated to assess gender differences in the association between physical limitation and food insecurity, and whether indicators of economic resources mediated an observed interaction. Results demonstrate that food insecurity accounted for about one-tenthof the association between functional limitation and depressive symptoms. Furthermore, these associations were more pronounced among women and were not explained by variation in economic resources. Food insecurity thus appears to be an indicator of psychological adversity among people with functional limitations, especially women, independent of other indicators of economic resources and hardship. Health promotion and social programs should address food insecurity as a unique dimension of adversity in efforts to improve health and well-being.


Does the prosthesis weight matter? 3D finite element analysis of a fixed implant-supported prosthesis at different weights and implant numbers.
This study evaluated the influence of prosthesis weight and number of implants on the bone tissue microstrain. Fifteen (15) fixed full-arch implant-supported prosthesis designs were created using a modeling software with different numbers of implants (4, 6, or 8) and prosthesis weights (10, 15, 20, 40, or 60 g). Each solid was imported to the computer aided engineering software and tetrahedral elements formed the mesh. The material properties were assigned to each solid with isotropic and homogeneous behavior. The friction coefficient was set as 0.3 between all the metallic interfaces, 0.65 for the cortical bone-implant interface, and 0.77 for the cancellous bone-implant interface. The standard earth gravity was defined along the Z-axis and the bone was fixed. The resulting equivalent strain was assumed as failure criteria. The prosthesis weight was related to the bone strain. The more implants installed, the less the amount of strain generated in the bone. The most critical situation was the use of a 60 g prosthesis supported by 4 implants with the largest calculated magnitude of 39.9 mm/mm, thereby suggesting that there was no group able to induce bone remodeling simply due to the prosthesis weight. Heavier prostheses under the effect of gravity force are related to more strain being generated around the implants. Installing more implants to support the prosthesis enables attenuating the effects observed in the bone. The simulated prostheses were not able to generate harmful values of peri-implant bone strain.


Retentiveness of various luting agents used with implant-supported prosthesis: an in vitro study.
Desired retrievability of cemented implant-supported fixed prosthesis makes the retentive strength of cementing agents an important consideration. The aim of the study was to evaluate the retentiveness of purposely designed implant cement and compare its retentiveness with dental cements that are commonly used with implant systems. Ten implant analogs were embedded in auto-polymerizing acrylic resin blocks and titanium abutments were attached to them. Fifty standardized copings were waxed directly on the abutment and casted. The cements used were: (1) resin-bonded zinc oxide eugenol cement, (2) purposely designed implant cement, (3) zinc phosphate cement, (4) zinc polycarboxylate cement, and (5) glass ionomer cement. After cementation, each sample was subjected to a pull-out test using universal testing machine and loads required to remove the crowns were recorded. The mean values and standard deviations of cement failure loads were analyzed using ANOVA and Bonferroni test. The mean values (± SD) of loads at failure (n = 10) for various cements were as follows (N): resin-bonded zinc oxide eugenol cement 394.62 (± 9.76), Premier implant cement 333.86 (± 18.91), zinc phosphate cement 629.30 (± 20.65), zinc polycarboxylate cement 810.08 (± 11.52), and glass ionomer cement 750.17 (± 13.78). The results do not suggest that one cement type is better than another, but they do provide a ranking order of the cements regarding their ability to retain the prosthesis and facilitate easy retrievability.


Position of nuclear medicine modalities in the diagnostic workup of cancer patients: lung cancer.
This review summarizes the current literature and tries to define the status of nuclear medicine in the clinical workup of lung cancer patients. Nuclear medicine procedures and positron emission tomography (PET) with the EMEA-approved radiopharmaceutical fluorodeo-xyglucose (FDG) are indicated for the characterization of lung lesions; the nodal staging of non-small cell lung cancer (NSCLC); the detection of distant metastases; and for the diagnosis of recurrent disease. Recent studies have shown the clinical efficacy of nuclear medicine and especially of FDG-PET in the workup of lung cancer patients and its significant impact on patients' management. Conventional nuclear medicine procedures are established for the pre-therapeutic assessment of pulmonary perfusion and function (lung perfusion and ventilation scintigraphy) and for the detection of bone metastases (skeletal scintigraphy). In studies in thousands of patients, FDG-PET has been proved to be the most accurate non-invasive diagnostic test for the characterization of lung nodules and masses. It can be recommended at least for patients with increased risk at surgery. FDG-PET should be applied in candidates for surgery of lung cancer, as mediastinoscopy may be omitted if PET shows no metastases in the mediastinum, and because FDG-PET avoids futile surgery by a more accurate selection of patients, especially by the detection of unexpected distant metastases. In candidates for thoracic radiotherapy, FDG-PET can help to exclude extrathoracic disease which needs systemic treatment and to better define the target volume for radiation therapy. The time has come for FDG-PET to find its place in new guidelines for the workup of lung cancer patients.


Efficacy of 1 week omeprazole or lansoprazole-amoxycillin-clarithromycin therapy for Helicobacter pylori infection in the Japanese population.
The effectiveness of curative therapy for Helicobacter pylori may vary according to the geographic region and patient population, thus the efficacy of each treatment regimen should be determined according to the specific patient population. However, there is no literature available concerning the efficacy of 1 week omeprazole-amoxycillin-clarithromycin (OAC) regimens for the cure of H. pylori infection in Japan. Helicobacter pylori-positive patients (224) with peptic ulcer disease or non-ulcer dyspepsia were randomized to receive one of three different omeprazole or lansoprazole-amoxycillin-clarithromycin (PPI/AC) regimens for 7 days: (1) OAC 20 regimen (n = 76), omeprazole (OPZ) 20 mg daily, amoxycillin (AMOX) 500 mg t.d.s. and clarithromycin (CAM) 200 mg b.d.; (2) LAC 30 regimen (n = 73), Lansoprazole (LPZ) 30 mg daily, AMOX 500 mg t.d.s. and CAM 200 mg b.d.; and (3) OPZ 40 regimen (n = 75), OPZ 20 b.d., AMOX 500 mg t.d.s. and CAM 200 mg b.d. Cure of the infection was determined by the [13C]-urea breath test, 1 month after completion of the treatment. Intention-to-treat based cure rates for OAC 20, LAC 30 and OAC 40 regimens were 75.0% (95% CI, 64-84%), 82.2% (95%, CI 72-90), and 80.0% (95% CI, 69-88), respectively and per-protocol based cure rates of these regimens were 79.2% (95% CI, 68-88%), 83.3% (95%, CI 73-91), and 83.1% (95% CI, 72-91%), respectively. Adverse effects, which included diarrhoea, glossitis or skin rash, were reported by 26.1% of the patients. However, these were mild and did not affect compliance. One week PPI/AC regimens for H. pylori infection with smaller proton pump inhibitors and antimicrobial dosages compared to regimens used in Western countries were revealed to provide sufficient cure rate (more than 80% by ITT analysis) with mild adverse effects in the Japanese population.


Capture of attention in selective frequency listening.
Four signal-detection experiments demonstrated robust stimulus-driven, or exogenous, attentional processes in selective frequency listening. Detection of just-above-threshold signal tones was consistently better when the, signal matched the frequency of an uninformative cue tone, even with relatively long cue-signal delays (Experiment 1) or when as few as 1 in 8 signals were at the cued frequency (Experiment 2). Experiments 3 and 4 compared performance with informative and uninformative cues. The involvement of intentional, or endogenous, processes was found to only slightly increase the size of the cuing effect beyond that evident with solely exogenous processes, although the attention band, a measure of how narrowly attention is focused, was found to be wider when cues were informative. The implications for models of auditory attention are discussed.


Altered sialylation of osteopontin prevents its receptor-mediated binding on the surface of oncogenically transformed tsB77 cells.
It has been reported previously that oncogenically transformed cells secrete different molecular forms of osteopontin (OPN), a sialic acid-rich, adhesive, phosphoglycoprotein, than OPNs secreted by their nontransformed counterparts. However, the origin of the OPN isoform secreted by the transformed cells and whether it has different physiological properties which may serve transformation-specific functions remain poorly understood. Here, we report that Rat-1 cells transformed by a temperature-sensitive mutant of Rous sarcoma virus (tsB77) secrete two discrete molecular forms of OPN, a 69-kDa OPN at the nonpermissive temperature (41 degrees C) and a 62-kDa form at the permissive temperature (34 degrees C). However, tsB77 cells at both temperatures transcribe a single 1.6 kb OPN mRNA and contain only the 69-kDa form of OPN intracellularly, suggesting that the 69-kDa OPN is modified to the 62-kDa form prior to or immediately after secretion by cells at 34 degrees C. We ruled out proteolytic cleavage, differential phosphorylation, or lack of N- or O-linked carbohydrates as the possible mechanism, but found that the 62-kDa OPN contains significantly reduced levels of sialic acid, as compared to its 69-kDa form. The binding assays using 32P-labeled OPN revealed that only the 69-kDa OPN, not its 62-kDa form, undergoes receptor-mediated localization on the cell surface, although tsB77 cells synthesize OPN receptors (alpha(v)beta3 integrins) at both permissive and nonpermissive temperatures. Furthermore, 125I-labeled purified milk OPN, which is highly sialylated and shows cell surface binding, upon digestion with neuraminidase failed to interact with the cell surface. Taken together, these results suggest that the difference between the 69-kDa and 62-kDa isoforms of OPN resides in their sialic acid content, and sialylation of OPN is crucial for its receptor-mediated binding on tsB77 cells. The data presented here demonstrate for the first time a physiological role of sialic acids in this protein, and raise the possibility that oncogenically transformed tsB77 cells may exploit the lack of OPN-receptor interactions for their invasive behavior.


Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia.
Through bibliometric analysis, we aim to comprehensively understand the research dynamics in this field, reveal key scientific research achievements and breakthrough discoveries, and provide valuable reference and guidance for future research directions. Utilizing the Web of Science, we retrieved the literature pertaining to ultrasonics-guided regional anesthesiology (1994-2022). CiteSpace and VOSviewer were used for bibliometric and knowledge mapping analysis. Our examination encompassed publication trends, authorship patterns, institutional contributions, frequently occurring keywords, keyword clustering, and emerging terminology trends. Of the 570 papers reviewed, there was a rising trend in publications each year. The main keywords in regional anesthesia were ultrasound guidance, nerve, analgesia, and pain score. Key research areas were regional anesthesia, ultrasound guidance, approach, pain score, and plane block. The U.S. led in research. Stanford University, University of Toronto, and Cork University Hospital were central institutions. Chan V was the top author with 24 articles, while Marhofer P was the most cited at 150 times. Regional anesthesia and pain medicine were the predominant journal in both publications and citations. In conclusion, research in this field consistently grew yearly, and visualization showcased trends in ultrasound-guided regional anesthesia. These visuals provided key bibliometric insights, helping researchers further explore and understand this domain.


Formation and decomposition of ethane, propane, and carbon dioxide hydrates in silica gel mesopores under high pressure.
The experimental data on decomposition temperatures for the gas hydrates of ethane, propane, and carbon dioxide dispersed in silica gel mesopores are reported. The studies were performed at pressures up to 1 GPa. It is shown that the experimental dependence of hydrate decomposition temperature on the size of pores that limit the size of hydrate particles can be described on the basis of the Gibbs-Thomson equation only if one takes into account changes in the shape coefficient that is present in the equation; in turn, the value of this coefficient depends on a method of mesopore size determination. A mechanism of hydrate formation in mesoporous medium is proposed. Experimental data providing evidence of the possibility of the formation of hydrate compounds in hydrophobic matrixes under high pressure are reported. Decomposition temperature of those hydrate compounds is higher than that for the bulk hydrates of the corresponding gases.


Long-retained metabolites of delta9- and delta8-tetrahydrocannabinols identified as novel fatty acid conjugates.
Long-retained metabolites of delta9-tetrahydrocannabinol (delta9-THC) and delta8-tetrahydrocannabinol (delta8-THC) previously detected in the liver, spleen, fat, and bone marrow of the rat after I.V. or I.P. injections of 14C-delta8-THC or 14C-delta9-THC, have been identified as fatty acid conjugates of 11-hydroxy-delta9-THC and 11-hydroxy-delta8-THC. Characterization of the metabolites was facilitated by their large-scale in vitro production from 11-hydroxy-delta9-THC and 11-hydroxy-delta8-THC with a rat-liver microsomal enzyme system. Conjugation of long-chain fatty acids to drugs or their hydroxylated metabolites may have considerable biological significance.


Evaluating the clinical and economic burden of healthcare-associated infections during hospitalization for surgery in France.
Over 4 million patients suffer nosocomial infections annually in the European Union. This study aimed to estimate the healthcare burden associated with healthcare-associated infections (HAIs) following surgery in France, and explore the potential impact of infection control strategies and interventions on the clinical and economic burden of disease. Data on the frequency of HAIs were gathered from the 2010 Programme de Médicalisation des Systèmes d'Information (PMSI), and cost data were taken from the 2009 Echelle Nationale de Coûts à Méthodologie Commune (ENCC). It was estimated that 3% of surgical procedures performed in 2010 in France resulted in infection, resulting in an annual cost of €57 892 715. Patients experiencing a HAI had a significantly increased mortality risk (4.15-fold) and an increased length of hospital stay (threefold). Scenario analysis in which HAI incidence following surgery was reduced by 8% (based on a study of the effectiveness of triclosan-coated sutures), suggested that, annually, 20 205 hospital days and €4 588 519 could be saved. Analyses of 20% and 30% reductions in incidence (based on an estimate of the number of preventable nosocomial infections) suggested that annual savings of €11 548 057 and €17 334 696, respectively, could be made. New infection control interventions which reduce HAI incidence during hospitalization for surgery have the potential to provide valuable cost savings to healthcare providers.


The antioxidant effects of statins.
Oxidative stress contributes to the initiation and the development of atherosclerotic plaques and adversely influences myocardial integrity. Statins interfere with oxidation in several ways that may contribute to reducing the atherogenic process. In addition to direct antioxidant effects, statins reduce circulating oxidized low-density lipoproteins (oxLDL) and inhibit their uptake by macrophages. They also reduce circulating markers of oxidation such as F2-isoprostane and nitrotyrosine. Statins inhibit oxidant enzymes activity such as that of reduced nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase and myeloperoxidase and up-regulate the activity of antioxidant enzymes such as catalase and paraoxonase. They reduce endothelial dysfunction mainly by their ability to enhance endothelial nitric oxide bioavailability, which is achieved by several mechanisms. The antioxidant properties of statins extend to organ protection especially the myocardium and the lungs.


[Neuromeningeal tuberculosis in northeastern suburbs of Paris. Nineteen cases].
Analyze characteristics of neuromeningeal tuberculosis in the northeastern suburbs of Paris. Retrospective study of 19 observations between 1988 and 1999. Thirteen cases of meningitis, 3 cases of meningitis associated with a tuberculoma and 3 cases with isolated tuberculoma were described. Young subjects (average age 46.4), foreign born (73.7%) were preferentially affected. Three patients were infected by the human immunodeficiency virus. Weight-loss and weakness (84%), fever (79%), headache (63%) dominate the clinical manifestations. The diagnosis delay was 56.6 days, and the therapeutic time, 8.6 days. The search for acid fast bacilli was positive only in one case on direct examination of the cerebrospinal fluid, whereas the culture was positive in 68.7% of the cases. Cerebral imagery was abnormal in13 patients. Average duration of antituberculous treatment was 13,4 months (range: 9-24). Corticosteroids were associated in 12 patients. Thirteen patients were cured, 3 died and 3 were lost to follow up. The characteristics of neuromeningeal tuberculosis are not modified, but the diagnosis delay of the neuromeningeal tuberculosis, which conditions the prognosis, remains significant. The optimal duration of the antituberculous treatment and the conditions of the steroid therapy have to be specified.


Effects of fatty acids and hormones on fatty acid metabolism and gluconeogenesis in bovine hepatocytes.
Primary cultures of hepatocytes were used to study the effects of extracellular oleate concentration and hormones on fatty acid metabolism and gluconeogenesis. Rates of oleate uptake and oxidation to acid-soluble products varied linearly as oleate concentrations increased (0.1 to 2 mM), but rates of triglyceride accumulation varied quadratically. Insulin increased the proportion of oleate that was esterified by 22% without affecting the formation of acid-soluble products. Cells incubated with 2 mM [1-(14)C]oleate for 24 h eliminated 9.6% of the labeled intracellular lipid as acid-soluble products in the following 24 h when no oleate was present during depletion and eliminated 7.7% when 2 mM oleate was present. Insulin reduced labeled triglyceride depletion by 49%. Gluconeogenesis from [2-(14)C] propionate was depressed by 24%, and formation of acid-soluble products was increased by 46% in cells infiltrated with lipid because of previous exposure to 2 mM oleate for 45 h. Rates of gluconeogenesis from propionate were reduced 23% when 2 mM oleate was present during the 3-h period that gluconeogenesis was measured, and the effect was not modified by lipid infiltration. Lipid infiltration influenced hepatic function, and insulin regulated hepatic triglyceride concentration.


Mechanical properties of biomimetic tissue adhesive based on the microbial transglutaminase-catalyzed crosslinking of gelatin.
Fibrin sealants are a type of soft tissue adhesive that employs biochemical reactions from the late stages of the blood coagulation cascade. Intrinsic to these adhesives are a structural protein and a transglutaminase crosslinking enzyme. We are investigating an alternative biomimetic adhesive based on gelatin and a calcium-independent microbial transglutaminase (mTG). Rheological measurements show that mTG catalyzes the conversion of gelatin solutions into hydrogels, and gel times are on the order of minutes depending on the gelatin type and concentration. Tensile static and dynamic loading of the adhesive hydrogels in bulk form demonstrated that the Young's modulus ranged from 15 to 120 kPa, and these bulk properties were comparable to those reported for hydrogels obtained from fibrin-based sealants. Lap-shear adhesion tests of porcine tissue were performed using a newly published American Society for Testing and Materials (ASTM) standard for tissue adhesives. The gelatin-mTG adhesive bound the opposing tissues together with ultimate adhesive strengths of 12-23 kPa which were significantly higher than the strength observed for fibrin sealants. Even after failure, strands of the gelatin-mTG adhesive remained attached to both of the opposing tissues. These results suggest that gelatin-mTG adhesives may offer the benefits of fibrin sealants without the need for blood products.


IgE recognition of the house dust mite allergen Der p 37 is associated with asthma.
House dust mite (HDM) allergens are major elicitors of allergic reactions worldwide. Identification, characterization, and evaluation of diagnostic utility of a new important HDM allergen was performed. A cDNA coding for a new Dermatophagoides pteronyssinus (Dp) allergen, Der p 37, was isolated from a Dp expression library with allergic patients' IgE antibodies. Recombinant Der p 37 (rDer p 37) expressed in Escherichia coli was purified, then characterized by mass spectrometry, circular dichroism, and IgE reactivity by ImmunoCAP ISAC technology with sera from 111 clinically defined HDM-allergic patients. The allergenic activity of rDer p 37 was studied by basophil activation and CD4+ T-cell responses by carboxyfluorescein diacetate succinimidyl ester dilution assays. Specific antibodies raised against rDer p 37 were used for the ultrastructural localization of Der p 37 in mites by immunogold transmission electron microscopy. Der p 37, a 26 kDa allergen with homology to chitin-binding proteins, is immunologically distinct from Der p 15, 18, and 23. It is located in the peritrophic membrane of fecal pellets. Der p 37 reacted with IgE antibodies from a third of HDM-allergic patients and induced specific basophil- and CD4+ T-cell activation. Der p 37 IgE-positive patients had significantly higher IgE levels to major HDM allergens, reacted with more HDM allergens, and had a higher risk (odds ratio = 3.1) of asthma compared to Der p 37-negative patients. Der p 37, a new Dp allergen recognized by a third of HDM-allergic patients, may serve as a surrogate marker for severe HDM sensitization and asthma.


[Poor health at an earlier age: frailty in people with intellectual disabilities].
A study with 1050 people over the age of 50 years with mild to severe intellectual disabilities showed that the health of this group declined at a much younger age than in the general population of the same age. The cardiovascular risk was often higher and depression and sleep disorders were more common in people aged over 50 years with intellectual disabilities, but these were often not diagnosed. Recognising the underlying causes and determining which approach to take to them require specialist knowledge. The accumulation of unfavourable factors from childhood may lead to people becoming frail at an earlier age, which in this population is predictive of a decline in health and independence and a high risk of death within 3 years. The prevalences of multimorbidity and polypharmacy in people over 50 with intellectual disabilities are comparable to those of the Dutch nursing home population. In order to maintain the health and independence of people with an intellectual disability for longer, an improvement in vocational training for carers, development of multidisciplinary guidelines, and enhancement of the quality and availability of outpatient clinics with intellectual disability specialists are required.


Novel magnesium borides and their superconductivity.
With the motivation of searching for new superconductors in the Mg-B system, we performed ab initio evolutionary searches for all the stable compounds in this binary system in the pressure range of 0-200 GPa. We found previously unknown, yet thermodynamically stable, compositions MgB3 and Mg3B10. Experimentally known MgB2 is stable in the entire pressure range 0-200 GPa, while MgB7 and MgB12 are stable at pressures below 90 GPa and 35 GPa, respectively. We predict a reentrant behavior for MgB4, which becomes unstable against decomposition into MgB2 and MgB7 at 4 GPa and then becomes stable above 61 GPa. We find ubiquity of phases with boron sandwich structures analogous to the AlB2-type structure. However, with the exception of MgB2, all other magnesium borides have low electron-phonon coupling constants λ of 0.32-0.39 and are predicted to have Tc below 3 K.


Enhancing oscillations in intracranial electrophysiological recordings with data-driven spatial filters.
In invasive electrophysiological recordings, a variety of neural oscillations can be detected across the cortex, with overlap in space and time. This overlap complicates measurement of neural oscillations using standard referencing schemes, like common average or bipolar referencing. Here, we illustrate the effects of spatial mixing on measuring neural oscillations in invasive electrophysiological recordings and demonstrate the benefits of using data-driven referencing schemes in order to improve measurement of neural oscillations. We discuss referencing as the application of a spatial filter. Spatio-spectral decomposition is used to estimate data-driven spatial filters, a computationally fast method which specifically enhances signal-to-noise ratio for oscillations in a frequency band of interest. We show that application of these data-driven spatial filters has benefits for data exploration, investigation of temporal dynamics and assessment of peak frequencies of neural oscillations. We demonstrate multiple use cases, exploring between-participant variability in presence of oscillations, spatial spread and waveform shape of different rhythms as well as narrowband noise removal with the aid of spatial filters. We find high between-participant variability in the presence of neural oscillations, a large variation in spatial spread of individual rhythms and many non-sinusoidal rhythms across the cortex. Improved measurement of cortical rhythms will yield better conditions for establishing links between cortical activity and behavior, as well as bridging scales between the invasive intracranial measurements and noninvasive macroscale scalp measurements.


High-density self-contained microfluidic KOALA kits for use by everyone.
Cell-based assays are essential tools used by research labs in a wide range of fields, including cell biology, toxicology, and natural product discovery labs. However, in some situations, the need for cell-based assays does not justify the costs of maintaining cell culture facilities and retaining skilled staff. The kit-on-a-lid assay (KOALA) technology enables accessible low-cost and prepackageable microfluidic platforms that can be operated with minimal infrastructure or training. Here, we demonstrate and characterize high-density KOALA methods for high-throughput applications, achieving an assay density comparable to that of a 384-well plate and usability by hand with no liquid-handling equipment. We show the potential for high-content screening and complex assays such as quantitative immunochemistry assays requiring multiple steps and reagents.


Infrequent stromal expression of gelatinase A and intact basement membrane in intraductal neoplasms of the pancreas.
Basement membrane disruption is a characteristic of invasive carcinoma. Gelatinases (also called type IV collagenases) that degrade type IV collagen are believed to play an important role in tumor invasion and metastasis. Intraductal neoplasm (IDN) of the pancreas is a unique tumor that grows intraductally with an infrequent stromal invasion. However, in IDN, basement membrane anomaly and gelatinase expression have not been clarified. The aim of this study was to examine the relationships between basement membrane disruption and the expression of gelatinase A in relation to the biological behavior of IDN or pancreatic duct cell carcinoma (DCC). Disruption of basement membrane and expression of gelatinase A were immunohistochemically investigated in 14 cases of IDN and 16 cases of DCC. Basement membrane was intact in all cases of IDN, whereas focal to severe disruption was observed in DCC. Stromal expression of gelatinase A was higher in DCC than in IDN, and the intensity of expression was related to the degree of disruption of the basement membrane in DCC. Stromal expression of gelatinase A and disruption of basement membrane, common characteristics of invasive cancer, were not prominent in IDN. This may be related to the benign biological behavior of IDN.


Correcting the wavelength-induced phase deviation of Pancharatnam-Berry lenses.
Liquid-crystal-based Pancharatnam-Berry optical elements are widely used in virtual reality and augmented reality. However, the mismatch between exposure wavelength and operating wavelength leads to an undesirable phase deviation to the lenses, which in turn causes severe aberration especially when the f-number is small. To overcome the mismatched wavelength problem and to obtain a nearly ideal lens phase profile, a new exposure method using two template lenses with different focal lengths is proposed and experimentally validated. Our results indicate that such a lens indeed exhibits a better imaging performance than that fabricated by traditional interference method.


Fabrication and electrochemical application of monolayers of well-ordered macroporous silica.
Highly ordered macroporous silica films with a monolayer thickness and regular array of spherical pores with diameters of about 305 nm are prepared using templates self-assembled by polymethylmethacrylate (PMMA) spheres on solid surfaces by spin coating. The macropores are uniform in size and completely exposed on the bottom surface of the film after the PMMA spheres are etched out. Based on electrochemical experiments, the film allows for easy mass transport of Ru(bpy)3(2+) to the ITO surface. Electrochemical detection of DNA hybridization was also carried out in model oligonucleotide hybrids immobilized on the macroporous silica film.


An appropriate in vitro culture condition for the induction of human TCR gamma delta + cells by heat-killed bacteria.
TCR gamma delta + cells proliferated when MNC were stimulated with various heat-killed bacteria. We investigated here the culture conditions for their maximum proliferation. MNC were cultured for 6 days with Streptococcus pyogenes, and for 3 days with T cell mitogens, PHA and anti-CD3 mAb, in medium supplemented with various concentrations (0.05-50%) of human sera. TCR gamma delta + and TCR gamma delta- CD2+3- double negative cells induced by Str. pyogenes required high concentrations of sera (greater than 6%) for their proliferation. Moreover, increased sera (up to 50%) greatly augmented their proliferation. On the other hand, TCR alpha beta + cell proliferation induced by T cell mitogens was supported by a small concentration (even 0.1%) of the sera, and the addition of high concentrations of sera (greater than 6%) somewhat suppressed responses. Similar serum requirement patterns were evident for the induction of cytotoxic cells. These results clearly demonstrated the existence of an appropriate culture condition for the proliferation of TCR gamma delta + cells induced in vitro.


Leuprolide versus diethylstilbestrol for previously untreated stage D2 prostate cancer. Results of a prospectively randomized trial.
In a randomized, prospective trial, 199 previously untreated patients with Stage D2 prostatic cancer were treated with 3 mg/day diethylstilbestrol (DES) or 1 mg/day leuprolide acetate, a luteinizing hormone releasing hormone analog. Both DES and leuprolide suppressed testosterone to the desired castrate levels. Objective measures of disease, such as acid phosphatase levels, and subjective measures, such as bone pain, performance status, and mobility, showed similar decreases in both groups. No progression of disease was seen in 86 per cent of the leuprolide-treated group, compared with 85 per cent of the DES-treated group. The time to disease progression, development of adverse reaction requiring discontinuation of treatment, or death was identical for the two groups. Hot flashes were more common with leuprolide than with DES. Gynecomastia and breast tenderness, nausea and vomiting, and peripheral edema occurred more often in the DES group. Of those taking DES, 13 per cent discontinued treatment because of side effects, compared with 3 per cent of those taking leuprolide.


Perception of men's beauty and attractiveness by women with low sexual desire.
Despite the high prevalence of hypoactive sexual desire disorder (HSDD), especially among women, this sexual disorder remains poorly understood. Among the multiple factors possibly involved in HSDD, particularities in the cognitive evaluations of social stimuli need to be better characterized. Especially, beauty and attractiveness judgments, two dimensions of interpersonal perception that are related but differ on their underlying motivational aspects, may vary according to the level of sexual desire. The main goal of this study was to investigate whether women with and without HSDD differ in their evaluations of beauty and attractiveness of men's faces and voices. Young women from the general population (controls, n = 16) and with HSDD (patients, n = 16) took part in the study. They were presented with a series of neutral/nonerotic voices and faces of young men from the GEneva Faces And Voices database. Ratings of beauty (i.e., assessments of aesthetic pleasure) and of attractiveness (i.e., assessments of the personal propensity to feel attracted to someone) and the frequency to which the participants pressed a key to see or listen to each stimulus again were the main outcome measures. Ratings of attractiveness were lower than ratings of beauty in both groups of women. The dissociation between beauty and attractiveness was larger in women with HSDD than in control participants. Patients gave lower attractiveness ratings than the controls and replayed the stimuli significantly less often. These results suggest that women with HSDD are characterized by specific alterations of the motivational component of men's perception, very early in the process of interpersonal relationships. Our findings have significant implications, both in better understanding the specific cognitive processes underlying hypoactive sexual desire and more largely the evaluative processes involved in human mate choice.


[Laser therapy of penile carcinoma].
The conventional treatment for superficial penile cancer is amputation of the penis. In contrast, the use of the neodymium-YAG laser yields better survival rates without mutilation. In a long-term follow-up (7 years) we found a survival rate of 95%. There may be an additional advantage in combined use of the laser in the treatment of advanced cases of penile cancer. We conclude that the neodymium-YAG laser should be used as first-line therapy.


Characterizing nucleotide variation and expansion dynamics in human-specific variable number tandem repeats.
There are more than 55,000 variable number tandem repeats (VNTRs) in the human genome, notable for both their striking polymorphism and mutability. Despite their role in human evolution and genomic variation, they have yet to be studied collectively and in detail, partially owing to their large size, variability, and predominant location in noncoding regions. Here, we examine 467 VNTRs that are human-specific expansions, unique to one location in the genome, and not associated with retrotransposons. We leverage publicly available long-read genomes, including from the Human Genome Structural Variant Consortium, to ascertain the exact nucleotide composition of these VNTRs and compare their composition of alleles. We then confirm repeat unit composition in more than 3000 short-read samples from the 1000 Genomes Project. Our analysis reveals that these VNTRs contain highly structured repeat motif organization, modified by frequent deletion and duplication events. Although overall VNTR compositions tend to remain similar between 1000 Genomes Project superpopulations, we describe a notable exception with substantial differences in repeat composition (in PCBP3), as well as several VNTRs that are significantly different in length between superpopulations (in ART1, PROP1, DYNC2I1, and LOC102723906). We also observe that most of these VNTRs are expanded in archaic human genomes, yet remain stable in length between single generations. Collectively, our findings indicate that repeat motif variability, repeat composition, and repeat length are all informative modalities to consider when characterizing VNTRs and their contribution to genomic variation.


circNFIC suppresses breast cancer progression by sponging miR-658.
Background: Circular RNAs (circRNAs) have been reported to play important roles in cancer progression. However, the potential involvement of circRNAs in breast cancer metastasis to the lung remains unclear. Methods: High-throughput circular RNA microarray assays of primary breast cancer tissues and lung metastatic tissues were performed. Reactome pathway analysis and GO analysis of the linear mRNA transcripts corresponding to the circRNAs were conducted. The expression of the top downregulated circRNA was confirmed by qRT-PCR in breast cancer cell lines. Kaplan-Meier survival analysis was conducted to analyze the clinical significance of the selected circRNA in breast cancer. A series of in vitro and in vivo experiments, including cell proliferation and migration, was performed to explore the functions of the selected circRNA in breast cancer progression. We further investigated the regulatory effect of the selected circRNA on a miRNA and its target genes to explore the potential mechanisms. Results: We found that circNFIC (hsa_circ_0002018) was the most downregulated circRNA in lung metastatic tissues. Kaplan-Meier survival analysis revealed that low levels of circNFIC were related to poor outcome of breast cancer. Further experiments revealed that overexpressing circNFIC suppressed breast cancer cell proliferation and migration to the lung. A mechanistic study showed that circNFIC acted as a sponge for miR-658 and competed for binding to miR-658 with UPK1A, leading to increased expression of UPK1A. Conclusion: Our study highlighted the regulatory function of the circNFIC/miR-658/UPK1A pathway in breast cancer progression, which could be a potential therapeutic target for breast cancer.


CYP2B6 and OPRM1 gene variations predict methadone-related deaths.
The largest proportion of methadone-associated deaths occurs during the drug induction phase. We analysed methadone-related fatalities for gene variations linked with methadone action. A significant association between high methadone concentrations and the CYP2B6*6 allele characteristic of the slow metabolizer phenotype was identified. We suggest that the risk of methadone fatality may be predetermined in part by the CYP2B6*6 allele. A significant correlation was also observed between post-mortem benzodiazepine concentrations and the OPRM1 A118G allele GA in methadone-related fatalities. Screening for these susceptibility variations prior to methadone prescription could assist in reducing the potential for serious adverse effects.


Non-invasive detection of adeno-associated viral gene transfer using a genetically encoded CEST-MRI reporter gene in the murine heart.
Research into gene therapy for heart failure has gained renewed interest as a result of improved safety and availability of adeno-associated viral vectors (AAV). While magnetic resonance imaging (MRI) is standard for functional assessment of gene therapy outcomes, quantitation of gene transfer/expression relies upon tissue biopsy, fluorescence or nuclear imaging. Imaging of gene expression through the use of genetically encoded chemical exchange saturation transfer (CEST)-MRI reporter genes could be combined with clinical cardiac MRI methods to comprehensively probe therapeutic gene expression and subsequent outcomes. The CEST-MRI reporter gene Lysine Rich Protein (LRP) was cloned into an AAV9 vector and either administered systemically via tail vein injection or directly injected into the left ventricular free wall of mice. Longitudinal in vivo CEST-MRI performed at days 15 and 45 after direct injection or at 1, 60 and 90 days after systemic injection revealed robust CEST contrast in myocardium that was later confirmed to express LRP by immunostaining. Ventricular structure and function were not impacted by expression of LRP in either study arm. The ability to quantify and link therapeutic gene expression to functional outcomes can provide rich data for further development of gene therapy for heart failure.


Adolescent chronic pain and disability: A review of the current evidence in assessment and treatment.
Adolescents who suffer from chronic pain also report complex syndrome-associated disability and distress that can detrimentally affect the quality of their lives and the lives of their family members. Over the past 10 years, there have been significant developments in both methods of assessment and in treatment programs. There have also been good developments in clinical assessment tools, although many need further study. However, the evidence base of available treatments remains small, and there is an urgent need for new trials in both pharmacological and nonpharmacological treatments. The greatest challenges are organizational, and the concern is how to bring patients in contact with available treatments. Many patients who could benefit from evidence-supported treatments are not currently able to access treatment. Theoretical developments aimed at explaining chronic pain within the context of the family, as well as family attempts at coping with complex disability, are underway.


Leg disorders in broiler chickens: a review of current knowledge.
Ensuring improved leg health is an important prerequisite for broilers to achieve optimal production performance and welfare status. Broiler leg disease is characterized by leg muscle weakness, leg bone deformation, joint cysts, arthritis, femoral head necrosis, and other symptoms that result in lameness or paralysis. These conditions significantly affect movement, feeding and broiler growth performance. Nowadays, the high incidence of leg abnormalities in broiler chickens has become an important issue that hampers the development of broiler farming. Therefore, it is imperative to prevent leg diseases and improve the health of broiler legs. This review mainly discusses the current prevalence of broiler leg diseases and describes the risk factors, diagnosis, and prevention of leg diseases to provide a scientific basis for addressing broiler leg health problems.


Grandmothering and cognitive resources are required for the emergence of menopause and extensive post-reproductive lifespan.
Menopause, the permanent cessation of ovulation, occurs in humans well before the end of the expected lifespan, leading to an extensive post-reproductive period which remains a puzzle for evolutionary biologists. All human populations display this particularity; thus, it is difficult to empirically evaluate the conditions for its emergence. In this study, we used artificial neural networks to model the emergence and evolution of allocation decisions related to reproduction in simulated populations. When allocation decisions were allowed to freely evolve, both menopause and extensive post-reproductive life-span emerged under some ecological conditions. This result allowed us to test various hypotheses about the required conditions for the emergence of menopause and extensive post-reproductive life-span. Our findings did not support the Maternal Hypothesis (menopause has evolved to avoid the risk of dying in childbirth, which is higher in older women). In contrast, results supported a shared prediction from the Grandmother Hypothesis and the Embodied Capital Model. Indeed, we found that extensive post-reproductive lifespan allows resource reallocation to increase fertility of the children and survival of the grandchildren. Furthermore, neural capital development and the skill intensiveness of the foraging niche, rather than strength, played a major role in shaping the age profile of somatic and cognitive senescence in our simulated populations. This result supports the Embodied Capital Model rather than the Grand-Mother Hypothesis. Finally, in simulated populations where menopause had already evolved, we found that reduced post-reproductive lifespan lead to reduced children's fertility and grandchildren's survival. The results are discussed in the context of the evolutionary emergence of menopause and extensive post-reproductive life-span.


Action selection for single-camera SLAM.
A method for evaluating, at video rate, the quality of actions for a single camera while mapping unknown indoor environments is presented. The strategy maximizes mutual information between measurements and states to help the camera avoid making ill-conditioned measurements that are appropriate to lack of depth in monocular vision systems. Our system prompts a user with the appropriate motion commands during 6-DOF visual simultaneous localization and mapping with a handheld camera. Additionally, the system has been ported to a mobile robotic platform, thus closing the control-estimation loop. To show the viability of the approach, simulations and experiments are presented for the unconstrained motion of a handheld camera and for the motion of a mobile robot with nonholonomic constraints. When combined with a path planner, the technique safely drives to a marked goal while, at the same time, producing an optimal estimated map.


Observations on normal and degenerating human otoconia.
Specimens of human otoconia obtained from autopsy material and representing various stages from fetal to advanced old age, were studied by microdissection, scanning electron microscopy, electron microprobe analysis, and x-ray powder diffraction. The typical adult otoconial configuration is a cylindrical, finely serrated body with pointed ends; crystallographically, it corresponds to a single crystal of calcite. Other, less numerous typed include jointed otoconia, pure rhombohedrons and multifaceted, presumably immature forms. Many otoconia achieve the adult configuration during fetal development. The multifaceted otoconia are most numerous, and the rhombohedrons proliferate, during childhon in the young adult, but saccular otoconia are the larger. In middle and advanced age the otoconia decrease in number, especially in the saccule. Saccular otoconia degenerate progressively in a posteroanterior direction across the macula; they assume a specific, fibours, hollowed-out appearance, which is not duplicated by either chemical etching or autolysis. Neogenesis and growth of otoconia appear to occur postnatally, with different characteristic growth potentials for those of the saccule and the utricle. Age-related saccular otoconial degeneration appears to involve the organic material, which disappears either before or simultaneously with the mineral substance.


Long-Term Follow-Up Results of Adjuvant Intensity-Modulated Radiotherapy with Concurrent Paclitaxel and Cisplatin in High-Risk Endometrial Cancer Patients.
The purpose of this study was to retrospectively review the outcomes of patients with high-risk endometrial cancer treated with adjuvant radiotherapy with concurrent paclitaxel and cisplatin (TP). Patients with endometrial cancer who underwent radical surgery were screened between Jan 2005 and Dec 2018. Patients with high-risk factors who received adjuvant chemoradiotherapy were included in the study. High risks included stage I, endometrioid-type grade 3 with deep myometrial invasion or lymphovascular space invasion (or both), endometrioid-type stage II to IVa, or stage I to III with serous or clear cell histology. The adjuvant treatment regimen included one cycle of TP chemotherapy, followed by pelvic intensity-modulated radiotherapy (IMRT) with concurrent TP, followed by an additional one cycle of TP. Failure free survival (FFS) and overall survival (OS) were estimated. Patterns of recurrence and occurrence of adverse events were described. A total of 450 patients with high-risk endometrial cancer were screened, 231 of whom were included in this study. After a median follow-up of 70 months, the 5-year OS was 94.7%, and the 6-year OS was 91.8%. The 5-y and 6-y FFS were 90.8% and 87.9%, respectively, which were related to stage (P < 0.05). A total of 14 patients experienced tumor recurrence, including 7 pelvic recurrence and 7 distant metastases. Seven patients died, all due to tumor progression. A total of 164 patients (71%) completed the prescribed course of treatment. A total of 205 patients had adverse events, 46 patients (20%) had grade 1, 92 patients (40%) had grade 2, 49 patients (21%) had grade 3, and 18 patients (8%) had grade 4. There were 83 nonhematologic and 122 hematologic toxicities (26 grade 3 and 18 grade 4). Adjuvant pelvic radiotherapy combined with synchronous TP chemotherapy can achieve excellent long-term survival for high-risk endometrial cancer patients. Moreover, this combination therapy has good safety and feasibility, which is worthy of further study and verification.


[Biochemical aspects of chronic rheumatic inflammation].
Morphological phenomena in rheumatoid arthritis are closely correlated to the biochemical aberrations of connective tissue metabolism. Both, morphological and biochemical analysis of the altered tissue portions demonstrate evidence for uncontrolled proliferation resp. metabolism similar to human and experimental malignoma. The present state of biochemical knowledge in this field permits to describe the metabolic state of the afflicted tissue by means of enzyme activity and substrate pattern and to draw some conclusions in respect to the pathogenesis of inflammatory processes involved in chronic rheumatic diseases.


Using 1,8-cineole plasma with both pulsed and continuous depositions to modify commercially available wound dressing materials.
The current clinical standards for infected chronic wounds are oral and topical antibiotics. These strategies are problematic because antibiotic resistance can occur with prolonged use. As an alternative to clinical methods, essential oils show promise in preventing bacterial growth. Specifically, 1,8-cineole-an active component in eucalyptus oil-exhibits antifungal, anti-inflammatory, and antibacterial properties. Applying 1,8-cineole directly onto a wound is challenging, however, due to its volatile nature. To combat this issue, plasma-enhanced chemical vapor deposition (PECVD) has been established as a method to deposit a stable 1,8-cineole-derived film on model surfaces (e.g., glass and electrospun polystyrene nanofibers). The current study represents an extension of previous work, where both pulsed and continuous 1,8-cineole plasmas were used to deposit a 1,8-cineole-derived film on two commercially available wound dressings. Three surface analyses were conducted to characterize the plasma-modified dressings. First, water contact angle goniometry data demonstrated a decrease in hydrofiber wettability after treatment. Through scanning electron spectroscopy, the surface morphology of both materials did not change upon treatment. When comparing pulsed and continuous treatments, deconvolution of high-resolution C1s x-ray photoelectron spectra showed no differences in functional group retention. Importantly, the chemical compositions of treated wound dressings were different compared to untreated materials. Overall, this work seeks to elucidate how different PECVD parameters affect the surface properties of wound dressings. Understanding these parameters represents a key step toward developing alternative chronic wound therapies.


TFEB-mediated Enhancement of the Autophagy-lysosomal Pathway Dually Modulates the Process of Amyloid β-Protein Generation in Neurons.
Abnormalities of the autophagy-lysosomal pathway (ALP) have been implicated in the pathology of Alzheimer's disease (AD). Activation of TFEB (transcription factor EB), a master regulator of the ALP, leads to ALP facilitation. The present study sought to clarify whether TFEB-mediated ALP facilitation influences the process of amyloid β-protein (Aβ) generation in neurons. TFEB was overexpressed in mature rat primary cortical neurons via recombinant adenoviruses, without (basal conditions) or with co-overexpression of wild-type amyloid precursor protein (APP) or its β-C-terminal fragment (β-CTF). We confirmed that TFEB overexpression upregulated the lysosomal proteins, cathepsin D and LAMP-1. In TFEB-expressing neurons, protein levels of ADAM10 were profoundly increased, whereas those of APP, BACE1, or γ-secretase complex proteins were unaffected. However, TFEB did not affect ADAM10 mRNA levels. TFEB overexpression had different effects on Aβ production depending on the expression level of APP or β-CTF: TFEB slightly decreased Aβ secretion under basal conditions; clearly increased α-CTF levels and marginally increased β-CTF levels with modest increases in secreted Aβ in APP-expressing neurons; and caused a remarkable increase in β-CTF levels with a significant increase in secreted Aβ in β-CTF-expressing neurons. Inhibition of proteasomes, but not lysosomes, markedly increased β-CTF levels in β-CTF-expressing neurons. These results collectively indicate that TFEB modulates Aβ production not only by increasing α-secretase processing of APP through ADAM10 upregulation but also by augmenting β-CTF levels possibly via altered proteasome-mediated catabolism. Thus, TFEB-mediated ALP enhancement appears to have dual, but opposite, effects on Aβ production in neurons.


Chronic respiratory diseases: A rapidly emerging public health menace.
Chronic respiratory diseases, especially the common chronic obstructive pulmonary disease (COPD) and asthma, are increasing at a swift pace. Although smoking is the most typical risk factor globally, indoor and outdoor air pollution is more important in India. Deaths due to COPD have been next to coronary heart disease since 2014. It causes about 64 deaths per lakh population. It is a chronic and progressive disease having many exacerbations. Mostly senior males are affected. Often, the exacerbation needs intensive care, which may be taxing to the limited intensive care units and may deprive other more warranting patients. The diagnosis requires spirometry, which is available only in private or government tertiary care hospitals. The mainstay of treating both diseases is the inhalation of bronchodilators with or without steroids. The diagnosis and treatment are costly, and treatment is required lifelong. Reduction in risk factors is a challenging and long journey. It requires behavioral change communication. The government in the health sector has critical options. On the one hand, the disease is increasing for various reasons; on the other hand, resources are enormously required for prevention and management. The ASHA system and health and wellness centers, which have not been given due importance, can screen, diagnose, and manage majorly patients. Public health specialists should forcefully advocate for resources required for training and equipment.


Life history and natural enemy associations of calico scale (Homoptera: Coccidae) in Kentucky.
Seasonal phenology of calico scale, Eulecanium cerasorum (Cockerell), was monitored for 3 yr on various deciduous tree species in central Kentucky. Infestations were found on 16 host species in six plant families. Calico scale is a univoltine parthenogenic species that overwinters as second instars on bark. Nymphs molted to adult females around mid-April and began producing eggs in late April. Mean fecundity ranged from 3,728 to 4,654 eggs per female, depending on host plant species. Date of first crawler hatch in 2001-2003 ranged from 21 to 26 May, corresponding to a mean accumulation of 818 +/- 2 Celsius degree-days (DDC), calculated from 1 January and a base of 4.4 degrees C. This value predicted crawler hatch within 2 d in Lexington, KY, in 2004. Crawler dispersal lasted 2 to 3 wk. Upon hatching, crawlers move to leaves where they feed during summer. Crawlers primarily settled on the abaxial side of leaves and their within-leaf distribution varied between different tree species. Settled crawlers molted in mid-July and second instars remained on leaves until late September through mid-October, when they returned to bark to overwinter. On hackberry, Celtis occidentalis L., they were concentrated toward the basal end of shoots, primarily because leaf flush continued beyond the end of the crawler dispersal period. Crawler distribution did not differ between upper and lower canopy zones. Fourteen species of parasitoids and a coccinellid beetle were reared from individual scales. Monitoring with sticky traps in tree canopies confirmed that targeting crawlers with insecticides during late May or June would not coincide with peak flight activity of the scale's primary parasitoids.