Do microbial decomposers find micro- and nanoplastics to be harmful stressors in the aquatic environment? A systematic review of in vitro toxicological research.
Microbial decomposers (bacteria and fungi) are likely to interact with plastic particles introduced into natural systems, particularly micro- and nanoplastics (MNPs), exposing them to a variety of risks. In vitro testing has proven to be an accessible and viable method for gaining insights into how microbial decomposers behave individually and systemically toward MNPs. Recent advances have enhanced our understanding of MNP interactions with organisms, revealing the molecular foundations of adaptive responses as well as the biological impact and potential risks to MNPs. Despite widespread attention, this topic has not yet been reviewed. Here, we conducted a systematic review of the available research to critically assess and highlight the most recent advances in two major areas: (1) methods for in vitro evaluation of environmentally relevant microbial decomposers to MNPs; and (2) current understanding of the underlying toxicity mechanisms gained from in vitro assessments. We also addressed the key considerations throughout and proposed available opportunities in the field. Our analysis revealed that MNPs' toxicity has been studied in vitro either alone or in combination with other contaminants (e.g., antibiotics and metallic nanoparticles), with Escherichia coli and polystyrene particles receiving the most attention. Moreover, there were methodological differences in terms of MNP size, shape, polymer, surface characteristics, exposure period, and concentrations. A combination of methods, including growth-viability tests, biochemical assays, and omics profiling (metabolomics and transcriptomics), were employed to detect the effects of MNP exposure and explain its toxicity mechanism. The current literature suggests that the impacts of MNPs on microbial decomposers include alterations in the antioxidative system, gene expression levels and cell-membrane permeability and oxidative damage, all of which can be further influenced by MNPs interaction with other contaminants. This review will thus provide critical insights and up-to-date knowledge to assist novices and experts in promoting advancements and research.


Multivariant Transcriptome Analysis Identifies Modules and Hub Genes Associated with Poor Outcomes in Newly Diagnosed Multiple Myeloma Patients.
The molecular mechanisms underlying chemoresistance in some newly diagnosed multiple myeloma (MM) patients receiving standard therapies (lenalidomide, bortezomib, and dexamethasone) are poorly understood. Identifying clinically relevant gene networks associated with death due to MM may uncover novel mechanisms, drug targets, and prognostic biomarkers to improve the treatment of the disease. This study used data from the MMRF CoMMpass RNA-seq dataset (N = 270) for weighted gene co-expression network analysis (WGCNA), which identified 21 modules of co-expressed genes. Genes differentially expressed in patients with poor outcomes were assessed using two independent sample t-tests (dead and alive MM patients). The clinical performance of biomarker candidates was evaluated using overall survival via a log-rank Kaplan-Meier and ROC test. Four distinct modules (M10, M13, M15, and M20) were significantly correlated with MM vital status and differentially expressed between the dead (poor outcomes) and the alive MM patients within two years. The biological functions of modules positively correlated with death (M10, M13, and M20) were G-protein coupled receptor protein, cell-cell adhesion, cell cycle regulation genes, and cellular membrane fusion genes. In contrast, a negatively correlated module to MM mortality (M15) was the regulation of B-cell activation and lymphocyte differentiation. MM biomarkers CTAG2, MAGEA6, CCND2, NEK2, and E2F2 were co-expressed in positively correlated modules to MM vital status, which was associated with MM's lower overall survival.


Skin burns after laser exposure: histological analysis and predictive simulation.
Thermal effects of laser irradiation on skin are investigated in this paper. The main purpose is to determine the damage level induced by a laser exposure. Potential burns induced by two lasers (wavelength 808nm and 1940nm) are studied and animal experimentations are performed. Several exposure durations and laser powers are tested. Based on previous works, a mathematical model dedicated to temperature prediction is proposed and finite-element method is implemented. This numerical predictive tool based on the bioheat equation takes into account heat losses due to the convection on skin surface, blood circulatory and also evaporation. Thermal behavior of each skin layer is also described considering distinct thermal and optical properties. Since the mathematical model is able to estimate damage levels, histological analyses were also carried through. It is confirmed that the mathematical model is an efficient predictive tool for estimation of damage caused by lasers and that thermal effects sharply depend on laser wavelength.


Effective Patient-Provider Communication in Pediatric Obesity.
Effective patient-provider communication is not a primary focus of medical school curricula. Motivational interviewing (MI) is a patient-centered, directive communication framework appropriate for in health care. Research on MI's causal mechanisms has established patient change talk as a mediator of behavior change. Current MI research focuses on identifying which provider communication skills are responsible for evoking change talk. MI recommends informing, asking, and listening. Research provides evidence that asking for and reflecting patient change talk are effective communication strategies, but cautions providers to inform judiciously. Supporting a patient's decision making autonomy is an important strategy to promote health behaviors.


Treatment of essential thrombocythemia with anagrelide.
Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by persistent elevation in platelet count. It is a rare disorder in children, and children who have symptoms require treatment. We report the successful use of anagrelide, with few toxic effects, in the treatment of three children with ET.


Inhibitory effect of Toxoplasma lysate antigen on the multiplication of transplanted tumor in mice.
Tachyzoites of the RH strain of Toxoplasma gondii were pretreated by a process of freezing and thawing followed by ultrasonication. After ultracentrifugation at 144,000 g for 120 minutes, the resulting supernatant contained a protein (TLA 144), which consisted mainly of a component of protozoan origin with a molecular weight of 10,000-20,000, and additional sugars, peptides, and amino acids. TLA 144 was soluble in water and of very low toxicity. Mice that had been inoculated with allogeneic (S-180) and syngeneic (Meth A) transplantable tumor cells, were injected intramuscularly with 100 micrograms of TLA 144 once a week for some time beginning one week after transplantation. It was found that after TLA treatment the multiplication of tumor cells was more intensely inhibited than following administration of OK-432, one of the biological response modifiers (BRMs).


Atrioventricular sequential pacing using transesophageal atrial pacing in combination with a temporary DDD pacemaker for atrial tracking and ventricular pacing.
To determine whether atrioventricular (A-V) sequential pacing can be accomplished using transesophageal atrial pacing (TAP) in combination with a temporary DDD pacemaker for tracking the TAP stimuli and pacing the ventricle via temporary epicardial electrodes. Prospective; patients enrolled consecutively. Nonuniversity teaching hospital. Ten adults undergoing cardiac surgery requiring cardiopulmonary bypass. Two to six hours after the termination of cardiopulmonary bypass, atrial pacing was initiated via TAP. The atrial system of a temporary DDD pacemaker was connected to surface electrocardiogram (ECG) electrodes. If the temporary pacemaker could track the TAP stimuli and emit pacing stimuli resulting in ventricular capture, A-V sequential pacing was considered to have occurred. The patients were immediately restudied in the same manner with the change that the temporary DDD pacemaker sensed the TAP stimuli via temporary atrial bipolar epicardial electrodes rather than surface ECG electrodes. Dual pacemaker A-V sequential pacing was accomplished in 17 out of 20 attempts. The atrial system of the temporary DDD pacemaker was able to sense the TAP stimulus via temporary atrial bipolar epicardial leads in 10 out of 10 patients and directly from surface ECG electrodes (right arm/left arm) in 7 out of 10 patients. This report demonstrates that it is possible to A-V sequentially pace using TAP in combination with a temporary DDD pacemaker for tracking the TAP stimulus and pacing the ventricle via temporary epicardial leads. This technique may be useful when A-V sequential pacing is needed and functional temporary atrial leads are not available.


Technical modification of the double-balloon endoscopy to access to the proximal side of the stenosis in the distal colon.
The inability to pass endoscopes beyond strictures is a considerable problem in patients with a colonic stricture. In patients with bowel obstruction, we have modified the insertion method for double-balloon endoscopy with a long, transnasal decompression tube. We have succeeded in reaching the proximal side of the stricture from the oral approach across the entire small bowel in a patient. This modified double-balloon enteroscopy is useful for patients with bowel obstruction in whom a long decompression tube is already placed.


Microdoses of Recombinant Human Erythropoietin Enhance Time Trial Performance in Trained Males and Females.
We investigated the effects of recombinant human erythropoietin (rHuEPO) administration on exercise endurance, maximal aerobic performance, and total hemoglobin mass (tHb). We hypothesized that frequent, small intravenous injections of epoetin β would increase time trial performance, peak oxygen uptake (V̇O 2peak ), and tHb in both males and females. We included 48 healthy, recreational to trained males ( n = 24, mean ± SD V̇O 2peak = 55 ± 5 mL O 2 ·kg -1 ⋅min -1 ) and females ( n = 24; V̇O 2peak of 46 ± 4 mL O 2 ·kg -1 ⋅min -1 ) in a counterbalanced, double-blind, randomized, placebo-controlled study design stratified by sex. Time trial performance, V̇O 2peak , and tHb were determined before and after intravenous injections of either rHuEPO (9 IU·kg bw -1 epoetin β) or saline (0.9% NaCl) three times weekly for 4 wk. A time-treatment effect ( P < 0.05) existed for time trial performance. Within the rHuEPO group, mean power output increased by 4.1% ± 4.2% ( P < 0.001). Likewise, a time-treatment effect ( P < 0.001) existed for V̇O 2peak , where the rHuEPO group improved V̇O 2peak and peak aerobic power by 4.2% ± 6.1% ( P < 0.001) and 2.9% ± 4.0% ( P < 0.01), respectively. A time-treatment effect ( P < 0.001) existed for tHb, where the rHuEPO group increased tHb by 6.7% ± 3.4% ( P < 0.001). A main effect of "sex" alone was also evident ( P < 0.001), but no sex-specific interactions were found. No changes were observed in the placebo group for mean power output, V̇O 2peak , peak aerobic power, or tHb. Microdoses with intravenous rHuEPO provide a sufficient erythropoietic stimuli to augment tHb and enhance aerobic-dominated performance in both trained males and females.


Small-molecule autocatalysis drives compartment growth, competition and reproduction.
Sustained autocatalysis coupled to compartment growth and division is a key step in the origin of life, but an experimental demonstration of this phenomenon in an artificial system has previously proven elusive. We show that autocatalytic reactions within compartments-when autocatalysis, and reactant and solvent exchange outpace product exchange-drive osmosis and diffusion, resulting in compartment growth. We demonstrate, using the formose reaction compartmentalized in aqueous droplets in an emulsion, that compartment volume can more than double. Competition for a common reactant (formaldehyde) causes variation in droplet growth rate based on the composition of the surrounding droplets. These growth rate variations are partially transmitted after selective division of the largest droplets by shearing, which converts growth-rate differences into differences in droplet frequency. This shows how a combination of properties of living systems (growth, division, variation, competition, rudimentary heredity and selection) can arise from simple physical-chemical processes and may have paved the way for the emergence of evolution by natural selection.


Perception of various stakeholders regarding clinical drug trial industry in India.
Though India has been thought to be an ideal destination for conduct of clinical drug trials, other smaller countries seem to be doing better. The pace of growth observed during 2005-2009 seems to be plateaued in 2010. There is an urgent need for introspection and corrective actions. An online survey was conducted among various stakeholders from clinical drug trial industry in India regarding their perception about clinical drug trial industry in India. Respondents were requested to rate training of investigator sites, industry, performance of regulatory, etc. Majority of respondent felt that the clinical drug trial industry in India is growing, though India is not utilizing its full potential. Lack of trained investigators and delay in regulatory approvals came out as biggest hurdles. Urgent steps need to be taken in terms of proper training of all stakeholders. Regulatory bodies ought to bring about some radical changes in the system so as to match the other competing nations.


'My pupil has gone black!' Subluxation of a total cataractous lens.
A patient with a history of longstanding opaque cataract and a white pupil reported a return to a black pupil, which was the result of lens subluxation. The case was complicated by optic nerve coloboma of the Morning Glory syndrome type and a total retinal detachment.


Therapeutic innovations in endocrine diseases - Part 2: Modified-release glucocorticoid compounds: What good do they provide to the adrenal insufficient patient?
Intensive researches on modified-release hydrocortisone compounds developed in the last decade have paved the way for obtaining near-physiological glucocorticoid replacement in the adrenal insufficient patient. The dual-release Duocort (Plenadren) allows a unique morning intake and closely mimics the circadian rhythm of cortisol secretion, except for the progressive nocturnal increase and the morning cortisol peak observed in healthy subjects. Duocort treatment during a 6-month period was associated with favorable changes in weight, blood pressure and glycemic control in patients with diabetes mellitus. Chronocort, a multiparticulate formulation with sustained-release properties replaces endogenous cortisol in a near-physiologic manner and fully restores the end of night cortisol peak. A twice-daily Chronocort regimen was effective in controlling androgen excess in adults with CAH. Recently, the new multiparticulate formulation Infacort was designed for the treatment of adrenal insufficiency during infancy. Long term effectiveness and safety studies are needed until these promising hydrocortisone formulations become routine therapeutic tools in adrenal insufficiency.


Relativistic state equations for the interface.
Relativistic state equations were obtained for various interfaces and cases. The relativistic state equation was done for perfect gases as well.


Gene expression meta-analysis reveals immune response convergence on the IFNγ-STAT1-IRF1 axis and adaptive immune resistance mechanisms in lymphoma.
Cancers adapt to immune-surveillance through evasion. Immune responses against carcinoma and melanoma converge on cytotoxic effectors and IFNγ-STAT1-IRF1 signalling. Local IFN-driven immune checkpoint expression can mediate feedback inhibition and adaptive immune resistance. Whether such coupled immune polarization and adaptive resistance is generalisable to lymphoid malignancies is incompletely defined. The host response in diffuse large B-cell lymphoma (DLBCL), the commonest aggressive lymphoid malignancy, provides an empirical model. Using ten publicly available gene expression data sets encompassing 2030 cases we explore the nature of host response in DLBCL. Starting from the "cell of origin" paradigm for DLBCL classification, we use the consistency of differential expression to define polarized patterns of immune response genes in DLBCL, and derive a linear classifier of immune response gene expression. We validate and extend the results in an approach independent of "cell of origin" classification based on gene expression correlations across all data sets. T-cell and cytotoxic gene expression with polarization along the IFNγ-STAT1-IRF1 axis provides a defining feature of the immune response in DLBCL. This response is associated with improved outcome, particularly in the germinal centre B-cell subsets of DLBCL. Analysis of gene correlations across all data sets, independent of "cell of origin" class, demonstrates a consistent association with a hierarchy of immune-regulatory gene expression that places IDO1, LAG3 and FGL2 ahead of PD1-ligands CD274 and PDCD1LG2. Immune responses in DLBCL converge onto the IFNγ-STAT1-IRF1 axis and link to diverse potential mediators of adaptive immune resistance identifying future therapeutic targets.


Impact of pr-10a overexpression on the cryopreservation success of Solanum tuberosum suspension cultures.
Although many genes are supposed to be a part of plant cell tolerance mechanisms against osmotic or salt stress, their influence on tolerance towards stress during cryopreservation procedures has rarely been investigated. For instance, the overexpression of the pathogenesis-related gene 10a (pr-10a) leads to improved osmotic tolerance in a transgenic cell culture of Solanum tuberosum cv. Désirée. In this study, a cryopreservation method, consisting of osmotic pretreatment, cryoprotection with DMSO and controlled-rate freezing, was used to characterize the relation between cryopreservation success and pr-10a expression in suspension cultures of S. tuberosum wild-type cells and cells overexpressing pathogenesis-related protein 10a (Pr-10a). By varying the sorbitol concentration, thus modifying the strength of the osmotic stress during the pretreatment phase, it can be shown that the wild type can successfully be cryopreserved only in a relatively narrow range of sorbitol concentrations, while the pr-10a overexpression leads to an enhanced cryopreservation success over the whole range of applied sorbitol concentrations. Together with transcription data we show that the pr-10a overexpression causes an enhanced osmotic tolerance, which in turn leads to enhanced cryopreservability, but also indicates a role of pr-10a in signal transduction. An increased cryopreservability of the transgenic cell line occurs for pretreatments longer than 24 h. Since both genotypes, characterized by distinct baseline levels of expression, exhibited similar patterns of expression induction, the induction of pr-10a appears to be a key step in the stress signal transduction of plant cells under osmotic stress.


Effect of arachidonic acid on cultured cerebromicrovascular endothelium: permeability, lipid peroxidation and membrane "fluidity".
The relationship of free arachidonic acid (AA) to cellular permeability, lipid peroxidation and physical state "fluidity" of the membrane was investigated in cultured endothelial cells (EC) dissociated from cerebral microvessels of rats. The results demonstrate that AA can induce a reversible alteration of endothelial permeability to trypan blue albumin (TBA). Exposure of EC to AA increases membrane "fluidity" as measured by fluorescence anisotropy using 1,6-diphenyl-1,3,5 hexatriene as a fluorescent probe. The AA modification of EC membrane "fluidity" is not associated with changes in EC permeability. Addition of AA and H2O2 to the incubation medium of EC leads to persistant alteration of EC permeability which can be prevented by catalase treatment. Both AA and H2O2 induce a greater formation of malondialdehyde, the product of lipid peroxidation, than AA alone. These findings strongly suggest that a release of AA either from the capillary or cellular membrane of the brain under a pathological condition may alone or through a peroxidative process alter the function of blood-brain barrier.


Purification and characterization of glycogen phosphorylase B from skeletal muscle of the mullet Liza ramada: amino acid sequence of the phosphorylation site.
1. Skeletal muscle glycogen phosphorylase b has been purified from Liza ramada (mullet). 2. The Mr of the purified enzyme subunit was found to be 97,000. By gel filtration a relative Mr of 190,000 was found. 3. Proteolytic digestion of 32P-phosphorylated mullet phosphorylase gave a [32P]-labelled peptide which is observed to contain Ser, its sequence being -Gln-Ile-Ser-Val-Pro-. 4. During 'in vitro' phosphorylation of mullet phosphorylase, 32P was incorporated in different protein bands resolved by isoelectric focusing. The degree of radioactivity associated with each one changed with the incubation time.


Reactions of n-hexanal with glycine in model systems.
n-Hexanal a common component of off-flavor of various foodstuffs forms in ethanol-water solutions brown coloured pigments with glycine very slowly. The changes in the ultra-violet region of spectrum, especially at the maximum at 280 nm are much quicker. Due to the fact that only the non-protonised amino acid reacts, the reaction rate is the highest in alkaline medium, especially at pH value 8.5-9. The primary product of the condensation of n-hexanal with glycine, the Schiff base, is not stable, as confirmed by the decreasing of the polarographic wave heights. The reaction rate constants of this decomposition were the highest at pH-value 8.5-9 similarly as the changes in the UV-Spectra. The effect of the temperature was negligible.


Impact of blood glucose monitoring affect on family conflict and glycemic control in adolescents with type 1 diabetes.
This longitudinal study examined whether diabetes-specific family conflict and glycemic control were impacted/explained by negative affective responses to blood glucose checks (Negative BGM Affect). Adolescents (N=150, ages 13-18 years) with type 1 diabetes, and their caregivers, completed measures of Negative BGM Affect, diabetes-specific family conflict, and glycemic control (i.e., hemoglobin A1c) at baseline, 6-, and 12-months. Caregiver Negative BGM Affect predicted higher A1c values at 12 months. Diabetes-specific family conflict mediated and explained 39% of the Negative BGM Affect-A1c relationship. Conflict around direct management tasks mediated the caregiver Negative BGM Affect-A1c relationship for adolescents (30.6% of variance). The impact of Negative BGM Affect on diabetes-specific family conflict is more pervasive for caregivers (direct and indirect diabetes management tasks) than adolescents (direct diabetes management tasks only). Caregiver Negative BGM Affect is an important contributor to A1c via diabetes-specific family conflict. Identifying and intervening with families who endorse high levels of Negative BGM Affect may prevent diabetes-specific family conflict, thereby minimizing the impact of family conflict on glycemic control. Brief clinic-based interventions to address Negative BGM Affect can be incorporated into clinical practice to prevent long-term negative impact on glycemic control.


A rapid method for the quantification of C, N and O in biomedical samples by proton-induced gamma-ray emission analysis applied to human placental samples.
A new fast, accurate and simple quantification method for C, N and O in biomedical samples by external-beam proton-induced gamma-ray emission analysis is presented. Concentration values for C, N and O in commercial standards of NBS bovine liver 1577a, IAEA animal muscle H-4 and IAEA horse kidney H-8 were determined using the new method. The concentrations of C, N, O, Na, Mg and P were determined from placental samples of 13 alcoholic mothers and from 16 abstinent controls. The values obtained for C, N, O, Mg and P were the first values ever obtained for human placentas.


Intraoperative radiotherapy for esophageal carcinoma--significance of IORT dose for the incidence of fatal tracheal complication.
The feasibility of intraoperative radiotherapy (IORT) combined with modified regional lymphatic dissection (plus esophagectomy) for advanced esophageal carcinoma was tested. The quality of life in the patients was expected to improve by modified surgery, securing a good local control by additional IORT. Total esophagectomy plus modified three-regional lymphatic dissection with upper mediastinal IORT followed by postoperative external beam irradiation was systematically given to 62 patients between August 1989 and June 1992. Sixty-five percent of the patients were age over 60, and 76% (47/62) of the patients were Stage III or IV by pTNM. Several techniques for the IORT were developed and used throughout this period, including a temporary collapse of the right lung by unilateral tracheal incubation (for the insertion of IORT applicator) and an in vivo dosimetry to know the appropriate range (energy) of electron beam. The method of surgical treatment, the dose of external beam irradiation were kept standardized, and only the dose of IORT was randomized either to 20 or 25 Gy. IORT-related complications and the pattern of failures were carefully monitored. (a) Most prominent IORT-related complication was the late tracheal damage, which occurred 6 of 44 patients who were at risk for more than a year. (b) The incidence of IORT-induced tracheal damage was sharply dependent on the dose of IORT; 6 out of 21 patients who received single dose of 25 Gy, and none out of 33 who were given 20 Gy or less. (c) 2-year cause-specific survival and actuarial 2-year survival were 75.0 +/- 14.5% and 62.5 +/- 13.2%, respectively. No loco-regional recurrence has been detected at the time of analysis. IORT in combination with modified total esophagectomy is an effective and safe method to obtain a local control in advanced esophageal carcinomas, if the dose of IORT does not exceed 20 Gy.


Local modulation of noradrenaline release in vivo: presynaptic beta 2-adrenoceptors and endogenous adrenaline.
Isoprenaline bitartrate (0.5 microgram/kg/min i.v.) increased the rate of noradrenaline release into the circulation of pentobarbitone-anesthetized rabbits. This increase was much greater than that produced by an equi-hypotensive dose of the vasodilator hydralazine (0.2 mg/kg i.v.), suggesting that it was only partly due to baro-reflex activation of sympathetic nerves. This facilitatory effect of isoprenaline was also observed in the nephrectomized, pithed rabbit, with electrically stimulated sympathetic outflow, ruling out central nervous system and renin-angiotensin effects. ICI 118,551 HCl (0.3 mg/kg + 0.1 mg/kg/h i.v.) blocked the isoprenaline-induced hypotension, but did not affect the isoprenaline-induced tachycardia, suggesting that it selectively blocked beta 2-adrenoceptors. ICI 118,551 totally abolished the isoprenaline-induced increase in noradrenaline release, suggesting a beta 2-effect. Atenolol (0.3 mg/kg + 0.1 mg/kg/h) blocked the isoprenaline-induced tachycardia, a beta 1-effect, but only slightly attenuated the isoprenaline-induced increase in noradrenaline release. Atenolol by itself decreased heart rate and arterial pressure, but there was no reflex rise in the noradrenaline release rate, which suggests that atenolol impairs baroreceptor activation of sympathetic nerves. In another series of experiments, also in the pentobarbitone-anesthetized rabbit, adrenaline was released into the circulation by splanchnic nerve stimulation. This resulted in prolonged increases of adrenaline levels in heart tissue. After the plasma adrenaline levels had returned to prestimulation values, the rate of noradrenaline release into the plasma was enhanced. This increase was not observed in rabbits treated with either desipramine HCl (1 mg/kg i.v.) or propranolol HCl (2 mg/kg i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of scrape, swab, and cytobrush samples for the diagnosis of cervical chlamydial infection by immunofluorescence.
An endocervical swab, cytologic scraper, and endocervical cytobrush were used to prepare simultaneous full-slide smears for immunofluorescence for the diagnosis of cervical chlamydial infection. The cytobrush produced the best sample, with significantly higher numbers of organisms. Most of the false negative results were obtained with the cytologic scraper. The optimum technique appears to be to use a cytobrush sample; however, a swab should be used with pregnant patients.


Expression of chemerin receptors CMKLR1, GPR1 and CCRL2 in the porcine pituitary during the oestrous cycle and early pregnancy and the effect of chemerin on MAPK/Erk1/2, Akt and AMPK signalling pathways.
Studies on adipokines, substances that are produced in adipose tissue, indicate that they influence both metabolism and reproduction. Chemerin is a novel addition to the adipokine family. It is believed that chemerin receptors are expressed in different structures of the hypothalamic-pituitary-gonadal (HPG) axis, which are crucial for endocrine control of reproductive functions, including the pituitary. The aim of this study was to investigate the expression of chemerin receptors (CMKLR1, GPR1, CCRL2) genes and proteins in the porcine pituitary. The effect of chemerin on MAPK/Erk1/2, Akt and AMPK signalling pathways was also investigated. The anterior (AP) and posterior (PP) lobes of the pituitary were examined on days 2 to 3, 10 to 12, 14 to 16, and 17 to 19 of the oestrous cycle and on days 10 to 11, 12 to 13, 15 to 16, and 27 to 28 of pregnancy. This is the first study to demonstrate that CMKLR1, GPR1 and CCRL2 are expressed in the porcine AP and PP, which implies that this gland is sensitive to chemerin action. The expression of the studied chemerin receptors fluctuated during different phases of the cycle and early gestation, which could be related to changes in the endocrine status of female pigs. The study also revealed that CMKLR1 and CCRL2 proteins were present in gonadotrophs and thyrotrophs, whereas CCRL2 was also present in somatotrophs, during the cycle and early pregnancy. We observed that chemerin affected MAPK/Erk1/2, Akt and AMPK signalling pathways in the porcine AP. These results suggest that chemerin may participate in the regulation of reproductive functions at the level of the pituitary.


Establishing the pattern of the vertebrate limb.
The vertebrate limb continues to serve as an influential model of growth, morphogenesis and pattern formation. With this Review, we aim to give an up-to-date picture of how a population of undifferentiated cells develops into the complex pattern of the limb. Focussing largely on mouse and chick studies, we concentrate on the positioning of the limbs, the formation of the limb bud, the establishment of the principal limb axes, the specification of pattern, the integration of pattern formation with growth and the determination of digit number. We also discuss the important, but little understood, topic of how gene expression is interpreted into morphology.


Detection of multiple druggable mutations of lung cancer from cytology specimens by MINtS: An advanced medicine A trial.
Most multigene mutation tests require tissue specimens. However, cytological specimens are easily obtained in the clinical practice and provide high-quality DNA and RNA. We aimed to establish a test that utilizes cytological specimens and performed a multi-institutional study to investigate the performance of MINtS, a test based on next-generation sequencing. A standard procedure for specimen isolation was defined. The specimens were considered suitable for the test if >100 ng DNA and >50 ng RNA could be extracted from them. In total, 500 specimens from 19 institutions were investigated. MINtS detected druggable mutations in 63% (136 of 222) of adenocarcinomas. Discordant results between MINtS and the companion diagnostics were observed in 14 of 310 specimens for the EGFR gene, and 6 of 339 specimens for the ALK fusion genes. Confirmation by other companion diagnostics for the EGFR mutations or the clinical response to an ALK inhibitor all supported the results obtained by MINtS. MINtS along with the isolation procedure presented in the current study will be a platform to establish multigene mutation tests that utilize cytological specimens. UMIN000040415.


Riboflavin transport by rabbit renal basolateral membrane vesicles.
The present study examined riboflavin (RF) uptake by isolated rabbit renal basolateral membrane (BLM). RF uptake was linear during the initial 10 seconds and leveled off thereafter with longer incubation. Studies on RF uptake as a function of incubation medium osmolarity indicated that the BLM RF uptake was the results of transport (approximately 45%) into the intravesicular space as well as binding (approximately 55%) to membrane surfaces. The RF binding to BLM was Na+-dependent so that replacement of Na+ by other cations eliminated the binding component of RF uptake. The process of BLM RF uptake was saturable as a function of substrate concentration and was significantly inhibited by cis-addition of its structural analogs, lumiflavin and lumichrome, indicating the involvement of a carrier-mediated process. The BLM RF uptake was affected by changes in extravesicular pH so that, as compared to pH 7.5, RF uptake was lower at pH 6.5 and higher at pH 8.5. The effect of extravesicular pH persisted when the transmembrane H+ gradient was dissipated by FCCP, indicating the direct effect of pH on BLM RF uptake. The BLM RF uptake was not affected by alterations of the transmembrane electrical potential, induced by either the presence of anions with different membrane permeability (Cl-=NO-3>SO-4>gluconate-) or using nigericin (10 microg/mg protein) with an outwardly or inwardly directed transmembrane K+ gradient. The BLM RF uptake was, however, inhibited by probenecid and p-aminohippurate, and was enhanced by trans-RF. In summary, these results demonstrate the existence of a Na+-dependent BLM binding of RF and a membrane-associated carrier system for RF uptake by renal BLM.


Endobronchial mucosal nodules and actinomycosis in a child with activated phosphatidylinositol 3-kinase delta syndrome (APDS).
In this report, we describe a case of a 5-year-old girl with poor growth and unresolving pneumonia. Bronchoscopy showed numerous endobronchial mucosal nodules, consisting of dense lymphoid infiltrates. Bacterial culture of the nodule biopsy suggested endobronchial actinomycosis. Genetic test confirmed the diagnosis of APDS.


Privacy-preserving harmonization via distributed ComBat.
Challenges in clinical data sharing and the need to protect data privacy have led to the development and popularization of methods that do not require directly transferring patient data. In neuroimaging, integration of data across multiple institutions also introduces unwanted biases driven by scanner differences. These scanner effects have been shown by several research groups to severely affect downstream analyses. To facilitate the need of removing scanner effects in a distributed data setting, we introduce distributed ComBat, an adaptation of a popular harmonization method for multivariate data that borrows information across features. We present our fast and simple distributed algorithm and show that it yields equivalent results using data from the Alzheimer's Disease Neuroimaging Initiative. Our method enables harmonization while ensuring maximal privacy protection, thus facilitating a broad range of downstream analyses in functional and structural imaging studies.


Activation of succinate dehydrogenase from adult Fasciola hepatica (Trematoda).
The succinate dehydrogenase of adult Fasciola hepatica was found to exist in active and in active forms. The enzyme was inactivated by 1 micron oxaloacetate and activated by incubation with compounds which bind to the active site (succinate, fumarate, malonate) or by incubation with anions and certain nucleotides. The activation of the enzyme by succinate followed first-order kinetics. The extent of activation of F. hepatica succinate dehydrogenase depended on the nature and concentration of the activator and on the pH. The rate of activation of the enzyme depended on the temperature. In contrast, the fumarate reductase activity of F. hepatica was not activated by incubation with substrate or anions and was not inhibited by oxaloacetate (100 micron). The significance of these results in the regulation of the tricarboxylic acid cycle in parasitic helminths is discussed.


Modified Cortex Mori Capsules improving the successful rate of functional filtering blebs after reclinical glaucoma filtering surgery.
The major reason for filtering bleb failure or scarring of the bleb site is due to excessive scarring after glaucoma filtration surgery in the clinic. Traditional Chinese medicine has preeminence in the prevention of fibrosis formation through the regulation of systemic circulation and improvement of the properties of the inflammatory cells in the blood. To examine the clinical efficacy of using the Modified Cortex Mori Capsules (MCMC; Chinese name: Jiawei Sangbaipi Capsules) in the success rate of functional filtering blebs after glaucoma filtering surgery in clinical patients. Sixty resurgery glaucoma patients were randomly divided into two groups: 30 patients in surgery with the placebo group and 30 patients in surgery with the MCMC group. Patients took either the placebo or the MCMC 2 wk before and after surgery. Postoperative morphology and function filtering bleb, visual acuity, intraocular pressure, postoperative complications, the success rate of filtration surgery and clinical efficacy were observed. Fifty patients completed the study. The percentage of functional filtering blebs in the surgery plus MCMC group was 84% at 6 mo after surgery, which was higher than surgery plus placebo group (64%, P < 0.05). The surgical success rate in the MCMC and placebo groups were 79% ± 8.3% and 57% ± 10.6% respectively (P < 0.05). The visual acuity, intraocular pressure and the postoperative complications in the two groups had no significant differences. Glaucoma filtering surgery while taking MCMC not only reduced excessive scar formation and increased the success rate of functional filtering blebs but also improved the success of glaucoma filtration operations.


Apoptosis and apoptosis-related proteins in human endometrium.
Apoptosis has been shown to be an important regulator of endometrium function. To study the regulation of apoptosis in the endometrium during the normal menstrual cycle, the expression of the apoptosis related proteins Bcl-2 and Bax and their correlation to serum estradiol and progesterone, as well as to a replication-related antigen Ki-67 were analyzed. Nine uterine tissue samples and thirty-nine endometrial biopsy specimens were studied. Apoptosis was studied quantitatively by Southern blot analysis of internucleosomal cleavage of genomic DNA, and qualitatively by using in situ 3'-end labeling of fragmented DNA, and Bcl-2, Bax and Ki-67 were detected and quantified immunohistochemically. Apoptotic cells were mostly detected in the glandular epithelium of late secretory and menstruating endometrium. Immunostaining of Ki-67 was detected predominantly in proliferative endometrium. The expression of Bcl-2 was high in proliferative endometrium and decreased in the secretory phase, being very low or absent in the mid- and late secretory and menstruatory phases. Similarly, Bax expression also decreased, but was still present throughout the secretory phase. In human endometrium, apoptosis occurs predominantly in the late secretory and menstrual phases, and is related to alterations in the expression of Bcl-2 and Bax. A decrease in the Bcl-2/Bax ratio in the early secretory phase precedes DNA fragmentation and may predispose the cells to apoptosis.


A K+ transport ATPase in Escherichia coli.
A K+ -stimulated ATPase in membranes of Escherichia coli has been identified as an activity of the Kdp system, and ATP-driven K+ transport system. Three characteristics support association of the ATPase with the Kdp system: (i) ATPase and Kdp transport are both repressed by growth in media containing high concentrations of K+; (ii) the ATPase and Kdp system accept only K+ as substrate, neither requires Na+ nor accepts Rb+ as a substrate; (iii) the affinity of the ATPase and that of th Kdp system for K+ is similar and is altered by mutations in the structural genes of the Kdp system. Discovery of an ATPase associated with a bacterial transport system suggests functional similarities with the ATP-driven transport systems of animal cells.


Selective inactivation of the exonuclease activity of bacteriophage T7 DNA polymerase by in vitro mutagenesis.
The 3' to 5' exonuclease activity of bacteriophage T7 DNA polymerase (gene 5 protein) can be inactivated selectively by reactive oxygen species. Differences in the enzymatic properties between the two forms are exploited to show by a chemical screen that modification of a histidine residue reduces selectively the exonuclease activity. In vitro mutagenesis of the histidine at residue 123, and of the neighboring residues, results in varying reduction of the exonuclease activity, including mutant enzymes that have no detectable exonuclease activity; as a consequence their polymerase activity is increased up to 9-fold. T7 phage containing the mutant genes have a greatly reduced burst size and demonstrate up to a 14-fold increase in the spontaneous mutation rate.


Priority acute and preventive migraine treatment benefits: Results of the Migraine Clinical Outcome Assessment System (MiCOAS) qualitative study of people living with migraine.
There is renewed emphasis on including patients in determining, defining, and prioritizing outcomes for migraine treatment. To obtain insights directly from people living with migraine on their priorities for treatment. A total of 40 qualitative interviews were conducted as part of the Migraine Clinical Outcome Assessment System project, a United States Food and Drug Administration grant-funded program to develop a core set of patient-centered outcome measures for migraine clinical trials. Interviews included a structured exercise in which participants rank-ordered pre-defined lists of potential benefits for acute and preventive migraine therapy. The 40 study participants who reported being diagnosed with migraine by a clinician ranked the benefits and explained their rationale. Study participants consistently ranked either pain relief or absence of pain as their top priority for acute treatment. Relief/absence of other migraine symptoms and improved functioning were also prioritized. For preventive treatment, participants prioritized reductions in migraine frequency, symptom severity, and attack duration. Few differences were found between participants with episodic migraine and those with chronic migraine. However, participants with chronic migraine ranked "increased predictability of attacks" much higher than those with episodic migraine. Participants' rankings were influenced by prior expectations and experiences of migraine treatments, which caused many participants to deprioritize desired benefits as unrealistic. Participants also identified several additional priorities, including limited side-effects and reliable treatment efficacy in both acute and preventive treatments. The results showed the participants prioritized treatment benefits aligned with existing core clinical outcomes used in migraine research, but also valued benefits that are not typically assessed, such as predictability. Participants also deprioritized important benefits when they believed treatment was unlikely to deliver those outcomes.


A short sperm-oocyte incubation time ZBA in the dog.
The fertilising capacity of a semen sample can be predicted by evaluation of spermatozoa with in vitro tests. The zona pellucida binding assay (ZBA) accounts for several parameters and interprets the interaction between the spermatozoa and the oocyte. The present study was made in two parts. The aim of the first experiment was to evaluate whether the sperm binding capacity of oocytes varies between different oocyte pools. Each zona binding was made with oocytes from different bitches, using pooled frozen-thawed semen from the same two dogs. The sperm-oocyte complexes were incubated for 1h. There was a significant difference between the six replicates in the number of sperm bound to the zona pellucida (ZP), which indicates that the sperm binding capacity of the ZP differs between oocyte pools. The aims of the second experiment were to evaluate the effects of five different treatments of the spermatozoa on the ZBA, and to evaluate two different incubation times of the sperm-oocyte complexes. ZBAs were made with: fresh semen; semen kept chilled for 1 or 2 days prior to the ZBA; and with semen that had been frozen with or without Equex. The oocytes and spermatozoa were incubated for 1 or 4h. For fresh semen and for semen frozen without Equex, incubation for 1h resulted in a higher number of bound spermatozoa per oocyte than incubation for 4h (P<0.0001). When the effect of the different sperm treatments on the number of spermatozoa bound to the ZP was evaluated, it was found that this number was higher for fresh spermatozoa than for chilled or frozen-thawed spermatozoa both after 1 and 4h of co-incubation (P<0.0001). After 1-h incubation of the sperm-oocyte complexes, spermatozoa chilled for 1 day showed better zona binding capacity than spermatozoa chilled for 2 days, and spermatozoa frozen without Equex had a better zona binding capacity than spermatozoa frozen with Equex. Sperm motility and sperm plasma membrane integrity were higher in fresh than in chilled and frozen-thawed semen. The acrosome integrity was high in all groups of treated semen. In conclusion, 1-h incubation of the sperm-oocyte complexes seems to be sufficient for fresh and chilled semen. Further studies are required to establish the optimal incubation time for sperm-oocyte complexes when frozen-thawed semen is evaluated, as a comparison between semen frozen with Equex and semen frozen without Equex gave different results depending on whether the incubation time was 1 or 4h (in the present study), or 6h [Ström Holst B, Larsson B, Linde-Forsberg C, Rodriguez-Martinez H. Evaluating chilled and frozen-thawed dog spermatozoa using a zona pellucida binding assay.


Microbore liquid chromatography and refractive index gradient detection of low-nanogram and low-ppm quantities of carbohydrates.
A refractive index gradient detector is presented as a universal detector in the microbore high-performance liquid chromatography analysis of carbohydrates. Simultaneously, low-ng and low-ppm injected quantities of carbohydrates were detected at the 3 x root-mean-square baseline noise level. A typical microbore high-performance liquid chromatography chromatogram separating fructose from sucrose followed by refractive index gradient (RIG) detection is reported. Use of a position sensitive detector (PSD) in the RIG detector design is reported and experimental considerations discussed. Optimization of the PSD-based RIG detector is addressed. Potential for the device in industrial and clinical applications is considered.


Determinants of iron accumulation in the normal aging brain.
In a recent postmortem study, R2* relaxometry in gray matter (GM) of the brain has been validated as a noninvasive measure for iron content in brain tissue. Iron accumulation in the normal aging brain is a common finding and relates to brain maturation and degeneration. The goal of this study was to assess the determinants of iron accumulation during brain aging. The study cohort consisted of 314 healthy community-dwelling participants of the Austrian Stroke Prevention Study. Their age ranged from 38-82 years. Quantitative magnetic resonance imaging was performed on 3T and included R2* mapping, based on a 3D multi-echo gradient echo sequence. The median of R2* values was measured in all GM regions, which were segmented automatically using FreeSurfer. We investigated 25 possible determinants for cerebral iron deposition. These included demographics, brain volume, lifestyle factors, cerebrovascular risk factors, serum levels of iron, and single nucleotide polymorphisms related to iron regulating genes (rs1800562, rs3811647, rs1799945, and rs1049296). The body mass index (BMI) was significantly related to R2* in 15/32 analyzed brain regions with the strongest correlations found in the amygdala (p = 0.0091), medial temporal lobe (p = 0.0002), and hippocampus (p ≤ 0.0001). Further associations to R2* values were found in deep GM for age and smoking. No significant associations were found for gender, GM volume, serum levels of iron, or iron-associated genetic polymorphisms. In conclusion, besides age, the BMI and smoking are the only significant determinants of brain iron accumulation in normally aging subjects. Smoking relates to iron deposition in the basal ganglia, whereas higher BMI is associated with iron content in the neocortex following an Alzheimer-like distribution.


Nuclearity enlargement from [PW9O34@Ag51] to [(PW9O34)2@Ag72] and 2D and 3D network formation driven by bipyridines.
The structural transformations of metal nanoclusters are typically quite complex processes involving the formation and breakage of several bonds, and thus are challenging to study. Herein, we report a case where two lacunary Keggin polyoxometallate templated silver single-pods [PW9O34@Ag51] (SD/Ag51b) fuse to a double-pod [(PW9O34)2@Ag72] by reacting with 4,4'-bipyridine (bipy) or 1,4-bis(4-pyridinylmethyl)piperazine (pi-bipy). Their crystal structures reveal the formation of a 2D 44-sql layer (SD/Ag72a) with bipy and a 3D pcu framework (SD/Ag72c) with pi-bipy. The PW9O349- retains its structure during the cluster fusion and cluster-based network formation. Although the two processes, stripping of an Ag-ligands interface followed by fusion, and polymerization, are difficult to envisage, electrospray ionization mass spectrometry provides enough evidences for such a proposal to be made. Through this example, we expect the structural transformation to become a powerful method for synthesizing silver nanoclusters and their infinite networks, and to evolve from trial-and-error to rational.


Transportation of thermal and velocity slip factors on three-dimensional dual phase nanomaterials liquid flow towards an exponentially stretchable surface.
The fundamental purpose of this research is to elaborate on slip boundary conditions and the flow of three-dimensional, stable, incompressible, rotating movements of nanoparticles lying across a stretchable sheet. The mathematical model for fluid flow is created using the assumptions stated above. The partial differentials are produced after utilizing boundary layer estimates. The partial differential governing equations are reduced into three coupled ordinary differential equations by using similarity transformations. After, applying transformations the system is solved numerically. Numerical results are approved with the help of the MATLAB bvp4c algorithm. The analysis shows that velocity and temperature are strongly dependent on essential parameters like stretching ratio, velocity slip, rotation, thermal slip parameter, and Prandtl number. Numerical values of distinct parameters on heat flux and skin friction factors are shown in a tabulated form. Partial velocity and thermal slip are applied to the temperature surface. The comparison among the nano-sized particles copper oxide and silver with water base nanofluid affecting velocity and temperature fields are used for analysis. Moreover, the Graphical depiction designates that the velocity and temperature spreading of the thermal slip parameter is increasing. It is observed that Ag-water is the best heat carrier as compared to CuO-water nanofluid.


ERα prevents tumorigenesis of both liver and breast cancer cells through CCN5.
Estrogen receptor alpha (ERα)-mediated estrogen signaling has also shown to prevent hepatic tumorigenesis in mice. Consistent with this, hormone replacement therapy with estrogen supplementation dramatically reduced the risk of hepatocellular carcinoma. Silencing of ERα is also a key event for the transformation of ERα-positive breast cancer cells into malignant triple-negative breast cancer cells. However, the mechanisms underlying ERα-mediated prevention of both hepatic and mammary tumorigenesis in humans are still unclear. Here, we present a functional genomics study of ERα targeting by comparing human liver cancer cells with human breast cancer cells using "loss or gain of function" genetic assays of ERα in vitro and in vivo. We discover that cellular communication network factor 5 (CCN5) is a direct downstream target of ERα; ERα suppresses growth and prevents tumorigenesis and malignant transformation of both liver and breast cancer cells through CCN5 in humans. The ERα-CCN5 regulatory axis functions as suppressors for both hepatic and mammary tumors, which is a common mechanism of preventing tumorigenesis for both liver cancer and breast cancer in humans.


Multicentre study of non-surgical management of diverticulitis with abscess formation.
This multicentre retrospective cohort study included 447 patients with Hinchey Ib and II diverticular abscesses, who were treated with antibiotics, with or without percutaneous drainage. Abscesses of 3 and 5 cm in size were at higher risk of short-term treatment failure and emergency surgery respectively. Initial non-surgical treatment of Hinchey Ib and II diverticular abscesses was comparable between patients treated with antibiotics only and those who underwent percutaneous drainage in combination with antibiotics, with regard to short- and long-term outcomes. Most do not need drainage.


[Priority setting in healthcare. What can Germany learn from other countries?].
Internationally, priority setting has been debated since the late 1980s, partly only regarding underlying principles, but partly with real implications for the benefit basket. Whereas all approaches reviewed (Norway, Sweden, Denmark, Oregon, The Netherlands, New Zealand) are convincing, those that relied on public consensus and left the priority-setting principles to the discretion of individual healthcare professionals had no effect as early prioritization efforts in the Scandinavian countries show. Prioritization approaches that have relied on concrete lists of indication-treatment pairs (for example, in the U.S. state of Oregon across all areas of care and in Sweden the form of guidelines within indication groups) have led to changes but not always to the expected results: expenditure was only moderately reduced but the provision of care has become more transparent. Regardless of the differences between the various countries, they have several things in common: a heated public debate, a very long implementation timeline, and the lack of a (much feared) prioritization according to age, gender, or social status. Recently, priority setting has been seen as complementary to health technology assessments, guidelines, and quality assurance, all with their own focuses.


Effects of the intramyocardial implantation of stromal vascular fraction in patients with chronic ischemic cardiomyopathy.
Stromal vascular fraction (SVF) can easily be obtained from a mini-lipoaspirate procedure of fat tissue. The SVF contains a mixture of cells including ADSCs and growth factors and has been depleted of the adipocyte (fat cell) population. We evaluated the safety and efficacy of administering SVF intra-myocardially into patients with chronic ischemic cardiomyopathy. A total of 28 patients underwent a local tumescent liposuction procedure to remove approximately 60 ml of fat tissue. The fat was separated to isolate the SVF and the cells were delivered into the akinetic myocardial scar region using a transendocardial delivery system (MyoCath(®)) in patients who had experienced a previous myocardial infarct. The subjects were then monitored for adverse events, ejection fraction via echocardiogram and six-minute walk test (6MWT) over a period of 6 months. The average EF was 29 % at baseline and significantly increased to 35 % at both 3 and 6 months. Patients walked an average of 349 m at baseline and demonstrated a statistically significant improvement at 3 and 6 months' post treatment of more than 80 m. Overall, patients were pleased with the treatment results. More importantly, the procedure demonstrated a strong safety profile with no severe adverse events or complications linked to the therapy. Trial registration NCT01502514 Name of registry: http://www.clinicaltrials.gov URL: https://www.clinicaltrials.gov/ct2/show/NCT01502514?term=adipose+cells+heart&rank=4 Date of registration: December 27, 2011 Date of enrollment: January 2012.


Cerebral ischemia after treatment of posterior communicating artery aneurysms: clipping versus coiling.
This study aimed to compare the incidence of cerebral ischemia and outcomes between surgical clipping and endovascular coiling in patients with posterior communicating artery (PCoA) aneurysms. Clinical and imaging data of patients with at least one PCoA aneurysm who underwent surgical clipping or endovascular coiling in our institution from January 2017 to December 2019 were analyzed. Three hundred sixty-three aneurysms in 353 patients were included for analysis, 257 in the clipping group, and 106 in the coiling group. The groups did not differ in terms of baseline characteristics. The incidence of postoperative cerebral ischemia (23.35% vs. 11.32%, p = 0.029) was higher in the clipping group. The proportion of patients with a modified Rankin Scale score ≥ 2 was significantly higher in the clipping group at discharge (35.80% vs. 15.09%; p < 0.05) but not six months after discharge (15.56% vs. 8.49%; p > 0.05). In the clipping group, the mean age was significantly higher in patients who developed cerebral ischemia than in those who did not. In the coiling group, modified Fisher grade and incidence of fetal PCoA were significantly higher in patients who developed ischemia. The incidence of postoperative cerebral ischemia was higher after PCoA aneurysm clipping than after coiling. The causes and characteristics of postoperative cerebral ischemia after PCoA clipping and coiling are different; therefore, treatment should be selected accordingly.


Gut microbes influence the development of central nervous system disorders through epigenetic inheritance.
Central nervous system (CNS) disorders, such as depression, anxiety, and Alzheimer's disease (AD), affect quality of life of patients and pose significant economic and social burdens worldwide. Due to their obscure and complex pathogeneses, current therapies for these diseases have limited efficacy. Over the past decade, the gut microbiome has been shown to exhibit direct and indirect influences on the structure and function of the CNS, affecting multiple pathological pathways. In addition to the direct interactions between the gut microbiota and CNS, the gut microbiota and their metabolites can regulate epigenetic processes, including DNA methylation, histone modification, and regulation of non-coding RNAs. In this review, we discuss the tripartite relationship among gut microbiota, epigenetic inheritance, and CNS disorders. We suggest that gut microbes and their metabolites influence the pathogenesis of CNS disorders at the epigenetic level, which may inform the development of effective therapeutic strategies for CNS disorders.


The conducting tissues in primitive ventricle with outlet chamber. Two different possibilities.
The conducting tissues have been studied in two cases of primitive ventricle with outlet chamber. In one case the outlet chamber was to the right and in the other, to the left. In both cases there was an anterior node related to the anterior part of the right atrioventricular anulus. In the specimen with a left-sided outlet chamber (l-loop), the bundle passed through the atrioventricular-semilunar fibrous continuity and was intimately related to the posterior artery. Such a relation was absent in the specimen with a right-sided outlet chamber (d-loop), wherein the bundle directly descended on the posterior part of the septum between the main and outlet chambers. The septum is not considered to be the true ventricular septum but rather a hypertrophied trabecula septomarginalis.


Development and validation of a pharmacy migraine questionnaire to assess suitability for treatment with a triptan.
A questionnaire (Migraine Questionnaire; MQ) was developed to help pharmacists identify consumers with migraine suitable for non-prescription treatment with a triptan. Adults, who knew or thought that they had migraine, participated in three, sequential, community-based studies to validate the MQ. Overall, 1,353 subjects completed independent assessments with a pharmacist and a clinician (reference standard). The accuracy of the pharmacist assessment of suitability for a triptan was compared with the clinician assessment. Clinicians using their standard practice determined that triptan therapy was suitable in 76.8% of cases compared with 48.8% for pharmacists using the MQ. The lack of concordance between pharmacists and clinicians in the false-positive cases (n = 113 of 660 subjects considered suitable for triptan by the pharmacists) usually related to headache diagnosis (57.5%), not safety aspects. The MQ is an effective tool for pharmacists to guide appropriate recommendation of a non-prescription triptan for migraine.


Photoactivated DNA cleavage and anticancer activity of pyrenyl-terpyridine lanthanide complexes.
Lanthanide(III) complexes [Ln(R-tpy)(acac)(NO(3))(2)] (Ln = La(III) in 1, 2; Gd(III) in 4, 5) and [Ln(py-tpy)(sacac)(NO(3))(2)] (Ln = La(III), 3; Gd(III), 6), where R-tpy is 4'-phenyl-2,2':6',2″-terpyridine (ph-tpy in 1, 4), 4'-(1-pyrenyl)-2,2':6',2″-terpyridine (py-tpy in 2, 3, 5 and 6), acac is acetylacetonate and sacac is 4-hydroxy-6-{4-[(β-d-glucopyranoside)oxy]phenyl}hex-3,5-dien-2-onate, were prepared to study their DNA photocleavage activity and photocytotoxicity. Complexes [La(ph-tpy)(acac)(EtOH)(NO(3))(2)] (1a) and [Gd(ph-tpy)(acac)(NO(3))(2)] (4) were characterized by X-ray crystallography. The 1:1 electrolytic complexes bind to calf thymus DNA. The py-tpy complexes cleave pUC19 DNA and exhibit remarkable photocytotoxicity in HeLa cells in UV-A light of 365 nm with apoptotic cell death (IC(50): ∼40 nM in light, >200 μM in dark). Confocal microscopy using HeLa cells reveal primarily cytosolic localization of the complexes.


Perceived health status and life satisfaction in old age, and the moderating role of social support.
The aim of this study was on one hand to examine the associations between health impairment and life satisfaction, as well as social support and life satisfaction, and on the other, to analyze the moderating effect of social support with regard to health impairment and life satisfaction in a sample of community-dwelling older adults from urban areas of Granada, southern Spain. This was a cross-sectional survey in which a sample of 406 older adults with ages between 65 and 99 years old (Mage = 74.88, SD = 6.75) was selected. Multiple stepwise regression analysis was used to assess the impact of health impairment and perceived social support on life satisfaction. Moderation analysis was performed using the bias-corrected and accelerated bootstrapping approach. Significant differences in life satisfaction scores were found by number and type of disease, restrictions in daily life activities and subjective health. Perceived health and perceived social support predicted life satisfaction. Besides global social support, emotional and affectionate support moderated the link between perceived health and life satisfaction. Older people who do not rate their health status positively and indicate low levels of social support have a higher risk of being dissatisfied with their lives and due to this they should receive special attention from gerontologists.


Ultrashort intracorporeally maneuverable cryoprobes for laparoscopic renal cryoablation in the porcine model.
To determine the feasibility and efficacy of laparoscopic renal cryosurgery using a novel ultrathin ultrashort intracorporeal cryoprobe in a porcine model. Novel cryoprobes 4 cm in length and 1.5 mm in diameter were manipulated intracorporeally after insertion via a designated 15 mm laparoscopic port. Renal cryoablative lesions were induced laparoscopically in four 40 kg female piglets. We correlated between intraoperative temperature, ice ball geometry, intraoperative ultrasonographic properties, and histology. Laparoscopic manipulation of the cryoprobes was straightforward. No port site bleeding occurred during insertion, freezing, thawing or upon removal of the probes. The 0 degrees C, -20 degrees C, and -40 degrees C isotherms were measured at 6, 8, and 12 mm from the probe circumferentially. Ice-ball volume stabilization as determined by ultrasound occurred after 10 min of activation. Lower temperatures were reached after 10 min of probe activation as compared with 5 min (ice ball diameter 30 mm, DeltaT = 13-21 degrees C). Using a second 10-min-long freeze cycle resulted in a 14-22 degrees C lower temperature within the ice ball compared to a single cycle. Full coagulative necrosis was noted in the areas between the inserted probes with an additional 1-2 mm circumferential rim of severe tubular damage and apoptosis. Our novel cryoprobe can be used effectively and conveniently in laparoscopic renal cryosurgery. Considering the size of the cryogenic lesion, using a cluster of probes may be advisable.


Association of dairy consumption patterns with the incidence of type 2 diabetes: Findings from Alberta's Tomorrow Project.
We aimed to extract dairy consumption patterns of men and women from a population-based cohort and then assess the association of each consumption pattern with incident T2D risk. This prospective study was conducted within the framework of Alberta's Tomorrow Project (ATP), in which 8615 men and 15,016 women provided information on dietary intake by completing a food-frequency questionnaire at baseline, and then were followed up over time to determine the incidence of T2D via questionnaires. Principal Component Analysis (PCA) was used to extract dairy consumption patterns (DCPs). The association between each extracted pattern and T2D incidence was estimated using multivariable logistic regression models.The incidence of T2D among men and women was 3.8 and 3.2%, respectively, and the mean duration of follow-up was 5.2 years. Three major DCPs were identified. After controlling for potential confounders, the OR for risk of T2D in men in the highest compared with those in the lowest quartile of the DCP3 (whole milk, regular cheese, and non-fat milk as a beverage and in cereal) was 0.64 (95%CI: 0.47 to 0.88, P-trend=0.001), whereas it was not significant for women. DCP1 and DCP2 were not associated with incident T2D in men or women. Adherence to a DCP characterized by higher consumption of whole milk, regular cheese, and non-fat milk was associated with decreased risk of incident T2D only in men. Our results support current evidence that a combination of different dairy products, regardless of their fat content, might be favorable for health maintenance, at least in men.


Controlling working memory with learned instructions.
Many neural network models of cognition rely heavily on the modeler for control over aspects of model behavior, such as when to learn and whether an item is judged to be present in memory. Developing neurocomputational methods that allow these cognitive control mechanisms to be performed autonomously has proven to be surprisingly difficult. Here we present a general purpose framework called GALIS that we believe is amenable to developing a broad range of cognitive control models. Models built using GALIS consist of a network of interacting "regions" inspired by the organization of primate cerebral cortex. Each region is an attractor network capable of learning temporal sequences, and the individual regions not only exchange task-specific information with each other, but also gate the others' functions and interactions. As a result, GALIS models can learn both task-specific content and also the necessary cognitive control procedures (instructions) needed to perform a task in the first place. As an initial test of this approach, we use GALIS to implement a model that is trained simultaneously to perform five versions of the n-Back task. Not only does the resulting n-Back model function correctly, determining when to learn or remove items in working memory, but its accuracy and response times correlate strongly with those of human subjects performing the same task. The n-Back model also makes testable predictions about how human accuracy would be affected by intra-trial changes in n's value. We conclude that GALIS opens a potentially effective pathway toward developing a range of cognitive control models with improved autonomy.


[Ectopic pregnancy on uterine scar from cesarean section]
Ectopic pregnancy is defined as the implantation of the fertilized egg outside the uterine cavity. About 95% of ectopic pregnancies are located in the tube. Non-tubal forms, in particular on the scar of a cesarean section, are a very rare entity whose early diagnosis and treatment are essential to avoid serious complications and preserve fertility.


A review of the genus Sinocentrus Yuan (Hemiptera, Membracidae, Centrotinae) with description of a new species from China.
A new species of the treehopper genus Sinocentrus Yuan, S. brevicornis Li & Chen, sp. nov. from China, is described and illustrated. A checklist and key to species of the Sinocentrus are provided.


A highly stable adenosine triphosphatase from a thermophillie bacterium. Purification, properties, and reconstitution.
1. A highly stable ATPase (TF1) was purified to a monodispersed state from the membranes of a thermophilic bacterium PS3. Its molecular weight was 380,000, and it was composed of five subunits alpha, beta, gamma, sigma', and sigma with molecular weights of 56,000, 53,000, 32,000, 15,500, and 11,000, respectively. 2. TF1 was stable against dissociating agents such as 5.5 M urea and 4.0 M LiCl, organic solvents, such as 60% acetone, heavy metals, and detergents. Low concentrations of all these agents stimulated its activity at 60 degrees. 3. TF1 was not cold-labile and showed a maximal activity at 70 degrees. Its CD spectrum revealed that its conformation changed between 81 and 96 degrees, and that its contents of alpha helices and beta structures were 27.3 and 12.8%, respectively, at 75 degrees. 4. TF1 was completely dissociated by treatment with dodecyl sulfate at 60 degrees and then with 7.1 M urea. The dissociated TF1 was reconstituted by treatment with Dowex 1-X2, and then dialysis. 5. [3H]Acetyl-TF1 bound to TF1-depleted membranes. TF1 only catalyzed 32Pi-ATP exchange and showed sensitivity to inhibitors of energy transfer when bound to the membranes. 6. A hydrophobic membrance component (TFo) was isolated which rendered TF1 sensitive to inhibitors of energy transfer. It was composed of three subunits (with molecular weights of 19,000, 13,500, and 5,400) and P-lipids.


Pharmacokinetics of etonogestrel released from the contraceptive implant Implanon.
Eight healthy women between 22 and 40 years of age participated in this prospective open study of 2 years' duration. Either on or between days 1 to 7 of a spontaneous menses, an intravenous bolus dose of 150 micrograms etonogestrel (3-ketodesogestrel) was given. During days 1-5 of a subsequent spontaneous cycle, the single-rod contraceptive implant (Implanon) was inserted in the upper arm of the volunteer. One year after placement of the implant, another intravenous bolus dose was given (implant in place), and a third bolus dose was given after 2 years, with the implant removed. Frequent serum sampling immediately after the intravenous dosings of etonogestrel was done to study the primary pharmacokinetic parameters, i.e., volume of distribution and clearance, allowing the calculation of the absorption rate and bioavailability of the implant, as a function of time. Results showed that etonogestrel released from Implanon has an absorption rate of approximately 60 micrograms/day after 3 months, which slowly decreases to 30 micrograms/day at the end of 2 years. The bioavailability over this period of time was constant and close to 100%. The clearance remained around 7.5 L/h. With a bioavailability and clearance that remained constant, it may be concluded that there is no accumulation of etonogestrel.


In Silico Analysis of an Exercise-Safe Artificial Pancreas With Multistage Model Predictive Control and Insulin Safety System.
Maintaining glycemic equilibrium can be challenging for people living with type 1 diabetes (T1D) as many factors (eg, length, type, duration, insulin on board, stress, and training) will impact the metabolic changes triggered by physical activity potentially leading to both hypoglycemia and hyperglycemia. Therefore, and despite the noted health benefits, many individuals with T1D do not exercise as much as their healthy peers. While technology advances have improved glucose control during and immediately after exercise, it remains one of the key limitations of artificial pancreas (AP) systems, largely because stopping insulin at the onset of exercise may not be enough to prevent impending, exercise-induced hypoglycemia. A hybrid AP algorithm with subject-specific exercise behavior recognition and anticipatory action is designed to prevent hypoglycemic events during and after moderate-intensity exercise. Our approach relies on a number of key innovations, namely, an activity informed premeal bolus calculator, personalized exercise pattern recognition, and a multistage model predictive control (MS-MPC) strategy that can transition between reactive and anticipatory modes. This AP design was evaluated on 100 in silico subjects from the most up-to-date FDA-accepted UVA/Padova metabolic simulator, emulating an outpatient clinical trial setting. Results with a baseline controller, a regular MPC (rMPC), are also included for comparison purposes. In silico experiments reveal that the proposed MS-MPC strategy markedly reduces the number of exercise-related hypoglycemic events (8 vs 68). An anticipatory mode for insulin administration of a monohormonal AP controller reduces the occurrence of hypoglycemia during moderate-intensity exercise.


[Monotherapy of epileptic children with monitoring of the serum levels of anticonvulsive drugs].
In 46 children with partial and primarily generalized seizures monotherapy was started with amizepine, luminal, mysodin or phenytoin. The treatment was monitored determining serum concentrations of the drugs. Monotherapy was effective in 74% of cases. In 89% of them the duration of treatment was one year, at least. In some children the values of amizepine, luminal and mysodin concentrations below the therapeutic level were effective. The evolution of electroencephalographic changes failed to correspond strictly to the clinical results of the treatment.


pH-driven enhancement of anti-tubercular drug loading on iron oxide nanoparticles for drug delivery in macrophages.
Nanoparticle deployment in drug delivery is contingent upon controlled drug loading and a desired release profile, with simultaneous biocompatibility and cellular targeting. Iron oxide nanoparticles (IONPs), being biocompatible, are used as drug carriers. However, to prevent aggregation of bare IONPs, they are coated with stabilizing agents. We hypothesize that, zwitterionic drugs like norfloxacin (NOR, a fluoroquinolone) can manifest dual functionality - nanoparticle stabilization and antibiotic activity, eliminating the need of a separate stabilizing agent. Since these drugs have different charges, depending on the surrounding pH, drug loading enhancement could be pH dependent. Hence, upon synthesizing IONPs, they were coated with NOR, either at pH 5 (predominantly as cationic, NOR+) or at pH 10 (predominantly as anionic, NOR-). We observed that, drug loading at pH 5 exceeded that at pH 10 by 4.7-5.7 times. Furthermore, only the former (pH 5 system) exhibited a desirable slower drug release profile, compared to the free drug. NOR-coated IONPs also enable a 22 times higher drug accumulation in macrophages, compared to identical extracellular concentrations of the free drug. Thus, lowering the drug coating pH to 5 imparts multiple benefits - improved IONP stability, enhanced drug coating, higher drug uptake in macrophages at reduced toxicity and slower drug release.


[Comparative immunogenicity of irradiated and nonirradiated syngeneic and xenogeneic tumor cells containing a common specific transplantation antigen].
The authors compared the immunogenic activity for Syrian hamsters of native and irradiated syngeneic and xenogeneic tumour cells bearing on their surface common and SV40-specific transplantational antigen. The results obtained showed syngeneic tumour cells to be more immunogenic for the recipient than the xenogeneic tumour cells containing an antigen of the same specificity. Irradiation renders tumour cells, including the xenogeneic ones, more immunogenic, this possibly being associated with the capacity of nonirradiated cells to escape from immune recognition through their ability to divide.


In vivo protective efficacy of astaxanthin against ionizing radiation-induced DNA damage.
Astaxanthin, a carotenoid pigment, is believed to be effective in the repair of DNA damage. Our study evaluates the effect of astaxanthin on DNA damage in rats exposed to whole-body radiotherapy using the comet assay. Thirty-two male rats were randomly divided into four groups (control, ionizing radiation, astaxanthin, and radiation+astaxanthin). The radiation and radiation+astaxanthin groups were exposed to X-rays at a dose of 8 gray (0.62 gray/min). Astaxanthin was administered at 4 mg/kg by gavage for 7 days starting from irradiation. The %TailDNA parameter was chosen as an indicator of DNA damage and the results were compared using one-way ANOVA. %TailDNA was 3.24 ± 3.12 in the control group, 2.85 ± 2.73 in the astaxanthin group, 4.11 ± 7.90 in the radiation group, and 3.59 ± 4.05 in the radiation+astaxanthin group. There was a significant increase in DNA damage in the radiation group, compared with the control and astaxanthin groups (p < .001). DNA damage was reduced in the radiation+astaxanthin group compared with the radiation group (p < .05). Although this decrease did not reduce damage to the level of the control group, it was significant. The decrease in radiation-induced DNA damage by astaxanthin administration in our study supports the hypothesis that astaxanthin is a promising agent for against/reducing DNA damage.


Supersensitivity to isoprenaline and epinephrine in right atria isolated from rats submitted to a single swimming session.
1. The effects of swim-induced stress on rat atrial norepinephrine content, plasma corticosterone level and pacemaker sensitivity to catecholamines were studied. 2. Swimming for 50 min reduced the atrial norepinephrine content and induced a long-lasting increase in the plasma corticosterone level. 3. Pacemakers isolated from swim stressed rats showed supersensitivity to the chronotropic effect of isoprenaline. Sensitivity to norepinephrine was not significantly altered. Bilateral adrenalectomy or metyrapone pretreatment prevented the development of swimming-induced supersensitivity to isoprenaline. After in vitro denervation and addition of cocaine supersensitivity to epinephrine was demonstrated. 4. It is concluded that corticosterone, at least partially, mediates the supersensitivity to isoprenaline and epinephrine in pacemaker isolated from acutely swim stressed rats.


Screen-printed carbon electrode modified with de-bundled single-walled carbon nanotubes for voltammetric determination of norepinephrine in ex vivo rat tissue.
A voltammetric sensor for norepinephrine (NE) detection was developed by modifying a disposable screen-printed carbon electrode (SPCE) with de-bundled single-walled carbon nanotubes (D-SWCNTs). The de-bundling was carried out using a newly synthesized polymeric dispersant, a co-polymer of polystyrene sulfonate and methacrylate of lipoic acid. The D-SWCNTs/SPCE showed better sensitivity towards NE compared to the bare SPCE and that modified with bundled SWCNTs. The sensor was optimized for detecting NE by differential pulse voltammetry (DPV) in terms of the D-SWCNTs concentration, DPV parameters, and solution pH. Under the optimum conditions, the sensor exhibited a dynamic linear range of 100 nM-2.0 µM NE, and the detection limit was 62.0 nM (S/N = 3). Additionally, the effects of possible interferents were investigated. The relative standard deviation for five successive measurements of 2.0 µM NE was 7.6%, and approximately 75.8% of the sensor activity was retained after four weeks of storage. The practical potential of this sensor was demonstrated by quantifying NE in ex vivo rat tissue samples.


Vascularized Composite Allografts: Procurement, Allocation, and Implementation.
Vascularized composite allotransplantation is a continuously evolving area of modern transplant medicine. Recently, vascularized composite allografts (VCAs) have been formally classified as 'organs'. In this review, key aspects of VCA procurement are discussed, with a special focus on interaction with the procurement of classical solid organs. In addition, options for a matching and allocation system that ensures VCA donor organs are allocated to the best-suited recipients are looked at. Finally, the different steps needed to promote VCA transplantation in society in general and in the medical community in particular are highlighted.


The chromatin remodeling protein BPTF mediates cell cycle, proliferation and apoptosis in porcine ovarian granulosa cells.
Bromodomain PHD finger transcription factor (BPTF), a core subunit of nucleosome-remodeling factor (NURF) complex, plays an important role in chromatin remodeling. However, few information of BPTF is available in pig, especially in mammalian follicular granulosa cells (GCs). The present study firstly confirmed that BPTF in porcine was relative close to human and mouse. The expression of BPTF could be detected in ovary, testes, lung, kidney, large intestine, and small intestine. And a relative high expression of BPTF was observed in ovarian follicles and GCs. When BPTF was knocked down (BPTF-siRNA), the viability of GCs was affected. And the expression level of CDK1, cyclin B1, CDK4 and CDK2 was higher than the control, which might indicate that the cell cycle of GCs was inhibited from S to G2/M phase. Although the apoptosis level was induced in the BPTF-siRNA GCs, the reduced level of H3K4 methylation was detected with the down regulation of SMYD3, EHMT2 and DPY30. Thereby, results in the present might provide the primary knowledge of BPTF in GCs and the follicular development in pig.


Evolution of the clinical manifestations of infection during the course of febrile neutropenia in patients with malignancy.
The impact of a standardized set of diagnostic interventions on the further management of 968 episodes of fever in neutropenic cancer patients who did not respond to initial therapy was assessed prospectively. At the onset of fever, 65% of patients had no additional signs of infection, whereas skin and soft tissue infections were present in 12%, and clinical sepsis and gastrointestinal infections in 8% each. After 72 h, 41% of the fevers still remained unexplained. New foci of infection emerged in 11% of the cases involving mainly the lungs, skin and soft tissues, and urinary tract. The presence of a lower respiratory tract infection or a microbiologically defined infection of any sort was associated with higher mortality than other types of infection were. Changes in initial antibiotic therapy were based on the results of the diagnostic measures specified in the protocol in only 15% of the cases.


Evolution of vitreomacular traction following the use of the dexamethasone intravitreal implant (Ozurdex) in the treatment of macular edema secondary to central retinal vein occlusion.
To report a case of worsening of vitreomacular traction (VMT) after the dexamethasone intravitreal implant (Ozurdex; Allergan, Inc., Irvine, CA) for the treatment of macular edema secondary to central retinal vein occlusion (CRVO). A 71-year-old man who presented with macular edema secondary to CRVO was treated by intravitreal injections of bevacizumab followed by Ozurdex. VMT developed during the course of treatment and became more evident when macular edema resolved after treatment with Ozurdex. VMT may become apparent and worsen after resolution of macular edema treated with intravitreal Ozurdex.


Severe food insecurity is associated with obesity among Brazilian adolescent females.
To determine whether household food insecurity (HFI) is associated with a higher prevalence of excessive weight (EW) in a large random sample of Brazilian female adolescents. Nationally representative cross-sectional study. EW was the outcome variable (BMI ≥ 85th percentile of WHO reference for adolescents aged 15-18 years and BMI ≥ 25 kg/m(2) for those aged 19 years). HFI was measured with the Brazilian Food Insecurity Scale. Associations were measured using crude and adjusted prevalence ratios (PR) with 95 % confidence intervals through Poisson regression models taking into account the complex sampling design. Data were derived from the third wave of the Demographic and Health Survey conducted in 2006-2007, in Brazil. The sample included 1529 female adolescents aged 15-19 years. The prevalence of any level of HFI was 40.8 %, with 26.6 % of households experiencing mild, 9.4 % moderate and 4.8 % severe food insecurity. The overall prevalence of EW was 21.9 % (12.9 % were overweight and 9.0 % obese). EW prevalence among those living in severely, moderately and mildly food-insecure households was 36.8 %, 14.9 % and 16.5 %, respectively (P for the overall association = 0.036). Women living in severely food-insecure households had an increased prevalence of EW compared with their food-secure counterparts (PR = 1.96; 95 % CI 1.18, 3.27; P = 0.007), after adjusting for important confounders. The study suggests that severe but not mild or moderate HFI is independently associated with EW among adolescents residing in Brazil, a middle-income country undergoing the nutrition transition.


Concept attainment, tracking, and shifting in adolescent polydrug abusers.
Multiple drug use in adults has been shown to result in impaired functioning of the brain's "frontal system," producing deficits in concept tracking, shifting, and learning. In the present study, adolescents with histories of severe, though time-limited, polydrug abuse were found to perform as well as nonabusers on two very sensitive indicators of frontal system functioning. The results are discussed in terms of the natural history of drug-related neuropsychological deficits.


Emerging therapies for thyroid carcinoma.
Thyroid carcinoma is the most commonly diagnosed endocrine malignancy. Its incidence is currently rising worldwide. The discovery of genetic mutations associated with the development of thyroid cancer, such as BRAF and RET, has lead to the development of new drugs which target the pathways which they influence. Despite recent advances, the prognosis of anaplastic thyroid carcinoma is still unfavourable. In this review we look at emerging novel therapies for the treatment of well-differentiated and medullary thyroid carcinoma, and advances and future directions in the management of anaplastic thyroid carcinoma.


Regulation of HepG2 cell apoptosis by hepatitis C virus (HCV) core protein via the sirt1-p53-bax pathway.
Hepatitis C virus (HCV) core protein stimulates many signaling pathways related to apoptosis inhibition resulting in hepatocellular carcinoma (HCC). It has been reported that sirt1 is involved in regulating apoptosis; therefore, we investigated the influence of HCV core protein on sirt1 expression and apoptosis in human HepG2 cells. Our study showed that HCV core protein inhibited apoptosis of HepG2 cells as well as caspase-3 expression and activity (P < 0.05). At the same time, sirt1 expression was increased at both the mRNA (P < 0.05) and protein (P < 0.05) levels. Furthermore, apoptosis inhibition was reversed when sirt1 was knocked down (P < 0.05). Our study provides further evidence that the sirt1-p53-Bax signaling pathway plays an important role in regulating the suppression of cell apoptosis induced by HCV core protein.


Neuropsychological characteristics of dementia with Lewy bodies and Parkinson's disease with dementia: differentiation, early detection, and implications for "mild cognitive impairment" and biomarkers.
Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are neurodegenerative conditions sharing a disorder of alpha-synuclein metabolism. Temporal differences in the emergence of symptoms and clinical features warrant the continued clinical distinction between DLB and PDD. While DLB and PDD groups' neuropsychological profiles often differ from those in Alzheimer's disease (AD), the diagnostic sensitivity, specificity, and predictive values of these profiles remain largely unknown. PDD and DLB neuropsychological profiles share sufficient similarity to resist accurate and reliable differentiation. Although heterogeneous cognitive changes (predominantly in memory and executive function) may manifest earlier and more frequently than previously appreciated in Parkinson's disease (PD), and executive deficits may be harbingers of dementia, the enthusiasm to uncritically extend the concept of mild cognitive impairment (MCI) to PD should be tempered. Instead, future research might strive to identify the precise neuropsychological characteristics of the prodromal stages of PD, PDD, and DLB which, in conjunction with other potential biomarkers, facilitate early and accurate diagnosis, and the definition of neuroprotective, neurorestorative, and symptomatic treatment endpoints.


Randomized clinical trial of two laparoscopic treatments of endometriomas: cystectomy versus drainage and coagulation.
To assess the efficacy of two laparoscopic methods for the management of endometriomas with regard to pain relief, pregnancy rate, and disease recurrence. Prospective, randomized clinical trial. Tertiary care hospital. Sixty-four patients with advanced stages of endometriosis. Patients were randomly allocated at the time of laparoscopy to undergo either cystectomy of the endometrioma (group 1) or drainage of the endometrioma and bipolar coagulation of the inner lining (group 2). Pain relief and pregnancy rate. Thirty-two patients were enrolled in each group. The 24-month cumulative recurrence rates of dysmenorrhea, deep dyspareunia, and nonmenstrual pelvic pain were lower in group 1 than in group 2 (dysmenorrhea: 15.8% versus 52.9%; deep dyspareunia: 20% versus 75%; nonmenstrual pelvic pain: 10% versus 52.9%). The median interval between the operation and the recurrence of moderate to severe pelvic pain was longer in group 1 than in group 2 (19 months [range, 13.5-24 months] versus 9.5 months [range, 3-20 months]). The 24-month cumulative pregnancy rate was higher in group 1 than in group 2 (66.7% versus 23.5%). For the treatment of ovarian endometriomas, a better outcome with a similar rate of complications is achieved with laparoscopic cystectomy than with drainage and coagulation.


Low SARS-CoV-2 antibody titers may be associated with poor clinical outcomes for patients with severe COVID-19.
Recently, immune response to coronavirus disease (COVID-19) has attracted attention where an association between higher antibody titer and worsening disease severity has been reported. However, our experiences with severe COVID-19 patients with low antibody titers led to hypothesizing that suppressed humoral immune response may be associated with poorer prognosis in severe COVID19. In this study, antibody titers in severe COVID19 patients were measured at 7, 10, 12, and 14 days after onset. Patients were divided into survivors and non-survivors. SARS-CoV-2 IgM in survivors and non-survivors were 0.06 AU and 0.02 AU (P = 0.048) at 10 days, 0.1 AU and 0.03 AU (P = 0.02) at 12 days, and 0.17 AU and 0.06 AU (P = 0.02) at 14 days. IgG in survivors and non-survivors were 0.01 AU and 0.01 AU (P = 0.04) at 7 days, 0.42 AU and 0.01 AU (P = 0.04) at 12 days, and 0.42 AU and 0.01 AU (P = 0.02) at 14 days. Multivariate analysis showed better survival among patients with IgM positivity at 12 days (P = 0.04), IgG positivity at 12 days (P = 0.04), IgM positivity at 14 days (P = 0.008), and IgG positivity at 14 days (P = 0.005). In severe COVID-19, low antibody titers on days 12 and 14 after onset were associated with poorer prognosis.


The effect of substance(s) associated with malarial parasites on C3b inactivator.
The effects of a substance or substances associated with malarial parasites on the inhibitory role of C3b inactivator in immune adherence were investigated. The test system involved adherence of immune complexes of complement-bearing sheep erythrocytes and rabbit antibody, using human group O erythrocytes and human renal glomerular tissues as indicators. Malarial antigen and other soluble by-products of the malarial parasites, presumably present in spent culture medium, did not interfere with the inhibitory role of C3b inactivator. However, malarial pigment, both crude and purified, enhanced immune adherence in the presence of C3b inactivator. It is suggested that malarial pigment, by inhibiting the action of C3b inactivator, may play a significant role in the immunopathogenesis of renal lesions associated with malarial infections.


Deep learning reconstruction CT for liver metastases: low-dose dual-energy vs standard-dose single-energy.
To assess image quality and liver metastasis detection of reduced-dose dual-energy CT (DECT) with deep learning image reconstruction (DLIR) compared to standard-dose single-energy CT (SECT) with DLIR or iterative reconstruction (IR). In this prospective study, two groups of 40 participants each underwent abdominal contrast-enhanced scans with full-dose SECT (120-kVp images, DLIR and IR algorithms) or reduced-dose DECT (40- to 60-keV virtual monochromatic images [VMIs], DLIR algorithm), with 122 and 106 metastases, respectively. Groups were matched by age, sex ratio, body mass index, and cross-sectional area. Noise power spectrum of liver images and task-based transfer function of metastases were calculated to assess the noise texture and low-contrast resolution. The image noise, signal-to-noise ratios (SNR) of liver and portal vein, liver-to-lesion contrast-to-noise ratio (LLR), lesion conspicuity, lesion detection rate, and the subjective image quality metrics were compared between groups on 1.25-mm reconstructed images. Compared to 120-kVp images with IR, 40- and 50-keV VMIs with DLIR showed similar noise texture and LLR, similar or higher image noise and low-contrast resolution, improved SNR and lesion conspicuity, and similar or better perceptual image quality. When compared to 120-kVp images with DLIR, 50-keV VMIs with DLIR had similar low-contrast resolution, SNR, LLR, lesion conspicuity, and perceptual image quality but lower frequency noise texture and higher image noise. For the detection of hepatic metastases, reduced-dose DECT by 34% maintained observer lesion detection rates. DECT assisted with DLIR enables a 34% dose reduction for detecting hepatic metastases while maintaining comparable perceptual image quality to full-dose SECT. Reduced-dose dual-energy CT with deep learning image reconstruction is as accurate as standard-dose single-energy CT for the detection of liver metastases and saves more than 30% of the radiation dose. • The 40- and 50-keV virtual monochromatic images (VMIs) with deep learning image reconstruction (DLIR) improved lesion conspicuity compared with 120-kVp images with iterative reconstruction while providing similar or better perceptual image quality. • The 50-keV VMIs with DLIR provided comparable perceptual image quality and lesion conspicuity to 120-kVp images with DLIR. • The reduction of radiation by 34% by DLIR in low-keV VMIs is clinically sufficient for detecting low-contrast hepatic metastases.


Managing pollution from antibiotics manufacturing: charting actors, incentives and disincentives.
Emissions of high concentrations of antibiotics from manufacturing sites select for resistant bacteria and may contribute to the emergence of new forms of resistance in pathogens. Many scientists, industry, policy makers and other stakeholders recognize such pollution as an unnecessary and unacceptable risk to global public health. An attempt to assess and reduce such discharges, however, quickly meets with complex realities that need to be understood to identify effective ways to move forward. This paper charts relevant key actor-types, their main stakes and interests, incentives that can motivate them to act to improve the situation, as well as disincentives that may undermine such motivation. The actor types and their respective interests have been identified using research literature, publicly available documents, websites, and the knowledge of the authors. Thirty-three different actor-types were identified, representing e.g. commercial actors, public agencies, states and international institutions. These are in complex ways connected by interests that sometimes may conflict and sometimes pull in the same direction. Some actor types can act to create incentives and disincentives for others in this area. The analysis demonstrates and clarifies the challenges in addressing industrial emissions of antibiotics, notably the complexity of the relations between different types of actors, their international dependency and the need for transparency. The analysis however also suggests possible ways of initiating incentive-chains to eventually improve the prospects of motivating industry to reduce emissions. High-resource consumer states, especially in multinational cooperation, hold a key position to initiate such chains.