Population perspectives on functional genomic variation in yeast.
Advances in high-throughput sequencing have facilitated large-scale surveys of genomic variation in the budding yeast,Saccharomyces cerevisiae These surveys have revealed extensive sequence variation between yeast strains. However, much less is known about how such variation influences the amount and nature of variation for functional genomic traits within and between yeast lineages. We review population-level studies of functional genomic variation, with a particular focus on how population functional genomic approaches can provide insights into both genome function and the evolutionary process. Although variation in functional genomics phenotypes is pervasive, our understanding of the consequences of this variation, either in physiological or evolutionary terms, is still rudimentary and thus motivates increased attention to appropriate null models. To date, much of the focus of population functional genomic studies has been on gene expression variation, but other functional genomic data types are just as likely to reveal important insights at the population level, suggesting a pressing need for more studies that go beyond transcription. Finally, we discuss how a population functional genomic perspective can be a powerful approach for developing a mechanistic understanding of the processes that link genomic variation to organismal phenotypes through gene networks.


Regional performance of carotid endarterectomy. Appropriateness, outcomes, and risk factors for complications.
Guided by the findings of randomized controlled trials evaluating carotid endarterectomy (CEA), we examined the appropriateness of CEAs performed in our city and determined the incidences and risk factors for postoperative stroke, death, and cardiac complications. Using health records, we retrospectively reviewed 291 consecutive CEAs performed in our region over 18 months. Based on randomized controlled trial results and standardized remeasurements of angiographic carotid stenoses, indications for CEA were considered appropriate for symptomatic carotid stenoses > or = 70%, uncertain for < 70% symptomatic or > or = 60% asymptomatic stenoses, or inappropriate for < 60% asymptomatic stenoses and for patients with preoperative neurological or medical instability. We found that 41% of patients (118/291) were asymptomatic. Surgical indications were appropriate in 33% of cases (92/281), uncertain in 49% (138/281), and inappropriate in 18% (51/281). Stroke or death occurred within 30 days postoperatively in 5.2% (9/174) of symptomatic patients and 5.1% (6/117) of asymptomatic patients. At least one cardiac complication (angina, congestive heart failure, dysrhythmia, or myocardial infarction) developed in 8.9% (26/291). Independent preoperative risk factors for stroke or death were histories of angina or congestive heart failure and lack of antiplatelet medication; for cardiac complications, risk factors were age > 75 years and a history of congestive heart failure. Almost 1 in 5 patients underwent CEA inappropriately, which was most commonly due to apparent over-estimation of stenosis severity, and half had uncertain indications. Our high complication rate possibly negated any overall surgical benefit in the large group of asymptomatic patients.


Nuclear DNA Damage and Repair in Normal Ovarian Cells Caused by Epothilone B.
This study was designed to assess, whether a new chemotherapeutic microtubule inhibitor, Epothilone B (EpoB, Patupilone), can induce DNA damage in normal ovarian cells (MM14.Ov), and to evaluate if such damage could be repaired. The changes were compared with the effect of paclitaxel (PTX) commonly employed in the clinic. The alkaline comet assay technique and TUNEL assay were used. The kinetics of DNA damage formation and the level of apoptotic cells were determined after treatment with IC50 concentrations of EpoB and PTX. It was observed that PTX generated significantly higher apoptotic and genotoxic changes than EpoB. The peak was observed after 48 h of treatment when the DNA damage had a maximal level. The DNA damage induced by both tested drugs was almost completely repaired. As EpoB in normal cells causes less damage to DNA it might be a promising anticancer drug with potential for the treatment of ovarian tumors.


Traumatic events, daily stressors and posttraumatic stress in unaccompanied young refugees during their flight: a longitudinal cross-country study.
Unaccompanied young refugees constitute an especially vulnerable population, reporting high rates of trauma and mental health problems. There is a significant gap in the literature on trauma and posttraumatic stress symptoms (PTSS) in unaccompanied young refugees who are still on the move and live in precarious circumstances such as refugee camps. This study therefore aimed to contribute to this gap by investigating pre- and peri-migration (potentially) traumatic experiences of unaccompanied young refugees; longitudinal trajectories of trauma, daily stressors and PTSS; and the impact of gender, trauma, and daily stressors on PTSS over time. This longitudinal, mixed-method, and multi-country study was conducted in various settings (e.g. refugee camps, reception centers) across nine European countries. A heterogeneous sample of N = 187 unaccompanied young refugees (78.4% male) from 29 different countries was assessed via interviews at 3 time-points during a period of 27 months. Data was analyzed via growth curve modelling. Prevalence rates of (potentially) traumatic experiences ranged from 29.5 to 91.9%. Peri-migration traumatization remained stable over time (b = - 0.02; p = 0.371), but the number of reported daily stressors (b = - 0.24; p = 0.001) and PTSS scores significantly decreased over time (b = - 0.98; p = 0.004). Females reported higher PTSS compared with males at baseline (p = 0.002), but gender did not influence the longitudinal trajectory of PTSS. The pre-migration trauma load and daily stressors at baseline did not have a significant effect on PTSS at baseline or on the longitudinal trajectory. This is the first study to document not only the high numbers of traumatic events for unaccompanied young refugees pre- and peri- migration, but also the continued traumatization during flight, as well as high rates of daily stressors and PTSS. Humanitarian and political assistance is urgently needed to curb the often life-threatening conditions unaccompanied young refugees face during migration.


Efficacy of ursolic acid against Echinococcus granulosus in vitro and in a murine infection model.
Cystic echinococcosis is a global public health problem; however, the drugs (albendazole and mebendazole) currently recommended by WHO for its treatment, have limited efficacy. Therefore, novel drugs are required to provide more choices for the treatment of this disease. The anthelmintic effects of ursolic acid (UA) were tested on Echinococcus granulosus protoscoleces, germinal cells and metacestodes in vitro. The in vivo efficacy of UA was investigated in mice following secondary infection with E. granulosus. Furthermore, the corresponding ultrastructural damage induced by UA was evaluated by electron microscopy. In vitro, 45.95 ± 5.30% of protoscoleces were killed by UA at 40 μg/ml, while the growth of more than 90% of germinal cells was inhibited by UA at 10 to 40 μg/ml. The same effect was observed in metacestodes 7 days after treatment with UA at 10, 20 and 40 μg/ml, and more than 50% of metacestodes showed loss of integrity at the end of the experiment. In vivo, metacestode weight was significantly reduced following oral administration of UA at 200 and 100 mg/kg (39.5 and 38.3%, respectively). Additionally, ultrastructural damage, such as alternations in germinal cell morphology and formation of vacuoles and lipid granules were observed in parasites treated with UA in vitro, while detachment of the germinal layer from the laminated layer was also seen in metacestodes in vivo. UA was demonstrated to exert parasiticidal activity against E. granulosus in vitro and in vivo, thus implicating UA as a potential anti-echinococcosis agent.


Chlorogenic acid induces apoptosis and cell-cycle arrest in colorectal cancer cells.
Apoptotic agents from natural products like phenolic compounds can be used effectively in the treatment of cancer. Chlorogenic acid (CGA) is one of the phenolic compounds in medicinal plants with anti-cancer properties. In this research, we aimed to explore the anti-cancer mode of action of CGA on colorectal cancer (CRC) cells in vitro conditions. HT-29 and HEK-293 cells were cultured after MTT assay for 24 h with CGA 100 µM, and without CGA. Then, flow cytometry assays and the expression of apoptosis-related genes including caspase 3 and 9, Bcl-2 and Bax, and cell cycle-related genes including P21, P53 and NF-κB at mRNA and protein levels were examined. Finally, we measured the amount of intracellular reactive oxygen species (ROS). The cell viability of all two-cell lines decreased in a dose-dependent manner. Moreover, CGA induces cell cycle arrest in HT-29 cells by increasing the expression of P21 and P53. It also induces apoptosis in HT-29 cells by mitigating Bcl-2 and NF-κB expression and elevating caspase 3 and 9 expression and ROS levels. Considering the cytotoxicity and cell cycle arrest and induction of apoptosis in the colon cancer cell line by CGA, it can be concluded that CGA is a suitable option for the treatment of colon cancer.


SERS substrates fabricated using ceramic filters for the detection of bacteria.
SERS substrates were fabricated by filtering either Ag or Au colloidal particles onto rigid, ceramic filters - onto which suspensions of bacteria were then filtered. SERS spectra of the bacteria were obtained using a Raman spectrometer that has an 'orbital raster scan' capability. It was shown that bacteria samples prepared in this manner were uniformly distributed onto the surface of the SERS substrate. The effect of common buffer systems on the SERS spectra was investigated and the utility of using the SERS technique for speciation of bacteria was explored.


Wernicke-Korsakoff syndrome as a rare phenotype of sporadic Creutzfeldt-Jakob disease.
We reported the case of a patient with Wernicke-Korsakoff syndrome (WKs) as an early clinical manifestation of sporadic Creutzfeld-Jakob disease (sCJD). The 66-year-old female complained of dizziness and imbalance which mostly occurred while walking. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk as well as memory disturbances with confabulations. The disturbances increased during the course of the disease, which led to the death of the patient four months after the appearance of the signs. The patient was finally diagnosed with sCJD disease. The most useful ancillary examination results supporting sCJD diagnosis were brain diffusion DWI MRI (diffusion weighted magnetic resonance imaging) and the presence of 14-3-3 protein in CSF (cerebrospinal fluid). Since that manifestation of sCJD is very unique other causes should be taken into consideration while making a final diagnosis.


Genome-wide transcriptomics of aging in the rotifer Brachionus manjavacas, an emerging model system.
Understanding gene expression changes over lifespan in diverse animal species will lead to insights to conserved processes in the biology of aging and allow development of interventions to improve health. Rotifers are small aquatic invertebrates that have been used in aging studies for nearly 100 years and are now re-emerging as a modern model system. To provide a baseline to evaluate genetic responses to interventions that change health throughout lifespan and a framework for new hypotheses about the molecular genetic mechanisms of aging, we examined the transcriptome of an asexual female lineage of the rotifer Brachionus manjavacas at five life stages: eggs, neonates, and early-, late-, and post-reproductive adults. There are widespread shifts in gene expression over the lifespan of B. manjavacas; the largest change occurs between neonates and early reproductive adults and is characterized by down-regulation of developmental genes and up-regulation of genes involved in reproduction. The expression profile of post-reproductive adults was distinct from that of other life stages. While few genes were significantly differentially expressed in the late- to post-reproductive transition, gene set enrichment analysis revealed multiple down-regulated pathways in metabolism, maintenance and repair, and proteostasis, united by genes involved in mitochondrial function and oxidative phosphorylation. This study provides the first examination of changes in gene expression over lifespan in rotifers. We detected differential expression of many genes with human orthologs that are absent in Drosophila and C. elegans, highlighting the potential of the rotifer model in aging studies. Our findings suggest that small but coordinated changes in expression of many genes in pathways that integrate diverse functions drive the aging process. The observation of simultaneous declines in expression of genes in multiple pathways may have consequences for health and longevity not detected by single- or multi-gene knockdown in otherwise healthy animals. Investigation of subtle but genome-wide change in these pathways during aging is an important area for future study.


Existence of activin-A in A- and D-cells of rat pancreatic islet.
Activin-A, a member of the transforming growth factor-beta supergene family, stimulates insulin secretion in rat pancreatic islets and causes glycogenolysis in isolated rat hepatocytes. These observations prompted us to determine whether activin-A existed in rat pancreas by using an immunocytochemical method. Cells in pancreatic islets were stained by antibody against activin-A, whereas no immunoreactivity was observed in exocrine pancreas. Cells localized in the mantle of the islets were densely stained by the antibody. Immunoelectron microscopic study showed that activin-A existed in secretory granules in both A- and D-cells. Furthermore, studies using a double labeling method revealed that activin-A coexisted with glucagon in secretory granules in A-cells and with somatostatin in D-cells. Antibody against inhibin-A weakly stained cells in both the core and mantle of the islets only when the rat was pretreated with colchicine. Subtypes of activin subunit in islets were identified to be beta A by a reverse transcription-polymerase chain reaction method. In addition, mRNA for inhibin alpha-subunit was expressed in islets. However, mRNA for these inhibin subunits was not detected in exocrine pancreas. To further examine the action of activin-A on insulin secretion, we examined the effect of activin-A in a flow-through perifusion system. Activin-A induced a biphasic insulin secretory response in the presence of 2.8 mM glucose, and a low concentration of activin-A, which does not stimulate insulin secretion by itself, markedly enhanced glucose-mediated insulin secretion at concentrations above 2.8 mM glucose. Inhibin-A did not affect insulin secretion. These results suggest the existence of activin-A in A- and D-cells of rat pancreatic islets and raise the possibility that activin-A acts as a physiological regulator of carbohydrate metabolism.


Di-oleoyl phosphatidylcholine (PC-18:1) stimulates paraoxonase 1 (PON1) enzymatic and biological activities: in vitro and in vivo studies.
Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme which possess anti-atherogenic properties. Our aim was to analyze the effect of HDL phospholipids on HDL-associated paraoxonase (PON1) catalytic and biological activities. In HDL isolated from di-oleoyl-phosphatidylcholine (PC-18:1)-enriched serum, HDL-PC-18:1 levels, as well as PON1 lactonase, arylesterase and paraoxonase activities were increased by 23%, 35%, 47% and 63%, respectively, as compared to control HDL (p<0.01). Furthermore, PON1 contribution to HDL-mediated cholesterol efflux from J774A.1 macrophages was higher in PC-18:1-enriched HDL in comparison to control HDL. In vivo olive oil consumption by Balb C mice increased HDL phospholipids/protein (30%), and HDL-PON1 arylesterase (150%) and lactonase (94%) activities (p<0.01). Furthermore, in the olive oil-treated mice PON1 contribution to HDL-mediated macrophage cholesterol efflux was higher by 100%, in comparison to placebo mouse HDL (p<0.01). Similarly, olive oil consumption by healthy subjects increased HDL-PC-18:1 levels, HDL-PON1 arylesterase (88%), lactonase (52%), paraoxonase (140%) activities and PON1 stimulatory effect on HDL-mediated cholesterol efflux (53%) as compared to HDL before treatment (p<0.01). PC-18:1 stimulatory effect on recombinant PON1 mutant (lacks 20 amino acids at the N-terminal region) paraoxonase and lactonase activities was lower by 56% and 57%, respectively, in comparison to its effect on wild type PON1 (p<0.01). Intervention to increase PON1 activities by HDL enrichment with PC-18:1 could be proven as a beneficial anti-atherogenic therapy.


Celebrity traumatic deaths: are gangster rappers really "gangsta"?
Celebrity injury-related deaths are a common topic of conversation and receive wide media coverage. Despite stereotypes and broad generalizations, it is unclear if the mechanisms of demise echo those of the general population. The objective of this study was to evaluate the epidemiology underlying celebrity traumatic deaths. We evaluated all known injury-related deaths in celebrities (musicians, athletes, actors, politicians and celebrity socialites) that occurred between Jan. 1, 2000, and Sept. 1, 2011. Exclusion criteria were drug/alcohol overdoses and suicides. We used standard statistical methodology. Among 389 celebrities who died because of their injuries, motor vehicle collisions remained the most common mechanism overall. Rappers and politicians had a higher proportion of deaths due to interpersonal violence than all other celebrities. Gunshot wounds were most common in these cohorts (83% and 63%, respectively). Rappers and athletes also died at a younger mean age than other celebrities. Sport-related deaths were most common in boxing and mixed martial arts. Additional mechanisms included airplane crashes, animal interactions and recreational activities. Despite occasionally exotic scenarios, most celebrities die of injury mechanisms similar to those of the general population. It is also apparent that rappers and politicians die by violent means at young and middle ages, respectively, more commonly than all other celebrities.


Identifying a robust design space for glycosylation during monoclonal antibody production.
Glycan distribution has been identified as a "critical quality attribute" for many biopharmaceutical products, including monoclonal antibodies. Consequently, determining quantitatively how process variables affect glycan distribution is important during process development to control antibody glycosylation. In this work, we assess the effect of six bioreactor process variables on the glycan distribution of an IgG1 produced in CHO cells. Our analysis established that glucose and glutamine media concentration, temperature, pH, agitation rate, and dissolved oxygen (DO) had small but significant effects on the relative percentage of various glycans. In addition, we assessed glycosylation enzyme transcript levels and intracellular sugar nucleotide concentrations within the CHO cells to provide a biological explanation for the observed effects on glycan distributions. From these results we identified a robust operating region, or design space, in which the IgG1 could be produced with a consistent glycan distribution. Since our results indicate that perturbations to bioreactor process variables will cause only small (even if significant) changes to the relative percentage of various glycans (<±1.5%)-changes that are too small to affect the bioactivity and efficacy of this IgG1 significantly-it follows that the glycan distribution obtained will be consistent even with relatively large variations in bioreactor process variables. However, for therapeutic proteins where bioactivity and efficacy are affected by small changes to the relative percentage of glycans, the same analysis would identify the manipulated variables capable of changing glycan distribution, and hence can be used to implement a glycosylation control strategy. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1149-1162, 2016.


Clonal proliferation and cytokine requirement of murine progenitors for natural killer cells.
We have established a clonal cell culture system that supports the proliferation of committed natural killer (NK) cell progenitors of mice to investigate the pathway and cytokine regulation of NK cell development. Day 14 fetal thymocytes cultured in methylcellulose with interleukin-7 (IL-7), IL-15, and steel factor (SF) formed diffuse colonies that could not be classified to known colony types. Single-cell origin of the colonies was established by micromanipulation of the colony-forming cells. Cells in the colonies are very blastic, showing no cytoplasmic differentiation, and express Ly5, Thy-1, and CD25 but not myeloid, B, mature T, or NK cell markers. The cells lack T, B, and myeloid potentials but can differentiate to mature NK cells in fetal thymus organ culture, suggesting that the colonies consist of NK committed progenitors. Examination of the minimal cytokine requirement for the NK colony formation showed that IL-7 and SF are indispensable for the formation of immature NK cell colonies. Both IL-2 and IL-15 increased the frequency of colonies. In contrast to IL-2, IL-7, and IL-15, IL-4 strongly inhibited the formation of the colonies. This quantitative clonal culture will provide a useful means to examine the mechanism of NK cell development.


Holistic healing for women with breast cancer through a mind, body, and spirit self-empowerment program.
This article reports results of an integrated mind-body-spirit self-empowerment program for breast cancer survivors. Fifty-one women at various stages of breast cancer completed a series of eclectic lessons offered in a support group format. The program followed an integrated and cumulative lesson plan that progressively and systematically introduced multiple strategies for creating a balance among mental, emotional, spiritual, and physical health. The program's goals were to enable participants to experience a reduction in distress, improve perceived quality of life, reach a deeper sense of meaning and purpose in life, and experience a greater sense of perceived wellness. Self-assessments were obtained on four well-documented measures relating to both pre- and postprogram participation. Differences in pre- and postscores showed statistically significant improvement and large estimated effect sizes on all four measures. Participants' written comments provide examples of the scope and benefits of the program.


Endometriosis presenting as a vaginal mass.
A 43-year-old woman with an anterior vaginal wall mass was referred to gynaecology outpatient for diagnosis and management. Clinical assessment was indicative of a urethral diverticulum, however MRI and ultrasound imaging suggested a Gartner's duct cyst. Following excision of the lesion, histology revealed evidence of an endometriotic cyst. The patient had no other symptoms of endometriosis and remained asymptomatic 3 months following excision. This case highlights the widespread locations in which endometrial tissue can be found, and therefore the range of symptomatology. This in turn lends itself to diagnostic difficulty without histological confirmation.


The chronic consequences of severe sepsis.
The early events of severe sepsis set in motion a cascade of events that significantly contributes to the morbidity and mortality observed during the first few days of this syndrome. Although sepsis is a deadly, acute disease, survivors also suffer long-term consequences. Clinical data underscore subsequent high mortality rates associated with patients who are long-term survivors of the acute septic episode. Within 1 year of surviving severe sepsis, there is a 26% predicted mortality rate, and many patients succumb to lung complications. In this review, we focus on the cellular and molecular mechanisms that dictate the longer-term sequela of sepsis and related lung injury. We have established a murine model of experimental sepsis [cecal ligation and puncture (CLP)], which results in an approximate 60% survival rate. Our studies have demonstrated that these survivors are susceptible to a fungal infection with 100% mortality when challenged 3 days or 15 days post-recovery from the initial CLP. This increased mortality correlates with changes in cytokines and Toll-like receptor expression and alterations in lung leukocyte populations. We hypothesize that the lung becomes predisposed to nosocomial infections for extended periods of time after severe sepsis via mechanisms that include alterations in inflammatory cytokines and an increase in immunomodulatory chemokines, such as monocyte chemoattractant protein-1 and C10. These mediators may alter the innate-immune response by affecting dendritic cells and macrophages, which could provide a mechanism for the immunosuppression observed following sepsis.


Carbon complexes as electronically and sterically tunable analogues of carbon monoxide in coordination chemistry.
Quantum chemical calculations at DFT (BP86) and ab initio levels (CCSD(T)) have been carried out for transition metal carbon complexes [MX2(PR3)2(C)] with various combinations of M = Fe, Ru, Os, X = F, Cl, Br, I, and R = H, Me, Ph, Cyc. Calculations have also been performed for [RuCl2(PMe3)(NHC)(C)] and [RuCl2(NHC)2(C)] where NHC = N-heterocyclic carbene and for [M(Por)(C)] (M = Fe, Ru, Os; Por = porphyrin). The properties of the carbon complexes as donor ligands were studied by calculating the geometries and bond dissociation energies of the Lewis acid-base adducts with the Lewis acids M(CO)5 (M = Cr, Mo, W), PdCl2SMe2, BH3, BCl3, and Fe2(CO)8. The latter species are compared to the analogous CO complexes. The nature of the donor-acceptor interactions between the Lewis acids LA and carbon complexes [TM]C-LA is compared to the bonding in OC-LA. The bonding analysis was carried out with charge- and energy-partitioning methods. The bond strength and the donor-acceptor properties of metal carbon complexes closely resemble those of CO, and thus carbon complexes may be considered as electronically tuneable analogues of carbon monoxide. Similar properties are also calculated for the porphyrin carbon complexes 10MC, which bind more strongly and are slightly stronger pi acceptors than the [(X2(R)2M(C)] species. The carbon complexes [(X2(R)2M(C)] are slightly weaker pi acceptors than CO, and thus they tend to have slightly weaker bonds than CO in group-6 donor-acceptor complexes. The calculations suggest that bond energies of carbon complexes as ligands with d10 transition metals are larger than those of CO. The theoretical results let it seem possible that adducts with more than one carbon complex as ligands may be synthesized and that even homoleptic complexes may be prepared.


Diversified cardiovascular actions of six homologous natriuretic peptides (ANP, BNP, VNP, CNP1, CNP3, and CNP4) in conscious eels.
The natriuretic peptide (NP) family consists of seven paralogs [atrial NP (ANP), brain NP (BNP), ventricular NP (VNP), and C-type NP 1-4 (CNP1-4)] in teleosts, but relative biological activity of the seven NPs has not been comprehensively examined using homologous peptides. In this study, we newly identified CNP3 and CNP4 in eels to use homologous peptides, but the CNP2 gene may have been silenced in this species. The CNP4 gene was expressed exclusively in the brain as CNP1, but the CNP3 gene, from which cardiac ANP, BNP, and VNP were generated by tandem duplication, was most abundantly expressed in the pituitary, suggesting its local action. All NPs induced hypotension dose dependently after intra-arterial injection with a potency order of ANP > VNP > BNP > CNP4 > CNP1 = CNP3. The degree of hypotension was similar at the ventral and dorsal aorta, indicating similar actions on the branchial and systemic circulation. The hypotension induced by cardiac NPs was longer lasting than CNPs, probably because of the difference in preferential receptors. Among cardiac NPs, the hypotensive effect of VNP lasted much longer than those of ANP and BNP, even though VNP disappeared from the blood more quickly than ANP. To analyze the unique effect of VNP, we examined possible involvement of the autonomic nervous system using ANP, VNP, and CNP3. Beta-adrenergic blockade diminished hypotensive effects of all three NPs, but alpha-adrenergic and cholinergic blockade enhanced only the effect of VNP, suggesting a specific mechanism for the VNP action. The NP-induced tachycardia was diminished by all blockers examined. Furthermore, the cardiovascular action of VNP was not impaired by a blocker of NP receptor, HS-142-1. Taken together, the homologous NPs exhibit diverse cardiovascular actions in eels partially through the autonomic nervous system, and the unique VNP action may be mediated by a novel receptor that has not been identified in teleosts.


Histiocytosis X with unusual skin symptoms.
A 4-year-old boy with skin symptoms resembling verruca plana juvenile was observed. The light- and electron-microscopic picture showed the typical features of histiocytosis X (Letterer-Siwe syndrome). Beside the skin manifestations some less dense areas in the skull bones were found by X-ray examination. Vinblastine and prednisolone treatment for one year resulted in complete remission.


Development and In Vitro Release of Isoniazid and Rifampicin-Loaded Bovine Serum Albumin Nanoparticles.
BACKGROUND Bovine serum albumin nanoparticles loaded with isoniazid and rifampicin (INH-RFP-BSA-NPs) were prepared and their release characteristics were studied in vitro. MATERIAL AND METHODS The INH-RFP-BSA-NPs were prepared by a modified self-emulsion solvent diffusion method, with albumin and polylactic acid used as carriers and to form the nanoparticles structure. Transmission electron microscopy was used to observe the morphology of the INH-RFP-BSA-NPs. The size distribution of the INH-RFP-BSA-NPs were assessed using a submicron particle-size analyzer for drug loadings, and the coating rate of the INH-RFP-BSA-NPs was measured by high-performance liquid chromatography. A dynamic membrane dialysis method was used to study the in vitro release characteristics of the INH-RFP-BSA-NPs. RESULTS The INH-RFP-BSA-NPs were smooth, sphere-like, relatively uniform in size, and well-dispersed, and the average diameter was 60.5±4.6 nm. Drug loading and entrapment efficiencies were high, at 19.8% and 87.8% for isoniazid, respectively, and 20.1% and 98.0% for rifampicin, respectively. Drug release was slow and sustained with 97.02% INH cumulative release at 6 days, and full release of RFP requiring 5 days. CONCLUSIONS INH-RFP-BSA-NPs exhibit uniform NP diameter, good dispersion, high drug loading and encapsulation rates, and have sustained release properties.


Ultralong Hydroxyapatite Nanowire-Based Filter Paper for High-Performance Water Purification.
A new kind of environmentally friendly filter paper based on ultralong hydroxyapatite nanowires (HAPNWs) and cellulose fibers (CFs) with excellent filtration and adsorption properties has been developed for the application in high-performance water purification. The use of polyamidoamine-epichlorohydrin (PAE) resin increases the wet mechanical strength of the as-prepared HAPNW/CF filter paper. The addition of CFs enhances the mechanical strength of the HAPNW/CF filter paper. Owing to the porous structure and superhydrophilicity of the as-prepared HAPNW/CF filter paper, the pure water flux is as high as 287.28 L m-2 h-1 bar-1 under cross-flow conditions, which is about 3200 times higher than that of the cellulose fiber paper with addition of PAE. More importantly, the as-prepared HAPNW/CF filter paper shows superior performance in the removal of TiO2 nanoparticles (>98.61%) and bacteria (up to 100%) in water by the size exclusion and blocking effect. In addition, the HAPNW/CF filter paper also exhibits high adsorption capacities for methyl blue (273.97 mg g-1) and Pb2+ ions (508.16 mg g-1). The adsorption mechanism of the HAPNW/CF filter paper is investigated. The as-prepared environmentally friendly HAPNW/CF filter paper with both excellent filtration and adsorption properties has promising application in high-performance water purification to tackle the worldwide water scarcity problem.


Mortality and alcohol-related morbidity in patients with delirium tremens, alcohol withdrawal state or alcohol dependence in Norway: A register-based prospective cohort study.
Little is known about long-term consequences of delirium tremens (DT). This study aimed to compare all-cause and cause-specific mortality and alcohol-related morbidity between patients with: (i) DT, (ii) alcohol withdrawal state (AWS) and (iii) alcohol dependence (AD). A national longitudinal health registry study with linked data from the Norwegian Patient Registry and the Norwegian Cause of Death Registry. Norway. All patients registered in the Norwegian Patient Registry between 2009 and 2015 with a diagnosis of AD (ICD-10 code F10.2), AWS (F10.3) or DT (F10.4) and aged 20-79 years were included (n = 36 287). Patients were categorized into three mutually exclusive groups; those with DT diagnosis were categorized as DT patients regardless of whether or not they had received another alcohol use disorder diagnosis during the observation period or not. Outcome measures were: annual mortality rate, standardized mortality ratios (SMR) for all-cause and cause-specific mortality and proportion of alcohol-related morbidities which were registered in the period from 2 years before to 1 year after the index diagnosis. DT patients had higher annual mortality rate (8.0%) than AWS (5.0%) and AD (3.6%) patients, respectively. DT patients had higher mortality [SMR = 9.8, 95% confidence interval (CI) = 8.9-10.7] than AD patients (SMR = 7.0, 95% CI = 6.8-7.2) and AWS patients (SMR = 7.8, 95% CI = 7.2-8.4). SMR was particularly elevated for unnatural causes of death, and more so for DT patients (SMR = 26.9, 95% CI = 21.7-33.4) than for AD patients (SMR = 15.2, 95% CI = 14.2-16.3) or AWS patients (SMR = 20.1, 95% CI = 16.9-23.9). For all comorbidities, we observed a higher proportion among DT patients than among AWS or AD patients (P < 0.001). People treated for delirium tremens appear to have higher rates of mortality and comorbidity than people with other alcohol use disorders.


Under pressure: Effect of a ransomware and a screen failure on trust and driving performance in an automated car simulation.
One major challenge for automated cars is to not only be safe, but also secure. Indeed, connected vehicles are vulnerable to cyberattacks, which may jeopardize individuals' trust in these vehicles and their safety. In a driving simulator experiment, 38 participants were exposed to two screen failures: silent (i.e., no turn signals on the in-vehicle screen and instrument cluster) and explicit (i.e., ransomware attack), both while performing a non-driving related task (NDRT) in a conditionally automated vehicle. Results showed that objective trust decreased after experiencing the failures. Drivers took over control of the vehicle and stopped their NDRT more often after the explicit failure than after the silent failure. Lateral control of the vehicle was compromised when taking over control after both failures compared to automated driving performance. However, longitudinal control proved to be smoother in terms of speed homogeneity compared to automated driving performance. These findings suggest that connectivity failures negatively affect trust in automation and manual driving performance after taking over control. This research posits the question of the importance of connectivity in the realm of trust in automation. Finally, we argue that engagement in a NDRT while riding in automated mode is an indicator of trust in the system and could be used as a surrogate measure for trust.


Evaluation of the environmental sustainability of different waste-to-energy plant configurations.
Residual municipal solid waste (MSW) has an average lower heating value higher than 10GJ/Mg in the EU, and can be recovered in modern Waste-to-Energy (WtE) plants, producing combined heat and power (CHP) and reaching high levels of energy recovery. CHP is pinpointed as the best technique for energy recovery from waste. However, in some cases, heat recovery is not technically feasible - due to the absence of a thermal user (industrial plant or district heating) in the vicinity of the WtE plant - and power production remains the sole possibility. In these cases, there are some challenges involved in increasing the energy performance as much as possible. High energy recovery efficiency values are very important for the environmental sustainability of WtE plants. The more electricity and heat is produced, the better the saving of natural resources that can be achieved. Within this frame, the aim of this work is to carry out an environmental assessment, through Life Cycle Assessment, of an MSW WtE plant, considering different sizes and operated in different ways, from power production only to full cogeneration. The main assumption is that the electric conversion efficiency increases as the plant size increases, introducing technical improvements thanks to the economies of scale. Impact assessment results were calculated using ReCiPe 2008 methods. The climate change indicator is positive when the WtE plant is operated in power production only mode, with values decreasing for the increasing size. Values for the climate change are negative when cogeneration is applied, requiring increasing cogeneration ratios for decreasing size. Similarly, the fossil fuel depletion indicator benefits from increase of both the plant size and the cogeneration rate, but it is always negative, meaning that the residual MSW burning with energy recovery always provides a saving of fossil primary energy. Other indicator values are in general negative and are also beneficially affected by increasing the plant size, but they worsen when increasing the cogeneration rate. The remaining indicators - i.e. human toxicity and terrestrial ecotoxicity - always have positive values, which decrease for increasing plant size and increase as the cogeneration rate increases. However, the local context should be evaluated carefully with reference to the type of electricity which is substituted and in view of a future massive production of renewable electricity, because conclusions change accordingly. Finally, it was evaluated that the inclusion of bottom ash recovery - instead of landfilling - can significantly improve the values of several impact assessment indicators.


Burnout Syndrome and Logotherapy: Logotherapy as Useful Conceptual Framework for Explanation and Prevention of Burnout.
Burnout syndrome is a state of total exhaustion related to work conditions and stress from work. Recent findings suggest that logotherapy and the concepts of existential meaning and life fulfilment could provide a useful framework for explaining and potentially preventing burnout. This review article summarizes and reflects current knowledge concerning the relation between burnout syndrome and existential vacuum as a potential correlate. It also explores the risks of burnout and the need of better definition of this condition including more precise diagnostic criteria and internationally recognized measurement tools. Intensified research on relations between burnout and lack of existential fulfilment and meaning could help with future prevention and intervention design.


The Involvement of ERCC2/XPD and ERCC6/CSB Wild Type Alleles in Protection Against Aging and Cancer.
DNA helicases maintain genome stability, and their deficiency is associated with disorders resembling premature aging as well as contributes to carcinogenesis. Their functions are determined by the respective genes encoding nucleotide excision repair initiating proteins, e.g. XPD and CSB. The present study aimed to investigate the influence of genetic variations in ERCC2/XPD (rs1799793, rs13181) and ERCC6/CSB (rs2228526, rs2228528) loci on lifespan and developing age-related bladder cancer focusing on homozygous wild type alleles. The allelic variants were identified in 354 clinically healthy controls and 418 bladder cancer patients using the PCR-RFLP method. The age-depended increase in frequencies of homozygous carriers of wild-type XPD 312Asp and XPD 751Lys alleles was observed among controls, especially among subjects over 80 years (r = 0.67, p = 0.012). The statistically significant correlation was also found between the frequency of homozygous wild type alleles at all tested loci and age in healthy population over 60 years (r = 0.35, p = 0.046) suggesting the relationship between lifespan and longevity, on one hand, and normal functioning of these genes and their products, on the other hand. Homozygous carriers of wild type alleles were less susceptible to bladder cancer, tumor invasion, increase in grade of malignancy and recurrence, but their effects were specific with respect to clinicopathological and lifestyle characteristics. Homozygous wild type alleles encoding XPD and CSB proteins with optimal properties were shown to affect human lifespan, risk of developing bladder cancer, its progression and recurrence under certain conditions.


Electro-elastic tuning of single particles in individual self-assembled quantum dots.
We investigate the effect of uniaxial stress on InGaAs quantum dots in a charge tunable device. Using Coulomb blockade and photoluminescence, we observe that significant tuning of single particle energies (≈-0.22 meV/MPa) leads to variable tuning of exciton energies (+18 to -0.9 μeV/MPa) under tensile stress. Modest tuning of the permanent dipole, Coulomb interaction and fine-structure splitting energies is also measured. We exploit the variable exciton response to tune multiple quantum dots on the same chip into resonance.


Dietary patterns and physical activity in people with schizophrenia and increased waist circumference.
People with severe mental disorders die 10-25years earlier than people in the Western background population, mainly due to lifestyle related diseases, with cardiovascular disease (CVD) being the most frequent cause of death. Major contributors to this excess morbidity and mortality are unhealthy lifestyle factors including tobacco smoking, unhealthy eating habits and lower levels of physical activity. The aim of this study was to investigate the dietary habits and levels of physical activity in people with schizophrenia spectrum disorders and overweight and to compare the results with the current recommendations and with results from the general Danish population. We interviewed a sample of 428 people with schizophrenia spectrum disorders and increased waist circumference enrolled in the CHANGE trial using a Food Frequency Questionnaire (FFQ) and a 24h recall interview, a Physical Activity Scale (PAS), scale for assessment of positive and negative symptoms (SAPS and SANS, respectively), Brief Assessment of Cognition in Schizophrenia (BACS) and Global Assessment of Functioning (GAF). We compared with information on dietary intake and physical activity in the general Danish population from the Danish National Survey of Dietary Habits and Physical Activity in 2011-2013 (DANSDA). The CHANGE participants reported a very low energy intake and their distribution of nutrients (i.e. fat, protein and carbohydrates) harmonized with the recommendations from the Danish Health Authorities, and were similar to the latest report on the dietary habits in the Danish general population. However, the intake of saturated fat, sugar and alcohol exceed the recommended amounts and the corresponding intake in the general population. The intake of fiber, vegetables and fruit and fish were insufficient and also less than in the general population. The overall estimated quality of the dietary habits was poor, only 10.7% of the participants had healthy dietary patterns, and the quality was poorer than in the general population. Even with a very liberal definition of the term "homecooked", only 62% of the participants had taken any part in the preparation of their food. The level of physical activity was low and only one fifth of the participants complied with the recommendations of min. 30min daily moderate-to-vigorous activity. Half of the CHANGE participants were smokers, compared to 17% in the general population. Negative symptoms were significantly associated with poorer dietary quality and less physical activity, whereas no such significant associations were found for cognition, positive symptoms or antipsychotic medication. Even when accounting for some error from recall - and social desirability bias, the findings point in the direction that the average energy intake in obese people with schizophrenia spectrum disorders is not exceeding that of the general population, and that overweight may to some degree be a result of physical inactivity and metabolic adverse effects of antipsychotic medication. The physical activity level is low and the rate of tobacco smoking is high, and our results suggest that negative symptoms play a significant role. Future research should focus on bringing about lifestyle changes in this fragile population in order to reduce the excess risk of CVD and mortality.


Strabismus and the Oculomotor System: Insights from Macaque Models.
Disrupting binocular vision in infancy leads to strabismus and oftentimes to a variety of associated visual sensory deficits and oculomotor abnormalities. Investigation of this disorder has been aided by the development of various animal models, each of which has advantages and disadvantages. In comparison to studies of binocular visual responses in cortical structures, investigations of neural oculomotor structures that mediate the misalignment and abnormalities of eye movements have been more recent, and these studies have shown that different brain areas are intimately involved in driving several aspects of the strabismic condition, including horizontal misalignment, dissociated deviations, A and V patterns of strabismus, disconjugate eye movements, nystagmus, and fixation switch. The responses of cells in visual and oculomotor areas that potentially drive the sensory deficits and also eye alignment and eye movement abnormalities follow a general theme of disrupted calibration, lower sensitivity, and poorer specificity compared with the normally developed visual oculomotor system.


Hypersensitivity Reaction and Rapid Drug Desensitization with Chemotherapeutics: A Tertiary Reference Center Experiences.
Chemotherapy drugs have been in our lives for a long time, and all agents have the potential to develop hypersensitivity. Rapid drug desensitization is an option when hypersensitivity develops. The aim of this study was to examine the characteristics, diagnostic processes, and treatment results of patients with chemotherapeutic agent hypersensitivity who applied to our tertiary reference center. Patients who applied to our tertiary allergy outpatient clinic between January 2016 and September 2022 due to chemotherapy-induced drug hypersensitivity were examined. Demographic data of the patients, cancer diagnoses, chemotherapy regimens, skin tests, premedication scheme, desensitization cycle were evaluated. We applied a 16-step desensitization in patients with index reaction anaphylaxis or positive skin tests. If the index reaction was not anaphylaxis or skin tests were negative, we applied a 12-step desensitization. If the prick test with chemotherapeutic drugs was negative especially with taxanes, premedication was administered. We used the montelukast, cetirizine, and methylprednisolone for premedication. Fifty-one patients were evaluated; 35 (68.6%) were female. The most common malignancy was colorectal cancer in 17 (33.3%) patients. The most common agent responsible for hypersensitivity was oxaliplatin in 17 (33.3%) patients, followed by paclitaxel in 13 (25.4%). When the symptoms of immediate reaction to chemotherapeutic drugs were analyzed as described in the EAACI position paper, only skin and mucosal involvement was seen in 24 (46.8%) patients; only respiratory system involvement or back pain was seen in 3 (6.2%) patients; multisystem involvement meeting the criteria for anaphylaxis was seen in 24 (47%) patients. Skin test was positive in 17 (56.6%) of 30 patients who developed a reaction with platin. Prolonged anaphylaxis was developed in 1 patient, and desensitization was not performed again. Fifty of 51 patients were able to receive the target chemotherapy dose by desensitization. In total, a 172-step desensitization was applied to 51 patients. If completing the cycle is considered a treatment success, this was achieved in 98% (50/51) patients with rapid drug desensitization. This gives us the opportunity to use first-line chemotherapy agents.


[Adipokines Level in Metabolically Healthy Obese Saint-Petersburg Inhabitants (ESSE-RF)].
to elucidate prevalence of phenotypes of metabolically heathy obesity (MHO) among inhabitants of Saint-Petersburg using various criteria and assess dependence levels of adipokines on obesity phenotype. Within a framework of epidemiologic study ESSE-RF we formed a random sample of 1600 Saint-Petersburg inhabitants stratified according to gender and age. Examination of participants included anthropometry with measurement of waist circumference CRP and estimation of body mass index (BMI), measurement of arterial pressure, determination of fasting blood glucose, insulin (with calculation of index of insulin resistance -IIR), lipid spectrum, C-reactive protein (CRP), adiponectin, leptin. In subjects with obesity (BMI more or equal 30 kg/m) we used Meigs and Wildman MHO criteria. To Wildman criteria we applied 3 variants of definition of elevated CRP and IIR: 90th percentile among subjects with BMI <25 kg/m (variant 1) or among all participants (variant 2), and (variant 3) definition from publication by E.Oliveros et al. (2014). Obesity (BMI more or equal 30 kg/m) was found in 430 participants. Numbers/rates of MHO according to the Wildman criteria were the following: variant 1 - 49/12% (among them 13/10% men and 36/14% women, =0.15); variant 2 - 85/22% (24/18% men, 61/23% women, =0.13); variant 3 - 59/15% (13/10% men, 46/18% women, =0.02). Portion of MHO according to Meigs criteria was 138/35% (among them 48/36% men, 90/35% women, =0.4). Significant differences in adipokines levels between subjects with MHO and metabolically unhealthy obesity (MUHO) were revealed only among women. There was no difference in leptin level between subjects with MHO and MUHO irrespective of gender. Rate of MHO phenotype in a sample of inhabitants of Saint-Petersburg varied from 12 to 35% depending on criteria used. Gender differences in MHO rates were minimal and depended on selected criteria. Elevated adiponectin level among obese women could be presumably related to more favorable metabolic profile.


Laplacian of the Hamiltonian Kinetic Energy Density as an Indicator of Binding and Weak Interactions.
The kinetic energy is the center of a controversy between two opposite points of view about its role in the formation of a chemical bond. One school states that a lowering of the kinetic energy associated with electron delocalization is the key stabilization mechanism of covalent bonding. In contrast, the opposite school holds that a chemical bond is formed by a decrease in the potential energy due to a concentration of electron density within the binding region. In this work, a topographic analysis of the Hamiltonian Kinetic Energy Density (KED) and its laplacian is presented to gain more insight into the role of the kinetic energy within chemical interactions. This study is focused on atoms, diatomic and organic molecules, along with their dimers. In addition, it is shown that the laplacian of the Hamiltonian KED exhibits a shell structure in atoms and that their outermost shell merge when a molecule is formed. A covalent bond is characterized by a concentration of kinetic energy, potential energy and electron densities along the internuclear axis, whereas a charge-shift bond is characterized by a fusion of external concentration shells and a depletion in the bonding region. In the case of weak intermolecular interactions, the external shell of the molecules merge into each other resulting in an intermolecular surface comparable to that obtained by the Non-covalent interaction (NCI) analysis.


Supervised weekly rinsing with a 0.2% neutral NaF solution: results from a demonstration program after three school years.
A school-based fluoride rinsing program was instituted in 1975 in the Three Village Central School District, Long Island, NY. The children rinsed once a week with a 0.2% neutral NaF solution under supervision of the homeroom teachers. After three years, the participants had rinsed an average of 77 times. Children in grades 3 through 7 who had participated during all three years of rinsing had a reduction in caries prevalence of 30.9% for DMFS and 28.5% for DMFT. The greatest reduction occurred on proximal surfaces (48.7%), followed by buccolingual surfaces (30.0%) and occlusal surfaces (28.2%). The benefits of fluoride rinsing increased with the duration of the program.


[Serologic examination for childhood herpes simplex virus infection].
This study was designed to investigate the value of serologic examination in the diagnosis of childhood herpes simplex virus (HSV) infection. Serum samples were collected from 2 436 outpatients and inpatients. The samples were divided into two groups. Group 1 consisted of 321 samples which were assayed for HSV-1 IgG, HSV-1 IgM, HSV-2 IgG or HSV-2 IgM antibody using herpes simplex virus antibody kits between January 2003 and November 2005. Group 2 consisted of 2115 samples which were assayed for HSV-2 IgG and IgM antibodies by TORCH testing between October 2004 and November 2005. In Group 1, the total seroprevalence of HSV infection was 44.6%, with 38.9% being HSV-1 positive and 15.9% HSV-2 positive; HSV-IgM positivity was found in 41.1% and 25.5% were HSV-IgG positive; HSV-1 seroprevalence significantly increased with age (P < 0.05). In Group 2 the seroprevalence of HSV-2 infection was 1.9%; all of the samples were HSV-2 IgG positive. HSV serologic examination is useful in the diagnosis of HSV infection in children.


[Hereditary, recurrent corneal erosions].
The review presents a clinical case of 40 years old female patient with bilateral recurrent corneal erosions (r.c.e.), without an obvious cause. It is relevant to mention the present of the r.c.e. in her family during 4 generations. The acute corneal lesions looked like a "map-dot-fingerprint" dystrophy and 3 weeks later cornea became normal.


Sulphomucins and precancerous lesions of the human stomach.
The histochemical demonstration of sulphomucin secretion by gastric adenomatous polyps and adjacent metaplastic epithelium suggests this glycoprotein may be a marker of premalignant change. A possible relationship with fetal sulphoglycoprotein antigen is discussed.


Second-line treatment in inoperable pancreatic adenocarcinoma: A systematic review and synthesis of all clinical trials.
There remains uncertainty regarding the optimal second-line chemotherapy in advanced pancreatic ductal adenocarcinoma (PDAC). The current recommendation of 5-fluorouracil and oxaliplatin may not be relevant in current practice, as FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) has become a more popular first line therapy in fit patients. The majority of studies in this setting are single-arm Phase II trials with significant heterogeneity of patient populations, treatments and outcomes. In this review, we sought to systematically review and synthesise all prospective data available for the second-line treatment of advanced PDAC.


Identification and activation of profollipsin, a latent precursor form of porcine follipsin.
A latent protease has been identified in column fractions obtained during the purification of the porcine ovarian serine protease follipsin. The latent enzyme was readily activated by trypsin treatment. The trypsin-activated enzyme was purified using a benzamidine-Sepharose 6B column and was shown to be composed of two distinct, covalently associated polypeptides with Mr of 45000 and 32000. This polypeptide chain composition, together with its substrate specificity, inhibition profile using various protease inhibitors, cross-reactivity with anti-follipsin antibody, and ability to activate single-chain precursor tissue plasminogen activator, indicated its identity as porcine follipsin. The activation of the enzyme with trypsin was found to occur by the hydrolysis of an internal peptide bond resulting in a two-chain structure. Thus, we conclude that the latent enzyme is the inactive precursor form (profollipsin) of follipsin. The present study also shows that the follicular fluid of porcine ovary contains a profollipsin-activating enzyme activity.


[A case of gastric cancer with peritoneal metastasis successfully treated with multidisciplinary therapy].
A 56-year-old woman with advanced gastric cancer with peritoneal metastasis was successfully treated with multidisciplinary therapy. Gastrectomy and total resection of the peritoneal metastasis were performed initially. Subsequently, combined chemotherapy with S-1/polysaccharide-Kureha( PSK) and intraperitoneal infusion( IP) of docetaxel( TXT) was continued for 9 months. Because of the appearance of hepatic metastasis, the anti -cancer drug was changed to irinotecan (CPT-11) that was administered by dropping intravenously( DIV therapy) and continued for 10 months. Despite the reduction of the hepatic metastasis, ascites was increased. All metastatic lesions disappeared after 3-months of paclitaxel (TXL) DIV therapy. Five years after the operation, the peritoneal metastasis recurred. Combined DIV and IP TXL therapy was administered for 2 months. The peritoneal metastasis was reduced and the TXL DIV therapy was continued for 6 months. Due to increased levels of tumor markers, capecitabine( Xeloda)/cisplatin( CDDP) was introduced; however, it could not be continued because of the side effects. Subsequent TXT DIV therapy was not effective; chemotherapy was switched to CPT-11 DIV therapy, which was effective for 14 months. S-1 and TXL IP therapy was initiated because of the appearance of a new peritoneal tumor. This therapy effectively controlled the disease until today. The patient is in good health at 8 years after the start of therapy.


Revision of the Unstable Picrotoxinin Hydrolysis Product.
The plant metabolite picrotoxinin (PXN) is a widely used tool in neuroscience for the identification of GABAergic signaling. Its hydrolysis in weakly alkaline media has been observed for over a century and the structure of the unstable hydrolysis intermediate was assigned by analogy to the degradation product picrotoxic acid. Here we show this assignment to be in error and we revise the structure of the hydrolysis product by spectroscopic characterization in situ. Counterintuitively, hydrolysis occurs at a lactone that remains closed in the major isolable degradation product, which accounts for the longstanding mistake in the literature.


Intraoral orthotic therapy.
Despite the unanswered questions on the physiologic mechanisms that explain the effectiveness of intraoral orthotics on reducing symptoms of TMD, there is still a plethora of documentation that intraoral orthotics, when appropriately used in the management plan, can contribute to the relief of TMD symptoms. The clinician is encouraged to evaluate fully each particular patient case in an effort to develop a differential diagnosis that leads to an effective management plan, which, in turn, addresses the cause(s) as best as possible. Before commencing any intraoral orthotic therapy for a TMD, the clinician should be confident that the patient will benefit from the therapeutic approach to be employed or, at least, that the resultant effect, or lack thereof, on the symptoms will provide additional diagnostic information. The clinician also needs to take into account that approximately 40% of patients suffering from TMD demonstrate a favorable response to intraoral orthotic therapy just from a placebo effect. As with any treatment, a good patient-dentist relationship concomitant with patient education can allay patient concerns and anxieties, which, in and of themselves, can contribute to a positive and favorable response to intraoral orthotic therapy.


Binding of arylsulfatase A to mouse sperm inhibits gamete interaction and induces the acrosome reaction.
We have shown previously that male germ cell-specific sulfoglycolipid, sulfogalactosylglycerolipid (SGG), is involved in sperm-zona pellucida binding, and that SGG and its desulfating enzyme, arylsulfatase A (AS-A), coexist in the same sperm head area. However, AS-A exists at a markedly low level in sperm as compared to SGG (i.e., 1/400 of SGG molar concentration). In the present study, we investigated whether perturbation of this molar ratio would interfere with sperm-egg interaction. We demonstrated that purified AS-A bound to the mouse sperm surface through its high affinity with SGG. When capacitated, Percoll gradient-centrifuged mouse sperm were treated for 1 h with various concentrations of AS-A, their binding to zona-intact eggs was inhibited in a dose-dependent manner and reached the background level with 63 nM AS-A. This inhibition could be partially explained by an increase in premature acrosome reaction. The acrosome-reacted sperm population of the 63 nM AS-A-treated sperm sample was twice that of the control sample (treated with 63 nM ovalbumin) at 1 h (i.e., 32% vs. 15%) and rose to 53% at 2 h. This induction was presumably due to SGG aggregation attributed to AS-A, existing as a dimer at neutral pH, and could be mimicked by anti-SGG immunoglobulin (Ig) G/IgM + secondary IgG antibody. Drastic inhibition (75%) of in vivo fertilization was also observed in females inseminated with sperm suspension containing 630 nM AS-A as compared to the rate in females inseminated with sperm suspension included with 630 nM ovalbumin. Our results demonstrate a promising potential for AS-A as a nonhormonal, vaginal contraceptive.


Chemotherapy-induced interstitial pneumonitis during treatment of small cell anaplastic lung cancer.
Twelve cases of interstitial pneumonitis were seen in 50 patients (24%) treated with cyclophosphamide, methotrexate, and etoposide (VP-16-213) for small cell anaplastic lung cancer. The clinical course and pathologic characteristics were consistent with drug-induced pneumonitis in all 12 cases. One additional patient had concurrent histologic evidence of interstitial pneumonitis, pneumocystis infection, and perivascular metastases. Patients presented with severe dyspnea, hypoxemia, cough, fever, and bilateral interstitial infiltrates on chest films. The onset was rapid and unpredictable, following as little as one month or as much as five months of therapy. Nine patients recovered but there were three deaths in the acute period directly attributable to the drug-induced pneumonitis. Although the use of twice weekly oral methotrexate may have been a causative factor, a previously unsuspected drug interaction with etoposide may be the etiologic factor resulting in this unusually high incidence of pulmonary toxicity. The difficulty in establishing a diagnosis of interstitial pneumonitis in this group of patients with chronic lung disease and lung cancer is well known. The extent of morbidity and mortality seen in this study and the commercial availability of etoposide make earlier clinical recognition of this complication imperative.


Lymphangitis carcinomatosa in thin section computed tomography.
High resolution computed tomography is a diagnostic method of choice in the evaluation of lung parenchyma. HRCT enables the evaluation of small interstitial changes, invisible on plain chest radiographs, and their assessment at the level of the lung lobule. The aim of the study was the assessment of typical findings in HRCT in lymphangitis carcinomatosa, enabling differential diagnosis. Material comprises a group of 18 patients with lymphangitic spread of carcinoma, in whom HRCT examination was performed. Nodular thickening of the peribronchovascular interstitium and interlobular septa are typical in lymphangitic spread of carcinoma. Smooth peribronchovascular and septal thickenings are typical in sarcoidosis, and are only seen in some patients in the lymphangitic spread of carcinoma. In lymphangitis carcinomatosa lung architecture remains unchanged, which allows differentiating from sarcoidosis.


Essential concepts in the care of children with chronic illness.
Children with chronic illness constitute an increasingly significant segment of the child population seeking care in Western industrialized countries. There are concerns that traditional disease-specific ways of thinking about these children and organizing their care may not meet the real life needs of the children and their families. This article examines a series of concepts that are fundamental for the humane and biomedically sound care of children with chronic illness, and a model of care is proposed. Relevant data from one program are presented.


Exercise training comprising of single 20-s cycle sprints does not provide a sufficient stimulus for improving maximal aerobic capacity in sedentary individuals.
Sprint interval training (SIT) provides a potent stimulus for improving maximal aerobic capacity ([Formula: see text]), which is among the strongest markers for future cardiovascular health and premature mortality. Cycling-based SIT protocols involving six or more 'all-out' 30-s Wingate sprints per training session improve [Formula: see text], but we have recently demonstrated that similar improvements in [Formula: see text] can be achieved with as few as two 20-s sprints. This suggests that the volume of sprint exercise has limited influence on subsequent training adaptations. Therefore, the aim of the present study was to examine whether a single 20-s cycle sprint per training session can provide a sufficient stimulus for improving [Formula: see text]. Thirty sedentary or recreationally active participants (10 men/20 women; mean ± SD age: 24 ± 6 years, BMI: 22.6 ± 4.0 kg m(-2), [Formula: see text]: 33 ± 7 mL kg(-1) min(-1)) were randomised to a training group or a no-intervention control group. Training involved three exercise sessions per week for 4 weeks, consisting of a single 20-s Wingate sprint (no warm-up or cool-down). [Formula: see text] was determined prior to training and 3 days following the final training session. Mean [Formula: see text] did not significantly change in the training group (2.15 ± 0.62 vs. 2.22 ± 0.64 L min(-1)) or the control group (2.07 ± 0.69 vs. 2.08 ± 0.68 L min(-1); effect of time: P = 0.17; group × time interaction effect: P = 0.26). Although we have previously demonstrated that regularly performing two repeated 20-s 'all-out' cycle sprints provides a sufficient training stimulus for a robust increase in [Formula: see text], our present study suggests that this is not the case when training sessions are limited to a single sprint.


Predicting Cardiovascular and Cerebrovascular Events Based on Instantaneous High-Order Singular Entropy and Deep Belief Network.
Automatically predicting cardiovascular and cerebrovascular events (CCEs) is a key technology that can prevent deaths and disabilities. Herein, we propose predicting CCE occurrences based on heart rate variability (HRV) analysis and a deep belief network (DBN). The proposed prediction algorithm uses eight novel HRV signal features, which are calculated based on the following steps. First, the instantaneous amplitude (IA), instantaneous frequency (IF), and instantaneous phase (IP) are calculated for the HRV signals. Second, the high-order cumulant is estimated for the HRV and its IA, IF, and IP. Third, a high-order singular entropy is calculated to measure the fluctuation in signals. Fourth, eight novel features are obtained and processed using a DBN classifier designed for CCE prediction. The DBN classification method, with the novel HRV features, outperformed existing methods in terms of accuracy. Thus, the scheme proposed herein provided a novel direction for predicting CCEs.


Modulation of phenotypic and functional properties of normal human mononuclear phagocytes by granulocyte-macrophage colony-stimulating factor.
In asthma, alveolar macrophages (AMs) are hyperreactive releasing large amounts of mediators and expressing high levels of surface markers. Granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulates monocytes and AMs, and may be involved in the hyperreactivity of AMs. The effects of GM-CSF were tested on monocytes and AMs from normal subjects by examining the expression of factors thought to be upregulated in asthma. After various incubation times of GM-CSF, the expression of CD23 and beta 2-integrins (CD11a, CD11b, CD11c) was studied by FACS and the release of sCD23 was measured by ELISA. The priming and stimulatory effects of GM-CSF were tested on monocytes and AMs and the release of leukotriene B4 (LTB4) was measured by ELISA. GM-CSF induced the expression of CD11c and CD23 and the release of sCD23. GM-CSF primed and stimulated monocytes and AMs to release LTB4. The effects of GM-CSF may explain partly the hyperreactivity of AMs in asthma.


Hepatitis B virus genetic heterogeneity and drug resistance among jaundiced patients at Coast General Teaching and Referral Hospital, Mombasa County, Kenya.
Hepatitis B virus (HBV) infection and emergence of drug resistance have remained one of the major public health puzzles. This study determined circulating HBV genotypes and nucleoside analog resistance to provide information in choosing the best therapy. A cross-sectional study was conducted among jaundiced patients visiting Coast General Teaching and Referral Hospital during the period between February and August 2018. A total of 222 patients were recruited and screened for HBsAg following the ethical procedure. Viral DNA was extracted from positive samples, partial HBV-pol gene amplified, and directly sequenced and analyzed using web-based software prediction to genotypic resistance mutations. Forty-seven (21.2%) of the 222 patients tested positive for HBV. Of the 45 samples successfully sequenced, 12 (26.4%) had drug resistance. Six patients (13.3%) had rtV173L, rtL180M, and rtM204V mutations; five subjects (11.1%) with rtL180M and rtM204V while 1 patient (2.2%) had rtM204V mutations. Therefore, all patients had cross-resistance to lamivudine and entecavir. Phylogenetic analysis revealed that HBV genotype A1 35 (74.5%) was predominant. HBV genotypes A3, B, and C2 each occurred once (0.02%). In addition, existence of new HBV genotypes A3, B, and C2 1 (0.02%) in the country was also detected. Findings suggest that HBV-infected patients should not be put on lamivudine monotherapy. These patients should be on a combination therapy; tenofovir plus lamivudine or emtricitabine to prevent emergence of drug resistance variants. In addition, HBV genotype A1 remains the most predominant genotype in this region. The detected new genotypes variants indicate a possible existence of 0.02% circulation within the population.


Safety of fibrinogen concentrate: analysis of more than 27 years of pharmacovigilance data.
Fibrinogen concentrate use as a haemostatic agent has been increasingly explored. This study evaluates spontaneous reports of potential adverse drug reactions (ADRs) that occurred during postmarketing pharmacovigilance of Haemocomplettan P/RiaSTAP, and reviews published safety data. This descriptive study analysed postmarketing safety reports recorded in the CSL Behring pharmacovigilance database from January 1986 to December 2013. A literature review of clinical studies published during the same period was performed. Commercial data indicated that 2,611,294 g of fibrinogen concentrate were distributed over the pharmacovigilance period, corresponding to 652,824 standard doses of 4 g each, across a range of clinical settings and indications. A total of 383 ADRs in 106 cases were reported (approximately 1 per 24,600 g or 6,200 standard doses). Events of special interest included possible hypersensitivity reactions in 20 cases (1 per 130,600 g or 32,600 doses), possible thromboembolic events in 28 cases (1 per 93,300 g or 23,300 doses), and suspected virus transmission in 21 cases (1 per 124,300 g or 31,000 doses). One virus transmission case could not be analysed due to insufficient data; for all other cases, a causal relationship was assessed as unlikely due to negative polymerase chain reaction tests and/or alternative explanations. The published literature revealed a similar safety profile. In conclusion, underreporting of ADRs is a known limitation of pharmacovigilance. However, the present assessment indicates that fibrinogen concentrate is administered across a range of indications, with few ADRs and a low thromboembolic event rate. Overall, fibrinogen concentrate showed a promising safety profile.


Total laparoscopic cystogastrostomy for the treatment of pancreatic pseudocyst.
Laparoscopic surgery may be performed for the treatment of pancreatic pseudocyst when decompression is indicated. Most of reported laparoscopic procedures are performed by inserting trocars via the anterior gastric wall and operating intraluminally with gastric insufflation and endoscopic guidance. We report a patient who was treated successfully with laparoscopic stapled cystogastrostomy and discuss the feasibility and features of such a technique performed with a totally abdominal approach.


Association Between Daily Internet Use and Incidence of Chronic Diseases Among Older Adults: Prospective Cohort Study.
Chronic disease incidence among the elderly is increasing, which is correlated with the acceleration of population aging. Evolving internet technologies may help prevent and provide interventions for chronic diseases in an accelerating aging process. However, the impact of daily internet use on the incidence of chronic diseases is not well understood. This study aims to investigate whether daily internet use by middle-aged and older adults may inhibit or promote the occurrence of chronic diseases. We included participants from the China Health and Retirement Longitudinal Study (CHARLS), a longitudinal survey of Chinese residents aged ≥45 years. We assessed 8-year data from wave 1 (June 2011-March 2012) to wave 4 (July-September 2018) in CHARLS. Data from wave 4 were used for a cross-sectional study, and data from all 4 waves were used for a longitudinal study. Self-reported data were used to track variables, including internet use, use frequency, and the incidence of different chronic diseases. Cox proportional hazards modeling was applied in the longitudinal study to examine the relationship between daily internet use and chronic diseases among middle-aged and older adults, while adjusting for sociodemographic characteristics and health behaviors. In addition, longitudinal data were used to analyze internet usage trends, and cross-sectional data were used to analyze the factors influencing internet use. Among the 20,113 participants included in the longitudinal analyses, internet use increased significantly, from 2% to 12.3%, between 2011 and 2018. The adjusted model found statistically significant relationships between daily internet use and a lower incidence of the following chronic diseases: hypertension (hazard ratio [HR] 0.78, 95% CI 0.65-0.95, P=.01), chronic lung disease (HR 0.74, 95% CI 0.57-0.97, P=.03), stroke (HR 0.69, 95% CI 0.50-0.94, P=.02), digestive disease (HR 0.73, 95% CI 0.58-0.91, P=.005), memory-related disorders (HR 0.58, 95% CI 0.37-0.91, P=.02), arthritis or rheumatism (HR 0.60, 95% CI 0.48-0.76, P<.001), asthma (HR 0.52, 95% CI 0.33-0.84, P=.007), depression (HR 0.80, 95% CI 0.71-0.89, P<.001), and vision impairment (HR 0.83, 95% CI 0.74-0.93, P=.004). Moreover, our study also showed that with increasing frequency of internet use, the risk of some chronic diseases decreases. This study found that middle-aged and older adults who use the internet have a reduced risk of developing chronic diseases versus those who do not use the internet. The increasing prevalence of daily internet use among middle-aged and older adults may stimulate contemplation of the potential role of internet platforms in future research on chronic disease prevention.


Plasma brain natriuretic peptide and atrial natriuretic peptide concentrations correlate with left ventricular end-diastolic pressure.
The present study was designed to investigate whether brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations correlate with left ventricular end-diastolic pressure (LVEDP), pulmonary capillary wedge pressure (PCWP), diastolic pulmonary arterial pressure (DPAP), right atrial pressure (RAP), or ejection fraction (EF). Plasma BNP and ANP levels were determined by commercial radioimmunoassays (Peninsula) after Sep Pak C18 extraction in blood samples withdrawn from the pulmonary artery and the left ventricle or from the left ventricle and the femoral vein in 85 patients undergoing diagnostic cardiac catheterization. Linear and nonlinear regression analysis and the paired sample t-test were applied to the data. Pulmonary arterial plasma BNP and ANP levels showed a close nonlinear correlation with LVEDP (BNP: r = 0.94, p < 0.001; ANP: r = 0.81, p < 0.001), a significant linear correlation with PCWP, DPAP, and RAP, and a significant negative correlation with EF. ANP concentrations decreased significantly from the pulmonary artery to the left ventricle and from the left ventricle to the femoral vein (p < 0.001). BNP levels also decreased significantly between the left ventricle and the femoral vein (p < 0.001), but there was no significant difference between pulmonary arterial and left ventricular BNP concentrations. BNP and ANP concentrations correlated significantly between pulmonary arterial and left ventricular blood samples (BNP: r = 0.99, ANP: r = 0.93, p < 0.001) and between left ventricular and peripheral blood samples (BNP: r = 0.99, ANP: r = 0.94, p < 0.001). The present data suggest that peripheral plasma BNP and ANP levels are useful non-invasive indices of cardiac performance.


A Cross-Sectional Study on the Estimation of Urine Albumin for the Early Diagnosis of Diabetic Nephropathy Among Patients With Diabetes Mellitus at a Tertiary Care Hospital in Central India.
Background Diabetic nephropathy is a significant concern among individuals with diabetes mellitus, warranting early diagnosis for effective management. This study focuses on the potential of urine albumin estimation as an early diagnostic tool for diabetic nephropathy among patients in central India. Methods A cross-sectional methodology involved 65 individuals diagnosed with diabetes mellitus at a tertiary care hospital. Demographic factors, including age, gender, family history, duration of diabetes, and dietary patterns, were gathered. Urine albumin levels were categorized as "normal," "microalbuminuria," and "macroalbuminuria." The collected data were analyzed using IBM SPSS Statistics, version 24.0 (IBM Corp., Armonk, NY). Qualitative variables were presented as percentages and counts. The comparison between groups was conducted using the chi-square exact test. Quantitative variables were described as mean (±standard deviation) and median. Results The study reveals that 78.5% of cases exhibited normal levels below 30 mg, with a mean value of 1.00 ± 0.414. Microalbuminuria, characterized by 30-300 mg levels, was observed in 21.5% of cases. Importantly, no instances of macroalbuminuria, with levels exceeding 300 mg, were detected among the participants. There are associations between demographic variables and diabetic nephropathy findings. Age and gender displayed non-significant associations. Family history of diseases, particularly diabetes, showed significance. Diabetes duration demonstrated a significant link, while diet patterns displayed no significant associations. Conclusion This study contributes insights into the complex interactions of demographic factors in diabetic nephropathy. Early identification and intervention, guided by the associations observed, could enhance patient outcomes and mitigate the burden of diabetic nephropathy-related complications. Further research is warranted to validate and extend these findings to diverse populations.


Geometry and Topology of Two-Dimensional Dry Foams: Computer Simulation and Experimental Characterization.
Pseudo-two-dimensional (2D) foams are commonly used in foam studies as it is experimentally easier to measure the bubble size distribution and other geometric and topological properties of these foams than it is for a 3D foam. Despite the widespread use of 2D foams in both simulation and experimental studies, many important geometric and topological relationships are still not well understood. Film size, for example, is a key parameter in the stability of bubbles and the overall structure of foams. The relationship between the size distribution of the films in a foam and that of the bubbles themselves is thus a key relationship in the modeling and simulation of unstable foams. This work uses structural simulation from Surface Evolver to statistically analyze this relationship and to ultimately formulate a relationship for the film size in 2D foams that is shown to be valid across a wide range of different bubble polydispersities. These results and other topological features are then validated using digital image analysis of experimental pseudo-2D foams produced in a vertical Hele-Shaw cell, which contains a monolayer of bubbles between two plates. From both the experimental and computational results, it is shown that there is a distribution of sizes that a film can adopt and that this distribution is very strongly dependent on the sizes of the two bubbles to which the film is attached, especially the smaller one, but that it is virtually independent of the underlying polydispersity of the foam.


High progesterone levels during the luteal phase related to the use of an aromatase inhibitor in breast cancer patients.
To evaluate the hormonal profile in three breast cancer patients who underwent controlled ovarian stimulation in the presence of the aromatase inhibitor letrozole. In IVF University referral center, a case series of three breast cancer patients who underwent controlled ovarian stimulation (COS) with recombinant FSH and letrozole were investigated. Ovulation was induced with hCG (case No. 1) or with GnRH agonist (case No. 2-3). The primary outcome of our study was the detection of progesterone levels in the luteal phase. Very high progesterone values (mean 186.6 ± 43.6 ng/mL) during the luteal phase were recorded in all three cases. High progesterone levels can be related to the use of letrozole independently of the most commonly used trigger regimen. Although progesterone has long been considered a protective factor against breast cancer, several studies have demonstrated that progesterone could expand a transformation-sensitive stem cell population in the mammary glands. The estrogen negative feedback effect on the hypothalamus-pituitary axis and the disruption of steroid biosynthesis and could represent an intriguing reason behind this phenomenon. Our results highlight the need to evaluate further the increase in progesterone levels in the luteal phase in women with breast cancer undergoing COS with letrozole.


Combined effect of biopesticides on the digestive enzymatic profiles of Aedes aegypti (Diptera: Culicidae).
This study evaluated efficiency of two bacterial mosquito larvicides and a plant extract one against Aedes aegypti larvae when used in combinations with each other under laboratory conditions, is an integrated method of control. Plant extracts, especially botanical insecticides, are currently studied more and more because of the possibility of their use in plant protection. Many of the natural plant compounds and organic compounds used in the control of insect pests are known to affect digestive enzymes. When fed a diet of rice leaves treated with botanical insecticides and bacterial toxins in bioassays, activities of the digestive enzymes protease, amylase, and lipase in the A. aegypti larvae are affected. Digestive enzyme activities were affected by botanical insecticides and bacterial toxins individually and in combination. When combined, the effect was more severe at low concentration. There were statistically significant differences (P < or = 0.05) in enzyme activities in combined and individual treatments. The combination of Btk and botanical insecticides caused a two-fold decrease in enzyme activity even at reduced concentration. Clear dose-response relationships were established with respect to enzyme activity. A synergistic effect of botanical insecticides and bacterial toxins was found when combined in low doses. These effects are most pronounced in early instars.


Aozan: an automated post-sequencing data-processing pipeline.
Data management and quality control of output from Illumina sequencers is a disk space- and time-consuming task. Thus, we developed Aozan to automatically handle data transfer, demultiplexing, conversion and quality control once a run has finished. This software greatly improves run data management and the monitoring of run statistics via automatic emails and HTML web reports. Aozan is implemented in Java and Python, supported on Linux systems, and distributed under the GPLv3 License at: http://www.outils.genomique.biologie.ens.fr/aozan/ . Aozan source code is available on GitHub: https://github.com/GenomicParisCentre/aozan . email@example.com.


Association study of 69 genes in the ret pathway identifies low-penetrance loci in sporadic medullary thyroid carcinoma.
To date, few association studies have been done to better understand the genetic basis for the development of sporadic medullary thyroid carcinoma (sMTC). To identify additional low-penetrance genes, we have done a two-stage case-control study in two European populations using high-throughput genotyping. We selected 417 single nucleotide polymorphisms (SNP) belonging to 69 genes either related to RET signaling pathway/functions or involved in key processes for cancer development. TagSNPs and functional variants were included where possible. These SNPs were initially studied in the largest known series of sMTC cases (n = 266) and controls (n = 422), all of Spanish origin. In stage II, an independent British series of 155 sMTC patients and 531 controls was included to validate the previous results. Associations were assessed by an exhaustive analysis of individual SNPs but also considering gene- and linkage disequilibrium-based haplotypes. This strategy allowed us to identify seven low-penetrance genes, six of them (STAT1, AURKA, BCL2, CDKN2B, CDK6, and COMT) consistently associated with sMTC risk in the two case-control series and a seventh (HRAS) with individual SNPs and haplotypes associated with sMTC in the Spanish data set. The potential role of CDKN2B was confirmed by a functional assay showing a role of a SNP (rs7044859) in the promoter region in altering the binding of the transcription factor HNF1. These results highlight the utility of association studies using homogeneous series of cases for better understanding complex diseases.


General and specific abilities to recognise negative emotions, especially disgust, as portrayed in the face and the body.
We examined the ability of 150-166 undergraduate students to assign four negative emotions (sadness, fear, disgust, and anger) to five sets of emotion expression stimuli: a standard of face photographs expressing basic emotions, faces that were morphs of standards for these emotions, a special set of faces that was designed to detect different components of disgust expressions, and two sets of dynamic, video clips displays of emotions as described in traditional Hindu scriptures and used in classical Hindu dance. One of these sets presented the full body traditional displays (including hands and face), while in the second set, the same clips were used but the facial expressions were blocked out. Participants also completed an obsessive compulsive inventory and the disgust scale. Major findings are that: (a) there are some substantial individual differences in ability to correctly identify emotions; (b) the ability to detect facial emotions correlates substantially (.49) with ability to detect bodily emotions; (c) there is no evidence for specific deficits in the detection of any particular emotion; and (d) there is no relation between individual differences in obsessive-compulsive disorder (OCD) tendencies or disgust sensitivity, in a normal sample and the ability to detect disgust.


[Effect of the light-dark cycle over the growth of male rats with different health status].
The light-dark cycle exerts an influence over the lipostatic mechanism in the superior vertebrate animals promoting an acceleration in the lipid synthesis rate during the dark period (in the case of rodents) and a higher lipolitic rate during the day. This cycle, the feeding habits, and the awake-sleep cycle are syncronized. The Growth Hormone is a molecule that facilitates the lipolysis and the protein synthesis. This hormone is released, by the pituitary gland, during the puberty and during the short wave sleep period. Modifying the light-dark cycle and in consequence the sleep-awake cycle and the food consumption, we pretend to study its influence over the growth rate in weight and length in animals that consume 100% of its nutritional requirements. Also want to dilucidate if an alteration of the cycle (18 h light 6 h dark) in the malnourished animals can revert the deficiency of the growth rate expected in these animals. Male Wistar rats (160); 21 days old, adapted to the temperature and to the light-dark cycle (12 h-12 h) during a week. Then, four groups were formed; Group I: Well nourished rats with a light-dark (12 h-12 h) cycle; Group II: Well nourished rats with a light-dark (18 h-6 h) cycle; Group III: Malnourished rats with a light-dark (12 h-12 h) cycle; Group IV: Malnourished rats with a light-dark (18 h-6 h) cycle. Its length and weight were registered weekly, obtained its growth rates, and the results were analysed by the ONE-WAY ANOVA and orthogonal contrasts. It was found a significant difference in the growth rate in weight between the Groups I and II; the growth rate in weight in the Group III had a higher slope than the rate in the Group IV but we did not find a significant difference. The growth rate in length did not show a significant difference between the Groups III and IV. The last weight in the malnourished animals represented 55% of the control animals last weight; and 47% of the Group IV. The last length of the animals of the Group III represented 90% of the control value, and the last length in the Group IV represented 82% of the control animals value. The feeding habits are modified changing the cycle to 18 h light and 6 h dark. Modifying the light-dark cycle appears an accelerating rate in the growth rate in weight in the well nourished animals, but not in the malnourished ones.


Diffuse large B-cell lymphoma of Waldeyer's ring has distinct clinicopathologic features: a GELA study.
Diffuse large B-cell lymphomas (DLBCLs) arising in specific extranodal sites have peculiar clinicopathologic features. We analyzed a cohort of 187 primary Waldeyer's ring (WR) DLBCLs retrieved from GELA protocols using anthracyclin-based polychemotherapy. Most patients (92%) had stage I-II disease. A germinal center B-cell-like (GCB) immunophenotype was observed in 61%, and BCL2 expression in 55%, of WR DLBCLs. BCL2, BCL6, IRF4 and MYC breakpoints were observed in, respectively, 3 of 42 (7%), 9 of 36 (25%), 2 of 26 (8%) and 4 of 40 (10%) contributive cases. A variable follicular pattern was evidenced in 30 of 68 (44%) large biopsy specimens. The 5-year progression-free survival (PFS) and the overall survival (OS) of 153 WR DLBCL patients with survival information were 69.5% and 77.8%, respectively. The GCB immunophenotype correlated with a better OS (P = 0.0015), while BCL2 expression predicted a worse OS (P = 0.037), an effect overcome by the GCB/non-GCB classification. Compared with matched nodal DLBCLs, WR DLBCLs with no age-adjusted international prognostic index factor disclosed a better 5-year PFS rate (77.5% versus 70.7%; P = 0.03). WR DLBCLs display distinct clinicopathologic features compared with conventional DLBCLs, with usual localized-stage disease, common follicular features and a high frequency of GCB immunophenotype contrasting with a low rate of BCL2 rearrangements. In addition, they seem to be associated with a better outcome than their nodal counterpart.


Epigenome-wide DNA methylation profiling of conditioned pain modulation in individuals with non-specific chronic low back pain.
The pathoanatomic cause of chronic low back pain (cLBP) cannot be identified for up to 90% of individuals. However, dysfunctional processing of endogenous nociceptive input, measured as conditioned pain modulation (CPM), has been associated with cLBP and may involve changes in neuronal gene expression. Epigenetic-induced changes such as DNA methylation (DNAm) have been associated with cLBP. In the present study, the relationship between CPM and DNAm changes in a sample of community-dwelling adults with nonspecific cLBP (n = 48) and pain-free controls (PFC; n = 50) was examined using reduced representation bisulfite sequencing. Gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to identify key pathways involved in efficient versus deficient CPM. Based on CPM efficiency, we identified 6006 and 18,305 differentially methylated CpG sites (DMCs) with q values < 0.01 among individuals with cLBP and PFCs, respectively. Most of the DMCs were hypomethylated and annotated to genes of relevance to pain, including OPRM1, ADRB2, CACNA2D3, GNA12, LPL, NAXD, and ASPHD1. In both cLBP and PFC groups, the DMCs annotated genes enriched many GO terms relevant to pain processing, including transcription regulation by RNA polymerase II, nervous system development, generation of neurons, neuron differentiation, and neurogenesis. Both groups also enriched the pathways involved in Rap1-signaling, cancer, and dopaminergic neurogenesis. However, MAPK-Ras signaling pathways were enriched in the cLBP, not the PFC group. This is the first study to investigate the genome-scale DNA methylation profiles of CPM phenotype in adults with cLBP and PFCs. Based on CPM efficiency, fewer DMC enrichment pathways were unique to the cLBP than the PFCs group. Our results suggest that epigenetically induced modification of neuronal development/differentiation pathways may affect CPM efficiency, suggesting novel potential therapeutic targets for central sensitization. However, CPM efficiency and the experience of nonspecific cLBP may be independent. Further mechanistic studies are required to confirm the relationship between CPM, central sensitization, and nonspecific cLBP.


Descemet stripping automated endothelial keratoplasty in complex eyes: results with a donor insertion device.
Descemet stripping automated endothelial keratoplasty (DSAEK) in eyes with complex anterior segment pathology or previous intraocular surgery is at risk of surgical complications and graft failure. We evaluated the use of the EndoGlide donor insertion device for DSAEK in these complex cases. This was a retrospective interventional series of 45 consecutive eyes with endothelial dysfunction and higher risk ocular comorbidities that underwent DSAEK with the EndoGlide. We included eyes with aphakia, glaucoma surgery, prior vitrectomy, anterior chamber intraocular lenses, failed cornea grafts, and primary angle closure glaucoma. Demographic and clinical details, intraoperative and postoperative complications, and postoperative graft clarity, and endothelial cell density (ECD) loss were documented. The average age was 62 years (range, 16-88 years), and the majority were Chinese (n = 28). The commonest risk factors identified were previous trabeculectomy (n = 13) and failed penetrating keratoplasty (n = 12). Preoperative donor ECD averaged 2790 ± 230 cells per square millimeter and modal graft diameter was 9.0 mm (range, 7.75-9.75 mm). One eye (2.2%) had primary graft failure, and 3 eyes (6.7%) had graft dislocation. Another 3 eyes suffered late graft failure within the first year and 2 were in eyes with an anterior chamber intraocular lenses. At 6 months, the mean ECD was 2363 + 242 cells/mm2 and the mean ECD loss was 17.9% (n = 16). By 12 months, the mean ECD was 2098 + 462 cells/mm2 and the mean ECD loss was 27.0% (n = 20). Donor insertion with this device can help address inherent intraoperative challenges and minimize endothelial cell damage during DSAEK in complex cases.


Successful Prolonged Mechanical CPR in a Severely Poisoned Hypothermic Patient: A Case Report.
Mechanical cardiopulmonary resuscitation (m-CPR) devices are an alternative to manual CPR, but their efficacy has been subject to debate. We present a case of a patient with full-neurologic recovery after prolonged m-CPR. The patient presented with severe hypothermia (internal temperature 24°C) and poisoning (sedatives/hypnotics). Hepatic perfusion and metabolism are considered keys to restore spontaneous circulation. During this period no problems related to the device or patient positioning were encountered. Delivery of high-quality CPR and prolonged resuscitation were achieved. We confirm that ventilations asynchronous with chest compressions can be a problem. Reduction in chest measurements can hamper lung ventilation. A synchronous mode of manual ventilation (30 : 2) seems to be the best solution. The patient had an initial period of manual CPR. No damage to any organ or structure was noted. This case is of further interest because our EMS helicopters can fly 24 hours a day and m-CPR devices could play an important role as a "bridge" in patients when active rewarming by cardiopulmonary bypass is indicated (CPB).